Toxics

31 pages, 1381 KB

Open AccessEditor’s ChoiceReview

Neurotoxic Effects of Nanoplastics: Current Evidence and Mechanistic Insights

by Fuxin Wan, Xiaohan Liu, Jiayue Pan, Linping Ke, Zhekai Zheng and Jingling Liao

Toxics 2026, 14(5), 387; https://doi.org/10.3390/toxics14050387 - 30 Apr 2026

Viewed by 3388

Plastic products are extensively utilized in various industrial goods and consumer items. However, when these plastics fail to undergo complete degradation, they generate nanoplastic particles (NPs). As emerging environmental pollutants, such nanoplastics are highly likely to have widespread and adverse impacts on human [...] Read more.

Plastic products are extensively utilized in various industrial goods and consumer items. However, when these plastics fail to undergo complete degradation, they generate nanoplastic particles (NPs). As emerging environmental pollutants, such nanoplastics are highly likely to have widespread and adverse impacts on human health. Accumulating evidence indicates that NPs can penetrate biological barriers and exert toxic effects on multiple organs, including the nervous system. Although extensive studies have investigated the toxicity of NPs, the mechanisms underlying their long-term neurotoxic effects remain poorly understood. Here, we summarize the current understanding on the exposure pathways of NPs, their neurotoxic effects, and the molecular mechanisms involved in neurotoxicity. Emerging evidence suggests that NPs induce neurological damage through various mechanisms, including oxidative stress, neuroinflammation, ferroptosis, autophagy dysregulation, and gut–brain axis imbalance. A comprehensive understanding of these mechanisms will provide new insights into the potential impacts of environmental NPs exposure on the nervous system and contribute to more accurate health risk assessments. Full article

(This article belongs to the Section Neurotoxicity)

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11 pages, 1921 KB

Open AccessEditor’s ChoiceArticle

An Exploratory Investigation into the Effects of Methanol and Ethylene Glycol on the Growth and Development of Medaka (Oryzias melastigma) and Yellowstripe Goby (Mugilogobius chulae)

by Zhenxiong Yang, Minxia Zhang, Tongfei Xu, Shasha Qi, Lu Tang, Juan Guo, Chuqian Lu and Shaobo Ma

Toxics 2026, 14(5), 380; https://doi.org/10.3390/toxics14050380 - 29 Apr 2026

Viewed by 1417

Abstract

This study aimed to investigate the acute and chronic toxic effects of two thermodynamic inhibitors (methanol and ethylene glycol) widely used in deep-sea oil and gas operations on two typical marine fish species, the medaka (Oryzias melastigma) and the yellowstripe goby [...] Read more.

This study aimed to investigate the acute and chronic toxic effects of two thermodynamic inhibitors (methanol and ethylene glycol) widely used in deep-sea oil and gas operations on two typical marine fish species, the medaka (Oryzias melastigma) and the yellowstripe goby (Mugilogobius chulae), to assess their potential ecological risks in marine environments. The 96-h median lethal concentration (LC₅₀) was determined through acute toxicity tests. A 56-day chronic toxicity test was conducted to evaluate the effects on fish growth (body length) and the antioxidant defense system, specifically the activities of superoxide dismutase (SOD) and catalase (CAT). The results revealed marked species-specific differences. In terms of acute toxicity, medaka exhibited exceptionally high sensitivity to ethylene glycol (LC₅₀ 15.77 g/L), while the yellowstripe goby showed greater tolerance (LC₅₀ 22.17 g/L). Chronic exposure led to concentration-dependent growth inhibition in both species, and medaka showed significantly higher mortality than yellowstripe goby. Under methanol exposure, medaka exhibited significantly higher mortality (30–45%) than yellowstripe goby (5–20%). When exposed to ethylene glycol, medaka showed markedly high mortality (55–85%), while yellowstripe goby mortality remained below 15%. At the molecular level, both chemicals induced oxidative stress, but the response patterns of the antioxidant enzymes (SOD and CAT) were species-specific, indicating differences in toxic mechanisms and detoxification capacities. Methanol and ethylene glycol pose non-negligible ecotoxicological risks to marine fish, and the toxicity intensity is influenced by species specificity, exposure concentration, and the effectiveness of the antioxidant defense system. This study emphasizes that environmental risk assessments for such chemicals must fully account for species differences and sublethal effects, providing critical scientific evidence for formulating precise environmental safety standards for marine hydrocarbon exploitation. Full article

(This article belongs to the Special Issue Fish Physiological Responses to Environmental Stressors)

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31 pages, 9404 KB

Open AccessEditor’s ChoiceArticle

Spatiotemporal Variability Analysis of PM_2.5 and O₃ Pollution Characteristics in the Fenwei Plain

by Jingyue Xue, Yushuang Wang, Tingting Fan and Jian Peng

Toxics 2026, 14(5), 378; https://doi.org/10.3390/toxics14050378 - 28 Apr 2026

Viewed by 1364

Abstract

The Fenwei Plain (FWP) is a typical basin-type region in northern China characterized by complex PM_2.5 and O₃ composite pollution. Based on hourly monitoring data from 11 cities (2015–2024), this study integrated the Mann–Kendall test, standard deviation ellipse (SDE), spatio-temporal cross-correlation [...] Read more.

The Fenwei Plain (FWP) is a typical basin-type region in northern China characterized by complex PM_2.5 and O₃ composite pollution. Based on hourly monitoring data from 11 cities (2015–2024), this study integrated the Mann–Kendall test, standard deviation ellipse (SDE), spatio-temporal cross-correlation function (STCCF), and spatio-temporal geographically weighted regression (GTWR) to systematically analyze decadal pollution patterns and coupling mechanisms. Results revealed a profound transition from particulate-dominated to photochemical-regime pollution: PM_2.5 concentrations decreased significantly by 32%, whereas MDA8 O₃ rose by 47%. Spring emerged as the critical compound pollution window, accounting for 66.7% of simultaneous exceedances. Spatially, both pollutants maintained a consistent Northeast–Southwest orientation, with PM_2.5 hotspots concentrated along the Weihe River Valley. Cluster analysis categorized the 11 cities into O₃-dominant, compound-high-risk, and PM_2.5-dominant clusters. Furthermore, a dominant positive synergy was observed on an annual scale, although a localized “see-saw” effect occurred at a 150–200 km distance with a 3-year lag. The GTWR model demonstrated high robustness (R²: 0.75–0.86), underscoring the influence of localized driving forces. These findings provide a scientific basis for synergistic governance and precision air quality management in northern basin-type regions. Full article

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16 pages, 835 KB

Open AccessEditor’s ChoiceReview

Renal Effects of Energy Drink Consumption: A Systematic Review and Meta-Analysis of Preclinical Studies

by Alfredo G. Casanova, Ana I. Morales and Laura Vicente Vicente

Toxics 2026, 14(5), 376; https://doi.org/10.3390/toxics14050376 - 28 Apr 2026

Cited by 1 | Viewed by 8138

Abstract

In recent decades, there has been a worrying increase in the consumption of energy drinks, especially among the young population. These beverages have been linked to effects primarily on the nervous and cardiovascular systems; however, renal consequences remain poorly understood, particularly those associated [...] Read more.

In recent decades, there has been a worrying increase in the consumption of energy drinks, especially among the young population. These beverages have been linked to effects primarily on the nervous and cardiovascular systems; however, renal consequences remain poorly understood, particularly those associated with long-term consumption. The heterogeneity in consumption patterns, together with variability in consumer profiles, has limited the ability to obtain conclusive and consistent evidence on this issue. Therefore, it is essential to address this topic from a preclinical perspective under controlled experimental conditions. The aim of the present study was to evaluate the available preclinical evidence through a systematic review followed by a meta-analysis. Nineteen studies met the inclusion criteria, with rats being the most commonly used experimental model. Overall, the results show a significant association between energy drink consumption and impaired kidney function, as reflected in elevated levels of serum biomarkers such as creatinine, urea, and uric acid. Among these, serum creatinine (mean Hedges’ g = −1.40; 95% confidence interval: −2.55 to −0.25) and urea (Hedges’ g = −1.93; 95% confidence interval: −2.99 to −0.87) had the highest effect sizes and greater statistical robustness, suggesting a particularly significant impact on kidney function. Although fewer studies reported increased uric acid levels, this parameter may have pathophysiological relevance. Elevated uric acid has been associated with mechanisms such as inflammation, oxidative stress, and endothelial dysfunction, which may contribute to the progression of renal damage. Additionally, morphological alterations in glomerular and tubular structures were observed, particularly after prolonged exposure and at high doses. Despite the need for methodological improvements in future research, these findings highlight potential adverse renal effects that should be considered in the development of regulatory policies on energy drink consumption. Full article

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49 pages, 1021 KB

Open AccessEditor’s ChoiceReview

Beyond Blast Injury: Occupational Hygiene, Safety, and Toxicology Considerations for Mixed-Metal and Energetic-Chemical Exposures to Explosive Ordnance Disposal Personnel

by Bryan G. Fry, Kelly Johnstone and Stacey Pizzino

Toxics 2026, 14(5), 379; https://doi.org/10.3390/toxics14050379 - 28 Apr 2026

Cited by 1 | Viewed by 7396

Abstract

Explosive ordnance (EO), including AXO (abandoned explosive ordnance), IEDs (improvised explosives devices), and UXO (unexploded ordnance), are widely recognised for their blast and fragmentation hazards, but they also represent a persistent and under-addressed source of occupational chemical exposure for explosive ordnance disposal (EOD) [...] Read more.

Explosive ordnance (EO), including AXO (abandoned explosive ordnance), IEDs (improvised explosives devices), and UXO (unexploded ordnance), are widely recognised for their blast and fragmentation hazards, but they also represent a persistent and under-addressed source of occupational chemical exposure for explosive ordnance disposal (EOD) personnel. EOD core activities liberate mixed metals and energetic chemicals, resulting in exposures that are multi-route (inhalation of dusts and fumes, dermal loading amplified by sweat and glove occlusion, and ingestion via hand-to-mouth transfer during eating, drinking, or smoking) and multi-temporal (repeated low-dose background plus task-driven spikes), as well as chemically complex. Clinically, this can present as syndromic overlap across acute and chronic domains, with symptoms that are easily misattributed to heat stress, dehydration, infection, or fatigue. Acute effects of concern include neurotoxic presentations (headache, dizziness, confusion, tremor, and seizure), respiratory and mucosal irritation following dust or fume events, gastrointestinal symptoms, and patterns suggestive of acute hepatic or renal stress, particularly when high-intensity tasks occur in hot environments that compound physiologic strain. Chronic outcomes relevant to repeatedly exposed EOD personnel include renal function decline, neurocognitive effects that can degrade operational decision making and safety, persistent haematologic abnormalities, and endocrine disruption signals, with long-latency risks requiring cautious interpretation given sparse longitudinal data and confounding co-exposures. This review synthesises the current evidence base through an EOD lens and translates it into pragmatic clinical and programmatic actions: task-based exposure characterisation; tiered biomonitoring and medical surveillance aligned to operational tempo; incident-triggered assessment pathways after high-residue events; and prevention strategies that work under field constraints, including contamination control zones, hygiene enforcement, glove and respiratory protection optimisation, tool and vehicle decontamination, and measures to prevent secondary transfer and take-home exposure. The central takeaway is practical: EOD programs can reduce morbidity and improve readiness by treating explosive ordnance as a chemical mixture exposure problem, adopting mixture-aware clinical triage, and embedding surveillance and controls that match how EOD work is actually performed. Full article

(This article belongs to the Special Issue Occupational Exposure to Heavy Metals in Environmentally Vulnerable Areas)

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18 pages, 3769 KB

Open AccessEditor’s ChoiceReview

Genetic Polymorphisms as Modifiers of Health Risks from Exposure to Toxic Elements: A Traditional Literature Review

by Mariangela Palazzo, Andrea Borghini, Elisa Bustaffa, Silvia Baldacci, Francesca Gorini and Fabrizio Minichilli

Toxics 2026, 14(5), 375; https://doi.org/10.3390/toxics14050375 - 27 Apr 2026

Cited by 2 | Viewed by 2424

Abstract

A growing body of epidemiological and toxicological evidence indicates that exposure to toxic elements (TEs), including As, Cd, Cr(VI), Pb, and Hg, is associated with a wide range of adverse health outcomes, including cancer, neurological and cardiovascular diseases. Given their widespread presence and [...] Read more.

A growing body of epidemiological and toxicological evidence indicates that exposure to toxic elements (TEs), including As, Cd, Cr(VI), Pb, and Hg, is associated with a wide range of adverse health outcomes, including cancer, neurological and cardiovascular diseases. Given their widespread presence and toxicity, understanding the factors underlying inter-individual differences in susceptibility is essential, as not all exposed individuals develop the same health effects. Genetic variability, particularly single-nucleotide polymorphisms (SNPs), is increasingly recognized as a key determinant of individual responses to TE exposure. Variants in genes involved in metal transport, detoxification, and DNA repair, including DMT1, GSTP1, MT2A, hOGG1, and XRCC1, may influence internal dose and biological effects and have been proposed as potential susceptibility markers. However, current evidence remains inconsistent due to small sample sizes, heterogeneous exposure assessments, and limited considerations of ethnic diversity and gene–environment interactions. Future research should prioritize large and well-characterized populations integrating detailed exposure and lifestyle data. This review focuses on genetic susceptibility and gene–environment interactions in TE exposure, with particular emphasis on SNPs as key modulators of individual risk. It summarizes major toxic metals, reviews epidemiological evidence of the associated health risks, and highlights the role of genetic background in modulating TE-induced toxicity. Full article

(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants—2nd Edition)

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13 pages, 1253 KB

Open AccessEditor’s ChoiceArticle

Early-Life Exposure to Ambient Air Quality and Infant Health-Related Quality of Life: A Longitudinal Multi-Center Cohort in China

by Yulin Wu, Ju Chen, Siting Zheng, Jieling Luo, Zhiyong Xie, Yi Liu, Mingxian Wu, Suxia Sun and Zheqing Zhang

Toxics 2026, 14(5), 371; https://doi.org/10.3390/toxics14050371 - 26 Apr 2026

Viewed by 1302

Abstract

Air pollution poses a major public health threat, yet longitudinal evidence on its impact on infant health-related quality of life (HRQoL) remains limited. This study investigated the longitudinal associations between early-life exposure to outdoor air pollution and infant HRQoL, focusing on psychological and [...] Read more.

Air pollution poses a major public health threat, yet longitudinal evidence on its impact on infant health-related quality of life (HRQoL) remains limited. This study investigated the longitudinal associations between early-life exposure to outdoor air pollution and infant HRQoL, focusing on psychological and physiological domains. Between November 2021 and September 2022, 779 mother–newborn pairs were recruited, with 696 completing follow-up at 12 months. HRQoL was assessed at 1, 4, 6, and 12 months using the Pediatric Quality of Life Inventory™, and exposures to PM_2.5, PM₁₀, NO₂, and SO₂ were analyzed using linear mixed-effects models adjusted for infant sex, household income, sibling status, and other covariates. Higher concentrations of all pollutants were associated with lower total HRQoL scores. Stratified analyses showed that PM_2.5, PM₁₀, and SO₂, but not NO₂, were associated with steeper age-related declines in total scores. Inverse associations with psychosocial health were consistent across pollutants, with pronounced age-related declines in high-exposure groups; for physical health, only SO₂ and NO₂ remained significant after adjustment, with modest age-related changes. These findings suggest that early-life air pollution exposure is associated with smaller gains in HRQoL during infancy, particularly in psychosocial well-being, highlighting the importance of improving air quality to support early development. Full article

(This article belongs to the Special Issue Multi-Media Exposure to Emerging Contaminants and Health Effects Across Physiological Systems: Exposure Pathways, Risk Assessment and Public Health Implications)

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20 pages, 1104 KB

Open AccessEditor’s ChoiceReview

Do Perfluorinated Chemicals Enhance the Toxicity of Other Contaminants in Aquatic Organisms? A Review

by Eliana Maira Agostini Valle, Emma Ivantsova, Maria Luisa Pracchia, Calvin Quessada Cabello, Hueder Paulo Moisés de Oliveira, Lucia Codognoto and Christopher J. Martyniuk

Toxics 2026, 14(5), 373; https://doi.org/10.3390/toxics14050373 - 26 Apr 2026

Cited by 2 | Viewed by 2684

Abstract

Environmental contaminants pose threats to exposed organisms and negatively impact the nervous, cardiovascular, immune, and reproductive systems. Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are ubiquitous in the environment. Given that mixtures of environmental contaminants have the potential to exacerbate toxicity, [...] Read more.

Environmental contaminants pose threats to exposed organisms and negatively impact the nervous, cardiovascular, immune, and reproductive systems. Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are ubiquitous in the environment. Given that mixtures of environmental contaminants have the potential to exacerbate toxicity, we reviewed the current literature on pesticides, microplastics, or metal exposure in combination with PFAS on aquatic vertebrates and invertebrates. The objectives were to evaluate the toxicological effects of mixtures of the selected contaminants with PFAS on aquatic organisms to better understand biological responses in animals. Based on our review, data suggest that PFAS can modify the toxicity of co-occurring pollutants. For example, synergistic effects on toxicity include chlorpyrifos + perfluorohexanoic acid (PFHxA), which increased reactive oxygen species (ROS) and upregulated neurotoxicity-related genes in zebrafish, and perfluorooctanoic acid (PFOA) + atrazine, which increased the presence of malformations and oxidative stress. However, antagonistic interactions were also observed, for example, reduced herbicide toxicity in PFOA + 2,4-dichlorophenoxyacetic acid (2,4-D) mixtures. PFAS combined with microplastics often intensified oxidative stress and developmental or reproductive effects, though polyethylene microplastics attenuated perfluorooctane sulfonic acid (PFOS)-induced immunotoxicity in fish like seabass. Interactions with metals also varied, with copper and cadmium enhancing oxidative stress while mercury mixtures with PFAS showed antagonism, underscoring the complexity of mixture effects in real environments. A computational approach demonstrated that PFOS can engage in intermolecular interactions with pesticides, microplastic monomers, and metals, suggesting chemical-level effects that could modify toxicity or bioavailability. Future studies should focus on elucidating the mechanisms underlying these complex interactions, investigating effects at different trophic levels and in a broader range of species, and should consider environmentally relevant mixtures. Full article

(This article belongs to the Section Emerging Contaminants)

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21 pages, 4670 KB

Open AccessEditor’s ChoiceReview

Toxicological Effects and Health Impacts of Per- and Polyfluoroalkyl Substances (PFAS) in Humans

by Jie Ma, Ge Gao, Bitan Meng, Xinni Wei, Long Zhao and Zaiming Ge

Toxics 2026, 14(5), 374; https://doi.org/10.3390/toxics14050374 - 26 Apr 2026

Cited by 4 | Viewed by 4099

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals notable for their high persistence and extensive applications. With the advancement of detection technologies in recent years, PFAS have been frequently identified in environmental media and human biological samples, raising significant global [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals notable for their high persistence and extensive applications. With the advancement of detection technologies in recent years, PFAS have been frequently identified in environmental media and human biological samples, raising significant global concerns about their potential health risks. PFAS exhibit distinctive toxicokinetic behaviors, including efficient absorption, strong protein binding, limited metabolism, and slow excretion, which lead to prolonged biological half-lives and considerable bioaccumulation in humans. These properties contribute to a range of adverse health outcomes, such as endocrine disruption, immune suppression, liver damage, reproductive toxicity, carcinogenic potential, and cardiovascular disease. This review synthesizes evidence on PFAS-associated health risks from a multisystem, multitarget perspective, elucidating the key molecular pathways involved, thereby providing a scientific basis for understanding their complex toxicological effects and for developing targeted prevention and control strategies. Future research should prioritize characterizing the toxicological profiles of individual PFAS compounds, evaluating the health impacts of combined (mixture) exposures, and assessing risks associated with chronic, low-dose exposure to support the development of public health strategies and regulatory decisions. Full article

(This article belongs to the Special Issue Effects of Exposure to Emerging Environmental Pollutants on Human Health)

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22 pages, 9778 KB

Open AccessEditor’s ChoiceArticle

Pollution Characteristics and Assessment of Carcinogenic and Non-Carcinogenic Risks of Volatile Halogenated Hydrocarbons in a Medium-Sized City of the Sichuan Basin, Southwest China

by Xia Wan, Xiaoxin Fu, Zhou Zhang, Yao Rao, Mei Yang, Jianping Wang and Xinming Wang

Toxics 2026, 14(5), 370; https://doi.org/10.3390/toxics14050370 - 25 Apr 2026

Viewed by 1431

Abstract

Volatile halogenated hydrocarbons (VHHs) are critical air toxic pollutants, with some ozone-depleting substances (ODSs) strictly regulated by the Montreal Protocol. However, current understanding of the pollution characteristics, sources, and health risks of atmospheric VHHs in Southwest China remains insufficient. This study performed field [...] Read more.

Volatile halogenated hydrocarbons (VHHs) are critical air toxic pollutants, with some ozone-depleting substances (ODSs) strictly regulated by the Montreal Protocol. However, current understanding of the pollution characteristics, sources, and health risks of atmospheric VHHs in Southwest China remains insufficient. This study performed field observations of atmospheric VHHs in summer in Mianyang, a medium-sized industrial city in the Sichuan Basin. Freon-12 (563 ± 20 ppt) and Freon-11 (264 ± 15 ppt) were the most abundant chlorofluorocarbons (CFCs); chloromethane (785 ± 261 ppt) and methylene chloride (563 ± 505 ppt) dominated among VSLSs. The mean concentration of regulated ODSs (1037 ± 33 pptv) was notably lower than unregulated very short-lived chlorinated substances (1887 ± 745 pptv), reflecting effective ODSs phase-out locally, yet enhancements relative to Northern Hemisphere background implied potential leakage from residual tanks. Methylene chloride and trichloroethylene concentrations exceeded global background levels by over 10 times, indicating strong anthropogenic industrial influences. Phased-out CFCs displayed negligible diurnal variation due to stringent emission controls, whereas unregulated VSLSs exhibited a distinct U-shaped diurnal cycle, with peaks driven by morning boundary layer dynamics and evening accumulation. Positive matrix factorization revealed that industrial sources, including electronic solvents (28.6%), industrial processes (27.8%), and solvent usage (23.7%), accounted for 80.1% of total VHHs. The total carcinogenic risk (2.3 × 10⁻⁵) surpassed the acceptable threshold (1 × 10⁻⁶), dominated by 1,2-dichloroethane, chloroform, carbon tetrachloride, and 1,2-dichloropropane. All individual compounds exhibited mean hazard quotients (HQs) below the non-carcinogenic risk threshold. The cumulative hazard index reached 1.5, suggesting combined non-carcinogenic risks to the local population. These results support VHHs health risk management and ODSs control in Southwest Chinese industrial cities. Full article

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16 pages, 2317 KB

Open AccessEditor’s ChoiceArticle

Genome-Wide DNA Methylation Analysis of the Toxicological Responses to Foliar Cerium Application in Soybean

by Cheng Guo and Lizong Sun

Toxics 2026, 14(5), 369; https://doi.org/10.3390/toxics14050369 - 25 Apr 2026

Viewed by 1314

Abstract

The increasing agricultural and industrial use of rare earth elements (REEs) has raised growing concerns about their environmental accumulation and ecotoxicity, yet the molecular and epigenetic basis underlying their dose-dependent effects on crops remains poorly understood. In this study, soybean plants were foliar [...] Read more.

The increasing agricultural and industrial use of rare earth elements (REEs) has raised growing concerns about their environmental accumulation and ecotoxicity, yet the molecular and epigenetic basis underlying their dose-dependent effects on crops remains poorly understood. In this study, soybean plants were foliar treated with Cerium (Ce) at 0, 5, 10, and 50 mg·L⁻¹. Growth, elemental uptake, genome wide DNA methylation, and gene expression were analyzed using ICP-MS, WGBS, and qRT-PCR. Low dose Ce (5 mg·L⁻¹) showed a hormetic effect, promoting growth and grain quality, whereas high dose Ce (50 mg·L⁻¹) markedly inhibited growth. Foliar absorbed Ce was poorly translocated to roots and seeds, thus reducing food chain contamination risk. Ce significantly altered methylation levels of CG, CHG, and CHH contexts in soybean leaves. Low Ce increased CG methylation, while high Ce decreased CHH methylation. Differentially methylated genes (Low-dose Ce induced 52 hypermethylated DMGs and 23 hypomethylated DMGs, while high-dose Ce induced 76 hypomethylated DMGs and 17 hypermethylated DMGs) were enriched in oxidation–reduction, DNA repair, and cell cycle pathways. qRT-PCR confirmed that Ce mediated toxic responses and growth by regulating methylation related enzymes, oxidative detoxification, and DNA repair genes. This study provides novel genome-wide bisulfite sequencing evidence linking foliar Ce exposure to context-specific DNA methylation reprogramming in a major legume crop. These results demonstrate that the dose-dependent phytotoxicity of Ce in soybean is associated with context-specific changes in genome-wide DNA methylation, supporting the safety evaluation and rational agricultural application of rare earth elements. Full article

(This article belongs to the Section Ecotoxicology)

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13 pages, 1023 KB

Open AccessEditor’s ChoiceArticle

Optimized Zebrafish In Vitro Maturation with Real-Time Morphometric Workflow Reveals Inhibition by 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE)

by Tao Xu, Lihua Yang, Yindan Zhang, Huijia Tang, Yue Guo, Yanmin Guo, Mingpu Du, Ruiwen Li, Biran Zhu, Jian Han and Bingsheng Zhou

Toxics 2026, 14(5), 368; https://doi.org/10.3390/toxics14050368 - 25 Apr 2026

Viewed by 1504

Abstract

Novel brominated flame retardants (NBFRs), including 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), are emerging endocrine-disrupting chemicals, though their direct effects on female gamete maturation remain insufficiently characterized. In this study, we used a refined zebrafish oocyte in vitro maturation (IVM) model integrating germinal vesicle breakdown (GVBD) assessment [...] Read more.

Novel brominated flame retardants (NBFRs), including 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), are emerging endocrine-disrupting chemicals, though their direct effects on female gamete maturation remain insufficiently characterized. In this study, we used a refined zebrafish oocyte in vitro maturation (IVM) model integrating germinal vesicle breakdown (GVBD) assessment with real-time, image-based oocyte diameter quantification. The workflow incorporated donor-condition optimization and diameter-based quality control during sorting. Oocytes from donors 4 to 5 months post-fertilization (mpf) showed more consistent diameter dynamics at the dish level than those from donors 3 to 4 mpf. Mixed-sex co-housing was associated with higher GVBD and larger Δdiameter than separated housing, although this comparison should be considered preliminary. Under DHP induction, BTBPE (1–1000 nM) consistently suppressed GVBD and attenuated maturation-associated diameter increases, with a non-monotonic-like response pattern. These findings indicate that BTBPE impairs oocyte maturation competence in vitro and supports real-time morphometric tracking as a practical QC component for zebrafish IVM workflows. Full article

(This article belongs to the Special Issue Aquatic Toxicity of Emerging Contaminants)

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30 pages, 4617 KB

Open AccessFeature PaperEditor’s ChoiceArticle

The Invasive Blue Crab Callinectes sapidus as a Model for Assessing Sub-Lethal Effects of Polyvinyl Alcohol

by Alessandra Maganza, Giorgia Zicarelli, Giuseppe Esposito, Annalisa Cotugno, Alice Gabetti, Camilla Mossotto, Alessia Merialdi, Francesca Provenza, Serena Anselmi, Marzia Pezzolato, Elena Bozzetta, Monia Renzi, Marino Prearo, Caterina Faggio, Edoardo Turolla, Antonia Concetta Elia and Paolo Pastorino

Toxics 2026, 14(5), 358; https://doi.org/10.3390/toxics14050358 - 24 Apr 2026

Viewed by 939

Abstract

Polyvinyl alcohols (PVAs) are synthetic, water-soluble polymers widely used in industrial, medical, and personal care products. Their slow biodegradation raises concerns about potential impacts on marine ecosystems. This study examined how PVA exposure affects the blue crab Callinectes sapidus, an invasive species [...] Read more.

Polyvinyl alcohols (PVAs) are synthetic, water-soluble polymers widely used in industrial, medical, and personal care products. Their slow biodegradation raises concerns about potential impacts on marine ecosystems. This study examined how PVA exposure affects the blue crab Callinectes sapidus, an invasive species in the Mediterranean Sea. Crabs were exposed to three PVA concentrations (0.5, 5, and 25 mg L⁻¹) along with a control group, for periods of 10 and 20 days. Oxidative stress was assessed by measuring antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), and lipid peroxidation levels in muscle, gill, and hepatopancreas. Cell viability in the hemolymph and hepatopancreas was also evaluated. The results showed that hepatopancreas cells were more sensitive than hemolymph cells. Oxidative stress increased with exposure time and concentration, as indicated by elevated antioxidant enzyme activity and lipid peroxidation. After 10 days, early detoxification responses were observed, while after 20 days of exposure, clear dose- and time-dependent trends were evident, highlighting an intensification of physiological dysfunctions with increasing PVA concentrations and prolonged exposure duration. The histopathological observations showed limited alterations in muscle and hepatopancreas tissue but evident structural changes in gill tissues, particularly after prolonged exposure. The findings reveal a concentration- and time-dependent biological response to PVA, highlighting physiological changes at higher exposure levels and the need for further research on environmental consequences. Full article

(This article belongs to the Special Issue Toxic Effects of Emerging Pollutants on Aquatic Organisms and Humans)

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20 pages, 14986 KB

Open AccessEditor’s ChoiceReview

Microplastic Neurotoxicity in the Prefrontal Cortex: A Review of Mechanisms and Neuropsychiatric Associations

by Zixuan Liang, Enguo Zhang, Bing Han, Zhenhao Yang, Xiangjing Meng, Yu Zhang, Jiazi Ma, Ziyang Xu, Mengjie Cheng, Hua Shao and Shangya Chen

Toxics 2026, 14(5), 359; https://doi.org/10.3390/toxics14050359 - 24 Apr 2026

Cited by 1 | Viewed by 2307

Abstract

The escalating crisis of plastic pollution has positioned microplastics (MPs) as globally pervasive environmental contaminants, with a documented presence across aquatic, terrestrial, and atmospheric ecosystems, as well as within biological organisms. A growing body of evidence suggests that MPs not only threaten ecological [...] Read more.

The escalating crisis of plastic pollution has positioned microplastics (MPs) as globally pervasive environmental contaminants, with a documented presence across aquatic, terrestrial, and atmospheric ecosystems, as well as within biological organisms. A growing body of evidence suggests that MPs not only threaten ecological integrity but may also induce multifaceted neurotoxic effects in humans, particularly targeting the functional architecture of the prefrontal cortex (PFC). As the central regulator of cognition, emotional processing, and behavioral control, PFC dysfunction has been hypothesized to be associated with cognitive deficits, emotional dysregulation, and behavioral abnormalities. In this comprehensive review, we synthesize the current understanding of MP-mediated neurotoxicity through three interconnected pathways: (1) structural and functional impairment of PFC neural networks, (2) disruption of neurotransmitter homeostasis, and (3) potential associations with neuropsychiatric pathogenesis. By integrating these mechanistic insights, this work aims to provide a scientific foundation for risk assessment frameworks and evidence-based environmental health policies. Full article

(This article belongs to the Special Issue Insights into Toxicological Effects of Micro- and Nano-Plastics)

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25 pages, 3287 KB

Open AccessFeature PaperEditor’s ChoiceArticle

From Soil to Serum: Matrix-Specific Per- and Polyfluoroalkyl Substance Accumulation and Potentially Associated Environmental Exposure Determinants in Teenagers Residing near an Industrial Hotspot

by Jodie Buytaert, Bianca Cox, Thimo Groffen, Robin Lasters, Lieven Bervoets, Elly Den Hond, Stefan Voorspoels, Liesbeth Bruckers, Nicolas Van Larebeke, Greet Schoeters, Marcel Eens, Dries Coertjens and Ann Colles

Toxics 2026, 14(5), 360; https://doi.org/10.3390/toxics14050360 - 24 Apr 2026

Viewed by 1710

Abstract

The extensive production and use of per- and polyfluoroalkyl substances (PFAS) over recent decades have resulted in their pervasive distribution in environmental compartments worldwide. PFAS concentrations in soil and biota near fluorochemical manufacturing facilities tend to be typically higher near hotspots, which suggests [...] Read more.

The extensive production and use of per- and polyfluoroalkyl substances (PFAS) over recent decades have resulted in their pervasive distribution in environmental compartments worldwide. PFAS concentrations in soil and biota near fluorochemical manufacturing facilities tend to be typically higher near hotspots, which suggests that the consumption of home-produced foods near such hotspots most likely results in higher human exposure. One prominent European hotspot is located near the 3M fluorochemical production facility in Zwijndrecht (Belgium), where the relative contributions of different exposure pathways remain insufficiently characterised. This study therefore aimed to assess the PFAS concentrations and compositional profiles in serum, dwellings and gardens of teenagers residing near this hotspot. Serum samples from teenagers, along with multiple environmental matrices (i.e., soil, compost, vegetables/fruits/nuts, chicken eggs, rainwater and indoor house dust) were analysed for 21 selected PFAS. Additionally, potential determinants of PFAS occurrence and distribution across matrices were investigated using detailed questionnaire data. We found perfluorooctane sulfonic acid (PFOS) to be the predominant compound in both soil and serum, while perfluorobutanoic acid (PFBA) was most dominant in rainwater, compost, house dust and pods. Perfluorobutane sulfonic acid (PFBS) was most abundant in fruits and chicken eggs, while perfluorododecanoic acid (PFDoDA) was predominant in rooting vegetables and nuts. N-methylperfluorooctane sulfonamidoacetic acid (MePFOSAA) was the dominant compound in fruiting, stem, and leafy vegetables. These results indicate differences in accumulation pathways among the different media and/or differences in affinities of different PFAS in the matrices. Additionally, several environmental and behavioural factors were identified as determinants for PFAS in soil, compost, tree fruits, fruiting vegetables, chicken eggs and house dust, providing insight into potential drivers of exposure variability. The most important factors were related to the soil characteristics, the composting of grass and weeds, the chicken feed (i.e., bread, commercial feed), the type and frequency of ventilation and the frequency of cleaning. Full article

(This article belongs to the Special Issue Human Biomonitoring, Exposure Assessment and Quantitative Analysis of PFASs)

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15 pages, 2873 KB

Open AccessEditor’s ChoiceArticle

Developmental Toxicity and Stress Response Profiles of a Commercial Aloe vera Extract in Zebrafish Embryos

by Cláudia A. Rocha, João Pereira, Enrique Moreira, Bruno Sousa, Ana Luzio, Sandra M. Monteiro, Carlos Venâncio and Luís Félix

Toxics 2026, 14(5), 362; https://doi.org/10.3390/toxics14050362 - 24 Apr 2026

Cited by 1 | Viewed by 1840

Abstract

Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC [...] Read more.

Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC₅₀ was determined to be 0.03%. Embryos at 2 h post-fertilization (hpf) were exposed for 96 h to 0.0004% (LC₁₀) and 0.03% (LC₅₀). Exposure to 0.0004% caused no significant effects compared to controls. In contrast, exposure to 0.03% significantly increased mortality, reduced heart rate, impaired locomotion, and induced multiple malformations. Biochemical analyses revealed alterations in redox-associated biomarkers, characterized by unchanged ROS levels and mitochondrial activity, increased antioxidant enzyme activities (SOD, GPx, GR), and a decreased GSH:GSSG ratio. Lipid peroxidation levels were reduced, while a significant increase in DNA double-strand breaks (DSBs) was observed. Additionally, Nrf2 protein expression was upregulated at 0.03%. Together, these findings suggest concentration-dependent developmental toxicity correlated with alterations in redox homeostasis and genomic stability during early zebrafish development. This study provides new insight into the developmental hazard potential of a commercial Aloe vera extract in an aquatic vertebrate model. Full article

(This article belongs to the Section Ecotoxicology)

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22 pages, 17474 KB

Open AccessEditor’s ChoiceArticle

Heavy Metals Risk Assessment and Source Apportionment in Agricultural Soils of the Central Yunnan Dry-Hot Valley

by Lin Song, Tao Zhang, Hedian Yan, Jie Xu, Weizhi Chen, Yong Ba, Hu Wang, Kun Qian, Yuanlong Li, Wenlin Wu and Ya Zhang

Toxics 2026, 14(5), 366; https://doi.org/10.3390/toxics14050366 - 24 Apr 2026

Cited by 1 | Viewed by 1746

Abstract

Heavy metal contamination in agricultural soils threatens ecosystem safety and sustainable land use, particularly in geologically sensitive areas. This study aimed to assess the pollution status, ecological risks and source contributions of eight heavy metals (Hg, Cd, Pb, As, Cr, Cu, Ni and [...] Read more.

Heavy metal contamination in agricultural soils threatens ecosystem safety and sustainable land use, particularly in geologically sensitive areas. This study aimed to assess the pollution status, ecological risks and source contributions of eight heavy metals (Hg, Cd, Pb, As, Cr, Cu, Ni and Zn) in soils from a dry-hot agricultural region of central Yunnan, China. To improve source apportionment, this study applied and compared three models: APCS-MLR, PMF, and Random Forest. Analysis of 1790 soil samples showed mean concentrations (mg/kg) of 0.03 for Hg, 0.17 for Cd, 25.01 for Pb, 7.46 for As, 85.91 for Cr, 36.20 for Cu, 31.75 for Ni, and 69.24 for Zn. Pollution assessment indicated that Cu and Cd were the main pollutants, while ecological risk assessment identified Cd and Hg as the dominant ecological risk factors. Four major sources were identified: industrial hybrid sources, natural background, atmospheric deposition and agricultural activities, with industrial hybrid sources contributing the largest share. These results indicate that integrating APCS-MLR, PMF, and Random Forest provides a more reliable framework for source identification and supports targeted soil pollution control in regions affected by both natural and anthropogenic inputs. Full article

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17 pages, 17003 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Development and Validation of a Method for Quantitative UPLC-MS/MS Determination of Selected Perfluorocarboxylic and Perfluorosulfonic Acids in Human Urine

by Isotta Cursi, Nicola Iacovella, Anna Maria Ingelido and Annalisa Abballe

Toxics 2026, 14(5), 364; https://doi.org/10.3390/toxics14050364 - 24 Apr 2026

Viewed by 1665

Abstract

Per- and polyfluoroalkyl substances (PFASs) are a large class of thousands of synthetic organofluorine chemical compounds used for many industrial applications. Humans are exposed to PFASs mainly through diet and contaminated drinking water. Studies show that PFASs induce several adverse effects on humans. [...] Read more.

Per- and polyfluoroalkyl substances (PFASs) are a large class of thousands of synthetic organofluorine chemical compounds used for many industrial applications. Humans are exposed to PFASs mainly through diet and contaminated drinking water. Studies show that PFASs induce several adverse effects on humans. A great number of human biomonitoring studies have been widely conducted with the aim of estimating exposure to PFASs. The matrices mainly investigated are blood, serum and breast milk. However, in many cases, the need for non-invasive sampling methods with a minimal impact on donors has become paramount to comply with modern ethical standards and regulations. For this reason, we developed a streamlined and efficient method for the analysis of eight perfluorocarboxylic and perfluorosulfonic acids (PFHpA; PFHxS; PFOA; PFHpS; PFNA; PFOS; PFDA; and PFUdA) in human urine samples by UPLC chromatography tandem mass spectrometry. Chromatographic and MS parameters were optimized; the method was validated for: repeatability (<20%), within-lab reproducibility (<20%), trueness (within the set 20% variation limit of agreement between the mean of the data set and the true value), efficiency (51–97%), linearity (R² > 0.99), limits of detection (0.0003 ng/mL), and limits of quantification (0.001 ng/mL). To our knowledge, this is the first published method in Italy for the detection of PFASs in human urine. Full article

(This article belongs to the Section Exposome Analysis and Risk Assessment)

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26 pages, 6075 KB

Open AccessEditor’s ChoiceArticle

Exposure to Polystyrene Microplastics Disrupts Blood Cell Homeostasis and Metabolic Profiles in Pregnant Mice and Offspring: The Role of Oxidative Stress and Inflammation

by Lin Lin, Ti-Zhen Yan, Hai-Wen Zhuo, Rong-Hua Zhang, Hong-Yi Liu, Xing-He Wang, Qing-Wo Lu, Rui Guo, Jian-Feng Qiu, Bo Zhang and Qing-Ming Luo

Toxics 2026, 14(5), 354; https://doi.org/10.3390/toxics14050354 - 23 Apr 2026

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Abstract

Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams [...] Read more.

Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams and offspring. PS-MPs accumulated in multiple tissues, including blood, indicating maternal-to-offspring transfer. Continuous exposure reduced litter size, induced hepatic oxidative stress, and increased IL-6 and TNF-α levels in a dose-dependent manner in both dams and offspring. In dams, PS-MPs also decreased red blood cell and platelet counts and altered leukocyte composition, with increased lymphocyte and decreased neutrophil percentages at the high dose. Untargeted serum metabolomics revealed distinct exposure-related metabolic profiles, including 18 putatively annotated signature metabolites and 26 differentially abundant metabolites. Bilirubin and presqualene diphosphate were exclusively detected in exposed animals, whereas metabolites associated with lipid oxidation and mitochondrial fatty acid β-oxidation were elevated after exposure. RT-qPCR further supported altered expression of genes involved in these pathways. Overall, PS-MPs disrupted hematological homeostasis and metabolic regulation, likely through hepatic lipid peroxidation and systemic inflammation, and serum bilirubin and presqualene diphosphate may serve as candidate biomarkers of exposure. Full article

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16 pages, 17645 KB

Open AccessEditor’s ChoiceArticle

Lime and Fly Ash Co-Solidification Treatment of Oil-Contaminated Soil: Characteristics in Different Water Environments and Evaluation of Engineering Reuse

by Hemiao Yu, Pei Gao, Hui Li and Min Li

Toxics 2026, 14(5), 357; https://doi.org/10.3390/toxics14050357 - 23 Apr 2026

Viewed by 1160

Abstract

Stabilization/solidification (S/S) is a crucial technology for the engineering reuse of oil-contaminated soil. A key challenge, however, is preventing the migration of residual oil under varying hydraulic conditions. This study investigates the efficacy of a lime and fly ash binder in treating oil-contaminated [...] Read more.

Stabilization/solidification (S/S) is a crucial technology for the engineering reuse of oil-contaminated soil. A key challenge, however, is preventing the migration of residual oil under varying hydraulic conditions. This study investigates the efficacy of a lime and fly ash binder in treating oil-contaminated soil. We systematically compared the performance of untreated (UOCS) and treated (TOCS) soils under different aqueous environments (humidity injection, water injection, and permeation). We evaluated oil migration, water-holding capacity, and permeability characteristics. The results demonstrate that the lime–fly ash treatment effectively adsorbed and immobilized oil contaminants, restricting their mobility to a remarkably low range of 0.54% to 4.90%. Furthermore, the S/S treatment significantly improved the soil’s hydraulic properties: it enhanced the water-holding capacity, reduced the soil-water characteristic curve hysteresis, and counteracted the oil-induced hydrophobicity. Consequently, the effective permeation channels were restored, leading to a higher permeability coefficient in TOCS compared to UOCS. Crucially, the hydro-mechanical performance of the treated soil met the criteria of the Solidification/Stabilization Resource Guide, confirming its suitability for engineering applications. Full article

(This article belongs to the Special Issue Environmental Risks, Migration and Remediation of Legacy and Emerging Toxicants)

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26 pages, 1586 KB

Open AccessEditor’s ChoiceArticle

Microbial Biodegradation of Chlorothalonil Residual Pollutants in Soil and Tomato Plants by Microencapsulated Proteus terrae ZQ02

by Sajjad Ahmad, Jie Liu and Murugesan Chandrasekaran

Toxics 2026, 14(5), 352; https://doi.org/10.3390/toxics14050352 - 22 Apr 2026

Viewed by 2308

Abstract

Chlorothalonil is a widely used fungicide in agriculture, but its excessive application can lead to environmental contamination. This study investigated the biodegradation potential of Proteus terrae ZQ02 in free and immobilized forms. Under optimal conditions (37 °C, pH 7), free cells degraded 97.2–98.7% [...] Read more.

Chlorothalonil is a widely used fungicide in agriculture, but its excessive application can lead to environmental contamination. This study investigated the biodegradation potential of Proteus terrae ZQ02 in free and immobilized forms. Under optimal conditions (37 °C, pH 7), free cells degraded 97.2–98.7% of chlorothalonil (50 mg/L) within seven days. Bacterial microcapsules were prepared using 3% sodium alginate, 2% calcium chloride, and 60 g/L wet biomass, with encapsulation times ranging from 6 to 12 h. The microcapsules displayed uniform size, high mechanical strength, porous structure, and excellent mass transfer, ensuring stable degradation activity. Encapsulated cells demonstrate enhanced tolerance to variations in pH, temperature, and salinity compared to free cells. In soil, microcapsules reduced chlorothalonil half-lives to 1.33–5.45 days for concentrations of 10–30 mg/L, achieving 92–96% degradation over 14–35 days. In tomato-planted soils, encapsulated and free cells degraded 96.3% and 81.6% of residues, respectively, after 28 days, significantly exceeding the control. These findings highlight that immobilization improves the stability, reusability, and efficiency of P. terrae ZQ02, making it a promising strategy for sustainable chlorothalonil biodegradation. The study demonstrates the potential of combining microbial strains with carrier materials for effective pesticide remediation and environmental protection, providing a foundation for large-scale applications in contaminated agroecosystems. Full article

(This article belongs to the Special Issue Degradation and Remediation of Environmental Pollutants)

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25 pages, 3184 KB

Open AccessEditor’s ChoiceArticle

Soil–Plant Transfer and Environmental Levels of Potentially Toxic Elements in Agricultural, Urban and Industrial Areas of the València Region (Eastern Spain)

by Eva Fernández-Gómez, Luis Roca-Pérez, Jaume Bech, José Antonio Rodríguez-Martín and Rafael Boluda

Toxics 2026, 14(5), 353; https://doi.org/10.3390/toxics14050353 - 22 Apr 2026

Cited by 1 | Viewed by 1750

Abstract

The evaluation of potentially toxic element concentrations (PTEs) in soils and plants is essential for understanding environmental quality and potential human exposure in areas affected by intense anthropogenic activity. This study addresses a research gap in the Valencian Region, focusing on soil–plant interactions [...] Read more.

The evaluation of potentially toxic element concentrations (PTEs) in soils and plants is essential for understanding environmental quality and potential human exposure in areas affected by intense anthropogenic activity. This study addresses a research gap in the Valencian Region, focusing on soil–plant interactions of PTEs in urban and industrial environments. We assess the status of the soil–plant system in a region of the Valencian Community (eastern Spain) subjected to strong urban, industrial and agricultural pressure. A total of 55 soil samples and 47 plant samples were collected from agricultural, urban and industrial sites and analysed for soil properties, major elements (Al, Mg, Fe) and PTEs (As, Cd, Co, Cr, Cu, Li, Mn, Ni, Sr, V and Zn). Land use significantly influenced soil physicochemical characteristics, with clear differentiation among environments. Soil texture and organic matter were the main factors controlling element retention, while Al, Fe and Mg dominated the geochemical composition, consistent with Mediterranean calcareous soils. Correlation analyses revealed strong co-occurrence patterns among lithogenic elements (e.g., Fe-Al, r = 0.917 p < 0.01), soil texture and chemical properties, indicating a shared origin and preferential retention in the fine fraction and soil organic matter. Contamination indices identified potential environmental risk mainly associated with Cu, Pb, Sr and Zn, particularly in densely populated areas. Mean concentrations of Cd, Cr, Cu, Pb and Zn were, respectively, 0.63 mg kg⁻¹, 42.25 mg kg⁻¹, 31.49 mg kg⁻¹, 56.91 mg kg⁻¹ and 76.08 mg kg⁻¹. These elements exceeded Spanish regulatory reference values in several soils. Bioaccumulation indices indicated notable plant uptake of As, Sr and Zn, highlighting their potential for trophic transfer. Full article

(This article belongs to the Special Issue Heavy Metals and Emerging Contaminants in Aquatic and Soil Environments: Migration, Transformation, Ecological Risks, and Remediation)

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15 pages, 4523 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Co-Exposure to Food-Grade and Nano-TiO₂ with High-Fat Diet Induces Multi-Organ Injury in Liver, Intestine, Brain, and Testicles

by Ying Ma, Nairui Yu, Yi Zhang, Jiaqi Shi, Xinyan Zhou, Xiaojin Li, Li Guan, Guang Jia and Zhangjian Chen

Toxics 2026, 14(4), 350; https://doi.org/10.3390/toxics14040350 - 21 Apr 2026

Viewed by 1316

Abstract

Titanium dioxide nanoparticles (TiO₂ NPs), widely used as food additives, frequently coexist with high-fat diets (HD) in modern dietary patterns, yet their combined in vivo toxicity remains poorly understood. This study investigated the multi-organ effects of co-exposure to TiO₂ NPs or [...] Read more.

Titanium dioxide nanoparticles (TiO₂ NPs), widely used as food additives, frequently coexist with high-fat diets (HD) in modern dietary patterns, yet their combined in vivo toxicity remains poorly understood. This study investigated the multi-organ effects of co-exposure to TiO₂ NPs or food-grade E171 and HD in male C57BL/6J mice. Mice were randomly assigned to six groups and fed regular or high-fat diets containing 1 wt% TiO₂ NPs or E171 for 13 weeks. Histopathology, serum biochemistry, organ coefficients, and open-field behavioral tests were used to assess tissue injury and functional alterations. Co-exposure to TiO₂ NPs and HD markedly exacerbated tissue damage across multiple organs. In the liver, more severe ballooning degeneration, necrosis, and inflammatory infiltration were observed, accompanied by altered liver enzymes and reduced organ coefficients. Intestinal injury was characterized by crypt distortion and increased inflammation, particularly in the HD + TiO₂ group. Testicular tissues showed disorganized seminiferous tubules, loss of spermatogenic cells, and interstitial hyperplasia. In the brain, hippocampal neurons exhibited pyknosis and disarray, with decreased brain coefficients and impaired exploratory behavior. E171 induced similar but milder effects. These findings indicate that HD enhances TiO₂ NPs induced multi-organ toxicity, highlighting the health risks of realistic co-exposure to dietary nanoparticles and high-fat foods. Full article

(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants—2nd Edition)

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17 pages, 679 KB

Open AccessEditor’s ChoiceArticle

The Characteristics of PCDD/F and PCB Occurrence and the Effect of Age in Matched Tissues of Cattle and Sheep from Southern Italy

by Roberta Ceci, Gianfranco Diletti, Giampiero Scortichini, Ettore Franco, Angelo Pellegrino, Iain R. Lake and Alwyn R. Fernandes

Toxics 2026, 14(4), 348; https://doi.org/10.3390/toxics14040348 - 21 Apr 2026

Cited by 1 | Viewed by 839

Abstract

Toxic environmental contaminants, such as polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polychlorinated biphenyls (PCBs) occur differentially in animal tissues. This study examined paired liver and muscle tissues from the same animals, reducing the uncertainty inherent in other studies that source tissues [...] Read more.

Toxic environmental contaminants, such as polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polychlorinated biphenyls (PCBs) occur differentially in animal tissues. This study examined paired liver and muscle tissues from the same animals, reducing the uncertainty inherent in other studies that source tissues from different animals. Investigations were carried out on cattle and sheep from two separate herds in Southern Italy. As all animals experienced the same environmental impacts, husbandry, and feed regimes, contaminant distribution between tissues would result from physiological considerations, which would also allow for better examination of the effects of age. In both investigations, PCDD/F and PCB concentrations were significantly higher (p < 0.01) in the liver relative to muscle. A characteristic occurrence pattern showed PCBs dominating the combined toxic equivalence (TEQ) by >95% in cattle tissues and 78% and 67% in sheep muscle and liver, respectively. A majority of liver samples exceeded regulated maximum limits, and the herds were excluded from the food supply. Subsequent regional monitoring showed regulatory compliance of cattle/sheep meat and liver, but prominence of PCB-TEQ persisted. Concentrations of both contaminants declined strongly in the tissues of both species with increasing age of juveniles but stabilized in older animals (>one year in sheep; 2/3 years in cattle). Although weight gain might partly account for this pattern, the initial decline may also relate to inadequate levels of CYP enzymes in the youngest juveniles, but this would need to be confirmed in both species by targeted toxicokinetic studies during this perinatal period. The expression of these detoxifying enzymes is reported to rise rapidly with increasing postnatal age in many animal species, including sheep. Full article

(This article belongs to the Special Issue Environmental Exposure to Persistent Organic Pollutants: Determination and Implications for Food Safety and Public Health)

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17 pages, 2906 KB

Open AccessEditor’s ChoiceArticle

Assessing the Interactive Effects of Graphene Oxide and Marine Heatwave Stressors on Estuarine Bivalves

by Valéria Giménez, Beatriz Neves, Etelvina Figueira, Paula Marques and Adília Pires

Toxics 2026, 14(4), 339; https://doi.org/10.3390/toxics14040339 - 17 Apr 2026

Cited by 1 | Viewed by 1013

Abstract

Coastal ecosystems are increasingly threatened by climate change, especially the rising frequency of marine heatwaves (MHWs), which often co-occur with emerging nanomaterials such as graphene oxide (GO), whose ecological risks are still being evaluated. While the effects of GO have been studied in [...] Read more.

Coastal ecosystems are increasingly threatened by climate change, especially the rising frequency of marine heatwaves (MHWs), which often co-occur with emerging nanomaterials such as graphene oxide (GO), whose ecological risks are still being evaluated. While the effects of GO have been studied in isolation, little is known about its interaction with thermal stress events. This research studied the combined effects of temperature (18 °C and 23 °C, simulating control and MHW conditions) and GO nanosheets exposure (0.01 mg/L) on two key estuarine bivalves: the clam Scrobicularia plana and the mussel Mytilus galloprovincialis. After 7 days of exposure (duration of many MHWs), energy metabolism, antioxidant defenses, oxidative damage, and neurotransmission were assessed. The results revealed that clams exhibited lower ETS and SOD activity when exposed to MHWs and lower SOD and AChE activities at MHW + GO, compared to the control treatment. Mussels relied primarily on SOD activity across treatments but showed increased susceptibility to GO nanosheets, with higher LPO levels and a significant reduction in AChE activity when exposed to GO at both temperatures. Overall, our findings suggest that S. plana shows a stronger response to the environmental alterations tested than M. galloprovincialis. Combined exposure to GO + MHW triggers species-specific biochemical responses in estuarine bivalves, highlighting how physiological traits shape the assessment of ecological risks posed by nanomaterial pollution under climate change. Full article

(This article belongs to the Special Issue Impact of Pollutants on Aquatic Ecosystems and Food Safety)

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17 pages, 1878 KB

Open AccessEditor’s ChoiceArticle

QSAR Models for Repeated Dose Toxicity in Rats Using the CORAL Software

by Alla P. Toropova, Andrey A. Toropov, Nadia Iovine, Gianluca Selvestrel, Alessandra Roncaglioni and Emilio Benfenati

Toxics 2026, 14(4), 338; https://doi.org/10.3390/toxics14040338 - 17 Apr 2026

Viewed by 1318

Abstract

The evaluation of the safety of chemical substances requires the identification of a safe dose, which has no adverse effects on humans. This is obtained through animal studies, with exposure prolonged for months. Repeated-dose toxicity is a term in toxicology and pharmacology referring [...] Read more.

The evaluation of the safety of chemical substances requires the identification of a safe dose, which has no adverse effects on humans. This is obtained through animal studies, with exposure prolonged for months. Repeated-dose toxicity is a term in toxicology and pharmacology referring to the highest tested dose of a substance, so-called No Observed Adverse Effect Level (NOAEL). Experimental data on NOAEL taken from the literature and the OpenFoodTox database (total n = 848). To speed up the processing of the enormous number of substances we are exposed to, in silico models are an attractive solution. Monte Carlo technique, incorporating the Las Vegas algorithm, was applied to develop models for repeated-dose toxicity in rats. Optimal descriptors were calculated using correlation weights for attributes of the Simplified Molecular Input Line Entry System (SMILES). Computational experiments were conducted 5 times, with splits obtained using the Las Vegas algorithm. Good predictive potential was observed for these models, with an average determination coefficient on the validation set of 0.77 ± 0.04. Full article

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13 pages, 553 KB

Open AccessEditor’s ChoiceArticle

Association Between Exposure to Air Pollutant Mixture and Risk of Inflammatory Bowel Disease: Modifying Effects of Healthy Lifestyle and Residential Greenspace

by Runze Bai, Xiaochi Zhang, Guoao Li, Yiyi Wang, Hujia Zhang, Baopeng Liu, Xiuli Zuo, Jie Yan and Qi Zhao

Toxics 2026, 14(4), 333; https://doi.org/10.3390/toxics14040333 - 16 Apr 2026

Viewed by 890

Abstract

Background: Although air pollution is increasingly considered an environmental hazard for inflammatory bowel disease (IBD), existing evidence predominantly relies on single-pollutant models that fail to capture mixed exposures, with modifying effects of individual lifestyle and residential environments remaining largely unexplored. Methods: We conducted [...] Read more.

Background: Although air pollution is increasingly considered an environmental hazard for inflammatory bowel disease (IBD), existing evidence predominantly relies on single-pollutant models that fail to capture mixed exposures, with modifying effects of individual lifestyle and residential environments remaining largely unexplored. Methods: We conducted a prospective cohort study using UK Biobank data, including 323,608 participants followed for incident IBD. Annual mean concentrations of five air pollutants [nitrogen dioxide (NO₂), nitrogen oxides (NO_x), and PM with aerodynamic diameters of ≤2.5, 2.5–10, and ≤10 μm (PM_2.5, PM_2.5–10, PM₁₀)] and greenspace percentage within 300 m and 1000 m buffers were assigned to each participant’s residential address. A healthy lifestyle score was defined by five factors: smoking status, alcohol consumption, physical activity, sleep patterns, and dietary quality. Cox proportional hazards models with quantile g-computation (QGC) were employed to examine associations between single- and mixed-air-pollutant exposures and IBD risk. Stratified analyses were performed by healthy lifestyle, lifestyle score, and greenspace percentage. Results: During the follow-up period, 1649 and 805 participants developed ulcerative colitis (UC) and Crohn’s disease (CD), respectively. Single-pollutant models suggested that exposures to most air pollutants were substantially associated with increased risk of IBD, and the association strengths were more pronounced for UC than for CD. QGC analyses indicated that the hazard ratios (HR) of IBD risk were 1.068 (95%CI: 1.018–1.121) for each one-quantile increase in the air pollutant mixture, with NO₂ weighted as the largest contributor. High physical activity was significantly linked to an attenuated UC-pollutant mixture association. Conclusions: This study found that exposure to an air pollutant mixture was associated with increased risk of IBD, especially for UC, with NO₂ contributing the largest effect size. The certain attenuated air pollution effects of healthy lifestyles and residential greenspaces underscore the need for integrated public health strategies with environmental management. Full article

(This article belongs to the Special Issue Emerging Pollutants in the Air and Health Risks)

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22 pages, 5076 KB

Open AccessEditor’s ChoiceArticle

Reprogramming of the m⁶A Epitranscriptome Drives Triptolide-Induced Reproductive Toxicity in HTR-8/SVneo Cells

by Xinru Liu, Yunli Wu, Jin Tian, Jiaxin Wen, Yuan Shi, Lili Wang, An Zhu and Zekai Wu

Toxics 2026, 14(4), 334; https://doi.org/10.3390/toxics14040334 - 16 Apr 2026

Viewed by 751

Abstract

Triptolide (TPL), the core active component of the traditional Chinese medicinal herb Tripterygium wilfordii Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the [...] Read more.

Triptolide (TPL), the core active component of the traditional Chinese medicinal herb Tripterygium wilfordii Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the mechanism of which remains poorly understood. Using an integrated analysis of MeRIP-seq and mRNA-seq data, coupled with experimental validation in HTR-8/SVneo cells, we systematically elucidated the molecular mechanism by which TPL induces trophoblast cell injury. Our findings revealed that TPL significantly altered intracellular N⁶-methyladenosine (m⁶A) modification and gene expression profiles, with 1774 genes displaying hypomethylation concurrent with mRNA upregulation. According to the functional enrichment analysis, these genes showed significant enrichment in several key pathways associated with reproduction, including autophagy, DNA damage response, mitochondrial outer membrane, and positive regulation of apoptotic process. Molecular docking further demonstrated direct and stable binding of TPL to key m⁶A regulators, leading to specific demethylation of targets including E2F1 and PPP1CC. This study uncovers a novel post-transcriptional mechanism where TPL disrupts m⁶A modification, thereby perturbing essential trophoblast functions and driving reproductive toxicity. Full article

(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)

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18 pages, 333 KB

Open AccessEditor’s ChoiceReview

Per- and Polyfluoroalkyl Substances in Fish: Global Occurrence, Bioaccumulation, Analytical Approaches, and Human Exposure Risks—A Review

by Ines Varga, Nina Bilandžić, Jelena Kaurinović, Andrea Gross Bošković and Tomislav Klapec

Toxics 2026, 14(4), 336; https://doi.org/10.3390/toxics14040336 - 16 Apr 2026

Cited by 1 | Viewed by 2211

Abstract

Per- and polyfluoroalkyl substances (PFAS) are highly stable and persistent environmental contaminants. Their exceptional chemical stability prevents natural breakdown, leading to global distribution and bioaccumulation in aquatic organisms. Long-chain PFAS, such as perfluorooctane sulfonic acid (PFOS), tend to accumulate in the liver, kidneys, [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are highly stable and persistent environmental contaminants. Their exceptional chemical stability prevents natural breakdown, leading to global distribution and bioaccumulation in aquatic organisms. Long-chain PFAS, such as perfluorooctane sulfonic acid (PFOS), tend to accumulate in the liver, kidneys, and muscle tissues, whereas short-chain PFAS remain largely dissolved in water and show lower accumulation. Freshwater fish generally contain higher PFAS levels than marine fish, with concentrations varying according to species, habitat, trophic level, contamination site, and other factors. Human exposure primarily occurs through the consumption of contaminated fish and seafood, as well as through drinking water, inhalation, and skin contact. Such exposure is associated with immunosuppression, high cholesterol, hormonal disruption, cancer, and other health risks. Regulatory limits exist for four PFAS compounds, while many others, including emerging compounds, remain unregulated. This review synthesizes the current knowledge on the global distribution of PFAS across various fish species, analytical approaches including sample preparation (e.g., SPE, QuEChERS) and instrumental techniques (e.g., LC-MS/MS, HRMS), human dietary exposure, and the related health risks. By integrating environmental distribution, bioaccumulation, analytical challenges, and health issues, this review provides an up-to-date perspective on PFAS in fish and emphasizes the need for ongoing monitoring and stricter regulatory frameworks to ensure food safety and protect both human health and ecosystems. Full article

(This article belongs to the Special Issue Persistent Pollutants and Biotoxins in Aquatic Environments: Ecotoxicological and Human Health Perspectives)

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15 pages, 1744 KB

Open AccessEditor’s ChoiceArticle

Characterisation of PAHs in Outdoor Air Pollution at Schools in a Medium-Sized Town, Hungary

by Bettina Eck-Varanka, Nóra Kováts, Attila Szűcs and Katalin Hubai

Toxics 2026, 14(4), 326; https://doi.org/10.3390/toxics14040326 - 15 Apr 2026

Viewed by 846

Abstract

Atmospheric particulate matter poses a high risk by carrying potentially toxic components such as polycyclic aromatic hydrocarbons (PAHs). The major sources of these potentially toxic compounds include traffic-related emissions and winter heating, implying the combustion of fossil fuels or biomass. Air pollution, especially [...] Read more.

Atmospheric particulate matter poses a high risk by carrying potentially toxic components such as polycyclic aromatic hydrocarbons (PAHs). The major sources of these potentially toxic compounds include traffic-related emissions and winter heating, implying the combustion of fossil fuels or biomass. Air pollution, especially chronic exposure, poses the most serious human health hazard in childhood, and several studies emphasise the importance of research on the potential impacts of air pollution in school environments. While indoor air quality studies are already available in Hungary, investigations on outdoor air pollution in school environments are missing. To fill this gap, in a medium-sized Hungarian town, Veszprém, six schools were selected to assess air quality in the outdoor environments where schoolchildren spend their breaks and have physical training. These schools represent different locations and conditions, from high-trafficked sites to suburban environments. Using resuspended dust samples, environmental quality was assessed based on PAH contents of the samples and ecotoxicity tests (Vibrio fischeri bacterial bioassay). Ecotoxicity of the samples moved in a wide range, from highly toxic to non-toxic. PAH measurements indicated considerable contamination in the case of one sample taken from a suburban area. Source apportionment demonstrated that winter heating is also an important pollution source. Full article

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26 pages, 1092 KB

Open AccessEditor’s ChoiceReview

ABCG2 Genetic Variability in Drug Exposure and Toxicity: Implications for Clinical Practice

by Tamara Božina, Livija Šimičević, Lana Ganoci, Mila Lovrić, Iva Klarica Domjanović, Vladimir Trkulja and Nada Božina

Toxics 2026, 14(4), 327; https://doi.org/10.3390/toxics14040327 - 15 Apr 2026

Cited by 2 | Viewed by 1959

Abstract

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 [...] Read more.

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug–drug–gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy. Full article

(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)

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23 pages, 9961 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Size- and Time-Dependent Impacts of Polyvinyl Chloride Microplastics on Turbot (Scophthalmus maximus L.): Intestinal Tolerance, Hepatic Injury, and Intestinal Microbiota Dysbiosis

by Xiaoyang Yao, Jinzhu Yang, Kangsen Mai and Yanjiao Zhang

Toxics 2026, 14(4), 321; https://doi.org/10.3390/toxics14040321 - 12 Apr 2026

Cited by 1 | Viewed by 1153

Abstract

The present study aimed to investigate the effects of polyvinyl chloride microplastics with different sizes on the growth, intestinal and hepatic health of turbot (Scophthalmus maximus L.) at 3 and 9 weeks of exposure. Three diets were formulated: a control diet with [...] Read more.

The present study aimed to investigate the effects of polyvinyl chloride microplastics with different sizes on the growth, intestinal and hepatic health of turbot (Scophthalmus maximus L.) at 3 and 9 weeks of exposure. Three diets were formulated: a control diet with no microplastics, a diet containing 2% micrometer-sized plastics (MPs), and a diet containing 2% nanoplastics (NPs), with four replicates (40 fish/tank, 12 tanks total). The results showed that MPs and NPs had no significant effects on the growth performance of turbot. Analyses of intestinal histology and gene expression (intestinal barrier-related and antioxidant-related genes) indicated that the turbot intestine exhibited a certain degree of tolerance and adaptability to MPs and NPs exposure. Observations of liver histology and analyses of gene expression (inflammatory cytokines, apoptosis-related, and antioxidant-related genes) revealed that the liver damage induced by microplastics in turbot exhibited obvious size-dependent and time-cumulative effects, with NPs exerting a stronger impact. Compared with MPs, long-term exposure to NPs can induce obvious intestinal microbiota dysbiosis in turbot. In summary, particle size and exposure duration are important factors regulating the impacts of PVC microplastics on the intestinal and hepatic health of turbot. Full article

(This article belongs to the Section Emerging Contaminants)

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21 pages, 7433 KB

Open AccessEditor’s ChoiceArticle

Toxicokinetic-Oriented Assessment of Nepetalactone Using In Silico ADMET Modeling, In Vitro Rat and Human Liver Microsomes, and UHPLC–MS/MS Metabolite Characterization

by Nicolae-Bodgan Stoica, Antonio Cascajosa-Lira, Adriana Morea, Giorgiana M. Catunescu, Ruth Hornedo-Ortega and Remedios Guzmán-Guillén

Toxics 2026, 14(4), 319; https://doi.org/10.3390/toxics14040319 - 12 Apr 2026

Viewed by 1648

Abstract

Nepetalactone (NL) is a volatile iridoid monoterpene widely used in biopesticidal and repellent applications, yet its toxicokinetic behavior and metabolic fate as a pure compound remain poorly characterized. This study aimed to provide an integrated toxicokinetic evaluation of NL by combining in silico [...] Read more.

Nepetalactone (NL) is a volatile iridoid monoterpene widely used in biopesticidal and repellent applications, yet its toxicokinetic behavior and metabolic fate as a pure compound remain poorly characterized. This study aimed to provide an integrated toxicokinetic evaluation of NL by combining in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) modeling with in vitro metabolism assays using rat and human liver microsomes, supported by UHPLC–MS/MS analysis for metabolite identification. The in silico biotransformation predicted extensive phase I oxidation followed by phase II conjugation, while ADMET predictions indicated low systemic persistence and limited toxicological concern for most metabolites. The performed in vitro microsomal assays confirmed the in silico prediction by a rapid and time-dependent NL metabolism via both oxidative (86% reduction in NL concentration after 120 min) and conjugative (89% reduction in NL concentration after 120 min) pathways in rat and human systems, with comparable depletion kinetics between species. UHPLC–MS/MS enabled the identification of multiple phase I and phase II metabolites, pointing to pronounced interspecies differences in conjugative metabolism. In this sense, while oxidoreduction and hydrolysis reactions were consistent with previously reported iridoid metabolism. This study suggests the possible formation of previously unreported amino acid-related derivatives, although these require further confirmation. Overall, these findings advance the understanding of NL biotransformation, propose a new, previously unknown, metabolic pathway for iridoids, and provide relevant data to support human health and environmental risk assessment frameworks. Full article

(This article belongs to the Collection Predictive Toxicology)

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14 pages, 730 KB

Open AccessEditor’s ChoiceArticle

Effects of 52-Day Oral Exposure to Fluorescent Polystyrene Microplastics on Hormonal Profile, Sperm Parameters, and Fertility in Male Wistar Rats

by Hristiyana Kanzova, Madlena Andreeva, Yana Goranova, Rosen Ivanov, Stefan Manchev, Hristo Gagov, Iliyana Sazdova, Milena Mishonova, Neli Raikova, Lea Koceva, Dilyana Doncheva-Stoimenova, Pavel Rashev, Albena Alexandrova and Elina Tsvetanova

Toxics 2026, 14(4), 318; https://doi.org/10.3390/toxics14040318 - 9 Apr 2026

Cited by 5 | Viewed by 1680

Abstract

Increasing environmental contamination with microplastics (MPs) raises significant concerns regarding their potential impact on reproductive health. This study evaluated the effects of prolonged oral exposure to fluorescent polystyrene microplastics (FPS-MPs) of different sizes on the male reproductive system in Wistar rats. Juvenile male [...] Read more.

Increasing environmental contamination with microplastics (MPs) raises significant concerns regarding their potential impact on reproductive health. This study evaluated the effects of prolonged oral exposure to fluorescent polystyrene microplastics (FPS-MPs) of different sizes on the male reproductive system in Wistar rats. Juvenile male rats at 21 days of age were exposed to FPS-MPs of 1 µm and 5 µm for 52 days, covering the period of sexual maturation and a complete spermatogenesis cycle. Body weight, reproductive organ indices, serum levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as sperm motility and morphology, were assessed. Reproductive potential and accumulation of microplastics in reproductive tissues were also evaluated. No significant differences were observed in body weight or most reproductive organ indices, except for a slight reduction in the left epididymis index in the group exposed to 5 µm particles. FPS-MPs induced size-dependent changes in the hormonal profile, including decreases in T and E2 and compensatory increases in FSH and LH, as well as impairments in sperm quality, which were more pronounced in rats exposed to smaller particles. In conclusion, fertility potential remained preserved, while FPS-MPs accumulated in the testes and epididymides, demonstrating subclinical, size-dependent effects on the male reproductive system. Full article

(This article belongs to the Special Issue Multi-Media Exposure to Emerging Contaminants and Health Effects Across Physiological Systems: Exposure Pathways, Risk Assessment and Public Health Implications)

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24 pages, 4284 KB

Open AccessEditor’s ChoiceArticle

Spatial Distribution, Source Apportionment and Risk Assessment of Heavy Metal Pollution in Typical Redevelopment Sites in Pudong New District, Shanghai

by Cheng Shen, Jian Wu and Ye Li

Toxics 2026, 14(4), 315; https://doi.org/10.3390/toxics14040315 - 8 Apr 2026

Cited by 1 | Viewed by 1332

Abstract

To investigate the characteristics and health risks of heavy metal (HM) contamination in soils of typical industrial sites during urban renewal, this study selected Pudong New District, Shanghai, as a case. Seven HMs (Cd, Pb, Cu, Zn, Ni, Hg, and As) were analyzed [...] Read more.

To investigate the characteristics and health risks of heavy metal (HM) contamination in soils of typical industrial sites during urban renewal, this study selected Pudong New District, Shanghai, as a case. Seven HMs (Cd, Pb, Cu, Zn, Ni, Hg, and As) were analyzed for their concentrations, ecological risks, spatial patterns, and potential sources. Inverse Distance Weighted (IDW) interpolation was used to assess spatial distribution, Random Forest (RF) regression to predict HM concentrations, and a two-dimensional Monte Carlo simulation to evaluate human health risks. The results showed that all HMs except As exceeded Shanghai background values in surface soils, with varying levels observed in subsoil and saturated layers. The Index of Geoaccumulation (Igeo) and Risk Index (RI) indicated low contamination and moderate ecological risk. Pearson correlation combined with Positive Matrix Factorization (PMF) identified four major sources: traffic emissions dominated by Cd and Zn, combustion-related sources dominated by Pb and Hg, industry-related inputs dominated by Cu and Ni, and a natural source dominated by As. The RF model demonstrated strong predictive accuracy for Cd, Pb, Hg, and As (R² = 0.80–0.94), and predicted values were consistent with observations. Monte Carlo results showed that non-carcinogenic risks for children and adults were within acceptable limits, while carcinogenic risks reached “notable” levels with probabilities of 62.06%, 55.65%, and 22.49% for children, adult females, and adult males, respectively. Cd and As were identified as key contributors. This work provides scientific support for soil pollution prevention and remediation during urban renewal. Full article

(This article belongs to the Special Issue Fate and Transport of Heavy Metals in Polluted Soils)

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26 pages, 5073 KB

Open AccessEditor’s ChoiceArticle

Differential Effects of Phenanthrene and Its Chlorinated Congeners on Hormone Production and Mitochondrial Function in Ovarian Granulosa Cells

by Genevieve A. Perono, Laiba Jamshed, Rohita Dutt, Reese S. Cameron, James J. Petrik, Philippe J. Thomas and Alison C. Holloway

Toxics 2026, 14(4), 313; https://doi.org/10.3390/toxics14040313 - 7 Apr 2026

Viewed by 1844

Abstract

Halogenated derivatives of polycyclic aromatic hydrocarbons (PAHs), such as chlorinated PAHs (ClPAHs), are an emerging class of contaminants that are being detected in the environment as well as in wildlife and human populations. Previous studies have shown that chemical substitution of PAHs, including [...] Read more.

Halogenated derivatives of polycyclic aromatic hydrocarbons (PAHs), such as chlorinated PAHs (ClPAHs), are an emerging class of contaminants that are being detected in the environment as well as in wildlife and human populations. Previous studies have shown that chemical substitution of PAHs, including chlorination, may alter the toxicity of parent PAHs; however, whether chlorination affects their endocrine-disrupting potential remains unexplored. In this study, we examined the effects of phenanthrene (Phe), one of the most prevalent PAHs, and its chlorinated congeners, 9-chlorophenanthrene (9ClPhe) and 9,10-dichlorophenanthrene (9,10Cl₂Phe), on hormone production in granulosa cells, key hormone-secreting cells of the ovary. We observed that Phe and its chlorinated congeners differentially altered anti-Müllerian hormone (AMH), estradiol (E2), and progesterone (P4) secretion. Since mitochondria are central to steroidogenesis, we further evaluated mitochondrial function. While Phe increased ATP production, both 9ClPhe and 9,10Cl₂Phe increased ROS, decreased mitochondrial membrane potential, and reduced the expression of markers for mitochondrial dynamics and mitophagy without altering ATP levels. We further tested impacts on cell fate and found that neither Phe nor its chlorinated congeners altered granulosa cell apoptosis. Together, these results suggest that chlorination of Phe leads to dose-dependent, differential effects on hormone production and mitochondrial pathways without inducing cell death in granulosa cells. This study highlights the potential adverse impacts of ClPAH exposure on ovarian follicle development and female fertility by disrupting steroidogenesis and mitochondrial quality control. Full article

(This article belongs to the Special Issue Effects and Mechanism of Endocrine Disruption and Reproductive Abnormality of Emerging Pollutant)

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17 pages, 2076 KB

Open AccessEditor’s ChoiceArticle

A Toxicological Assessment of Airborne Microplastics in Beijing

by Susu Fan, Ziyu Guo, Longyi Shao, Pengju Liu, Tim Jones, Yaxin Cao, Wen-Jing Deng, Hong Li and Kelly BéruBé

Toxics 2026, 14(4), 312; https://doi.org/10.3390/toxics14040312 - 7 Apr 2026

Viewed by 1631

Abstract

Microplastics have emerged as a relatively new type of pollutant and have attracted significant global attention. This study focuses on toxicology of microplastics in ambient PM_2.5 and road dustfall in Beijing. It utilizes the Plasmid Scission Assay to toxicologically evaluate the oxidative [...] Read more.

Microplastics have emerged as a relatively new type of pollutant and have attracted significant global attention. This study focuses on toxicology of microplastics in ambient PM_2.5 and road dustfall in Beijing. It utilizes the Plasmid Scission Assay to toxicologically evaluate the oxidative damage capacity of microplastics as a component of PM_2.5. The Pollution Load Index (PLI) method, based on the mass concentration of microplastics in ambient air, was employed to assess the ecological risk of atmospheric dustfall microplastics in Beijing. The results showed that both standard microplastic samples and mixed samples of microplastics with ambient PM_2.5 exhibited a dose–response relationship in DNA damage rates. At the same dose, microplastic samples with smaller particle sizes have a higher DNA damage rate. Based on the PLI results, most road dustfall microplastics in Beijing exhibit significant spatial variation. Analysis of road dustfall along the east–west main road across Beijing’s urban area revealed that microplastic pollution levels are higher in the eastern zone than in the western zone. Comparisons of pollution levels across functional areas in Beijing showed that university areas > residential areas > industrial areas > commercial areas > agricultural areas. In vertically collected samples, higher elevations (PLI_13.6m = 3.54) exhibit greater pollution levels than lower (PLI_1.5m = 1), which warrants special attention. These findings highlight the complex relationship between atmospheric microplastic accumulation and their oxidative capacity, providing essential insights for the design of targeted emission reduction strategies. Full article

(This article belongs to the Special Issue Insights into Toxicological Effects of Micro- and Nano-Plastics)

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21 pages, 370 KB

Open AccessEditor’s ChoiceArticle

The Energy–Quality Nexus in Atmospheric Water Generation: A Review of Contaminants, Performance Metrics, and the Proposal of the AWEQI

by Lucia Cattani, Paolo Cattani and Anna Magrini

Toxics 2026, 14(4), 310; https://doi.org/10.3390/toxics14040310 - 3 Apr 2026

Cited by 2 | Viewed by 2252

Abstract

Atmospheric water (AW) is currently recognized as a promising solution to mitigate the global water crisis. Nevertheless, its harvesting techniques should balance three main aspects: energy consumption, yield, and the quality of produced water. Water quality is of the utmost importance, because the [...] Read more.

Atmospheric water (AW) is currently recognized as a promising solution to mitigate the global water crisis. Nevertheless, its harvesting techniques should balance three main aspects: energy consumption, yield, and the quality of produced water. Water quality is of the utmost importance, because the potential uses of atmospheric water—and therefore its value—ultimately depend on this characteristic. Currently, existing indices and indicators intended as evaluation tools for different harvesting techniques generally focus on the first two aspects only, overlooking the quality perspective, with the risk of overestimating the performance of systems that require less energy but provide low-quality water. This study fills this knowledge gap by proposing a new evaluation tool, the Atmospheric Water Energy–Quality Index (AWEQI). This index links the energy evaluation of an Atmospheric Water Generator (AWG)—a term referring to all active, passive, or hybrid systems for atmospheric water collection—to the quality of the produced water. The index is constructed through an appropriate reformulation and combination of the Water Energy Transformation (WET) indicator and the Water Quality Index (WQI) to obtain a monotonic function whose values increase with improved performance, both in terms of energy efficiency and water quality. Moreover, based on a literature review, the study presents an analysis of potential AW contaminants and their sources, and proposes two parameter sets to be considered in the WQI calculation. Full article

(This article belongs to the Topic Sustainable Environmental Technologies—2nd Edition)

19 pages, 3189 KB

Open AccessEditor’s ChoiceArticle

Ecotoxicity of Combined Polylactic Acid Microplastics and Thallium Pollution on the Functional Traits of Folsomia candida

by Yuying Chen, Guoliang Xu, Zhijian Wu, Cao Hao, Chen Yang and Xiaohua Chen

Toxics 2026, 14(4), 307; https://doi.org/10.3390/toxics14040307 - 2 Apr 2026

Viewed by 1962

Abstract

Microplastics can bind with toxic metals via surface complexation and chelation, forming combined pollutants. However, research regarding the toxicological impacts of these combined pollutants on soil fauna remains limited. This study employed Folsomia candida in a 28-day incubation experiment to investigate the ecotoxicological [...] Read more.

Microplastics can bind with toxic metals via surface complexation and chelation, forming combined pollutants. However, research regarding the toxicological impacts of these combined pollutants on soil fauna remains limited. This study employed Folsomia candida in a 28-day incubation experiment to investigate the ecotoxicological effects of combined pollution by polylactic acid microplastics (PLA-MPs) and thallium (Tl) on the functional traits of Folsomia candida, including biology, morphology, and gut microbiota. The results showed that the combined effects of PLA-MPs and Tl on these functional traits were characterized by amplified toxicity and trait-specific responses. Morphological traits exhibited lower sensitivity to the pollution treatments compared to other indicators. Exposure to high-concentration PLA-MPs (10%) significantly affected mortality and fecundity, and reduced gut bacterial diversity. Conversely, low-concentration Tl (1 mg/kg) significantly inhibited body length and antenna length while increasing gut bacterial diversity. Structured equation modeling further revealed that the pollution treatments exerted significant negative effects on the functional traits of Folsomia candida, both directly and indirectly by altering soil properties and soil microbiota. These findings provide valuable insights into the ecotoxicological effects of combined PLA-MPs and Tl pollution on soil fauna, contributing to ecological health risk assessments of microplastics and toxic metals in terrestrial ecosystems. Full article

(This article belongs to the Section Ecotoxicology)

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27 pages, 8144 KB

Open AccessEditor’s ChoiceArticle

Occurrence of Potentially Toxic Elements (PTEs) Coupled with Mineralogical and Morphological Characteristics of Residential Indoor Vacuum Dusts from the City of Thessaloniki, Northern Greece

by Christina Kotsakostoudi, Anna Bourliva, Lambrini Papadopoulou and Nikolaos Kantiranis

Toxics 2026, 14(4), 306; https://doi.org/10.3390/toxics14040306 - 31 Mar 2026

Viewed by 3391

Abstract

This study investigates the occurrence, sources, and health risks of PTEs in residential vacuum dusts from the city of Thessaloniki, Greece. A total of 20 dust samples were collected and analyzed for their chemical, mineralogical, and morphological characteristics using pXRF, XRD, and SEM-EDS [...] Read more.

This study investigates the occurrence, sources, and health risks of PTEs in residential vacuum dusts from the city of Thessaloniki, Greece. A total of 20 dust samples were collected and analyzed for their chemical, mineralogical, and morphological characteristics using pXRF, XRD, and SEM-EDS techniques. The results revealed elevated concentrations of Zn (623 mg kg⁻¹), Mn (392 mg kg⁻¹), Cu (204 mg kg⁻¹), and Cr (185 mg kg⁻¹) exceeding crustal averages and global urban soil baselines. Notably, Cr and Mn levels were among the highest recorded for non-industrial urban settings. Source apportionment identified distinct geogenic and anthropogenic contributors, including construction materials, outdoor soil resuspension, and indoor alloy-related sources such as stainless steel and soldering components. Health risk assessment based on USEPA models showed ingestion as the dominant exposure route, particularly for children. Chromium and As were identified as the main non-carcinogenic and carcinogenic contributors, with children’s hazard index (HI) values exceeding safety thresholds (HI = 1.04) in some cases. The cancer risk (CR) for Cr ranged from 2.49 × 10⁻⁵ to 6.55 × 10^−5, not exceeding the acceptable limit (10⁻⁴). The findings highlight the multifaceted nature of indoor dust contamination in urban environments and underscore the need for continued monitoring and targeted mitigation to protect vulnerable populations. Full article

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24 pages, 2957 KB

Open AccessEditor’s ChoiceReview

Microplastics in Natural Waters: Occurrence, Risks and Mitigation Strategies

by Shuwen Zheng, Zhenyu Zhai, Zheming Zhang, Jianxiong Xiang, Jingsi Chen, Zhuorong Du and Xiaoyan Qian

Toxics 2026, 14(4), 296; https://doi.org/10.3390/toxics14040296 - 29 Mar 2026

Cited by 1 | Viewed by 2277

Abstract

Microplastics have become a ubiquitous environmental contaminant in natural waters, raising significant concerns regarding aquatic ecosystem health and potential human exposure. A comprehensive synthesis of current knowledge on microplastic pollution in freshwater and marine systems is presented, focusing on sources, distribution patterns, environmental [...] Read more.

Microplastics have become a ubiquitous environmental contaminant in natural waters, raising significant concerns regarding aquatic ecosystem health and potential human exposure. A comprehensive synthesis of current knowledge on microplastic pollution in freshwater and marine systems is presented, focusing on sources, distribution patterns, environmental behavior, and associated risks. In freshwater environments, microplastic inputs are closely linked to human activities and land use, with wastewater treatment plant effluent, urban runoff, and agricultural drainage serving as major pathways. In marine systems, microplastics undergo dynamic transport influenced by particle properties, hydrodynamic conditions, and biological interactions such as biofouling and aggregation, leading to widespread distribution from coastal zones to deep sea sediments. Importantly, the role of the freshwater–estuarine–marine continuum is emphasized, highlighting the coupled processes of transport, retention, and remobilisation that govern the spatiotemporal distribution and ultimate fate of microplastics across interconnected aquatic systems. Toxicological effects on aquatic organisms are further examined, particularly immunotoxicity and neurotoxicity, alongside potential human health risks via ingestion, inhalation, and dermal exposure. Attention is drawn to the discrepancy between experimental exposure conditions and environmentally relevant concentrations, which constrains robust risk assessment. Current mitigation strategies, including source reduction, wastewater treatment upgrades, transport interception, and degradation technologies, are critically evaluated in terms of effectiveness and limitations. A clear distinction is made between apparent removal and actual degradation, with further consideration of the environmental implications associated with sludge retention and degradation byproducts. Finally, key research priorities are identified, including the need for standardized detection methods, improved exposure assessment, development of environmentally benign alternatives, and strengthened policy-driven source control. These insights provide a basis for advancing sustainable management strategies for microplastic pollution in natural waters. Full article

(This article belongs to the Section Emerging Contaminants)

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15 pages, 19871 KB

Open AccessEditor’s ChoiceCase Report

Fatal Intoxication of European Yew (Taxus baccata L.) in Two Donkeys in North-Eastern Italy: A Case Report

by Luca Spadotto, Silva Rubini, Laura Cornara, Federica Betuzzi, Mariarosaria Ingegneri, Antonella Smeriglio, Domenico Trombetta, Cinzia Centelleghe and Sandro Mazzariol

Toxics 2026, 14(4), 294; https://doi.org/10.3390/toxics14040294 - 28 Mar 2026

Viewed by 1767

Abstract

Poisoning caused by Taxus baccata is a well-known cause of sudden death in domestic animals due to the cardiotoxic effects of taxine alkaloids. This study describes two cases of fatal intoxication in donkeys (Equus africanus asinus) and demonstrates a multidisciplinary diagnostic [...] Read more.

Poisoning caused by Taxus baccata is a well-known cause of sudden death in domestic animals due to the cardiotoxic effects of taxine alkaloids. This study describes two cases of fatal intoxication in donkeys (Equus africanus asinus) and demonstrates a multidisciplinary diagnostic approach combining pathology, botanical identification, and toxicology. Two animals were found dead without prior clinical signs on a farm in north-eastern Italy. Necropsies were performed, and samples were collected for further investigations. Histopathological findings were limited and non-specific, consistent with the hyperacute course typical of yew poisoning. Fragments of plant material resembling yew needles and twigs were identified in the gastric contents. Toxicological analysis using liquid chromatography–electrospray ionization mass spectrometry confirmed the presence of taxane alkaloids, supporting the diagnosis of yew poisoning. These data highlight the importance of integrating necropsy results with botanical examination and targeted toxicological analyses in cases of suspected plant poisoning. This multidisciplinary approach provides a reliable diagnostic framework for confirming yew poisoning in veterinary investigations. Full article

(This article belongs to the Special Issue Perspectives in Veterinary Toxicology and One Health)

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16 pages, 1289 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Common Carp Kidney as a Multipurpose Biomarker Organ: Insights from Perfluorooctanoic Acid Exposure

by Maurizio Manera, Cosma Manera and Luisa Giari

Toxics 2026, 14(4), 287; https://doi.org/10.3390/toxics14040287 - 28 Mar 2026

Cited by 1 | Viewed by 1698

Abstract

The common carp (Cyprinus carpio) kidney uniquely integrates excretory nephrons, renal hematopoietic tissue, and hormonally active thyroid follicles, positioning it as a candidate “multipurpose biomarker organ” for pollutants like perfluorooctanoic acid (PFOA), a prototype long-chain PFAS and persistent organic pollutant exhibiting [...] Read more.

The common carp (Cyprinus carpio) kidney uniquely integrates excretory nephrons, renal hematopoietic tissue, and hormonally active thyroid follicles, positioning it as a candidate “multipurpose biomarker organ” for pollutants like perfluorooctanoic acid (PFOA), a prototype long-chain PFAS and persistent organic pollutant exhibiting nephrotoxic, immunotoxic, and thyroid-disrupting effects. Building on prior histological, ultrastructural, and morphometric analyses from carp exposed to waterborne PFOA (0, 200 ng L⁻¹, 2 mg L⁻¹ for 56 days), a hierarchical multipurpose index comprising nephrotoxic, immunotoxic, and thyrotoxic subindices was developed from z-scored light-, electron-microscopy, and morphometric features, enabling cross-scale integration; proximal tubule vesiculations and effete rodlet cells (RCs) were newly quantified from archival electron micrographs. The subindices captured PFOA-induced glomerular hyperfiltration with proximal protein reabsorption and collecting duct RCs recruitment (nephrotoxic); hematopoietic tissue RCs recruitment, clustering, and exocytosis (immunotoxic); and increased thyroid follicle abundance/vesiculation, cross-sectional area, and perimeter (thyrotoxic). Quantification of previously only qualitatively assessed features provided statistical validation, while radar plot integration rendered results more intuitively evident—particularly highlighting the non-monotonic thyroid response—condensing organ-level complexity into a coherent framework supporting carp kidney as a translational One Health model for multi-endpoint waterborne pollutant assessment. Full article

(This article belongs to the Special Issue Per- and Polyfluoroalkyl Substances: Ecological Impacts and Human Health Risks)

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16 pages, 3098 KB

Open AccessEditor’s ChoiceArticle

A High-Throughput, High-Content Analysis of Dopaminergic Neurodegeneration in Caenorhabditis elegans Exposed to Per- and Polyfluoroalkyl Substances

by David Benson, Seth Currie, Jia-Sheng Wang and Lili Tang

Toxics 2026, 14(4), 278; https://doi.org/10.3390/toxics14040278 - 26 Mar 2026

Viewed by 1726

Abstract

Dopaminergic neurodegeneration is a hallmark of Parkinson’s disease (PD), and environmental contaminants have been implicated in disrupting dopaminergic pathways. However, practical in vivo workflows for rapid, standardized, and accessible assessment of dopaminergic neurotoxicity remain limited. In this study, we built on our laboratory’s [...] Read more.

Dopaminergic neurodegeneration is a hallmark of Parkinson’s disease (PD), and environmental contaminants have been implicated in disrupting dopaminergic pathways. However, practical in vivo workflows for rapid, standardized, and accessible assessment of dopaminergic neurotoxicity remain limited. In this study, we built on our laboratory’s established high-throughput framework and implemented a high-content imaging workflow to quantify DA neurodegeneration in Caenorhabditis elegans following exposure to representative per- and polyfluoroalkyl substances (PFAS). We evaluated the neurotoxic effects of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorohexanoic acid (PFHxA), and three PFAS mixtures with environmentally relevant component ratios. Functional relevance was assessed using dopamine-dependent behavioral endpoints, including basal slowing response (BSR) and area-restricted search (ARS). PFOS exhibited the greatest potency, followed by PFHxS, PFHxA, and PFOA, based on morphological degeneration and benchmark concentration modeling. Structural neuronal damage was significantly associated with behavioral impairment. Under mixture conditions, neurotoxicity was more strongly associated with PFOS molar fraction than with total PFAS concentration (ΣPFAS), suggesting a composition-dependent toxicity profile. Collectively, these findings establish a scalable in vivo framework for assessing PFAS-induced dopaminergic neurotoxicity and support the potential use of this platform for screening environmental pollutants with dopaminergic neurotoxic potential. Full article

(This article belongs to the Special Issue Caenorhabditis elegans as a Test Model in Environmental Toxicology)

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21 pages, 765 KB

Open AccessEditor’s ChoiceCase Report

Fatal Outcome Following Polysubstance Use: A Case Report of Rhabdomyolysis, Acute Kidney Injury, and Deep Vein Thrombosis

by Stanila Stoeva-Grigorova, Ivanesa Yarabanova, Ivelina Panayotova, Maya Radeva-Ilieva, Georgi Bonchev, Milan Tsekov, Delyan Ivanov, Mario Milkov, Simeon Marinov, Petko Marinov and Snezha Zlateva

Toxics 2026, 14(4), 273; https://doi.org/10.3390/toxics14040273 - 25 Mar 2026

Cited by 1 | Viewed by 3540

Abstract

Background: Polysubstance use, particularly the combination of opioids and stimulants, represents a growing public health concern due to its high risk of severe multisystem complications and mortality. Here, we present a case illustrating the lethal synergy of opioid–stimulant co-use. Methods: A 37-year-old male [...] Read more.

Background: Polysubstance use, particularly the combination of opioids and stimulants, represents a growing public health concern due to its high risk of severe multisystem complications and mortality. Here, we present a case illustrating the lethal synergy of opioid–stimulant co-use. Methods: A 37-year-old male with chronic Hepatitis C and documented polysubstance use reported recent use of fentanyl, cocaine, methamphetamine, and cannabis. He presented with generalized weakness, left lower limb pain, tense edema, and anuria. Clinical assessment included monitoring of vital signs, physical examination, capillary blood gas analysis, extended laboratory panels (muscle and cardiac enzymes, electrolytes, and coagulation parameters), urinalysis, and Doppler imaging. Management over five days included intravenous hydration, diuretics, urinary alkalinization, electrolyte correction, anticoagulation, metabolic and vitamin therapy, hemodialysis, and comprehensive supportive care. Results: Laboratory evaluation revealed massive rhabdomyolysis (peak CK 161,050 U/L), severe hyperkalemia (K⁺ 8.4 mmol/L), metabolic acidosis, acute kidney injury with oligoanuria, and left-sided deep vein thrombosis. Despite intensive multidisciplinary interventions, the patient’s repeated refusal of ongoing treatment critically contributed to a fatal outcome. Conclusions: This case underscores the high mortality risk associated with opioid–stimulant co-use and the crucial impact of treatment refusal. Clinicians and public health stakeholders should recognize the rapid progression of multisystem dysfunction in polysubstance users and prioritize early, aggressive interventions combined with patient engagement strategies to mitigate fatal outcomes. Full article

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18 pages, 2574 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Inhalation Exposure to 2,4-Dichlorophenoxyacetic Acid Causes Tracheal Damage—A Study in Rats

by Anna Carolina Ferretti Wisenfad, Isabela Vieira Duran, Luciana Shiraichi Barga and Gisele Alborghetti Nai

Toxics 2026, 14(4), 271; https://doi.org/10.3390/toxics14040271 - 24 Mar 2026

Viewed by 2167

Abstract

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) occurs mainly by inhalation. Studies indicate that respiratory allergic reactions are induced by this pesticide. This study analyzed the effects of chronic inhalation exposure to 2,4-D in the trachea of rats. We exposed the animals during six months [...] Read more.

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) occurs mainly by inhalation. Studies indicate that respiratory allergic reactions are induced by this pesticide. This study analyzed the effects of chronic inhalation exposure to 2,4-D in the trachea of rats. We exposed the animals during six months to three different concentrations of 2,4-D used for crop spraying. Animals exposed to low concentrations had an increase in the mast cells count, showing that this herbicide can cause allergic reactions in the airways. The tracheal epithelium thickness, the nuclear area and number of nucleolar organizing regions increased proportionally to the exposure concentration and in correlation with each other. These histological tissue changes correspond to epithelial hypertrophy and increased cell activity and multiplication, and show an adaptation to tissue damage caused by 2,4-D. There was a tendency for inversion in the mucus pattern to acid and a decrease in goblet cells in the groups exposed to 2,4-D, which alters the protective mechanisms of the respiratory tract. The 2,4-D induced adaptations in the tracheal epithelium associated with an increase in herbicide concentrations, which may compromise mucociliary function and predispose the epithelium to additional lesions over time. Therefore, it should be used with appropriate respiratory protection equipment to avoid injury. Full article

(This article belongs to the Section Agrochemicals and Food Toxicology)

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29 pages, 1203 KB

Open AccessEditor’s ChoiceArticle

Ba–Sr–V as Geogenic and Traffic Tracers in Paediatric Hair from Urban–Industrial Spain, with Co-Located Topsoil Vanadium

by Antonio Peña-Fernández, Roberto Valiente, Manuel Higueras, Rafael Moreno-Gómez-Toledano and M. Carmen Lobo-Bedmar

Toxics 2026, 14(3), 268; https://doi.org/10.3390/toxics14030268 - 19 Mar 2026

Cited by 2 | Viewed by 2146

Abstract

Urban–industrial environments can generate mixed geogenic and traffic-related metal signatures in paediatric scalp hair, yet interpretation is challenged by left-censoring and limited health-based guidance values for hair. We quantified barium (Ba), strontium (Sr) and vanadium (V) in archived scalp hair collected in 2001 [...] Read more.

Urban–industrial environments can generate mixed geogenic and traffic-related metal signatures in paediatric scalp hair, yet interpretation is challenged by left-censoring and limited health-based guidance values for hair. We quantified barium (Ba), strontium (Sr) and vanadium (V) in archived scalp hair collected in 2001 from children (6–9 years, n = 120) and adolescents (13–16 years, n = 97) residing in Alcalá de Henares (central Spain). Samples were washed, digested and quantified by Inductively coupled plasma mass spectrometry (ICP–MS; laboratory processing in 2025); results below the limit of detection (LoD) were treated as left-censored using NADA2 (no substitution). In children, Ba and Sr were frequently quantifiable (medians 0.193 and 0.412 µg/g; 38.3% and 23.3% <LoD), whereas V was heavily censored (74.2% <LoD; median 0.003 µg/g). Adolescents showed higher Ba and Sr and broader upper tails (Ba median 0.287 µg/g, P95 2.061 µg/g; Sr median 1.105 µg/g, P95 4.995 µg/g), while V remained low (median 0.011 µg/g, P95 0.052 µg/g). Ba and Sr displayed strong spatial gradients across four residential zones in adolescents (censored-data Peto–Peto tests p < 1 × 10⁻⁸), but V did not (p = 0.162). Co-located residential topsoils were available only for V and showed limited between-zone contrast; soil–hair correspondence was weak overall but moderate in adolescent girls (Spearman ρ = 0.433). These findings provide a historical baseline and support a cautious tracer-oriented interpretation in which the observed Ba–Sr spatial patterning is consistent with heterogeneous contact with dust- and traffic-influenced surface materials, while V appears less discriminatory in low-contrast community settings. Full article

(This article belongs to the Special Issue Occupational Exposure to Heavy Metals in Environmentally Vulnerable Areas)

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20 pages, 3661 KB

Open AccessEditor’s ChoiceArticle

PCB Exposure in Adult Male Mice Reduces Proliferating Cells in the Prostate but Minimally Alters Voiding

by Kathy Wang, Audrey Spiegelhoff, Tamryn Jordan, Thomas Lavery, Conner L. Kennedy, Monica M. Ridlon and Kimberly P. Keil Stietz

Toxics 2026, 14(3), 265; https://doi.org/10.3390/toxics14030265 - 18 Mar 2026

Cited by 1 | Viewed by 1107

Abstract

Lower urinary tract dysfunction (LUTD) is a multifactorial disease process that encompasses diverse symptoms ranging from issues with storage and sensation to impaired emptying of the bladder. Furthermore, symptoms tend to worsen with age and other comorbidities and in men can also be [...] Read more.

Lower urinary tract dysfunction (LUTD) is a multifactorial disease process that encompasses diverse symptoms ranging from issues with storage and sensation to impaired emptying of the bladder. Furthermore, symptoms tend to worsen with age and other comorbidities and in men can also be influenced by changes to the prostate, making diagnosis and treatment difficult to manage. Environmental factors are thought to contribute to disease risk. In mice, previous work has found that developmental exposure to polychlorinated biphenyls (PCBs) is capable of altering voiding function in offspring. However, the effects of PCB exposure in adulthood instead of development are not well known. Whether changes in voiding are a consequence of early or later life exposures remains an important area of study, as environmental chemicals and exposures can occur across the lifespan and can be mitigated. Here, we test whether PCB exposure in adulthood alters voiding or prostate morphology in male mice. C57Bl/6J adult male mice were exposed to the human-relevant MARBLES PCB mixture (0, 0.1, 1, and 6 mg/kg/d) orally daily for two months. Lower urinary tract function was then assessed through urodynamic testing including void spot assay, uroflowmetry, and anesthetized cystometry. Prostate lobes were collected for histology. The only change to voiding function was a reduction in void duration in the 6 versus 1 mg/kg/d PCB group but not to the vehicle control. Prostate, seminal vesicle, and testes wet weights were unchanged. However, PCB exposure reduced the number of Ki67-positive proliferating cells in the anterior and ventral prostate lobes only at the 1 mg/kg/d dose, with no change to caspase 3-positive cells or smooth muscle thickness. Together, these data indicate that 2-month exposure to PCBs in adult mice has little impact on voiding but is a sufficient exposure to produce changes in cell proliferation in the prostate. The mechanistic impacts of these changes remains to be investigated but could help better understand individual risk for LUTD. Full article

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20 pages, 3020 KB

Open AccessEditor’s ChoiceArticle

Dual Fluorescence–Lipid Endpoints Resolve Species- and Metal-Specific Toxicity Patterns in Marine Diatoms

by Hojun Lee, Taejun Han and Jihae Park

Toxics 2026, 14(3), 267; https://doi.org/10.3390/toxics14030267 - 18 Mar 2026

Viewed by 1577

Abstract

Trace metals are persistent stressors in coastal ecosystems, yet most marine algal toxicity assessments still rely on freshwater model species and growth-based endpoints that provide limited mechanistic resolution. Here, we quantified the sensitivity of two ecologically contrasting marine diatoms—the benthic Cylindrotheca closterium and [...] Read more.

Trace metals are persistent stressors in coastal ecosystems, yet most marine algal toxicity assessments still rely on freshwater model species and growth-based endpoints that provide limited mechanistic resolution. Here, we quantified the sensitivity of two ecologically contrasting marine diatoms—the benthic Cylindrotheca closterium and the planktonic Thalassiosira weissflogii—to ten environmentally relevant metals using a dual-endpoint approach that integrates chlorophyll fluorescence (photosystem function) and Nile Red-based lipid-body fluorescence (metabolic reallocation). Fluorescence-based EC₁₀ values revealed distinct species- and metal-specific patterns, with C. closterium consistently responding at lower concentrations and Hg producing the strongest inhibition in both species (EC₁₀ ≈ 0.04–0.06 mg L⁻¹). Lipid-body accumulation detected earlier metabolic disturbance for several metals, particularly Hg, As, Cr(VI), and Cd, and frequently occurred at concentrations where fluorescence remained minimally affected. These sequential thresholds indicate that pigment impairment and metabolic reallocation represent mechanistically distinct stages of the cellular stress response that differ among metals and between diatom guilds. Comparison with published toxicity data shows that the dual-endpoint sensitivities observed here fall within, or slightly above, the upper range of reported microalgal responses, underscoring the pronounced susceptibility of benthic diatoms to redox-active and thiol-reactive metals. The strong agreement between fluorescence-based EC values and traditional growth-derived benchmarks for key metals further supports fluorescence as an operationally efficient endpoint suitable for integration into emerging ISO marine algal bioassays. Overall, this study demonstrates that pairing a rapid functional marker with a mechanistically informative metabolic biomarker enables metal-specific toxicity fingerprinting and provides an ecologically grounded basis for incorporating benthic diatoms into coastal metal risk assessment frameworks. Full article

(This article belongs to the Section Ecotoxicology)

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20 pages, 2148 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Evaluating Toxicity and Anti-Osteogenic Activity of Artemisinin-Inspired Endoperoxides in Zebrafish Larvae

by Yaryna S. Buzan, Gil Martins, Bruno M. S. Ferreira, Inês C. C. Costa, Maria L. S. Cristiano and Paulo J. Gavaia

Toxics 2026, 14(3), 261; https://doi.org/10.3390/toxics14030261 - 17 Mar 2026

Cited by 1 | Viewed by 1090

Abstract

Endoperoxide-containing molecules based on the antimalarial drug artemisinin have demonstrated various biological properties, including modulation of calcium homeostasis. This study evaluated the toxicity and osteogenic activity of five newly developed tetraoxanes (YB1, YB9, YB11, YB17 and T2), alongside three of their non-peroxidic analogues [...] Read more.

Endoperoxide-containing molecules based on the antimalarial drug artemisinin have demonstrated various biological properties, including modulation of calcium homeostasis. This study evaluated the toxicity and osteogenic activity of five newly developed tetraoxanes (YB1, YB9, YB11, YB17 and T2), alongside three of their non-peroxidic analogues (IC22, IC26 and IC33), in zebrafish (Danio rerio) larvae. For each compound, LC₅₀ values were first determined. Behavioural responses and morphological alterations were studied as indicators of toxicological impact. The osteogenic activity was assessed through the operculum assay, followed by the analysis of gene expression markers related to calcium homeostasis (atp2a1), oxidative stress (sod1, cat), and osteogenesis (sp7, oc2). All the compounds evaluated induced an inhibition of osteogenic activity. T2, YB11, IC33 and IC26 affected the locomotor function by decreasing swimming activity. IC26 and IC33 induced morphological toxicity, characterized by a curved trunk and alterations in larval body curvature. From all the compounds studied, YB1, YB9, YB17 and IC22 showed selective anti-osteogenic activity, without displaying significant behavioural or morphological toxicity. In conclusion, the presence of a peroxide bond in the molecular structure of the compounds increases the anti-osteogenic activity at lower concentrations. All evaluated compounds exhibited anti-osteogenic activity and can be regarded as anti-osteogenic agents. However, YB17 did not induce transcription alterations in the genes analyzed and may thus represent the most promising compound in conditions where a controlled inhibition of bone formation is desirable. Full article

(This article belongs to the Special Issue Toxicological Studies Using Zebrafish Models)

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