Toxics

20 pages, 3343 KiB

Open AccessArticle

Influencing Factors of Phosphorus Mobility and Retention in the Sediment of Three Typical Plateau Lakes

by Xue Wu, Yancai Wang, Lixin Jiao, Jia He, Hongbin Zhou and Zhengzheng Hao

Toxics 2025, 13(2), 120; https://doi.org/10.3390/toxics13020120 - 3 Feb 2025

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The mechanisms driving changes in the stability of phosphorus (P) in sediments under lake ecosystem degradation remain poorly understood. This study investigated the P-binding forms in sediments from three plateau lakes with different trophic states in Yunnan Province, China, aiming to elucidate the [...] Read more.

The mechanisms driving changes in the stability of phosphorus (P) in sediments under lake ecosystem degradation remain poorly understood. This study investigated the P-binding forms in sediments from three plateau lakes with different trophic states in Yunnan Province, China, aiming to elucidate the responses of sediment P compositions to human activities, lake trophic status, and dissolved organic matter (DOM) characteristics. The results showed that human activity directly contributed to sediment P retention. The trophic type of lake exerted a discernible effect on P mobility in the sediments, as eutrophic algae-type lakes had a higher content of sediment mobile-P. Moreover, the sediment DOM promoted the adsorption of BD-P and NH₄Cl-P. Generally, exogenous pollution caused by human activity leads to lake eutrophication and a decline in lake ecosystem stability. This variation was largely influenced by water depth. A decrease in lake ecosystem stability leads to increased P mobility in sediments, which increases the risk of endogenous pollution. The DOM plays an important role in the mobility of sediment P. These insights offer a novel perspective for understanding how lake ecosystem characteristics are related to endogenous P loads in lakes. Full article

(This article belongs to the Special Issue Occurrence and Environmental Risks of Organic Pollutants in Aquatic Environment)

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27 pages, 6214 KiB

Open AccessReview

The Role of Epigenetic Mechanisms in the Development of PM_2.5-Induced Cognitive Impairment

by Lishan Jiang, Mingxia Shao, Chao Song, Li Zhou, Wenke Nie, Hang Yu, Siqi Wang, Yongping Liu and Li Yu

Toxics 2025, 13(2), 119; https://doi.org/10.3390/toxics13020119 - 2 Feb 2025

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Abstract

PM_2.5 is fine particulate matter with a diameter of less than 2.5 μm. Recent evidence has shown that exposure to PM_2.5 markedly elevates the risk of neurodegenerative diseases, neurodevelopmental disorders, and cardiovascular diseases, which may culminate in cognitive impairment. Nevertheless, the [...] Read more.

PM_2.5 is fine particulate matter with a diameter of less than 2.5 μm. Recent evidence has shown that exposure to PM_2.5 markedly elevates the risk of neurodegenerative diseases, neurodevelopmental disorders, and cardiovascular diseases, which may culminate in cognitive impairment. Nevertheless, the precise mechanisms through which PM_2.5 affects cognitive function are unclear. Recent studies have demonstrated that PM_2.5-induced epigenetic alterations are associated with the development of cognitive impairment. Epigenetic alterations include modifications to DNA methylation, histone modifications, and non-coding RNAs. The underlying mechanisms of epigenetic alterations are related to inflammation, synaptic dysfunction, cardiovascular factors, and alterations in neuronal structure and function. This review reports the latest findings on the relationship between PM_2.5-induced epigenetic alterations and the development of cognitive disorders, offering novel insights into the cognitive effects of air pollution. Full article

(This article belongs to the Special Issue Neuronal Injury and Disease Induced by Environmental Toxicants)

20 pages, 2213 KiB

Open AccessArticle

Comprehensive Cross-Sectional Study of the Triglyceride Glucose Index, Organophosphate Pesticide Exposure, and Cardiovascular Diseases: A Machine Learning Integrated Approach

by Xuehai Wang, Mengxin Tian, Zengxu Shen, Kai Tian, Yue Fei, Yulan Cheng, Jialing Ruan, Siyi Mo, Jingjing Dai, Weiyi Xia, Mengna Jiang, Xinyuan Zhao, Jinfeng Zhu and Jing Xiao

Toxics 2025, 13(2), 118; https://doi.org/10.3390/toxics13020118 - 1 Feb 2025

Viewed by 385

Abstract

Using NHANES data from 2003 to 2008, 2011 to 2012, and 2015 to 2020, we examined the relationship between urinary organophosphate pesticide (OPP) metabolites and the triglyceride glucose (TyG) index. The TyG index evaluates insulin resistance, a crucial factor in metabolic diseases. Linear [...] Read more.

Using NHANES data from 2003 to 2008, 2011 to 2012, and 2015 to 2020, we examined the relationship between urinary organophosphate pesticide (OPP) metabolites and the triglyceride glucose (TyG) index. The TyG index evaluates insulin resistance, a crucial factor in metabolic diseases. Linear regression analyzed urinary metabolites in relation to the TyG index and OPPs. An RCS (restricted cubic spline) model explored the nonlinear relationship of a single OPP metabolite to TyG. A weighted quantile regression and quantile-based g-computation assessed the impact of combined OPP exposure on the TyG index. XGBoost, Random Forest, Support Vector Machines, logistic regression, and SHapley Additive exPlanations models investigated the impact of OPPs on the TyG index and cardiovascular disease. Network toxicology identified CVD targets associated with OPPs. This study included 4429 participants based on specific criteria. Linear regression analysis indicated that diethyl thiophosphate was positively correlated with the TyG index. The positive correlation between OPP metabolites and the TyG index at low to moderate concentrations was confirmed by WQS and QGC analyses. The machine learning results aligned with traditional statistical findings. Network toxicology identified PTGS3, PPARG, HSP40AA1, and CXCL8 as targets influenced by OPPs. OPP exposure influences IR and cardiometabolic health, highlighting the importance of public health prevention. Full article

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17 pages, 1562 KiB

Open AccessArticle

Ozone Exposure and Gestational Diabetes in Twin Pregnancies: Exploring Critical Windows and Synergistic Risks

by Anda Zhao, Yuanqing Xia, Ruoyu Lu, Wenhui Kang, Lili Huang, Renyi Hua, Shuping Lyu, Yan Zhao, Jianyu Chen, Yanlin Wang and Shenghui Li

Toxics 2025, 13(2), 117; https://doi.org/10.3390/toxics13020117 - 1 Feb 2025

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Abstract

The relationship between ozone (O₃) exposure and gestational diabetes mellitus (GDM) in twin pregnancies remains unexplored. This study aimed to investigate the association between O₃ exposure and GDM risk in twin pregnancies, and to explore the synergistic effects of O [...] Read more.

The relationship between ozone (O₃) exposure and gestational diabetes mellitus (GDM) in twin pregnancies remains unexplored. This study aimed to investigate the association between O₃ exposure and GDM risk in twin pregnancies, and to explore the synergistic effects of O₃ exposure with other maternal factors. A total of 428 pregnancies recruited from a prospective twin cohort were included. Cox proportional hazard models with distributed lag non-linear models (DLNMs) were applied to examine the associations between O₃ exposure and the risk of GDM and to identify the critical windows. The multiplicative and additive interaction were further analyzed to test the synergistic effects. A 10 μg/m³ increase in average O₃ exposure during the 12 weeks before pregnancy was associated with a 26% higher risk of GDM. The critical windows were identified in the period from the 3rd week before gestation to the 2nd gestational week as well as from the 17th to 19th gestational week. There were synergistic effects between high O₃ exposure during preconception and advanced maternal age, and a history of preterm birth/abortion/stillbirth. Periconceptional O₃ exposure could increase the risk of GDM in twin pregnancy women, and the synergism of O₃ exposure with certain GDM risk factors was observed. Full article

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24 pages, 1210 KiB

Open AccessArticle

Per- and Poly-Fluoroalkyl Substances, and Organophosphate Flame Retardants in the Upper Yangtze River: Occurrence, Spatiotemporal Distribution, and Risk Assessment

by Wen Sun, Zhiyou Fu, Yueyue Liu, Yingchen Bai, Yuyan Zhao, Chen Wang and Fengchang Wu

Toxics 2025, 13(2), 116; https://doi.org/10.3390/toxics13020116 - 1 Feb 2025

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Abstract

Contaminants of Emerging Concern (CECs), including per- and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs), have raised global concerns due to their persistence, bioaccumulation potential, and toxicity. This study presents a comprehensive investigation of the occurrence, spatiotemporal distribution, potential sources, and the [...] Read more.

Contaminants of Emerging Concern (CECs), including per- and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs), have raised global concerns due to their persistence, bioaccumulation potential, and toxicity. This study presents a comprehensive investigation of the occurrence, spatiotemporal distribution, potential sources, and the ecological and human health risks associated with 18 PFASs and 9 OPFRs in the surface waters of the upper Yangtze River, China. The water samples were collected from the main stream and five major tributaries (Min, Jinsha, Tuo, Jialing, and Wu Rivers) in 2022 and 2023. The total concentration of PFASs and OPFRs ranged from 16.07 to 927.19 ng/L, and 17.36 to 190.42 ng/L, respectively, with a consistently higher concentration observed in the main stream compared to the tributaries. Ultra-short-chain PFASs (e.g., TFMS) and halogenated OPFRs (e.g., TCPP) were the predominant compounds, likely originating from industrial discharges, wastewater effluents, and other anthropogenic sources. Ecological risk assessments indicated low-to-moderate risks at most sampling sites, with higher risks near wastewater discharge points. Human health risk evaluations suggested negligible non-carcinogenic risks but identified potential carcinogenic risks from OPFR exposure for adults at specific locations, particularly in Leshan city. This study highlights the importance of understanding the fate and impacts of PFASs and OPFRs in the upper Yangtze River, and provides valuable insights for developing targeted pollution control strategies and risk management measures. Full article

(This article belongs to the Special Issue Occurrence and Environmental Risks of Organic Pollutants in Aquatic Environment)

11 pages, 209 KiB

Open AccessArticle

Ethephon Poisoning: Clinical Characteristics and Outcomes

by Satariya Trakulsrichai, Kanokrat Chuayaupakarn, Phantakan Tansuwannarat, Panee Rittilert, Achara Tongpoo, Charuwan Sriapha and Winai Wananukul

Toxics 2025, 13(2), 115; https://doi.org/10.3390/toxics13020115 - 31 Jan 2025

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Abstract

Ethephon (2-chloroethylphosphonic acid) is a generally used plant growth regulator, but the data on its toxic effects, especially in humans, are very limited. This study was conducted to describe the clinical characteristics, management, and outcomes of patients exposed to products containing ethephon. We [...] Read more.

Ethephon (2-chloroethylphosphonic acid) is a generally used plant growth regulator, but the data on its toxic effects, especially in humans, are very limited. This study was conducted to describe the clinical characteristics, management, and outcomes of patients exposed to products containing ethephon. We performed an 8-year retrospective study using data from the Ramathibodi Poison Center database (2013–2020), which included 252 patients. Most patients were male, with a median age of 32 years. Almost all patients were exposed through ingestion, mainly in unintentional circumstances. The clinical presentations included local effects, gastrointestinal (GI), neurological, and respiratory symptoms. Some patients required hospital admission; specifically, seven patients received inotropic drugs, and six were intubated with ventilator support. Most patients had either no or only minor clinical effects. However, six patients experienced moderate/severe effects, and two patients died. Age, intentional exposure, and the presence of initial neurological symptoms could prognosticate moderate to fatal outcomes. In conclusion, exposure to ethephon predominantly resulted in no or minor effects, and GI symptoms were the most common clinical manifestation. The cholinergic toxic syndrome was not frequently observed. The mortality rate was very low. Patients presenting with factors associated with worse outcomes should be monitored closely for clinical deterioration and appropriately managed. Full article

(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)

22 pages, 2953 KiB

Open AccessSystematic Review

Epigenetic Biomarkers Driven by Environmental Toxins Associated with Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the United States: A Systematic Review

by Melanie Engstrom Newell, Anumitha Aravindan, Ayesha Babbrah and Rolf U. Halden

Toxics 2025, 13(2), 114; https://doi.org/10.3390/toxics13020114 - 31 Jan 2025

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Abstract

Environmental toxins and epigenetic changes have been linked to neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and amyotrophic lateral sclerosis (ALS). This paper aimed to (i) identify environmental toxins associated with AD, PD, and ALS, (ii) locate potential industrial sources of [...] Read more.

Environmental toxins and epigenetic changes have been linked to neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and amyotrophic lateral sclerosis (ALS). This paper aimed to (i) identify environmental toxins associated with AD, PD, and ALS, (ii) locate potential industrial sources of toxins in the United States (U.S.), and (iii) assess epigenetic changes driven by exposure to toxins reported by patients. Environmental factors and epigenetic biomarkers of neurodegeneration were compiled from 69 studies in the literature using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and geographic information system approaches. Some 127 environmental toxins have been associated or putatively associated with AD, PD, or ALS, with four toxic metals (As, Cd, Mn, and Hg) common to all three of these neurodegenerative diseases. Environmental toxins associated with epigenetic changes (e.g., DNA methylation) in patients include air pollutants, metals, and organic chemicals (e.g., pesticides, mycotoxins, and cyanotoxins). Geographic analysis showed that study locations (e.g., U.S., Europe, and East Asia) were selected by researchers based on convenience of access rather than exposure risk and disease prevalence. We conclude that several toxins and epigenetic markers shared among neurodegenerative diseases could serve as attractive future targets guiding environmental quality improvements and aiding in early disease detection. Full article

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13 pages, 644 KiB

Open AccessArticle

The Influence of Different Protocols on the Application of the Dithiothreitol Assay in Determining the Oxidative Potential of Ambient Particles

by Maja Jovanović, Marija Živković, Bojana Petrović, Saima Iram, Milena Jovašević-Stojanović and Svetlana Stevanović

Toxics 2025, 13(2), 113; https://doi.org/10.3390/toxics13020113 - 30 Jan 2025

Viewed by 454

Abstract

Environmental particulate matter (PM) exposure has been widely recognized for its significant adverse effects on human health. Monitoring PM levels is one of the essential parameters of air quality assessment. However, PM mass concentration alone does not sufficiently explain its toxicological impacts and [...] Read more.

Environmental particulate matter (PM) exposure has been widely recognized for its significant adverse effects on human health. Monitoring PM levels is one of the essential parameters of air quality assessment. However, PM mass concentration alone does not sufficiently explain its toxicological impacts and effects on health. This study highlights the importance of oxidative potential (OP) as a promising metric for evaluating PM toxicity. It focuses on standardizing the dithiothreitol (DTT) assay as a tool for OP measurement. In order to investigate the impact of various extraction techniques, reagent concentrations, and assay conditions, four previously established protocols were tested without modification, while a novel protocol was introduced based on an extensive literature review. Results revealed strong positive correlations between the new and most established protocols. These findings highlight the significance of the new protocol in advancing the development of standardized methodologies for applying the DTT assay and demonstrating its reliability and relevance. While developing a standardized DTT assay involves addressing numerous parameters—from filter extraction to assay application—this research provides a solid base for achieving consistency in OP measurements and overcoming this critical issue. Full article

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11 pages, 2280 KiB

Open AccessArticle

Apigenin Induces Apoptosis and Inhibits Migration in Human Cholangiocarcinoma Cells

by Mayurachat Kaewmanee, Temduang Limpaiboon and Nipaporn Ngernyuang

Toxics 2025, 13(2), 112; https://doi.org/10.3390/toxics13020112 - 30 Jan 2025

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Abstract

Cholangiocarcinoma (CCA) is a rare and highly aggressive cancer of the biliary tract, associated with poor clinical outcomes due to late diagnosis, extensive metastasis, drug resistance, and limited treatment options. Apigenin, a natural flavonoid, has been found to exhibit anticancer properties in several [...] Read more.

Cholangiocarcinoma (CCA) is a rare and highly aggressive cancer of the biliary tract, associated with poor clinical outcomes due to late diagnosis, extensive metastasis, drug resistance, and limited treatment options. Apigenin, a natural flavonoid, has been found to exhibit anticancer properties in several types of human cancer cells. Therefore, apigenin may be relevant to developing chemotherapeutic agents for cancer treatment. In this study, we examined the effects of apigenin on cell viability, cell cycle distribution, apoptosis, and cell migration in human CCA cell lines (KKU-M055) under in vitro conditions. The results demonstrate that apigenin significantly suppressed specific CCA cell proliferation by inducing cell cycle arrest at the G2/M phase and promoting cell apoptosis in KKU-M055 cells while exhibiting low toxicity in immortalized MMNK1 cells. Apigenin enhanced apoptotic features, including nuclear fragmentation and the loss of mitochondrial membrane potential. Furthermore, apigenin induced the apoptosis of KKU-M055 cells in both extrinsic and intrinsic pathways by activating caspase-8, -9, and -3/7. Moreover, apigenin inhibited KKU-M055 migration. Our study suggests apigenin as a promising candidate for treating CCA, and these findings provide theoretical support for the further development and potential application of apigenin in clinical CCA therapy. Full article

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31 pages, 1158 KiB

Open AccessArticle

Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period

by R. Pavani, K. Venkaiah, P. Gnana Prakasam, Vijaya R. Dirisala, P. Gopi Krishna, B. Kishori and S. B. Sainath

Toxics 2025, 13(2), 111; https://doi.org/10.3390/toxics13020111 - 29 Jan 2025

Viewed by 319

Abstract

The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats [...] Read more.

The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats of the Wistar strain (23 days old) were allocated into four groups. Rats in group I did not receive any treatment, while rats in groups II, III, and IV received RES, PFOA, and RES + PFOA, respectively, between days 23 and 56 and were monitored for up to 90 days. Exposure to PFOA resulted in a significant reduction in spermiogram parameters, testicular 3β- and 17β-HSD activity levels, and circulatory levels of testosterone. A significant elevation in LPx, PCs, H₂O₂, and O₂⁻, associated with a concomitant reduction in SOD, CAT, GPx, GR, and GSH, was noticed in the testes, as well as region-specific changes in pro- and antioxidants in the epididymides of exposed rats compared to controls. A significant increase in serum FSH and LH, testicular cholesterol levels, and caspase-3 activity was observed in PFOA-exposed rats compared to controls. Histological analysis revealed that the integrity of the testes was deteriorated in PFOA-exposed rats. Transcriptomic profiling of the testes and epididymides revealed 98 and 611 altered genes, respectively. In the testes, apoptosis and glutathione pathways were disrupted, while in the epididymides, glutathione and bile secretion pathways were altered in PFOA-exposed rats. PFOA exposure resulted in the down-regulation in the testes of 17β-HSD, StAR, nfe2l2, ar, Lhcgr, and mRNA levels, associated with the up-regulation of casp3 mRNA, and down-regulation of alpha 1 adrenoceptor, muscarinic choline receptor 3, and androgen receptor in the epididymides of exposed rats compared to the controls. These events might lead to male infertility in PFOA-exposed rats. In contrast, restoration of selected reproductive variables was observed in RES plus PFOA-exposed rats compared to rats exposed to PFOA alone. Taken together, we postulate that prepubertal exposure to PFOA triggered oxidative damage and altered genes in the testes and epididymides, leading to suppressed male reproductive health in adult rats, while RES, with its steroidogenic, antiapoptotic, and antioxidant effects, restored PFOA-induced fertility potential in rats. Full article

(This article belongs to the Special Issue Human Exposure to per- and Polyfluoroalkyl Substances (PFASs): Toxicity, Health Effects, and Mitigation)

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12 pages, 938 KiB

Open AccessFeature PaperArticle

Next Generation Risk Assessment to Address Disease-Related Vulnerability—A Proof of Concept for the Sunscreen Octocrylene

by María-Elena Fernández-Martín and Jose V. Tarazona

Toxics 2025, 13(2), 110; https://doi.org/10.3390/toxics13020110 - 29 Jan 2025

Viewed by 531

Abstract

Risk assessment for cosmetics in the European Union (EU) are triggered by a ban on animal testing and concerns of endocrine disruption (ED). The risk assessment focuses on healthy populations and, for potential ED, includes specific developmental stages as vulnerable due to specific [...] Read more.

Risk assessment for cosmetics in the European Union (EU) are triggered by a ban on animal testing and concerns of endocrine disruption (ED). The risk assessment focuses on healthy populations and, for potential ED, includes specific developmental stages as vulnerable due to specific concerns on endocrine effects. However, the assessment focuses on healthy individuals and does not consider that some pathologies may increase dermal absorption and even vulnerability to endocrine disruptors. Data from the EU risk assessment, human pharmacokinetic studies and ToxCast bioactivity were combined in a hypothesis-driven Next-Generation Risk Assessment to identify possible risk drivers for vulnerable populations including oncological patients and atopic dermatitis. In vitro effects are observed at concentration in the order of measured plasmatic levels under normal use patterns. The induction of hepatic enzymes is the most relevant bioactivity endpoint, in line with animal findings. The information on endocrine potential is inconclusive, and the possibility for skin effects and endocrine mechanism linked to tumor induction require further elucidation. The information on octocrylene (CAS number: 6197-30-4) bioactivity is limited, lacking information on the metabolites and the immunotoxicity potential, particularly relevant for oncological patients. Full article

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

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20 pages, 2282 KiB

Open AccessReview

Contamination Characterization, Toxicological Properties, and Health Risk Assessment of Bisphenols in Multiple Media: Current Research Status and Future Perspectives

by Fangyun Long, Yanqin Ren, Fang Bi, Zhenhai Wu, Haijie Zhang, Junling Li, Rui Gao, Zhengyang Liu and Hong Li

Toxics 2025, 13(2), 109; https://doi.org/10.3390/toxics13020109 - 29 Jan 2025

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Abstract

Bisphenols (BPs) are ubiquitous environmental endocrine disruptors that cause various human health hazards and pollute water, soil, and the atmosphere to varying degrees. Although various studies have investigated the pollution characteristics and health hazards of BPs in different media, a systematic review of [...] Read more.

Bisphenols (BPs) are ubiquitous environmental endocrine disruptors that cause various human health hazards and pollute water, soil, and the atmosphere to varying degrees. Although various studies have investigated the pollution characteristics and health hazards of BPs in different media, a systematic review of BPs in the broader environmental context is still lacking. This study highlights the pollution characteristics, detection methods, and risk assessment status of BPs by combining relevant studies from both domestic and international sources, and their environmental distribution characteristics are summarized. The results show that BP pollution is a widespread and complex global phenomenon. Bisphenol A (BPA) remains the predominant component of BPs, which can damage the nervous and reproductive systems. At present, high-performance liquid chromatography–tandem mass spectrometry, high-performance liquid chromatography, and liquid chromatography–tandem mass spectrometry are the main detection methods used for BPs. BPs can also damage the reproductive system, leading to germ cell apoptosis and ovarian damage. Future research should focus on expanding the BP testing repertoire, advancing rapid detection techniques, elucidating toxic mechanisms, conducting comprehensive safety assessments, and developing systematic health risk assessment methods. These efforts will provide a scientific foundation for preventing and controlling emerging pollutants. Full article

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

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20 pages, 3800 KiB

Open AccessArticle

Copper-Induced Neurodegenerative Disorders and Therapeutic Potential of Curcumin-Loaded Nanoemulsion

by Govind Hake, Akshada Mhaske, Rahul Shukla and Swaran Jeet Singh Flora

Toxics 2025, 13(2), 108; https://doi.org/10.3390/toxics13020108 - 29 Jan 2025

Viewed by 361

Abstract

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side [...] Read more.

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side effects, creating a need for safer therapeutic alternatives. To address this, we developed a curcumin-loaded nanoemulsion (CUR-NE) using the spontaneous emulsification technique, aimed at enhancing the bioavailability and therapeutic efficacy of curcumin. The optimized nanoemulsion displayed a particle size of 76.42 nm, a zeta potential of −20.4 mV, and a high encapsulation efficiency of 93.69%, with a stable and uniform structure. The in vitro tests on SH-SY5Y neuroblastoma cells demonstrated that CUR-NE effectively protected against copper-induced toxicity, promoting significant cellular uptake. Pharmacokinetic studies revealed that CUR-NE exhibited a longer half-life and extended circulation time compared to free curcumin. Additionally, pharmacodynamic evaluations, including biochemical assays and histopathological analysis, confirmed that CUR-NE provided superior neuroprotection in copper overload conditions. These results emphasize the ability of CUR-NE to augment the therapeutic effects of curcumin, presenting a novel approach for managing copper-induced neurodegeneration. The study highlights the effectiveness of nanoemulsion-based delivery platforms in improving chelation treatments for neurological diseases. Full article

(This article belongs to the Special Issue Heavy Metal Contamination and Its Effects on Ecosystems and Human Health: Challenges and Solutions)

22 pages, 959 KiB

Open AccessReview

Red Mud as an Adsorbent for Hazardous Metal Ions: Trends in Utilization

by Maja Rajković, Ivana Jelić, Marija Janković, Dragi Antonijević and Marija Šljivić-Ivanović

Toxics 2025, 13(2), 107; https://doi.org/10.3390/toxics13020107 - 28 Jan 2025

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Abstract

The increasing importance of waste materials utilization with the necessary modification to remove various pollutants from industrial wastewater has been a research focus over the past few decades. Using waste material from one industry to solve pollution problems in another ultimately leads toward [...] Read more.

The increasing importance of waste materials utilization with the necessary modification to remove various pollutants from industrial wastewater has been a research focus over the past few decades. Using waste material from one industry to solve pollution problems in another ultimately leads toward sustainable and circular approaches in environmental engineering, solving waste management and wastewater treatment issues simultaneously. In contemporary research and industry, there is a notable trend toward utilizing industrial wastes as precursors for adsorbent formation with a wide application range. In line with this trend, red mud, a byproduct generated during alumina production, is increasingly viewed as a material with the potential for beneficial reuse rather than strictly a waste. One of the potential uses of red mud, due to its specific composition, is in the removal of heavy metal and radionuclide ions. This study summarizes red mud’s potential as an adsorbent for wastewater treatment, emphasizing techno-economic analysis and sorption capacities. An overview of the existing research includes a critical evaluation of the adsorption performance, factors influencing efficiency rather than efficacy, and the potential for specific pollutant adsorption from aqueous solutions. This review provides a new approach to a circular economy implementation in wastewater treatment while guiding future research directions for sustainable and cost-effective solutions. Full article

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15 pages, 1108 KiB

Open AccessArticle

Air, Skin, and Biological Monitoring of French Fire Instructors’ Exposure to Particles/PAHs During Controlled Fire and Mitigation Strategies

by Pauline Zangl, Clément Collart and Renaud Persoons

Toxics 2025, 13(2), 106; https://doi.org/10.3390/toxics13020106 - 28 Jan 2025

Viewed by 335

Abstract

Occupational exposure as a firefighter was recently classified as carcinogenic to humans by the IARC. Fire instructors’ exposure to carcinogenic PAHs is a major concern, and studies that have tried to assess the determinants of their exposure are scarce. An air and biomonitoring [...] Read more.

Occupational exposure as a firefighter was recently classified as carcinogenic to humans by the IARC. Fire instructors’ exposure to carcinogenic PAHs is a major concern, and studies that have tried to assess the determinants of their exposure are scarce. An air and biomonitoring study was conducted in fire instructors performing simulated training exercises in enclosed containers. Air samples were collected, as well as urine samples from 22 firefighting instructors, and skin wipes were collected from FFs’ skin at the end of the exercises. PAH metabolites (1-hydroxypyrene, 3-hydroxybenzo(a)pyrene, 2/3-hydroxyfluorene, and 2/3-hydroxyphenanthrene) were measured in urine samples at three sampling times (beginning of shift, end of shift, and next morning). Airborne PAHs were dominated by low molecular weight compounds (naphthalene), and levels were as high as 67 µg·m⁻³ close to the containers, decreasing at higher distances. Skin contamination was observed both on the neck/face and hands/wrists of fire instructors and pilots. Ten times lower skin contamination was observed when nitrile undergloves were worn. High internal exposure was measured, with 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene levels frequently exceeding maximum recommended values in occupational settings (up to 2.8 µmol/mol creatinine for 1-OHP, 14 µmol/mol creatinine for SOH-PAH, and 1.0 nmol/mol creatinine for 3-OHBaP), whereas benzene exposure was revealed to be very low. These types of exposure were found to derive both from dermal absorption (combustion products deposited on the skin) and inhalation (when removing SCBA outside the containers). Several recommendations are proposed in order to reduce both exposure routes (nitrile undergloves and half-masks in the vicinity of containers), harmonise decontamination (PPEs) and cleaning procedures, and prevent the dermal absorption of PAH from turnout gear. This study emphasises the complex PAH exposure profiles of fire instructors and characterises the main drivers of exposure, highlighting the need for better mitigation strategies. Full article

(This article belongs to the Special Issue Firefighters’ Occupational Exposures and Health Risks)

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12 pages, 2220 KiB

Open AccessArticle

Significance of Morphology in Characterizing Human Health Risk from di(2-ethylhexyl) Phthalate in Polyvinyl Chloride Microplastics in Groundwater

by Ki-Han Song, Sang-Gyu Yoon, Jin-Yong Lee and Jinsung An

Toxics 2025, 13(2), 105; https://doi.org/10.3390/toxics13020105 - 28 Jan 2025

Viewed by 402

Abstract

In this study, a human health risk assessment was performed on the ingestion route of groundwater containing polyvinyl chloride (PVC) microplastics (MPs), and the carcinogenic and non-carcinogenic risks of di(2-ethylhexyl) phthalate (DEHP), a representative additive, were determined. In particular, the impact of volume [...] Read more.

In this study, a human health risk assessment was performed on the ingestion route of groundwater containing polyvinyl chloride (PVC) microplastics (MPs), and the carcinogenic and non-carcinogenic risks of di(2-ethylhexyl) phthalate (DEHP), a representative additive, were determined. In particular, the impact of volume diversity according to the shape (morphology) of PVC MP (fragment, fiber, film) on the risk characterization was intensively explored. Firstly, a continuous particle size distribution following a power function was derived using the abundance ratio of PVC MPs by size in the investigated groundwater, and human health risk assessment for DEHP in the PVC MPs was performed through the volume distribution according to the shape of MPs. DEHP human health risk assessment showed an excess cancer risk (ECR) of below 10⁻⁶ for a 95% cumulative probability for all MP shapes, but the values varied depending on the shape. Sensitivity analysis showed that the parameter that most affected human health risk was MP volume, second to concentration, which is dependent on MP shape. Therefore, it is necessary to consider the variety of MP shapes during human health risk assessment, and it can be achieved through probabilistic risk assessment utilizing the probability distribution for size and shape of MPs. Full article

(This article belongs to the Special Issue Exposure and Toxicity of Emerging Organic Pollutants in Environment and Human)

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16 pages, 494 KiB

Open AccessSystematic Review

New Methodologies and Techniques for Biomonitoring Pesticide Exposure in Agricultural Workers: A Systematic Review

by Andreia Moreira, Joana Guedes and Manuela Vieira da Silva

Toxics 2025, 13(2), 104; https://doi.org/10.3390/toxics13020104 - 28 Jan 2025

Viewed by 306

Abstract

Biomonitoring allows for the assessment of internal exposure to various pesticides and metabolites. Following PRISMA guidelines, this systematic review aims to summarise innovative biomonitoring techniques for assessing pesticide exposure in agricultural workers, their advantages and limitations, and their applicability. The search of the [...] Read more.

Biomonitoring allows for the assessment of internal exposure to various pesticides and metabolites. Following PRISMA guidelines, this systematic review aims to summarise innovative biomonitoring techniques for assessing pesticide exposure in agricultural workers, their advantages and limitations, and their applicability. The search of the Medline/PubMed, ScienceDirect, Scopus, and Web of Science databases identified 14 articles dealing with new techniques for biomonitoring pesticide exposure in agricultural workers. These new methodologies have identified several biomarkers associated with exposure to organophosphates. Most of the included studies combine and/or improve traditional methods to overcome their limitations. This leads to more sensitive, specific, and precise techniques with lower detection and quantification limits. Therefore, it is necessary to thoroughly analyse and test new biomonitoring methods for assessing pesticide exposure. These techniques can complement qualitative risk assessments and aid in developing strategies to protect public health and the environment. Full article

(This article belongs to the Special Issue Pesticide Risk Assessment, Emerging and Re-Emerging Problems)

13 pages, 1330 KiB

Open AccessFeature PaperArticle

Element Levels in Feathers of Atlantic Puffins (Fratercula arctica) in Iceland: Establishing Background Levels in an Arctic Migratory Species

by Joanna Burger, Erpur Snær Hansen, Kelly Ng and Michael Gochfeld

Toxics 2025, 13(2), 103; https://doi.org/10.3390/toxics13020103 - 28 Jan 2025

Viewed by 758

Abstract

Examining contaminant concentrations in birds in Arctic environments is important for managing species for assessing long-term trends. Recent reports on mercury (Hg) concentrations in Arctic species of seabirds has identified a need for data from missing regions or species. We measured arsenic (As), [...] Read more.

Examining contaminant concentrations in birds in Arctic environments is important for managing species for assessing long-term trends. Recent reports on mercury (Hg) concentrations in Arctic species of seabirds has identified a need for data from missing regions or species. We measured arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), Hg and selenium (Se) in the body feathers of Atlantic Puffin (Fratercula arctica) from four colonies in Iceland in 2011 and one in 2009. Puffins forage on small fish at an intermediate trophic concentration. We found that (1) concentrations examined in the colony in 2009 were lower than in 2011 for all metals except As and Hg, and (2) concentrations of Cd and Se varied significantly among colonies for feathers collected in 2011. Pb concentrations in Puffin feathers in one colony were 14-fold higher in 2009 than in 2011 (mean of 805 ng.g⁻¹ vs. 58 ng.g⁻¹). The highest mean Hg concentration in 2011 was 362 ng.g⁻¹ and was 4880 ng.g⁻¹ for Se. The concentrations of Hg in the Atlantic Puffins reported in this study were similar to, or lower than those reported for the same species elsewhere and for Tufted Puffin from the Pacific. Full article

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16 pages, 1686 KiB

Open AccessArticle

Trace Detection of Di-Isopropyl Methyl Phosphonate DIMP, a By-Product, Precursor, and Simulant of Sarin, Using Either Ion Mobility Spectrometry or GC-MS

by Victor Bocoș-Bințințan, Paul-Flaviu Bocoș-Bințințan, Tomáš Rozsypal and Mihail Simion Beldean-Galea

Toxics 2025, 13(2), 102; https://doi.org/10.3390/toxics13020102 - 28 Jan 2025

Viewed by 384

Abstract

Di-isopropyl methyl phosphonate (DIMP) has no major commercial uses but is a by-product or a precursor in the synthesis of the nerve agent sarin (GB). Also, DIMP is utilized as a simulant compound for the chemical warfare agents sarin and soman in order [...] Read more.

Di-isopropyl methyl phosphonate (DIMP) has no major commercial uses but is a by-product or a precursor in the synthesis of the nerve agent sarin (GB). Also, DIMP is utilized as a simulant compound for the chemical warfare agents sarin and soman in order to test and calibrate sensitive IMS instrumentation that warns against the deadly chemical weapons. DIMP was measured from 2 ppb_v (15 μg m⁻³) to 500 ppb_v in the air using a pocket-held ToF ion mobility spectrometer, model LCD-3.2E, with a non-radioactive ionization source and ammonia doping in positive ion mode. Excellent sensitivity (LoD of 0.24 ppb_v and LoQ of 0.80 ppb_v) was noticed; the linear response was up to 10 ppb_v, while saturation occurred at >500 ppb_v. DIMP identification by IMS relies on the formation of two distinct peaks: the monomer M·NH₄⁺, with a reduced ion mobility K₀ = 1.41 cm² V⁻¹ s⁻¹, and the dimer M₂·NH₄⁺, with K₀ = 1.04 cm² V⁻¹ s⁻¹ (where M is the DIMP molecule); positive reactant ions (Pos RIP) have K₀ = 2.31 cm² V⁻¹ s⁻¹. Quantification of DIMP at trace levels was also achieved by GC-MS over the concentration range of 1.5 to 150 μg mL⁻¹; using a capillary column (30 m × 0.25 mm × 0.25 μm) with a TG-5 SilMS stationary phase and temperature programming from 60 to 110 °C, DIMP retention time (RT) was ca. 8.5 min. The lowest amount of DIMP measured by GC-MS was 1.5 ng, with an LoD of 0.21 μg mL⁻¹ and an LoQ of 0.62 μg mL⁻¹ DIMP. Our results demonstrate that these methods provide robust tools for both on-site and off-site detection and quantification of DIMP at trace levels, a finding which has significant implications for forensic investigations of chemical agent use and for environmental monitoring of contamination by organophosphorus compounds. Full article

(This article belongs to the Section Drugs Toxicity)

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15 pages, 4079 KiB

Open AccessArticle

Investigation of the Earliest Ozone Pollution Events in Hangzhou Bay, China Based on Observations and ERA5 Reanalysis Data

by Tianen Yao, Xinhao Li, Zhi Li, Xinyu Yang, Jinjia Zhang, Yaqi Wang, Jianhui Guo and Jing Li

Toxics 2025, 13(2), 99; https://doi.org/10.3390/toxics13020099 - 27 Jan 2025

Viewed by 305

Abstract

Abstract: Ozone pollution in Hangzhou Bay, one of the seven petrochemical clusters in China, is severe. Early ozone pollution has been detected recently, such as the maximum daily 8 h average (MDA8) ozone concentration in Jiaxing achieving 171.0 μg/m³ on 7 [...] Read more.

Abstract: Ozone pollution in Hangzhou Bay, one of the seven petrochemical clusters in China, is severe. Early ozone pollution has been detected recently, such as the maximum daily 8 h average (MDA8) ozone concentration in Jiaxing achieving 171.0 μg/m³ on 7 March 2023. Satellites have observed tropospheric column concentrations of ozone precursors formaldehyde (HCHO) and nitrogen dioxide (NO_x), and quantitative models are proposed to reveal the causes of the early onset of ozone pollution. VOC-limited and transitional regimes dominate most areas in Hangzhou Bay, and NO_x-limited regimes dominate the region around Hangzhou Bay, such as northeastern Jiangsu Province. Results show that HCHO column concentrations are increasing in VOC-limited regions, and NO_x column concentrations are increasing more rapidly than HCHO in NO_x-limited regions. According to multivariate linear regression (MLR), early spring ozone pollution in Hangzhou Bay is mainly caused by meteorological drivers. Hangzhou Bay has formed an atmospheric meteorological environment with high temperature and low humidity. The richer solar radiation intensifies the photochemical reactions associated with tropospheric ozone formation, producing more tropospheric ozone. Based on the Shapley Additive Explanation (SHAP) algorithm, ozone pollution increases when solar radiation exceeds 12 million J/m² and is accompanied by high temperatures. Overall, reducing VOC emissions helps to mitigate ozone growth in Shanghai and northern Hangzhou Bay, while reducing NO_x emissions is more effective in northeastern Jiangsu Province. Full article

13 pages, 1519 KiB

Open AccessArticle

Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury

by Yingying Zeng, Guiping Zhu, Wenjun Peng, Hui Cai, Chong Lu, Ling Ye, Meiling Jin and Jian Wang

Toxics 2025, 13(2), 98; https://doi.org/10.3390/toxics13020098 - 27 Jan 2025

Viewed by 359

Abstract

Background: N6-methyladenosine (m⁶A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m⁶A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) [...] Read more.

Background: N6-methyladenosine (m⁶A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m⁶A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored. Methods: Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches. Results: A total of 664 hypermethylated m⁶A peaks on 644 lncRNAs and 367 hypomethylated m⁶A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m⁶A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m⁶A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m⁶A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response. Conclusions: This study first provides a comprehensive transcriptome-wide analysis of m⁶A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m⁶A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury. Full article

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14 pages, 3958 KiB

Open AccessArticle

Sleep Deprivation and Subchronic Arsenite Exposure Synergistically Induced Skeletal Muscle Aging by Disrupting Melatonin and Cortisol Secretion in Mice

by Hongyi Yang, Xingyu Chen, Xuanfeng Yu, Baofei Sun, Junyan Tao and Xiong Chen

Toxics 2025, 13(2), 97; https://doi.org/10.3390/toxics13020097 - 27 Jan 2025

Viewed by 310

Abstract

In recent years, the influence of environmental factors on organismal aging has garnered increasing attention. Studies have shown that sleep deprivation and environmental pollutants could accelerate the emergence of multiple organismal aging phenotypes. In addition, studies have shown that chronic exposure to sodium [...] Read more.

In recent years, the influence of environmental factors on organismal aging has garnered increasing attention. Studies have shown that sleep deprivation and environmental pollutants could accelerate the emergence of multiple organismal aging phenotypes. In addition, studies have shown that chronic exposure to sodium arsenite (iAs) induces skeletal muscle atrophy and the inhibition of melatonin secretion in rats. This study aimed to reveal the synergistic effect of sleep deprivation and arsenite exposure on skeletal muscle aging, including reduced limb grip strength and skeletal muscle mass, along with the serum levels of melatonin (MT) and cortisol (COR) in C57BL/6J mice. The results demonstrated that while exposure to arsenite for 12 weeks or sleep deprivation (SD) for 4 weeks did not exert significant effects on limb grip strength or skeletal muscle mass, their combination exhibited a synergistic effect on skeletal muscle aging. Notably, the iAs+SD group exhibited a significant decline in limb grip strength by Week 12, accompanied by a reduced gastrocnemius muscle mass and muscle index. The pathological analysis showed muscle fiber atrophy, a shift towards slow-twitch muscle fibers (type I), and shortened telomere length. Additionally, oxidative damage was increased in the SD and iAs+SD groups, with decreased levels of SOD and GPx and elevated levels of MDA in the iAs+SD group. The serum MT level and MT/COR ratio were significantly reduced, while the serum COR level was elevated in the iAs+SD group compared to the other groups. A correlation analysis further revealed that the serum MT level and the MT/COR ratio were positively correlated with limb grip strength, muscle index, and telomere length, whereas the serum COR level exhibited negative correlations with these parameters. These findings suggest that sleep deprivation and subchronic exposure to arsenite synergistically induce skeletal muscle aging, and that the disruption of the balance between MT and COR potentially serves as a significant risk factor. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Disease Caused from Environmental Fluoride and Arsenic Exposures)

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11 pages, 611 KiB

Open AccessArticle

Temporal Changes in Lead and Cadmium Levels in Amanita muscaria Samples Collected in Poland

by Michal Ordak, Aleksandra Galazka, Pawel Konieczynski, Marek Wesolowski, Alina Plenis, Elzbieta Muszynska, Przemyslaw Kurowski and Magdalena Bujalska-Zadrozny

Toxics 2025, 13(2), 101; https://doi.org/10.3390/toxics13020101 - 27 Jan 2025

Viewed by 635

Abstract

In recent years, an increasing popularity of consuming Amanita muscaria has been observed in Poland, aimed at reducing various medical symptoms. However, there is a lack of data regarding the impact of variations in the content of toxic elements, such as cadmium (Cd) [...] Read more.

In recent years, an increasing popularity of consuming Amanita muscaria has been observed in Poland, aimed at reducing various medical symptoms. However, there is a lack of data regarding the impact of variations in the content of toxic elements, such as cadmium (Cd) and lead (Pb), in Amanita muscaria collected during late summer and mid-fall. The aim of this study was to determine the concentrations of Pb and Cd in Amanita muscaria samples collected at different times of the year, compare the concentrations of these elements in samples with and without cap skin, and compare the obtained values to permissible limits in dietary supplements. A total of 44 Amanita muscaria samples were collected during three different harvesting periods (August, September, and October 2023) from Puszcza Biała, located approximately 80 km from Warsaw. The mushrooms were subjected to mineralization using concentrated nitric acid and hydrogen peroxide, followed by the determination of Pb and Cd concentrations using an atomic absorption spectrometer. Significant statistical differences were found in the Pb concentrations of samples collected in three different seasons (η² = 0.67, p < 0.001), with the concentration increasing progressively, reaching its highest value in October. Similarly, the Cd concentration also increased in the later collections, although the effect of time was weaker (η² = 0.13, p = 0.03). No significant differences were observed in Pb and Cd concentrations between samples with and without cap skin. The average Cd concentrations in mushrooms were significantly higher than the permissible levels in dietary supplements; they were four times higher in August (p < 0.001), six times higher in September (p < 0.001), and nine times higher in October (p < 0.001). The Pb concentration in the October samples was close to the permissible limit but did not exceed it in a statistically significant manner (p = 0.85). Due to the high Cd concentrations and potentially hazardous levels of Pb, the consumption of Amanita muscaria carries a significant risk of toxicity, which may lead to serious health hazards, particularly in the context of prolonged exposure. Full article

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17 pages, 2706 KiB

Open AccessArticle

Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium

by Xin Tan, Nengyong Ouyang, Wenjun Wang and Junting Qiu

Toxics 2025, 13(2), 100; https://doi.org/10.3390/toxics13020100 - 27 Jan 2025

Viewed by 389

Abstract

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects [...] Read more.

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration. Full article

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

26 pages, 509 KiB

Open AccessArticle

Identification, Evaluation and Prioritization of Chemicals for National Human Biomonitoring Program: Insights from Latvia

by Linda Matisāne, Lāsma Akūlova, Žanna Martinsone, Ilona Pavlovska, Laura Komarovska, Kristiāna Venžega, Dace Jakimova, Kristīne Sproģe, Normunds Kadiķis, Inese Mārtiņsone, Madlen David, Marike Kolossa-Gehring and Ivars Vanadziņš

Toxics 2025, 13(2), 96; https://doi.org/10.3390/toxics13020096 - 26 Jan 2025

Viewed by 618

Abstract

Human biomonitoring (HBM) is a critical tool for assessing chemical exposure in populations and informing public health policies. This study aimed to prioritize chemical substances for the development of a national HBM program in Latvia, addressing the need for systematic evaluation of chemicals [...] Read more.

Human biomonitoring (HBM) is a critical tool for assessing chemical exposure in populations and informing public health policies. This study aimed to prioritize chemical substances for the development of a national HBM program in Latvia, addressing the need for systematic evaluation of chemicals in the local context. Initially, 318 chemical substances were reviewed, of which 130 were shortlisted and assessed using an adapted Hanlon methodology. Substances were assessed based on their health significance, hazardous properties, exposure characteristics, national relevance, and public interest. The results identified 30 high-priority substances across various categories, providing a foundation for the HBM4LV program. This prioritization process highlighted the challenges of data gaps, resource limitations, and the need to balance national priorities with alignment to European frameworks. Despite addressing key methodological challenges, the study highlights the importance for ongoing refinement, robust data collection, and strengthened international collaboration to enhance the program’s scope and long-term sustainability. While the methodology addressed key challenges, further refinement and international collaboration are essential to enhance the program’s scope and sustainability. Full article

(This article belongs to the Special Issue Human Exposure to Emerging Contaminants: Pathways, Biomarkers, Characteristics, and Health Risks)

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21 pages, 2977 KiB

Open AccessArticle

Fluoride-Mediated Immune Damage Through Cytokine Network Regulation of Tregs

by Bingshu Liu, Siqi Zhu, Qiong Zhang, Fengyu Xie, Dan Wei, Guiyu Fu, Liu Yang, Yanhui Gao and Wei Wei

Toxics 2025, 13(2), 95; https://doi.org/10.3390/toxics13020095 - 26 Jan 2025

Viewed by 312

Abstract

Long-term fluoride exposure can induce inflammatory responses in various tissues of the body, thereby affecting the inflammatory microenvironment. To explore how fluoride induces changes in immune function within this microenvironment, this study collected baseline information and biological samples from participants in areas with [...] Read more.

Long-term fluoride exposure can induce inflammatory responses in various tissues of the body, thereby affecting the inflammatory microenvironment. To explore how fluoride induces changes in immune function within this microenvironment, this study collected baseline information and biological samples from participants in areas with the drinking water type of fluorosis, and simultaneously established Wistar rat models with a 12-week and 24-week fluoride exposure, as well as a 12-week fluoride exposure followed by 12-week pure water feeding regimen. Luminex multiplex assays and enzyme-linked immunosorbent assays (ELISAs) were used to measure cytokine expression levels. Subsequently, correlation analysis, multiple linear regression, and mediation analysis were employed to explore the long-term effects induced by the complex cytokine network during fluoride exposure. The population survey results indicated that fluoride suppressed the expression of pro-inflammatory factors such as Interleukin-2 (IL-2), Interleukin-12 (IL-12), Interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and anti-inflammatory factors such as Interleukin-4 (IL-4), Interleukin-13 (IL-13), and Interleukin-37 (IL-37), while promoting an increase in the proportion of regulatory T cells (Tregs) in peripheral blood. Among these, IL-2 and IFN-γ mediated the fluoride-induced peripheral Tregs expansion. Animal experiments indicate that the proportion of Tregs in peripheral blood and immune organs increases in a time-dependent manner with fluoride exposure. After reducing the fluoride concentration in the drinking water of rats, the number of Tregs remained significantly elevated. The changes in Treg numbers in the 12-week fluoride feeding group, 24-week fluoride feeding group, and 12-week fluoride feeding followed by 12-week water improvement group were related to the cytokine levels. Therefore, the impact of fluoride on the immune homeostasis has cumulative and long-term effects, and may be related to the accumulation and migration of Tregs induced by fluoride in an inflammatory environment, mediated by cytokines. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Disease Caused from Environmental Fluoride and Arsenic Exposures)

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18 pages, 1065 KiB

Open AccessArticle

Salvia connivens Methanolic Extract Against Spodoptera frugiperda and Tenebrio molitor and Its Effect on Poecilia reticulata and Danio rerio

by Manolo Rodríguez-Cervantes, Luis Ricardo León-Herrera, Salvador Alejandro Ventura-Salcedo, María del Carmen Monroy-Dosta, Eloy Rodríguez-deLeón, Mamadou Moustapha Bah, Juan Campos-Guillén, Aldo Amaro-Reyes, Carlos Eduardo Zavala-Gómez, Rodolfo Figueroa-Brito, Karla Elizabeth Mariscal-Ureta, Héctor Pool, Itzel Ramos-Mayorga and Miguel Angel Ramos-López

Toxics 2025, 13(2), 94; https://doi.org/10.3390/toxics13020094 - 26 Jan 2025

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Abstract

Spodoptera frugiperda (Lepidoptera: Noctuidae) and Tenebrio molitor (Coleoptera: Tenebrionidae) are two prominent pests of maize and its stored grains, respectively. Botanical pesticides have been proposed as an alternative for their management. This study evaluated the insecticidal activity of Salvia connivens (Lamiaceae) methanolic extract [...] Read more.

Spodoptera frugiperda (Lepidoptera: Noctuidae) and Tenebrio molitor (Coleoptera: Tenebrionidae) are two prominent pests of maize and its stored grains, respectively. Botanical pesticides have been proposed as an alternative for their management. This study evaluated the insecticidal activity of Salvia connivens (Lamiaceae) methanolic extract and rosmarinic acid against S. frugiperda and T. molitor by adding them to an artificial diet, as well as their ecotoxicological effects on Poecilia reticulata (Cyprinodontiformes: Poeciliidae) and Danio rerio (Cypriniformes: Danionidae) through acute toxicity tests. The methanolic extract showed higher mortality activity against S. frugiperda (LC₅₀ = 874.28 ppm) than against T. molitor (LC₅₀ = 1856.94 ppm) and was non-toxic to fish. Rosmarinic acid, the most abundant compound in the extract (80.45 mg g⁻¹), showed higher activity against S. frugiperda (LC₅₀ = 176.81 ppm). This compound did not cause a toxic effect on adult P. reticulata at the tested concentrations. However, in P. reticulata fingerlings and D. rerio adults, it was non-toxic, except in D. rerio embryos, where it was slightly toxic. These findings suggest that S. connivens methanolic extract has potential as a botanical product for the management of S. frugiperda and T. molitor with low ecotoxicological impact, while rosmarinic acid may be a useful compound for the management of S. frugiperda. Full article

(This article belongs to the Special Issue Impacts of Agrochemicals on Insects and Soil Organisms)

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14 pages, 1035 KiB

Open AccessArticle

Background Values of Soil Heavy Metals in the Huang-Huai-Hai Plain in Henan Province, China

by Yuling Jiang, Jianhua Ma, Yuanbo Wang and Yahan Yang

Toxics 2025, 13(2), 93; https://doi.org/10.3390/toxics13020093 - 26 Jan 2025

Viewed by 281

Abstract

Due to the continuous lack of specific background values (BVs) for soil heavy metals in the Huang-Huai-Hai Plain in Henan province (HPHP), many researchers have used soil heavy BVs specific to Henan Province (HP) or Fluvisols of China (FC) as reference criteria to [...] Read more.

Due to the continuous lack of specific background values (BVs) for soil heavy metals in the Huang-Huai-Hai Plain in Henan province (HPHP), many researchers have used soil heavy BVs specific to Henan Province (HP) or Fluvisols of China (FC) as reference criteria to assess soil heavy metal pollution. However, spatial differences in the soil heavy metal BVs between HPHP, HP, and FC, as well as within the HPHP, remain uncertain, affecting the reliability of evaluation results. A total of 897 surface soil samples were collected from the HPHP, with 336 and 561 samples collected from the southern and northern parts of the Shaying River, respectively. According to the obtained results, the BVs of soil Hg, As, Cd, Cr, Pb, Cu, Zn, and Ni in the HPHP were 0.064, 6.67, 0.129, 53.24, 19.67, 22.87, 64.00, and 26.25 mg·kg⁻¹, respectively. The BVs of soil Hg and Cd were higher than those in HP, Fluvisols in Henan Province, and FC, showing strong and extremely strong levels. The BVs of other soil heavy metals exhibited slight differences from the reference BVs. On the other hand, the BVs of soil Hg, As, Cd, Cr, Pb, Cu, Zn, and Ni were 0.066, 4.11, 0.130, 56.72, 20.97, 23.31, 59.21, and 24.03 mg·kg⁻¹ in the southern part and 0.061, 7.45, 0.129, 51.92, 18.96, 22.72, 66.96, and 27.16 mg·kg⁻¹ in the northern part of the Shaying River, respectively. In addition, there were no significant differences in the Hg and Cd BVs between the two parts. Cu BVs in the southern part were significantly higher than those observed in the northern part, while the As, Zn, and Ni BVs in the northern part were significantly higher than those revealed in the southern part. In contrast, the Cr and Pb BVs in the northern part were significantly lower than those observed in the southern part. Full article

(This article belongs to the Special Issue Assessment and Remediation of Heavy Metal Contamination in Soil)

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21 pages, 1432 KiB

Open AccessArticle

Association Between Heavy Metal Exposure and Central Nervous System Tumors: A Case-Control Study Using Single and Multi-Metal Models

by Sen Luo, Haixia Wu, Fang Xiao, Tianwen Yang, Wei Wang, Hang Du and Peng Su

Toxics 2025, 13(2), 92; https://doi.org/10.3390/toxics13020092 - 26 Jan 2025

Viewed by 340

Abstract

(1) Background: Neoplasms of the central nervous system (CNS) encompass a cluster of malignant diseases originating from tissues or structures within the CNS. Environmental factors, including heavy metals, may contribute to their development. Therefore, this research was to investigate the association between heavy [...] Read more.

(1) Background: Neoplasms of the central nervous system (CNS) encompass a cluster of malignant diseases originating from tissues or structures within the CNS. Environmental factors, including heavy metals, may contribute to their development. Therefore, this research was to investigate the association between heavy metal exposure and CNS tumor susceptibility using single and muti-metal models. (2) Methods: 63 CNS tumor patients and 71 controls were included. Urine samples from the CNS tumor patients and controls were analyzed for 47 metals using inductively coupled plasma-mass spectrometry in this study. Statistical analyses included conditional Wilcoxon rank-sum tests, logistic regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Bayesian Kernel Machine Regression (BKMR). (3) Results: In the single metal model, higher levels of seventeen metals might be associated with a lower incidence of CNS tumor, while higher exposure levels of five metals are associated with a higher incidence of tumor. LASSO regression selected nine metals for further BKMR analysis. The joint effects showed decreased tumor risk with increased metal mixture concentration. The level of the metals Ge, As, Rb, Zr, and Sn may be related to the incidence of meningiomas and gliomas. (4) Conclusions: This study explored the association between various metals and CNS tumors, providing ideas for future prospective cohort studies and laboratory studies, and providing a foundation for new ideas in the prevention and treatment of CNS tumors. Full article

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

17 pages, 948 KiB

Open AccessArticle

Concentrations of Serum Per- and Polyfluoroalkyl Substances and Lipid Health in Adolescents: A Cross-Sectional Study from the Korean National Environmental Health Survey 2018–2020

by Min-Won Shin, Habyeong Kang and Shin-Hye Kim

Toxics 2025, 13(2), 91; https://doi.org/10.3390/toxics13020091 - 25 Jan 2025

Viewed by 434

Abstract

Emerging evidence indicates that environmental exposure to per- and polyfluoroalkyl substances (PFASs) may influence lipid metabolism, though studies on adolescents remain scarce. This study aimed to investigate the association between PFAS mixture exposure and lipid profiles in Korean adolescents. Using data from the [...] Read more.

Emerging evidence indicates that environmental exposure to per- and polyfluoroalkyl substances (PFASs) may influence lipid metabolism, though studies on adolescents remain scarce. This study aimed to investigate the association between PFAS mixture exposure and lipid profiles in Korean adolescents. Using data from the Korean National Environmental Health Survey (2018–2020), we analyzed 824 adolescents aged 12–17 years. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDeA), and lipid profiles were assessed. In multivariate regression models, PFDeA and PFNA were positively associated with elevated total cholesterol and low-density lipoprotein cholesterol levels, and PFDeA was associated with hypercholesterolemia risk in boys. In girls, PFDeA was associated with higher high-density lipoprotein cholesterol and lower triglycerides, though no significant association with hypercholesterolemia risk was observed. Bayesian kernel machine regression demonstrated positive associations between PFAS mixture exposure and hypercholesterolemia risk in boys but not in girls. The quantile g-computation model also demonstrated an odds ratio (OR) of 1.47 (95% CI: 0.99–2.19, p = 0.057) for PFAS mixture exposure in boys, suggesting borderline statistical significance. These findings suggest that PFAS exposure may disrupt lipid metabolism, elevating hypercholesterolemia risk in adolescents, particularly boys. Full article

(This article belongs to the Special Issue Health Effects and Toxicology Studies of Emerging Contaminants)

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