Environmental Health Perspectives最新文献

{"title":"Associations of gestational and childhood urinary triclosan concentrations with atopic and allergic symptoms in Health Outcomes and Measures of the Environment (HOME) Study participants ages 1-12 years.","authors":"Hannah E Laue, Elvira S Fleury, Medina S Jackson-Browne, Antonia M Calafat, Aimin Chen, Kimberly Yolton, Kim M Cecil, Nicholas C Newman, Jessie Buckley, Bruce P Lanphear, Joseph M Braun","doi":"10.1289/EHP16710","DOIUrl":"10.1289/EHP16710","url":null,"abstract":"<p><strong>Background: </strong>Triclosan, an antimicrobial chemical that was widely used in consumer products, may increase risk of allergic diseases in children, but prospective studies are needed to clarify the association.</p><p><strong>Objectives: </strong>To elucidate the associations of time-varying urinary triclosan concentrations with eczema, allergic rhinitis, and wheeze.</p><p><strong>Methods: </strong>In the HOME Study, a prospective pregnancy and birth cohort, we quantified urinary triclosan concentrations in mother-child pairs up to ten times between 16 weeks' gestation and age 12 years. Caregivers reported eczema, allergic rhinitis, and wheeze symptoms biannually until children were aged 6 years and again when they were aged 8- and 12 years. We used generalized estimating equations to estimate the covariate-adjusted association of gestational and childhood triclosan concentrations with the risk of reporting eczema, allergic rhinitis, or wheezing symptoms.</p><p><strong>Results: </strong>Three hundred forty-seven mother-child dyads contributed >3,000 visits to the analysis of gestational exposures and >2,600 visits to childhood analyses. Each 2-fold higher childhood triclosan concentration was associated with a 1.23 (95% CI: 1.04, 1.46) and 1.12 (95% CI: 1.01, 1.25) times higher risk of reporting eczema and allergic rhinitis, respectively, but not wheezing (RR=0.98 [95% CI: 0.82, 1.16]). We did not observe modification by child sex. Associations of gestational triclosan with eczema, allergic rhinitis, or wheezing symptoms were null in the full sample. Child sex modified the association of gestational triclosan with allergic rhinitis and wheezing (p-interaction_Allergy: 0.02; p-interaction_Wheezing:0.10), with 1.09 (95% CI: 1.00, 1.19) and 0.91 (95% CI: 0.83, 1.00) times the risk of allergic rhinitis symptoms among males and females respectively.</p><p><strong>Conclusion: </strong>Childhood urinary triclosan concentrations were associated with caregiver reported eczema, and more weakly with allergic rhinitis. Associations of gestational triclosan with allergic outcomes differed by child sex, suggesting heightened susceptibility to triclosan among males. https://doi.org/10.1289/EHP16710.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Unlocking the Power of Data Harmonization in Environmental Health Sciences: A Comprehensive Exploration of Significance, Use Cases, and Recommendations for Standardization Efforts.","authors":"Jeanette A Stingone, H C Bledsoe, Grace Cooney, Mireya Diaz-Insua, Elaine Faustman, Karamarie Fecho, Ramkiran Gouripeddi, Philip Holmes, David Kaeli, Oswaldo Lozoya, Anna Maria Masci, Hina Narayan, Charles Schmitt, Maria Shatz, Wren Tracy","doi":"10.1289/EHP15410","DOIUrl":"10.1289/EHP15410","url":null,"abstract":"<p><strong>Background: </strong>The field of environmental health sciences increasingly demands comprehensive and diverse datasets, particularly in response to emerging research areas such as climate change, mixtures, and exposomics. The data needed to address the complexity of environmental health research questions often extend beyond the boundaries of a single study or data resource. Traditional data management approaches struggle to harmonize the ever-expanding and heterogeneous data sources needed for research in the environmental health sciences. Harmonization may help address this issue as it involves aligning and standardizing various elements of data to allow comprehensive analysis, data pooling and interpretation across studies.</p><p><strong>Objectives: </strong>The primary objective is to inform researchers about the transformative potential of embracing harmonization methodologies and to motivate contributions to ongoing efforts, thereby fostering advancements.</p><p><strong>Methods: </strong>Using the Environmental Health Language Collaborative's Data Harmonization Use Case, we provide a practical illustration of existing data harmonization approaches, identify gaps, and emphasize future research and application directions. We selected two publicly available environmental epidemiology studies on the topic of childhood asthma and three studies on the topic of biomarkers of metals exposure during pregnancy and birth outcomes and applied several existing harmonization approaches to assess interoperability.</p><p><strong>Discussion: </strong>Our process revealed the potential limitations of many existing harmonization approaches, with notable failures to identify common variables across independent datasets and lack of agreement between human and computer-based approaches. This use case identified various challenges with existing approaches, including reliance on often incomplete data documentation and large amounts of manual effort. To address these challenges, we recommend the continued advancement and dissemination of community data standards, the development of software and tools to facilitate harmonization through automation, and strategic efforts to promote engagement in data harmonization within the environmental health sciences community. Collaborative science is needed to advance our understanding of environmental contributors to health, and realizing the harmonization potential of our scientific data is a step toward improved collaboration. https://doi.org/10.1289/EHP15410.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Trends in serum levels of emerging and legacy per- and polyfluoroalkyl substances from 2008 to 2018: a longitudinal study in China.","authors":"Xu Cheng, Yu Wang, Jin Zhang, Hong Guo, Lin Liu, Lu Liu, Junya Gao, Meian He","doi":"10.1289/EHP15340","DOIUrl":"https://doi.org/10.1289/EHP15340","url":null,"abstract":"<p><strong>Background: </strong>China is an important producer and consumer of per- and polyfluoroalkyl substances (PFAS), but there is limited understanding of longitudinal trends of PFAS in Chinese people.</p><p><strong>Objectives: </strong>This study investigated decadal trends in PFAS and potential sources of exposure in the Dongfeng-Tongji cohort of Chinese people and explored potential misclassification bias.</p><p><strong>Methods: </strong>We repeatedly measured serum PFAS (containing 11 perfluorocarboxylic acids (PFCAs), 9 perfluorosulfonic acids (PFSAs), 6 PFAS precursors, and 4 PFAS alternatives) in 648 samples (collected in 2008, 2013, and 2018) from 216 Chinese residents in Hubei Province. We used linear mixed effect model to examine trends in PFAS concentrations over survey time. We also assessed the potential exposure sources of PFAS using principal component analysis-multiple linear regression (PCA-MLR) model.</p><p><strong>Results: </strong>Eleven PFAS were detected in at least 80% of the population, PFOS, PFOA, and 6:2CL-PFESA being the predominant PFAS. We found a slight decrease in linear-PFOS during the 10-year period; at the same time, the levels of PFOA doubled and the detection rate of short-chain PFCAs (PFBA, PFHpA) rose. 6:2CL-PFESA (China specific PFAS alternative) remained high for a decade. Similar correlation trends between PFAS were observed at three timepoints. Comparison of our findings with those from other studies suggests the study population was exposed to three potential sources of contamination, which may represent ingestion of contaminated diets, long-range transport of atmospheric PFAS, and exposures acquired from dust, drinking water, and daily commodities. We found that serum PFAS measurement at on timepoint was similar to levels over a 5-year period but not a 10-year period.</p><p><strong>Discussion: </strong>Our study provides information on serum PFAS levels in Chinese retired workers in the Dongfeng-Tongji cohort, and highlights that the risk of exposure to novel PFCAs and PFAS alternatives deserves continued attention. For longitudinal studies with long-term follow-up (e.g. more than 5 years), relying only on a single baseline serum PFAS level may generate misclassification bias resulting in expected bias towards the null and affect the estimation of health effects. https://doi.org/10.1289/EHP15340.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Expanded Tox21 biological assay panel for the prediction of drug-induced liver injury and cardiotoxicity.","authors":"Tuan Xu, Masato Ooka, Jinghua Zhao, Srilatha Sakamuru, Deborah K Ngan, Li Zhang, Shu Yang, Jameson Travers, Menghang Xia, Tongan Zhao, Carleen Klumpp-Thomas, Hu Zhu, Mathew D Hall, Stephen Ferguson, Natalie D Shaw, David M Reif, Anton Simeonov, Ruili Huang","doi":"10.1289/EHP16190","DOIUrl":"10.1289/EHP16190","url":null,"abstract":"<p><strong>Background: </strong>Toxicology in the 21^st Century (Tox21) assay data provide a valuable resource for the prediction of <i>in vivo</i> toxicity using machine learning models. However, the performances of these models previously developed using the pre-existing Tox21 assay data were less than ideal, likely due to insufficient coverage of the biological response space by the assay targets.</p><p><strong>Objectives: </strong>This study aimed to assess whether expanding the Tox21 portfolio with new assays that probe under-represented targets/pathways related to unanticipated adverse drug effects could improve the predictive capacity of <i>in vitro</i> assay data for <i>in vivo</i> toxicity such as drug induced liver injury (DILI) and cardiotoxicity (DICT).</p><p><strong>Methods: </strong>Models were constructed using data from the pre-existing panel of 36 assay targets and the expanded panel of 49 assay targets. A feature selection approach was used to determine the optimal number of assays needed for each model. The models were then applied to predict the potential hepatotoxicity and cardiotoxicity of compounds in the Tox21 10K compound library.</p><p><strong>Results: </strong>For both DILI and DICT prediction, the best-performing models developed using the expanded assay panel required a smaller number of assays to achieve the same level of performance compared to those based on the pre-existing assays. Models constructed by combining both assay data (pre-existing + expanded) and chemical structure consistently outperformed those constructed based on assay data alone, but showed similar performance to those constructed based on chemical structure. The compounds predicted to have the highest toxic potential were experimentally verified to demonstrate the effectiveness of our models in identifying new potentially toxic compounds.</p><p><strong>Discussion: </strong>The expansion of the Tox21 assay panel has significantly enhanced the predictive capacity of assay data for predicting DILI and DICT potential. This improvement underscores the importance of a diverse and comprehensive <i>in vitro</i> assay portfolio in advancing safety assessment. https://doi.org/10.1289/EHP16190.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood.","authors":"Thanh T Hoang, Marta Cosin-Tomas, Yunsung Lee, Giulietta Monasso, Zongli Xu, Sebastian Shaobo Li, Xuehuo Zeng, Anne P Starling, Brigitte Reimann, Stefan Röder, Lea Zillich, Dereje D Jima, Chris H L Thio, Giancarlo Pesce, Elin T G Kersten, Charles E Breeze, Adam B Burkholder, Mikyeong Lee, James M Ward, Bios Consortium, Rossella Alfano, Michael Deuschle, Liesbeth Duijts, Akhgar Ghassabian, Laura-Concepció Gómez Herrera, Vincent Wv Jaddoe, Alison A Motsinger-Reif, Rolv T Lie, Tim S Nawrot, Christian M Page, Tabea S Send, Gemma Sharp, Dan J Stein, Fabian Streit, Jordi Sunyer, Allen J Wilcox, Heather J Zar, Gerard H Koppelman, Isabella Annesi-Maesano, Eva Corpeleijn, Harold Snieder, Cathrine Hoyo, Anke Hüls, Lea Sirignano, Stephanie H Witt, Gunda Herberth, Michelle Plusquin, Dana Dabelea, Edwina Yeung, Joseph L Wiemels, Rebecca C Richmond, Jack A Taylor, Janine F Felix, Siri E Håberg, Mariona Bustamante, Stephanie J London","doi":"10.1289/EHP16303","DOIUrl":"10.1289/EHP16303","url":null,"abstract":"<p><strong>Background: </strong>Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear.</p><p><strong>Objective: </strong>To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, paternal quitting before pregnancy).</p><p><strong>Methods: </strong>We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array.</p><p><strong>Results: </strong>Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] <0.05) at 8,862 CpGs on the 450K (n=8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (<i>MED13L</i>) was associated with paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues.</p><p><strong>Conclusions: </strong>Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking and paternal smoking. https://doi.org/10.1289/EHP16303.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"A new mouse model for ozone health effects research.","authors":"Gregory J Smith, Robert M Immormino, Martin T Ferris, Sarah A Lester, Timothy P Moran, Jack R Harkema, Samir N P Kelada","doi":"10.1289/EHP15745","DOIUrl":"10.1289/EHP15745","url":null,"abstract":"<p><strong>Background: </strong>Exposure to the ambient air pollutant ozone (O₃) is associated with adverse respiratory health outcomes. Rodent models have been used to identify mechanisms of response to O₃ but their utility has been questioned owing to species differences in physiologic response, most notably exposure-induced hypothermia, which renders rodents relatively resistant to O₃ compared to humans.</p><p><strong>Objectives: </strong>First, to test whether a recombinant inbred mouse strain from the Collaborative Cross population, CC002/Unc, provides a sensitive model of ozone response by benchmarking it to the most commonly used inbred strain, C57BL/6J. Second, to identify the genetic basis of CC002/Unc's sensitivity.</p><p><strong>Methods: </strong>We examined the responses of CC002/Unc and C57BL/6J mice to either acute (0.4 or 0.8 ppm O₃ x 4 hours) or repeated (0.8 ppm O₃ x 4 hours/day x 3 or 9 weekdays) O₃ exposure. Then, we mapped quantitative trait loci (QTL) for responses to 9 days of O₃ in a CC002/Unc x CC005/TauUnc (O₃-resistant) backcross population.</p><p><strong>Results: </strong>CC002/Unc was far more responsive to acute O₃ than C57BL/6J, exhibiting significant inflammation following a single 0.4 ppm O₃ exposure and greater inflammation and injury after 0.8 ppm O₃. Enhanced sensitivity of CC002/Unc mice was associated with decreased breathing frequency and diminished hypothermic responses. Following repeated exposure, C57BL/6J lungs appeared normal, while CC002/Unc lungs had eosinophilic inflammation and centriacinar fibrosis. We identified five QTLs for airway eosinophilia, including a large-effect QTL on chromosome 11 that accounted for 18% of phenotypic variation and contains genes with plausible links to aberrant immune responses.</p><p><strong>Discussion: </strong>The CC002/Unc strain provides an improved model to study the effects of acute and repeated O₃ exposure due to its enhanced sensitivity vs. C57BL/6J and more human-like thermoregulatory response. Further genetic analysis to pinpoint causal genes underlying CC002/Unc's susceptibility will provide new insights into mechanisms of O₃-induced lung disease. https://doi.org/10.1289/EHP15745.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Exposures to drinking water contaminants in community water systems and risk of ovarian cancer in the California Teachers Study cohort.","authors":"Maya Spaur, Lauren M Hurwitz, Danielle N Medgyesi, Alexander P Keil, Laura E Beane Freeman, Jared A Fisher, Jessica M Madrigal, Samantha Ammons, Emma S Spielfogel, Komal Bangia, Paul S Albert, Tiffany R Sanchez, James V Lacey, Rena R Jones, Mary H Ward","doi":"10.1289/EHP16582","DOIUrl":"https://doi.org/10.1289/EHP16582","url":null,"abstract":"<p><strong>Background: </strong>Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators.</p><p><strong>Methods: </strong>Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation.</p><p><strong>Results: </strong>Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HR_perlog2=1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HR_perlog2=1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype.</p><p><strong>Conclusions: </strong>Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation. https://doi.org/10.1289/EHP16582.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Association of Blood Lead with Cardiovascular Disease Incidence and Mortality: Findings from the Strong Heart Study Cohort.","authors":"Wil Lieberman-Cribbin, Anne E Nigra, Allison Kupsco, Arce Domingo-Relloso, Kathrin Schilling, Ying Zhang, Amanda M Fretts, Shelley Cole, Jason G Umans, Jeffery M Jarrett, Michael Lewin, Patricia Ruiz, Zheng Li, Ana Navas-Acien","doi":"10.1289/EHP16309","DOIUrl":"10.1289/EHP16309","url":null,"abstract":"<p><strong>Background: </strong>Evidence on lead and the burden of cardiovascular disease (CVD) derived from National Health and Nutrition Examination Survey (NHANES) data, a general sample of the U.S. population, lacks sufficient representation of American Indians. Moreover, there is limited prospective evidence on lead and incident CVD outcomes.</p><p><strong>Objectives: </strong>We evaluated if blood lead levels were associated with CVD mortality and incidence in American Indian adults from the Strong Heart Study (SHS).</p><p><strong>Methods: </strong>Whole blood samples collected in 1998-1999 among 1,818 participants was analyzed for lead using inductively coupled plasma mass spectrometry. CVD incidence and mortality were available through 2019. We used progressively adjusted multivariable Cox proportional hazards models to estimate the risk of composite CVD and coronary heart disease (CHD) mortality and incidence by baseline blood lead levels.</p><p><strong>Results: </strong>The median (p20, p80) blood lead was 22.5 (14.2, 37.3) µg/L, similar to that of a representative sample of US adults in NHANES 1999-2000. During follow-up, 578 (31.8%) participants had a composite CVD event and 454 (25.0%) participants had a CHD event. After adjustment for demographic, lifestyle, and cardiovascular risk factors, the hazard ratio (95% CI) per change across the 80^th to 20^th quantiles in blood lead was 1.15 (1.02-1.30) and 1.22 (1.08- 1.37) for CVD and CHD mortality, respectively, and 1.13 (1.02-1.24) and 1.12 (0.99-1.25) for CVD and CHD incidence, respectively. In flexible dose-response models, the associations appeared to be non-linear, with a clear increased risk of CVD and CHD mortality at blood lead concentrations above 35 µg/L.</p><p><strong>Discussion: </strong>Blood lead levels in American Indian adults, which are comparable to populations in the U.S. and globally, were associated with increased risk of CVD and CHD incidence and mortality. These findings highlight the importance of further reducing lead exposure, including American Indian communities. https://doi.org/10.1289/EHP16309.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Environmentally-relevant doses of bisphenol A and S exposure in utero disrupt germ cell programming across generations resolved by single nucleus multi-omics.","authors":"Liang Zhao, Mingxin Shi, Sarayut Winuthayanon, James A MacLean Ii, Nathan C Law, Kanako Hayashi","doi":"10.1289/EHP16981","DOIUrl":"10.1289/EHP16981","url":null,"abstract":"<p><strong>Background: </strong>Exposure to endocrine-disrupting chemicals (EDCs), such as bisphenol (BP) A, disrupts reproduction across generations. Germ cell epigenetic alterations are proposed to mediate these transgenerational defects. Previously, we have shown that prenatal exposure to environmentally relevant doses of BPA or its substitute, BPS, caused transgenerationally maintained reproductive impairments associated with neonatal spermatogonial epigenetic changes in male mice. However, the mechanisms sustaining these changes across generations remain unclear.</p><p><strong>Objectives: </strong>This study aimed to systematically elucidate the mechanism of transgenerational inherence by prenatal BPA and BPS exposure in the murine germline from F1 to F3 generations at both transcriptomic and epigenetic levels.</p><p><strong>Methods: </strong>Pregnant CD-1 females (F0) were orally administered BPA or BPS at doses of 0 (vehicle control), 0.5, 50, or 1000 µg/kg/b.w./day from gestational day 7 to birth. Sperm counts and motility were examined in F1, F2, and F3 adult males. THY1⁺ germ cells on postnatal day 6 from F1, F2, and F3 males at a dose of 50 µg/kg/b.w./day were used for analysis by single-nucleus (sn) multi-omics (paired snRNA-seq and snATAC-seq on the same nucleus).</p><p><strong>Results: </strong>Prenatal exposure to BPA and BPS with 0.5, 50, and 1000 µg/kg/b.w./day reduced sperm counts in mice across F1 to F3 generations. In the F1 generation, BPA or BPS exposure with 50 µg/kg/b.w./day disrupted the balance between maintaining the undifferentiated and differentiating spermatogonial populations. Differentially accessible peaks (DAPs) by snATAC-seq were primarily located in the promoter regions, with elevated activity of key transcription factors, including SP1, SP4, and DMRT1. Notably, similar gene expression and chromatin changes were observed in directly exposed F1 and F2 generations but differed in the indirectly exposed F3 generation. Approximately 80% of DAPs in F1 and F2 spermatogonia overlapped with histone post-translational modifications linked to transcription activation (e.g., H3K4me1/2/3 and H3K27ac). Across F1 to F3 generations, although BPA exerted more potent effects on gene expression in F1 spermatogonia, BPS induced longer-lasting effects. Interestingly, DMRT1 motif activity was persistently elevated in all three generations following ancestral BPA or BPS exposure.</p><p><strong>Discussion: </strong>Our work provides the first systematic analyses of transgenerational gene and chromatin dynamics following prenatal exposure to BPA or BPS. These results suggest that prenatal exposure to environmentally relevant doses of BPA or BPS alters chromatin accessibility and transcription factor motif activities, consequently contributing to disrupted transcriptional levels in neonatal spermatogonia, and some are sustained to F3 generations, ultimately leading to the reduction of sperm counts in adults. https://doi.org/","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Time-varying exposure to element mixtures and children's cognition at 5 years of age: findings from the New Hampshire Birth Cohort Study.","authors":"Leyre Notario Barandiaran, Julie A Bauer, Hannah E Laue, Antonio J Signes-Pastor, Brian P Jackson, Janet L Peacock, Juliette Madan, David C Bellinger, Susan Korrick, Margaret R Karagas","doi":"10.1289/EHP16752","DOIUrl":"10.1289/EHP16752","url":null,"abstract":"<p><strong>Background: </strong>Exposure to metals and metalloids (hereafter referred to as 'metals') during gestation and early childhood may affect children's neurodevelopment. However, few studies have simultaneously evaluated the impact of exposure to both essential and non-essential metals across specific windows of exposure on children's neurodevelopmental outcomes.</p><p><strong>Objective: </strong>To investigate whether levels of metals during gestation and the early postnatal period, individually and as a mixture, are related to child cognition at 5 years of age among participants in the New Hampshire Birth Cohort Study (NHBCS).</p><p><strong>Methods: </strong>We followed 278 NHBCS pregnancy-offspring dyads up to approximately 5 years of age. Total arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) were measured in toenail samples collected from pregnant persons at ~24 to 28 weeks of gestation (representing periconception and early pregnancy), and at ~6 weeks postpartum (representing mid-pregnancy), and their infants at ~6 weeks of age (representing early infancy). Cognitive development at 5 years was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) which includes measures of full-scale intelligence quotient (FSIQ) and five composite indices. Associations between ln-metal toenail concentrations across multiple exposure windows and the six WPPSI-IV scores were estimated through mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR). Potential effect modification by other elements in the mixture as well as sex were further explored.</p><p><strong>Results: </strong>Biomarkers of As exposures of periconception and early pregnancy, mid-pregnancy and early infancy were associated with lower cognitive scores at 5 years of age (e.g., FSIQ: -0.16 (95% Credible Interval (CrI): -0.24, -0.08) SD change). Periconception and early pregnancy exposures to Mn and Cu were associated with higher child cognitive scores. Sex differences were observed, especially with Mn exposure, with stronger positive associations among males during periconception and early pregnancy and among females during mid-pregnancy. For Pb and Zn exposures, associations with cognitive scores differed across exposure windows, exhibiting both positive and negative associations.</p><p><strong>Discussion: </strong>By evaluating multiple essential and non-essential elements across the three previously mentioned exposure windows, we found evidence of sensitive periods of susceptibility to child cognitive measures. While results for As indicated detrimental effects, those for Cu and Mn suggested beneficial trends across all exposure windows. https://doi.org/10.1289/EHP16752.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}