Toxics doi: 10.3390/toxics14050431

Authors: Fausto Jaime Miranda de de Araujo Eloisa Dutra Caldas

Firefighters and forest brigades engaged in wildfire suppression are routinely exposed to smoke containing toxic compounds that pose acute and chronic health risks, and it is important to understand how they perceive these risks during their work. This study aimed to evaluate health risk perception among military firefighters and contracted forest brigades in the Federal District, Brazil, the use of respiratory protection equipment (RPE), and institutional support. A questionnaire was administered to 150 firefighters and 22 brigades in 2023 and 2024. Most respondents were between 30 and 40 years old, with firefighters having a significantly higher education level than brigades (p < 0.0001). Most were concerned about smoke exposure and recognized its high health risk, including respiratory diseases and cancer, with brigades showing a higher risk perception than firefighters (p < 0.0001). Despite this high perceived risk, about 80% of firefighters and 86% of brigades reported not using RPE, mainly because it was not provided by their institutions (according to 53.8% of firefighters and 73.7% of brigades). The level of concern about wildfire smoke among participants correlated positively with age, years of experience, perceived necessity of RPE, and willingness to use it if provided. Firefighters rated their institution’s performance on occupational health and safety significantly less positively than brigades (p < 0.0001). The results of this study demonstrated that the lack of preventive and protective practices is not due to low risk perception, but rather to institutional failures in guidance, support, and provision of RPE.

Toxics doi: 10.3390/toxics14050430

Authors: Haobo Qu Xiaoyu Zhao Yifan Wang Sichao Mao Xingxiang Chen Kehe Huang Xinyi Xu

Cadmium (Cd) is a persistent environmental pollutant that poses a significant health risk to humans and animals, with acute exposure known to induce kidney injury. Fucoidan (Fc), a natural bioactive polysaccharide derived from brown algae, exhibits diverse biological activities; however, its potential to protect against Cd-induced kidney damage and the underlying mechanisms remain unclear. In this study, we investigated the effects of Fc on Cd-induced renal injury in vitro and further explored the role of transcription factor EB (TFEB) in regulating autophagy in its protective mechanism. Our results demonstrate that in Cd-exposed porcine kidney cells (PK-15), Fc suppressed the expression of renal inflammatory factors (TNF-α, IL-1β) and kidney injury markers (NGAL, NTN-1, KIM-1), reduced reactive oxygen species (ROS) production, and downregulated apoptosis-related proteins (cleaved caspase-3 and cleaved caspase-9). Mechanistically, Fc upregulated TFEB protein expression, enhanced the levels of lysosomal function-related proteins (Cathepsin B, CTSB; Cathepsin D, CTSD), and reversed Cd-induced autophagic flux blockade. Importantly, TFEB silencing abolished the protective effects of Fc. Collectively, these findings suggest that Fc exerts renoprotective effects against Cd-induced injury by restoring autophagic flux, a process that involves TFEB.

Toxics doi: 10.3390/toxics14050429

Authors: Custodio V. Muianga Gregory M. Zarus Katie Stallings Gaston Casillas Mohammad Shoeb Kimberly Gehle Mohammad Moiz Mumtaz Christopher M. Reh

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

Toxics doi: 10.3390/toxics14050428

Authors: Zhuo Sun Siyu Yang Tong Zhang Hongyin Li Peng Gao Liqiu Zhang Li Feng Qi Han

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

Toxics doi: 10.3390/toxics14050427

Authors: Yuanxin Cao Xiaoxin Zhang Yubo Yan Qiao Li

Water contamination by phenolic endocrine-disrupting chemicals (EDCs) is a global environmental concern. Yet, the occurrence of phenolic EDCs in artificial water diversion systems remains poorly understood. Thus, the Eastern Route of the South-to-North Water Diversion Project, the world’s longest water diversion project, was chosen as the study area to investigate the spatiotemporal distribution of alkylphenols (APs) and bisphenol A (BPA), typical phenolic EDCs, and to evaluate their risks. During the diversion operation, higher mean ΣAP concentrations were observed in lakes of Nansi and Dongping relative to the Luoma Lake–Dongping Lake and Yangtze–Luoma Lake diversion channels. The AP composition in the two lakes was also different from that in the two channels. These findings demonstrated that the canal water was not a key source of AP contamination in the lakes, highlighting the importance of local wastewater inputs. The spatial distribution of ΣAP and BPA concentrations in the lakes was mainly affected by the riverine inputs. For ecological risks, 4-n-nonylphenol (4-n-NP) exhibited moderate ecological risks at 81.3% of sampling sites in Dongping Lake and 68.8% of those in Luoma Lake, highlighting the need for heightened attention in future studies. Even under the high exposure scenario, 4-n-NP and BPA would not produce health risks to residents through water intakes. Overall, surface water resources of the Eastern Route Project were confirmed to be safe for human consumption.

Toxics doi: 10.3390/toxics14050426

Authors: Jae-Won Choi Shin-Young Park Cheol-Min Lee

Personal exposure assessment is essential in environmental and epidemiological studies. However, conventional methods often do not adequately reflect individuals’ spatiotemporal activity characteristics. This study evaluates the suitability of personal exposure assessment methods using PM2.5 as a case study, comparing measured personal exposure concentrations with three exposure estimation scenarios (S1–S3). S1 relies on fixed-site monitoring data, S2 incorporates location-based outdoor concentrations and a single indoor measurement, and S3 integrates individual location with microenvironment-specific concentrations. Using personal PM2.5 measurements and time–activity data (TAD) from adults in the Seoul metropolitan area, exposure levels showed substantial variation depending on activity patterns and time spent in different microenvironments. Time-weighted average (TWA)-based estimates differed across scenarios; among them, the one integrating microenvironmental concentrations and TAD showed the closest agreement with measured exposure. In contrast, S1 and S2 generally overestimated exposure. Although S3 slightly underestimated short-term high-concentration events, it showed high correlation (r = 0.78) and low errors (RMSE = 4.79, MAE = 3.70), effectively capturing relative variability in personal exposure. These results suggest that integrating time–activity patterns with microenvironmental concentrations improves the accuracy and reliability of personal exposure assessment and is expected to further enhance the reliability of personal exposure assessment.

Toxics doi: 10.3390/toxics14050424

Authors: Faiz N. Alenezi Marwa S. Zaghloul Manar A. Nader Marwa E. Abdelmageed

Objective: The existing work was designed to appraise whether Secukinumab diminishes acute kidney injury in a Cisplatin- induced rat model and to explore the potential underlying mechanisms for this protective effect. Methods: In vivo study, rats were distributed haphazardly into five sets (six animals in each group): control, Secukinumab control, Cisplatin (8 mg/kg, a single dose, intraperitoneally (IP)), and two pretreated groups; Secukinumab (10 and 20 mg/kg single subcutaneous (SC) injection) + Cisplatin. Blood samples and kidney tissues were gathered and analyzed histopathologically and biochemically. In vitro investigation, MCF-7 human breast cancer cells were treated with Cisplatin alone with Secukinumab, and cell viability (MTT assay), combination index, and apoptosis-related markers were analyzed. Results: Secukinumab administration lowered serum levels of BUN, creatinine and LDH with marked elevation in renal TAC and a significant reduction in MDA, iNOS, KIM-1 and NGAL compared to Cisplatin. Additionally, Secukinumab pre-treatment markedly suppressed the inflammatory process and enhanced autophagy, reflected by elevated AMPKα1, SIRT1, and Beclin-1, accompanied by reduced P38 MAPK and NF-κB p65 (Phospho-Ser536) levels and expression levels of IL-6 and P62/SQSTM1 in kidney tissues, contrasted with the Cisplatin group. Secukinumab administration effectively protected against kidney injury, and histopathological examinations of the kidneys confirmed these results. On the other hand, in vitro study results revealed that the combination of Cisplatin and Secukinumab had a synergistic cytotoxic effect and an enhancing effect on the apoptotic pathway (increased P53 and BAX and decreased BCL-2). Secukinumab effectively protects against Cisplatin- induced acute kidney injury by decreasing oxidative stress, inflammation, and enhancing autophagy. Additionally, it synergizes with Cisplatin in vitro to promote cancer cell apoptosis, highlighting its dual reno-protective and anticancer potential.

Toxics doi: 10.3390/toxics14050425

Authors: Maja Lazarus Božena Skoko Mikael Hult Tatjana Orct Maja Ferenčaković Ivana Coha Josip Kusak Slaven Reljić Gerd Marissens Heiko Stroh

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

Toxics doi: 10.3390/toxics14050423

Authors: Xiao Hu Yuxuan Huang Xiaohan Shao Yuehua Liu Tingting Peng Bo Zhu Jianzhang Huang Hanyang Man

Volatile organic compound (VOC) emissions exhibit strong process-level heterogeneity, yet regional source characterization still commonly relies on sector-average profiles, introducing substantial uncertainty into source identification and control prioritization. In this study, process-resolved VOC source profiles were established for five representative industrial sectors in Deyang, a typical industrial city in the Chengdu–Chongqing region, including pharmaceutical manufacturing, industrial coating, chemical industry, food manufacturing, and the textile industry. A total of 19 organized emission samples were collected from 9 enterprises, and 123 VOC species were quantified. These measured profiles were further integrated with literature-derived profiles and a bottom-up emission inventory to construct an emission-weighted regional composite source profile for 17 major industrial sectors. An emission-based hydroxyl radical (OH) reactivity-weighted framework was then introduced to compare mass-dominant and chemically dominant VOC sources. The results showed pronounced process- and sector-specific differences in composition. Pharmaceutical manufacturing was mainly dominated by oxygenated VOCs (OVOCs), industrial coating by low-carbon halocarbons, the chemical industry by methanol and reactive low-carbon compounds, food manufacturing by alkenes and OVOCs, and the textile industry by light alkanes. At the regional scale, industrial VOC emissions were dominated by OVOCs (35.67%), followed by alkanes (19.01%) and aromatics (15.99%). Ethyl acetate, 1,4-dioxane, 1,1,2,2-tetrachloroethane, and m/p-xylene were identified as the most abundant species. However, OH reactivity was largely dominated by alkenes, and substantial discrepancies were observed between emission contribution and OH-reactivity-weighted contribution across sectors. In particular, the chemical industry contributed 21.10 ± 8.43% of reactive organic gas emissions but 28.82 ± 11.61% of OH-weighted emissions, whereas printing contributed 13.55 ± 13.42% of mass emissions but only 7.66 ± 13.08% of OH-weighted emissions. These findings demonstrate that regional VOC management should move beyond bulk mass reduction and prioritize high-reactivity sectors and process units to maximize O3 mitigation benefits.

Toxics doi: 10.3390/toxics14050421

Authors: Nadia Saadat Soundara Viveka Thangaraj Jasmin Chovatiya Ravikumar Jagani Syam S. Andra Vasantha Padmanabhan

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

Toxics doi: 10.3390/toxics14050422

Authors: Shun-Hsin Liang Justin A. Steimling

Ultrashort-chain (USC) per- and polyfluoroalkyl substances (PFAS) are highly polar, mobile, and persistent emerging pollutants. While the environmental distribution of USC species is well-documented, their presence in widely consumed beverages remains under-characterized due to the analytical difficulty of capturing such highly polar species. This study established a robust workflow for the simultaneous determination of C1 to C14 perfluoroalkyl carboxylic and sulfonic acids, alongside other PFAS classes, in diverse beverage matrices including teas and fruit juices. Chromatographic separation was achieved using a mixed-mode inert-coated alkyl-phase LC column to enhance USC retention while maintaining performance for longer-chain analytes. A high-throughput, minimal-handling sample preparation was optimized to mitigate matrix effects and contamination. Method performance was evaluated using fortified beverage samples across 2–500 ng/L, with calibration ranges of 1–2000 ng/L and incorporation of 13 isotopically labeled internal standards. Results demonstrated acceptable accuracy (recoveries within 30% of nominal values) and optimal precision (%RSD < 12%). Application to commercial samples revealed frequent PFAS occurrence, specifically highlighting the prevalence of previously overlooked USC species in the human diet. These results demonstrate that ready-to-drink beverages are a significant pathway for human exposure, necessitating the inclusion of USC compounds in future food safety monitoring and risk assessments.

Toxics doi: 10.3390/toxics14050420

Authors: Nicole Geraldine de Paula Marques Witt Daiana Castro Barros Bruna Franciscon de Oliveira Breno Lourenzzo Salgado Guimarães Diego Dias Sudul Philippe Juneau Marcelo Pedrosa Gomes

Background: The increasing consumption of psychoactive pharmaceuticals has led to their continuous release into aquatic environments. Methods: This study assessed the ecotoxicological responses, phytoremediation capacity, and ecological risk of seven psychoactive pharmaceuticals—citalopram (CIT), sertraline (SER), fluoxetine (FLU), alprazolam (ALP), clonazepam (CLO), risperidone (RIS), and topiramate (TOP)—using Lemna minor under controlled exposure conditions. Plants were exposed to a concentration gradient, and physiological endpoints, including relative growth rate, chlorophyll content, and maximum photosystem II efficiency (Fv/Fm), were evaluated alongside compound removal and abiotic degradation. Results: Dose–response modeling revealed substantial variability in toxicity, with TOP (EC50 = 74.11 ng L−1), CLO (104.8 ng L−1), and RIS (138.5 ng L−1) exhibiting the highest potency, whereas FLU (1751 ng L−1), CIT (89,941 ng L−1), and ALP (465,351 ng L−1) were less toxic. Relative growth rate was the most sensitive endpoint. Mixture exposure did not result in additional toxicity compared to the most responsive individual compounds. Abiotic degradation was negligible for most compounds (<3%), except for SER (~42%) and FLU (~22%). In contrast, L. minor achieved net removal efficiencies of up to 81%, although reductions occurred under mixed conditions. Probabilistic risk assessment indicated a high ecological risk (msPAFtotal = 1.0), with RIS as the dominant contributor.

Toxics doi: 10.3390/toxics14050419

Authors: Tai Pham-The Hang Thi Nguyet Pham William R. Folk Nghi Ngoc Tran Tuyet-Hanh Tran-Thi Hisao Nishijo Muneko Nishijo

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

Toxics doi: 10.3390/toxics14050418

Authors: Bolanle Akinyemi Emmanuel Obeng-Gyasi

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

Toxics doi: 10.3390/toxics14050417

Authors: Jose L. Domingo Marília Cristina Oliveira Souza Fernando Barbosa

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

Toxics doi: 10.3390/toxics14050415

Authors: Yongpeng Ji Zhiming Zhang Shengping Chen Qiuju Shi Jiaxin Wang Baocong Zhao Weina Zhang Jiangyao Chen Yuemeng Ji

Atmospheric sea spray aerosol (SSA) undergoes chemical aging during long-distance transport, leading to significant alterations in its climate effects. However, the aging mechanisms of SSA driven by oxygenated volatile organic compounds (OVOCs) remain unclear. Hence, the aging processes of NaCl particles driven by glyoxal (GL), a representative OVOC, are systematically investigated using molecular dynamics (MD) simulations and density functional theory (DFT) calculations. MD simulations with high GL coverage show that GL readily mixes with NaCl and preferentially orients its carbonyl groups toward the NaCl surface. The adsorption of GL on the NaCl surface is dominated by the interaction between the O atom of GL (OGL) and the Na atom of the surface. DFT calculations with single GL coverage further reveal the formation of the OGL–Na bond between GL and NaCl. The mixing process of GL and NaCl is regulated by both the number of aldehyde groups engaging in the interfacial coordination and the corresponding lengths of OGL–Na bonds. The subsequent heterogeneous oxidation of GL by an OH radical proceeds mainly via a barrierless H-abstraction pathway to form HC(O)CO radicals, which may further react with methylamine/ammonia and contribute to brown carbon formation. Our results reveal the importance of incorporating such aging mechanisms into atmospheric models to improve climate predictions.

Toxics doi: 10.3390/toxics14050416

Authors: Junyu Xuan Jinquan Wan Lanhui Wen Yan Wang Ji Shiming

Microplastics are emerging contaminants widely present in aquatic environments, yet their toxic effects on submerged plants and associated microbial communities under saline conditions remain unclear. In this study, Myriophyllum spicatum was exposed to polystyrene (PS) microplastics (0, 10, 30, 60, and 100 mg·L−1) under 0.5% salinity. We investigated plant growth, physiological responses, nitrogen and phosphorus removal, transcriptomic changes, and phyllosphere microbial communities. Results showed a concentration-dependent response, with low-dose stimulation and high-dose inhibition. At 30 mg·L−1, PS promoted growth, maintained membrane integrity and photosynthetic pigment levels, and enhanced nutrient removal. In contrast, 100 mg·L−1 PS caused membrane damage, photosynthetic inhibition, oxidative stress, and reduced nutrient uptake, indicating clear toxic effects. Transcriptomic analysis revealed that high PS significantly affected genes related to photosynthesis, antioxidant defense, energy metabolism, and nutrient transport. Microplastics promoted biofilm formation on leaf surfaces but did not significantly alter overall microbial community structure or diversity, instead shifting functionally related taxa associated with plant oxidative responses and nutrient removal. These findings demonstrate that PS microplastics exert phytotoxic effects under saline conditions by disrupting physiological processes and are associated with shifts in functional microbial groups, with potential implications for aquatic ecosystem health.

Toxics doi: 10.3390/toxics14050414

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

(1) Background: This study investigated the characteristics and influencing factors of exposure to fine particulate matter (PM2.5) and its chemical composition among elderly residents, with the aim of revealing potential differences in exposure. (2) Methods: A total of 258 elderly individuals were monitored for 72 h through individual, indoor, and outdoor PM2.5 measurements. Concentrations were determined, and non-targeted components were analyzed by gas chromatography-mass spectrometry (GC-MS). Through Spearman correlation analysis, generalized linear model, and linear regression to explore the influencing factors. (3) Results: The individual PM2.5 concentration was higher than both the indoor and outdoor concentrations. A total of 20,962 compounds were detected in personal PM2.5 samples, 6794 in indoor PM2.5 samples, among which 4285 compounds were shared between the two sample types. The components were mainly esters, aromatic compounds, and amines. PM2.5 concentration was correlated with age, housing area, humidifier use, and second-hand smoke exposure. Chemical composition is related to outdoor pollution, furniture material, and daily behavior. (4) Conclusions: The individual PM2.5 concentration is higher than the environmental concentration, and its chemical composition overlaps with the indoor and outdoor environment, which is jointly affected by demography, living conditions, and daily behavior.

Toxics doi: 10.3390/toxics14050413

Authors: Mirjami Jolma Mikko Koivu-Jolma Nunzia La Maida Simona Pichini Adele Minutillo Ilona Autti-Rämö Hanna Kahila

Prenatal alcohol exposure (PAE) is a major public health concern, yet maternal self-reporting remains unreliable. Meconium accumulates alcohol metabolites during the second half of gestation, and ethyl glucuronide (EtG) is considered a stable and specific biomarker of late-pregnancy alcohol exposure. Diapers containing meconium may serve as a noninvasive method for collecting anonymous biological samples, which could help reduce participation bias in studies of this sensitive subject. This pilot study assessed the feasibility of anonymously collecting meconium-containing diapers for subsequent quantitative EtG analysis after extended periods of frozen storage and international transport, and examined intra-pair consistency in samples from the same newborn. Mothers collected their newborns’ diapers, which were then divided into two aliquots (A and B) by a study assistant and stored at −80 °C until analysis. Out of 178 samples collected from 105 infants, 137 samples were analyzable. Eleven samples exceeded the limit of quantification (10 ng/g), while two samples (one pair) surpassed the 30 ng/g cutoff, indicating significant PAE. EtG concentrations showed high intra-pair agreement, supporting the robustness of the biomarker and analytical method. Anonymous diaper-based meconium collection is feasible but operationally demanding. Although the low participation rate and methodological factors, including sample loss, precluded true prevalence estimation, making it exploratory, the detection of quantifiable EtG in 8% of analyzable samples suggests that PAE remains an issue.

Toxics doi: 10.3390/toxics14050412

Authors: Xueyi Wu Wenqi Xie Zhengfan Chen Ziyi Jiang Jiazhe Jiang Lei Xie Yongpu Zhang

Copper is a common pollutant in aquatic environments. Excess copper in water can enter aquatic organisms through respiration, feeding, and adsorption, thereby exerting serious adverse effects on their health. In this study, NEW Genetically Improved Farmed (GIFT) Nile tilapia (Oreochromis niloticus L.) was used to explore the effect of copper on the hepatopancreas and post-exposure recovery. Acute exposure was simulated via an intraperitoneal injection of 3.75 mg Cu2+/kg body mass, while physiological saline injections served as the control. Samples were collected on days 1, 7, 14, and 21 post-exposure to evaluate growth performance, histopathological changes, antioxidant enzyme activities, and the expression of oxidative stress-related genes in the hepatopancreas. The results show that body length and mass increased within 21 days of the injection and copper exposure did not significantly affect fish growth. On day 1 after copper injection, numerous vacuoles appeared in hepatopancreatic tissues. On day 14, congestion and obvious hepatic sinusoids were observed. However, on day 21, the tissue structure showed gradually recovery. Compared to the control group, superoxide dismutase (SOD) activity was significantly higher in the exposed group on days 1, 14, and 21, and SOD gene expression was significantly elevated on day 21. Catalase (CAT) activity was significantly higher on day 7, and the expression of the CAT gene increased significantly on days 1 and 21. Glutathione peroxidase (GSH-Px) activity decreased significantly on day 7, whereas GPX gene expression increased significantly at the same time point. No significant difference in acetylcholinesterase (AChE) activity was observed during the experiment. In conclusion, copper administered via intraperitoneal injections induced significant activation of the antioxidant defense system and histopathological damage in the hepatopancreas of tilapia. Although tissue damage gradually recovered over time, the activation of the antioxidant defense system partially persisted. Ultimately, copper exposure did not significantly affect growth indicators such as body length and mass. These results advance our understanding of copper toxicity in farmed fish and provide a scientific reference for safe aquaculture production.

Toxics doi: 10.3390/toxics14050411

Authors: Alejandro Ruiz-Marin Claudia Alejandra Aguilar-Ucan Carlos Montalvo-Romero Julia G. Cerón-Breton Francisco Anguebes-Franseschi

This study evaluated the seasonal variability, origin, and ecological risk of heavy metals in the Pom–Atasta lagoon system, a tropical estuary in southeastern Mexico subject to increasing anthropogenic pressure. The main objective was to determine how seasonal changes influence the distribution, bioavailability, and risk of metals in sediments and benthic organisms. Thirty sampling stations were monitored during dry, rainy, and north wind seasons. Sediment concentrations of As, Cd, Cr, Ni, Pb, and V were measured, and bioaccumulation was assessed in the bivalve Rangia cuneata. Ecotoxicological risk was evaluated using the Adverse Effects Index (AEI), Toxic Risk Index (TRI), and potential ecological risk index (ERI). The results showed higher metal concentrations during the rainy and north wind seasons, likely due to increased runoff and sediment resuspension. Cr and Ni exhibited the highest enrichment, with values from 115.0 to 130.4 µg g−1 and from 60.5 to 75.9 µg g−1, respectively. Ni showed the highest bioaccumulation factor (BSAF > 1.51) in R. cuneata, indicating high mobility and environmental availability. Weak correlations among some metals (As, Cr, and Pb) suggest mixed natural and anthropogenic sources. TRI values indicated low to moderate toxic risk, and ERI classified most sites as low risk (ERI < 60) at several stations. Organic carbon levels remained within tolerable limits (<10%) for benthic fauna. These findings highlight the role of seasonal dynamics in metal distribution and confirm R. cuneata as a suitable bioindicator for monitoring ecological health in tropical estuarine systems.

Toxics doi: 10.3390/toxics14050410

Authors: Lufuno Ratshisusu Omphile E. Simani Nakisani B. Moyo Lufuno G. Mavhandu-Ramarumo Ntakadzeni E. Madala Jason T. Blackard Selokela G. Selabe

Nyaope is a highly addictive street drug that is widely used in South Africa, particularly in urban and peri-urban settings. Although it is traditionally consumed by smoking, increasing injection use has raised serious public health concerns due to an elevated risk of bloodborne viral infections and other drug-related health complications. The composition of nyaope is highly variable, frequently adulterated, and continually evolving, thus highlighting the need for detailed chemical characterization to support forensic investigations and public health interventions. An exploratory study design was conducted using eight nyaope samples seized from six sites within the City of Tshwane Metropolitan Municipality that were provided by the South African Police Service Forensic Science Chemistry Laboratory (SAPS-FSCL). Samples were analyzed using Ultra-High-Performance Liquid Chromatography coupled to Quadrupole-Time-of-Flight Mass Spectrometry (UHPLC-qTOF-MS) operated in data-dependent acquisition mode under positive ionization. Raw data from the methanolic extracts of nyaope was converted to mzML format and processed using SIRIUS software for compound annotation based on isotope pattern ranking and fragmentation analysis. Chemical profiling revealed multiple opiate-related compounds, including noscapine, heroin, papaverine, and codeine. Molecular networking revealed chemically diverse yet structurally related metabolites consistent with a poppy-derived botanical origin. In addition, multiple synthetic pharmaceutical adulterants were detected. Notably, one sample contained formaline, a toxic rodenticide structurally related to protopine, highlighting the risk of misidentification using less advanced analytical approaches. This study demonstrates the value of advanced computational metabolomics, including molecular networking and machine-learning-assisted mass spectrometry interpretation, for comprehensive characterization of complex illicit drug mixtures. These approaches enhance forensic accuracy and support informed public health and law-enforcement responses.

Toxics doi: 10.3390/toxics14050409

Authors: Wenxuan Wei Wenqian Cao Ruijuan Qu Zunyao Wang

Phenolic pollutants are toxic and widespread, making their removal an urgent priority. Metal-modified biochar (MBC) shows great potential for non-radical activation of persulfate (PS), enabling efficient and low-carbon removal of phenolic pollutants. However, regulating the non-radical mechanism remains challenging due to the lack of systematic understanding of how metal-modification-related preparation parameters influence the reaction pathway. Herein, a machine learning (ML) framework focusing on metal modification parameters was introduced. Five ML algorithms were used to build binary classification models. XGBoost achieved the best performance, with an area under the receiver operating characteristic curve (AUC) of 0.711 on the independent test set and both precision and recall of 0.733 for identifying the non-radical-dominated mechanism. SHapley Additive exPlanations (SHAP) and partial dependence analysis reveal that high temperatures (>800 °C) and moderate heat treatment time (1.7–2.5 h) favor non-radical pathways, with Cu introduction and multi-metal synergy serving as key regulatory factors. Based on SHAP dependency analysis and metal combination statistics, two strategies for the targeted design of non-radical-dominated systems are proposed: (1) prepare Cu-modified biochar at 900 °C; (2) prepare Cu-Fe bimetallic-modified biochar at 600 °C. This work provides a data-driven theoretical framework and operational strategies for targeted regulation of the non-radical mechanism in the MBC/PS system, opening new avenues for the efficient and low-carbon treatment of phenol-containing wastewater.

Toxics doi: 10.3390/toxics14050408

Authors: Soisungwan Satarug

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

Toxics doi: 10.3390/toxics14050407

Authors: Mo Li Jun Wang Weiyue Meng Liqiang Du Dongming Li Yanfeng Sun

Microplastic (MP) pollution poses a threat to wild animals, but its toxicological impact on terrestrial passerines remains unclear. To address this gap, we conducted the first systematic study investigating how microplastic particle size and dosage jointly influence gut microbiota and multi-system physiological functions in a small terrestrial bird. Eurasian tree sparrows (Passer montanus) were exposed to polystyrene microplastics (PS-MPs) of two particle sizes (0.5 and 15 μm in diameter) and two dosages (100 and 500 μg/d) via oral ingestion for 21 days. After exposure, body status, peripheral blood cell profiles, organ indices, intestinal histomorphology, oxidative stress, and barrier integrity markers displayed no significant changes compared with the control group. In the gut microbiota, large PS-MP particles significantly enhanced microbial species richness and phylogenetic diversity, and their effect was more pronounced than that of small ones. Additionally, structural alterations and distinct community compositions emerged across groups. Both particle size and dosage affected gut microbial composition and taxa abundance, with particle size exhibiting a relatively stronger effect. However, the relative abundance of the top 10 dominant phyla and predicted microbial functional profiles exhibited no significant intergroup differences. In summary, short-term PS-MP exposure primarily impacts the gut microbial structure of Eurasian tree sparrows without disrupting their key physiological functions. This suggests that the birds possess a certain buffering capacity against short-term PS-MP stress, though their long-term ecological tolerance to complex, real-world MP mixtures remains to be further investigated.

Toxics doi: 10.3390/toxics14050406

Authors: Shu Cao Ping Wang

The Yangtze River Economic Belt supports over 400 million people and contributes nearly half of China’s GDP, yet decades of industrialization, urbanization, and agricultural intensification have resulted in severe contamination and pressing environmental challenges. This systematic review synthesizes three decades of peer-reviewed and governmental data to examine the spatiotemporal distribution, sources, and ecological and human health risks of major pollutants, including heavy metals, microplastics, persistent organic pollutants, and excess nutrients. While point-source emission of heavy metals such as cadmium, lead, and mercury have decreased by 35–42% since 2013 following policy interventions like the 10-Point Water Plan and the Yangtze River Protection Law, legacy contaminants in sediments and diffuse agricultural inputs continue to pose significant risks. Cadmium levels in rice still exceed food safety standards, arsenic in groundwater surpasses health guidelines, and microplastic flux into the East China Sea has reached 8.3 × 1012 particles per year. Nutrient surpluses also drive extensive algal blooms, causing substantial economic losses. This review evaluates remediation strategies such as dredging, phytoremediation, wetland restoration, and AI-enhanced monitoring, which show removal efficiencies of 60–90% at reduced costs. However, critical gaps remain in understanding chronic mixture toxicity, the long-term fate of emerging contaminants, and pollutant–climate interactions. We propose an integrated basin-wide roadmap combining zero-liquid-discharge mandates, green infrastructure, and adaptive, performance-based governance to secure the Yangtze’s ecological and economic sustainability. This framework offers a transferable model for large-scale watershed management worldwide.

Toxics doi: 10.3390/toxics14050405

Authors: Manuel Isaac Morales-Olivares María Luisa Castrejón-Godínez Patricia Mussali-Galante Efraín Tovar-Sánchez Alexis Rodríguez

Paraquat is an herbicide widely used to control weeds in various crops. Due to its use in large quantities, its dispersal into the environment is frequent, leading to contamination and negative health effects on non-target organisms because of its high toxicity and persistence in soils. Therefore, it is necessary to develop sustainable strategies to remediate sites contaminated by this compound. Bacterial remediation is a promising alternative for removing paraquat from the environment; however, the metabolic pathways used by bacteria for its degradation have not yet been precisely described. In this context, it is essential to characterize bacterial species capable of resisting and degrading paraquat, as well as to elucidate the molecular mechanisms involved in these processes. The objective of this work was to evaluate the paraquat resistance and degradation potential of the bacterial strain Caballeronia zhejiangensis CEIB S4-3, and to identify genes with a possible role in the resistance and degradation of this herbicide by analyzing the strain’s genome. The results of this research showed that, in solid medium, C. zhejiangensis CEIB S4-3 can withstand concentrations of up to 200 mg/L of paraquat supplemented as a commercial formulation (Gramoxone®) and 400 mg/L of analytical-grade paraquat. In tryptic soy broth, the strain grew in the presence of both the commercial formulation and analytical-grade paraquat at concentrations up to 15 mg/L, whereas in mineral salts medium, supplemented with paraquat or its commercial formulation as the sole nutrient source, the strain survived exposure to paraquat at the same concentrations. Furthermore, the bacterial strain removed 40.8% of the paraquat supplemented in the culture medium at a concentration of 12 mg/L within 48 h. Finally, genomic analysis revealed the presence of genes related to paraquat resistance mechanisms and encoding enzymes involved in the degradation of this herbicide. These results position C. zhejiangensis CEIB S4-3 as a promising candidate for developing remediation alternatives for sites contaminated with this herbicide.

Toxics doi: 10.3390/toxics14050404

Authors: Jiaqing Wu Chun Chen Hong Geng Bixin Zhao Jian Gao

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

Toxics doi: 10.3390/toxics14050403

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

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

Toxics doi: 10.3390/toxics14050402

Authors: Kyla Charlebois Eva N. Nyutu

Several issues about the quality of urban surface waters, such as the Detroit River, are becoming a concern due to the increasing detection of emerging contaminants. Although the emerging contaminants are present in low concentrations—ranging from nanograms per liter (ng/L) to micrograms per liter (µg/L)—these raise serious concerns about long-term effects on human health and aquatic ecosystems, particularly when left unregulated. Municipal wastewater effluent has been reported as one of the major pathways for these emerging contaminants. Most treatment plants are not equipped to effectively remove many emerging contaminants, allowing them to enter surface waters. To assess the presence of these emerging contaminants, water samples were collected during the summer from sites near the upstream and downstream of the Detroit wastewater treatment plant. Among the sixteen emerging contaminants analyzed were pharmaceuticals, personal care products, and pesticides. Ten of these, such as sucralose, caffeine, acetaminophen, and bisphenol A, were detected at both locations, with concentrations ranging from 42 to 4100 ug/L. Elevated contaminant levels found downstream can come from various sources, such as agricultural runoff, leachate from landfills, overland flow, and Combined Sewer Overflows (CSOs). Furthermore, local pharmaceutical usage patterns and the effectiveness of our treatment facilities play significant roles in the contaminant concentrations we see. Tracking emerging contaminants both upstream and downstream of treatment plants is crucial for pinpointing vulnerable watersheds. This vital information enables us to establish a solid baseline and craft effective strategies to lower contaminant levels.

Toxics doi: 10.3390/toxics14050401

Authors: Wenhui Cui Sibi Huang Huaqing Zeng Yutong Li Leyi Zheng Changhua Xu

Pyropia haitanensis (P. haitanensis) is a commercially significant alga in China, and the vitality of its industry is closely associated with coastal economic stability and food safety. Intensifying coastal pollution and deteriorating aquaculture conditions have exacerbated heavy metal accumulation in P. haitanensis, threatening sustainable development and limiting industry viability. Conventional processing methods exhibit substantial limitations in heavy metal removal, nutrient retention, and preservation of algal tissue structure, restricting their ability to meet market demands. To address this challenge, we developed a synergistic ultrasound-assisted citric acid treatment technology. In this process, ultrasound facilitates the release of heavy metal from algal tissue, while citric acid chelates and removes them, termed the “Release–Chelation” effect. The approach aims to efficiently remove heavy metal while maintaining P. haitanensis quality and nutritional value. Under optimized conditions of citric acid concentration, sonication time, and power, heavy metal residues were effectively reduced below national regulatory standards. SEM and FT-IR analyses indicate that removal occurs with minimal structural damage. Nutritional analyses revealed slight reductions in crude protein and amino acid content, yet overall nutritional quality remained satisfactory. These results demonstrate that the technology preserves the edible value of P. haitanensis while efficiently removing heavy metals, highlighting its potential to advance the algae industry toward safer and more sustainable practices.

Toxics doi: 10.3390/toxics14050399

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

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

Toxics doi: 10.3390/toxics14050400

Authors: Habib Ullah Durakshan Iqbal Waqar-Un-Nisa Jawaria Abid Fiza Sarwar Maria Ashfaq Ahmed Mahmoud Ismail Xin Pan Boya Kuang

The widespread presence of pharmaceutical residues, particularly emerging antibiotics such as levofloxacin (LVX) and amoxicillin (AMOX), in aquatic environments poses serious risks to ecosystems and public health. In this study, magnetically modified biochar was synthesized from orange peel waste and evaluated for the percentage removal of LVX and AMOX from synthetic wastewater. The biochar was chemically modified with iron to enhance its adsorption capacity and facilitate magnetic separation. The physicochemical properties of raw and iron-modified biochar were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Batch adsorption experiments were conducted to investigate the effects of temperature, contact time, adsorbent dosage, pH, and initial antibiotic concentration on removal efficiency. Antibiotic concentrations were quantified using UV–Vis spectrophotometry. Batch adsorption experiments revealed that iron-modified biochar (FeMBC) significantly outperformed raw biochar (RBC) in antibiotic removal. Optimal removal efficiencies of 90% for AMOX and 92% for LVX were achieved at an adsorbent dosage of 0.1 g, antibiotic concentration of 10 mg L−1, contact time of 120 min, and temperature of 30 °C. Equilibrium data were best described by the Langmuir isotherm model, indicating monolayer adsorption, with correlation coefficients of 0.98 for AMOX and 0.97 for LVX. Kinetic analysis showed that the pseudo-second-order model provided the best fit, suggesting that chemisorption dominated the adsorption process. Thermodynamic studies confirmed that the adsorption was spontaneous and exothermic. Overall, the results demonstrate that iron-modified orange peel biochar is an efficient (90% better removal efficiency than RBC), low-cost, and environmentally sustainable adsorbent for the removal of emerging antibiotics from pharmaceutical wastewater, offering strong potential for practical water treatment applications.

Toxics doi: 10.3390/toxics14050398

Authors: Sangwon Gil Hogeon Lee Seung Ha Lee Seung A. Shin Dal Woong Choi Kyung-Min Lim

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

Toxics doi: 10.3390/toxics14050397

Authors: Stephanny Curaz-Leiva María José Díaz Iván Sola Jhoel Ruiz Macarena Pérez Daniel González-Labra Brittany Paredes-Ocaranza M. Gabriela Lobos Celine Lavergne Sebastián A. Klarian Verónica Molina Claudio A. Sáez

Although Quintero-Puchuncaví Bay, Chile, is a coastal area historically known to be subject to multiple industrial pressures, few studies have focused on the associated risks to marine ecosystems and, through edible species, to human health. We studied concentrations of Cd, Cr, Cu, Mn, Pb, V, Zn, and Hg in marine species and sediments from Quintero-Puchuncaví Bay and a reference site. Results were compared with seafood safety guidelines, and target hazard quotients (THQs) were evaluated. Sediments and biota from the impacted area generally exhibited higher metal concentrations. Zinc (Zn) and copper (Cu) levels were the highest across all species, particularly in crustaceans, reflecting both physiological requirements and anthropogenic inputs. Cadmium (Cd) concentrations were higher in pelagic species from the impacted bay, but no differences were found in sediments or benthic species, suggesting the influence of upwelling conditions. Comparison with seafood safety guidelines revealed that Cd and Pb concentrations exceeded permissible limits in crabs, fish, and mussel species, and THQ ≥ 1 values were found for Cd concentrations in benthic species from the impacted bay, highlighting potential risks to consumers. The absence of permissible thresholds for certain environmentally relevant metals in Chilean regulations underscores the need to align with international standards, certainly to protect coastal ecosystems and human health.

Toxics doi: 10.3390/toxics14050396

Authors: Zhilu Pei Dayu Hu Jie Sun Weiyue Hu

Background: Glufosinate ammonium (GLA) is a widely used herbicide, yet potential neurodevelopmental risks related to paternal exposure before conception remain insufficiently defined. Methods: In this study, adult male C57BL/6J mice received GLA at 0.2 mg/kg·day for 10 consecutive weeks and were then mated with unexposed females to generate F1 offspring. Offspring growth was monitored, and neurobehavior was assessed at 5 weeks of age. Results: In behavioral tests, female offspring showed reduced social novelty preference in the three-chamber test and impaired spatial learning and memory in the Morris water maze test, while open field, elevated plus maze, and rotarod performance were not altered. Male offspring showed no clear group differences in these memory-related endpoints. Golgi staining revealed reduced dendritic complexity and spine density in the hippocampus and prefrontal cortex. Glial markers were elevated, and neuronal marker changes showed region-dependent shifts. TUNEL staining indicated increased apoptosis during embryonic development and persistent apoptotic signals in the juvenile prefrontal cortex, accompanied by cytokine imbalance with increased IL-1β and decreased IL-10 in the hippocampus. Conclusion: These results suggest that paternal preconception GLA exposure is associated with selective memory-related behavioral deficits in juvenile offspring and with convergent glial, inflammatory, and apoptosis-related brain changes. These findings support the consideration of paternal exposure in developmental risk assessment frameworks.

Toxics doi: 10.3390/toxics14050395

Authors: Zhicheng Zhang Wenyan Huang Jinfeng Ding Wenli Liu Ruoxuan Xia Worou Chabi Noel Zhongjian Li Hui Chen Jun Yao

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

Toxics doi: 10.3390/toxics14050394

Authors: Faustina Acquaah Emmanuel Obeng-Gyasi

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

Toxics doi: 10.3390/toxics14050393

Authors: Vojin Ćućuz Gordana Jovanović Timea Bezdan Snježana Herceg Romanić Bosiljka Mustać Andreja Stojić Mirjana Perišić

Polychlorinated biphenyls (PCBs) remain a major concern in marine ecosystems, where bioaccumulation in fish occurs as complex congener mixtures whose dynamics challenge conventional indicator approaches. This study develops and evaluates a data-driven framework for refining mixture-based indicators of PCB contamination by integrating ensemble machine learning with explainable artificial intelligence. Focusing on PCB-138 as a target indicator of cumulative PCB burden, we analyse concentrations of 24 organochlorines together with biological covariates in four Mediterranean edible pelagic fish species (sardine, anchovy, horse mackerel, and chub mackerel). Comparative evaluation of indicator performance shows that alternative congener combinations, including i4 PCBs (-138, -153, -170, -180), i6 PCBs (-138, -153, -170, -180, -118, -123), and mixtures incorporating DDD and DDE, more effectively represent total PCB burden than traditional indicator groups. Clustering identifies two distinct bioaccumulation settings, characterized by high-concentration coherent congener effects and low-concentration heterogeneous responses, demonstrating that indicator performance depends on concentration range and mixture context. The study illustrates how interpretable machine learning approaches can serve as formal tools for indicator evaluation and optimisation, strengthening long-term monitoring and management of legacy contaminants in marine ecosystems, particularly under conditions of persistent exposure and renewed inputs from sediment remobilization and riverine transport.

Toxics doi: 10.3390/toxics14050392

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

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

Toxics doi: 10.3390/toxics14050390

Authors: Rungroj Benjakul Sutthiphong Taweelarp Morrakot Khebchareon Schradh Saenton Nipada Santha

Groundwater contamination by dissolved metals and metalloids in the Chiang Mai Basin is an important drinking-water concern, yet the coupled depth patterns, hydrogeochemical controls, composite contamination status, and screening-level health implications have not previously been assessed in an integrated basin-scale framework. This study evaluated 120 groundwater samples from alluvial wells classified by depth as shallow (≤30 m, n = 40), intermediate (31–60 m, n = 35), and deep (>60 m, n = 45). Samples were analyzed for nine dissolved metals and metalloids (Fe, Mn, As, Cd, Pb, Cr, Zn, Hg, and Se) together with pH, Eh, and total dissolved solids (TDS). The highest exceedance frequencies were observed for Fe (72.5% of samples, >0.3 mg/L acceptability threshold), Mn (65.0%, >0.08 mg/L), and As (45.8%, >10 μg/L). Fe and Mn increased significantly with depth, whereas As was enriched in deep wells but showed no statistically significant depth dependence. Pearson correlation and principal component analysis consistently identified a dominant redox-associated component in which Fe, Mn, and As covaried negatively with Eh, supporting redox-sensitive co-enrichment in deeper groundwater. Contamination factors calculated relative to selected global groundwater background values were >6 for all seven evaluated metals (Fe, Mn, As, Cd, Pb, Cr, and Zn), and the overall pollution load index (PLI) was 9.11, with the highest depth-specific PLI in deep wells (10.42). These indices are interpreted here as background-relative screening tools rather than stand-alone regulatory measures. A screening-level ingestion risk assessment identified arsenic as the dominant toxicological driver, with hazard quotients (HQ) of 1.97 for adults and 4.60 for children, and an estimated lifetime cancer risk (LCR) of 8.87 × 10–4. The results support targeted monitoring of deeper wells, routine screening for As and Mn, and treatment strategies that can address the co-occurring Fe–Mn–As assemblage in alluvial groundwater.

Toxics doi: 10.3390/toxics14050391

Authors: Na Zhang Lulu Liu Junrong Chen Yingjie Liu Shen Yang Mei Zhang Yu Xiong Xin Ma Yan Wang Xiaoqiang Han

Pneumoconiosis, characterized by progressive pulmonary fibrosis, remains a predominant occupational disease in China, with coal workers’ pneumoconiosis (CWP) and silicosis being the primary subtypes. Despite extensive research, its underlying pathogenic mechanisms are not yet fully understood. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are crucial subcellular microdomains that govern Ca2+ transport, sustain cellular bioenergetics, and maintain systemic homeostasis. Emerging evidence has linked the structural and functional dysregulation of MAMs to the pathogenesis of various fibrotic disorders. Apoptosis, a highly regulated cell death process, is a key driver in pneumoconiosis progression, in which Ca2+ imbalance serves as a critical signaling cascade. Mitofusin 2 (MFN2), a core regulator of MAMs’ structural integrity, mediates mitochondrial fusion and directly bridges the ER with the outer mitochondrial membrane, thereby stabilizing ER–mitochondrial coupling. However, whether MFN2 mitigates fibrosis by preserving MAMs’ integrity and subsequently suppressing Ca2+-dependent apoptosis remains elusive. In this study, we established SD rat and A549 cell models of CWP. Our results demonstrated that MFN2 expression was downregulated after coal dust exposure, accompanied by MAMs impairment, Ca2+ imbalance, and increased apoptosis, which ultimately drove the pathological progression of pulmonary fibrosis. Notably, MFN2 overexpression restored MAMs’ structure and Ca2+ homeostasis, alleviated abnormal apoptosis, and subsequently inhibited fibrosis. This study highlights the importance of the MFN2–MAMs–Ca2+–apoptosis axis and identifies MFN2 as a potential therapeutic target for pneumoconiosis.

Toxics doi: 10.3390/toxics14050389

Authors: Yiting Luo Yihui Zhou Tao Xu Rongkui Su Xiancheng Ma Wende Yan

The overuse of antibiotics has led to their widespread environmental residues, posing a significant threat to the ecological environment. In this study, a flower-like spherical CoFe-layered double hydroxide (CoFe-LDH) catalyst was prepared using a hydrothermal method. The degradation performance of the CoFe-LDH/peroxymonosulfate (PMS) system was systematically investigated using tetracycline (TC) as a model pollutant. The CoFe-LDH exhibited a three-dimensional nanoflower-like spherical structure formed by interlaced nanosheets, featuring smooth surfaces and well-defined edges. This hierarchical porous structure facilitates the exposure of active sites. The CoFe-LDH/PMS system demonstrated remarkable degradation efficiency, achieving over 90.17% TC removal within 10 min. As the dosage of CoFe-LDH and PMS increases, the degradation rate of TC improves significantly, but the marginal improvement effect decreases. TC degradation efficiency increased with pH up to an optimum at pH 5.0, beyond which it declined. The anions—Cl−, NO3−, and SO42−—all exhibited inhibitory effects on TC degradation; the TC removal rates decreased to 77.88%, 80.58%, and 82.78%, respectively. The removal experiments of different organic pollutants, such as oxytetracycline (88.91%), methylene blue (98.36%), and ciprofloxacin (84.52%), as well as actual water experiments, such as lake water (92.48%) and tap water (80.86%), have demonstrated the good universality of the CoFe-LDH/PMS system. Radical quenching experiments confirmed that •OH and SO4•− were the dominant reactive species.

Toxics doi: 10.3390/toxics14050388

Authors: Xiaoli Wu Xinyue Zhang Zengliang Ruan

Trans,trans-2,4-decadienal (tt-DDE), the primary aldehyde component found in cooking oil fumes, is a prevalent environmental pollutant. However, its potential adverse effects on ocular development remain largely unexplored. This study evaluated its toxicity on ocular development and angiogenesis in zebrafish larvae, as well as on human retinal vascular endothelial cells (HRECs). Zebrafish (Danio rerio) larvae at 48 h post-fertilization were microinjected intraocularly with various doses of tt-DDE (65.87–521.3 mM) for 24 h. We observed dose-dependent impairments in ocular development following tt-DDE exposure. It significantly reduced eye size and inhibited the intraocular vascular area at concentrations of 128.9 mM and above. Histopathological analysis revealed retinal structural disorganization, eye shrinkage, and a clear dose-dependent increase in acridine orange (AO) fluorescence intensity. Apoptosis assays confirmed a significant escalation in ocular cell death at higher exposure doses. Additionally, our results demonstrated that tt-DDE (5–100 μM) significantly reduced the viability of HRECs in vitro. These findings suggest that early-life exposure to tt-DDE impairs ocular development in zebrafish by inducing histopathological damage, inhibiting angiogenesis, and promoting apoptosis, and also exerts direct cytotoxicity to human retinal cells. This study underscores the potential risk of tt-DDE exposure as an environmental factor contributing to ocular developmental toxicity.

Toxics doi: 10.3390/toxics14050384

Authors: María Fernanda Romo-García Oliver Mendoza-Cano Mónica Ríos-Silva Jaime Alberto Bricio-Barrios Pedro Rincón-Avalos Herguin B. Cuevas-Arellano Miguel A. Martínez-Preciado Ángel Gabriel Hilerio-López Mario López-Rojas Juan Manuel Uribe-Ramos Agustín Lugo-Radillo Yolitzy Cárdenas Efrén Murillo-Zamora Juan José Oropeza-Valdez Mariana Haydee García-Hernández Bruno Rivas Santiago Irma Elizabeth González-Curiel Rafael Julio Macedo-Barragán

Air pollution with fine particulates is a recent global concern as it has been identified as a risk factor for several health problems. The molecular mechanism linking PM exposure to adverse health effects has not yet been fully elucidated but was found to be linked with inflammatory responses across many investigated exposure settings. In particular, children and juveniles turned out to be highly vulnerable in this regard, with exposure potentially leading to long-term effects on development. We therefore investigated how air pollution in an area where local exposure is traditionally linked with sugar cane production, a potential source of high PM-levels, is affecting the immunologic profile of a pediatric population. Samples were collected from pediatric populations residing in various study sites, including sites with identified sources of high PM emission like sugar cane harvest and thermoelectrical activities and sites with no identified emission sources as control non-exposed population. Significantly elevated TSLP concentrations were observed in serum samples of the pediatric population exposed to particulate matter, along with a distinctive cytokine profile characterized by increased rations of IL-2, IL-4, INF-γ, and IL-6, suggesting alterations in Th2 response. In the present study, no chemical characterization of PM was carried out; however, it was observed by air quality monitoring PM2.5 concentrations exceeded permissible limits, suggesting potential exposure of the pediatric population to PM from agricultural activities. These findings underscore the intricate relationship between environmental factors and immune response in vulnerable pediatric populations and explore TSLP response to PM exposition.

Toxics doi: 10.3390/toxics14050387

Authors: Fuxin Wan Xiaohan Liu Jiayue Pan Linping Ke Zhekai Zheng Jingling Liao

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

Toxics doi: 10.3390/toxics14050386

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

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

Toxics doi: 10.3390/toxics14050385

Authors: Doris Chirinos-Peinado Jorge Castro-Bedriñana Elva Ríos-Ríos Gianfranco Castro-Chirinos Mery Baquerizo-Canchumanya

Bovine milk is a primary dietary source of nutrients and bioactive compounds. However, its safety is increasingly under threat due to contamination from mining and intensive agriculture. In the Peruvian Andes, where small-scale dairy farming coexists with historical environmental liabilities, identifying the transfer of metals into the food chain is essential for public health. This study quantifies the concentrations of lead (Pb) and cadmium (Cd) in raw milk from small-scale producers in rural districts in the province of Huancayo. Non-carcinogenic risks for populations aged 2–85 years were assessed under three consumption scenarios. Forty-five samples were analyzed using microwave plasma atomic emission spectrometry (MP-AES). The mean concentrations of Pb and Cd were 11.30 ± 18.94 µg/kg and 7.85 ± 18.11 µg/kg, respectively, which are below the maximum permissible limits (MPL). However, spatial analysis identified critical hotspots near smelters, where Pb levels reached 103 µg/kg, which is a significant exceedance of the MPL of 20 µg/kg. Toxicological modelling showed that the Hazard Index (HI) remained below the unity threshold (HI < 1) for all scenarios, ruling out immediate systemic risks. Nevertheless, the highest HI (0.78) was observed in two-year-old children in the high-consumption scenario, highlighting a localized neurodevelopmental concern. These findings emphasize the importance of georeferenced environmental monitoring and differentiated public health policies to mitigate the chronic low-level exposure to metals in vulnerable, high-altitude populations.

Toxics doi: 10.3390/toxics14050383

Authors: Alaa Hlail Dahham Mohamed Korish Samir Mohamed El Rayes Nadia A. El-Fahla Ibrahim E. Helal Heba M. A. Abdelrazek

This study evaluated the protective effects of green coffee (Coffea arabica L.) extract (GCE) against metabolic and endocrine disturbances induced by fipronil (FIP) in male rats. Animals were randomly allocated into four groups (n = 6): control, GCE (100 mg/kg), FIP (4.85 mg/kg), and combined FIP + GCE, and treated orally for 90 days. FIP exposure significantly impaired glucose homeostasis, as indicated by a 14.8% increase in the oral glucose tolerance test (OGTT) response and a 2.4-fold increase in the homeostatic model assessment of insulin resistance (HOMA-IR). It also disrupted lipid metabolism, with marked elevations in triglycerides (74.10%) and total cholesterol (57.55%). Endocrine imbalance was evident, including increased resistin levels (113.86%) and reduced triiodothyronine (T3; −37.5%), adiponectin (−42.73%), and high-density lipoprotein (HDL; −9.31%). Oxidative stress and inflammation were significantly enhanced, as demonstrated by elevated malondialdehyde (MDA; +93.56%) and pro-inflammatory cytokines (IL-1β: +246.56%; IL-6: +275%), alongside a reduction in total antioxidant capacity (TAC; −45.24%). Additionally, serum albumin levels decreased markedly (−54%). Co-administration of GCE significantly improved metabolic, hormonal, and inflammatory parameters, including insulin resistance (HOMA-IR). Histopathological analysis further confirmed its protective effects on hepatic and renal tissues. Overall, GCE mitigates FIP-induced metabolic and endocrine dysfunction, likely through its antioxidant and anti-inflammatory properties.

Toxics doi: 10.3390/toxics14050382

Authors: Edwina Brennan Priya Das Pearl Wasif Xianyu F. Wang Jochen F. Mueller Chang He Jean V. Varghese Alexandra E. Butler Stephen L. Atkin Naji Alamuddin

Introduction: Intermittent fasting (IF) is becoming increasingly popular as a method of weight management, but it is unknown whether it affects plasticiser intake with resultant changes in glycaemic control in diabetes and vitamin D (VitD) levels; therefore, this study was undertaken in a cohort of control and type-2 diabetic (T2D) subjects during Ramadan time-restricted feeding (TRF). Methods: In T2D subjects (n = 19) and controls (n = 31) undertaking TRF, 24 h urinary levels of phthalate metabolites, bisphenols and serum VitD were determined pre- and post-TRF by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Anthropometric data and glycosylated haemoglobin (HbA1c) were measured. Results: T2D subjects were older (52 versus 36.73 years, p < 0.001), and had higher BMI (36.54 versus 27.67 kg/m2, p < 0.001), body weight (101.77 versus 80.36 kg, p < 0.001), and HbA1c (8.38 versus 5.46%, p < 0.001) compared to controls, while VitD levels did not differ (60.43 versus 63.95 nmol/L, p > 0.05). Post-TRF, HbA1c was unchanged in T2D subjects and there was no difference in weight, BMI or VitD. Increased mono-iso-butyl phthalate (MiBP) in T2D subjects (10 versus 6.1 ng/mL, p = 0.001) and mono-n-butyl phthalate (MnBP) in T2D subjects (37 versus 13 ng/mL, p = 0.018) and controls (8.3 versus 5.4 ng/mL, p = 0.007) were observed post-TRF; however, significance was lost after adjusting for baseline differences in age, BMI, and HbA1c using a general linear model (GLM) repeated-measures ANOVA. Despite having no median differences in DEHP (di-2-ethylhexyl phthalate) metabolites pre- and post-TRF, analyses revealed a significant time × HbA1c interaction for [mono(2-ethyl-5-carboxypentyl) phthalate, MECPP: F(1,42) = 4.79, p = 0.03, mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP: F(1,42) = 8.56, p = 0.006, mono(2-ethylhexyl) phthalate, MEHP: F(1,42) = 4.64, p = 0.03 and mono(2-ethyl-5-oxohexyl) phthalate, MEOHP: F(1,42) = 8.19, p = 0.007] and time × group interactions [MEHHP: F(1,42) = 14.27, p < 0.001, MEHP: F(1,42) = 6.35, p = 0.01 and MEOHP: F(1,42) = 10.30, p = 0.003]. Estimated marginal means (adjusted for age, BMI, HbA1c, and VitD) further confirmed higher concentrations of DEHP metabolites [MECPP, MEHHP, MEHP, and MEOHP] in T2D participants over time compared with controls. Additionally, monomethyl phthalate (MMP) trajectories were significantly influenced by the time × group interaction (F(1,42) = 4.28, p = 0.04), with post-TRF elevations observed in T2D subjects. Vitamin D status was observed to modify MCPP and MEP trajectories over time. Conclusion: Ramadan TRF is associated with changes in plasticiser metabolite levels, with estimated increased levels in T2D subjects versus healthy controls. Metabolite levels were influenced by HbA1c and vitamin D, though BMI was not observed to be a contributing factor.

Toxics doi: 10.3390/toxics14050381

Authors: Imane Berni Aziza Menouni Matteo Creta Kaoutar Chbihi Hala Chetouani Said Abou-Said Lode Godderis Samir El Jaafari Radu-Corneliu Duca

Levels of glyphosate and their metabolite AMPA were measured in urine of farmers and their spouses that lived in intensively farmed area in Morocco. The levels were used as proxies to determine the exposure of these target population to herbicides. Determinants of exposure to glyphosate were also assessed. Urine was collected from 104 farmers, 50 spouses and 50 people from the general adult population and information from sociodemographic characteristics and occupational exposure was collected from questionnaires administrated to farmers and spouses. The detection frequency was 67% for glyphosate and 62% for AMPA among farmers, and 56% for glyphosate and 48% for AMPA among spouses, with the mean concentration of 1.22 μg L−1 and 0.85 μg L−1 among farmers, and 0.58 μg L−1 and 0.50 μg L−1 among spouses, respectively. Nevertheless, mean values of glyphosate and AMPA for general population were below the reported quantification limits. Multiple regression analysis showed that smoking status, applying glyphosate in the last 7 days, and glove use are the most important contribution to urinary levels of glyphosate and AMPA among farmers, and proximity of home to spraying area, and herbicides drift enters house are the main predictors of urinary glyphosate and AMPA exposure among spouses. The GMs of estimated daily intake were 1.26 and 1.39 µg/kg BW/day for glyphosate and AMPA among farmers, and 0.56 and 0.96 µg/kg BW/day for glyphosate and AMPA among spouses, respectively. This study provides further evidence on factors associated with glyphosate and AMPA exposure, especially in developing countries.

Toxics doi: 10.3390/toxics14050380

Authors: Zhenxiong Yang Minxia Zhang Tongfei Xu Shasha Qi Lu Tang Juan Guo Chuqian Lu Shaobo Ma

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

Toxics doi: 10.3390/toxics14050379

Authors: Bryan G. Fry Kelly Johnstone Stacey Pizzino

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

Toxics doi: 10.3390/toxics14050378

Authors: Jingyue Xue Yushuang Wang Tingting Fan Jian Peng

The Fenwei Plain (FWP) is a typical basin-type region in northern China characterized by complex PM2.5 and O3 composite pollution. Based on hourly monitoring data from 11 cities (2015–2024), this study integrated the Mann–Kendall test, standard deviation ellipse (SDE), spatio-temporal cross-correlation function (STCCF), and spatio-temporal geographically weighted regression (GTWR) to systematically analyze decadal pollution patterns and coupling mechanisms. Results revealed a profound transition from particulate-dominated to photochemical-regime pollution: PM2.5 concentrations decreased significantly by 32%, whereas MDA8 O3 rose by 47%. Spring emerged as the critical compound pollution window, accounting for 66.7% of simultaneous exceedances. Spatially, both pollutants maintained a consistent Northeast–Southwest orientation, with PM2.5 hotspots concentrated along the Weihe River Valley. Cluster analysis categorized the 11 cities into O3-dominant, compound-high-risk, and PM2.5-dominant clusters. Furthermore, a dominant positive synergy was observed on an annual scale, although a localized “see-saw” effect occurred at a 150–200 km distance with a 3-year lag. The GTWR model demonstrated high robustness (R2: 0.75–0.86), underscoring the influence of localized driving forces. These findings provide a scientific basis for synergistic governance and precision air quality management in northern basin-type regions.

Toxics doi: 10.3390/toxics14050377

Authors: Mert Karacalı Burcu Onat Ülkü Alver Şahin Sabahattin Sıddık Cindoruk Berna Kırıl Mert

Fireworks are widely used at festive events worldwide and are commonly employed at indoor wedding ceremonies in Türkiye; however, their impact on indoor air quality has not been adequately investigated. This study examines particulate matter (PM) emissions generated by volcano-type fireworks used in indoor wedding halls. Particle samples were collected across five size fractions (>2.5, 1.0–2.5, 0.50–1.0, 0.25–0.50, and <0.25 µm) using a 5-stage Sioutas cascade impactor, and elemental compositions were determined by ICP-MS. PM2.5 concentrations ranged between 1518 and 7796 µg/m3, while total PM concentrations varied between 2088 and 8656 µg/m3. These values are substantially higher than the guideline limits reported by the World Health Organization (WHO) and the United States Environmental Protection Agency (USEPA), indicating very high short-term exposure levels. Fine particles (PM2.5) accounted for 56.5–92.4% of total PM, with particles smaller than 1 µm forming the dominant fraction. Among the analyzed elements, aluminum (Al), zinc (Zn), and iron (Fe) were the most abundant metals, predominantly associated with fine particles. The highest concentrations were generally observed in the 0.25–0.5 µm size range. These findings showed that the use of indoor fireworks can lead to high concentrations of fine particulate matter and metal-rich aerosols. This issue should be considered, as it may pose a health risk for those in enclosed spaces in future studies.

Toxics doi: 10.3390/toxics14050376

Authors: Alfredo G. Casanova Ana I. Morales Laura Vicente Vicente

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

Toxics doi: 10.3390/toxics14050375

Authors: Mariangela Palazzo Andrea Borghini Elisa Bustaffa Silvia Baldacci Francesca Gorini Fabrizio Minichilli

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

Toxics doi: 10.3390/toxics14050374

Authors: Jie Ma Ge Gao Bitan Meng Xinni Wei Long Zhao Zaiming Ge

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

Toxics doi: 10.3390/toxics14050373

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

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

Toxics doi: 10.3390/toxics14050372

Authors: Chao Xu Yuanzhen Li Lisha Chen Lujie He Ruihan Xu Tianyang Li Lili Niu Weiping Liu Zili Guo Chenjian Hu

The toxicity of radioactive metals arises from both chemical toxicity and radiotoxicity. 210Pb(II) is a long-lived radionuclide in the decay chain of natural uranium series 238U and exhibits extremely high toxicity. Both 210Pb(II) and Pb(II) are widely present in natural water bodies. However, their combined toxicity remains unclear. Based on this, this study used zebrafish embryos as model organisms to investigate developmental toxicity, behavioral toxicity, and thyroid disruption effects, through single and combined exposure to Pb(II) (0, 1, 10, 100 μg/L) and 210Pb(II) (0, 100, 1000 Bq/L) for 120 h by comparing the radiotoxicity of 210Pb(II) with the chemical toxicity of Pb(II) and further exploring their combined effects. The results showed that following exposure to different environmental concentrations of Pb(II) and environmental activity levels of 210Pb(II), exposure to Pb(II) alone caused an increase in the malformation rate of zebrafish embryos, a decrease in locomotor activity, and significant upregulation of thyroid-related genes, including thyroid hormone receptor beta (TRβ) and corticotropin-releasing hormone (CRH) in the larvae. Exposure to 210Pb(II) alone had no significant effects on zebrafish embryos. Notably, compared with the individual exposure groups, the toxic effects in the combined exposure group of Pb(II) and 210Pb(II) were further significantly enhanced. Furthermore, correlation analysis indicated a positive correlation between malformations in zebrafish embryos and the expression of key genes in the hypothalamic–pituitary–thyroid (HPT) axis. These findings suggest that under combined exposure, the chemical toxicity of Pb(II) plays a dominant role, while the radioactive component 210Pb(II) exerts a synergistic amplification effect. This study provides important scientific evidence for improving the environmental risk assessment of radioactive metals.

Toxics doi: 10.3390/toxics14050371

Authors: Yulin Wu Ju Chen Siting Zheng Jieling Luo Zhiyong Xie Yi Liu Mingxian Wu Suxia Sun Zheqing Zhang

Air pollution poses a major public health threat, yet longitudinal evidence on its impact on infant health-related quality of life (HRQoL) remains limited. This study investigated the longitudinal associations between early-life exposure to outdoor air pollution and infant HRQoL, focusing on psychological and physiological domains. Between November 2021 and September 2022, 779 mother–newborn pairs were recruited, with 696 completing follow-up at 12 months. HRQoL was assessed at 1, 4, 6, and 12 months using the Pediatric Quality of Life Inventory™, and exposures to PM2.5, PM10, NO2, and SO2 were analyzed using linear mixed-effects models adjusted for infant sex, household income, sibling status, and other covariates. Higher concentrations of all pollutants were associated with lower total HRQoL scores. Stratified analyses showed that PM2.5, PM10, and SO2, but not NO2, were associated with steeper age-related declines in total scores. Inverse associations with psychosocial health were consistent across pollutants, with pronounced age-related declines in high-exposure groups; for physical health, only SO2 and NO2 remained significant after adjustment, with modest age-related changes. These findings suggest that early-life air pollution exposure is associated with smaller gains in HRQoL during infancy, particularly in psychosocial well-being, highlighting the importance of improving air quality to support early development.

Toxics doi: 10.3390/toxics14050370

Authors: Xia Wan Xiaoxin Fu Zhou Zhang Yao Rao Mei Yang Jianping Wang Xinming Wang

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

Toxics doi: 10.3390/toxics14050368

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

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

Toxics doi: 10.3390/toxics14050369

Authors: Cheng Guo Lizong Sun

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

Toxics doi: 10.3390/toxics14050367

Authors: Evangelia Brozou Aspasia Grammenou Spyridon Petropoulos Georgios Thalassinos Anthoula Dimirkou Vasileios Antoniadis

Hexavalent chromium (Cr(VI)) contamination in agricultural soils poses a significant risk to environmental and food safety owing to its high mobility and acute toxicity. To investigate possible mitigation strategies, a greenhouse pot experiment was conducted using sandy loam and silty loam soils spiked with Cr(VI) at 30 mg kg−1 and amended with natural clinoptilolite and modified HDTMA-Br (hexadecyl-trimethyl-ammonium-bromide) zeolite, while celery (Apium graveolens) was cultivated to assess chromium bioavailability and plant accumulation. Hexavalent chromium concentrations declined in all treatments (up to 88.2% in sandy loam and 73.5% in silty loam), indicating progressive reduction to Cr(III), although amendment effectiveness varied by soil type. In addition, celery accumulated extremely high chromium concentrations, particularly in sandy loam soil, where root Cr(VI) reached 1776 mg kg−1, indicating substantial safety concerns. Translocation factor values were below 1 across treatments, indicating limited relocation of Cr from roots to shoots. In the zeolite treatments, Cr(VI) concentrations in aboveground biomass decreased; however, plant uptake was not completely inhibited. Nonetheless, the high bioaccumulation factor (Cr in plant over available Cr in soil) of as high as 34 in the Cr(VI)-amended treatment indicated an uptake potential under Cr load. We conclude that modified zeolite was successful in mitigating Cr(VI) uptake in plants. Further investigation on the effectiveness of the materials in open-field conditions is required to establish a remediation framework for Cr species.

Toxics doi: 10.3390/toxics14050366

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

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

Toxics doi: 10.3390/toxics14050365

Authors: Francisco Jiménez-Trejo Liliana Carmona-Aparicio Elvia Coballase-Urrutia Katia L. Jiménez-García Cristian Arriaga-Canon Luis A. Herrera

Serotoninomics, a nascent emerging discipline within the field of omics, provides a transdisciplinary framework for understanding reproductive toxicology via serotonergic signalling. This research investigates the neuroendocrine effects of permethrin, a commonly used pyrethroid insecticide often considered to pose a low risk to humans, and positions it as a model compound for evaluating reproductive susceptibility beyond conventional endocrine endpoints. It is hypothesized that serotonin, traditionally examined in neuropsychiatric contexts, plays an essential role in gonadal function, hormonal regulation, and emotional resilience. Although permethrins are generally regarded as safe, acute exposure may subtly interfere with serotonergic pathways, potentially resulting in molecular, biochemical, behavioural, and reproductive alterations. These effects could extend beyond immediate exposure, including during gestation, considering permethrins’ ability to cross the placental barrier and influence foetal development. By synthesizing evidence across molecular, organismal, and environmental domains, we advocate for a serotonergic approach to facilitate a more comprehensive assessment of risk and resilience. We emphasize the importance of fostering a transdisciplinary dialogue to redefine reproductive health through the perspectives of serotonergic vulnerability and systemic resilience.

Toxics doi: 10.3390/toxics14050364

Authors: Isotta Cursi Nicola Iacovella Anna Maria Ingelido Annalisa Abballe

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

Toxics doi: 10.3390/toxics14050362

Authors: Cláudia Rocha João Pereira Enrique Moreira Bruno Sousa Ana Luzio Sandra Monteiro Carlos Venâncio Luís Félix

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

Toxics doi: 10.3390/toxics14050363

Authors: Erika Maria Ricci Cecilia Bossa Francesca Marcon Lorenza Troncarelli Chiara Laura Battistelli

Assessing genotoxicity, specifically gene mutations and chromosomal aberrations, is fundamental to chemical risk assessment. Notably, the early identification of an aneugenic mechanism is of crucial importance, allowing, in principle, for a threshold-based risk assessment approach. To investigate this issue while pushing towards innovation in risk assessment by leveraging New Approach Methodologies, in silico approaches stand out as a particularly promising avenue. Building on these premises and given the lack of QSAR models for aneuploidy in the public domain, the present study exploited the genotoxicity-relevant alert lists implemented in the OECD QSAR Toolbox to base the investigation of structure-activity relationships for aneuploidy. To address the lack of relevant structured data resources, a dataset of 65 confirmed aneugenic substances was specifically curated and designed for the study. The results highlighted widely differing performances among the various profilers, confirming a general limited discriminatory power for aneuploidy. On the other hand, a granular analysis of the results from individual structural alerts enabled the successful isolation of some features associated with the aneugenic mode of action. Moreover, a subset of tubulin-binding chemicals was investigated to determine whether targeting a specific protein improves the characterization of toxicological alerts. The findings provide a refined definition of specific toxicity determinants for tubulin binders and serve as a promising tool for early hazard assessment, potentially informing relevant AOPs. While the computational approach appears promising, the overarching challenge that emerges is the limited availability of well-curated experimental data. In fact, reliable data on aneuploidy are scarce and fragmented across the literature. Furthermore, existing compilations of micronucleus study results are often complicated by conflicting interpretations.

Toxics doi: 10.3390/toxics14050361

Authors: Rongjie Shi Ning Liu Tao Lan Xiaoli Ye Zhimin Peng Li Wang Lintao Li Xiaoshu Yu Chuande Chen

An on-site investigation was conducted to analyze the causes of excessive trihalomethane (THM) formation in Plant A and to mitigate the health risks associated with THM exposure in drinking water. Adjacent Plant B was used as a reference plant. Both water treatment plants used the same source water but employed different pre-oxidants. Systematic stage-specific sampling and analysis of historical monitoring data were conducted to identify the key contributing stage for THM formation. The investigation revealed that 85% of the trichloromethane in Plant A’s finished water originated from the sodium hypochlorite pre-oxidation step, identifying this stage as the key contributing stage. THM concentrations were generally higher at Plant A than at Plant B. A multi-pathway health risk assessment of THM in drinking water indicates that non-carcinogenic risks are negligible, but lifetime carcinogenic risks warrant attention. The findings demonstrate that pre-oxidant selection is a significant governing factor of finished water disinfection by-product (DBP) levels. Following these findings, Plant A implemented measures, including enhanced chlorination management, reduced pre-chlorination, and upgraded sedimentation and V-shaped filters, which substantially reduced chlorinated DBPs in the finished water.

Toxics doi: 10.3390/toxics14050360

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

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

Toxics doi: 10.3390/toxics14050358

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

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

Toxics doi: 10.3390/toxics14050359

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

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

Toxics doi: 10.3390/toxics14050357

Authors: Hemiao Yu Pei Gao Hui Li Min Li

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

Toxics doi: 10.3390/toxics14050356

Authors: Yihao Yin Binbin Deng Wenzi Tu Yongtong Guo Lixian Chen Yongjin Liang Yanlong Zhao Shaoxian Du Yi Li

Substituted p-phenylenediamines (PPDs) and their quinone derivatives (PPD-Qs) are emerging contaminants associated with tire-related antioxidants and antiozonants and have raised increasing concern because of their potential environmental effects. However, information on their occurrence in estuarine systems, particularly their combined distribution in water and sediment, remains limited in the Pearl River Estuary. In this study, 30 water samples and five sediment samples collected from the Pearl River Estuary were analyzed for selected PPDs and PPD-Qs. Four target compounds were detected in water, whereas nine were found in sediments, indicating broader occurrence in the sediment phase. The total concentration of PPDs ranged from below the detection limit to 17.6 ng/L in water and from 0.140 to 1.37 ng/g in sediments. In water, 6PPD and 6PPD-Q showed relatively high detection frequencies, while elevated IPPD concentrations were observed at several sites near urbanized coastal areas. In sediments, the highest ΣPPDs level was recorded in Shenzhen Bay. The observed spatial patterns suggest that mixed anthropogenic inputs may influence the occurrence of these compounds in the estuary, although direct source attribution requires further investigation. Overall, this study provides preliminary baseline information on the occurrence and phase-specific distribution of PPDs and PPD-Qs in the Pearl River Estuary and supports future investigations into their environmental fate and ecological relevance.

Toxics doi: 10.3390/toxics14050355

Authors: Tijana Mutić Tijana Milićević Emilija Vukićević Jovana Roganović Gorica Veselinović Marija Janković Gordana Gajica

Peloids are natural materials widely used in balneotherapy and dermatological treatments because of their physicochemical and mineralogical properties. Despite Serbia’s long tradition of spa-based pelotherapy, comprehensive data on the chemical and radiological characteristics of local peloids remain limited. In this study, peloid samples from 13 spa locations across four regions of Serbia were systematically investigated. The aim was to determine their physicochemical properties, elemental composition, and natural radioactivity, to assess their suitability and safety for therapeutic use. The analyzed samples exhibited pronounced variability in pH (6.59–9.52), electrical conductivity (77.5–6610 μS/cm), salinity (below detection limit to 4%), and total dissolved solids, reflecting diverse geological and hydrochemical properties. Inductively coupled plasma optical emission spectrometry revealed site-specific variations in macro- and microelements, influenced primarily by local lithology and sedimentary environments, with limited indications of anthropogenic inputs. Gamma spectrometric analysis showed that the activity concentrations of naturally occurring radionuclides (226Ra, 232Th, 40K, 238U, 235U, 210Pb) were within ranges commonly reported for therapeutic muds worldwide, while anthropogenic 137Cs was generally low. Radiological hazard indices were below internationally recommended safety limits. A preliminary screening of dermal exposure to potentially toxic elements indicated no significant noncarcinogenic risk (HI < 1) and acceptable carcinogenic risk (TCR) levels. Overall, this study provides a comprehensive chemical and radiological baseline for Serbian peloids, supporting their safe use in controlled therapeutic and wellness applications and highlighting the importance of site-specific characterization for quality assessment.

Toxics doi: 10.3390/toxics14050354

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

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

Toxics doi: 10.3390/toxics14050353

Authors: Eva Fernández-Gómez Luis Roca-Pérez Jaume Bech José Antonio Rodríguez-Martín Rafael Boluda

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

Toxics doi: 10.3390/toxics14050352

Authors: Sajjad Ahmad Jie Liu Murugesan Chandrasekaran

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

Toxics doi: 10.3390/toxics14040350

Authors: Ying Ma Nairui Yu Yi Zhang Jiaqi Shi Xinyan Zhou Xiaojin Li Li Guan Guang Jia Zhangjian Chen

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.

Toxics doi: 10.3390/toxics14040351

Authors: Tianao Sun Zhanyue Zheng Yongjie Ma Minglian Pan Yingjie Zhou Jingxia Wei Xinyu Yuan Jinhao Wan You Li Yan Sun

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.

Toxics doi: 10.3390/toxics14040349

Authors: Lingfei Ma Haipu Li Zhaoguang Yang

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.

Toxics doi: 10.3390/toxics14040348

Authors: Roberta Ceci Gianfranco Diletti Giampiero Scortichini Ettore Franco Angelo Pellegrino Iain R. Lake Alwyn R. Fernandes

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.

Toxics doi: 10.3390/toxics14040347

Authors: Yulong Tao

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.

Toxics doi: 10.3390/toxics14040346

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

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.

Toxics doi: 10.3390/toxics14040345

Authors: Xueping Huang Shengping Zhang Yu Liu Shuai Liu Qiyu Wang Nannan Wan Shanghaojun Lu Yongming Wu Miao Zhang

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.

Toxics doi: 10.3390/toxics14040343

Authors: Fangni Du Wenjun Zhao Shaofei Cao Rui Zhang Yuchen Yin

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.

Toxics doi: 10.3390/toxics14040344

Authors: Maksim M. Ivanov Polina Fominykh Nadezhda Ivanova Sergei Krasnov Valentin Golosov

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.

Toxics doi: 10.3390/toxics14040342

Authors: Benedetta Villa Gaia Bolla Ginevra Boldrocchi Roberta Bettinetti

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.

Toxics doi: 10.3390/toxics14040341

Authors: Xin Liu Zhiyuan Han Kuibin Han Yuhan Pang Xiaoyue Zhao Yuting Wang Xiaoyan Wu Tuanwei Wang

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.

Toxics doi: 10.3390/toxics14040340

Authors: Zhicheng Zhao Huimei Shan Song Wei Zheying Li Qingsheng Li

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 qm 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 (qm = 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, pHPZC, and Mn surface-state changes, and hydrodynamic conditions in the polymetallic mining areas.

Toxics doi: 10.3390/toxics14040339

Authors: Valéria Giménez Beatriz Neves Etelvina Figueira Paula Marques Adília Pires

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.

Toxics doi: 10.3390/toxics14040338

Authors: Alla P. Toropova Andrey A. Toropov Nadia Iovine Gianluca Selvestrel Alessandra Roncaglioni Emilio Benfenati

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.

Toxics doi: 10.3390/toxics14040337

Authors: Sarah Pilling Kerry Mitchell Prakash V. A. K. Ramdass

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.

Toxics doi: 10.3390/toxics14040336

Authors: Ines Varga Nina Bilandžić Jelena Kaurinović Andrea Gross Bošković Tomislav Klapec

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.

Toxics doi: 10.3390/toxics14040335

Authors: Chang Liu Anfei He Jie Gu Mulan Ji Jie Hu Shufeng Qiao Fenghe Wang Jing Hua Jian Wang

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.

Toxics doi: 10.3390/toxics14040334

Authors: Xinru Liu Yunli Wu Jin Tian Jiaxin Wen Yuan Shi Lili Wang An Zhu Zekai Wu

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.

Toxics doi: 10.3390/toxics14040333

Authors: Runze Bai Xiaochi Zhang Guoao Li Yiyi Wang Hujia Zhang Baopeng Liu Xiuli Zuo Jie Yan Qi Zhao

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 (NOx), and PM with aerodynamic diameters of ≤2.5, 2.5–10, and ≤10 μm (PM2.5, PM2.5–10, 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.

Toxics doi: 10.3390/toxics14040332

Authors: Huanhuan Yang Fulan Zhang Jing Liu Dayong Cui

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.