Toxics

22 pages, 1830 KB

Open AccessArticle

Toward Animal-Free Phototoxicity Testing: A Keratinocyte-Based UVA Screening Assay to Distinguish Photoirritation from Photoallergy

by Adriana S. Maddaleno, Elisabet Teixidó, Laia Guardia-Escoté, Montserrat Mitjans and Maria Pilar Vinardell

Toxics 2026, 14(8), 726; https://doi.org/10.3390/toxics14080726 (registering DOI) - 16 Aug 2026

Abstract

Phototoxicity represents an increasing concern due to the presence of photoreactive chemicals in consumer products, including household products, pharmaceuticals, and cosmetic formulations. Upon exposure to solar radiation, these compounds may induce photoirritation, a non-immune-mediated inflammatory response, or photoallergy, an immune-mediated hypersensitivity reaction. However, [...] Read more.

Phototoxicity represents an increasing concern due to the presence of photoreactive chemicals in consumer products, including household products, pharmaceuticals, and cosmetic formulations. Upon exposure to solar radiation, these compounds may induce photoirritation, a non-immune-mediated inflammatory response, or photoallergy, an immune-mediated hypersensitivity reaction. However, the ability to discriminate between photoirritant and photoallergic responses remains an unmet need, as no validated in vitro assay is currently available for this purpose. Therefore, the development of reliable non-animal approaches is essential to address ethical concerns and comply with current regulatory restrictions on animal testing. Interleukin-18 (IL-18) has been proposed as a potential biomarker of allergic and photoallergic responses. In this study, we developed an in vitro assay adapted from OECD Test Guideline 432 using reference phototoxic compounds and demonstrated that exposure to the photoallergenic compound benzophenone induced IL-18 production. Furthermore, multiplex cytokine profiling identified two additional preliminary candidate biomarkers for discriminating between photoallergic and photoirritant responses. Matrix metalloproteinase-1 (MMP-1) was associated with photoallergic responses and was upregulated following exposure to chlorpromazine and benzophenone, whereas interleukin-6 (IL-6) was associated with photoirritant responses and was upregulated following exposure to 8-methoxypsoralen. Collectively, these findings provide proof-of-concept evidence supporting the future development of a novel non-animal strategy for predicting and discriminating between photoirritant and photoallergenic compounds. Full article

(This article belongs to the Special Issue Advancing Cosmetic Safety Science: Approaches for Skin Compatibility and Risk Assessment)

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25 pages, 2308 KB

Open AccessArticle

An Investigation of Heavy Metal Accumulation in Liver and Kidney Tissues of the European Hare (Lepus europaeus P.) in Samples Originating from Intensive Agricultural Environments in Hungary

by Attila Bende, László Bánáti, László Könyves, Balázs Berlinger and István Fekete

Toxics 2026, 14(8), 725; https://doi.org/10.3390/toxics14080725 (registering DOI) - 16 Aug 2026

Abstract

The aim of this study was to evaluate the concentrations of 17 heavy metals measured in the liver and kidney tissues of the European brown hare (Lepus europaeus) as a function of age, sex, organ type, and sampling area. In addition, [...] Read more.

The aim of this study was to evaluate the concentrations of 17 heavy metals measured in the liver and kidney tissues of the European brown hare (Lepus europaeus) as a function of age, sex, organ type, and sampling area. In addition, we assessed the relationships between trace element profiles and reproductive parameters and highlighted their potential relevance from a food-safety perspective. Age-related comparisons revealed significantly higher concentrations of Ti, Fe, Cd, and Hg in adult individuals, whereas no statistically significant differences were detected for the remaining elements. No significant sex-related differences were found for any of the investigated elements. In contrast, the organ-based analysis revealed substantial differences. The concentrations of all elements differed significantly between the liver and the kidney. Correlation analyses identified positive associations between Mn and Zn concentrations, as well as between Mn and Cu concentrations, in both organs. The relationship between Zn and Cd was also positive and statistically significant. A comparison among sampling areas showed no significant spatial differences in the concentrations of Cr, Fe, Cu, and Mo. The greatest spatial heterogeneity was observed for Co, Hg, Pb, and Se, with Se concentrations differing significantly among nearly all sampling areas. Our results indicate strongly overlapping spatial heavy metal profiles, suggesting a gradual rather than sharply differentiated geographical pattern and similar emission characteristics. This interpretation is further supported by the clustering and principal component analysis (PCA) results. PERMANOVA analyses indicated that trace element profiles did not significantly influence the number of placental scars. Furthermore, neither age nor its interaction with trace element profiles exerted a detectable effect on variation in placental scar numbers. Full article

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19 pages, 5330 KB

Open AccessArticle

In Vitro Three-Dimensional Human Liver Model for Drug-Induced Liver and Bile Duct Injury Prediction

by Xiaonan Fu, Jiangping Hu, Xintong Jiang, Yedan Sun, Wanling Xiang, Rong Kuang, Hua Kang, Licheng He and Jing Sang

Toxics 2026, 14(8), 724; https://doi.org/10.3390/toxics14080724 - 14 Aug 2026

Abstract

In drug-induced liver injury (DILI) prediction field, animal models and in vitro cell models are most commonly used. However, animal models require long experimental timelines and may exhibit species-specific differences compared with humans, whereas conventional two-dimensional (2D) cell culture models lack cell-to-cell and [...] Read more.

In drug-induced liver injury (DILI) prediction field, animal models and in vitro cell models are most commonly used. However, animal models require long experimental timelines and may exhibit species-specific differences compared with humans, whereas conventional two-dimensional (2D) cell culture models lack cell-to-cell and cell-to-extracellular matrix (ECM) interaction. Liver organoid models and liver organ-on-a-chip can better simulate the human liver microenvironment; however, the construction of liver organoids requires a long cycle and high costs, while liver organ-on-a-chip systems demand specialized equipment and professional technicians. Herein, we selected the human C3A cell line, characterized by its low cost and facile culture conditions to establish an in vitro three-dimensional (3D) liver model. Briefly, C3A cells were embedded in Matrigel and cultured for 7 days to allow model maturation. Compared with their 2D-cultured cell model, the established 3D model exhibited elevated mRNA expression levels of drug-metabolizing cytochrome P450 enzymes (CYPs). Moreover, the model displayed robust expression of key hepatic biomarkers, as well as bile duct biomarkers. To evaluate the model’s applicability for DILI prediction, we performed toxicity assessments using a panel of six well-characterized hepatotoxicants and three non-hepatotoxic compounds. Notably, the 3D C3A model achieved a sensitivity of 83.3%, specificity of 100%, and overall accuracy of 88.9%. Furthermore, treatment of this model with chlorpromazine, a well-characterized cholangiotoxic agent, resulted in suppressed expression of the bile duct biomarker cytokeratin 19 (CK19) and bile salt export pump (BSEP), accompanied by impaired bile acid transport capacity. Taken together, this study provided a simple, low-cost, easy to culture, and more readily scalable 3D hepatic model in comparison with conventional 2D primary human hepatocyte (PHHs) models and other advanced 3D liver models. Notably, the model displayed dual hepatic and biliary characteristics, supporting predictions of both DILI and drug-induced bile duct injury. It provided a promising in vitro platform for assessing drug-induced hepatobiliary toxicity, with potential to reduce reliance on animal experiments and accelerate early-stage screening of novel pharmaceutical candidates. Full article

(This article belongs to the Section Drugs Toxicity)

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31 pages, 1358 KB

Open AccessArticle

Occurrence and Detection Profiles of Technology-Critical Elements (Ga, Ge, Nb, Ta and W) in Wild Mushrooms from Leicester and Leicestershire, UK

by Antonio Peña-Fernández, Tomás Cámara-Pastor, Guillermo Torrado Durán and M. Carmen Lobo-Bedmar

Toxics 2026, 14(8), 723; https://doi.org/10.3390/toxics14080723 - 14 Aug 2026

Abstract

Technology-critical elements are increasingly used in electronics, renewable-energy systems, high-performance alloys and other strategic technologies, yet their occurrence in wild fungi remains poorly characterised. This study evaluated gallium (Ga), germanium (Ge), niobium (Nb), tantalum (Ta) and tungsten (W) in wild mushrooms collected from [...] Read more.

Technology-critical elements are increasingly used in electronics, renewable-energy systems, high-performance alloys and other strategic technologies, yet their occurrence in wild fungi remains poorly characterised. This study evaluated gallium (Ga), germanium (Ge), niobium (Nb), tantalum (Ta) and tungsten (W) in wild mushrooms collected from Leicester and Leicestershire, UK. The dataset was reconstructed at fruiting-body level to avoid pseudo-replication from paired cap and stem records, yielding 121 analytical units. Results were corrected using digestion-date acid blanks, interpreted against analytical-portion-specific working limits of detection and classified as fully quantified (FQ), partially censored (PC) or fully censored (FC). Ga was FQ in 106/121 units and was the only element with sufficient quantitative coverage for continuous distributional estimation; its regression-on-order-statistics median was 475.48 ng g⁻¹ dw (IQR: 278.70–941.63). The corresponding FQ counts were 16 for Ge, 33 for Nb, 10 for Ta and 24 for W, with 7, 4 and 4 additional PC observations for Nb, Ta and W, respectively. In 22 paired Agaricus bitorquis fruiting bodies, Ga concentrations were higher in stems than caps (Wilcoxon p = 5.25 × 10⁻⁵; BH-FDR = 1.05 × 10⁻⁴). Composite topsoils from 26 monitored sites provided park-scale geochemical context only and were not used to infer bioaccumulation or direct soil-to-fungus transfer. These findings establish a blank-corrected and censoring-aware occurrence baseline and suggest exploratory, site-specific potential for wild mushrooms as complementary biomonitoring matrices for selected technology-critical elements, while demonstrating that their usefulness is element-, taxon- and design-dependent. Full article

(This article belongs to the Section Emerging Contaminants)

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15 pages, 2744 KB

Open AccessProtocol

Effects of Per- and Polyfluoroalkyl Substances (PFAS) Exposure Reduction on Serum Lipids in the Copenhagen City Heart Study: A Protocol for an Observational Cohort Study Emulating a Target Trial

by Georges Khoury, Laura Deen, Lars Christian Lund, Erich Batzella, Michelle C. Turner, Gorm Boje Jensen, Tina Kold Jensen and Sandra Søgaard Tøttenborg

Toxics 2026, 14(8), 722; https://doi.org/10.3390/toxics14080722 - 14 Aug 2026

Abstract

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants associated with higher serum lipids, although primarily in cross-sectional studies, limiting causal inference. We aim to determine whether there is a causal relationship between PFAS and serum lipid levels by emulating a target trial of [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants associated with higher serum lipids, although primarily in cross-sectional studies, limiting causal inference. We aim to determine whether there is a causal relationship between PFAS and serum lipid levels by emulating a target trial of a hypothetical PFAS-reduction intervention using observational data. The target trial would enroll adults aged ≥20 years without prior cardiovascular, kidney, or liver disease, diabetes, or use of related medications. Participants would be randomly assigned to either PFAS-reduction counseling or no counseling, with adherence evaluated after 10 years, and then followed up after 10 years to assess effects on serum lipids. To emulate the target trial, we will use data from the Copenhagen City Heart Study on three successive clinical visits: baseline, follow-up, and outcome assessment visit, 10 years apart. Eligible participants meet the target trial criteria, have available blood samples for PFAS quantification at follow-up, and information on serum lipids at the outcome assessment. Intervention strategies will be evaluated based on observed reductions in PFAS concentrations between baseline and follow-up visit. Serum lipids are assessed at the outcome assessment visit. The emulation assumes exchangeability by adjusting for baseline and time-varying confounders using G-computation. This protocol explores applying the target trial emulation framework to improve causal inference in environmental epidemiology. Full article

(This article belongs to the Special Issue Association Between Environmental Pollutants Exposures and Chronic Disease)

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15 pages, 488 KB

Open AccessArticle

Discrepancies Between Predicted and Measured Microelements and Toxic Elements in Beetroot Supplemented Diets

by Michał S. Majewski, Łukasz Smyk, Anetta Hanć, Agnieszka Owczarczyk-Saczonek, Waldemar Jarosław Grzegorzewski, Joanna Majkowska-Gadomska and Anna Francke

Toxics 2026, 14(8), 721; https://doi.org/10.3390/toxics14080721 - 14 Aug 2026

Abstract

Background: Accurate assessment of microelement and toxic element content in animal diets is essential for diet formulation, quality control, and exposure assessment; however, predictive additive models may not fully account for variability arising from raw materials and processing factors. Methods: This [...] Read more.

Background: Accurate assessment of microelement and toxic element content in animal diets is essential for diet formulation, quality control, and exposure assessment; however, predictive additive models may not fully account for variability arising from raw materials and processing factors. Methods: This study evaluated the composition of microelements and toxic elements in the four diets enriched with 4% beetroot cultivars Boldor and Wodan, either without (level 1) or with (level 3) foliar application of the selenium–based plant growth stimulator. Predicted values (calculated using an additive model P = 0.96 × C _{basal diet} + 0.04 × C _{beetroot component}) were compared with experimentally measured concentrations (M). Four dietary variants Boldor 1, Boldor 3, Wodan 1 and Wodan 3 were analyzed. Elemental concentrations of Fe, Zn, Cu, Cr, Ni, Se, Pb, As, Cd, and Sb were determined using ICP-MS. Results: Substantial discrepancies between predicted (P) and measured (M) values were observed. The largest deviations occurred for Cr, Fe, and Sb. Cr and Sb were generally underestimated by the model, whereas Fe was consistently overestimated. Selenium (Se) showed moderate variability, while Cu, Zn, and Ni exhibited close agreement between predicted and measured values. The largest measured cultivar-related differences were observed for As (2.87-fold), Cd (2.78-fold), Pb (2.47-fold), Cr (2.37-fold), Fe (1.73-fold), Sb (1.57-fold), Cu (1.13-fold), and Zn (1.05-fold), all of which occurred at higher concentrations in Wodan than in Boldor. No statistically significant effect of the selenium–based plant growth stimulator was observed. Conclusions: Overall, the results demonstrate that additive models have limited accuracy in predicting trace element composition in complex diets, particularly for elements potentially affected by raw-material variability, sampling heterogeneity, and analytical uncertainty. The contribution of the dietary 4% beetroot component played a key role in shaping element distribution, particularly for elements with high component-to-basal diet ratios. These findings highlight the importance of proper mixing, prevention of segregation in powdered diets, and strict control of raw material quality. Full article

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19 pages, 1141 KB

Open AccessArticle

Can Post-Mortem Cartilage Reliably Preserve Ethanol? A Time-Course Comparison with Blood and Urine

by Aleksandra Zorychta, Małgorzata Głaz, Rafał Skowronek, Joanna Nowicka, Marcin Tomsia and Elżbieta Chełmecka

Toxics 2026, 14(8), 720; https://doi.org/10.3390/toxics14080720 - 14 Aug 2026

Abstract

The time interval between the collection of biological material and the performance of toxicological analyses is particularly important when the appropriate storage temperature cannot be maintained. This issue is especially relevant in the determination of ethanol concentration in specimens obtained from drivers suspected [...] Read more.

The time interval between the collection of biological material and the performance of toxicological analyses is particularly important when the appropriate storage temperature cannot be maintained. This issue is especially relevant in the determination of ethanol concentration in specimens obtained from drivers suspected of intoxication or being under the influence of ethanol, as well as in samples collected during post-mortem examinations. The present study evaluated the effect of room-temperature storage on ethanol concentrations in post-mortem blood, urine, costal cartilage, and intervertebral disc cartilage collected from 57 cadavers. According to Polish law, blood ethanol concentrations > 0.2 mg/mL and >0.5 mg/mL were classified as “after alcohol use” and “intoxication”, respectively. Two subgroups were therefore distinguished from the study group: 27 ethanol-positive > 0.5 mg/mL (intoxicated) and 30 ethanol-negative cases—less than or equal to 0.5 mg/mL (sober). Ethanol concentrations were determined using gas chromatography with flame ionization detection (GC-FID). Statistically significant differences in blood ethanol concentration were observed in ethanol-positive individuals depending on storage time after sample collection (p < 0.001). Under the storage conditions used in this study, no increase in ethanol concentration was observed in samples collected from ethanol-negative individuals. In ethanol-positive individuals, ethanol concentrations decreased progressively in all analyzed matrices during room-temperature storage. Urine showed the greatest stability throughout the observation period. In both cartilage matrices, ethanol was detectable up to day 3, whereas all measurements were negative from day 4 onward. Blood ethanol concentrations also decreased during storage. By day 4, the mean concentration was below the legal intoxication threshold. Full article

(This article belongs to the Special Issue Current Issues and Research Perspectives in Forensic Toxicology)

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18 pages, 4121 KB

Open AccessArticle

A Comparison of the Application of Four MEA-Based Neurotoxicity Screening Methods in Ni²⁺ Neurotoxicity Assessment

by Chen Meng, Yang Lu, Yan Huang, Zhi-Gong Wang and Xiao-Ying Lü

Toxics 2026, 14(8), 719; https://doi.org/10.3390/toxics14080719 - 14 Aug 2026

Abstract

Microelectrode array (MEA) technology is widely employed in electrophysiological research and, in recent years, has increasingly been applied in the screening of neurotoxicity. In this study, we investigated the neurotoxic effects of different concentrations of Ni²⁺ by analyzing its influence on the [...] Read more.

Microelectrode array (MEA) technology is widely employed in electrophysiological research and, in recent years, has increasingly been applied in the screening of neurotoxicity. In this study, we investigated the neurotoxic effects of different concentrations of Ni²⁺ by analyzing its influence on the mean firing and bursting rates of spontaneous activity, as well as the frequency of electrical-stimulation-evoked activity in the neocortical region in rat brain slices through MEA. Integrating our team’s prior findings on Ni²⁺’s influence on the electrical stimulation threshold of evoked activity, we compared the application effectiveness of the four MEA-based neurotoxicity screening methods in Ni²⁺ neurotoxicity research. Our results demonstrate that all of these methods can effectively assess the neurotoxic effects of Ni²⁺; however, they differ in certain aspects, such as the applicable neuronal networks and data-processing approaches. We also found that Ni²⁺ influences spontaneous and electrical-stimulation-evoked activity in the neocortical region in rat brain slices via distinct mechanisms. Full article

(This article belongs to the Section Neurotoxicity)

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20 pages, 1685 KB

Open AccessArticle

Probabilistic Ecological Risk Assessment of Synthetic Musk Compounds in the Han River Estuary: Integrating Multi-Year Monitoring and Explainable Machine Learning

by Jungmin Jo, Na Rae Choi, Eunjin Lee, Jae Won Yoo, Dong Sik Ahn, Ji Yi Lee and Yun Gyong Ahn

Toxics 2026, 14(8), 718; https://doi.org/10.3390/toxics14080718 - 13 Aug 2026

Abstract

Synthetic musk compounds (SMCs) are emerging contaminants frequently detected in aquatic environments due to their widespread use in personal care and household products. This study investigated the occurrence, environmental drivers, and ecological risks of twelve SMCs in the Han River estuary and adjacent [...] Read more.

Synthetic musk compounds (SMCs) are emerging contaminants frequently detected in aquatic environments due to their widespread use in personal care and household products. This study investigated the occurrence, environmental drivers, and ecological risks of twelve SMCs in the Han River estuary and adjacent coastal waters, Korea, using three years of monitoring data (2020–2022). A total of 222 water samples from 13 monitoring stations were analyzed by GC–MS. 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB) was the dominant compound, followed by musk ketone (MK). Total SMC concentrations ranged from non-detectable levels to 157.6 μg/L, with the highest concentrations consistently observed at wastewater treatment facilities. XGBoost-SHAP analysis identified total nitrogen (TN) as the most influential predictor of SMC occurrence. This association reflects the shared wastewater origin of the two rather than any causal link, so that TN serves as an indicator of wastewater influence rather than of SMC concentration itself. Ecological risks were evaluated using Monte Carlo-based probabilistic hazard quotient (HQ) analysis. HHCB and MK exhibited the highest risks, with mean HQ values exceeding 1.0 at wastewater treatment facilities, indicating potential ecological concern. In contrast, most coastal sites showed low risk levels. The observed spatial patterns identified wastewater discharge zones as major hotspots of SMC exposure and ecological risk. These findings highlight the importance of wastewater-derived SMCs as emerging contaminants in estuarine environments and demonstrate the utility of integrating long-term monitoring, explainable machine learning, and probabilistic risk assessment for ecological risk characterization. Full article

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

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22 pages, 1724 KB

Open AccessArticle

Basic Study on Mercury Methylation Under Oxic Conditions: Incubation Experiments Using Seawater from Minamata Bay, Japan

by Akito Matsuyama, Michiaki Kindaichi and Yoko Taniguchi

Toxics 2026, 14(8), 717; https://doi.org/10.3390/toxics14080717 - 13 Aug 2026

Abstract

Background: This study investigated the generation of dissolved methylmercury (diss-MeHg) under oxic conditions in the surface waters of Minamata Bay. Although mercury methylation has been extensively investigated under reducing conditions, its occurrence under oxic conditions remains poorly understood. Methods: Incubation conditions capable of [...] Read more.

Background: This study investigated the generation of dissolved methylmercury (diss-MeHg) under oxic conditions in the surface waters of Minamata Bay. Although mercury methylation has been extensively investigated under reducing conditions, its occurrence under oxic conditions remains poorly understood. Methods: Incubation conditions capable of artificially inducing mercury methylation were established for the first time. Incubation parameters were optimized using surface seawater samples. Results: Diss-MeHg production was positively correlated with dissolved organic carbon (DOC) concentrations (1–5 mg/L). The highest methylation was observed at 22 °C and 32.5‰ salinity, though no statistically significant differences were observed within the ranges of 18–22 °C and 30.5–34.5‰. Under the optimized conditions (22 °C, 32.5‰, 5 mg/L DOC), seawater samples were sequentially filtered through membranes of various pore sizes. Diss-MeHg was detected in fractions filtered through 0.8- and 3-µm membrane filters but was absent from the 0.45- and 0.2-µm fractions. Additionally, autoclaving the 0.8 µm filtrate prevented diss-MeHg production. Conclusions: These findings suggest the presence of a distinct biological mercury methylation process operating under oxic conditions in surface seawater. Full article

(This article belongs to the Section Ecotoxicology)

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16 pages, 1755 KB

Open AccessFeature PaperArticle

Pisolithus arhizus Inoculation Enhances Mercury Tolerance and Growth of Trifolium repens in Mining Soils

by Mónica López Velarde Santos, Adrian Ferrucio García-Morales, José Alberto Rodríguez Morales, Felix Leao Rodríguez Fierros, Yesenia Mendoza-Burguete, Juan Campos-Guillén, Miguel Angel Ramos-López, María del Carmen González-López, María Carolina Espinosa Arzate, Luisa Ramírez Granados and Ricardo Chaparro Sanchez

Toxics 2026, 14(8), 716; https://doi.org/10.3390/toxics14080716 - 13 Aug 2026

Abstract

While mining provides critical raw materials for modern infrastructure and the energy transition, it leaves behind severe environmental damages, such as soil mercury (Hg) contamination. In the present study, we present the first study evaluating the relationship of the ectomycorrhizal fungus Pisolithus arhizus [...] Read more.

While mining provides critical raw materials for modern infrastructure and the energy transition, it leaves behind severe environmental damages, such as soil mercury (Hg) contamination. In the present study, we present the first study evaluating the relationship of the ectomycorrhizal fungus Pisolithus arhizus with Trifolium repens (white clover) as a novel nature-based mycoremediation strategy for mercury-stressed soils. Through a controlled 2 × 2 factorial experiment over six months, we demonstrate that P. arhizus significantly enhances both plant biomass and heavy-metal tolerance. Inoculation achieved a 9.53% reduction in soil Hg and drove a dramatic 53% increase in stem growth under Hg stress (compared to 36% in non-contaminated conditions) once the extraradicular mycelial network was established. Furthermore, we report novel soil-chemistry dynamics under Hg stress, including a 16% shift in electrical conductivity alongside unexpected increases in the available potassium (+9%) and phosphorus (+3%). These findings present first results for a novel approach of mycoremediation by incorporating P. arhizus into T. repens co-cultivation as a viable remediation strategy, prior to field-scale remediation. Full article

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14 pages, 841 KB

Open AccessArticle

Advancing Lead Exposure Studies in Remote Settings: Method Development and Application of Lead Stable Isotope Analysis in Dried Blood Spots from Suriname, South America

by Manasi Simhan, Sean R. Scott, Martin M. Shafer, Jenny N. Poynter, Gaitree K. Baldewsingh, Wilco C. W. R. Zijlmans, Anisma R. Gokoel, Maureen Y. Lichtveld, Jeffrey K. Wickliffe and Shannon M. Sullivan

Toxics 2026, 14(8), 715; https://doi.org/10.3390/toxics14080715 - 13 Aug 2026

Abstract

Background: Lead (Pb) exposure remains a major global health issue, and Pb stable isotope ratio analysis is a powerful tool for identifying potential exposure sources. However, traditional whole blood collection is difficult to implement in remote or resource-limited settings. We developed and [...] Read more.

Background: Lead (Pb) exposure remains a major global health issue, and Pb stable isotope ratio analysis is a powerful tool for identifying potential exposure sources. However, traditional whole blood collection is difficult to implement in remote or resource-limited settings. We developed and validated a novel method for measuring Pb isotopic composition in dried blood spots (DBS) using a multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS) and applied it in a pilot study of DBS collected from children in Suriname, South America. Methods: Method accuracy was evaluated by comparing isotopic ratios (²⁰⁸Pb/²⁰⁶Pb and ²⁰⁷Pb/²⁰⁶Pb) measured in laboratory-spiked DBS (15 µL of blood per DBS) with those from matched whole blood samples (1 mL) across a range of Pb concentrations (2.1–28.9 µg/dL). The method was then applied to DBS collected from 18 children, ages 6 months to 5 years, in Suriname. Potential local exposure sources, including soil, shotgun pellets, and cooking utensils, were also analyzed for lead isotopic composition and compared with DBS isotope ratios to assess source concordance. Results: DBS isotopic ratios accurately reflected whole blood values when Pb concentrations exceeded ~315 pg/punch (~2.1 µg/dL), with greater accuracy observed above 5 µg/dL. In the Suriname DBSs, blank-corrected ²⁰⁸Pb/²⁰⁶Pb ratios were consistent across regions (mean 2.12 ± 0.018; n = 15) and showed no significant geographic stratification (p = 0.11). DBS signatures (isotope ratios) most closely aligned with shotgun pellets and soil samples, whereas those from cooking utensils did not match DBS signatures. A positive correlation was observed between estimated blood total Pb and soil Pb concentrations (ρ = 0.60, p = 0.20). Conclusions: Overall, DBS provided reliable Pb isotopic ratio measurements above ~2–5 µg/dL, spanning the current CDC reference value of 3.5 µg/dL at which children’s exposures warrant investigation. These findings support DBS as a minimally invasive, scalable tool for exposure source identification in environmental epidemiology, particularly in remote settings where traditional venipuncture is impractical. What this study adds: This study establishes the first validated method for high-precision lead (Pb) stable isotopic ratio analysis using dried blood spots (DBS). By implementing a sample blank correction, we demonstrate that DBS can accurately resolve isotopic signatures even at low blood lead concentrations. Applied in DBS collected in Suriname, the method successfully linked DBS signatures to local shotgun pellets and soils, illustrating a common exposure profile across diverse regions. This work expands the utility of DBS beyond simple screening, offering a minimally invasive, scalable tool for source attribution in global health research and environmental epidemiology in remote regions. Full article

(This article belongs to the Special Issue Analytical Methods for Trace Elements in Human Biofluids)

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23 pages, 6454 KB

Open AccessArticle

Transfer of ¹³⁷Cs into Maize (Zea mays L.) at Different Growth Stages in the Area Contaminated by the Chernobyl Chornobyl Fallout

by Tatiana Paramonova, Olga Denisova, Natalia Kuzmenkova, Leonid Turykhin, Maria Godyaeva and Alexei Konoplev

Toxics 2026, 14(8), 714; https://doi.org/10.3390/toxics14080714 - 12 Aug 2026

Abstract

Accumulation of radionuclides in crop products can pose public health risks. Parameters of ¹³⁷Cs root uptake by maize were investigated at four growth stages, from leaf development to ripening (June–September), in the post-Chornobyl area of the Plavsk radioactive hotspot (the Tula region [...] Read more.

Accumulation of radionuclides in crop products can pose public health risks. Parameters of ¹³⁷Cs root uptake by maize were investigated at four growth stages, from leaf development to ripening (June–September), in the post-Chornobyl area of the Plavsk radioactive hotspot (the Tula region of Russia). It was established that the chernozem of the agrosystem still contains about 180 kBq ¹³⁷Cs m⁻². Seasonal trends of ¹³⁷Cs activity concentrations in above- and belowground parts of maize differ appreciably. In aerial parts, the ¹³⁷Cs accumulation rate increases as vegetative organs develop from June to July, then drops when generative organs appear in August. In the belowground biomass, the ¹³⁷Cs content increases with the growth of fine roots, which serve as relative concentrators of the radionuclide. However, at all stages of growth, radionuclide transfer to maize occurs with low intensity. It does not directly depend on changes in biomass, dry matter content, or ⁴⁰K content, and only slightly relates to the ash content. The transfer factor is estimated to be 6.2 × 10⁻³ for cob kernels (grain) and 3.8 × 10⁻² for stems and leaves, which corresponds to the IAEA-recommended values and ensures acceptable levels of ¹³⁷Cs accumulation in crop products produced in the territory. Full article

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

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26 pages, 25848 KB

Open AccessArticle

Rutin-Loaded Nanostructured Lipid Carriers Attenuate Doxorubicin-Induced Nephrotoxicity and Modulate Epigenetic Regulation and MyD88/STAT3 Signaling

by Amina A. Farag, Walaa Bayoumie El Gazzar, Mahmoud Mostafa, Lina A. Mohammed, Azza S. El-Demerdash, Nagah E. M. Ali, Ranih Z. Amer, Heba S. Youssef, Noha Osama El-Shaer, Ibrahim A. Mostafa, Haidy M. Fakher and Sahar Soliman

Toxics 2026, 14(8), 713; https://doi.org/10.3390/toxics14080713 - 12 Aug 2026

Abstract

Doxorubicin (DOX)-induced nephrotoxicity remains a major limitation to its clinical use, yet the underlying epigenetic mechanisms are incompletely understood. This study investigated the role of epigenetic dysregulation and MyD88/STAT3 signaling in DOX-induced renal injury and evaluated the renoprotective efficacy of rutin-loaded nanostructured lipid [...] Read more.

Doxorubicin (DOX)-induced nephrotoxicity remains a major limitation to its clinical use, yet the underlying epigenetic mechanisms are incompletely understood. This study investigated the role of epigenetic dysregulation and MyD88/STAT3 signaling in DOX-induced renal injury and evaluated the renoprotective efficacy of rutin-loaded nanostructured lipid carriers (RUT-NLCs) compared with free rutin (RUT). Thirty-six rats were allocated to six experimental groups, and renal function, oxidative stress, inflammation, DNA damage, epigenetic modifications, MyD88/STAT3 signaling, histopathology, and ultrastructural changes were assessed. DOX administration induced severe renal dysfunction, oxidative stress, DNA damage, tubular injury, global DNA hypermethylation, aberrant histone methylation, Klotho promoter hypermethylation, and activation of the MyD88/STAT3 inflammatory pathway. Treatment with RUT-NLCs significantly attenuated these alterations by restoring antioxidant defenses, normalizing epigenetic markers, reducing DNA damage, suppressing MyD88/STAT3 signaling, and improving renal histopathological and ultrastructural architecture. Overall, RUT-NLCs provided greater nephroprotection than free rutin, suggesting that modulation of epigenetic alterations and MyD88/STAT3 signaling represents a key mechanism underlying their therapeutic efficacy against DOX-induced nephrotoxicity. Full article

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20 pages, 2008 KB

Open AccessArticle

Exposure to the Environmental Toxins Microcystin-LR and Roundup^® Causes Cellular Damage in the Hepatopancreas of the White River Crayfish (Procambarus acutus)

by Mona Khalil, Antonillamarein E. Hanna, Brandon T. Kenaya, Amira S. Abuhmoud, Sarah A. Magid, Miranda J. Jasinski, Shaza Ahmed, Andrew A. Bosah, Sabrina A. Cacanindin, Oswaldo Celestino Escobar, Yara A. El-Sheikh, Evelyn M. Rihacek, Kendra R. Evans, Gregory M. Grabowski, Levi Storks and Rachelle M. Belanger

Toxics 2026, 14(8), 712; https://doi.org/10.3390/toxics14080712 - 12 Aug 2026

Abstract

Aquatic ecosystems are routinely exposed to natural and anthropogenic stressors, and when multiple pollutants co-occur, their synergistic effects may exceed those of individual contaminants. This study evaluated the individual and combined effects of the widely used agrochemical Roundup^®, whose active ingredient [...] Read more.

Aquatic ecosystems are routinely exposed to natural and anthropogenic stressors, and when multiple pollutants co-occur, their synergistic effects may exceed those of individual contaminants. This study evaluated the individual and combined effects of the widely used agrochemical Roundup^®, whose active ingredient is glyphosate (GLY) and the cyanobacterial toxin microcystin-LR (MC-LR) on the hepatopancreas of crayfish. Following a seven-day exposure to MC-LR (15 ppb), GLY (75 ppb), or their combination (MC-LR + GLY), cellular and morphological alterations were assessed using flow cytometry and histological analyses. MC-LR exposure increased hepatopancreatic vacuole number 3.7-fold and vacuole proportion 6.8-fold relative to controls, whereas GLY increased vacuole proportion 5.2-fold. Combined exposure increased tubule lumen proportion by approximately 65%, while epithelial height remained unchanged. GLY reduced viable (fluorescein diacetate-positive) hepatopancreatic cells by approximately 86%, and both GLY and MC-LR + GLY increased non-viable (propidium iodide-positive) cells by 4.8-fold and 4.3-fold, respectively. MC-LR alone did not significantly affect cell viability. These findings indicate that MC-LR primarily induces structural alterations, whereas GLY causes pronounced cellular cytotoxicity. Although co-exposure did not consistently produce synergistic toxicity, it enhanced tissue remodeling, emphasizing the importance of evaluating environmentally relevant contaminant mixtures and their implications for freshwater ecosystem health. Full article

(This article belongs to the Special Issue Ecotoxicological Effects of Contaminants on Aquatic Organisms)

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18 pages, 1645 KB

Open AccessReview

Indoor Environmental Exposures and Dry Eye Disease: Mechanisms, Clinical Impact, and Prevention Strategies

by Yumeng Li, Ji Yang, Tao Xie, Ping Xiang, Lei Kong and Hai Liu

Toxics 2026, 14(8), 711; https://doi.org/10.3390/toxics14080711 - 12 Aug 2026

Abstract

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, discomfort, hyperosmolarity, inflammation, and neurosensory dysfunction. Since individuals spend a significant amount of time inside buildings, exposure to indoor environments has emerged as a noteworthy and adjustable factor [...] Read more.

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, discomfort, hyperosmolarity, inflammation, and neurosensory dysfunction. Since individuals spend a significant amount of time inside buildings, exposure to indoor environments has emerged as a noteworthy and adjustable factor influencing ocular surface disorders. This analysis consolidates recent findings connecting indoor air contaminants, such as particulate pollutants, volatile organic substances, formaldehyde, and other gaseous irritants, as well as tobacco and cooking fumes, heavy metals, organophosphate flame retardants, and liquid crystal compounds, with the mechanisms and symptoms associated with DED. Research suggests that indoor environmental factors can exacerbate DED by triggering interconnected mechanisms such as oxidative damage, inflammation, lipid degradation, meibomian gland issues, decreased tear production, impairment of goblet cells and the mucin layer, disruption of tight junctions, and damage to the corneal or conjunctival epithelium. The most robust clinical evidence currently pertains to tobacco smoke, particulate matter, indoor air pollution, low humidity, and poor ventilation. In contrast, although biological plausibility exists for heavy metals, flame retardants, and liquid crystal monomers, the supporting data remain relatively sparse, indirect, and less comprehensive. Harmonized exposure assessments, prospective cohort studies, analyses of pollutant mixtures, and experimental intervention trials are needed to better characterize dose–response relationships and to establish effective preventive measures. Assessment of environmental history and improvement of indoor air quality should be regarded as integral and interrelated components in the prevention and management of DED. Full article

(This article belongs to the Special Issue Air Pollutants: Sources, Characteristics, Environmental Impacts and Human Health Risks)

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20 pages, 4032 KB

Open AccessArticle

Health Status Assessment of Panamanian Pacific Coastal Areas Using Multi-Level Biomarkers in the Mangrove Cockle Anadara tuberculosa

by Nelva Elena Alvarado-González, Jenifer Ortega, Yulissa De Gracia, Maricselis Díaz, Enrique Medianero, Tifanie Briaudeau, Tamer Hafez, Maren Ortiz-Zarragoitia, Xabier Lekube and Beñat Zaldibar

Toxics 2026, 14(8), 710; https://doi.org/10.3390/toxics14080710 - 12 Aug 2026

Abstract

Tropical coastal ecosystems are highly productive but increasingly threatened by anthropogenic pressures, making environmental monitoring tools essential to determine the health status of the environment. In this study, the health status of three sites along the Pacific coast of Panama (Río Santa María, [...] Read more.

Tropical coastal ecosystems are highly productive but increasingly threatened by anthropogenic pressures, making environmental monitoring tools essential to determine the health status of the environment. In this study, the health status of three sites along the Pacific coast of Panama (Río Santa María, Cuchilluyo, and Montijo) was assessed using the bivalve mollusc Anadara tuberculosa as a sentinel species. A multilevel biomarker approach was employed, combining chemical analyses with biochemical and histological biomarkers. Metal concentrations in whole soft tissues were generally low-to-moderate, except for arsenic, and polycyclic aromatic hydrocarbon (PAH) concentrations were low in all sites, being dominated by low-molecular-weight compounds. Biomarker responses were consistent with the chemical data, with cockles from Montijo exhibiting lower glutathione S-transferase (GST) activity and reduced oxidative DNA damage. Histological analyses revealed only mild alterations, including hemocytic infiltration in the connective tissue of digestive glands and atrophy, with no major reproductive impairments. Overall, results indicate low to moderate pollution levels in the studied areas, with Montijo representing the least impacted site. The study supports the suitability of A. tuberculosa as a sentinel species and the relevance of a multilevel biomarker approach for assessing environmental health in tropical coastal ecosystems. Full article

(This article belongs to the Special Issue Ecotoxicological Effects of Anthropogenic Contaminants in Aquatic Organisms)

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18 pages, 1957 KB

Open AccessArticle

Prenatal Exposure to Size-Fractionated Particulate Matter and Fetal Growth Trajectories: Mediation by Maternal Glucose Metabolism in a Birth Cohort

by Qian Chen, Bijun Shi, Yu Liu, Xin Wang, Li Cai, Qiliang Cui, Xiaohua Tan and Yujing Chen

Toxics 2026, 14(8), 709; https://doi.org/10.3390/toxics14080709 - 12 Aug 2026

Abstract

The metabolic mechanisms linking prenatal particulate matter (PM) to fetal growth remain unclear. A prospective cohort of 616 mother–fetus pairs in Guangzhou had ultrasound-based fetal growth parameters repeatedly measured from mid to late pregnancy. Fetal head circumference (HC), abdominal circumference (AC), femur length [...] Read more.

The metabolic mechanisms linking prenatal particulate matter (PM) to fetal growth remain unclear. A prospective cohort of 616 mother–fetus pairs in Guangzhou had ultrasound-based fetal growth parameters repeatedly measured from mid to late pregnancy. Fetal head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD) were standardized as z-scores. Estimated fetal weight (EFW) trajectories were classified as average, slow, and rapid growth. Residential PM₁, PM_2.5, and PM₁₀ were assessed with 1 km spatiotemporal models. Multinomial logistic regression analyzed PM-EFW trajectory associations. Generalized estimating equations evaluated PM–fetal growth z-score relationships. Maternal plasma glucose and insulin levels at mid-pregnancy were examined as intermediate factors. Each 5 μg/m³ increase in PM was associated with higher odds of rapid EFW growth versus average growth (OR _PM1 = 1.56, 95% CI: 1.03, 2.37; OR _PM2.5 = 1.44, 95% CI: 1.10, 1.88; OR _PM10 = 1.28, 95% CI: 1.05, 1.56). Positive associations were also observed for BPD, HC, and AC z-scores, with PM₁ showing the numerically larger effect estimates. Maternal fasting plasma glucose and insulin resistance may partly explain the observed associations of PM exposure with rapid EFW growth and fetal growth parameters, with estimated proportions of 5.0–29.4%. This study highlights the potential risk of accelerated fetal growth associated with maternal PM exposures, and maternal glucose metabolism may represent a plausible pathway. Full article

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

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33 pages, 2522 KB

Open AccessReview

Mechanism and Application of Biochar as an Electron Shuttle in the Remediation of Soil Pollutants

by Lingling Feng, Ke Tan, Can Tang, Huan Zhao, Jiawen Zhu, Qingman Zhang, Jiayu Yan and Mengdi Xie

Toxics 2026, 14(8), 708; https://doi.org/10.3390/toxics14080708 - 11 Aug 2026

Abstract

Biochar has attracted increasing attention in soil remediation due to its porous structure, abundant surface functional groups, and environmental compatibility. Beyond its conventional roles as an adsorbent and soil amendment, biochar has increasingly been recognized as an electron shuttle that mediates electron transfer [...] Read more.

Biochar has attracted increasing attention in soil remediation due to its porous structure, abundant surface functional groups, and environmental compatibility. Beyond its conventional roles as an adsorbent and soil amendment, biochar has increasingly been recognized as an electron shuttle that mediates electron transfer between electron donors and acceptors, thereby promoting redox reactions involved in pollutant transformation, immobilization, and toxicity mitigation. However, the structural basis, influencing factors, and underlying electron-transfer mechanisms of biochar-mediated processes remain insufficiently integrated. This review summarizes biochar-mediated electron transfer in soil remediation. Three pathways are discussed: direct electron transfer through conductive carbon matrices, indirect electron transfer mediated by redox-active surface functional groups, and composite interfacial electron transfer involving microorganisms, metal oxides, and nanomaterials. By introducing the synergistic effects between biochar and microorganisms, metal oxides, and nanomaterials, the functions of biochar in immobilizing heavy metals and degrading organic pollutants are emphasized. Biochar’s electron-shuttling ability is closely related to aromatic carbon structures, redox-active functional groups, and persistent free radicals, while key factors affecting electron-shuttling performance, including feedstock properties, pyrolysis temperature, pH, coexisting ions, pollutant concentration, and modification strategies, are also discussed. This review offers guidance for the design of biochar-based soil remediation strategies. Full article

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