Toxics

20 pages, 4048 KB

Open AccessArticle

Mixed Heavy Metal Exposure During Pregnancy Induces GDM-like Metabolic Dysfunction Associated with Glycer-Ophospholipid Metabolic Reprogramming and Altered Insig1 Expression: A Multi-Omics Study in Rats

by Tianao Sun, Zhanyue Zheng, Yongjie Ma, Minglian Pan, Yingjie Zhou, Jingxia Wei, Xinyu Yuan, Jinhao Wan, You Li and Yan Sun

Toxics 2026, 14(4), 351; https://doi.org/10.3390/toxics14040351 - 21 Apr 2026

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Abstract

This study aimed to investigate whether mixed heavy metal exposure (lead, cadmium, manganese, and arsenic) during pregnancy induces gestational diabetes mellitus (GDM)-like phenotypes and to explore the associated molecular alterations. We examined the effects of exposure on metabolic disturbances using a Sprague-Dawley rat [...] Read more.

This study aimed to investigate whether mixed heavy metal exposure (lead, cadmium, manganese, and arsenic) during pregnancy induces gestational diabetes mellitus (GDM)-like phenotypes and to explore the associated molecular alterations. We examined the effects of exposure on metabolic disturbances using a Sprague-Dawley rat model exposed to low- and high-dose mixed heavy metals, with doses selected based on biomonitoring data. The results showed that high-dose mixed heavy metal exposure significantly increased blood glucose levels in rats, elevated the area under the curve (AUC) during the oral glucose tolerance test (OGTT), and induced insulin resistance and dyslipidemia. Concurrently, pathological examinations revealed hepatocyte steatosis, inflammatory cell infiltration, and mitochondrial abnormalities in liver tissues. Transcriptomic and metabolomic analyses identified significant disruption of the glycerophospholipid metabolic pathway following heavy metal exposure, suggesting the involvement of this pathway in the observed metabolic disturbances. Lasso regression analysis identified Insig1 as a candidate gene associated with lipid metabolic alterations, a finding subsequently validated by qPCR. Overall, mixed heavy metal exposure during pregnancy was associated with GDM-like metabolic abnormalities in rats. Disruption of glycerophospholipid metabolism and altered Insig1 expression likely contribute to these effects, providing molecular evidence linking mixed heavy metal exposure to gestational metabolic dysfunction. Full article

(This article belongs to the Special Issue Reproductive and Developmental Toxicity of Environmental Factors)

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15 pages, 4523 KB

Open AccessFeature PaperArticle

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

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

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

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Abstract

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

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

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

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17 pages, 8857 KB

Open AccessArticle

The Characteristics of AOM and Formation of DBPs: The Role of Molecular Weights and Hydrophobicity

by Lingfei Ma, Haipu Li and Zhaoguang Yang

Toxics 2026, 14(4), 349; https://doi.org/10.3390/toxics14040349 - 21 Apr 2026

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Abstract

This study investigates the impacts of algogenic organic matter (AOM) distribution characteristics, specifically molecular weight (MW) and hydrophobicity, on the formation of disinfection byproducts (DBPs) derived from Microcystis aeruginosa. This study focuses on both extracellular organic matter (EOM) and intracellular organic matter (IOM) [...] Read more.

This study investigates the impacts of algogenic organic matter (AOM) distribution characteristics, specifically molecular weight (MW) and hydrophobicity, on the formation of disinfection byproducts (DBPs) derived from Microcystis aeruginosa. This study focuses on both extracellular organic matter (EOM) and intracellular organic matter (IOM) and their contributions to DBP formation. AOM was divided into 12 fractions based on MW and hydrophobicity (transphilic, hydrophilic, and hydrophobic fractions). The results reveal that the hydrophobic fraction (HPO) contributes the most to IOM, while low-MW (<1 kDa) and high-MW (>100 kDa) organic matter are the main components of AOM. An analysis of fluorescent species indicates that humic acid-like and fulvic acid-like compounds derived from the hydrophilic fraction (HPI) of EOM and the hydrophobic fraction (HPO) of IOM are the dominant low-MW (<1 kDa) species. Additionally, aromatic proteins derived from HPO in both EOM and IOM are the dominant high-MW (>100 kDa) fluorescent species. This suggests that proteins or polysaccharides are the primary adsorbents on the membrane during ultrafiltration (UF), while the humic acid component is not significantly deposited. Furthermore, this study identifies that the >100 kDa HPO in IOM serves as the main precursor for trichloromethane (TCM), trichloroacetic acid (TCAA), and dichloroacetic acid (DCAA). In EOM, the precursor for the highest TCMFP (63.6 µg/mg-C) is the >100 kDa HPI, while the highest contribution to TCM (21%) is from the >100 kDa HPO. These findings provide crucial information for controlling DBPs derived from AOM through membrane filtration, particularly in eutrophic water environments. Full article

(This article belongs to the Special Issue Toxic Agent Analysis and Removal for Healthy Living and Safe Environment)

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17 pages, 679 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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

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17 pages, 5126 KB

Open AccessArticle

Understanding the Causes of High Organic Matter with Low Bioavailability in Cold-Zone Lake Water: A Case in Hulun Lake

by Yulong Tao

Toxics 2026, 14(4), 347; https://doi.org/10.3390/toxics14040347 - 20 Apr 2026

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Abstract

In cold-region lakes, high organic matter concentrations with low bioavailability are common, yet the underlying causes and stabilisation mechanisms remain unclear. This study conducted a 60-day microbial treatment experiment in Hulun Lake using algae (DOMa), grass (DOMg), and manure (DOMm) as DOM sources. [...] Read more.

In cold-region lakes, high organic matter concentrations with low bioavailability are common, yet the underlying causes and stabilisation mechanisms remain unclear. This study conducted a 60-day microbial treatment experiment in Hulun Lake using algae (DOMa), grass (DOMg), and manure (DOMm) as DOM sources. Fourier transform ion cyclotron resonance mass spectrometry and 16S rRNA analysis were employed to characterise DOM composition and bacterial communities. The bioavailability of DOMa, DOMg, and DOMm was 86.1%, 84.08%, and 70.9%, respectively. Differences in degradation cycles were mainly associated with the slowly biodegradable fraction; the half-lives of DOMa, DOMg, and DOMm were 49.51 days, 77.02 days, and 198.04 days, respectively. At the molecular level, proteins and lipids were rapidly utilised by microorganisms, leading to the generation of lignin, condensed aromatic hydrocarbons, and tannins, with many new molecules falling within the carboxylic acid-rich alicyclic molecule (CRAM) region. The overall community succession patterns of different DOM sources were highly similar, with initial DOM composition differences leading to variations in microbial communities during intermediate degradation stages (5~10 days). Moreover, microbiological processes facilitated the convergence of DOM source compositions and the accumulation of refractory organic matter. It is hypothesised that the regional climatic characteristics of the freeze–thaw cycle exacerbate organic matter accumulation by compressing the “effective degradation time”. These findings elucidate the causes of high organic matter and low bioavailability in cold-region lakes. Full article

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18 pages, 6877 KB

Open AccessArticle

Manganese-Enriched Biochar Reduces Cd Uptake and Accumulation in Rice by Altering Soil Cd Speciation and Enhancing Mn–Cd Antagonism

by Qian Wang, Xu Yan, Kexin Shao, Lingfei Zuo, Haoran Jiao, Wenjuan Fan, Juan Lin, Jinbiao Li, Min Lv, Anyong Hu and Yujie Han

Toxics 2026, 14(4), 346; https://doi.org/10.3390/toxics14040346 - 20 Apr 2026

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Abstract

Cadmium (Cd) contamination in paddy soils threatens rice production and food safety. This study investigated the effects of manganese (Mn)-enriched biochar on soil Cd immobilization and Cd accumulation in rice using a pot experiment with Cd-contaminated soil. Unenriched biochar and Mn-enriched biochar prepared [...] Read more.

Cadmium (Cd) contamination in paddy soils threatens rice production and food safety. This study investigated the effects of manganese (Mn)-enriched biochar on soil Cd immobilization and Cd accumulation in rice using a pot experiment with Cd-contaminated soil. Unenriched biochar and Mn-enriched biochar prepared from rice straw were applied at two rates (0.5% and 1.0%). Both biochar types significantly increased soil pH and organic matter and promoted the transformation of Cd from labile fractions to more stable residual forms, thereby reducing Cd bioavailability. As a result, Cd accumulation in rice tissues, including straw and brown rice, was significantly reduced. Correlation analysis further indicated that increased soil pH was associated with reduced Cd mobility and plant uptake. Mn-enriched biochar markedly increased Mn accumulation and uptake efficiency in rice while decreasing Cd uptake efficiency, indicating a strong antagonistic interaction between Mn and Cd in the soil–plant system. Notably, a low application rate of Mn-enriched biochar (0.5%) achieved Cd reduction effects comparable to those of a higher dose of unenriched biochar (1.0%). These results suggest that Mn-enriched biochar is an effective and potentially cost-efficient strategy for reducing Cd bioavailability in paddy soils and mitigating Cd accumulation in rice. Full article

(This article belongs to the Special Issue Heavy Metals and Pesticide Residue Remediation in Farmland)

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19 pages, 8170 KB

Open AccessFeature PaperArticle

Multi-Metal Leachate from Lithium Slag Induces Oxidative Stress, Circadian Disruption, and Neurobehavioural Toxicity in Zebrafish Larvae

by Xueping Huang, Shengping Zhang, Yu Liu, Shuai Liu, Qiyu Wang, Nannan Wan, Shanghaojun Lu, Yongming Wu and Miao Zhang

Toxics 2026, 14(4), 345; https://doi.org/10.3390/toxics14040345 - 20 Apr 2026

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Abstract

The rising global demand for lithium has led to substantial accumulation of lithium slag, a by-product of lithium carbonate production and a potential environmental contaminant. Leachates from this material contain various metal elements and may pose risks to ecosystems and organismal health. However, [...] Read more.

The rising global demand for lithium has led to substantial accumulation of lithium slag, a by-product of lithium carbonate production and a potential environmental contaminant. Leachates from this material contain various metal elements and may pose risks to ecosystems and organismal health. However, research on its neurotoxicity and underlying mechanisms remains limited. In this study, zebrafish embryos at 6 h post-fertilisation were exposed to varying concentrations of lithium slag leachate for 7 days. The leachate contained multiple metal ions (Li, Fe, Mn, Ni, Zn, As, Cr, Cu, Hg, Cd, Pb, etc.). Following exposure, significant metal accumulation was observed in larvae, accompanied by developmental malformations (yolk sac oedema, cardiac haemorrhage, and uninflated swim bladders). Behavioural assessment revealed reduced swimming distance and velocity, along with disrupted circadian rhythms. Biochemical analyses showed elevated Reactive oxygen species (ROS), Superoxide dismutase (SOD), Catalase (CAT), and Malondialdehyde (MDA), alongside decreased Glutathione (GSH), indicating oxidative stress. Transcriptomic analysis confirmed downregulation of core circadian genes. Neurotransmitter assays revealed decreased acetylcholine (Ach), noradrenaline (NE), and dopamine (DA), with increased gamma-aminobutyric acid (GABA) and serotonin (5-HT). These findings demonstrate that lithium slag leachate induces oxidative stress, circadian disruption, and neurobehavioural toxicity in zebrafish, providing important evidence for environmental risk assessment. Full article

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

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13 pages, 4073 KB

Open AccessArticle

Microplastics Decrease the Toxicity of ¹³⁷Cs in the Zebrafish Embryo-Larva

by Fangni Du, Wenjun Zhao, Shaofei Cao, Rui Zhang and Yuchen Yin

Toxics 2026, 14(4), 343; https://doi.org/10.3390/toxics14040343 - 20 Apr 2026

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Abstract

Large amounts of radionuclides and microplastics (MPs) have been released and will continue to be discharge into the environment. They will exist and interact in the aquatic environment over extended periods. However, the toxicological risks associated with their co-exposure remain poorly understood. In [...] Read more.

Large amounts of radionuclides and microplastics (MPs) have been released and will continue to be discharge into the environment. They will exist and interact in the aquatic environment over extended periods. However, the toxicological risks associated with their co-exposure remain poorly understood. In this study, the zebrafish (Danio rerio) embryos were exposed to ¹³⁷Cs (6.8 × 10⁴ Bq/L) in combination with 9.9 μm polystyrene MPs (PS-MPs, 10, 100 μg/L) for 7 days. Early developmental growth was significantly influenced in the ¹³⁷Cs-exposed groups. This was evidenced by delayed hatching, increased swimming total distance, and anxiety behavior (increasing swimming distance in the inner circle). Furthermore, transcriptomic analysis demonstrated that a higher number of differentially expressed genes were found in the ¹³⁷Cs group compared to other exposure groups. In ¹³⁷Cs groups, KEGG enrichment analysis highlighted significant disruptions in lipid metabolism pathways. ¹³⁷Cs can influence its neuro-related genes by inducing lipid metabolism toxicity, providing a mechanistic explanation for the observed locomotory abnormalities in larvae. Interestingly, during the early stage of development, MPs appeared to reduce the internal irradiation dose and toxic effect by absorbing the ¹³⁷Cs. Overall, this study enhances our understanding of the ecological risks posed by combined exposure to ¹³⁷Cs and MPs. Full article

(This article belongs to the Topic Environmental Exposures, Disasters, and Population Health: Epidemiology and Evaluation)

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19 pages, 12036 KB

Open AccessArticle

The Long-Term Dynamics of the Particulate ¹³⁷Cs Supply from Eroded Arable Slopes During the Post-Chernobyl Period

by Maksim M. Ivanov, Polina Fominykh, Nadezhda Ivanova, Sergei Krasnov and Valentin Golosov

Toxics 2026, 14(4), 344; https://doi.org/10.3390/toxics14040344 - 19 Apr 2026

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Abstract

In rural areas affected by Chernobyl, accelerated erosion has become a major source of particulate ¹³⁷Cs in sediment load. The long-term dynamics of the activity concentration in eroded soil material transported from individual slope catchments can be better understood by exploring the [...] Read more.

In rural areas affected by Chernobyl, accelerated erosion has become a major source of particulate ¹³⁷Cs in sediment load. The long-term dynamics of the activity concentration in eroded soil material transported from individual slope catchments can be better understood by exploring the ¹³⁷Cs depth distribution in sediments deposited near cultivated fields. This study focuses on three cultivated slope catchments located in the Chernobyl-affected area of Central Russia. A depth incremental campaign was conducted within zones of sediment accumulation in 2022–2025. The behavior of radiocaesium associated with particles after the Chernobyl accident was controlled by the prompt implementation of remediation measures. Shortly after the accident, the values decreased by more than two times. The radionuclide flux then began to depend on soil erosion processes. Gradually, the thickness of the upper soil that had been eroded became large enough to allow soil material from deeper layers to be involved during ordinary plowing and led to a subsequent decrease in the ¹³⁷Cs activity concentration. Given the decreasing snowmelt runoff and lack of increase in high-intensity rainfall in the 21st century, the activity concentration of ¹³⁷Cs in slope runoff has remained quite stable. This phenomenon requires consideration of whether a physically based model for the transport of particulate radionuclides should be developed. Full article

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

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12 pages, 1231 KB

Open AccessArticle

High-Resolution Detection of Microplastics in Zooplankton from Lake Como (Northern Italy): A Multi-Year Baseline for Large Deep Lakes

by Benedetta Villa, Gaia Bolla, Ginevra Boldrocchi and Roberta Bettinetti

Toxics 2026, 14(4), 342; https://doi.org/10.3390/toxics14040342 - 19 Apr 2026

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Abstract

Microplastics (MPs) are emerging contaminants in freshwater ecosystems, yet their ingestion by zooplankton remains poorly documented in large European lakes. This study provides the first evidence of MPs in zooplankton from Lake Como (Northern Italy), a major subalpine lake of ecological and socioeconomic [...] Read more.

Microplastics (MPs) are emerging contaminants in freshwater ecosystems, yet their ingestion by zooplankton remains poorly documented in large European lakes. This study provides the first evidence of MPs in zooplankton from Lake Como (Northern Italy), a major subalpine lake of ecological and socioeconomic relevance. Using high-resolution digital microscopy (detection limit: 2 µm), we quantified MPs across four sampling years (2016, 2017, 2018, 2025), capturing small size fractions typically overlooked by conventional methods. MPs were consistently detected, with mean concentrations of 0.06 ± 0.08 MPs ind.⁻¹ and 1.14 ± 1.22 MPs mg⁻¹ d.w., values comparable to those reported for freshwater zooplankton worldwide. No significant differences were observed between the lake’s two main branches, supporting a lake-wide interpretation of exposure. Clear seasonal patterns emerged, with higher MPs loads in autumn and winter. These findings highlight the potential for MPs to enter pelagic food webs and contribute to a lake-wide baseline for future harmonized monitoring and polymer-specific assessments. The main limitation of this study is the exclusive quantitative approach, which does not provide qualitative information on polymer composition. Overall, these results underscore the need to integrate zooplankton-based monitoring into freshwater microplastic risk assessment frameworks. Full article

(This article belongs to the Special Issue Ecotoxicology of Emerging Contaminants in the Water Environment)

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19 pages, 2614 KB

Open AccessArticle

Oxidative Stress, DNA Damage, DNA Repair Inhibition, and Apoptosis Induced by Lead and Cadmium Combined Exposure in TK6 Cells

by Xin Liu, Zhiyuan Han, Kuibin Han, Yuhan Pang, Xiaoyue Zhao, Yuting Wang, Xiaoyan Wu and Tuanwei Wang

Toxics 2026, 14(4), 341; https://doi.org/10.3390/toxics14040341 - 18 Apr 2026

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Abstract

Lead (Pb) and cadmium (Cd) are common environmental pollutants. Our previous population study revealed a significant positive association between Pb and Cd exposure and the micronuclei frequency among lead smelting workers. However, the underlying mechanisms remain unclear. In this study, human lymphoblastoid TK6 [...] Read more.

Lead (Pb) and cadmium (Cd) are common environmental pollutants. Our previous population study revealed a significant positive association between Pb and Cd exposure and the micronuclei frequency among lead smelting workers. However, the underlying mechanisms remain unclear. In this study, human lymphoblastoid TK6 cells were used to investigate the genotoxicity and its mechanisms induced by individual or combined exposure to Pb and Cd. Our results showed that Pb and Cd exposure, alone or in combination, triggered oxidative stress, as evidenced by reduced antioxidant enzyme activity (GSH, SOD and CAT) and increased content of ROS and GSSG. Both metals induced pronounced DNA damage, as shown by elevated Tail DNA% in the Comet assay and γ-H2AX fluorescence intensity. Furthermore, Pb and/or Cd exposure caused inhibition of the DNA repair proteins, including BRCA1, CtIP, RAD52, and XRCC2, indicating impaired DNA repair capacity; and upregulated Bax expression and the Bax/Bcl-2 ratio and Caspase-3 with downregulation of Bcl-2. Notably, Pb and Cd co-exposure produced an antagonistic effect, modulating oxidative stress indicators, cell-cycle arrest, DNA damage markers, DNA repair and apoptosis-related proteins. These findings demonstrate that Pb and Cd induce oxidative stress, DNA damage, inhibition of DNA repair, and apoptosis in TK6 cells. Our study provides new insights into the mechanisms of heavy metal combined exposure–induced genotoxicity and identifies potential molecular targets for intervention. Full article

(This article belongs to the Special Issue Exposure Level and Risk Assessment of Lead (Pb))

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32 pages, 11658 KB

Open AccessArticle

Removal Performance and Mechanistic Insights into As(V) Transport in Natural Manganese Minerals

by Zhicheng Zhao, Huimei Shan, Song Wei, Zheying Li and Qingsheng Li

Toxics 2026, 14(4), 340; https://doi.org/10.3390/toxics14040340 - 17 Apr 2026

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Abstract

Arsenic contamination in polymetallic mining areas is closely linked to surrounding iron-rich manganese minerals. However, conclusive evidence remains limited regarding the retention and migration process of As(V) in naturally manganese-rich manganese ores (especially those with different manganese/iron mass ratios) under dynamic flow conditions. [...] Read more.

Arsenic contamination in polymetallic mining areas is closely linked to surrounding iron-rich manganese minerals. However, conclusive evidence remains limited regarding the retention and migration process of As(V) in naturally manganese-rich manganese ores (especially those with different manganese/iron mass ratios) under dynamic flow conditions. This study investigated As(V) adsorption and transport by four natural manganese minerals (FM1–FM4) through batch/column experiments, characterization, and numerical modeling. Their Mn/Fe mass ratios were 22.7 for FM1, 4.2 for FM2, 3.7 for FM3, and 16.4 for FM4. Batch experiments showed that As(V) adsorption on FM1–FM3 was better described by the Freundlich model, indicating heterogeneous adsorption behavior. Under the tested experimental conditions, the apparent Langmuir q_m values of these minerals decreased from 0.066 to 0.015 mmol·g⁻¹ with decreasing Mn/Fe ratio. However, As(V) adsorption on FM4, which had the lowest Mn and Fe contents, followed the Langmuir model (q_m = 0.012 mmol·g⁻¹), suggesting monolayer adsorption. Column experiments demonstrated rapid As(V) retention for all minerals. In the time domain, increasing the flow rate from 0.5 to 2.0 mL·min⁻¹ generally advanced breakthrough and shortened the desorption tail, although the breakthrough behavior expressed in pore-volume coordinates was not strictly monotonic for all minerals. The Two-Site Kinetic Attachment Model (TSKAM) successfully simulated these dynamics (R² > 0.90, RMSE < 0.05), revealing adsorption controlled by fast and slow kinetic sites, with slow-site contributions diminishing at higher flow rates. Characterization results indicated that adsorbed arsenic on FM1 remained mainly as As(V) and was immobilized primarily through surface complexation involving surface hydroxyl and Fe/Mn–O groups. XRD and SEM-EDS suggested the participation of Fe/Mn-bearing phases, while XPS on FM1 showed pronounced changes in Mn surface species during adsorption. Therefore, As(V) removal by these natural manganese minerals is a coupled physicochemical process influenced by both mineral properties, including Mn/Fe ratio, specific surface area, pore structure, pH_PZC, and Mn surface-state changes, and hydrodynamic conditions in the polymetallic mining areas. Full article

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

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17 pages, 2906 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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

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17 pages, 1878 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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19 pages, 3922 KB

Open AccessSystematic Review

Per- and Polyfluoroalkyl Substances and Endometriosis: A Systematic Review and Meta-Analysis

by Sarah Pilling, Kerry Mitchell and Prakash V. A. K. Ramdass

Toxics 2026, 14(4), 337; https://doi.org/10.3390/toxics14040337 - 17 Apr 2026

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Abstract

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals implicated in reproductive dysfunction. Epidemiologic evidence examining their association with endometriosis remains inconsistent. Thus, we conducted a PRISMA-compliant systematic review and meta-analysis using PubMed, Embase, EBSCO Host, and Google Scholar databases. RStudio software was [...] Read more.

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals implicated in reproductive dysfunction. Epidemiologic evidence examining their association with endometriosis remains inconsistent. Thus, we conducted a PRISMA-compliant systematic review and meta-analysis using PubMed, Embase, EBSCO Host, and Google Scholar databases. RStudio software was used for all analyses. Random-effects or fixed-effects model was applied to estimate pooled odds ratios (ORs) and standardized mean difference (SMD) in PFAS levels between endometriosis patients and controls. Heterogeneity was assessed using I² statistics. Publication bias was evaluated using funnel plots, and Egger’s and Begg’s tests. Twelve studies met the inclusion criteria for the systematic review and eleven were included in the quantitative synthesis. Overall, PFSAs (OR: 1.50; 95% CI: 1.12–2.00) and PFCAs (OR: 1.46; 95% CI: 1.12–1.90) were significantly associated with increased odds of endometriosis, particularly PFOS and PFOA. However, analyses of pooled SMD did not demonstrate consistent concentration differences between endometriosis cases and controls. Heterogeneity was moderate to high for most compounds. Funnel plot symmetry and Egger’s and Begg’s tests suggest no publication bias. Exposure to PFASs, particularly PFOS and PFOA, may be associated with increased odds of endometriosis. Further prospective studies incorporating mixture modeling and emerging PFASs are warranted. Full article

(This article belongs to the Special Issue Molecular Mechanisms of PFAS-Induced Toxicity and Carcinogenicity)

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18 pages, 333 KB

Open AccessReview

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

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

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

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Abstract

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

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

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

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24 pages, 1136 KB

Open AccessReview

Explainable Deep Learning for Research on the Synergistic Mechanisms of Multiple Pollutants: A Critical Review

by Chang Liu, Anfei He, Jie Gu, Mulan Ji, Jie Hu, Shufeng Qiao, Fenghe Wang, Jing Hua and Jian Wang

Toxics 2026, 14(4), 335; https://doi.org/10.3390/toxics14040335 - 16 Apr 2026

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Abstract

The synergistic control of multiple pollutants is critically challenged by complex nonlinear interactions, strong spatiotemporal heterogeneity, and the difficulty of tracing causal drivers. Deep learning offers high predictive power but suffers from the “black-box” problem, limiting its acceptance in environmental decision-making. Explainable Deep [...] Read more.

The synergistic control of multiple pollutants is critically challenged by complex nonlinear interactions, strong spatiotemporal heterogeneity, and the difficulty of tracing causal drivers. Deep learning offers high predictive power but suffers from the “black-box” problem, limiting its acceptance in environmental decision-making. Explainable Deep Learning (XDL) integrates physical mechanisms with interpretable algorithms, achieving both prediction accuracy and explanatory transparency. This review systematically evaluates the effectiveness and limitations of XDL in analyzing multi-pollutant interactions, with a comparative focus on atmospheric and aquatic environments. Key techniques, including SHAP, attention mechanisms, and physics-informed neural networks, are examined for their roles in synergistic monitoring, source apportionment, and regulatory optimization. The main findings reveal that: (1) XDL, particularly the “tree model + SHAP” paradigm, has become a dominant tool for quantifying driving factors, yet most attributions remain correlational rather than causal; (2) physics-informed fusion (soft vs. hard constraints) improves physical consistency but faces unresolved conflicts between data and physical laws, with current models lacking a conflict detection mechanism; (3) cross-media comparison shows a unified technical logic of “physical mechanism guidance + post hoc feature attribution”, but atmospheric applications lead in embedding advection–diffusion constraints, while aquatic research excels in spatial topology modeling via graph neural networks; (4) critical bottlenecks include the lack of causal inference, uncertainty-unaware interpretations, and data scarcity. Future directions demand a shift from correlation-only to causal-aware attribution, from blind fusion to conflict-detecting systems, and from no evaluation standards to domain-specific validation benchmarks. XDL is poised to transform multi-pollutant governance from experience-driven to intelligence-driven approaches, provided that verifiable interpretability and physical consistency become core design principles. Full article

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22 pages, 5076 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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

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13 pages, 553 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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

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20 pages, 5141 KB

Open AccessArticle

Mechanism and Characteristics of Phosphorus Release from Sediments in Drawdown Zone Under Inundation/Drying Cycles

by Huanhuan Yang, Fulan Zhang, Jing Liu and Dayong Cui

Toxics 2026, 14(4), 332; https://doi.org/10.3390/toxics14040332 - 16 Apr 2026

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Abstract

Phosphorus release from sediments significantly influences eutrophication in shallow lakes; however, its dynamics in drawdown zones under alternating inundation and drying cycles remain understudied. This study investigates the mechanisms of phosphorus release from sediments in the drawdown zone of Nansi Lake, a key [...] Read more.

Phosphorus release from sediments significantly influences eutrophication in shallow lakes; however, its dynamics in drawdown zones under alternating inundation and drying cycles remain understudied. This study investigates the mechanisms of phosphorus release from sediments in the drawdown zone of Nansi Lake, a key reservoir along the eastern route of the South-to-North Water Diversion Project. Through field sampling and laboratory simulations, we analyzed the impact of inundation duration, physicochemical properties, and organic matter decomposition on phosphorus release. In Container a (first inundation period), phosphorus was rapidly released at the beginning of inundation, with total phosphorus (TP) in the overlying water increasing from 1.92 mg/L to 2.68 mg/L, and in the interstitial water from 8.45 mg/L to 15.24 mg/L. The second inundation period showed the highest phosphorus release, with TP reaching 3.61 mg/L in the overlying water and 21.51 mg/L in the interstitial water. Inorganic phosphorus dominated the release, with dissolved inorganic phosphorus (DIP) accounting for a higher proportion of TP than dissolved organic phosphorus (DOP). Changes in pH, oxidation-reduction potential (ORP), dissolved oxygen (DO), and total organic carbon (TOC) significantly influenced phosphorus distribution. The decomposition of organic matter during inundation increased dissolved organic matter levels, thereby affecting phosphorus release. These findings provide valuable insights into phosphorus dynamics and highlight the need for integrated management strategies to mitigate internal phosphorus loading and prevent eutrophication in Nansi Lake, offering guidance for water quality management and ecological protection in similar shallow lake systems. Full article

(This article belongs to the Section Ecotoxicology)

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22 pages, 1673 KB

Open AccessArticle

Hidden Hazards: Assessment of Exposure Risks from 3-Monochloropropane-1,2-diol Ester (3-MCPDE) and Glycidyl Ester (GE) Consumption Among Malaysian Consumers

by Siti Hajar Muhamad Rosli, Nurul Izzah Ahmad, Nurul Hidayati Surawi, Rohana Ani, Nor Kamilah Mohamad Alwi and Ami Fazlin Syed Mohamed

Toxics 2026, 14(4), 331; https://doi.org/10.3390/toxics14040331 - 16 Apr 2026

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Abstract

3-Monochloropropanediol esters (3-MCPDEs) and glycidyl esters (GEs) are food processing contaminants that raise significant food safety concerns due to their established potential for carcinogenicity. This study aimed to determine the occurrence of 3-MCPDEs and GEs in common Malaysian food items and to evaluate [...] Read more.

3-Monochloropropanediol esters (3-MCPDEs) and glycidyl esters (GEs) are food processing contaminants that raise significant food safety concerns due to their established potential for carcinogenicity. This study aimed to determine the occurrence of 3-MCPDEs and GEs in common Malaysian food items and to evaluate the associated health risks through dietary exposure assessment. A total of 251 samples, consisting of retail products and cooked/prepared meals, were analysed using GC-MS. The food consumption data were obtained from published national food surveys. Risk was characterised using health-based guidance values (HBGVs) and margin of exposure (MOE), lifetime cancer risk (LCR), and disability-adjusted life year (DALY) estimates. 3-MCPDE was detected in 94.8% of samples (range: ND to 7.77 mg/kg), while GE was found in 83.3% of samples (range: ND to 9.41 mg/kg). The highest levels were consistently observed in refined vegetable fats and oil products, specifically shortening (3-MCPDE: 3.53 [IQR 2.76–5.16] mg/kg; GE: 4.78 [IQR 3.52–6.14] mg/kg) and margarine (3-MCPDE: 2.50 [IQR 1.11–3.59] mg/kg; GE: 3.60 [IQR 1.18–5.26] mg/kg). Exposure assessment identified fried rice as the largest contributor to total daily intake (3-MCPDE: 3.16 μg/kg BW/day; GE: 1.36 μg/kg BW/day). Total exposure to 3-MCPDE exceeded the provisional maximum tolerable daily intake (PMTDI) established by JECFA by 39.5%, indicating a potential health concern. Low MOE estimates (<10,000) for 3-MCPDE and GE were determined for several food categories, including snacks, kuih-muih, and fried cooked dishes. Chronic GE exposure was estimated to cause up to 6.9 (for mean consumers) and 24.9 (for high consumers) cancer cases per year, with total the DALYs quantified at 124.2 years lost per 100,000 of the population. These data represent a worst-case scenario; however, risks could be minimised through continued surveillance, mitigation strategies by relevant authorities regarding food processing, and informed dietary choices. Full article

(This article belongs to the Special Issue Health Risk Evaluation of Hazardous Substances in Food)

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22 pages, 1245 KB

Open AccessArticle

Synthesis of Metal and Metal Oxide Nanoparticles by Flame Spray Pyrolysis and Safety Assessment

by Ioanna Efthimiou, Yiannis Georgiou, Dimitris Vlastos, Stefanos Dailianis, Yiannis Deligiannakis and Maria Antonopoulou

Toxics 2026, 14(4), 330; https://doi.org/10.3390/toxics14040330 - 15 Apr 2026

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Abstract

Zinc oxide (ZnO), silver (Ag) and titanium dioxide (TiO₂) nanoparticles (NPs), are three of the most widely manufactured NPs, while composite NPs have gained popularity due to their enhanced properties. NP release in environmental matrices increases chances of bioavailability and subsequent [...] Read more.

Zinc oxide (ZnO), silver (Ag) and titanium dioxide (TiO₂) nanoparticles (NPs), are three of the most widely manufactured NPs, while composite NPs have gained popularity due to their enhanced properties. NP release in environmental matrices increases chances of bioavailability and subsequent impact on human health. The current study focuses on manufacturing, characterization and cyto-genotoxic assessment of Ag, ZnO/Ag, TiO₂ and TiO₂/Ag NPs with and without humic acids (HAs), aiming for a holistic approach that leads to a comprehensive profile of said NPs. It entails (a) the synthesis of the aforementioned NPs via single-nozzle Flame Spray Pyrolysis (SN-FSP); (b) the characterization of NPs (in powder form and in dispersion media) using Powder X-ray Diffraction (PXRD), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS); and (c) the assessment of their genotoxicity and cytotoxicity against human lymphocytes in presence of two HAs, thus simulating actual environmental conditions, and without HAs, through the cytokinesis block micronucleus assay (CBMN) with cytochalasin-B. No genotoxicity was observed in any case, whereas cytotoxicity induction varied depending on the NP and the presence or absence of the two HAs. Therefore, it is indispensable to evaluate the toxic profile of NPs considering different environmental scenarios, while conducting an integrated characterization of NPs. Full article

(This article belongs to the Special Issue Environmental Behavior and Migration Mechanism of Microplastics)

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12 pages, 723 KB

Open AccessArticle

Effects of Different Drought Timing on the Reduction and Control of Cadmium Uptake in Rice

by Liqing Fu, Qiying Huang, Jiujin Lu, Jianmiao Gao, Yanfei Sheng, Nan Ye, Zhongcheng Lu, Jiawei Ma, Dan Liu and Yulei Wang

Toxics 2026, 14(4), 329; https://doi.org/10.3390/toxics14040329 - 15 Apr 2026

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Abstract

Rice is a globally important food crop, and its production is often affected by extreme climates such as drought and high temperatures. This study investigated how drought applied at different growth stages affects cadmium (Cd) uptake and accumulation in rice, as well as [...] Read more.

Rice is a globally important food crop, and its production is often affected by extreme climates such as drought and high temperatures. This study investigated how drought applied at different growth stages affects cadmium (Cd) uptake and accumulation in rice, as well as the underlying mechanisms. The results showed that drought treatments generally increased soil organic matter and alkali-hydrolyzed nitrogen content but decreased pH and available phosphorus content. The available Cd content in soil under the grain-filling stage drought treatment was lower than that under other treatments. Speciation analysis showed that under grain-filling stage drought, exchangeable Cd decreased by 3.04%, and residual Cd increased by 2.67%. Furthermore, drought treatments significantly enhanced soil urease and sucrase activities. Rice plant height and yield were significantly affected by the timing of drought, with the grain-filling stage drought treatment yielding the highest, while full growth stage and tillering stage drought treatments resulted in significantly lower yields. Cd content in various organs followed the order: root > stem > leaf > brown rice, with the brown rice Cd content being the lowest under grain-filling stage drought. In conclusion, drought treatment during the grain-filling stage had the least effect on Cd content in various rice tissues while maintaining a relatively high yield, providing a theoretical basis for water management in Cd-contaminated paddy fields. Full article

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23 pages, 1995 KB

Open AccessReview

The Impact of Micro/Nanoplastics on Human Hematopoietic Function: Exposure, Deposition, Toxicity, and Mitigation Strategies

by Yao Zhou, Xuanwei Chen, Jin Chen and Jian Xu

Toxics 2026, 14(4), 328; https://doi.org/10.3390/toxics14040328 - 15 Apr 2026

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Abstract

The continuous accumulation of micro- and nanoplastics in the human living environment and their deposition in various organs of the body have become a global public health concern with the widespread use of plastic products. This review summarizes the main categories of micro- [...] Read more.

The continuous accumulation of micro- and nanoplastics in the human living environment and their deposition in various organs of the body have become a global public health concern with the widespread use of plastic products. This review summarizes the main categories of micro- and nanoplastics entering the body through dietary intake and air inhalation, based on human exposure pathways. By integrating existing literature data, this review estimates the daily intake and excretion of micro- and nanoplastics in humans, summarizes evidence regarding their potential deposition patterns in blood cells and hematopoietic-related organs, mainly inferred from animal and in vitro studies, and discusses the possible impacts of such deposition on hematopoietic function. Furthermore, the toxic effects and potential hazards of micro- and nanoplastics on the human hematopoietic system at both cellular and animal levels, along with the underlying molecular mechanisms, are comprehensively reviewed. From the dual perspectives of environmental governance and bodily protection, exploratory research ideas are proposed, including biodegradation strategies and the application of medicinal and edible homologous substances. This review aims to provide insights for reducing the risk of hematopoietic system diseases and preventing harm caused by micro- and nanoplastics to the human body in the future. Full article

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26 pages, 1092 KB

Open AccessReview

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

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

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

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Abstract

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

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

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

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15 pages, 1744 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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12 pages, 616 KB

Open AccessArticle

PFAS Pesticides: Contamination Pathways in Italy and the Need for Integrated Regulation

by Emanuela Pace, Gianluca Maschio and Dania Esposito

Toxics 2026, 14(4), 325; https://doi.org/10.3390/toxics14040325 - 14 Apr 2026

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Abstract

In agriculture, the use of per- and polyfluoroalkyl substances (PFASs) as active substances in pesticides has increased over recent decades due to their chemical stability, their ability to alter cell membrane permeability, and their capacity to bind to target proteins. However, their intentional [...] Read more.

In agriculture, the use of per- and polyfluoroalkyl substances (PFASs) as active substances in pesticides has increased over recent decades due to their chemical stability, their ability to alter cell membrane permeability, and their capacity to bind to target proteins. However, their intentional application to agricultural soils has led to progressive environmental accumulation. Their high persistence, mobility, and bioaccumulation potential, combined with documented toxicological effects, raise concerns for aquatic organisms and ecosystems. Monitoring surface and groundwater is essential to assess PFAS contamination. Data from the Italian monitoring plan show widespread contamination, despite the existing European regulatory framework designed to safeguard ecosystems and public health. The contamination is likely underestimated because monitoring programs currently target only a limited number of substances and PFAS metabolites and co-formulants are not included. Approximately 46 PFASs have been identified as active ingredients in pesticides, 29 of which are still authorized within the European Union, posing challenges for drinking water production and ecosystem protection. Existing regulatory regimes also differ in their evaluation procedures, which may lead to inconsistent conclusions regarding PFAS applications. Within the framework of the European “One Substance One Assessment” (OSOA) approach aimed at to ensuring the protection of human health and natural resources, this paper examines the properties of PFASs used as active substances in pesticides, their regulatory status, and their monitoring in Italy, highlighting the regulatory inconsistencies that result in the differential treatment of these substances compared with PFASs used in other sectors. Full article

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

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17 pages, 2954 KB

Open AccessArticle

Metabolomics Profiling and In Vitro Genoprotective Effect of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. Leaf Extract

by Ghanya Al-Naqeb, Mauro Commisso, Sara Boussetta, Rachele De Giuseppe and Hellas Cena

Toxics 2026, 14(4), 324; https://doi.org/10.3390/toxics14040324 - 13 Apr 2026

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Abstract

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was [...] Read more.

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was determined using an untargeted metabolomic approach employing UPLC-HRMS. Cytotoxicity, genotoxicity, and antigenotoxicity were assessed in Chinese hamster ovary K1 (CHO-K1) cells using the in vitro cytokinesis-block micronucleus (CBMN) assay. The metabolic profile of A. deliciosa leaf extracts revealed the presence of three major classes of secondary/specialized metabolites: proanthocyanidins, flavonols, and triterpenoid saponins. Medium-polar metabolites were monomeric fla-van-3-ols, such as (+)-catechin and (−)-epicatechin, oligomeric procyanidins and prodelphinidins, and flavonols. Certain glycosylated flavonols and their derivatives, such as myricetin, quercetin, and kaempferol. Low-polarity metabolites were characterized by low-polarity triterpenoids such as maslinic, corosolic, oleanolic, and ursolic acids. At concentrations of 37.5, 75, and 150 µg/mL, the extract did not significantly increase micronuclei frequency compared to untreated control cells, indicating an absence of genotoxic potential. Moreover, co-treatment of CHO-K1 cells with the extract and mitomycin C (MMC) at 0.025 µg/mL resulted in a significant reduction in micronuclei formation induced by MMC at concentrations of 75 and 150 µg/mL, suggesting antigenotoxic activity likely associated with the phytochemical constituents presented in the extract. Full article

(This article belongs to the Special Issue Toxicological Effects of Natural Products Derived from Plants or Animals Used in Therapeutical Treatments)

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21 pages, 6618 KB

Open AccessArticle

Microplastic Pollution in Pavement Sediments of Beijing: Abundance, Characteristics, and Ecological Risk

by Donghai Yuan, Peinan Ye, Chenling Yan, Lili Xu, Jinggang Wang, Chen Wang, Ruiying Wu, Jun Cui and Yingying Kou

Toxics 2026, 14(4), 323; https://doi.org/10.3390/toxics14040323 - 13 Apr 2026

Viewed by 437

Abstract

Pavement sediments are a significant source of microplastics (MPs) in urban environments and a major contributor to stormwater runoff pollution. In this study, we investigated the abundance and characteristics of microplastics in Beijing’s major road networks and functional zones by collecting road sediment [...] Read more.

Pavement sediments are a significant source of microplastics (MPs) in urban environments and a major contributor to stormwater runoff pollution. In this study, we investigated the abundance and characteristics of microplastics in Beijing’s major road networks and functional zones by collecting road sediment samples, and assessed the ecological risks posed by microplastics in road surface sediments in Beijing. The results showed that the average abundance of microplastics in Beijing pavement sediments was 960.9 items/kg, with the highest abundance observed in commercial areas (1505.7 items/kg). The main characteristics of microplastics were black in color (22.4%), fibrous in shape (55.29%), small to medium in size (10–500 µm, 46.95%), with polyethylene (PE) being the most abundant polymer type (30.69%). The Polymer Risk Index (PRI) method showed clearer differentiation of spatial risk patterns in the Beijing study area, with 5 low-risk sites, 8 medium-risk sites and 15 high-risk sites among the sampling sites. Full article

(This article belongs to the Special Issue Fate and Impacts of Environmental Micro(nano)plastics—From Sampling and Analysis to Risk Assessment)

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27 pages, 1619 KB

Open AccessReview

From Analysis to Assessment: Machine Learning for Non-Target Screening of Pollutants Using Chromatography Coupled with (Ion Mobility) Mass Spectrometry

by Dongshan Lin, Zhenyue Wang, Jiaqi Liao, Nan Li and Xiaolei Li

Toxics 2026, 14(4), 322; https://doi.org/10.3390/toxics14040322 - 13 Apr 2026

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Abstract

The growing diversity of anthropogenic chemicals in the environment far exceeds the scope of routine analytical monitoring. Non-target screening (NTS) using high-resolution mass spectrometry (HRMS) has thus emerged to discover unknown organic contaminants. Liquid or gas chromatography (LC/GC) coupled with ion mobility–mass spectrometry [...] Read more.

The growing diversity of anthropogenic chemicals in the environment far exceeds the scope of routine analytical monitoring. Non-target screening (NTS) using high-resolution mass spectrometry (HRMS) has thus emerged to discover unknown organic contaminants. Liquid or gas chromatography (LC/GC) coupled with ion mobility–mass spectrometry (IM-MS) further enhances NTS by providing multidimensional, structurally informative data. Machine learning (ML) offers a powerful solution by efficiently processing high-dimensional data and uncovering patterns. Both supervised and unsupervised learning approaches show strong potential to streamline labor-intensive processes. This review provides an overview of key ML algorithms and representative workflows in LC/GC-(IM-) MS-related NTS, followed by a critical synthesis of recent advances in ML-enabled applications across the entire NTS procedure, from sample analysis to data acquisition, and ultimately risk assessment. Continued advances in ML are expected to transform NTS into a more efficient and robust tool for risk assessment. Full article

(This article belongs to the Special Issue From Detection to Risk: Data-Driven Advances in Analytical Chemistry and Toxicology)

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