Toxicology and Environmental Health Sciences

Wu, Yang; Li, Tian; Zhang, Jiucong; Zheng, Xiaofeng; Yu, Xiaohui

doi: 10.1007/s13530-026-00311-0pmid: N/A

ObjectiveThis study aims to investigate the underlying molecular mechanisms linking seven prevalent air pollutants (benzene, toluene, SO2, NO2, NO, CO, and O3) to the development and occurrence of hepatocellular carcinoma (HCC).MethodsSeven kinds of air pollutants and HCC-related genes were retrieved from several online databases, and their intersections were taken. PPI visualization analysis of intersection genes was performed. The potential biological mechanism of intersection genes was clarified by GO and KEGG enrichment analysis. Using five different algorithms to identify the core gene, the expression level of core gene in HCC was verified by TCGA database, and its diagnostic performance was evaluated by the ROC curve. Through KM survival analysis, the genes related to prognosis were further screened, and the relationship between them and immune cell infiltration was explored. The interaction between them and seven air pollutants was explored by molecular docking analysis.ResultsSeven common air pollutants and HCC-related genes have 55 cross genes. The enrichment analysis of GO and KEGG showed that these genes promoted the occurrence and development of HCC through cell carcinogenesis, signal transduction, genetic information processing, and metabolic correlation. Eight core genes were screened by five different algorithms. TCGA data confirmed that the eight core genes were differentially expressed in HCC, and ROC curve showed that all the eight core genes had a good diagnostic performance. KM survival curve further showed that six key genes were related to the poor prognosis of HCC patients. Immune infiltration analysis revealed that these six key genes play significant roles in the HCC immune microenvironment. Molecular docking further supported potential interactions between the air pollutants and these six key genes.ConclusionThe findings indicate that ESR1, MMP9, RELA, PARP1, DNMT1, and CDK1 are critically involved in HCC pathogenesis. This research enhances public understanding of air pollution risks.

Nimra, Afzal; Usman, Mahnoor; Khan, Javaireya; Afzal, Hanan; Gull, Amina; Sidra, Safdar; Afzal, Ali; Khawar, Muhammad Babar

doi: 10.1007/s13530-026-00306-xpmid: N/A

Pyrethroids have been documented to accumulate in animal bodies. Multiple experimental studies suggest potential disruption of male reproductive function, yet findings remain inconsistent. Therefore, a comprehensive synthesis is required to clarify overall reproductive risks. Herein, we aim to quantitatively synthesize evidence from mammalian studies investigating the impact of pyrethroid exposure on male reproductive outcomes. A systematic search of Google Scholar, EMBASE, PubMed, and Scopus was conducted. Data extraction included species, exposure characteristics, outcomes, and methodological quality. Meta-analyses were conducted using standardized mean differences. Heterogeneity was evaluated using I2 and Q statistics. Subgroup and sensitivity analyses were performed to explore sources of variation. Sixty-two studies were selected, which primarily involved rats, with oral exposure as the dominant route. Geographically, studies originated mainly from India, Egypt, and Tunisia. Across pooled analyses, pyrethroid exposure showed no statistically significant overall effect on sperm count, motility, viability, testes weight, or testosterone levels. Leave-one-out analyses demonstrated robust but consistent pooled effects. Rats showed stronger negative trends than mice. Overall, the pooled SMD for all reproductive outcomes combined was –2.30 (95% CI –3.80 to –0.81, p = 0.003). Our study demonstrates that pyrethroid exposure can adversely influence male reproductive endpoints. More standardized, mechanistic, and dose-controlled mammalian studies are needed to refine risk assessment.

Rehman, Amna; Rehman, Amna; Abdullah, ; Ayub, Mubashra; Khan, Abdul Majid; Afzal, Ali

doi: 10.1007/s13530-026-00308-9pmid: N/A

BackgroundMicroplastic (MP) pollution is a growing risk to aquatic organisms. However, its chronic physiological effects on fish remains poorly described. Here we investigate that how the chronic exposure of mixed MPs affects demographics and physiology of Oreochromis niloticus.MethodsWe exposed fish (n = 18) for 30 days to low-dose and high-dose concentrations of mixed MPs. Growth indices, liver biomarkers, serum markers, stress markers, oxidative stress-related enzymes, and bioaccumulation were assessed.ResultsThe somatic effect of MPs was not statistically significant (p>0.05). However, higher concentration of MPs induced a significant hepatic atrophy (p<0.01), a decline in hepatic function (p<0.001), hepatocellular disruption (p<0.01), metabolic imbalance, endocrine stress, and inflammatory activation (p<0.05-0.001), an oxidative damage and impaired defense. FTIR and stereomicroscopy further confirmed the significant bioaccumulation of polymers in muscles but traces in brain.ConclusionsOur findings highlight subtle; yet, significant physiological risks in O. niloticus from chronic MP exposure.

Tamayo-Cabeza, Guillermo; Zenni, Michael; Castiblanco-Rubio, Gina A.; Lippert, Frank; Flora, David B.; Peacock, Janet L.; Till, Christine; Goodman, Carly V.; Lanphear, Bruce P.; Korrick, Susan A.; Karagas, Margaret R.; Martinez-Mier, E. Angeles

doi: 10.1007/s13530-026-00321-ypmid: N/A

ObjectiveThis study aimed to determine the minimum toenail mass needed for reliable fluoride analysis, and to compare fluoride extraction efficiency (%FE) using two protocols.MethodsToenail samples (n = 98 from 11 participants) were grouped into masses ranging from 1.0 to 5.0 mg (± 0.5 mg). Fluoride content was analyzed using a hexamethyldisiloxane(HMDS)-facilitated diffusion method and a fluoride-ion selective electrode. Pooled toenail samples (3.0 ± 0.5 mg) from four participants were analyzed using two protocols: protocol-A used 1 mL of HMDS-saturated 3N sulfuric acid/2 mL DI water; and protocol-B used 3 mL/3 mL. Samples were re-analyzed twice to calculate %FE. Minimum mass-threshold was determined by intraclass correlation coefficients (ICC) with 95%-confidence intervals (CI) from linear mixed-effects models and change-point analysis, accounting for intra-participant variability. F-tests compared the variance in %FE between protocols.ResultsFluoride content ranged from 0.82 to 9.22 µg/g. Excellent reliability (ICC = 0.90, 95%CI:[0.71, 0.95]) was observed in samples ≥ 2.5 mg. A change-point was identified at 2.20 mg(95%CI:[1.70, 2.70 mg]). A less variable %FE was observed with protocol-A (43–58%) compared to protocol-B (38–80%) (F-ratio = 0.23, p = 0.02).ConclusionToenail sample mass affects the reliability of fluoride analysis. The use of a minimum toenail mass of about 2.2–2.5 mg increases the reliability of fluoride analysis at the participant level. Variability in %FE should be considered in future efforts to standardize analytical protocols.

Mao, Wenjuan; Zhao, Hui; Sun, Ye; Liu, Guangyan; Yang, Biao

doi: 10.1007/s13530-026-00314-xpmid: N/A

BackgroundFine air particulates (PM2.5) are identified as a significant environmental factor contributing to the progression of non-small cell lung cancer (NSCLC). This study aims to explore the underlying mechanisms on PM2.5 and the biological behaviors of cancer cells.MethodsBy employing a series of the vitro assays, we assessed cell viability, invasion capacity and wound healing ability following the PM2.5 exposure. Additionally, gene expression profiling was conducted to identify potential key genes and pathways involved in this process.ResultsOur results demonstrated that to PM2.5 exposure enhances the migratory and invasive capabilities of NSCLC. The 126 eventful differentially expressed genes (DEGs) were identified by RNA-Seq in PM2.5-exposed H1299 cells. Meanwhile, according to the qRT-PCR, we found expression of these genes were similar to the trends in the RNA-Seq data.ConclusionsThese results provide novel insights into the role of PM2.5 in NSCLC prognosis and may pave the way for targeted therapeutic strategies.

Zhu, Weiwei; Chen, Yuxin; Hong, Xuanyu; Chen, Yi; Chen, Wei; Ouyang, Zedong; Gui, Shiheng; Fan, Ruifang

doi: 10.1007/s13530-026-00309-8pmid: N/A

ObjectiveThe influence of aromatic hydrocarbons (PAHs) structure on activating the aryl hydrocarbon receptor (AhR) was investigated.MethodsIn silico and in vitro assays were conducted using 20 PAHs and their halogenated and nitro derivatives as targets based on AhR activation as the initial molecular event.ResultsAll PAHs can bind to AhR, and their binding ability is related to their molecular weight, as reflected by the Gibbs free energy of high molecular weight (HMW) PAHs binding to AhR is generally lower than that of low-molecular weight PAHs. Compared with the parent PAHs, substituent modification significantly enhances their binding affinity to AhR. Moreover, the conformational stability of the complex formed by HMW PAHs and their halogenated and nitro derivatives with AhR is higher, likely stabilized by key interactions with Phe12, Ile42, and Phe68. Their energetic contributions and key roles were further confirmed by free energy decomposition and amino acid mutation. Subsequently, studies in HepG2 cells confirmed that stronger binding activates AhR signaling, reflected by oxidative stress levels and the upregulation of CYP1A1 and CYP1B1. These results demonstrate that AhR activation is closely related to molecular structure.ConclusionThese findings support toxicity risk assessment based on the structure–affinity–toxicity logical relationship and provide detailed molecular sites for studying the mechanism of action of PAHs on AhR, which may facilitate the development of AhR-targeted antagonists or modulators for mitigating PAH-induced toxicity.

Mukhopadhyay, Debraj; Cherchi, Roberto; Spanu, Alice; Cusano, Roberto; Zavattari, Patrizia; Cocco, Pierluigi; De Matteis, Sara

doi: 10.1007/s13530-026-00315-wpmid: N/A

ObjectiveThis pilot study aims to investigate the role of microRNAs (miRNAs) as early diagnostic biomarkers for asbestos-related respiratory diseases.MethodsWe conducted a pilot study to explore the plasma miRNA profile in 28 subjects, including 9 unexposed population controls, 9 ILD-free subjects formerly exposed to asbestos, and 10 cases of asbestos-related interstitial lung disease (ILD). Current smokers or subjects with other lung diseases were excluded. We used the receiver operator characteristic (ROC) area under the curve (AUC) to estimate the potential diagnostic accuracy of miRNAs. We also conducted a meta-analysis to estimate the pooled quantitative diagnostic accuracy of the differentially expressed miRNAs, based on their AUC and related 95% confidence intervals (CIs).ResultsIn total, 346 miRNAs were detected in the plasma samples of all study subjects. Both, miR-3679-5p and miR-574-5p, showed a 89% diagnostic accuracy (95% CI 0.73–1.00) in discriminating ILD-free asbestos-exposed from unexposed subjects. miR-6516-5p, miR-942-5p, and let-7f-5p showed a 92% diagnostic accuracy (95% CI 0.76–1.00) in differentiating asbestos-related ILD cases from ILD-free subjects formerly exposed to asbestos. miR-4714-3p and miR-20a-5p showed a 91% diagnostic accuracy (95% CI 0.78–1.00) in discriminating asbestos-related ILD cases from unexposed subjects.ConclusionWe successfully tested the effectiveness of our standard operating procedures in detecting differences in the plasma miRNA expression between subjects formerly exposed to asbestos, with and without interstitial lung disease and unexposed controls. Our results suggest that the plasma microRNA profile might be a potential biomarker of asbestos-related lung diseases.Graphical abstract[graphic not available: see fulltext]

Shukla, Rajendra Kumar; Chandravanshi, Lalit P.; Gupta, Richa

doi: 10.1007/s13530-026-00307-wpmid: N/A

Aim and ObjectiveStress has become an integral part of life, often triggering various biological systems involved in maintaining homeostasis and causing a range of physiological and pathological changes depending on the type and duration of the stress. Further, environmental chemical significantly contributes to intensify the stress.MethodsThis study investigated how prior exposure to chronic psychological stress (immobilization stress, IMS) or physical stress (forced swim stress, FSS) modifies lambda-cyhalothrin (LCT)-induced dopaminergic and neurobehavioral impairments.Neither IMS (one session, 15 min/day in restrainer for 28 days), FSS (one session,3 min/day for 28 days), nor LCT alone (3.0 mg/kg body weight, p.o. for 3 days on days 26–28) produced significant changes in motor activity, rotarod performance, or DA-D2 receptor in the corpus striatum brain region as compared with controls. These treatments alone caused only marginal alterations in tyrosine hydroxylase (TH) mRNA expression, TH immunoreactivity, and Nissl staining in the striatum region. However, pre-exposure to IMS or FSS for 28 days followed by LCT treatment distinctly impaired motor activity and rotarod performance. Exhibit changes in striatal dopamine receptor binding, TH mRNA expression and immunoreactivity and altered Nissl staining compared with IMS, FSS, or LCT alone.ConclusionThese findings suggest that chronic psychological or physical stressors enhance the brain's susceptibility to LCT-induced dopaminergic impairments, leading to measurable neurobehavioral deficits.Graphical abstractEnhanced vulnerability to lambda-cyhalothrin induced neurotoxicity in rats pre-exposed to stress.[graphic not available: see fulltext]

Raj, Vishnu; Thekkuveettil, Anoopkumar

doi: 10.1007/s13530-026-00310-1pmid: N/A

IntroductionManganism is a disease characterized by the degeneration of dopamine neurons and shares distinct similarities with Parkinson’s Disease (PD). One of the environmental risk factors for PD is exposure to manganese (Mn). However, the precise role of dopamine (DA) in Mn-mediated neurodegeneration, as well as its developmental effects, has not been well studied.Materials and methodsTo understand the mechanisms involved in Mn-induced neurotoxicity, we used C. elegans as a genetic and behavioral model system to assess dopaminergic neurodegeneration, survival, and locomotor function following MnCl2 and dopamine exposure.ResultsOur results showed that adult worms treated with 50 and 100 mM MnCl2 have significantly increased DA neurodegeneration. Interestingly L1 larvae did not show neurodegeneration when treated with MnCl2 alone but showed a significant increase in neurodegeneration (50%) when MnCl2 exposure was given after DA pretreatment. However, both adult and larval exposure to MnCl2 demonstrated significant toxicity by reducing the survival rate. In adult worms, treatment with 100 mM MnCl2 after DA pretreatment led to a greater percentage of neurodegeneration. Adult worms exposed to Mn or DA alone showed recovery of neuronal dopamine function within 24 h; however, those exposed to both exogenous DA and Mn showed prolonged behavioural defects. The cat-2 mutants, which lack DA, were resistant to Mn-mediated neurodegeneration. In contrast, cat-2 overexpressing strain displayed severe neurodegeneration at lower concentrations of MnCl2 (50 mM).ConclusionOur results on biochemical, behavioural and genetic assays confirmed that both endogenous and exogenous DA plays a crucial role in determining the sensitivity to Mn-induced dopaminergic neurotoxicity.

Khorsandi, Joshua; Blank, Liahm; Thatcher, Spencer; Ahmed, Abu-Bakr; Batra, Kavita; DeAndrea, G.; Merchant, Aftab

doi: 10.1007/s13530-026-00312-zpmid: N/A

ObjectiveWe aimed to synthesize and interpret available evidence on microplastics released from plastic cutting boards, the resulting contamination of food, potential human health effects, and environmental pathways, and to identify practical mitigation options.MethodsA literature review was conducted using PubMed, Google Scholar, and relevant journal websites, focusing on 2018–2025, with sentinel studies from 2008–2017 included. Search terms addressed microplastics, nanoplastics, and food-contact contexts, supplemented by reference checks to capture additional relevant work. Exclusion criteria removed inaccessible or irrelevant reports. In total, 98 publications were thematically synthesized to assess microplastic release, exposure, toxicology, and environmental implications.ResultsLaboratory abrasion tests and Raman-imaging studies show that routine knife work on polypropylene and polyethylene boards releases micro- to nanoplastics, with yields influenced by material, cutting force, food hardness, temperature, and board wear, and several datasets indicate higher shedding from polypropylene than polyethylene. Field investigations detect microplastics in meats and fish prepared on plastic boards and demonstrate persistence through rinsing and cooking. Ingestion represents the dominant exposure pathway, with plausible gastrointestinal irritation and potential systemic translocation for small particles. Shed particles also enter wastewater and soils, supporting environmental recirculation. Practical mitigations include material substitution for high-force tasks, timely board replacement, sharp-knife and low-force techniques, and improved cleaning practices.ConclusionsPlastic cutting boards constitute a direct and modifiable source of dietary and environmental microplastics at the point of food preparation. Integrating cutting board shedding into exposure assessments and advancing standardized methods, nanoplastics quantification, and product and food-contact guidance can reduce avoidable exposure and inform risk management. These findings underscore the need for regulatory attention to mechanical shedding from food-contact plastics, a risk pathway currently overlooked in food safety frameworks.