Environmental Health Perspectives最新文献

{"title":"Long-Term Exposure to\u0000Environmental Mixtures and Risk\u0000of Type 2 Diabetes in Three U.S. Prospective Cohorts","authors":"Jie Chen,Jaime E. Hart,Melissa R. Fiffer,Peter James,Liming Liang,Jonathan S. Williams,Qi Sun,Francine Laden","doi":"10.1021/ehp.6c01287","DOIUrl":"https://doi.org/10.1021/ehp.6c01287","url":null,"abstract":"Abstract Aims/hypothesis: To examine the risk of type 2 diabetes (T2D) associated with long-term simultaneous exposure to air pollution, noise, surrounding greenness, and neighborhood socioeconomic status (SES), in three U.S. adult prospective cohorts. Methods: We followed 235,101 health professionals from June 1992/1993 to T2D diagnosis, loss to follow-up, death, or May 2018/2019. Time-varying address-level exposures to modeled fine particles (PM2.5), nitrogen dioxide (NO2), nighttime noise, satellite-based greenness, and Census tract-level neighborhood SES were appended. We applied Cox proportional hazards models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident T2D associated with environmental exposures, individually and collectively, adjusting for potential confounders. We used quantile g-computation to assess the joint association of the exposure mixture. Analyses were performed in individual cohorts and meta-analyzed using random-effects models. Results: We observed 22,029 incident T2D cases over 26 years of follow-up. In single-exposure models, T2D risk was (borderline) positively associated with PM2.5, NO2, and noise, and negatively associated with greenness and neighborhood SES. In multiexposure models, PM2.5 and NO2 associations attenuated and included unity, while greenness, noise, and neighborhood SES associations persisted: HRs (95% CIs) per interquartile range (IQR) increase were 1.05 (0.97–1.13), 0.99 (0.94–1.03), 0.96 (0.93–0.98), 1.04 (1.02–1.06), and 0.92 (0.88–0.97), respectively. The joint association derived from quantile g-computation for one IQR change across the mixture was 1.25 (1.15–1.35). Conclusions/interpretation: Simultaneous exposure to greater noise, lower greenness, and less advantaged neighborhoods was associated with increased T2D risk, whereas air pollution showed an inconsistent association.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"24 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209761","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":"Per- and Polyfluoroalkyl\u0000Substances Are Associated\u0000with Increased Vasomotor Symptom Prevalence and Incident Occurrence\u0000among Midlife Women in the United States","authors":"Jiaxin Wu,Wenzhiyuan Zhang,Rachael A. Brooks,Carrie A. Karvonen-Gutierrez,Xin Wang,Zhenke Wu,Bhramar Mukherjee,John F. Randolph,Ellen B. Gold,Siobán D. Harlow,Sung Kyun Park","doi":"10.1021/ehp.6c00592","DOIUrl":"https://doi.org/10.1021/ehp.6c00592","url":null,"abstract":"Abstract Vasomotor symptoms (VMS), including hot flashes and night sweats, are frequently reported by women during the menopause transition. Per- and polyfluoroalkyl substances (PFAS) are linked to elevated follicle-stimulating hormone, decreased estrogen, and earlier menopause, but their associations with VMS remain unexplored. This study assessed individual PFAS levels and their patterns in association with prevalent and incident VMS using data from 1,400 women aged 45−56 years at baseline PFAS measurement in the Study of Women’s Health Across the Nation (1999−2000), who were followed through 2016. VMS were defined as any hot flashes or night sweats reported in the previous 2 weeks at each visit. Serum concentrations of seven PFAS with high detection rates (>96%) were included. Multiple imputation was used to impute missing values in covariates and left-truncation weights. Modified Poisson regression estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) in cross-sectional analyses; weighted interval-censored accelerated failure time models with a Weibull distribution computed time ratios (TRs), which were converted to hazard ratios (HRs) and 95% CIs in longitudinal analyses. Three clusters of participants with distinct PFAS exposure profiles (low-, medium-, or high-exposure patterns across all measured PFAS) were identified using k-means clustering and evaluated in relation to VMS prevalence and incidence. Adjusting for baseline sociodemographic, behavioral, psychosocial, and clinical factors, a doubling of linear perfluorooctanoic acid (n-PFOA) and 2-(N-methyl-perfluorooctane sulfonamido)acetic acid (MeFOSAA) was associated with modestly higher VMS prevalence (n-PFOA: PR = 1.05, 95% CI: 1.01−1.09; MeFOSAA: PR = 1.03, 95% CI: 1.01−1.06) and incidence (n-PFOA: HR = 1.11, 95% CI: 1.05−1.16; MeFOSAA: HR = 1.07, 95% CI: 1.03−1.11). Results of dose−response analyses indicated an increasing hazard of VMS occurrence with higher concentrations of several PFAS. Analyses using clusters indicated that women with medium PFAS exposure patterns had higher VMS prevalence and incidence compared to the low exposure group (PR = 1.13, 95% CI: 1.06−1.22; HR = 1.27, 95% CI: 1.17−1.39). Women with high exposure patterns had modestly higher VMS incidence and prevalence (PR = 1.10, 95% CI: 1.01−1.20; HR = 1.14, 95% CI: 1.02−1.28). These findings suggest that certain PFAS may increase VMS prevalence and accelerate the onset of VMS, potentially influencing quality of life in midlife women.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"35 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209751","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":"Shifting Dominant Air\u0000Pollution Sources in Sub-Saharan\u0000Africa’s Changing Urban Environment: Analysis of Elemental\u0000Composition and Source Contributions of Ambient Fine Particulate Matter\u0000(PM2.5) Pollution in Accra, Ghana","authors":"Carissa L. Lange,Aaron J. Specht,Abosede S. Alli,Sierra N. Clark,James Nimo,Thomas Grier,Raji Balasubramanian,Michael Brauer,Allison F. Hughes,Majid Ezzati,Raphael E. Arku","doi":"10.1021/ehp.6c00323","DOIUrl":"https://doi.org/10.1021/ehp.6c00323","url":null,"abstract":"Abstract Urban and economic expansion across Sub-Saharan Africa (SSA) may be shifting the relative contributions of dominant ambient air pollution sources, influencing both pollutant concentrations and composition, along with their associated health risks. However, city-scale data on the composition and source contributions are scarce, hindering source- and sector-specific policy interventions. Using samples from a large-scale, citywide monitoring campaign, we characterized the elemental composition and source contributions of PM2.5 pollution across the Accra metropolis, a major SSA city. From April 2019 to June 2020, we collected over 600 weekly gravimetric (filter-based) PM2.5 samples from 146 unique sites spanning diverse land-use across the city. Filters were analyzed for several elements using energy dispersive x-ray fluorescence (ED-XRF), and positive matrix factorization (PMF) was applied to identify major sources, and changes in their relative contributions, at four legacy sites from a decade prior (2007-2008). Concentrations of elements associated with biomass burning (K, Br, Pb) and vehicle emissions (Ti, Fe, Cu, Zn) were highest in high-density residential and heavily trafficked areas, respectively. There was strong temporal variation in several elements (Al, Si, Fe, Ti, K, Ca, Mn) across seasons, with elevated concentrations during the dusty Harmattan season, when crustal dust accounted for 52-68% of total elemental PM2.5 mass. In the non-Harmattan period, we identified 4-6 major sources including biomass burning (comprising 11-32% of total PM2.5 elemental mass), traffic emissions and road dust (9-36%), solid and electronic waste combustion (0-35%), construction dust (0-30%), crustal dust (11-47%), and sea salt (8-67%). Compared to a decade prior, the contribution from biomass burning to overall PM2.5 has decreased by ∼16% (95% CI: 5.2-25.8; p-value = 0.017). Contrarily, the composite traffic/road dust factor remained stable, though increasing traffic emissions may have been offset by declining road-dust contributions. Most notably, contributions from solid and electronic waste burning have risen significantly (mean difference = 23%; 95% CI: 15.9-30.0; p-value = 0.002) to levels approaching those of biomass burning and traffic-related sources at legacy sites. Our findings indicate that household biomass use remains a dominant source of PM2.5 in Accra, although its relative contribution appears to have declined. This reduction may be partially offset by increasing contributions from solid and electronic waste burning in many locations. These shifts in PM2.5 composition and relative source contributions underscore the need for source- or sector-specific policy actions in the region.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"28 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150853","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":"Deep Learning on Satellite\u0000Imagery Reveals Landscape\u0000Drivers of Metabolic Syndrome","authors":"Ruizhe Chen,Zehui Xue,Kang Fu,Yu Zhang,Bing Wu,Jie Wu,Lanjuan Li","doi":"10.1021/ehp.6c00354","DOIUrl":"https://doi.org/10.1021/ehp.6c00354","url":null,"abstract":"Abstract Background: Understanding how environmental contexts influence metabolic syndrome (MetS) is limited by conventional exposure metrics that fail to capture complex, visually perceived neighborhood features. We aimed to develop a satellite-based deep learning framework to characterize fine-scale environmental exposures and examine their associations with MetS. Methods: We developed VISTAnet to extract latent geographic features from 49,050 high-resolution satellite images and identified eight landscape types through unsupervised clustering. 1,34,675 adults from Deqing, China, were included in this study. For each participant, environmental exposure was quantified as the Isochrone Landscape Proportion (ILP) within a 15 min walking isochrone around the residence. Associations between ILP and MetS were evaluated using mixed-effects logistic regression models. Stratified analyses were conducted by age, sex, educational level, employment status, and community type, and sensitivity analyses were conducted to assess the robustness of the findings. Results: Greater exposure to nature-dominated environments was associated with lower odds of MetS. Participants in the highest exposure quartile had significantly lower odds of having MetS for Dense Vegetation (adjusted odds ratio [aOR] 0.818, 95% CI 0.728–0.918), Wetland (0.941, 0.901–0.983), and Dry Farmland (0.838, 0.798–0.881). In contrast, higher exposure to Dense Residential Area (1.101, 1.058–1.145) and Industrial Zone (1.203, 1.151–1.257) was associated with increased odds of MetS. Findings were robust in sensitivity analyses. Conclusions: Nature-dominated landscapes were linked to lower MetS risk, whereas dense residential and industrial environments were linked to higher risk. This framework may support scalable environmental health assessment and health-oriented urban planning.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"53 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150854","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 Health Impacts of\u0000the January 2025 Los Angeles\u0000Wildfires among Unhoused Communities","authors":"Evan Michael Shannon,Jessie Chien,Benjamin F. Henwood,Randall Kuhn","doi":"10.1021/ehp.6c00626","DOIUrl":"https://doi.org/10.1021/ehp.6c00626","url":null,"abstract":"Abstract The impact of the devastating January 2025 Los Angeles (LA) County wildfire and extreme wind event (“firestorm”) on the health trajectory of people experiencing homelessness (PEH) is unknown. The study objective was to determine the health and social impacts of the firestorm on PEH in LA County. We analyzed data from the Periodic Assessment of Trajectories of Housing, Homelessness, and Health Study (PATHS), an ongoing longitudinal monthly panel survey of roughly 500 PEH in LA County. We administered survey questions on firestorm exposure 2 weeks after the firestorm began. We conducted analyses to assess relationships between sociodemographic factors and firestorm exposure and performed difference-in-differences analyses using mixed-effects logistic regression models to determine associations between firestorm exposure variables and self-reported health, controlling for sociodemographic variables. Of the 534 active PATHS participants, 403 were included in the primary analytic sample. 55.6% of survey participants reported disruption from the firestorm. Non-Hispanic Black/African American respondents had higher odds of reporting disruption compared to non-Hispanic White respondents (aOR = 2.24, 95% CI: 1.16–4.40), as did those who were primarily unsheltered (aOR = 4.43, 95% CI: 2.70–7.40) or displaced (aOR = 2.75, 95% CI: 1.68–4.56) in the past month. Difference-in-differences analyses found no consistent evidence of associations between firestorm-related disruption and subsequent outcomes, with confidence intervals for all estimates spanning the null. Our findings suggest that unsheltered PEH were especially vulnerable to the firestorm but that the firestorm did not significantly affect longitudinal measurements of self-reported health, which were already poor at baseline.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"25 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090719","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":"Wildfire-Emitted Particulate\u0000Matter Induces Ovarian\u0000Hyperandrogenism through Aryl Hydrocarbon Receptor Activation","authors":"Kuhelika Mali,Delong Zhang,Lila Bazina,Kunlin Ou,Elena Abramova,Jiyang Zhang,Tingjie Zhan,Pawat Pattarawat,Constantinos Moularas,Congcong Zhang,Qiang Zhang,Audrey J. Gaskins,Andrew Gow,Philip Demokritou,Shuo Xiao","doi":"10.1021/ehp.6c00189","DOIUrl":"https://doi.org/10.1021/ehp.6c00189","url":null,"abstract":"Abstract Wildfires have become more frequent and intense worldwide, and this trend is projected to continue in the coming years. Wildfire-emitted particulate matter (WFPM) can be more toxic than urban background PM due to its greater content of nanosized PM (WFPM0.1) and more polar organic compounds, including polycyclic aromatic hydrocarbons (PAHs). While exposure to WFPMs has been linked to cardiovascular and respiratory diseases, their impact on female reproductive health remains elusive. We examined the female reproductive impacts of lab-synthesized (LS-) and real-world Canadian WFPM0.1 (C-WFPM0,1) collected during the June 2023 Canadian wildfires and investigated the toxic mechanisms involved. An in vivo mouse model through intratracheal exposure and a 3D in vitro ovarian follicle culture system, together with molecular, transcriptomic, and computational approaches, was used to examine the ovarian disrupting effects of LS- and C-WFPM0.1. Intratracheal in vivo exposure to an environmentally relevant dose of LS-WFPM0.1 disrupted mouse ovarian estrus cycles and elevated serum concentrations of testosterone. RT-qPCR and RNA-sequencing (RNA-seq) analyses revealed altered expression of steroidogenic genes, transcriptomic changes, and activation of the aryl hydrocarbon receptor (AhR) in antral follicles from mice treated with LS-WFPM0.1. LS-WFPM0.1 consistently increased testosterone secretion and stimulated genes related to androgen synthesis and AhR in vitro. Single-follicle and single-oocyte RNA-seq analyses identified differentially expressed genes related to inflammation in follicular somatic cells and mitochondrial health in oocytes. Both C-WFPM0.1 and established AhR agonists, including benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), reproduced these ovarian defects. Mechanistically, inhibition of AhR reversed the WFPM0.1-induced transcriptional changes of steroidogenic genes and ovarian hyperandrogenism. Together, our study suggests that exposure to WFPM0.1 disrupts ovarian hormone secretion by inducing hyperandrogenism, which is associated with AhR activation, underscoring an urgent need for further mechanistic and epidemiological studies to define the reproductive risks of wildfire smoke exposure in humans.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"25 2 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090718","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":"FAM45A-Mediated Persistent\u0000Memory-Like Fibroblast\u0000Reprogramming Drives PM2.5-Exacerbated Allergic Asthma","authors":"Bin Liu,Yan Feng,Guibing Ren,Shunjun Tang,Xinli Song,Yuntao Wu,Haoyue Zheng,Hui Huangfu,Shengzhang Zhang,Jianchao Wang,Yanyu Ye,Gui Yang,Pingchang Yang,Di Zhang","doi":"10.1021/ehp.6c00353","DOIUrl":"https://doi.org/10.1021/ehp.6c00353","url":null,"abstract":"Abstract Chronic coexposure to fine particulate matter (PM2.5) and house dust mite (HDM) allergen worsens allergic asthma outcomes, yet the stromal cell mechanisms linking combined environmental and allergic risk factors remain incompletely defined. Airway fibroblasts are traditionally viewed as structural matrix-producing cells, with limited published data describing their capacity to acquire antigen-presenting (APC) features after dual pollutant-allergen stimulation. Bronchoalveolar lavage fluid (BALF) fibroblasts represent a less invasive alternative to endobronchial biopsy tissue for primary stromal cell research, reducing procedural risks and sampling limitations in human asthma studies. BALF fibroblasts were isolated from 8 HDM-sensitized asthmatic participants and 8 HDM-sensitized nonasthmatic control subjects. An in vitro costimulation model was established to mimic concurrent PM2.5 and HDM exposure, with matched single-stimulus, vehicle, and TLR4 inhibitor control groups. We applied paired RNA-seq and ATAC-seq multiomics, antigen-specific CD4+ T cell coculture assays, CRISPR-Cas9 genetic editing, lentiviral complement, and humanized NSG mouse intervention experiments to characterize fibroblast functional shifts linked to air pollution. BALF fibroblasts from HDM-sensitized asthmatics displayed elevated HLA-DR, CD80, and CD86 surface markers alongside enhanced IL-33 secretion, and supported robust antigen-specific CD4+ T cell proliferation. Fibroblasts cultured with PM2.5 and HDM together acquired persistent memory-like functional alterations not observed under single-agent treatment. Integrated multiomic profiling identified FAM45A as the top transcript selectively upregulated only under dual exposure. In vitro assays demonstrated FAM45A interacts with V-ATPase complexes to slow lysosomal allergen degradation and amplifies NF-κB/AP-1 inflammatory signaling. CRISPR knockout and lentiviral rescue experiments support that FAM45A is required for the dual-stimulation-induced fibroblast phenotype. Neutralizing anti-FAM45A antibody reversed APC-like fibroblast activity in vitro and alleviated PM2.5/HDM-triggered airway inflammation in humanized mice. In a power-calculated expanded clinical cohort, fibroblast FAM45 protein levels positively correlated with residential PM2.5 exposure duration, serum HDM IgE, and GINA asthma severity. Concurrent PM2.5 and HDM exposure drives persistent memory-like functional and chromatin remodeling of human airway fibroblasts. FAM45A acts as a key molecular mediator of pollution-amplified allergic inflammation. BALF fibroblast FAM45A levels may serve as a correlative tissue marker reflecting combined environmental and allergic disease burden. Targeted FAM45A inhibition may offer a more tissue-restricted intervention relative to broad corticosteroid therapy, though comprehensive preclinical safety assessment across systemic immune compartments is needed to clarify off-target risks.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"32 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090720","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":"Embryonic Exposure to\u0000the Monoterpenes Thymol and\u0000 p\u0000 -Cymene Induces\u0000Social Deficits through KDM5 Inhibition","authors":"Baixi He,Ping Zhang,Catherine Hong,Maja Johnson,Anna Kim,Miles Huang,Jinghan Yu,Annabelle Chen,Emma Kong,Yijie Geng","doi":"10.1021/ehp.6c00534","DOIUrl":"https://doi.org/10.1021/ehp.6c00534","url":null,"abstract":"Abstract The increasing prevalence of autism spectrum disorder (ASD) has drawn significant attention to its environmental origin. Environmental factors are estimated to contribute to 40% of ASD risk. However, the identities of these factors and their mechanisms of action remain poorly understood due to limitations of current research approaches. To bridge this gap, we screened a subset of the ToxCast library using a high-throughput social behavioral assay platform, Fishbook, to discover emerging ASD-relevant toxicants. From the 165 toxicants screened, we identified thymol (TH) and p-cymene (PC), both belonging to the chemical class monoterpenes, as potent inhibitors of social behavioral development through embryonic exposure. Monoterpenes are natural compounds commonly found in food flavorings, essential oils, and personal care products. Through a proteome-wide inverse virtual screening, followed by in silico, in vitro, and in vivo validations, we discovered lysine demethylase 5 (KDM5) family proteins, in particular KDM5B, KDM5C, and KDM5D, as predicted binding targets of TH and PC. Both KDM5B and KDM5C genes have been previously associated with ASD. The KDM5 family proteins are histone demethylases that selectively remove methyl groups from histone H3 lysine 4 (H3K4me3/2/1), which are epigenetic marks typically associated with active gene transcription. Both compounds directly inhibited KDM5 demethylase activity in nuclear extracts from zebrafish larvae and from human cells, and embryonic exposure increased the global level of H3K4me3 in vivo. Consistent with elevated H3K4me3, RNA-sequencing detected profound up-regulation of genes associated with genetic risk factors of ASD following TH and PC exposure. Furthermore, chemical inhibition of the opposing H3K4 methyltransferase complex, MLL/WDR5, effectively rescued social deficits induced by TH and PC. In summary, this work discovered thymol and p-cymene as risk factors for social behavioral development and establishes KDM5 inhibition as a mechanism of their neurodevelopmental toxicity.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"37 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090730","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":"Heavy Rainfall, Dairy\u0000Cattle, and\u0000 Campylobacter\u0000 in Aotearoa New Zealand\u00002015 to 2019: Space-Time Stratified Case-Crossover\u0000Study","authors":"Simon Hales,Tim Chambers,Farnaz Pourzand,Alice Hyun Min Kim,Michael G. Baker","doi":"10.1021/ehp.6c00099","DOIUrl":"https://doi.org/10.1021/ehp.6c00099","url":null,"abstract":"Abstract Objective: It is well-established that contamination of water supplies by heavy rainfall can cause large outbreaks of enteric disease. Associations of rainfall with sporadic disease are less well understood. Here we investigate short-term associations between rainfall, dairy cattle density, drinking water characteristics, and notifications of sporadic campylobacteriosis. Methods: Daily notifications of Campylobacter were spatially linked to geographic boundaries of water distribution zones. We created 10 km circular buffer zones around source water abstraction points for each supply and calculated average rainfall and maximum temperature over 7-day lag periods within the source water abstraction zones. We fitted conditional Poisson regression models in a space-time stratified case-crossover study. Results: In a linear model, adjusted for temperature, there was a weak association between campylobacteriosis and rainfall in the 7 days prior to disease onset: incidence rate ratio (IRR) 1.01; 95% CI: 1.008–1.017. In the lowest quintile of dairy cattle density (zero cows/km2), there was an increased risk of Campylobacter in the 10th (highest) decile of 7-day average lagged rainfall: IRR 1.11 (95% CI: 1.02–1.22). In the highest quintile of dairy cattle density (∼150 cows/km2), there was an increased risk of Campylobacter in the sixth to 10th deciles of rainfall. Conclusions: The risk of sporadic campylobacteriosis was significantly associated with heavy rainfall in the 7 days prior to disease onset, especially in locations served by surface water supplies with a high density of dairy cattle. Implications for public health: Heavy rainfall may increase the risk of sporadic waterborne enteric disease, especially where there is a high environmental load of zoonotic pathogens.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"20 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088377","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":"Mapping ToxCast/Tox21\u0000Assay Endpoints to Key Characteristics\u0000of Carcinogens to Support Cancer Hazard Evaluation","authors":"Danila Cuomo,Agnes L. Karmaus,Bridgett N. Hill,Gwendolyn Osborne,Amy Wang,Bevin Blake,William H. Bisson,Gabrielle Rigutto,Cliona McHale,Martyn T. Smith,Caterina Facchin,Aline de Conti,Federica Madia,Nicole C Kleinstreuer,Weihsueh A. Chiu,Alexandre Borrel","doi":"10.1021/ehp.6c00478","DOIUrl":"https://doi.org/10.1021/ehp.6c00478","url":null,"abstract":"Abstract The Environmental Protection Agency’s Toxicity Forecaster (ToxCast) and the Toxicity Testing in the 21st Century federal consortium (Tox21) programs provide vast high-throughput screening data on thousands of chemicals, capturing a range of molecular and cellular responses relevant to toxicity. However, their application to cancer hazard identification requires a structured framework. The ten key characteristics of carcinogens (KCCs) offer a systematic approach for organizing this mechanistic evidence. We present an updated, comprehensive mapping of 1,570 ToxCast/Tox21 assay endpoints to the KCCs, developed through an expert-driven consensus process. A novel tiering approach was introduced to characterize each assay’s level of mechanistic relevance: Tier A indicates a direct effect linked to a KCC, while Tier B signifies an indirect or downstream effect. Additionally, we incorporated response directionality to correctly identify events contributing to, rather than merely associated with, a KCC. Of the 1,570 assay endpoints available in ToxCast/Tox21, 838 assay endpoints (53%) were mapped to the KCCs with some assay endpoints mapping to multiple KCCs. The majority of mapped assay endpoints were associated with KCC8 (modulates receptor-mediated effects) and KCC10 (alters cell proliferation, cell death, or nutrient supply). Some assay endpoints were mapped on different KCCs depending on the directionality of the response. No assay endpoints were mapped to KCC1 (is electrophilic or can be metabolically activated to electrophiles) or KCC9 (causes immortalization). This publicly available tiered mapping provides a crucial resource for interpreting high-throughput screening data in the context of carcinogenesis. It enables researchers and risk assessors to more systematically utilize such data for cancer hazard evaluation and chemical prioritization.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"1 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088074","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}