Environmental Health Perspectives最新文献

{"title":"Systematic Evidence Map for the Per- and Polyfluoroalkyl Substances (PFAS) Universe.","authors":"Avanti V Shirke, Elizabeth G Radke, Ryan Jones, Barrett D Allen, Cynthia J Lin, Amanda Ross, Nicole Vetter, Courtney Lemeris, Pamela Hartman, Sorina Eftim, Arun Varghese, Robyn Blain, Heidi Hubbard, Antony J Williams, Kristina A Thayer, Laura M Carlson","doi":"10.1021/EHP.6c00127","DOIUrl":"10.1021/EHP.6c00127","url":null,"abstract":"<p><p><b>BACKGROUND:</b> Per- and polyfluoroalkyl substances (PFAS) are a research priority for the U.S. Environmental Protection Agency (EPA). Because PFAS include thousands of structurally diverse chemicals, there is a pressing need for identifying what data are available to assess the human health hazard of these compounds. <b>OBJECTIVES:</b> We used systematic evidence map (SEM) methods to summarize the available epidemiological and mammalian bioassay evidence for ∼14,735 chemicals identified as PFAS by EPA's Center for Computational Toxicology and Exposure (CCTE). This work is a continuation of our previous 2022 and 2024 SEMs that inventoried evidence on a separate set of ∼500 PFAS. The Comprehensive PFAS Dashboard includes evidence identified from our past SEMs and completed EPA assessments. <b>METHODS:</b> We conducted literature searches from peer-reviewed and gray literature sources to identify, screen, and inventory mammalian bioassay and epidemiological literature. A combination of manual review and machine learning software were utilized. A diverse array of potentially relevant supplemental content was also tracked, including mechanistic data, exposure-only studies, and studies informing chemical toxicokinetics and clearance. For each study meeting predefined population, exposure, comparator, and outcome (PECO) criteria, experimental design details and health end points evaluated were summarized in interactive web-based literature inventory visuals. Epidemiology studies and animal bioassay studies with ≥21-day exposure duration or reproductive/developmental study design proceeded to undergo a study evaluation for risk of bias and sensitivity, as well as detailed extraction of health end point data. Underlying data are publicly available and can be downloaded. <b>RESULTS:</b> Scientific database searches retrieved 152,205 references. After full-text screening, there were 347 mammalian bioassay and 44 epidemiological studies that met PECO criteria. The mammalian bioassay and epidemiological evidence assessed 99 and 30 individual PFAS, respectively (<i>n</i> = 18 PFAS with both). The epidemiological evidence assessed 15 health systems and the mammalian bioassay evidence assessed 16 health systems. <b>DISCUSSION:</b> Results from our 2022 and 2024 SEMs and completed EPA assessments are compiled into Comprehensive PFAS Dashboard. This dashboard is a resource for better understanding the currently available PFAS human health hazard data. It can be used as a tool for researchers and regulators interested in PFAS data gaps and research needs. Across all the data sources compiled into the Comprehensive PFAS Dashboard, only 1.4% (214/14,735) of PFAS had any mammalian bioassay or epidemiological data available. The vast majority of PFAS lack publicly available information about the potential human health effects of exposure to these chemicals.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 3","pages":"252-273"},"PeriodicalIF":10.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419786","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":"Workflow for Statistical Analysis of Environmental Mixtures.","authors":"Bonnie R Joubert, Glenn Palmer, David Dunson, Marianthi-Anna Kioumourtzoglou, Brent A Coull","doi":"10.1021/EHP.6c00155","DOIUrl":"10.1021/EHP.6c00155","url":null,"abstract":"<p><p><b>BACKGROUND</b>: Human exposure to complex, changing, and variably correlated mixtures of environmental chemicals has presented analytical challenges to epidemiologists and human health researchers. There has been a wide variety of recent advances in statistical methods for analyzing mixtures data, with most methods having open-source software for implementation. However, there is no one-size-fits-all method for analyzing mixture data given the considerable heterogeneity in scientific focus and study design. For example, some methods focus on predicting the overall health effect of a mixture and others seek to disentangle main effects and pairwise interactions. Some methods are only appropriate for cross-sectional designs, while other methods can accommodate longitudinally measured exposures or outcomes. <b>OBJECTIVES</b>: This article focuses on simplifying the task of identifying which methods are most appropriate to a particular study design, data type, and scientific focus. <b>METHODS</b>: We present an organized workflow for statistical analysis considerations in environmental mixtures data and two example applications implementing the workflow. This systematic strategy builds on epidemiological and statistical principles, considering specific nuances for the mixtures' context. We also present an accompanying methods repository to increase awareness of and inform application of existing methods and new methods as they are developed. <b>DISCUSSION</b>: We note several methods may be equally appropriate for a specific context. This article does not present a comparison or contrast of methods or recommend one method over another. Rather, the presented workflow can be used to identify a set of methods that are appropriate for a given application. Accordingly, this effort will inform application, educate researchers (e.g., new researchers or trainees), and identify research gaps in statistical methods for environmental mixtures that warrant further development.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 1","pages":"8-22"},"PeriodicalIF":10.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962727","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":"Effect of Household Air Pollution on the Gut Microbiome and Virome of Adult Women Living in Uganda.","authors":"Ching-Ying Huang, Edwin Nuwagira, Michael Tisza, Minsik Kim, Mellon Tayebwa, Jacob Vieira, Nicholas Lam, Eli Wallach, Matthew Wiens, Alexander C Tsai, Linda Valeri, Jose Vallarino, Joseph G Allen, Peggy S Lai","doi":"10.1021/EHP.6c00064","DOIUrl":"10.1021/EHP.6c00064","url":null,"abstract":"<p><p><b>BACKGROUND:</b> Emerging observational studies suggest that air pollution can influence the gut microbiome. However, this association is often highly confounded by factors, such as diet and poverty. The gut virome may influence respiratory health independent of the gut microbiome. We recently demonstrated in a randomized waitlist-controlled trial (ClinicalTrials.gov NCT03351504) that a clean lighting intervention reduced the level of personal exposure to air pollution among adult women in rural Uganda. <b>OBJECTIVES:</b> To determine the effect of a solar lighting intervention on changes to the gut microbiome and virome and secondarily to determine the association between these changes on lung health. <b>METHODS:</b> Between 2018 and 2019, we collected stool samples and assessed respiratory symptoms and spirometry from 80 adult women living in rural Uganda at baseline and 12 and 18 months postrandomization. The intervention group received a solar lighting system after randomization, while the waitlist-controlled group received one at 12 months. Deep metagenomics sequencing of stool was performed and profiled for nonviral and viral taxonomic composition. The primary analysis focused on pre- vs postintervention changes due to power considerations, adjusting for potential confounding by age, diet, antibiotic use, and season. A sensitivity analysis was conducted using intention-to-treat principles. When comparing pre- vs postintervention periods, we used sparse partial least-squares models to identify nonviral and viral signatures of reduced air pollution exposure. Mixed effects models were used to evaluate changes in health outcomes as well as associations between microbial signatures of reduced air pollution exposure and health. <b>RESULTS:</b> The average age was 39.2 years. The solar lighting intervention led to larger changes in viral compared to nonviral microbial community structure and differential abundance of bacteria, eukaryotes, and viruses. Provision of solar lighting systems was associated with a reduction in the presence of respiratory symptoms from 57.1% to 36.1% (<i>p</i> = 0.002), while there was no impact on lung function. Microbiome and virome signatures had AUCs of 0.74 and 0.76, respectively, in predicting pre- vs postintervention stool samples. Microbiome signatures were associated with a lower risk of respiratory symptoms (OR = 0.68 (0.49 - 0.94), <i>p</i> = 0.020). <b>CONCLUSION:</b> Among adult women living in rural Uganda, both nonviral and viral components of the gut microbial community changed after a clean lighting intervention. Microbiome signatures reflective of lower air pollution exposures were associated with improved respiratory symptoms. These observations suggest that air pollution may influence lung health through the gut-lung axis, warranting further exploration in future intervention studies.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 1","pages":"75-90"},"PeriodicalIF":10.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962576","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":"Pesticide Exposure Estimation across Census Tracts in Washington State: Identifying Vulnerable Areas and Populations.","authors":"Solmaz Amiri, Jeffrey M Bryant, Daniel H Farber, Ofer Amram, Jennifer C Sabel","doi":"10.1021/EHP.6c00073","DOIUrl":"10.1021/EHP.6c00073","url":null,"abstract":"<p><strong>Introduction: </strong>Disparities in exposure to and harm associated with pesticides are established. However, high resolution spatial data on exposure to pesticides are lacking.</p><p><strong>Purpose: </strong>To describe the development of a pesticide metric for Washington State and to evaluate the associations between pesticide exposure and sociodemographic characteristics of census tracts.</p><p><strong>Methods: </strong>We used the US cropland data set to quantify the location and size of agricultural land. These data were overlaid with state- and county-level estimated annual agricultural pesticide use to estimate pesticide exposure at the census tract level. Sociodemographic characteristics of census tracts were from the US Centers for Disease Control and Prevention's Social Vulnerability Index (SVI). Generalized additive models evaluated the associations between pesticide exposure and each of the SVI variables.</p><p><strong>Results: </strong>The median exposure to pesticides was 1.5 lbs/sq mi. Significant associations were observed between exposure to pesticides and a higher percentage of population below poverty, populations unemployed, populations 65 and older, non-Hispanic white populations, those with limited English language proficiency, mobile homes, and group quarters.</p><p><strong>Conclusions: </strong>The results inform public health and policy efforts to identify areas and populations that are most vulnerable to pesticide exposure and improve the health and well-being of farmworkers and populations residing near agricultural areas.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 3","pages":"303-311"},"PeriodicalIF":10.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419617","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":"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":"10.1021/EHP.6c00062","DOIUrl":"10.1021/EHP.6c00062","url":null,"abstract":"<p><strong>Background: </strong>The field of environmental health sciences increasingly demands comprehensive and diverse data sets, 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 data sets 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.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 3","pages":"240-251"},"PeriodicalIF":10.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419706","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":"Mobilization of the Environmental Toxicant Chlorpyrifos during Weight Loss and Its Impact on Liver and Adipose Tissue Metabolism in Mice.","authors":"Yifan Xiang, Gaojian Tang, Xiaohu Hu, Xiaoxiao Yu, Yanrong Feng, Zhongzuo Huang, Yicheng Luo, Zongyou Jiang, Yue Lv, Xiaoying Sun, Yan Zhang, Long Cheng, Yu Xin, Yuxin Qian, Boyu Li, Bo Wang","doi":"10.1021/EHP.6c00042","DOIUrl":"10.1021/EHP.6c00042","url":null,"abstract":"<p><strong>Background: </strong>Fat-soluble toxicants, such as chlorpyrifos (CPF) can accumulate in adipose tissue and the liver. During weight loss, these compounds may be released into the circulation, but the metabolic consequences of this mobilization remain poorly understood.</p><p><strong>Objectives: </strong>This study aimed to investigate the mobilization of CPF during weight loss and its effects on liver health and adipose tissue metabolism in mice.</p><p><strong>Methods: </strong>C57BL/6J mice were fed a high-fat diet (HFD) or a low-fat diet (LFD) and exposed to 2 mg/kg BW/day CPF by oral gavage. Weight loss was induced by β3-adrenergic stimulation (CL316243) or treadmill exercise for 4 or 10 weeks. CPF was quantified in serum and tissues using HPLC. Tissue histology, expression of genes related to CPF metabolism, liver injury markers, and metabolic protein levels were assessed.</p><p><strong>Results: </strong>CPF-exposed LFD mice showed more severe liver fibrosis and adipose inflammation than did their HFD counterparts. While obese mice had lower adipose CPF concentrations, they showed higher hepatic accumulation. CPF-exposed weight loss mice had higher levels of CPF in adipose tissue, liver, and brain and higher expression of CPF metabolism-related genes, including Paraoxinase-1 and cytochrome P450 genes, and greater glucose intolerance compared to their counterparts without CPF administration. Molecular analyses revealed suppressed AMPK signaling and P62 accumulation, indicating mitophagy disruption in CPF-exposed mice after weight loss. These effects occurred even at human-relevant low doses (0.45 mg/kg of BW/day) and persisted across sexes.</p><p><strong>Discussion: </strong>Weight loss mobilizes CPF and its metabolites from fat stores, leading to tissue accumulation and damage. Even low-dose exposure contributes to hepatic and metabolic disruption in mice, highlighting the potential risk of toxicant mobilization during fat reduction.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 3","pages":"274-288"},"PeriodicalIF":10.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419683","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, 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":"10.1021/EHP.6c00142","DOIUrl":"https://doi.org/10.1021/EHP.6c00142","url":null,"abstract":"<p><p><b>BACKGROUND</b>: 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. <b>OBJECTIVE</b>: 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, and paternal quitting before pregnancy). <b>METHODS</b>: 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 for maternal SHS and smoking during pregnancy. Primary analyses used Illumina450 K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. <b>RESULTS</b>: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] < 0.05) at 8,862 CpGs on the 450 K (<i>n</i> = 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 former paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (<i>n</i> = 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. <b>CONCLUSIONS</b>: 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.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 3","pages":"289-302"},"PeriodicalIF":10.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419744","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":"Comparison of Temperature-Mortality Associations across the Middle East Using Different Exposure Estimation Approaches.","authors":"Yazan Alwadi, Barrak Alahmad, Marc G Weisskopf, Petros Koutrakis","doi":"10.1021/EHP.6c00063","DOIUrl":"10.1021/EHP.6c00063","url":null,"abstract":"<p><p><b>BACKGROUND:</b> Traditional temperature-health studies have predominantly relied on temperature measurements from stations or modeled spatial averages from gridded temperature data sets. It has been suggested that population-weighted spatial averages would perform better in remote regions with large temperature and population variability. This would be particularly true in regions other than North America and Europe where outcome data are often only available on a crude spatial scale, but no studies have examined this in such regions, where temperatures can be particularly hot. <b>OBJECTIVE:</b> Using the Middle East as a climate hotspot, our objective was to illustrate the utility of population weighting temperature exposures in understudied regions with large health data aggregation areas. <b>METHODS:</b> We used a daily 1 km × 1 km temperature data set for 152 administrative regions in 12 Middle Eastern countries. From 2003 to 2020, for each administrative region, we computed daily minimum and maximum population-weighted and unweighted spatial average temperatures. To illustrate, we examined temperature-mortality associations in two countries: Kuwait and Jordan. We used distributed lag nonlinear models to estimate the daily time series temperature-mortality associations in using three temperature exposure measurement approaches: station temperatures, unweighted spatial averages, and population-weighted temperatures. For each scenario, we fitted country-specific optimized parameters and compared them using three metrics: 1) exposure-response relationships, 2) minimum mortality temperatures, and 3) attributable mortality estimates. <b>RESULTS:</b> The study region had geographically sporadic yet densely populated areas within each country. In both Kuwait and Jordan, population-weighted and unweighted spatial average temperatures resulted in fairly similar exposure-response curves, whereas both were notably different from station temperatures. Minimum mortality temperatures were 30.2, 28.6, and 28.3 °C in Kuwait for station, unweighted spatial average, and population-weighted temperatures, respectively. In Jordan, the corresponding temperatures were 20.6, 20.9, and 20 °C. Heat attributable mortality calculated using population-weighted temperatures increased by 15% compared to the traditionally used station temperatures in Kuwait and Jordan, respectively, and -0.4% and 5% compared to unweighted spatial average temperatures. <b>DISCUSSION:</b> Spatial averaging, whether weighted or unweighted, is a valuable tool for estimating heat-attributable mortality. This is especially true in regions like the Middle East, where granular temperature data are often unavailable and health studies are urgently needed. Population-weighted temperatures may better capture localized exposures in areas with significant population clustering, though their exact added effect on top of unweighted spatial averages remains a tentative conclusion.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 1","pages":"67-74"},"PeriodicalIF":10.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962627","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":"Evaluating the Effects of Neburon Exposure on Ovarian Folliculogenesis Using Zebrafish and Mouse Granulosa Cell Line.","authors":"Chen Tang, Ying Zhang, Fucong Zhang, Yiwen Sun, Yue Zhu, Fanzheng Xue, Zhenhong Wang, You Wu, Jinpeng Ruan, Yiming Yue, Chunyan Yang, Wei Ge, Chengyong He, Zhenghong Zuo","doi":"10.1021/EHP.6c00111","DOIUrl":"10.1021/EHP.6c00111","url":null,"abstract":"<p><p><b>BACKGROUND</b>: Ovarian folliculogenesis is crucial for female reproduction. This can be disrupted by various factors, including pollutants with aryl hydrocarbon receptor (AHR) agonistic activity, but the underlying mechanisms remain unclear. <b>OBJECTIVES</b>: Using the herbicide neburon, a moderate AHR agonist among current pesticides, we investigated its effects on ovarian folliculogenesis in zebrafish through life-cycle exposure at environmentally relevant concentrations to elucidate the associated mechanisms. <b>METHODS</b>: Wild-type (WT) and three different genotypes of female zebrafish (<i>amh</i> ^±;<i>bmpr2a</i> ^+/+, <i>amh</i> ^+/+;<i>bmpr2a</i> ^±, <i>amh</i> ^±;<i>bmpr2a</i> ^±) were exposed to neburon for 150 days. Neburon and its metabolites in fish were quantified using LC-MS/MS. Ovarian pathology was assessed by H&E and TUNEL staining. The differentially expressed pathways were identified by transcriptome analysis, followed by validation using RT-qPCR, WB, IHC, and ELISA. Finally, AHR antagonist, ChIP-RT-qPCR, and other methods were used to further elucidate the mechanism in mouse granulosa cell line (KK1). <b>RESULTS</b>: After neburon exposure, only four metabolites of neburon were detected but not the metabolite itself, and all these metabolites had AHR agonistic activity, indicating the persistent toxicity of neburon. Neburon exposure altered the follicle-stage distribution and poorer oocyte quality in WT zebrafish. Further experiments found that neburon exposure induced greater secretion of anti-Mullerian hormone (Amh), greater expression of genes in the Amh/Bmpr2a pathway, accelerated follicular development, and lower expression of insulin-like growth factors, which was associated with oocyte atresia. Notably, <i>amh</i> ^±;<i>bmpr2a</i> ^± zebrafish showed a rescued phenotype with regard to these neburon-associated outcomes. Moreover, AHR exhibited specific binding to the <i>Amh</i> promoter in KK1 cells, and neburon treatment enhanced their interaction. <b>DISCUSSION</b>: In zebrafish, AMH was identified as a critical target for reproductive disorders following neburon exposure. Despite the short half-lives of the currently used pesticides, their metabolites might still have significant toxicological risks. This study provides novel insight into how one AHR agonistic pollutant affects female zebrafish reproduction.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 1","pages":"91-109"},"PeriodicalIF":10.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962654","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":"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, Julia 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":"10.1021/EHP.6c00030","DOIUrl":"10.1021/EHP.6c00030","url":null,"abstract":"<p><p><b>BACKGROUND</b>: 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 nonessential metals across specific windows of exposure on children's neurodevelopmental outcomes. <b>OBJECTIVE</b>: 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). <b>METHODS</b>: We followed 278 NHBCS pregnancy-offspring dyads for 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 midpregnancy), 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 the 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 was further explored. <b>RESULTS</b>: Biomarkers of As exposures of periconception and early pregnancy, midpregnancy, 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 midpregnancy. For Pb and Zn exposures, associations with cognitive scores differed across exposure windows, exhibiting both positive and negative associations. <b>DISCUSSION:</b> By evaluating multiple essential and nonessential 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.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"134 1","pages":"41-52"},"PeriodicalIF":10.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962746","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}