Ecotoxicology and Environmental Safety最新文献

{"title":"BDE-209 toxicity: From spermiogenesis to sexual maturity in F1 male mice","authors":"Xin Gao ,&nbsp;Qi Zheng ,&nbsp;Siju Chen ,&nbsp;Huan He ,&nbsp;Yu Wei ,&nbsp;Taifa Zhang ,&nbsp;Yi Wang ,&nbsp;Bo Wang ,&nbsp;Dake Huang ,&nbsp;Shengquan Zhang ,&nbsp;Sumei Zhang ,&nbsp;Jinxia Zhai","doi":"10.1016/j.ecoenv.2025.118231","DOIUrl":"10.1016/j.ecoenv.2025.118231","url":null,"abstract":"<div><div>Most studies of enviromental toxic chemicals focused on the meiosis stage during spermatogenesis, however, the research on the spermiogenesis damage phenotype of BDE-209 is limited. This study aimed to evaluate the processes by which BDE-209 regulates the formation of acrosomes and mitochondrial sheath (MS), key structures during spermiogenesis and fertilization. ICR mice were divided into control, low, medium, and high-dose BDE-209 groups and treated for 42 days. A comprehensive method combining ultrastructural analysis, transcriptomics, molecular biology, and fertility experiments was adopted. In mice exposed to BDE-209, testicular dysplasia, altered sex hormone concentrations, decreased semen quality, and head and tail deformities occurred. Chromatin condensation failure was present in BDE-209-exposed spermatozoa with decreased mRNA and protein levels of PRM1 and TNP1. BDE-209 disrupts the acrosome biogenesis process by disrupting the Golgi structure and the apical ectoplasmic specialization (ES) structure. BDE-209 exposure caused multiple damage to the MS and down-regulated the mRNA levels of Akap3, Akap4, Cfap44, Ccdc40, Dhah1, etc. These injuries resulted in subfertility in BDE-209 male mice, and the male offspring also exhibited gonadal dysplasia, sex hormonal changes, and decreased semen quality. Conclusively, BDE-209 exposure induced spermiogenesis defects and subfertility. F0 and F1 males showed a similar injury phenotype. This study advanced the understanding of the damage phenotype of spermiogenesis and complemented the reproductive toxicity of F1 male mice. These findings might be important for the study of related molecular mechanisms and the mitigation of BDE-209 exposure on offspring development.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118231"},"PeriodicalIF":6.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of pulmonary fibrosis and lung cancer induced by chronic PM2.5 exposure: Focus on the airway epithelial barrier and epithelial-mesenchymal transition","authors":"Yuyu Shi,&nbsp;Qi Shao,&nbsp;Zilin Ren,&nbsp;Guojiao Shang,&nbsp;Jinhua Han,&nbsp;Jialin Cheng,&nbsp;Yuxiao Zheng,&nbsp;Fafeng Cheng,&nbsp;Changxiang Li,&nbsp;Qingguo Wang,&nbsp;Xueqian Wang","doi":"10.1016/j.ecoenv.2025.118253","DOIUrl":"10.1016/j.ecoenv.2025.118253","url":null,"abstract":"<div><div>This study aims to provide new insights into PM_2.5-induced lung diseases through a focus on the pulmonary epithelial barrier and epithelial-mesenchymal transition (EMT). Firstly, we analyzed the mechanisms by which PM_2.5 damages the airway epithelial barrier, including inflammatory responses, immune imbalance, oxidative stress, apoptosis, and autophagy. Subsequently, we investigated the mechanisms by which PM_2.5 induces EMT, which involve the synergistic effect of oxidative stress and inflammation, the activation of key signaling pathways, and the regulatory role of non-coding RNAs. Furthermore, we explored the interaction between the airway epithelial barrier and EMT, especially the induction of EMT by epithelial barrier damage and the impact of EMT on epithelial barrier repair. Regarding lung injury diseases, we focused on the roles of the epithelial barrier and EMT in the development of pulmonary fibrosis and lung cancer, providing evidence from in vitro and in vivo studies. Emphasizing the translational prospects from basic research to clinical applications, and we proposed new ideas for treating PM_2.5-related lung diseases from four aspects-anti-inflammatory and antioxidant drugs, signaling pathway inhibitors, non-coding RNA-targeted therapies, and gene editing and cell therapies-by focusing on the two key links of the airway epithelial barrier and EMT.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118253"},"PeriodicalIF":6.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of lincRNAs and differential regulatory mechanisms in response to nanoplastic toxicity at environmentally relevant concentrations in Caenorhabditis elegans","authors":"Xiaoxiao Zhang ,&nbsp;Chenxi Zhou ,&nbsp;Zifan Wu ,&nbsp;Xinyi Jiang ,&nbsp;Qinlin Wu ,&nbsp;Yuhan An ,&nbsp;Zihan Yu ,&nbsp;Yunfei Liu ,&nbsp;Long Miao ,&nbsp;Xing Liu ,&nbsp;Man Qu ,&nbsp;He Chen","doi":"10.1016/j.ecoenv.2025.118245","DOIUrl":"10.1016/j.ecoenv.2025.118245","url":null,"abstract":"<div><div>Polystyrene nanoplastics (PS-NPs) at environmentally relevant concentrations have been shown to be toxic to living organisms, but the role of long noncoding RNAs (lncRNAs) in their toxicity regulation is not yet clear. Using <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) as a model organism, we investigate the mechanisms and roles of lncRNAs in PS-NPs toxicity at environmentally relevant concentrations. In this study, L1 larvae were exposed to 1–100 µg/L of 50 nm PS-NPs for 72 h, and high-throughput transcriptome sequencing was performed. Exposure to PS-NPs at concentrations of 10 µg/L, which is in the range of environmentally relevant concentrations of nanoplastics, or higher can lead to increased reactive oxygen species (ROS) production and decreased locomotion behavior in <em>C. elegans</em>, yet no significant toxic effects were observed for the leachate. The sequencing results revealed significant changes in G protein-coupled receptors and long intergenic noncoding RNAs (lincRNAs), which warranted further investigation. Additionally, a CRISPR-based knockout (KO) mutant library of <em>C. elegans</em> lincRNAs was employed for in-depth mechanistic studies. The findings indicate that multiple lincRNAs are involved in the regulatory response to the toxic effects of PS-NPs. Compared to wild-type nematodes, <em>linc-7</em>, <em>linc-9</em>, <em>linc-13</em>, <em>linc-21</em>, <em>linc-24</em>, <em>linc-49</em>, <em>linc-61</em>, and <em>linc-169</em> KO nematodes exhibited increased sensitivity to the toxicity of PS-NPs, while <em>linc-11</em> and <em>linc-50</em> nematodes showed resistance. Notably, our results indicate that the transcription process of <em>linc-11</em>, rather than its mature transcripts, played a crucial role in the response to PS-NPs. This is evidenced by the differing phenotypes observed in RNA interference (RNAi) knockdown (KD) and CRISPR KO nematodes following exposure to PS-NPs. Our results suggest that transcriptional regulation involving lncRNAs is integral to the organism's response to PS-NPs.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118245"},"PeriodicalIF":6.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of air pollution exposure in the alteration of brain cortical structure: A Mendelian randomization study","authors":"Chaojuan Huang ,&nbsp;Zimei Cheng ,&nbsp;Xu Wu ,&nbsp;Zhiwei Li ,&nbsp;Mingxu Li ,&nbsp;Qian Zhao ,&nbsp;Yuyang Zhang ,&nbsp;Xingliang Feng","doi":"10.1016/j.ecoenv.2025.118221","DOIUrl":"10.1016/j.ecoenv.2025.118221","url":null,"abstract":"<div><h3>Background</h3><div>Accumulating research has linked ambient air pollution exposure to alterations in cortical surface area (SA) and thickness; however, the causal inferences remain controversial. Our investigation aims to determine the causality between air pollution and brain cortical morphology using the Mendelian randomization (MR) approach.</div></div><div><h3>Methods</h3><div>Public accessible genome-wide association studies data on particulate matter 2.5 (PM_2.5), PM_2.5 absorbance, PM₁₀, PM_2.5–10, nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) concentration were screened to select instrumental variables. Univariable MR (UVMR) was performed to assess the causality of air pollution on brain cortical structure using five MR methods. Multivariable MR (MVMR) was further conducted to strengthen the robustness of the identified relationships by adjusting for related pollutant phenotypes, household income, and unhealthy eating habits.</div></div><div><h3>Results</h3><div>The UVMR analysis identified fourteen causal associations between air pollution susceptibility and alterations in brain cortical morphology, with nine showing negative effects and five showing positive effects concurrently. The MVMR models indicated negative causal relationships between PM_2.5 level and the SA of the inferior temporal cortex (beta [95 %CI] = -215.739 [-404.284 to -27.194], <em>p</em> = 0.025), NO₂ level and the SA of the lateral occipital cortex (beta [95 %CI] = -548.577 [-1086.450 to -10.699], <em>p</em> = 0.046), and a positive correlation between PM_2.5 absorbance and SA of the bankssts cortex (beta [95 %CI] = 76.491 [14.267–138.716], <em>p</em> = 0.016). No evidence of heterogeneity or pleiotropy was noticed.</div></div><div><h3>Conclusions</h3><div>Our exploration established causal relationships between air pollution exposure and brain cortical structure, underscoring the significance of mitigating air pollution to preserve brain cortical morphology.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118221"},"PeriodicalIF":6.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pollutants distribution profiles and health risks of groundwater and soil around the waste landfills: A study of 12 waste landfills in Guangxi province, China","authors":"Fengping Liu ,&nbsp;Hailin Zhu ,&nbsp;Qiongqiong Lu ,&nbsp;Yinan Zheng ,&nbsp;Zhenyu Ding ,&nbsp;Han Wang ,&nbsp;Yuhu Chang","doi":"10.1016/j.ecoenv.2025.118135","DOIUrl":"10.1016/j.ecoenv.2025.118135","url":null,"abstract":"<div><div>The waste landfill disposes of a large amount of urban garbage, and the harmful substances in the waste have serious impacts on the ecological environment of the landfill and its surroundings. To systematically investigate the pollution mechanisms and associated health risks posed by landfills, we conducted a comprehensive study in Guangxi Province, China by collecting water, soil, and leachate samples from 12 operational landfill sites. These samples were analyzed using inductively coupled plasma mass spectrometry and ultraviolet-visible spectroscopy to quantify concentrations of 18 priority pollutants, including heavy metals and nutrients. Geostatistical analysis revealed moderate spatial clustering of pollutants in soils and groundwater, with significant positive correlations observed between Mn, Cd, and Pb concentrations across leachate-soil-groundwater systems. Notably, as exhibited 2.3-fold higher carcinogenic risk values compared to Cd, while Zn demonstrated the highest non-carcinogenic hazard quotient among all studied pollutants. Contaminant transport pathways were evaluated through correlation models, revealing that Cu and Hg in leachate significantly influenced groundwater quality around landfills. These findings provide critical insights for implementing site-specific pollution control strategies and optimizing health risk management protocols in landfill-impacted regions.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118135"},"PeriodicalIF":6.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perfluorooctanoic acid disrupts thyroid hormone biosynthesis by altering glycosylation of Na+/I− symporter in larval zebrafish","authors":"Zhenzhen Cai ,&nbsp;Guangdi Zhou ,&nbsp;Xiaogang Yu ,&nbsp;Yatao Du ,&nbsp;Qiuhong Man ,&nbsp;Weiye Charles Wang","doi":"10.1016/j.ecoenv.2025.118249","DOIUrl":"10.1016/j.ecoenv.2025.118249","url":null,"abstract":"<div><div>Perfluorooctanoic acid (PFOA) is a well-known thyroid disruptor that has been found to induce hypothyroidism. However, the exact molecular mechanism by which PFOA reduces thyroid hormone levels remains unclear. In this study, we have discovered that PFOA disrupts the glycosylation process of the sodium/iodide symporter (NIS), which inhibits the translocation of NIS onto the plasma membrane of thyroid follicular cells. Our results also demonstrate that PFOA disrupts thyroid stimulating hormone (TSH)-dependent signaling pathways involved in cellular glycosylation, impairing NIS glycosylation and reducing the ability of iodine uptake. This leads to an insufficiency of iodine for thyroid hormone production inside the follicular cells of the thyroid, resulting in lower-than-normal thyroxine levels detected in zebrafish larvae. These findings are consistent with our previously published data, which showed that PFOA induces neural behavior changes during the early stages of neuronal development in zebrafish. This new discovery provides valuable insights into the molecular characteristics of endocrine-disrupting chemicals (EDCs) that are known to affect the thyroid. It may also contribute to a better understanding of how altered glycosylation could be a potential risk factor for the association between exposure to specific per- and polyfluoroalkyl substances (PFAS) and various health effects in humans.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118249"},"PeriodicalIF":6.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Source-oriented health risk assessment of heavy metals in soil and dust at coal resource-based urban parks in northern China based on bioaccessibilities","authors":"Yue Liu ,&nbsp;Wenqiang Guo ,&nbsp;Yeqiu Wu","doi":"10.1016/j.ecoenv.2025.118252","DOIUrl":"10.1016/j.ecoenv.2025.118252","url":null,"abstract":"<div><div>The mining and utilisation of coal release numerous heavy metals (HMs) into the urban environment, but there are few studies expanding on source-oriented health risk assessment based on bioaccessibility for the identification of health priority control pollutants at coal resource-based cities. Hence, dust and soil samples were collected from urban parks in Datong, Shanxi Province, known as the coal capital of China, to evaluate the pollution level, bioaccessibility, and source-specific health risk assessment. The results revealed severe contamination of As, Cd, and Pb in both soil and dust, with particularly high levels of Cd, which reached 16.07 and 15.09 times the background values in dust and soil, respectively. Overall, HM pollution and the corresponding ecological risks in dust and soil were categorized as moderate and high, respectively. Manganese (30.55 %) and Cr (1.36 %) in dust showed the highest and lowest percent bioaccessibility in the gastrointestinal system, respectively. High bioaccessibilities and high concentrations of HMs reflect the prevalence and severity of dust and soil pollution in Datong. Multivariate statistical analysis showed that natural sources, traffic sources, and industrial sources are the three determinants of HM accumulation. Their contribution rates to dust and soil are as follows: 40.35 %, 21.54 %, 6.89 %, and 32.21 %, 18.92 %, 13.09 %, respectively. Once bioaccessibility was accounted for, lower non-carcinogenic and carcinogenic risks of HMs were observed than those based on total HM concentrations. However, the average total carcinogenic risk value for adults and children still exceeded the safety threshold (1.0E-06). Among coal resource–based cities, natural sources were identified as the priority pollution source, and As emerged as the critical pollutant. In conclusion, this research provides insights into the prevention and control of HM pollution and health risk assessment in urban ecosystems.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118252"},"PeriodicalIF":6.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honeybee colony soundscapes: Decoding distance-based cues and environmental stressors","authors":"Nayan Di ,&nbsp;Chunjing Zhu ,&nbsp;Zongwen Hu ,&nbsp;Muhammad Zahid Sharif ,&nbsp;Baizhong Yu ,&nbsp;Fanglin Liu","doi":"10.1016/j.ecoenv.2025.118241","DOIUrl":"10.1016/j.ecoenv.2025.118241","url":null,"abstract":"<div><div>Honey bees play a crucial role in agricultural productivity and ecological stability, yet their interactions with environmental stressors, particularly volatile organic compounds (VOCs) and pollutants, pose significant challenges to their cognitive functions and behavior. This study investigates the effects of VOCs on the acoustic communication within honeybee colonies and foraging behavior, specifically focusing on how these compounds influence distance-related cues conveyed through colony sounds. Using OpenL3 embeddings and machine learning models, the study achieved accurate classification of food source distances based on acoustic features, with the K-Nearest Neighbors (KNN) model demonstrating superior performance. The introduction of ethyl acetate and acetone caused minor reductions in classification accuracy but had divergent impacts on foraging dynamics: ethyl acetate enhanced landing efficiency, whereas acetone disrupted foraging activity. These findings highlight the utility of acoustic analysis for studying honey bee behavior and underscore the importance of mitigating environmental stressors to sustain pollinator populations.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118241"},"PeriodicalIF":6.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing drinking water safety: Real-time prediction of trihalomethanes in a water distribution system using machine learning and multisensory technology","authors":"Antonio J. Aragón-Barroso ,&nbsp;David Ribes ,&nbsp;Francisco Osorio","doi":"10.1016/j.ecoenv.2025.118243","DOIUrl":"10.1016/j.ecoenv.2025.118243","url":null,"abstract":"<div><div>Prolonged exposure to high concentrations of trihalomethanes (THMs) may generate human health risks due to their carcinogenic and mutagenic properties. Therefore, monitoring THMs in drinking water distribution systems (DWDS) is essential. This study focused on the statistical modelling of THMs formation through multiple linear regression (MLR) method to develop simple predictive models that serve as preventive tools capable of alerting about potential increases in THMs within the water network. To achieve this, a dataset comprising 1192 observations of water quality measurements in the study area over five years was created. The independent variables selected to explain the formation of THMs were free residual chlorine (FRC), total organic carbon (TOC), conductivity, pH and turbidity. Then, following an exploratory analysis of the dataset using Pearson’s correlation matrix and an ANOVA test, multiple regression models were developed. In total, a total of two predictive models were built, based on data filtered by conductivity levels, with coefficients of determination (R²) of 0.64 and 0.47. The algorithms of these predictive models were integrated into the control center of the water company in the study area. On the other hand, a multisensory device was installed in a strategically located drinking water tank to measure the values of the independent variables used in the models. These measurements were transmitted online to the control center to continuously update the predictive models and provide real-time forecasts of THMs. Finally, model validation was performed by comparing the real-time predictions of the models with actual THMs levels obtained from laboratory analyses, achieving an average accuracy of 90 %.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118243"},"PeriodicalIF":6.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects","authors":"Yongbin Lu ,&nbsp;Yongxia Dang ,&nbsp;Yilin Chen ,&nbsp;Yizhuo Chen ,&nbsp;Xu Hui ,&nbsp;Xiaonan Li ,&nbsp;Xin Fan ,&nbsp;Jingru Yang ,&nbsp;Xiaoling Ling ,&nbsp;Li Ma ,&nbsp;Zhiyuan Cheng ,&nbsp;Kehu Yang","doi":"10.1016/j.ecoenv.2025.118247","DOIUrl":"10.1016/j.ecoenv.2025.118247","url":null,"abstract":"<div><div>Cadmium (Cd), an endocrine disruptor, has been linked to hormone-related cancers, including breast cancer (BC). However, previous studies investigating the association between Cd exposure and BC risk have yielded inconsistent results, and the effects of Cd on BC subtypes remain poorly understood. We employed logistic regression and restricted cubic splines (RCS) to examine the relationship between Cd exposure and BC. A meta-analysis was subsequently conducted to validate the association between Cd exposure and BC. Lastly, mediation analysis was applied to explore the underlying mechanisms linking Cd exposure to BC. Data from 5954 participants in the National Health and Nutrition Examination Survey (1999–2020) were analyzed. Elevated Cd levels in the fourth quartile were significantly associated with an increased BC risk (odds ratio (OR) = 3.74, 95 % confidence interval (CI): 1.45 - 9.62, P_trend = 0.019), compared to the first quartile group. A linear dose-response relationship was seen between urinary Cd levels and BC risk (P_non-linear = 0.532), with BC risk increasing 317 % (OR = 3.17, 95 % CI: 1.93 - 5.20, P_trend &lt; 0.001) for 1 μg/g creatinine increases in urinary Cd levels. The meta-analysis, which included 20 eligible studies, further observed a possible link between Cd exposure and BC risk (relative risk (RR) = 1.17, 95 % CI: 1.06 - 1.29, I² = 83 %), particularly in estrogen receptor-positive (ER⁺) subtypes (RR = 1.08, 95 % CI: 1.01 - 1.16, I² = 70 %). Mediation analysis further revealed that glycated hemoglobin (HbA1c) mediated 9.09 % of the Cd-BC risk association. In conclusion, the study results suggest a potential association between Cd levels and an increased BC risk, particularly in ER⁺ subtypes. Mechanistically, HbA1c was identified as a mediator in this association. These findings underscore the complex interplay between Cd exposure and metabolic dysregulation in the development of BC, highlighting the potential role of HbA1c in modulating BC risk among individuals exposed to Cd.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"297 ","pages":"Article 118247"},"PeriodicalIF":6.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}