Toxics

20 pages, 1975 KB

Open AccessEditor’s ChoiceArticle

Nationwide Monitoring and Hepatic Mixture Risk Assessment of PFASs in Korean Drinking Water Using Relative Potency Factors

by Yubeen Kim, Shervin Hashemi, Heesoo Pyo, Youngwook Lim, Changsoo Kim, Incheol Choi and Jiyeon Yang

Toxics 2026, 14(7), 577; https://doi.org/10.3390/toxics14070577 - 30 Jun 2026

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Abstract

This study evaluated the reliability and application of relative potency factors (RPFs) for assessing hepatic mixture risks of per- and polyfluoroalkyl substances (PFASs) in Korean finished drinking water. A total of 1254 finished water samples collected from 70 drinking water treatment plants between [...] Read more.

This study evaluated the reliability and application of relative potency factors (RPFs) for assessing hepatic mixture risks of per- and polyfluoroalkyl substances (PFASs) in Korean finished drinking water. A total of 1254 finished water samples collected from 70 drinking water treatment plants between 2018 and 2024 were analyzed for eight PFAS compounds. Hepatic RPFs proposed by the National Institute for Public Health and the Environment (RIVM) were assessed using a structured scoring system and applied to estimate PFOA-equivalent mixture risks. Hazard quotients (HQs) based on hepatic toxicity reference doses were also calculated for comparison. PFAS concentrations generally declined over time, including PFOA from 0.0032 to 0.0014 μg/L, PFOS from 0.0008 to 0.0003 μg/L, and PFHxS from 0.0072 to 0.0004 μg/L between 2018 and 2024. The RPF-based method produced higher cumulative risk estimates than the individual toxicity-based approach, suggesting that single-compound HQs may underestimate risks from co-occurring PFASs. Although total risks were generally below the non-carcinogenic threshold of 1.0, the 95th percentile PFOA-equivalent risk for PFNA exceeded the individual threshold of 0.1. These findings support endpoint-specific RPF-based assessment for PFAS mixtures in drinking water. Full article

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

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23 pages, 1863 KB

Open AccessEditor’s ChoiceSystematic Review

Mechanistic Evidence Mapping Ochratoxin A Toxicity onto Alzheimer’s Disease-Relevant Neurodegenerative Pathways: A Systematic Review of Experimental Models

by Raquel Penalva-Olcina, Felipe Franco-Campos, Mercedes Taroncher, María-José Ruiz and Mónica Fernández-Franzón

Toxics 2026, 14(7), 549; https://doi.org/10.3390/toxics14070549 - 24 Jun 2026

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Abstract

Ochratoxin A (OTA) is a prevalent foodborne mycotoxin that has been increasingly recognized as a potential environmental contributor to neurodegenerative diseases. Despite extensive research, a systematic integration of how OTA replicates the specific pathological hallmarks of Alzheimer’s Disease (AD) is currently lacking. This [...] Read more.

Ochratoxin A (OTA) is a prevalent foodborne mycotoxin that has been increasingly recognized as a potential environmental contributor to neurodegenerative diseases. Despite extensive research, a systematic integration of how OTA replicates the specific pathological hallmarks of Alzheimer’s Disease (AD) is currently lacking. This study provides a comprehensive systematic review of the mechanistic evidence linking OTA exposure to AD-related pathways, utilizing the Adverse Outcome Pathway (AOP) framework to categorize complex toxicological data into biological key events (KEs). A systematic literature search was conducted across PubMed, Scopus, and Web of Science. A total of 24 peer-reviewed articles were selected for synthesis, comprising 14 in vitro studies and 10 in vivo investigations. The integrated evidence demonstrates that OTA exposure triggers a robust toxicological cascade that replicates several key mechanistic pathways associated with AD in experimental models. Early molecular triggers involve significant redox imbalance and mitochondrial bioenergetic failure, which serve as catalysts for sustained neuroinflammation and microglial activation. In vivo data, from multiple animal models, consistently show that these cellular dysfunctions culminate in structural damage. This systematic integration provides a clearer roadmap for future risk assessment and emphasizes the urgent need for refined regulatory guidelines to protect neurological health from chronic mycotoxin exposure. Full article

(This article belongs to the Special Issue Health Risk Assessment of Emerging Pollutants—an Integration of Exposure Estimation and Mechanism-Based Toxicity Study)

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12 pages, 333 KB

Open AccessEditor’s ChoiceArticle

Sensitivity of Urinary Toxicant Co-Exposure Patterns to Demographic Adjustment and Marker Type: A Methodological Analysis

by Basant K. Puri and Jean A. Monro

Toxics 2026, 14(7), 546; https://doi.org/10.3390/toxics14070546 - 23 Jun 2026

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Abstract

Patients presenting with conditions attributed to environmental exposures face complex, multi-toxicant burdens, yet the stability of multivariate toxicant patterns under demographic adjustment remains poorly evaluated. This study assessed the sensitivity of principal component analysis (PCA) structures to demographic confounding and variable composition in [...] Read more.

Patients presenting with conditions attributed to environmental exposures face complex, multi-toxicant burdens, yet the stability of multivariate toxicant patterns under demographic adjustment remains poorly evaluated. This study assessed the sensitivity of principal component analysis (PCA) structures to demographic confounding and variable composition in 551 patients (aged <1–86 years) with environmentally related conditions. Nine urinary biomarkers were analysed using PCA with Varimax and Promax rotation on both raw data and residuals adjusted for age and sex. Among the identified patterns, the solvent/industrial cluster (xylene and styrene metabolites) was the most stable, persisting across both raw and residual analyses regardless of rotation method. However, overall component structures were sensitive to preprocessing: the clustering pattern of the herbicide 2,4-dichlorophenoxyacetic acid shifted markedly after demographic adjustment, illustrating indirect confounding whereby demographic effects on co-variables altered apparent biomarker associations. Notably, inclusion of an endogenous mitochondrial marker (tiglylglycine) alongside exogenous toxicant biomarkers produced Heywood cases (loadings > 1), violating factor analysis assumptions and indicating that mixing exposure and response variables destabilises the model. Cumulative variance explained was modest, consistent with the weak inter-biomarker correlations observed (KMO ≈ 0.52). These findings do not support the identification of robust, demographically stable clustering patterns in this cohort. Instead, they demonstrate that PCA-derived structures in heterogeneous clinical data are vulnerable to demographic confounding, variable selection and marker type, and caution against interpreting transient clustering patterns as definitive exposure signatures without rigorous validation. It should be noted that the absence of a non-clinical matched control group means that whether the identified co-exposure signatures are distinctive to symptomatic patients or reflective of general population exposure patterns cannot be determined; future studies should incorporate matched controls to address this directly. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

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18 pages, 6194 KB

Open AccessEditor’s ChoiceArticle

Life Stage-Dependent Toxicity and Interactions of Scrubber-Related Metal Mixtures in Marine Zooplankton

by Esther Bautista-Chamizo, María Cabrera-Bayarri, Enrique Nebot and Javier Moreno-Andrés

Toxics 2026, 14(6), 530; https://doi.org/10.3390/toxics14060530 - 19 Jun 2026

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Abstract

The adoption of exhaust gas cleaning systems (scrubbers) in maritime transport generates a complex metal-laden washwater that may pose a noteworthy threat to marine ecosystems. This study assessed the acute toxic effects (LC₅₀, 48 h) of four prevalent metals detected in [...] Read more.

The adoption of exhaust gas cleaning systems (scrubbers) in maritime transport generates a complex metal-laden washwater that may pose a noteworthy threat to marine ecosystems. This study assessed the acute toxic effects (LC₅₀, 48 h) of four prevalent metals detected in scrubber washwater—vanadium (V), iron (Fe), nickel (Ni), and zinc (Zn)—both individually and as a realistic mixture. For this purpose, multiple life stages of Artemia franciscana (nauplii, juveniles, and adults) and the rotifer Brachionus plicatilis have been tested under laboratory conditions. All metals induced concentration-dependent toxicity, but sensitivities varied through life stages and species tested. The sensitivity to contaminants generally decreased as the organism’s developmental stage progressed. Consequently, three different orders of toxicity can be detected. The order of metal toxicity (from highest to lowest toxicity, based on 48 h LC₅₀ values) was V > Fe > Ni > Zn for nauplii; V > Zn > Fe > Ni for juveniles and adults; and Fe > V > Zn > Ni for B. plicatilis. The Cumulative Toxic Unit (CTU) approach was utilized to compare the predicted additive effect with observed mixture toxicity. This analysis revealed a complex, life stage-dependent interaction; while antagonism dominated in nauplii (suggesting chemical mitigation), juveniles and adults of A. franciscana and the rotifer (B. plicatilis) exhibited significant synergism, amplifying the total toxicity beyond prediction. This study demonstrates that early life stages and small zooplankton are the most sensitive bioindicators of scrubber-related metal contamination, highlighting the potential ecological risk posed by metal-rich, acidic scrubber discharges that may enhance metal bioavailability and toxicity in marine environments. Full article

(This article belongs to the Section Ecotoxicology)

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21 pages, 404 KB

Open AccessEditor’s ChoiceReview

Human Exposure Pathways to Per- and Polyfluoroalkyl Substances (PFASs)—A Comprehensive Review of Sources, Physicochemical Properties, and Human Health Risk Assessment

by Andrzej R. Reindl and Jakub A. Zduńczuk

Toxics 2026, 14(6), 528; https://doi.org/10.3390/toxics14060528 - 18 Jun 2026

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Abstract

Per- and polyfluoroalkyl substances (PFASs) present a critical challenge to global public health and environmental integrity due to the exceptional stability of the carbon–fluorine (C–F) bond. This review synthesizes current knowledge on PFAS physicochemical properties, exposure pathways, and toxicological outcomes, while evaluating global [...] Read more.

Per- and polyfluoroalkyl substances (PFASs) present a critical challenge to global public health and environmental integrity due to the exceptional stability of the carbon–fluorine (C–F) bond. This review synthesizes current knowledge on PFAS physicochemical properties, exposure pathways, and toxicological outcomes, while evaluating global regulatory efficacy. A central problem addressed in this review is the widening discrepancy between rigid, yet deeply fragmented, international regulatory frameworks and the increasingly complex, non-linear epidemiological data regarding PFAS health risks. While historical paradigms focused heavily on direct carcinogenicity, recent high-resolution data reveal significant heterogeneity and methodological inconsistencies in cancer links. Instead, robust evidence points to severe systemic toxicities—including hepatotoxicity, immunotoxicity, and maternal–fetal disruptions—frequently driven by mixture co-exposures and sex-specific metabolic dimorphisms. Furthermore, the industrial transition to short-chain substitutes has inadvertently compounded the crisis due to their high environmental mobility and resistance to conventional water treatment. By critically evaluating these toxicological and regulatory contradictions, this review demonstrates that current substance-by-substance legislative models fail to mitigate real-world pollution trends. Ultimately, we emphasize the urgent need to transition to holistic mixture modeling, implement unified class-based global regulations, and accelerate advanced destructive remediation technologies to mineralize the resilient C–F bond. Full article

(This article belongs to the Section Emerging Contaminants)

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27 pages, 906 KB

Open AccessEditor’s ChoiceReview

Microplastics in Foods Intended for Health Purposes: From Dietary Supplements to Clinical Nutrition Products

by Kornelia Kadac-Czapska, Justyna Ośko, Katarzyna Jażdżewska and Małgorzata Grembecka

Toxics 2026, 14(6), 514; https://doi.org/10.3390/toxics14060514 - 12 Jun 2026

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Abstract

Microplastics (MPs) are pervasive contaminants that have been detected throughout the food chain. Their presence raises concerns in foods intended for health-related purposes, as these products are often consumed by vulnerable populations such as infants, older adults, and patients requiring clinical nutrition support. [...] Read more.

Microplastics (MPs) are pervasive contaminants that have been detected throughout the food chain. Their presence raises concerns in foods intended for health-related purposes, as these products are often consumed by vulnerable populations such as infants, older adults, and patients requiring clinical nutrition support. These groups may be more susceptible to contaminant exposure and may rely heavily on specialized foods. Therefore, understanding the occurrence and potential risks of MPs in such products is important. This review summarizes the current state of knowledge regarding the presence, sources, and health implications of plastic particles in several categories of health-oriented foods, including dietary supplements, medicinal herbs, plant-based beverages, honey, infant formulas, and clinical nutrition products, including enteral and parenteral formulations. Microplastics have been reported across these matrices. Fibers and fragments dominate, and common polymers include polyamide, polyethylene, polypropylene, and poly(ethylene terephthalate). These particles can originate from polluted water, soil, and air, as well as from production processes, packaging wear, and clinical delivery systems. Current evidence suggests that improving methodological consistency and expanding targeted toxicological research relevant to vulnerable populations will be crucial for strengthening risk assessment. Full article

(This article belongs to the Section Emerging Contaminants)

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23 pages, 6016 KB

Open AccessEditor’s ChoiceArticle

Hybrid Biochar from Corn Stover and Sewage Sludge for VOCs Adsorption: A Sustainable Waste Utilization Approach

by Zhen Zhang, Ninglu Zhang, Xiaohui Pan, Bingchao Zhao, Jun Liu, Shujian Tian, Liyu Hao and Zihao Zhao

Toxics 2026, 14(6), 516; https://doi.org/10.3390/toxics14060516 - 12 Jun 2026

Viewed by 618

Abstract

Volatile organic compounds (VOCs) are major contributors to air pollution and pose significant risks to both environmental quality and human health. Biochar-based adsorption technology is an efficient and sustainable approach to VOCs removal. Herein, hybrid biochar was prepared from corn stover and municipal [...] Read more.

Volatile organic compounds (VOCs) are major contributors to air pollution and pose significant risks to both environmental quality and human health. Biochar-based adsorption technology is an efficient and sustainable approach to VOCs removal. Herein, hybrid biochar was prepared from corn stover and municipal sewage sludge using the water vapor activation method, and its physicochemical characteristics and adsorption mechanisms for typical volatile organic compounds commonly produced during biomass-derived energy generation—such as methylbenzene, isopentane, and ethylene—were systematically investigated. The results show that hybrid biochar significantly outperformed single-source biochar, with its ability to adsorb methylbenzene, isopentane, and ethylene exceeding that of pure sludge biochar by 112.21%, 74.53%, and 66.72%, respectively, and surpassing pure corn stover biochar by 74.25%, 62.98%, and 55.25%, respectively. Competitive adsorption analysis indicated that the interaction strength between VOC molecules and the steam-treated hybrid carbon material was associated with their boiling points; compounds with higher boiling points tended to exhibit stronger affinity. This work provides an integrated waste utilization and pollution control strategy for VOCs removal. Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

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33 pages, 8274 KB

Open AccessEditor’s ChoiceReview

Implications of Endocrine-Disrupting Chemicals for Human Health and Effective Methods for Prevention and Reduction

by Codruța-Claudia Gherman-Lencu, Teodora-Gabriela Alexescu, Cristian Mureșanu, Cezara Andreea Gerdanovics, Mircea-Vasile Milaciu and Dana-Monica Iancu

Toxics 2026, 14(6), 515; https://doi.org/10.3390/toxics14060515 - 12 Jun 2026

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Abstract

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous compounds capable of interfering with hormonal homeostasis and endocrine-regulated physiological processes. Their widespread occurrence in food, water, air, consumer products and industrial materials has raised increasing concern regarding their contribution to chronic disease burden. [...] Read more.

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous compounds capable of interfering with hormonal homeostasis and endocrine-regulated physiological processes. Their widespread occurrence in food, water, air, consumer products and industrial materials has raised increasing concern regarding their contribution to chronic disease burden. This review synthesizes current evidence on the exposure characteristics, molecular mechanisms, health effects, and prevention strategies related to major EDC classes, including bisphenol A and phthalates, dioxins and polychlorinated biphenyls, per- and polyfluoroalkyl substances, pesticides, and brominated flame retardants. Evidence indicates that EDCs may act through receptor-mediated signaling, altered hormone synthesis and metabolism, oxidative stress, mitochondrial dysfunction, immune modulation, and epigenetic mechanisms, with effects that may vary according to dose, timing, sex, age, and developmental susceptibility. Reported health outcomes include metabolic and cardiovascular disorders, reproductive dysfunction, hormone-dependent cancers, thyroid disruption, immune dysregulation, and adverse developmental effects. Although complete avoidance is unrealistic, exposure reduction and risk mitigation can be achieved through coordinated individual, clinical, environmental, and regulatory interventions. A life-course approach is essential to limit the health burden associated with endocrine disruption. Full article

(This article belongs to the Special Issue Exposure and Effects of Endocrine Disrupting Chemicals)

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19 pages, 1577 KB

Open AccessEditor’s ChoiceArticle

Validation of the Electrophilic Allergen Screening Assay for Detection of Key Event 1 of the Skin Sensitization Adverse Outcome Pathway

by Emily N. Reinke, Elijah J. Petersen, John D. Gordon, Rick Uhl, Valerie H. Adams, Diego Rua, Victor J. Johnson, Gary R. Burleson, Judy Strickland, Robert Gutierrez, Catherine S. Sprankle, Tripp LaPratt, David M. Lehmann, Dori R. Germolec and Nicole C. Kleinstreuer

Toxics 2026, 14(6), 511; https://doi.org/10.3390/toxics14060511 - 11 Jun 2026

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Abstract

The electrophilic allergen screening assay (EASA) uses small-molecule probes as surrogates for skin proteins to measure hapten protein carrier complex formation, Key Event (KE) 1 in the adverse outcome pathway for skin sensitization. Although multiple assays are accepted for this purpose, the EASA [...] Read more.

The electrophilic allergen screening assay (EASA) uses small-molecule probes as surrogates for skin proteins to measure hapten protein carrier complex formation, Key Event (KE) 1 in the adverse outcome pathway for skin sensitization. Although multiple assays are accepted for this purpose, the EASA has higher throughput and needs less specialized equipment than other commonly used KE1 assays. This validation study assessed transferability of the EASA to naïve laboratories and within- and between-laboratory reproducibility. The predictive capacity of the assay in relation to reference data both from the murine local lymph node assay (LLNA) and, where available, human predictive patch tests, was estimated. The validation study was conducted using performance standards developed for methods that are under evaluation for inclusion in relevant test guidelines. The within- and between-laboratory reproducibility were cumulatively 96% and 85%, respectively. These scores exceeded the performance standard thresholds of 80%. Compared to reference LLNA data, the cumulative EASA results from the four laboratories had an overall sensitivity of 87%, specificity of 76%, and accuracy of 83%. The consensus results among the four laboratories had an overall sensitivity of 85%, specificity of 80%, and accuracy of 83%. For human reference data, the cumulative EASA results had an overall sensitivity of 81%, specificity of 76%, and accuracy of 70%. The EASA predicted sensitizers very well, although it had a slightly higher rate of misclassifying some negative test chemicals as positive with a specificity below the performance standards criterion of 80%. Our findings support further exploring use of the EASA in defined approaches to identify potential skin sensitizers. Full article

(This article belongs to the Special Issue Applicability of New Approach Methodologies (NAMs) to Skin Sensitization: Insights from Industry and Regulatory Perspectives)

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18 pages, 2446 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Effects of Pristine and Aged LDPE and PP Microplastic Leachates on Behavioural Responses of the Soil Arthropods Folsomia candida and Porcellionides pruinosus

by Andrea Masseroni, Lorenzo Federico, Alessandro Becchi, Maurizio Quinto, Francesco Saliu and Sara Villa

Toxics 2026, 14(6), 502; https://doi.org/10.3390/toxics14060502 - 9 Jun 2026

Viewed by 522

Abstract

This study investigated the behavioural responses of the arthropods Folsomia candida (springtails) and Porcellionides pruinosus (woodlice) to leachates released from additive-free plastic polymers. Avoidance behaviour was evaluated to assess potential reductions in soil habitat function, while aggregation status was investigated to highlight possible [...] Read more.

This study investigated the behavioural responses of the arthropods Folsomia candida (springtails) and Porcellionides pruinosus (woodlice) to leachates released from additive-free plastic polymers. Avoidance behaviour was evaluated to assess potential reductions in soil habitat function, while aggregation status was investigated to highlight possible functional impairments in the woodlice population. Leachates from pristine and artificially aged low-density polyethylene (LDPE) and polypropylene (PP) microplastics were tested at three different concentrations, ranging from environmentally relevant levels to a worst-case scenario of soil contamination. The distinct physicochemical structures of LDPE and PP led to different release compounds. The results revealed no statistically significant avoidance responses in arthropods for either treatment. Unlike PP, LDPE induced a statistically significant impairment of gregarious behaviour at the highest tested concentration (150 mg/kg d.w.). Furthermore, pristine LDPE induced more pronounced disaggregation than the aged one, suggesting that weathering may modulate behavioural responses depending on polymer type and endpoint. Therefore, it is recommended that high levels of plastic leachates can have an adverse effect on soil arthropods and that the aggregation behaviour of woodlice may be a more informative and sensitive biological endpoint than avoidance alone. Full article

(This article belongs to the Section Ecotoxicology)

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27 pages, 3837 KB

Open AccessEditor’s ChoiceReview

Advanced Degradation and Remediation Strategies for Per- and Polyfluoroalkyl Substances (PFASs): Challenges and Future Perspectives

by Xiaohui Zhang, Tongshun Han, Xiaofeng Yao, Rui Zhao, Wenjun Sun, Liang Pei, Jianguo Zhao and Peigao Duan

Toxics 2026, 14(6), 499; https://doi.org/10.3390/toxics14060499 - 7 Jun 2026

Viewed by 1153

Abstract

Per- and polyfluoroalkyl substances (PFASs) are persistent aquatic contaminants whose strong C–F bonds make conventional water treatment ineffective. This review critically synthesizes recent progress in aqueous PFAS degradation through four mechanistic routes: oxidation-driven, biodegradation, reduction-driven, and nonradical processes. Rather than evaluating technologies by [...] Read more.

Per- and polyfluoroalkyl substances (PFASs) are persistent aquatic contaminants whose strong C–F bonds make conventional water treatment ineffective. This review critically synthesizes recent progress in aqueous PFAS degradation through four mechanistic routes: oxidation-driven, biodegradation, reduction-driven, and nonradical processes. Rather than evaluating technologies by parent-compound disappearance alone, we compare their defluorination and mineralization capacities, matrix tolerance, byproduct risks, energy demand, operational stability, and technology readiness. Oxidative and reductive systems can promote rapid degradation or defluorination, but their performance is often constrained by radical/electron quenching, incomplete mineralization, and sensitivity to PFAS structure and water chemistry. Biodegradation and enzymatic approaches offer mild transformation pathways but remain limited by slow kinetics, narrow substrate specificity, and uncertain toxicity evolution. Nonradical and thermochemical processes show stronger potential for deep destruction, particularly in concentrated PFAS streams. Overall, electrochemical oxidation, plasma treatment, and thermal/supercritical oxidation appear closer to practical implementation for spent adsorbents, regenerants, industrial concentrates, and other high-strength wastes, whereas many photocatalytic, biological, and microdroplet systems remain laboratory-stage. Future research should prioritize integrated separation–destruction treatment trains and standardized metrics including total organic fluorine removal, fluoride release, final residual PFAS concentrations relative to regulatory thresholds, transformation-product toxicity, energy consumption, and life-cycle impacts. Full article

(This article belongs to the Special Issue Advanced Oxidation Processes (AOPs): Emerging Materials for Environmental Remediation)

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13 pages, 3924 KB

Open AccessEditor’s ChoiceArticle

Road Dust, PM₁₀ Exposure and Respiratory Health in Visby: An Updated Analysis of Mitigation Efforts

by Henrik Olstrup, Bertil Forsberg and Andreas Tornevi

Toxics 2026, 14(6), 497; https://doi.org/10.3390/toxics14060497 - 7 Jun 2026

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Abstract

Background: High concentrations of coarse particulate matter PM₁₀ from road dust are a major air quality concern in Visby, Sweden. To mitigate these levels, local authorities replaced soft limestone with crushed granite as an anti-slip material starting in the winter of 2023/2024. [...] Read more.

Background: High concentrations of coarse particulate matter PM₁₀ from road dust are a major air quality concern in Visby, Sweden. To mitigate these levels, local authorities replaced soft limestone with crushed granite as an anti-slip material starting in the winter of 2023/2024. This is a follow-up study evaluating the impact of this intervention on PM₁₀ concentrations and the associated short-term respiratory health effects. Methods: Daily counts of healthcare visits for respiratory diseases (ICD-10: J00–J99) and daily mean PM₁₀ concentrations were analyzed using a quasi-Poisson regression model. This study compared the limestone period (2015–2019) with the granite period (2023–2025), stratified by season (winter/spring and summer/autumn) and age group (children 0–17 years and adults >17 years). Results: The transition to crushed granite reduced peak PM₁₀ concentrations during the spring. For adults, the relative risks for respiratory visits during winter/spring decreased during the granite period when compared to the limestone period (Wald p < 0.05). However, when considering that there were a majority of non-statistically significant differences when comparing the granite and limestone periods, these results should be interpreted with caution. Among children, more pronounced associations were observed during summer, although no significant differences in risk were detected between the limestone and granite periods. Conclusions: Although the intervention effectively lowered particle mass concentrations, only minor changes were observed in the overall epidemiological pattern. This suggests that public health improvements may be limited by factors beyond total mass reduction, such as particle mineralogy or seasonal exposure dynamics. Full article

(This article belongs to the Section Air Pollution and Health)

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24 pages, 1955 KB

Open AccessEditor’s ChoiceArticle

QSAR Modeling to Predict Aquatic Toxicity Across Multiple Species

by Iglika Lessigiarska, Petko Alov, Maria Angelova, Stefan Ivanov, Parashkev Katerski, Radostina Nikolova-Kejova, Ilza Pajeva, Tania Pencheva and Ivanka Tsakovska

Toxics 2026, 14(6), 498; https://doi.org/10.3390/toxics14060498 - 7 Jun 2026

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Abstract

This study addresses the growing need for efficient and reliable application of New Approach Methodologies (NAMs) to assess aquatic toxicity of chemicals in response to increasing environmental contamination and regulatory demands. Particular emphasis is placed on in silico methods, especially quantitative structure–activity relationship [...] Read more.

This study addresses the growing need for efficient and reliable application of New Approach Methodologies (NAMs) to assess aquatic toxicity of chemicals in response to increasing environmental contamination and regulatory demands. Particular emphasis is placed on in silico methods, especially quantitative structure–activity relationship (QSAR) modeling. Curated and structurally diverse datasets were compiled for representative aquatic organisms from different trophic levels, including the microalga Raphidocelis subcapitata, the crustacean Daphnia magna, and fish species (zebrafish embryo and fathead minnow). The models demonstrated consistently strong predictive performance across the evaluated assays. They were based on interpretable molecular descriptors associated with lipophilicity, polarity, and molecular reactivity. Furthermore, interspecies quantitative structure–activity–activity relationship (QSAAR) models were developed, demonstrating that toxicity data from lower trophic levels, combined with structural descriptors, can effectively predict fish toxicity. These models support cross-species extrapolation and contribute to environmental hazard assessment and regulatory decision-making. Full article

(This article belongs to the Special Issue New Approach Methodologies in Environmental Risk Assessment of Chemical Contaminants)

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18 pages, 1824 KB

Open AccessEditor’s ChoiceArticle

Lipid Metabolic Effects Induced by Individual and Combined Exposure to Multiple Food Additives in Human Cells

by Zizhao Huang, Weichunbai Zhang, Xudong Jia, Hui Yang, Ling Yong, Jin Fang, Yan Song and Yi Wan

Toxics 2026, 14(6), 487; https://doi.org/10.3390/toxics14060487 - 3 Jun 2026

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Abstract

With the widespread coexistence of multiple food additives, their combined exposure has raised increasing health concerns. This study used high-content imaging to investigate the individual and combined effects of five common food additives on lipid metabolism in HepG2, Caco-2, and Jurkat T cells. [...] Read more.

With the widespread coexistence of multiple food additives, their combined exposure has raised increasing health concerns. This study used high-content imaging to investigate the individual and combined effects of five common food additives on lipid metabolism in HepG2, Caco-2, and Jurkat T cells. In HepG2 and Caco-2 cells, all additives dose-dependently induced lipid and free cholesterol accumulation; by contrast, Jurkat T cells exhibited only sporadic statistical differences without biologically relevant dose-dependent effects. Notably, lipid droplet accumulation appeared as a relatively early and readily detectable response, though its suitability as a definitive biomarker of metabolic disturbance warrants further validation. Combined-exposure experiments, conducted in HepG2 and Caco-2 cells, revealed cell-specific interaction patterns: additive interactions dominated in HepG2 cells, while sodium benzoate and sodium cyclamate showed synergistic disruption in Caco-2 cells. These results provide in vitro evidence that multi-component combined exposure causes cell-specific lipid-related perturbations not fully captured by single-additive assessment, suggesting that mixture toxicity models should be incorporated to improve food safety evaluation. Full article

(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)

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17 pages, 3770 KB

Open AccessEditor’s ChoiceArticle

A High-Resolution VOC Emission Inventory for Gas Stations in a Typical Yangtze River Delta City: Implications for Ozone Formation, Secondary Organic Aerosol Formation, and Health Risks

by Tianyu Chen, Xinmei Zheng, Chunlei Liu, Ming Wang, Fangjian Xie and Jing Li

Toxics 2026, 14(6), 486; https://doi.org/10.3390/toxics14060486 - 1 Jun 2026

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Abstract

Gasoline evaporation is a significant source of urban volatile organic compounds (VOCs). In this study, we selected Nanjing, a major city in the Yangtze River Delta of China, and developed a high-resolution (1 km × 1 km) gridded VOC species emission inventory for [...] Read more.

Gasoline evaporation is a significant source of urban volatile organic compounds (VOCs). In this study, we selected Nanjing, a major city in the Yangtze River Delta of China, and developed a high-resolution (1 km × 1 km) gridded VOC species emission inventory for gas stations based on measured VOC emission characteristics and statistical data on gasoline and diesel sales. The results show that VOC emissions from gas stations were correlated with population density and road networks, and were mainly concentrated in the downtown area. The emitted VOCs were dominated by alkanes (58%) and oxygenated VOCs (19%), with i-pentane, n-butane, and methyl tert-butyl ether (MTBE) as the major components. C4–C5 alkenes were identified as the key contributors to ozone (O₃) formation, while aromatics contributed most to secondary organic aerosol (SOA) formation. Health risk assessment indicates that, for gas station workers, both carcinogenic and non-carcinogenic risks associated with gasoline and diesel VOC evaporation exceed acceptable thresholds. Benzene, 1,2-dichloroethane, and 1,2-dibromoethane posed the highest carcinogenic risks, whereas acrolein, benzene, and 1,3-butadiene contributed most to non-carcinogenic risks. For urban residents, the health risks from gas station VOC emissions were generally within acceptable levels; however, under unfavorable meteorological conditions, residents living near gas stations may still face elevated health risks. This study highlights the significant impacts of gas station-related VOC emissions on air quality and human health, and informs targeted control and mitigation strategies for gasoline evaporation. Full article

(This article belongs to the Special Issue Volatile Organic Compounds (VOCs) Exposure and Human Health)

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12 pages, 2137 KB

Open AccessEditor’s ChoiceArticle

Fe-C Micro-Electrolysis of HMX: Performance Optimization, Degradation Mechanisms, and Toxicity Evolution Revealed by Toxicogenomics-Based Assay

by Xin Jiang, Dongqi Wang, Guodong Chai, Guangxiang Duan, Haoting Xiong, Yishi Qian, Lin Xie, Yi Xiao, Heyun Yang, Mingrui Fan, Jiake Li, Yishan Lin, Xiaoliang Li and Yuling Liu

Toxics 2026, 14(6), 484; https://doi.org/10.3390/toxics14060484 - 31 May 2026

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Abstract

This study evaluated the degradation of 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) in simulated wastewater using an iron-carbon (Fe-C) micro-electrolysis system. The treatment efficiency was systematically evaluated under varying initial pH, Fe dosage, and Fe/C mass ratios. Under the optimized operating conditions (initial pH of 4, Fe [...] Read more.

This study evaluated the degradation of 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) in simulated wastewater using an iron-carbon (Fe-C) micro-electrolysis system. The treatment efficiency was systematically evaluated under varying initial pH, Fe dosage, and Fe/C mass ratios. Under the optimized operating conditions (initial pH of 4, Fe dosage of 70 g/L, and an Fe/C mass rat of 1:1), the system achieved a maximum HMX removal efficiency of 98.4%. Kinetic analysis indicated that the degradation process conformed to pseudo-first-order kinetics. Mechanistically, HMX removal was attributed to interfacial adsorption and co-precipitation via in situ generated Fe²⁺ and Fe³⁺ hydroxides, alongside reductive transformation mediated by Fe, Fe²⁺, and nascent hydrogen ([H]) evolved during the micro-electrolysis process. To assess the molecular toxicity evolution of the treated wastewater, a toxicogenomic assay was deployed to evaluate the molecular toxicity evolution of the treated wastewater matrix. The transcriptomic profiling revealed that DNA damage and oxidative stress were the predominant cellular stress responses induced by the wastewater. While the total toxic effect transcript index (TELI_total) exhibited a transient initial increase before steadily declining, the overall toxic potency remained within a relatively stable range throughout the treatment cycle. Ultimately, this study provides critical insights into process optimization and pathway elucidation, demonstrating that Fe-C micro-electrolysis is a promising and scalable pretreatment technology for the remediation of energetic compound-laden industrial effluents. Full article

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23 pages, 4053 KB

Open AccessEditor’s ChoiceArticle

Environmental Exposure and Long-Term Mortality After Coronary Artery Bypass Grafting: A Multicenter Cohort Study Beyond Traditional Risk Factors

by Tomasz Urbanowicz, Sleiman Sebastian Aboul-Hassan, Krzysztof Skotak, Maria Luszczyn, Łukasz Moskal, Jakub Bratkowski, Mariusz Kowalewski, Jarosław Bartkowski, Bartłomiej Perek, Mirosław Wilczyński, Krzysztof J. Filipiak, Krzysztof Bartuś, Romuald Cichoń and Marek Jemielity

Toxics 2026, 14(6), 482; https://doi.org/10.3390/toxics14060482 - 31 May 2026

Viewed by 990

Abstract

Background: Ambient air pollution is an established cardiovascular risk factor; however, its impact on long-term outcomes after coronary artery bypass grafting (CABG) remains insufficiently defined. We aimed to evaluate whether chronic exposure to air pollutants may influence long-term mortality following surgical revascularization. Methods: [...] Read more.

Background: Ambient air pollution is an established cardiovascular risk factor; however, its impact on long-term outcomes after coronary artery bypass grafting (CABG) remains insufficiently defined. We aimed to evaluate whether chronic exposure to air pollutants may influence long-term mortality following surgical revascularization. Methods: In this multicenter retrospective cohort study, 1033 consecutive patients undergoing CABG with BIMA (bilateral internal mammary arteries) grafting were analyzed with a median follow-up of 8.1 years. Individual exposure to nitrogen dioxide (NO₂), particulate matter ≤10 μm (PM₁₀), and ≤2.5 μm (PM_2.5) was estimated based on residential data. Multivariable Cox proportional hazards models were used to assess associations with long-term mortality. Model performance was evaluated using receiver operating characteristic (ROC) analysis, while incremental prognostic value was quantified using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Kaplan–Meier analyses were performed using data-driven thresholds and model-based risk stratification. Results: During follow-up, 220 deaths (21.1%) occurred. In multivariable analysis, both NO₂ and PM₁₀ were associated with increased mortality (NO₂: HR 2.70 per 10 μg/m³, 95% CI 2.03–3.59; PM₁₀: HR 2.73 per 10 μg/m³, 95% CI 1.94–3.83; both p < 0.001), whereas PM_2.5 was not significant. The clinical model demonstrated moderate discrimination (AUC 0.73), which improved significantly after inclusion of pollution variables (AUC 0.84; ΔAUC 0.11). Reclassification analysis showed substantial improvement (NRI 0.42, p < 0.001; IDI 0.11, p < 0.001). Kaplan–Meier analysis confirmed enhanced risk stratification, with a hazard ratio of 2.70 for the clinical model and 7.02 for the combined clinical and pollution model (both p < 0.001). Conclusions: In this retrospective cohort of patients undergoing CABG with BIMA grafting, higher long-term residential exposure to NO₂ and PM₁₀ was associated with greater all-cause mortality after adjustment for measured clinical and procedural factors. These findings support further investigation of environmental exposure as a prognostic marker in surgically treated coronary disease, pending external validation and more granular control for contextual confounding. These findings suggest that environmental exposure may represent a relevant component of long-term risk stratification, although confirmation in large-volume cohorts is required. Full article

(This article belongs to the Special Issue Airway Exposure to Pollution from Ambient Particulate Matter (PM) and Health Effects)

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16 pages, 5606 KB

Open AccessEditor’s ChoiceArticle

Circadian Phase Modulates Embryonic Susceptibility to Bisphenol A-Induced ASD-Related Behavioral Alterations via nr1d1

by Ying Wu, Jianjun Liu, Pinyi Chen, Xinwei Wang, Yuting Wang, Xiaoyao Song and Jie Zhang

Toxics 2026, 14(6), 485; https://doi.org/10.3390/toxics14060485 - 31 May 2026

Viewed by 515

Abstract

Emerging evidence links environmental exposures and circadian dysregulation to autism spectrum disorder (ASD), yet whether circadian phase modulates vulnerability to developmental toxicants remains unclear. Here, we investigated whether embryonic bisphenol A (BPA) exposure induces circadian phase-dependent ASD-related behavioral alterations via disruption of nr1d1 [...] Read more.

Emerging evidence links environmental exposures and circadian dysregulation to autism spectrum disorder (ASD), yet whether circadian phase modulates vulnerability to developmental toxicants remains unclear. Here, we investigated whether embryonic bisphenol A (BPA) exposure induces circadian phase-dependent ASD-related behavioral alterations via disruption of nr1d1 rhythmicity in zebrafish. In control larvae, nr1d1 exhibited significant circadian oscillation, whereas BPA exposure reduced expression levels and dampened oscillation amplitude. Two-way ANOVA revealed significant treatment × phase interactions in nr1d1 expression. Pharmacological activation of Nr1d1 partially restored rhythmic expression. Behavioral assessments conducted at defined circadian phases demonstrated a significant treatment × phase interaction in social preference. BPA-exposed larvae exhibited reduced social preference selectively at circadian time 15 (CT15), corresponding to the trough phase of nr1d1 expression, whereas no differences were observed at circadian time 3 (CT3). In contrast, tactile hyper-responsiveness showed a significant treatment effect but no phase interaction. BPA exposure also induced phase-dependent alterations in ASD-related genes, including α-nrxn2a and β-nrxn3a, with significant treatment × phase interactions. At the molecular level, BPA increased reactive oxygen species, impaired antioxidant defense, enhanced neuroinflammatory responses, and disrupted excitatory–inhibitory balance. Several of these endpoints exhibited phase-dependent modulation and were partially attenuated by Nr1d1 activation. These findings indicate that circadian phase modulates embryonic susceptibility to BPA-induced ASD-related behavioral and molecular alterations. Disruption of nr1d1 rhythmicity may contribute to time-of-day-specific neurodevelopmental vulnerability following environmental exposure. Full article

(This article belongs to the Special Issue The Neuroexposome: Integrating Exposures with Physiology to Understand Brain Health and Disease)

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21 pages, 4751 KB

Open AccessEditor’s ChoiceArticle

The Toxicity of Tire Wear Particles and Their Leachates on Digestion and Gut Microbiota of Mytilus coruscus

by Yu Zhou, Qikun Yang, Lukuo Ma, Xuanjie Zhou, Shixiu Wang and Wei Huang

Toxics 2026, 14(6), 468; https://doi.org/10.3390/toxics14060468 - 27 May 2026

Viewed by 581

Abstract

Tire Wear Particles (TWPs) are a major type of microplastics (MPs). However, previous studies have predominantly focused on TWP leachates rather than the particles, and their toxic effects on marine organisms remain limited. In this study, the mussels were exposed to TWPs and [...] Read more.

Tire Wear Particles (TWPs) are a major type of microplastics (MPs). However, previous studies have predominantly focused on TWP leachates rather than the particles, and their toxic effects on marine organisms remain limited. In this study, the mussels were exposed to TWPs and their leachates for 21 days, followed by a 7-day recovery period in clean conditions. The results showed that the leachates contained organic pollutants (predominantly PAHs) and metal ions (predominantly Zn²⁺). Growth inhibition was observed in exposure to TWPs, while leachate exposure showed no significant effect. As for the antioxidant system, high-concentration TWP and their leachate exposures provoked significant oxidative stress, accompanied by inhibited superoxide dismutase (SOD) and catalase (CAT) activity as well as increased glutathione (GSH) and malondialdehyde (MDA) levels. Exposure to high concentrations of TWPs significantly inhibited acetylcholinesterase (AChE) and trypsin (TRS) activities. Gut microbiota analysis indicated that exposure to TWPs and their leachates modified community structure with significantly reduced relative abundance of Firmicutes, Bacteroidota, potentially attributed to the bacteriostatic activity of released Zn²⁺. Integrated Biomarker Response (IBR) analysis indicated that TWPs elicited stronger integrated toxicity compared to their leachates. This study provides a comparative perspective on the ecological toxicology of TWPs and their leachates. Full article

(This article belongs to the Section Emerging Contaminants)

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13 pages, 2231 KB

Open AccessEditor’s ChoiceArticle

Heterogeneous Chlorine Reactions on Mineral Dust During Dust Storm Events in the Coastal City of Qinhuangdao

by Yulong Wang, Jiajia Shao, Ting Wei, Ruihe Lyu, Pengju Liu, Chen Lin, Wenhua Wang and Longyi Shao

Toxics 2026, 14(6), 460; https://doi.org/10.3390/toxics14060460 - 25 May 2026

Viewed by 684

Abstract

Heterogeneous reactions on mineral dust surfaces during dust storm events significantly influence atmospheric chemistry by modifying aerosol composition. This study employed high-resolution scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX) to investigate the morphology and elemental composition of dust particles collected during [...] Read more.

Heterogeneous reactions on mineral dust surfaces during dust storm events significantly influence atmospheric chemistry by modifying aerosol composition. This study employed high-resolution scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX) to investigate the morphology and elemental composition of dust particles collected during four dust events in Qinhuangdao, a coastal city in Northern China. The results revealed that clay minerals were the most abundant (53.5% ± 13.7%), followed by feldspar (12.0% ± 3.6%), quartz (11.9% ± 3.2%) and carbonate minerals (7.3% ± 4.1%). In contrast, sulfate and NaCl particles constituted only a minor fraction, representing 1.1% and 0.9% of the particles, respectively. Elemental analysis indicated that sulfur (S)-containing particles, although scarce during the initial stages, increased as the dust storms evolved, eventually accounting for about half of the particles by the end of the events. This trend suggests increasing heterogeneous processing on dust particle surfaces. Furthermore, single-particle analysis demonstrated a marked increase in chlorine (Cl)-containing particles (excluding NaCl) from 2.4% at the onset to 30.9% ± 16.5% by the end of the dust events. In contrast to studies conducted in inland cities, where Cl-containing particles are seldom observed, our findings underscore the crucial role of marine aerosols in facilitating the chlorine enrichment of dust particles in coastal atmospheric environments. Overall, these findings provide new insights into the aging processes of mineral dust in coastal atmospheres and suggest potential interactions between dust particles and marine aerosols during heterogeneous halogen and sulfur processing in dust events. Full article

(This article belongs to the Special Issue Analysis of the Sources and Components of Aerosols in Air Pollution)

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14 pages, 3773 KB

Open AccessEditor’s ChoiceArticle

Oxygen Plasma Functionalization of Activated Carbon Pellets for Hazardous HCl Gas Mitigation: Balancing Surface Oxygenation and Pore Preservation

by Min Seong Han, Jong Hyun Lee, Do Hyun Kim and Byong Chol Bai

Toxics 2026, 14(6), 459; https://doi.org/10.3390/toxics14060459 - 24 May 2026

Viewed by 763

Abstract

Hydrogen chloride (HCl) is a hazardous acidic gas released from industrial processes and waste-treatment systems, posing risks to human health, process safety, and the surrounding environment. Accordingly, there is a need for practical adsorbent materials that can reduce HCl exposure without generating secondary [...] Read more.

Hydrogen chloride (HCl) is a hazardous acidic gas released from industrial processes and waste-treatment systems, posing risks to human health, process safety, and the surrounding environment. Accordingly, there is a need for practical adsorbent materials that can reduce HCl exposure without generating secondary liquid waste. In this study, pitch-based activated carbon pellets were surface-functionalized by oxygen plasma treatment to improve fixed-bed HCl removal performance. Plasma treatment was applied for 1, 2, and 4 min, and the resulting changes in surface chemistry, pore structure, and adsorption behavior were investigated using SEM, XPS, N₂ adsorption–desorption analysis, and breakthrough experiments. Oxygen plasma treatment increased the oxygen-containing surface functionalities of the pellets while largely preserving pellet morphology. Under moderate treatment conditions (1–2 min), the BET surface area and pore volume were mostly maintained, whereas prolonged treatment (4 min) reduced the accessible pore structure. In fixed-bed adsorption tests, the sample treated for 1 min showed the longest breakthrough behavior and the highest HCl uptake among the tested samples, while the sample treated for 2 min exhibited the shortest mass transfer zone and the highest bed utilization. These results indicate that controlled oxygen plasma treatment can improve the removal of hazardous HCl gas by balancing surface functionalization and pore preservation. The findings suggest that plasma-functionalized activated carbon pellets are a promising option for toxic acidic gas mitigation in air pollution control and waste-treatment applications. Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

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19 pages, 291 KB

Open AccessEditor’s ChoiceArticle

Unmet Information Needs of Spanish Female Breast Cancer Survivors on Chemical Pollutants: A Cross-Sectional Mixed-Method Study

by Laura García-Molina, Bibiana Navarro-Matillas, Blanca Riquelme-Gallego, Marina Zenobia Molina-Fernández, José Expósito, Juan Pedro Arrebola and Piedad Martin-Olmedo

Toxics 2026, 14(6), 456; https://doi.org/10.3390/toxics14060456 - 23 May 2026

Viewed by 816

Abstract

Breast cancer (BC) remains the most prevalent malignancy among women. Prolonged exposure to chemical pollutants has been identified as one of its potential risk factors. Despite increased access to health information, important informational gaps persist regarding chemical exposure. This concern is particularly pronounced [...] Read more.

Breast cancer (BC) remains the most prevalent malignancy among women. Prolonged exposure to chemical pollutants has been identified as one of its potential risk factors. Despite increased access to health information, important informational gaps persist regarding chemical exposure. This concern is particularly pronounced among female BC survivors due to their greater vulnerability. This study investigated unmet information needs related to chemical exposure among female BC survivors from Granada (Spain). The data were collected through 150 semi-structured interviews and focus groups between March 2023 and April 2024 and analyzed using the Framework Method. Most participants demonstrated limited awareness regarding BC and its potential association with chemical exposure. Nevertheless, 78.67% of them expressed concerns regarding the issue after diagnosis and anxiety surrounding the lack of reliable information from trusted sources on recurrence prevention. These findings highlight the need for public health communication that informs and empowers protective behavior. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

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16 pages, 1120 KB

Open AccessEditor’s ChoiceReview

Occurrence of Trifluoroacetic Acid in Wine and Its Relevance for Dietary Exposure and Human Health: A Narrative Review

by Andrea Moscato, Paola Rapisarda, Margherita Ferrante and Maria Fiore

Toxics 2026, 14(6), 454; https://doi.org/10.3390/toxics14060454 - 22 May 2026

Viewed by 724

Abstract

Trifluoroacetic acid (TFA) is an ultrashort-chain perfluoroalkyl substance (PFAS) characterized by environmental persistence, water solubility, and a growing global presence, resulting primarily from the degradation of fluorinated compounds. Evidence suggests that plant-based foods may represent an underestimated exposure route, with wine emerging as [...] Read more.

Trifluoroacetic acid (TFA) is an ultrashort-chain perfluoroalkyl substance (PFAS) characterized by environmental persistence, water solubility, and a growing global presence, resulting primarily from the degradation of fluorinated compounds. Evidence suggests that plant-based foods may represent an underestimated exposure route, with wine emerging as a significant dietary source due to accumulation in soils, irrigation water, and plant uptake. This review provides an updated summary of the evidence on the environmental sources and temporal evolution of TFA in wine, its analytical detection, its contribution to dietary exposure, potential implications for human health, and current regulatory attention. A structured but non-systematic literature search was conducted using PubMed and Scopus, supplemented by European reports and monitoring data, and in accordance with SANRA guidelines. Evidence shows that TFA concentrations in wine derive from widespread environmental sources and have increased over time, from negligible levels before the 1970s to a marked increase in recent decades. Reported concentrations range from tens to several hundred µg/L, despite analytical challenges. Exposure estimates indicate that wine may contribute significantly to total dietary TFA intake in regular consumers. Although toxicological data suggest low acute toxicity, uncertainties remain regarding long-term exposure, and regulatory limits for TFA in foods and beverages are lacking. Full article

(This article belongs to the Special Issue Emerging Contaminants in a Changing World: Implications for Human Health)

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33 pages, 2908 KB

Open AccessEditor’s ChoiceReview

Synergistic Effects of Air Pollutants and Extreme Temperature on Asthma: A Narrative Review of Mechanisms and Evidence

by Guanlin Li, Junliang Chen, Ao Wang, Shunjie Hao, Charles Obinwanne Okoye, Yueru Qiao, Yu Cheng, Hui Liang, Linjing Deng and Xunfeng Chen

Toxics 2026, 14(5), 452; https://doi.org/10.3390/toxics14050452 - 21 May 2026

Viewed by 820

Abstract

Global climate change and air pollution jointly threaten respiratory health. Asthma, a prevalent chronic inflammatory airway disease, is exacerbated by both traditional air pollutants such as particulate matter (PM_2.5), ozone (O₃), nitrogen dioxide (NO₂), sulfur dioxide (SO [...] Read more.

Global climate change and air pollution jointly threaten respiratory health. Asthma, a prevalent chronic inflammatory airway disease, is exacerbated by both traditional air pollutants such as particulate matter (PM_2.5), ozone (O₃), nitrogen dioxide (NO₂), sulfur dioxide (SO₂) and emerging contaminants like microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS), with effects amplified under extreme temperature conditions. In reality, individuals face complex combined exposures, yet the synergistic effects of these factors on asthma pathogenesis remain poorly understood. This narrative review synthesizes epidemiological and toxicological evidence. It aims to elucidate both the individual and the notably synergistic effects of these factors on asthma pathogenesis. The central mechanistic pathway is initiated by oxidative stress, which activates key inflammatory signaling pathways, thereby driving immune imbalance and airway inflammation. Our review underscores that the combined exposure to traditional pollutants, emerging pollutants, and extreme temperatures may pose a greater threat than individual factors. These findings underscore the critical need for an integrated perspective in asthma research and public health policy. Moving beyond single-pollutant approaches, we advocate for combinatorial risk assessment and synergistic intervention strategies to effectively mitigate the growing burden of asthma in a changing climate. Full article

(This article belongs to the Special Issue Air Pollution Monitoring and Epidemiology)

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27 pages, 8605 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

by Nicole M. Breese, Lisa Truong, Xueshu Li, Robyn L. Tanguay and Hans-Joachim Lehmler

Toxics 2026, 14(5), 444; https://doi.org/10.3390/toxics14050444 - 19 May 2026

Cited by 1 | Viewed by 899

Abstract

Polychlorinated biphenyls (PCBs) persist in the environment as complex mixtures and undergo extensive biotransformation, yet the developmental toxicity of PCB metabolites remains poorly defined. We evaluated developmental, neurobehavioral, and molecular effects of parent PCBs, hydroxylated, methoxylated, and sulfated metabolites, and environmentally relevant mixtures [...] Read more.

Polychlorinated biphenyls (PCBs) persist in the environment as complex mixtures and undergo extensive biotransformation, yet the developmental toxicity of PCB metabolites remains poorly defined. We evaluated developmental, neurobehavioral, and molecular effects of parent PCBs, hydroxylated, methoxylated, and sulfated metabolites, and environmentally relevant mixtures using embryonic zebrafish. This study employed a high-throughput screening approach using nominal exposure concentrations to enable rapid hazard identification and prioritization across a large chemical series. Morphological abnormalities and photomotor behavior were assessed across early development, followed by targeted cyp1a reporter analysis and transcriptomic profiling for a subset of potent exposures. Most chemicals induced morphological effects, with hydroxylated and sulfated metabolites producing effects more frequently and at lower benchmark concentrations than parent congeners. Behavioral alterations were more prevalent in embryonic photomotor response than larval photomotor response and generally co-occurred with morphological effects. Environmental mixtures elicited broad phenotypic profiles comparable to highly active individual compounds. Transcriptomic analyses revealed minimal responses for parent PCBs but robust, exposure-specific gene expression changes for select metabolites, particularly 5-OH-PCB11, and mixtures. Differentially expressed genes were enriched for xenobiotic metabolism, immune signaling, and neuroactive pathways, alongside consistent downregulation of circadian regulators. Together, these results demonstrate contributions of PCB metabolites and mixtures to toxicity. Full article

(This article belongs to the Special Issue Neurotoxicity from Exposure to Environmental Pollutants)

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23 pages, 1620 KB

Open AccessEditor’s ChoiceReview

Environmental Micro(nano)plastic Exposure and Associated Human Health Risks: A Comprehensive Review

by Weike Hu, Dongling Liu, Jianing Wang, Xia Huo and Xiang Zeng

Toxics 2026, 14(5), 442; https://doi.org/10.3390/toxics14050442 - 18 May 2026

Viewed by 1054

Abstract

Micro(nano)plastics (MNPs) represent a pervasive and escalating threat to global ecosystems and human health. This review provides a critical synthesis of MNPs’ exposure risks across marine, atmospheric, and terrestrial compartments, with a distinct emphasis on identifying cross-media linkages and methodological inconsistencies that limit [...] Read more.

Micro(nano)plastics (MNPs) represent a pervasive and escalating threat to global ecosystems and human health. This review provides a critical synthesis of MNPs’ exposure risks across marine, atmospheric, and terrestrial compartments, with a distinct emphasis on identifying cross-media linkages and methodological inconsistencies that limit current risk assessments. Within marine environments, pollution hazard indices reveal significant spatial heterogeneity, yet their utility is constrained by the absence of toxicity weighting and particle characteristic integration. Atmospheric exposure profiles show variable risks, and the MNPs’ concentration in indoor air (up to 15.8 particles/m³) is significantly higher than in outdoor environments, posing a greater inhalation risk to infants and children who spend more time indoors. A marked increase in MNPs’ concentrations within agricultural soils is identified, where the MNP content in mulched soils (average: 570.2 particles/kg) is more than twice that of non-mulched soils (259.6 particles/kg). Critically, studies have now detected MNPs within human tissues, including the blood, intestines, liver, kidneys, tonsils, and brain, highlighting an urgent need to elucidate their multi-organ toxicity mechanisms, with a novel synthesis of gut–brain axis disruption and transgenerational effects. By integrating exposure dynamics with mechanistic toxicity data, this review advances a cross-system framework that identifies priority research directions, namely standardized detection methodologies, combined pollutant toxicity, and cross-system toxicity mechanisms, which are essential for informing mitigation strategies amid this escalating public health crisis. Full article

(This article belongs to the Special Issue Human Exposure to Emerging Pollutants: Toxicological Effects and Health Risk Assessment)

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19 pages, 2932 KB

Open AccessEditor’s ChoiceArticle

Plasma Concentrations of Endotoxin Lipopolysaccharide and High-Mobility Group Box 1 Protein Are Consistent Sex-Specific Biomarkers of Alcohol Abstinence Associated with Alcohol Use Disorder

by Isaac Hurtado-Guerrero, Nuria García-Marchena, Jaime Martín-Martín, María Flores-López, Nerea Requena-Ocaña, María del Mar Fernández-Arjona, Antonio J. López-Gambero, Patricia Rivera, Leticia Rubio, Gabriel Rubio, Antonia Serrano, Fernando Rodríguez de Fonseca and Juan Suarez

Toxics 2026, 14(5), 440; https://doi.org/10.3390/toxics14050440 - 15 May 2026

Viewed by 1128

Abstract

Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone [...] Read more.

Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone leptin, are reliable biomarkers for the estimation of alcohol dependence and abstinence. AUD outpatients (N = 122) and healthy volunteers (N = 63) were recruited and assessed by using the Psychiatric Research Interview for Substance and Mental Disorders according to DSM-IV-TR after blood extraction. The results indicated that AUD patients had higher plasma concentrations of LPS and HMGB1, and lower plasma concentrations of leptin and SDF-1α compared to healthy subjects. Two logistic models, including HMGB1, leptin and SDF-1α (model 1) or LPS (model 2), provided high discriminatory powers to identify AUD patients [prognostic probability: model 1 = 0.90 (0.78); model 2 = 0.86 (0.79); p < 0.001]. LPS and HMGB1 positively correlated with alcohol abstinence duration in male AUD patients only. Linear logistic regression included LPS, HMGB1, fractalkine, SDF-1α and/or leptin to accurately estimate the duration of problematic alcohol use and alcohol abstinence when sexes were analyzed separately. These results suggest that LPS and HMGB1 are relevant sex-specific actors for predicting alcohol abstinence and problematic alcohol use in AUD patients. Full article

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

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17 pages, 1578 KB

Open AccessEditor’s ChoiceArticle

Cobinamide, a Vitamin B₁₂ Analog, Attenuates Benzo[a]pyrene and Pyrene Toxicity Through Selective Redox Modulation

by Anirudh Kalyanaraman, Connor B. Stauffer, Weirui Gao, Tong Zhong, Alexandra Nguyen, Darren E. Casteel, Renate B. Pilz, Gerry R. Boss, Hema Kalyanaraman and John Tat

Toxics 2026, 14(5), 439; https://doi.org/10.3390/toxics14050439 - 15 May 2026

Viewed by 707

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants formed during the incomplete combustion of organic material. Their persistence, bioaccumulation, and metabolic activation contribute to mutagenic and cytotoxic outcomes. Among these are benzo[a]pyrene (B[a]P), the most studied PAH and a benchmark compound for PAH [...] Read more.

Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants formed during the incomplete combustion of organic material. Their persistence, bioaccumulation, and metabolic activation contribute to mutagenic and cytotoxic outcomes. Among these are benzo[a]pyrene (B[a]P), the most studied PAH and a benchmark compound for PAH carcinogenicity, and pyrene, a PAH whose urinary metabolite 1-hydroxypyrene is widely used as a biomarker of PAH exposure. B[a]P undergoes CYP1A1-mediated oxidation to generate reactive oxygen species (ROS) via epoxide and quinone redox cycling, whereas pyrene produces ROS primarily through pyrene-quinone redox cycling. We investigated cobinamide, a vitamin B₁₂/cobalamin analog with potent antioxidant properties, for mitigating benzo[a]pyrene- and pyrene-induced injury. In H9C2 rat embryonic cardiomyoblasts and A549 human lung epithelial cells exposed to B[a]P (10 μM) or pyrene (10–100 μM), cobinamide (5–10 μM) attenuated PAH-induced reductions in cell number in both models, while in H9C2 cells, it also attenuated decreases in metabolic activity and reduced apoptosis. Cobinamide also returned JNK/p38 phosphorylation to near baseline levels, decreased DNA and protein oxidation and DNA strand breaks. Transcriptionally, cobinamide suppressed inflammatory (TNF-α, IL-1β, and IL-6) and oxidative stress genes (HMOX1 and NOX4), while enhancing oxidative response (SOD2) and xenobiotic metabolism (CYP1A1). In Drosophila melanogaster exposed to 5 mM B[a]P/pyrene, 2 mM cobinamide improved survival and fully restored locomotion, outperforming cobalamin (minimal benefit) and N-acetylcysteine (partial rescue). Spectroscopic analyses showed no direct cobinamide-PAH binding. These findings demonstrate that cobinamide efficiently limits ROS-mediated PAH injury through redox modulation while preserving xenobiotic metabolism, suggesting its potential therapeutic use to mitigate PAH-induced toxicity. Full article

(This article belongs to the Special Issue Toxic Threats to Sustainability: Mechanisms and Impacts of Environmental Contaminants on Health and Ecosystems)

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16 pages, 1712 KB

Open AccessEditor’s ChoiceArticle

Intermediate- and Long-Term Exposure to PM_2.5 and Its Chemical Components in Relation to Nocturnal Sleep Duration and Daytime Napping Duration

by Lidan Hu, Xiuhua Yan, Xinhui Qiu and Zhiyuan Li

Toxics 2026, 14(5), 437; https://doi.org/10.3390/toxics14050437 - 14 May 2026

Viewed by 748

Abstract

While the association between criteria air pollutants and sleep duration is well-documented, evidence on the impact of fine particulate matter (PM_2.5) chemical components on sleep remains limited. This study investigated the effects of intermediate- (6-month) and long-term (2-year) exposure to PM [...] Read more.

While the association between criteria air pollutants and sleep duration is well-documented, evidence on the impact of fine particulate matter (PM_2.5) chemical components on sleep remains limited. This study investigated the effects of intermediate- (6-month) and long-term (2-year) exposure to PM_2.5 and its five major components—black carbon (BC), organic matter (OM), sulfate (SO₄²⁻), nitrate (NO₃⁻), and ammonium (NH₄⁺)—on nocturnal sleep and daytime napping duration. We included 19,505 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). Residential PM_2.5 and component concentrations were estimated via the Tracking Air Pollution in China dataset, and sleep data were collected through self-reported questionnaires. Linear mixed-effects models and quantile-based g-computation (qgcomp) were used to assess single- and multi-pollutant effects. Results showed that both intermediate- and long-term exposure to PM_2.5 components was associated with shorter nocturnal sleep and longer daytime napping. Subgroup analyses revealed greater susceptibility among rural residents, solid fuel users, and individuals without pensions. These findings emphasize the need for component-specific PM_2.5 control strategies and targeted public health interventions to reduce sleep-related health inequalities, especially in socioeconomically disadvantaged populations. Full article

(This article belongs to the Special Issue Aerosol Particles: From Sources to Health Impacts)

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20 pages, 7963 KB

Open AccessEditor’s ChoiceArticle

Geochemical Assessment of Sediment Heavy Metal(loid) Concentrations in Lofa County, Northwestern Liberia: A Comparative Analysis of Average Shale and Upper Continental Crust Background Values

by Hafizou M. Sow, Quanrong Wang, Mohamed Hussein Yousif, Fred B. Wright, Kaixu Chen, Chong Chen and Abara A. Biabak Indrick

Toxics 2026, 14(5), 436; https://doi.org/10.3390/toxics14050436 - 14 May 2026

Viewed by 585

Abstract

Despite the proliferation of mining and industrial activities within the Mano River Union member states, sediment quality assessment remains limited due to the lack of a comprehensive geochemical dataset. To narrow this knowledge gap, we evaluated heavy metal(loid) concentrations in stream sediments from [...] Read more.

Despite the proliferation of mining and industrial activities within the Mano River Union member states, sediment quality assessment remains limited due to the lack of a comprehensive geochemical dataset. To narrow this knowledge gap, we evaluated heavy metal(loid) concentrations in stream sediments from Lofa County, Liberia. A total of 313 samples were collected and analyzed for eight metal(loid)s (Cu, Pb, Zn, Cr, Cd, Ni, As, and Hg). The contamination factor (CF), enrichment factor (EF), geoaccumulation index (Igeo), and potential ecological risk index (PERI) were calculated independently against two background values: the average shale and upper continental crust (UCC) values. The UCC background values proved more appropriate than average shale for Liberia’s geographic location and geological setting, providing results that align with the empirical data. The results show that zinc concentrations were consistently low across all sampling sites, indicating regional depletion of the micronutrient. Despite variations in the methodological approaches, assessment results from all four indices identified mercury and arsenic as the contaminants of primary concern. The varying degrees of metal(loid) enrichment and depletion necessitate further research in the study area. This study should guide policymakers in devising a sustainable plan for tackling site-based contamination and delivering on the United Nations Sustainable Development Goal 6.3. Full article

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17 pages, 8064 KB

Open AccessEditor’s ChoiceArticle

Highly Efficient Removal of Barium(II) from Nuclear Wastewater by Calcined Magnesium–Aluminum Layered Double Hydroxides

by Jun Wang, Zhaoxu Sun, Ziyi Liu, Xinglei Li, Yi Zhou, Ningchao Zheng, Qiang Wu, Chen Xu, Lu Gao, Hiroshi Watabe, Yanliang Chen, Yuezhou Wei and Xiangbiao Yin

Toxics 2026, 14(5), 432; https://doi.org/10.3390/toxics14050432 - 14 May 2026

Viewed by 836

Abstract

Radioactive Ba²⁺ poses significant risks to nuclear safety and environmental protection, yet its efficient removal from nuclear wastewater remains a considerable challenge. Herein, Mg-Al layered double hydroxides (LDHs) were synthesized via a co-precipitation method and systematically optimized by tuning the Mg/Al molar [...] Read more.

Radioactive Ba²⁺ poses significant risks to nuclear safety and environmental protection, yet its efficient removal from nuclear wastewater remains a considerable challenge. Herein, Mg-Al layered double hydroxides (LDHs) were synthesized via a co-precipitation method and systematically optimized by tuning the Mg/Al molar ratio and calcination temperature. The optimal material, obtained by calcining Mg-Al LDH with a Mg/Al ratio of 4:1 at 450 °C (denoted as HT-450), exhibited a high apparent Ba²⁺ uptake capacity of 416 mg g⁻¹ and reached equilibrium within 15 min. Structural and spectroscopic analyses indicate that Ba²⁺ immobilization is more appropriately described as a reconstruction-coupled, interfacially mediated mineralization process, in which insoluble BaCO₃ forms in close association with the reconstructed HT-450 surface rather than through simple reversible adsorption or ion exchange. HT-450 also exhibited stable performance over a wide pH range of 3–7, high selectivity toward Ba²⁺ in the presence of competing mono-, di-, and trivalent cations, and excellent radiation tolerance, retaining approximately 95% of its initial uptake capacity after exposure to 200 kGy high-energy electron irradiation. These results demonstrate that HT-450 is a promising candidate for the rapid and stable immobilization of Ba²⁺ from Ba-containing radioactive wastewater. Full article

(This article belongs to the Section Metals and Radioactive Substances)

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21 pages, 530 KB

Open AccessEditor’s ChoiceReview

Toxic Substances in Plastics, Micro- and Nanoplastics: Utilizing ATSDR’s Plastics-Related Toxicological Profile Tool and Mixtures Framework for Human Health Risk Assessment

by Custodio V. Muianga, Gregory M. Zarus, Katie Stallings, Gaston Casillas, Mohammad Shoeb, Kimberly Gehle, Mohammad Moiz Mumtaz and Christopher M. Reh

Toxics 2026, 14(5), 429; https://doi.org/10.3390/toxics14050429 - 13 May 2026

Viewed by 1079

Abstract

The prevalence of plastics in the environment raises concerns about their complex and poorly understood effects on human health. Research continues to uncover more sources of exposure and wider ranges of plastics within the body. Adverse health effects have been observed in animals, [...] Read more.

The prevalence of plastics in the environment raises concerns about their complex and poorly understood effects on human health. Research continues to uncover more sources of exposure and wider ranges of plastics within the body. Adverse health effects have been observed in animals, but their relevance to humans remains unclear. To address the growing need for reliable toxicity assessment resources and tools to aid in the synthesis of findings and the identification of data gaps and needs, we have developed a data visualization tool to provide streamlined access to the evaluated data on the chemical impacts of plastics on human health. The Plastics-Related Toxicology Profiles Tool uses Tableau Public to organize the extracted chemical-specific information from ATSDR Toxicological Profiles, the United Nations Environmental Program’s 2023 Chemicals in Plastics Technical Report, and a literature review of relevant research in Google Scholar and PubMed. The tool organizes extracted data from 98 ATSDR Toxicological Profiles representing over 476 substances related to plastics production in 16 tabulated health outcome categories associated with plastics exposure. The chemicals are organized into four categories based on their role in plastics manufacturing. The top four health endpoints impacted by all listed substance profiles are respiratory, neurologic, hepatic, and developmental effects. More than 30% of the substance profiles affected these systems as well as other non-cancer endpoints involving the immunological, renal, and reproductive systems, as well as increased cancer risk in respiratory and hepatic systems. Most monomers negatively impact development and the respiratory system, and most metal additives affect the respiratory system. We explain how this data visualization tool combined with ATSDR’s framework for assessing health impacts from multiple chemicals could be applied to identify the target organs impacted by components of the common plastic polyvinyl chloride. Hazard quotients and index show low toxicity and health risk of components in the cured product. This data provide a valuable resource for prioritizing health risk assessments. Use of this interactive tool can enhance the ability of public health professionals to navigate the expanding literature, synthesize findings, and identify future health risk assessment and research priorities. Full article

(This article belongs to the Section Emerging Contaminants)

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18 pages, 4113 KB

Open AccessEditor’s ChoiceArticle

The Fate of Antibiotic Resistance Genes and Their Influential Factors During Large-Scale Cattle Manure Composting

by Zhuo Sun, Siyu Yang, Tong Zhang, Hongyin Li, Peng Gao, Liqiu Zhang, Li Feng and Qi Han

Toxics 2026, 14(5), 428; https://doi.org/10.3390/toxics14050428 - 13 May 2026

Viewed by 674

Abstract

Animal manure represents a critical reservoir that facilitates the dissemination of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). However, the current understanding of ARG evolution during extensive composting remains insufficient. This study systematically investigated two common aerobic composting techniques: push-flow trough [...] Read more.

Animal manure represents a critical reservoir that facilitates the dissemination of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). However, the current understanding of ARG evolution during extensive composting remains insufficient. This study systematically investigated two common aerobic composting techniques: push-flow trough composting (FC) and membrane-covered composting (FM). Results indicated that both processes demonstrated substantial antibiotic removal capacities, achieving total removal rates of 88.89% (FC) and 79.20% (FM). Nevertheless, their effectiveness in removing ARGs varied considerably. During the 31 days of composting, the total removal rates of ARGs were 59.97% (FC) and 76.11% (FM), while the removal rates for class 1 integron (intI1) were 2.31% (FC) and 69.13% (FM). With the exception of tetX, tetG, and tetW, all other ARGs exhibited a rebound during the later stage of the FC process. In contrast, the FM process effectively reduced the risk of ARG rebound during this phase, which can be attributed to its extended thermophilic period and the physical barrier effect of the semi-permeable membrane. Network analysis indicated that ARGs were primarily associated with Bacillota and Pseudomonadota. The Partial Least Squares Path Model (PLS-PM) revealed that the bacterial community was the main factor influencing ARG dynamics in FC, while in FM, both the bacterial community and intI1 were the primary drivers. This study provides critical insights for optimizing composting strategies to prevent the dissemination of antibiotic resistance. Full article

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19 pages, 4320 KB

Open AccessEditor’s ChoiceArticle

Personal PM_2.5 Exposure Using Time-Weighted Average Scenarios in the Seoul Metropolitan Area

by Jae-Won Choi, Shin-Young Park and Cheol-Min Lee

Toxics 2026, 14(5), 426; https://doi.org/10.3390/toxics14050426 - 12 May 2026

Viewed by 594

Abstract

Personal exposure assessment is essential in environmental and epidemiological studies. However, conventional methods often do not adequately reflect individuals’ spatiotemporal activity characteristics. This study evaluates the suitability of personal exposure assessment methods using PM_2.5 as a case study, comparing measured personal exposure [...] Read more.

Personal exposure assessment is essential in environmental and epidemiological studies. However, conventional methods often do not adequately reflect individuals’ spatiotemporal activity characteristics. This study evaluates the suitability of personal exposure assessment methods using PM_2.5 as a case study, comparing measured personal exposure concentrations with three exposure estimation scenarios (S1–S3). S1 relies on fixed-site monitoring data, S2 incorporates location-based outdoor concentrations and a single indoor measurement, and S3 integrates individual location with microenvironment-specific concentrations. Using personal PM_2.5 measurements and time–activity data (TAD) from adults in the Seoul metropolitan area, exposure levels showed substantial variation depending on activity patterns and time spent in different microenvironments. Time-weighted average (TWA)-based estimates differed across scenarios; among them, the one integrating microenvironmental concentrations and TAD showed the closest agreement with measured exposure. In contrast, S1 and S2 generally overestimated exposure. Although S3 slightly underestimated short-term high-concentration events, it showed high correlation (r = 0.78) and low errors (RMSE = 4.79, MAE = 3.70), effectively capturing relative variability in personal exposure. These results suggest that integrating time–activity patterns with microenvironmental concentrations improves the accuracy and reliability of personal exposure assessment and is expected to further enhance the reliability of personal exposure assessment. Full article

(This article belongs to the Special Issue Atmospheric Emissions, Exposure, Monitoring and Prediction)

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23 pages, 671 KB

Open AccessEditor’s ChoiceArticle

Radionuclide and Trace Element Distribution in Grey Wolves (Canis lupus): Implications for Environmental Contamination and Transfer in Terrestrial Ecosystems

by Maja Lazarus, Božena Skoko, Mikael Hult, Tatjana Orct, Maja Ferenčaković, Ivana Coha, Josip Kusak, Slaven Reljić, Gerd Marissens and Heiko Stroh

Toxics 2026, 14(5), 425; https://doi.org/10.3390/toxics14050425 - 12 May 2026

Viewed by 690

Abstract

Anthropogenic pollution may impose additional pressure on European populations of large protected carnivores due to the systemic toxicity of contaminants such as cadmium, lead, and radiocaesium (¹³⁷Cs). Our aim was to carry out ¹³⁷Cs, radiopotassium (⁴⁰K), and stable [...] Read more.

Anthropogenic pollution may impose additional pressure on European populations of large protected carnivores due to the systemic toxicity of contaminants such as cadmium, lead, and radiocaesium (¹³⁷Cs). Our aim was to carry out ¹³⁷Cs, radiopotassium (⁴⁰K), and stable element distribution analysis through seven tissues of grey wolves (Canis lupus) from temperate forests of Croatia using ultra-low background gamma-ray spectrometry and ICPMS, respectively. In addition, radiolead (²¹⁰Pb) massic activity was quantified in femoral bone. The massic activity of ¹³⁷Cs in the heart, kidney, liver, spleen, lungs, and femoral bone (in decreasing order) ranged from 9–61% relative to muscle and showed strong inter-tissue correlations. However, correlations between radionuclides and their stable analogues in wolf tissues indicated considerable uncertainty in the use of stable element data for radiological risk assessment. In addition, concentration ratios (CR_{whole organism-soil}) derived from stable element data should be applied with caution when radionuclide data are lacking. Overall, radionuclide activities and element levels not subject to homeostatic regulation in grey wolves were comparable to or lower than those reported for other populations, particularly those from sub-Arctic regions. Despite being apex terrestrial predators, wolves inhabiting temperate ecosystems do not currently appear to be at risk of adverse health effects from exposure to the most relevant inorganic anthropogenic pollutants. Full article

(This article belongs to the Special Issue Radioactive Contamination and Its Impact on the Environment)

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24 pages, 5054 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Early Pregnancy Targeted Exposome: Biological Response and Maternal BMI

by Nadia Saadat, Soundara Viveka Thangaraj, Jasmin Chovatiya, Ravikumar Jagani, Syam S. Andra and Vasantha Padmanabhan

Toxics 2026, 14(5), 421; https://doi.org/10.3390/toxics14050421 - 12 May 2026

Viewed by 2217

Abstract

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; [...] Read more.

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; BMI < 25 = 64) from the Michigan Mother–Infant Pair cohort were profiled to assess how BMI influences urinary exposomes and related biological responses. A validated approach measured 96 chemicals and biomarkers of oxidative stress and glucocorticoids. Women in both groups reported similar lifestyles and consumer product use. Women with high BMI had lower urinary concentrations of several chemicals than women with low BMI. Phytoestrogens, polycyclic aromatic hydrocarbons, and insect repellants showed a higher magnitude of positive associations with other markers of exposure, oxidative and glucocorticoid stress in the high-BMI group, while UV filters, flame retardants, and phthalates showed a higher magnitude of positive associations with oxidative stress markers in the low-BMI group. The patterns of associations of exposure markers with stress markers and pregnancy outcomes (gestational age and birthweight) differed by maternal BMI. This highlights the importance of incorporating maternal BMI into the evaluation of exposure burden and its effects, as a factor that may actively shape biological responses. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

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33 pages, 4604 KB

Open AccessEditor’s ChoiceArticle

Mixture Effects of Metals, PCBs, Dioxins, and Furans on Liver Function

by Bolanle Akinyemi and Emmanuel Obeng-Gyasi

Toxics 2026, 14(5), 418; https://doi.org/10.3390/toxics14050418 - 11 May 2026

Cited by 1 | Viewed by 803

Abstract

Quantifying the mixture effects on humans exposed remains challenging because mixture components are correlated and may act bidirectionally by exhibiting nonlinear dose-response relationships, which may contribute to subclinical organ dysfunction. The liver is a vital organ in the body with broad functions, making [...] Read more.

Quantifying the mixture effects on humans exposed remains challenging because mixture components are correlated and may act bidirectionally by exhibiting nonlinear dose-response relationships, which may contribute to subclinical organ dysfunction. The liver is a vital organ in the body with broad functions, making it vulnerable to injury as it is the first organ exposed to circulating toxicants, which can precipitate hepatic damage. Our study’s objective was to evaluate the combined and component-specific associations of a multi-chemical exposure mixture of heavy metals, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (dioxins), and polychlorinated dibenzofurans (furans), with liver biomarkers, and to compare concentration-based results with the toxic equivalent (TEQ) potency of the weighted results for dioxin-like compounds. In an unweighted analytic sample of U.S. adults from NHANES 2003–2004 with 947 complete cases, we examined heavy metals (cadmium, lead, and mercury), PCBs (12 congeners), dioxins (7 congeners), and furans (10 congeners) in relation to eight liver biomarkers (albumin, ALP, ALT, AST, GGT, LDH, total bilirubin, and total protein). We applied multi-exposure linear regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR), with parallel TEQ-based models using WHO 2005 TEFs for dioxin-like PCBs, dioxins, and furans. Across mixture methods, the mixture structure was chemically sparse, with a limited set of recurring contributors. Total bilirubin showed the most consistent positive mixture association across qgcomp and BKMR and persisted under TEQ weighting, with prominent PCB- and dioxin-like contributions (notably PCB81/PCB TEQs and dioxin-related components). Albumin demonstrated inverse mixture patterns in BKMR and TEQ-BKMR, with dioxin-like components (notably Dioxin3 and Dioxin3_TEQ) repeatedly emerging as key drivers. For ALT, ALP, AST, GGT, LDH, and total protein, overall mixture effects were frequently attenuated or null in qgcomp despite structured component weights, indicating bidirectional sub-mixtures and internal counterbalancing. BKMR PIPs similarly concentrated on a small number of dominant predictors (e.g., lead for ALP, mercury for ALT, PCB28 for AST, and cadmium and PCB189 for LDH), while interaction summaries provided limited evidence of stable non-additivity. Using multiple complementary mixture methods, we identified outcome-specific mixture patterns suggesting hepatobiliary vulnerability. TEQ concordance supports toxicological relevance of the dioxin-like axis, while metals and non–dioxin-like mechanisms likely contribute additional pathways. Full article

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24 pages, 944 KB

Open AccessEditor’s ChoiceReview

Polycyclic Aromatic Hydrocarbons Through the One Health Lens: Integrating Human, Animal, and Environmental Health Perspectives

by Jose L. Domingo, Marília Cristina Oliveira Souza and Fernando Barbosa, Jr.

Toxics 2026, 14(5), 417; https://doi.org/10.3390/toxics14050417 - 11 May 2026

Viewed by 1434

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous combustion-derived contaminants that represent a significant cross-cutting threat to human, animal, and environmental health. Viewed through an explicit One Health lens, this review shows how the shared combustion sources, evolutionarily conserved toxicological mechanisms, and food-web linkages connecting [...] Read more.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous combustion-derived contaminants that represent a significant cross-cutting threat to human, animal, and environmental health. Viewed through an explicit One Health lens, this review shows how the shared combustion sources, evolutionarily conserved toxicological mechanisms, and food-web linkages connecting environmental contamination to wildlife and human exposure justify an integrated, cross-domain approach to PAH risk assessment and management. PAHs are generated predominantly through incomplete combustion of organic materials and are globally distributed through atmospheric transport, aquatic runoff, and food-web transfer, persisting in soils and sediments for decades. The present review synthesizes current knowledge on PAHs through an explicit One Health lens, examining shared sources, environmental fate, and convergent health effects across species and health domains, while also highlighting the need to move beyond the classical US EPA priority PAHs to include high-molecular-weight PAHs (>302 Da), alkylated homologues, and transformation products such as oxy- and nitro-PAHs. Common pathways such as dietary intake of grilled and smoked foods, inhalation of contaminated air, and occupational exposure create parallel toxicological burdens in both human and wildlife populations, particularly through genotoxic mechanisms mediated by aryl hydrocarbon receptor (AhR) activation and CYP1A1/CYP1B1-catalyzed bioactivation to reactive diol epoxides. The resulting DNA adduct formation links environmental PAH exposure to carcinogenicity, reproductive toxicity, immunosuppression, and developmental impairment across vertebrate species with remarkable mechanistic consistency. Wildlife, especially fish, marine mammals, and seabirds, serve as critical sentinels for environmental PAH contamination, while simultaneously facing direct health impacts on immune function, reproduction, and population viability. Vulnerable human populations, including children, subsistence communities, occupational workers, and residents near combustion-intensive industries, bear disproportionate burdens reflecting underlying environmental justice concerns. Integrated intervention strategies encompassing source control, dietary exposure reduction, site remediation, and coordinated biomonitoring are urgently needed. By incorporating emerging PAH classes with distinct persistence, trophic behavior, and toxicological potency, the One Health paradigm provides a more comprehensive conceptual framework for modern environmental surveillance, food safety, and integrated risk assessment, recognizing that the health of terrestrial and aquatic ecosystems is inseparable from that of the animals and humans within them. Full article

(This article belongs to the Special Issue Occurrence, Fate, and Ecotoxicological Effects of Persistent Organic Pollutants in Aquatic Environments)

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19 pages, 617 KB

Open AccessEditor’s ChoiceReview

Associations Between Neurological Diseases and Dioxin Exposure Originating from Agent Orange in Vietnam: A Narrative Review

by Tai Pham-The, Hang Thi Nguyet Pham, William R. Folk, Nghi Ngoc Tran, Tuyet-Hanh Tran-Thi, Hisao Nishijo and Muneko Nishijo

Toxics 2026, 14(5), 419; https://doi.org/10.3390/toxics14050419 - 11 May 2026

Viewed by 1406

Abstract

Now, half a century after the Vietnam War, Agent Orange exposure during the war is increasingly discussed as a risk factor for neurological diseases, particularly dementia and Alzheimer’s disease, among Korean and U.S. Vietnam War veterans. Emerging evidence supports associations between dioxin exposure [...] Read more.

Now, half a century after the Vietnam War, Agent Orange exposure during the war is increasingly discussed as a risk factor for neurological diseases, particularly dementia and Alzheimer’s disease, among Korean and U.S. Vietnam War veterans. Emerging evidence supports associations between dioxin exposure originating from Agent Orange and alterations in brain morphology and function among Vietnamese residents, including children living in areas around former U.S. airbases exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after the Vietnam War. This paper summarizes what is known about the effects of Agent Orange exposure in the context of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, attention-deficit/hyperactivity disorder, and psychiatric disorders. Molecular biological studies have reported that TCDD may increase the risks of these neurological diseases by accelerating brain aging and inducing atypical neurodevelopment, partly mediated by the aryl hydrocarbon receptor. However, the effects of TCDD, which is a highly toxic contaminant of Agent Orange, as well as dioxin congeners other than TCDD, exhibit some inconsistencies. This review aims to provide new insights for mitigating the adverse neurological effects of dioxin exposure from Agent Orange, contributing to a healthier life for residents in Vietnam. Full article

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31 pages, 28102 KB

Open AccessEditor’s ChoiceArticle

From Environmental Concentrations to Individual Inhalation: Analysis of Exposure Differences to PM_2.5 and Chemical Components in Elderly Populations and Their Influencing Factors

by Ruoyu Li, Fenghua Lin, Hao Zhang, Yuling Zhang, Shilin Chen, Dan Wang, Yongxin Wang, Haoneng Hu, Jianjun Xiang, Yu Jiang, Huaying Lin, Jianlin Zhu and Chuancheng Wu

Toxics 2026, 14(5), 414; https://doi.org/10.3390/toxics14050414 - 10 May 2026

Viewed by 662

Abstract

(1) Background: This study investigated the characteristics and influencing factors of exposure to fine particulate matter (PM_2.5) and its chemical composition among elderly residents, with the aim of revealing potential differences in exposure. (2) Methods: A total of 258 elderly individuals [...] Read more.

(1) Background: This study investigated the characteristics and influencing factors of exposure to fine particulate matter (PM_2.5) and its chemical composition among elderly residents, with the aim of revealing potential differences in exposure. (2) Methods: A total of 258 elderly individuals were monitored for 72 h through individual, indoor, and outdoor PM_2.5 measurements. Concentrations were determined, and non-targeted components were analyzed by gas chromatography-mass spectrometry (GC-MS). Through Spearman correlation analysis, generalized linear model, and linear regression to explore the influencing factors. (3) Results: The individual PM_2.5 concentration was higher than both the indoor and outdoor concentrations. A total of 20,962 compounds were detected in personal PM_2.5 samples, 6794 in indoor PM_2.5 samples, among which 4285 compounds were shared between the two sample types. The components were mainly esters, aromatic compounds, and amines. PM_2.5 concentration was correlated with age, housing area, humidifier use, and second-hand smoke exposure. Chemical composition is related to outdoor pollution, furniture material, and daily behavior. (4) Conclusions: The individual PM_2.5 concentration is higher than the environmental concentration, and its chemical composition overlaps with the indoor and outdoor environment, which is jointly affected by demography, living conditions, and daily behavior. Full article

(This article belongs to the Special Issue Atmospheric Emissions, Exposure, Monitoring and Prediction)

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27 pages, 33336 KB

Open AccessEditor’s ChoiceArticle

Water Quality Metrics of Fishponds During the Cold Season, with a Focus on the Potential Risk of Metals and Microplastics

by Marinela Mirica Gancea, Cristiana Radulescu, Andreea Laura Banica, Ioana Daniela Dulama, Raluca Maria Stirbescu, Ioan Alin Bucurica, Mioara Costache and Mariana Cristina Arcade

Toxics 2026, 14(5), 403; https://doi.org/10.3390/toxics14050403 - 8 May 2026

Viewed by 1391

Abstract

Aquaculture in ponds supplied by streams or rivers requires careful evaluation of key physicochemical parameters and potential pollution threats, particularly metals and microplastics. To address these challenges, this research aims to monitor daily climatic and physicochemical parameters and quantify potentially toxic metals and [...] Read more.

Aquaculture in ponds supplied by streams or rivers requires careful evaluation of key physicochemical parameters and potential pollution threats, particularly metals and microplastics. To address these challenges, this research aims to monitor daily climatic and physicochemical parameters and quantify potentially toxic metals and microplastics in the water of 19 fishponds in the SCDP Nucet, Romania, over one winter season (i.e., December 2024 to February 2025). During this season, unique hydrochemical conditions arise, such as lower temperatures, reduced light, and decreased activity, which can affect the ecological balance and fish health. Accordingly, a total of 4650 samples were collected and analyzed in terms of physicochemical parameters (i.e., alkalinity, bicarbonate, calcium ions, magnesium ions, Ca²⁺/Mg²⁺ ratio, organic matter, nitrates, nitrites, phosphates, ammonium, total hardness, resistivity, dissolved oxygen, conductivity, salinity, turbidity, free and total chlorine), metals, and microplastics. Statistical analysis revealed the influence of winter weather on water quality, highlighting links between air and water temperatures and physicochemical parameters. Furthermore, water analyses revealed notable levels of microplastics, including fibers and fragments of various colors, shapes, and sizes. Polypropylene, polyethene, and nylon were the most prevalent. While appreciable quantities of blue, green, black, and yellow fibers were found in size ranges (0.09–0.3 mm), irregular yellow fragments or translucent particles were found in sizes less than 0.5 mm. Metal (i.e., Cr, Fe, Ni, Co, Cu, Zn, Cd, and Pb) concentrations do not exceed the standard values set by national and European regulations. However, it is worth noting that microplastics can amplify or mitigate metal toxicity. The results emphasize the importance of integrated monitoring of physicochemical parameters and emerging pollutants during the cold season, thereby improving understanding of the chemical processes governing water quality in fishponds, providing scientific support for future environmental risk assessment, and promoting innovative, adaptive technologies. Full article

(This article belongs to the Special Issue Advances in Water, Air and Soil Pollution Monitoring, Modeling and Restoration, 2nd Edition)

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29 pages, 2190 KB

Open AccessEditor’s ChoiceReview

How Adequate Are the Guidelines for Dietary and Workplace Exposure to Cadmium?

by Soisungwan Satarug

Toxics 2026, 14(5), 408; https://doi.org/10.3390/toxics14050408 - 8 May 2026

Viewed by 1930

Abstract

Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet because of its presence in nearly all food types, including potatoes, vegetables, cereals, grains, legumes, shellfish, and organ meat. Cd has no physiological role or nutritional [...] Read more.

Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet because of its presence in nearly all food types, including potatoes, vegetables, cereals, grains, legumes, shellfish, and organ meat. Cd has no physiological role or nutritional value in the body and causes toxicity to multiple tissues and organs via oxidative stress and chronic inflammation; as such, at high prevalence, it is frequently associated with diseases, notably cancer, heart disease, diabetes, osteoporosis, and chronic kidney disease. Using kidneys and bones as critical toxicity targets, current dietary Cd exposure guidelines vary from 0.21 to 0.83 μg/kg b.w./d. There is a widespread concern about these guidelines because they were based on the excretion of β₂-microglobulin (β₂M) at a rate of 300 µg/g of creatinine as an endpoint. Concerningly, rice is a staple food for over 50% of the world’s population; however, the permissible Cd level in this commodity has not been adequately addressed. This narrative review focuses on critiquing existing food standards and exposure guidelines for Cd. It discusses the threshold-based risk assessment that was used to define the no-observed-adverse-effect level (NOAEL) for Cd, when β₂M excretion was used with Cd excretion at a rate of 5.24 µg/g of creatinine being a threshold. The estimated glomerular filtration rate (eGFR) is recommended as an appropriate kidney disease endpoint. The current view around how Cd uses various transport proteins to enter and induce toxicity to its target cells are summarized. The strategies to minimize Cd accumulation and mitigate its nephrotoxicity are highlighted. Full article

(This article belongs to the Special Issue Environmental Contamination by Toxic Metals and Metalloids, Exposure Limits, and Toxicity Thresholds)

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18 pages, 1123 KB

Open AccessEditor’s ChoiceReview

Source, Monitoring Techniques and Prospects of Bioaerosols: A Review

by Jiaqing Wu, Chun Chen, Hong Geng, Bixin Zhao and Jian Gao

Toxics 2026, 14(5), 404; https://doi.org/10.3390/toxics14050404 - 8 May 2026

Viewed by 1196

Abstract

Bioaerosols play significant roles in ecological interactions, climate change, and public health. Their diverse origins contribute to a dynamic atmospheric microbiome with considerable spatiotemporal variability, which are generally categorized as natural and anthropogenic sources. Accurate monitoring and source apportionment are critical for assessing [...] Read more.

Bioaerosols play significant roles in ecological interactions, climate change, and public health. Their diverse origins contribute to a dynamic atmospheric microbiome with considerable spatiotemporal variability, which are generally categorized as natural and anthropogenic sources. Accurate monitoring and source apportionment are critical for assessing environmental impacts and health risks. This review systematically summarizes the characteristics of bioaerosol sources and emphasizes emission risks from intensive human activities. This study also elucidates source apportionment strategies of bioaerosols and analyzes the technological evolution from traditional culture-based methods to advanced molecular and real-time physicochemical systems. In addition, the shift of bioaerosol monitoring technologies towards high-sensitivity, culture-independent, and online monitoring is emphasized in this review. An outlook on future research priorities is provided in the end. We emphasize the pressing need to establish localized characteristic databases, develop integrated real-time monitoring systems coupling rapid screening with deep biological analysis, and optimize the application of machine learning and AI algorithms to enhance the precision of multi-source contribution modeling in complex environments. Full article

(This article belongs to the Special Issue Sources, Characteristics, and Environmental Pollution Control of Organic Pollutants in the Atmosphere)

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23 pages, 12939 KB

Open AccessEditor’s ChoiceArticle

PFOA Damages Blood–Testis Barrier Integrity in Mice by Inhibited Glycolysis Caused H3K18 Lactylation Modification Impairment

by Zhengqi Song, Jinxin Ruan, Lingqiao Wang, Ke Cui, Zhiling Wu, Weiyan Chen, Yao Tan, Yiqi Wang, Guanghui Zhang, Guowei Zhang, Wenbin Liu, Zhiliang Cheng, Jun Li and Ziyuan Zhou

Toxics 2026, 14(5), 399; https://doi.org/10.3390/toxics14050399 - 7 May 2026

Viewed by 1364

Abstract

The molecular mechanism underlying male reproductive toxicity associated with Perfluorooctanoic acid (PFOA), a persistent environmental endocrine disruptor (EDC), has not yet been fully elucidated. Six-week-old male C57BL/6 mice were treated with PFOA by oral gavage at 0, 1.25, 5, 10, and 20 mg/kg/day [...] Read more.

The molecular mechanism underlying male reproductive toxicity associated with Perfluorooctanoic acid (PFOA), a persistent environmental endocrine disruptor (EDC), has not yet been fully elucidated. Six-week-old male C57BL/6 mice were treated with PFOA by oral gavage at 0, 1.25, 5, 10, and 20 mg/kg/day for 35 days to explore its toxic effects on the male reproductive system and the underlying mechanisms. Analyses of semen quality, testicular histopathology, and blood–testis barrier (BTB) integrity revealed that PFOA caused dose-dependent structural and functional damage to the BTB, leading to markedly reduced semen quality. Based on transcriptomic sequencing and differential gene enrichment analysis, the glycolytic pathway was identified as a key regulatory target for PFOA-induced damage to the reproductive system. Further validation revealed that PFOA exposure inhibited glycolysis-related enzymes (Hexokinase 1 (HK1), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDHA)), reduced lactate production and ATP synthesis, lowered Pan-Kla and H3K18la levels, and diminished H3K18la enrichment at the Hk1, Glut1, and Ldha promoters, whereas exogenous sodium lactate reversed these changes. This study is the first to identify the “glycolysis–lactate–H3K18la” chain as a key regulator in PFOA-induced BTB damage and spermatogenesis impairment, offering a new theoretical foundation for understanding EDC-induced male reproductive toxicity. Full article

(This article belongs to the Section Reproductive and Developmental Toxicity)

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20 pages, 957 KB

Open AccessEditor’s ChoiceArticle

Safety Assessment of Sophora flavescens Root Extract for Cosmetic Use: An Integrated Approach Using In Vitro, In Silico MoS, TTC, and History of Safe Use

by Sangwon Gil, Hogeon Lee, Seung Ha Lee, Seung A. Shin, Dal Woong Choi and Kyung-Min Lim

Toxics 2026, 14(5), 398; https://doi.org/10.3390/toxics14050398 - 6 May 2026

Viewed by 1283

Abstract

Evaluating the safety of botanical extracts for cosmetics has become mandatory, but it is often challenging because of their phytochemical complexity and limited toxicological data. In this study, the safety of aqueous Sophora flavescens root extract (SFRE), widely used in cosmetics, was assessed [...] Read more.

Evaluating the safety of botanical extracts for cosmetics has become mandatory, but it is often challenging because of their phytochemical complexity and limited toxicological data. In this study, the safety of aqueous Sophora flavescens root extract (SFRE), widely used in cosmetics, was assessed using an integrated approach combining in vitro, in silico, margin of safety (MoS), threshold of toxicological concern (TTC), and history of safe use (HSU). Chemical characterization was performed by literature review and LC–MS/MS analysis. SFRE was classified as non-irritant in in vitro skin and eye irritation tests conducted according to OECD TG439 and 492. Whole-extract and constituent-level in silico analysis and literature evaluation were conducted to assess genotoxicity and skin sensitization potential. For systemic toxicity, a 13-week oral repeat dose no-observed-adverse-effect level (NOAEL) of 10 mg/kg bw/day for a decocted Sophorae radix extract was employed without compositional adjustment to calculate the acceptable systemic exposure dose of 0.10 mg/kg bw/day, which was slightly lower than the current usage of SFRE in cosmetics (up to 0.13 mg/kg/day). The TTC approach revealed that many bioactive constituents fell outside the applicability domain due to steroid moieties. HSU data from dietary supplements (32–64.67 mg/kg/day) could support the safety of the current use of SFRE in cosmetics. The findings highlight that a combined, case-by-case application of MoS, TTC, and HSU is essential for the robust safety assessment of complex botanical ingredients. Full article

(This article belongs to the Special Issue New Approach Methodologies for Agrochemicals and Food Toxicology)

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28 pages, 7585 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Combined Effect of Per- and Polyfluoroalkyl Substances and Metals on Epigenetic Aging

by Faustina Acquaah and Emmanuel Obeng-Gyasi

Toxics 2026, 14(5), 394; https://doi.org/10.3390/toxics14050394 - 4 May 2026

Viewed by 1849

Abstract

Environmental contaminants such as per- and polyfluoroalkyl substances (PFAS) and toxic metals have been implicated in biological aging, yet their combined effects remain poorly understood. This study evaluated the associations of PFAS, lead, and cadmium mixtures with multiple DNA methylation-based measures of epigenetic [...] Read more.

Environmental contaminants such as per- and polyfluoroalkyl substances (PFAS) and toxic metals have been implicated in biological aging, yet their combined effects remain poorly understood. This study evaluated the associations of PFAS, lead, and cadmium mixtures with multiple DNA methylation-based measures of epigenetic aging in a nationally representative sample of U.S. adults aged ≥ 50 years. Data were obtained from the 1999–2000 and 2001–2002 National Health and Nutrition Examination Survey (NHANES). The analytic sample included 1119 participants with available data on seven PFAS, blood lead, cadmium, and DNA methylation measures. Epigenetic aging outcomes included HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge, and DunedinPoAm. Multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) were used to assess individual and joint exposure–response relationships. Cadmium showed the most consistent positive associations with epigenetic aging measures, particularly for the second-generation clocks PhenoAge and GrimAge. Lead was positively associated with GrimAge, while PFAS showed more variable and generally weaker associations, with PFNA demonstrating the most consistent signal. Mixture analyses indicated that higher combined exposure levels were associated with higher DNA methylation age estimates, with stronger patterns observed for second-generation clocks. These findings suggest that combined exposure to PFAS, lead, and cadmium is associated with higher epigenetic aging in older U.S. adults, with cadmium emerging as a key contributor to the observed mixture effects. Evaluating environmental exposures as mixtures may provide important insight into how co-occurring contaminants jointly influence biological aging. Full article

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21 pages, 1215 KB

Open AccessEditor’s ChoiceReview

From Static Assessment to Dynamic Management: A Paradigm Shift in Biotoxicity Evaluation of Activated Sludge for Pharmaceutical Wastewater Treatment

by Zhicheng Zhang, Wenyan Huang, Jinfeng Ding, Wenli Liu, Ruoxuan Xia, Worou Chabi Noel, Zhongjian Li, Hui Chen and Jun Yao

Toxics 2026, 14(5), 395; https://doi.org/10.3390/toxics14050395 - 4 May 2026

Viewed by 1628

Abstract

The activated sludge process serves as the core barrier in pharmaceutical wastewater treatment, yet its stability is inherently challenged by the extreme complexity of influent composition and the unpredictability of toxic shocks, particularly under contract development and manufacturing organization (CDMO) operations. Current biotoxicity [...] Read more.

The activated sludge process serves as the core barrier in pharmaceutical wastewater treatment, yet its stability is inherently challenged by the extreme complexity of influent composition and the unpredictability of toxic shocks, particularly under contract development and manufacturing organization (CDMO) operations. Current biotoxicity assessment methods face inherent trade-offs among timeliness, specificity, and matrix robustness, resulting in fragmented, reactive management that lacks predictive capacity. In response, this review critically synthesizes evidence on toxicity pathways and monitoring technologies, systematically evaluating their mechanistic basis and engineering applicability. Building on these findings, we propose a conceptual perception–cognition–response architecture that structures decision-making across three adaptive tiers: (i) a perception layer that tolerates false positives for rapid anomaly detection; (ii) a cognition layer that requires effect-based biological verification; and (iii) a response layer that authorizes resilience-oriented interventions. Rather than a linear pipeline, the three tiers form an adaptive feedback cycle that dynamically aligns monitoring intensity, verification depth, and response authority with real-time risk gradients and site-specific constraints. By explicitly linking biological mechanisms to assessment limitations and tiered decision rules, this review provides a hypothesis-generating roadmap that orients biotoxicity management from episodic, composition-based assessment toward adaptive, effect-driven control. The proposed framework is intended to guide future pilot validation, multi-sensor integration, and context-specific calibration, offering a unified narrative for advancing proactive biotoxicity control in complex pharmaceutical wastewater systems. Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

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17 pages, 24098 KB

Open AccessEditor’s ChoiceArticle

Dynamics of Attached Bacteria and Potentially Pathogenic Bacteria to Expanded Polystyrene Plastic Litter in Marine Field Experiments

by Hyun-Jung Kim, Gaeul Jeong, Kang Eun Kim, Jung Hoon Kang, Ok Hwan Yu, Won Joon Shim, Sang Heon Lee, Min-Chul Jang, Jae-Hyeok Lee and Seung Won Jung

Toxics 2026, 14(5), 392; https://doi.org/10.3390/toxics14050392 - 2 May 2026

Viewed by 1628

Abstract

Expanded polystyrene litter in marine environments harbors diverse and distinct microbial communities, referred to as the plastisphere. This study aimed to investigate the monthly dynamics of bacterial and potentially pathogenic bacterial (PPB) communities on expanded polystyrene over one year. Vibrio species dominated the [...] Read more.

Expanded polystyrene litter in marine environments harbors diverse and distinct microbial communities, referred to as the plastisphere. This study aimed to investigate the monthly dynamics of bacterial and potentially pathogenic bacterial (PPB) communities on expanded polystyrene over one year. Vibrio species dominated the PPB community, cooccurring at consistently higher abundances on expanded polystyrene than in the surrounding seawater, particularly under higher temperatures and low dissolved organic carbon (DOC) levels. At a temperature threshold of 16 °C, the abundance of zoonotic species, such as Vibrio parahaemolyticus and Vibrio alginolyticus, increased significantly. Some psychrotrophic Vibrio spp. were detected under moderately eutrophic conditions, suggesting that expanded polystyrene may also serve as a dispersal vector facilitating their transport to more favorable habitats. Multivariate analyses, including partial least squares path modeling, revealed temperature and DOC as the primary environmental factors influencing PPB community composition. However, environmental responses varied by taxonomic groups, with different preferences observed under varying eutrophic conditions. In conclusion, these findings demonstrate that expanded polystyrene litter supports a selective and environmentally responsive bacterial population, highlighting the potential role of plastic debris in promoting pathogenic bacterial persistence and spread in marine ecosystems, particularly under conditions associated with climate change, including warming and eutrophication. Full article

(This article belongs to the Topic Plastic Contamination (Plastamination): An Environmental and Public Health-Related Concern)

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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 2670

Abstract

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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37 pages, 3390 KB

Open AccessEditor’s ChoiceArticle

Hepatic Mitochondrial Dysfunction and Gut Dysbiosis Induced by Polyethylene Microplastics in FVB/n Mice: A Comparative Study of Fluorescent and Non-Fluorescent Particles

by Mónica G. Silva, Beatriz Medeiros-Fonseca, Adelina Gama, Isabel Gaivão, Sílvia Nunes, Mariana Fernandes, Paula A. Oliveira, Vicente Monedero, Manuel Zúñiga, Maria Manuel Oliveira and Francisco Peixoto

Toxics 2026, 14(5), 386; https://doi.org/10.3390/toxics14050386 - 30 Apr 2026

Cited by 1 | Viewed by 1916

Abstract

The emerging problem that microplastics pose to our society is reflected in the exponential growth in investigations devoted to uncovering their toxicological potential in humans. However, these studies present several limitations, one of the most significant being the use of microplastics that do [...] Read more.

The emerging problem that microplastics pose to our society is reflected in the exponential growth in investigations devoted to uncovering their toxicological potential in humans. However, these studies present several limitations, one of the most significant being the use of microplastics that do not represent their environmental counterparts. In this study, we evaluated the impact of two types of polyethylene microplastics (27–32 µm)—non-fluorescent and fluorescent—on the liver and intestine, targeting mitochondria. FVB/n mice were subjected to a subacute exposure to two concentrations representative of human exposure (0.002% (w/w) and 0.006% (w/w)). Both types of microplastics impaired mitochondrial respiration through disruption of NADH-linked pathways, with more pronounced effects at the highest concentration of fluorescent MPs. Electron transport chain complexes, particularly CIII and CIV, were affected, partially explaining the observed alterations in mitochondrial respiratory capacity. An increased SOD and GPx activity supported the link between mitochondrial dysfunction and increased reactive oxygen species overproduction under MPs exposure. Hepatic mitochondrial lipid remodelling was detected following exposure to fluorescent microplastics, while intestinal epithelial cells displayed impaired mitochondrial activity together with compromised cellular integrity, indicative of stress response. In parallel, shifts in gut composition suggest that PE MPs may contribute to intestinal barrier dysfunction. Overall, fluorescent MPs induced more severe mitochondrial and biochemical disturbances in both the liver and the intestine than their non-fluorescent counterparts. Our findings highlight mitochondria as central targets for microplastic-induced toxicity and underscore the need for improved MPs models in toxicological research. Full article

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