Environmental Health Perspectives[JOURNAL]
Sun
200 papers
Beyond the Surface: Mapping DDE's Metabolic Footprint on Adolescent Obesity.
Li Z, Pan S, Baumert BO … +21 more , Chen JC, Goodrich JA, Wang H, Rock S, Ryder J, Valvi D, Jenkins T, Sisley S, Lin X, Bartell SM, Inge TH, Xanthakos S, McNeil B, Robuck AR, Mullins CE, Eckel SP, McConnell RS, La Merrill MA, Walker DI, Conti DV, Chatzi L
Environ Health Perspect · 2025 Jun · PMID 40460320 · Publisher ↗
BACKGROUND: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight...
BACKGROUND: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored. OBJECTIVES: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics. METHODS: We conducted a longitudinal study involving 60 adolescents with severe obesity undergoing bariatric surgery. We quantified -DDE concentrations in visceral adipose tissue collected during surgery and analyzed metabolic profiles from both adipose tissues collected at surgery and plasma samples collected at surgery, 6 months, 1 year, and 3 years postoperatively, using gas/liquid chromatography and high-resolution mass spectrometry. We used meet-in-the-middle approach coupled with a series of metabolome-wide association analyses to identify overlapping metabolite associated with both DDE exposure and weight loss outcomes. RESULTS: Our findings revealed that DDE concentrations in visceral adipose tissue are associated with significant alterations in metabolites locally in adipose tissue pre-surgery and systemically in plasma post-surgery. Eight plasma metabolites were significantly associated with DDE exposure over time, while 27 were associated with BMI. Notably, methylbutyroylcarnitine was identified as a potential mediator, showing a positive association with both exposure and outcome. Eight adipose tissue metabolites were associated with both DDE and longitudinal changes in plasma metabolites, suggesting an indirect pathway linking DDE and weight changes. DISCUSSION: These findings enhance our understanding of DDE's obesogenic effect. The involved metabolic changes could attenuate the efficacy of bariatric surgery in achieving sustained weight loss, underscoring the importance of integrating environmental health considerations into clinical practice. https://doi.org/10.1289/EHP16341.
Multi-behavioral phenotyping in early-life-stage zebrafish for identifying disruptors of non-associative learning.
Leuthold D, Herold NK, Nerlich J … +6 more , Bartmann K, Scharkin I, Hallermann SJ, Schweiger N, Fritsche E, Tal T
Environ Health Perspect · 2025 May · PMID 40445242 · Publisher ↗
BACKGROUND: The vertebrate nervous system is vulnerable to chemical toxicity and the widespread release of chemicals into the environment outstrips the capacity to assess their safety. The zebrafish () is a powerful vert...
BACKGROUND: The vertebrate nervous system is vulnerable to chemical toxicity and the widespread release of chemicals into the environment outstrips the capacity to assess their safety. The zebrafish () is a powerful vertebrate model that can bridge the gap between and mammalian-based studies. However, the behavior-rich repertoire of larval zebrafish, a 3R-compliant model amenable to higher-throughput chemical screens, has yet to be fully deployed to identify and characterize chemical compounds that cause neurotoxicity. OBJECTIVE: We sought to establish a multi-behavioral phenotyping approach in larval zebrafish to identify and mechanistically elucidate neuroactive chemicals, with particular focus on chemical compounds that affect non-associative habituation learning. METHODS: We devised a battery of automated behavior assays in larval zebrafish. The battery captures stereotypical visual and acoustic behaviors including habituation, a form of non-associative learning. To elucidate mechanisms underlying exposure-induced behavioral alterations in zebrafish, target predictions, pharmacological interventions, patch-clamp recordings in cultured mouse cortical neurons, and human multi-neurotransmitter (hMNR) assay in 3D BrainSpheres were used. RESULTS: Known pharmacological modulators of habituation in zebrafish evoked distinct behavioral patterns. By screening chemicals positive for N-methyl-D-aspartate receptor (NMDAR) modulation, we identified chlorophene, a biocide that caused sedation, paradoxical excitation, and reduced habituation in zebrafish. Using target predictions and pharmacological interventions, we discovered that chlorophene acts via gamma-aminobutyric acid A receptors (GABARs), a previously unknown target site. Orthogonal validation in cultured mouse cortical neurons and human stem cell-derived BrainSpheres confirmed chlorophene's interaction with GABARs. Chlorophene's behavioral profile resembled that of flupirtine, a Kv7 potassium channel (M-current) activator, suggesting that habituation deficits stem from M-current rather than GABAR modulation. CONCLUSIONS: These studies combined a series of behavior assays in a phenotypically rich, rapid, and inexpensive non-mammalian vertebrate test system to screen chemicals for neurotoxicity. Together with target predictions and mouse- and human-based models, our findings establish multi-behavioral phenotyping in zebrafish as a powerful toolkit for neurotoxicity testing and mechanism identification, with relevance for humans. https://doi.org/10.1289/EHP16568.
Thirdhand Smoke Exposes Children Living with Smokers and Nonsmokers to Tobacco Smoke Toxicants: Racial, Income, and Housing Disparities in Hand Nicotine and Saliva Cotinine Levels.
Mahabee-Gittens EM, Merianos AL, Lopez-Galvez N … +6 more , Quintana PJE, Hoh E, Dodder NG, Stone L, Wullenweber CA, Matt GE
Environ Health Perspect · 2025 May · PMID 40440555 · Publisher ↗
BACKGROUND: Children may be involuntarily exposed to chemical residue from thirdhand tobacco smoke (THS) in environments where tobacco has previously been used. Factors contributing to this exposure among children of non...
BACKGROUND: Children may be involuntarily exposed to chemical residue from thirdhand tobacco smoke (THS) in environments where tobacco has previously been used. Factors contributing to this exposure among children of nonsmokers with no known secondhand smoke (SHS) exposure are currently unknown. OBJECTIVE: To understand the contribution of THS residue to the overall tobacco smoke exposure (TSE) among children of nonsmokers and smokers. METHODS: We conducted a prospective observational cohort study of parents and their children (≤11 years; N=1013) at a children's hospital in the US. Hand nicotine (HN) and saliva cotinine (SC) were markers of THS pollution and TSE, respectively. Children were considered protected from tobacco smoke if there were no household smokers or vapers, strict household smoking bans, and no SHS exposure during the past week. Cluster-adjusted regression models were used to test hypotheses about HN and SC levels. RESULTS: Overall, 94.5% and 98.9% of protected and unprotected children had detectable HN, respectively. Children who were Black and protected (GeoM= 6.0 ng/wipe; 95%CI=[3.8, 9.1]) or unprotected (GeoM= 43.8 ng/wipe; 95%CI=[33.6; 57.1]) had approximately three times higher HN levels than children who were White and protected (GeoM= 1.8 ng/wipe; 95%CI=1.6; 2.0]) or unprotected (GeoM= 15.0 ng/wipe; 95%CI=[11.2; 19.8]). Unprotected children whose parents had ≤high school education had HN levels that were almost 12 times higher (87.8 ng/wipe) than unprotected children of parents who graduated college (7.5 ng/wipe). Unprotected children with ≤$15,000 household income had HN levels >25 times higher (73.3 ng/wipe) than unprotected children with >$90,000 income (≤ 2.8 ng/wipe). Household smoking bans were unsuccessful in lowering HN levels in Black children, but they were successful for White children (χ(3)=12.7, p<0.01). HN was associated with SC in children with no SHS exposure (βˆ= 0.10), with stronger associations in the presence of 1 (βˆ= 0.28) and 2+ active smokers (βˆ= 0.32; all p<0.01). DISCUSSION: THS is a pervasive source of exposure to tobacco smoke pollutants. Stark disparities were noted, with higher exposure in Black and lower income children. Findings provide the strongest evidence to date on the contribution of THS as a significant source of overall TSE in children. https://doi.org/10.1289/EHP16332.
An integrated machine learning framework to understand zoonotic spillover emergence across anthropogenically modified landscapes.
Zhang Y, Wang J, Wang L … +7 more , Miao L, Sun Y, Yang X, Fang R, Guo Y, Vanwambeke S, Li S
Environ Health Perspect · 2025 May · PMID 40397827 · Publisher ↗
BACKGROUND: Anthropogenic land modification influences human-livestock-wildlife interactions and zoonotic spillover emergence. However, the extent of this impact remains unclear and could be better understood through the...
BACKGROUND: Anthropogenic land modification influences human-livestock-wildlife interactions and zoonotic spillover emergence. However, the extent of this impact remains unclear and could be better understood through the collaborative use of advanced predictive and explanatory analytical tools, alongside, an up-to-date dataset on zoonotic spillover events. OBJECTIVE: The main objective is to develop and evaluate an integrated modeling framework to predict and explain spatial patterns and nonlinear relationships of zoonotic spillover events, using updated datasets and the human modification index to differentiate anthropogenic pressures. METHODS: Our study expanded the historical datasets to include recent spillover events and a comprehensive set of predictors. By combining robustness of finely-tuned stacking algorithms with structural equation modeling, we considered global heterogeneity in relative reporting adequacy and mapped spillover patterns at different scales. Using the human modification index, we disentangled anthropogenic processes modifying natural ecosystem across land modification gradients, and described their linkages to spillover occurrence over the past three decades. RESULTS: This integrated approach effectively improved the model's predictive and explanatory power. Our analysis reveals that the intermediate levels of human pressure facilitated the zoonotic spillover. The indirect effects of anthropogenic pressure, mediated by specific cropping intensity, are strongly associated with zoonoses emergence. Livestock distribution serves as an indicator of spillover hotspots, acting as effective proxies for distinctive landscapes. DISCUSSION: Our findings identify high zoonotic spillover risks present across geographically and socioeconomically diverse regions worldwide, extending beyond tropical areas, including extensive regions experiencing high-intensity human modification. These insights support targeted surveillance in areas with potentially high relative risk or uncertainty, and demonstrate how zoonotic spillover responds to complex human-environment interactions. https://doi.org/10.1289/EHP15937.
Circulating per- and polyfluoroalkyl substances and liver cancer risk: a nested case-control analysis of individual participant data from 12 prospective cohorts.
Watling CZ, Petrick JL, Graubard BI … +31 more , Zhang X, Barnett MJ, Buring JE, Chen Y, Eliassen AH, Gaziano M, Kang JH, Koshiol J, Huang WY, Lee IM, Moore SC, Mucci LA, Neuhouser ML, Newton CC, Palmer JR, Rosenberg L, Sesso HD, Shrubsole M, Tinker L, Triplette M, Um CY, Visvanathan K, Wactawski-Wende J, Willett W, Wu F, Zheng W, Hofmann J, Purdue MP, Campbell PT, Barupal D, McGlynn KA
Environ Health Perspect · 2025 May · PMID 40397817 · Full text
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with numerous deleterious health outcomes including liver damage. However, whether exposure to PFAS is associated with liver cancer risk remains...
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with numerous deleterious health outcomes including liver damage. However, whether exposure to PFAS is associated with liver cancer risk remains unclear. METHODS: We conducted a matched nested case-control study among 12 prospective cohort studies located in the United States. Pre-diagnostic PFAS, namely perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS), were measured from blood samples among 853 individuals who developed liver cancer and 853 matched control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable-adjusted conditional logistic regression for liver cancer risk by study-specific quartiles of concentrations and per 90 vs. 10 percentile incremental increase. RESULTS: In the main multivariable-adjusted model, circulating PFOS, PFOA, and PFHxS levels were not associated with liver cancer risk (OR per 90 vs. 10 percentile increase: 1.00, 95% CI: 0.79-1.28; 0.92, 0.73-1.15; and 0.95, 0.75-1.21, respectively). However, when analyses were stratified by sex, PFOA concentrations were positively associated with liver cancer risk in males (OR per 90 vs. 10 percentile increase: 1.62 95% CI:1.07-2.45), whereas an inverse association was observed amongst females (OR per 90 vs. 10 percentile increase:0.68, 0.50-0.92; p-interaction=0.005). Analyses separating liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma, showed no evidence of heterogeneity, although associations were stronger but not significant for HCC. No evidence of interaction was observed by time to diagnosis, time period of blood draw, body mass index, alcohol intake, ethnicity, or diabetes status. CONCLUSIONS: In the largest study to date, none of the measured circulating PFAS were associated with liver cancer risk; however, PFOA associations appeared to differ by sex and further research is needed to explore these apparent differences by sex. https://doi.org/10.1289/EHP16980.
External Validation of STopTox - Novel Alternative Method (NAM) for Acute Systemic and Topical Toxicity.
Tieghi RS, Melo-Filho CC, Martin HJ … +7 more , Moreira-Filho JT, LaPratt T, Allen D, Strickland J, Tropsha A, Kleinstreuer N, Muratov EN
Environ Health Perspect · 2025 May · PMID 40393008 · Publisher ↗
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Statistical Methods for Chemical Mixtures: A Roadmap for Practitioners Using Simulation Studies and a Sample Data Analysis in the PROTECT Cohort.
Hao W, Cathey AL, Aung MM … +3 more , Boss J, Meeker JD, Mukherjee B
Environ Health Perspect · 2025 Jun · PMID 40392783 · Full text
BACKGROUND: Quantitative characterization of the health impacts associated with exposure to chemical mixtures has received considerable attention in current environmental and epidemiological studies. With many existing s...
BACKGROUND: Quantitative characterization of the health impacts associated with exposure to chemical mixtures has received considerable attention in current environmental and epidemiological studies. With many existing statistical methods and emerging approaches, it is important for practitioners to understand which method is best suited for their inferential goals. OBJECTIVE: The goal of this paper is to provide empirical simulation-based evidence regarding performance of mixture methods to help guide researchers on selecting the best available methods to address three scientific questions in mixtures analysis: identifying important components of a mixture, identifying interactions among mixture components, and creating a summary score for risk stratification and prediction. METHODS: We conducted a review and comparison of 11 analytical methods available for use in mixtures research through extensive simulation studies for continuous and binary outcomes. In addition, we carried out an illustrative data analysis using the PROTECT birth cohort from Puerto Rico to examine the associations between exposure to chemical mixtures-metals, polycyclic aromatic hydrocarbons (PAHs), phthalates, and phenols-and birth outcomes. RESULTS: Our simulation results suggest that the choice of methods depends on the goal of analysis and that there is no clear winner across the board. For selection of important toxicants in the mixtures and for identifying interactions, Elastic net (Enet) by Zou et al., Lasso for Hierarchical Interactions (HierNet) by Bien et al., and selection of nonlinear interactions by a forward stepwise algorithm (SNIF) by Narisetty et al. have the most stable performance across simulation settings. For overall summary or a cumulative measure, we find that using the Super Learner to combine multiple environmental risk scores can lead to improved risk stratification and prediction properties. CONCLUSIONS: We develop an integrated R package "CompMix" that provides a platform for mixtures analysis where the practitioners can implement a pipeline that includes several approaches for mixtures analysis. Our study offers guidelines for selecting appropriate statistical methods for addressing specific scientific questions related to mixtures research. We identify critical gaps where new and better methods are needed. https://doi.org/10.1289/EHP15305.
A prospective exposome-based gene-environment interaction study on the effects of prenatal environmental exposure on fetal growth in the Shanghai Birth Cohort.
Jiang W, Huang Y, Jin H … +6 more , Gan Y, Zhang Q, He X, Tian Y, Zhang J, The Shanghai Birth Cohort
Environ Health Perspect · 2025 May · PMID 40392608 · Publisher ↗
BACKGROUND: Both environmental exposure and type 2 diabetes (T2D) genetic susceptibility affect fetal growth. However, most previous studies used single exposure rather than an exposome strategy to explore the associatio...
BACKGROUND: Both environmental exposure and type 2 diabetes (T2D) genetic susceptibility affect fetal growth. However, most previous studies used single exposure rather than an exposome strategy to explore the association between environmental factors and fetal growth, and the interactions of environmental exposures with maternal and fetal genes were often overlooked. OBJECTIVES: To explore the associations between a broad range of prenatal environmental factors and fetal growth and further evaluate the effect modification of maternal and fetal T2D genetic susceptibility on the identified exposures. METHODS: From 1,933 mother-neonate pairs from the Shanghai Birth Cohort, we estimated the associations between 70 prenatal exposure measures (including outdoor environment, residential environment, chemical exposures, lifestyle factors, and psychosocial status) and fetal growth, measured by birth-weight-for-gestational-age z-score (WAZ). Single-exposure analysis, elastic net regression, sparse partial least squares regression, extreme gradient boosting, and random forest were applied jointly to screen for WAZ-associated exposures. Multivariable linear regression models were used to assess the interactions of WAZ-associated exposures with maternal and fetal T2D polygenetic risk score (PRS). RESULTS: Sixteen prenatal exposures were associated with fetal growth, of which manganese, strontium, and residential greenspace showed a positive association while bisphenol A (BPA), 2,4-dihydroxy benzophenone (BP-1), ethyl 4-hydroxybenzoate (EtP), 4-hydroxybenzophenone (4-HBP), artificial light at night, noise, nitrogen dioxide, rubidium, thallium, silver, and humidity had a negative association. Temperature had an inverse U-shaped association with WAZ. The interactions of BPA and silver with maternal and fetal T2D PRS and rubidium with fetal T2D PRS were statistically significant, with more pronounced exposure effects in individuals with high T2D genetic risks. DISCUSSION: Our study identified several prenatal environmental exposures within the outdoor environment, phenols, and metal(loid)s that were associated with fetal growth. Mother-neonate pairs with high T2D genetic susceptibility were particularly vulnerable to the environmental insults. https://doi.org/10.1289/EHP15902.
Preterm and early-term delivery after heat waves in eight US states: A case-crossover study using the High-resolution Urban Meteorology for Impacts Dataset (HUMID).
Fitch A, Huang M, Strickland M … +6 more , Newman A, Kalb C, Warren JL, Zheng X, Chang H, Darrow L
Environ Health Perspect · 2025 May · PMID 40392097 · Publisher ↗
BACKGROUND: Heat wave frequency and intensity is increasing and this trend is more pronounced in urban areas. Heat waves may be acutely associated with early birth. OBJECTIVES: To examine the acute relationship between h...
BACKGROUND: Heat wave frequency and intensity is increasing and this trend is more pronounced in urban areas. Heat waves may be acutely associated with early birth. OBJECTIVES: To examine the acute relationship between heat waves and preterm (<37 weeks) and early-term (37-38 weeks) birth in eight states: California, Florida, Georgia, Kansas, Nevada, New Jersey, North Carolina, and Oregon. METHODS: Daily mean temperatures from the novel High-resolution Urban Meteorology for Impacts Dataset (HUMID) were averaged by zip code tabulation area (ZCTA) and linked to singleton preterm and early-term births identified statewide from vital records. Heat waves were defined based on days exceeding the local 97.5%ile temperature threshold during the 4-day exposure window preceding birth. We conducted case-crossover (conditional logistic regression) state-specific analyses and pooled results using inverse-variance weighting to obtain summary effect estimates. We also calculated ORs adjusting for temporal changes in the pregnancy risk set, conducted an analysis excluding medically-induced early-term births, and modeled effects stratified by 97.5 mean temperature threshold categories. RESULTS: The analysis included 2,966,661 early-term and 945,869 preterm births occurring from May - September across the eight states from as early as 1990 to 2017. Results showed modestly elevated odds of early-term birth for heat waves occurring in the 4 days preceding birth. Pooled ORs (95%CIs) for 3- and 4-consecutive days above the 97.5 percentile mean temperature were 1.018 (1.011, 1.026) and 1.017 (1.005, 1.028), respectively. Preterm birth ORs were similar, but less precise; OR=1.015 (1.001, 1.029) and 1.019 (0.999, 1.041) for 3- and 4-consecutive days respectively. Estimated odds ratios tended to be stronger for ZCTAs in thesecond-lowest category of temperature threshold. DISCUSSION: Using fine-scale surface temperature data capturing urban-heat islands, we observed a modest acute overall effect of heat waves on preterm and early-term birth. https://doi.org/10.1289/EHP15953.
DeTox: an Alternative to Animal Testing for Predicting Developmental Toxicity Potential.
Tieghi RS, Rath M, Moreira-Filho JT … +7 more , Wellnitz J, Martin HJ, Gates K, Hogberg HT, Kleinstreuer N, Tropsha A, Muratov EN
Environ Health Perspect · 2025 May · PMID 40388119 · Publisher ↗
BACKGROUND: Medication use among pregnant women is common, yet the safety of these medications for the developing fetus/baby is widely understudied. Quantitative Structure-Activity Relationship (QSAR) models can be used...
BACKGROUND: Medication use among pregnant women is common, yet the safety of these medications for the developing fetus/baby is widely understudied. Quantitative Structure-Activity Relationship (QSAR) models can be used to predict the overall and trimester-specific developmental toxicity potential of chemicals, supporting the development of safer medications for pregnant women and regulatory assessment aligned with the 3Rs (efining, educing, and eplacing) of animal testing. OBJECTIVES: This study aimed to collect and curate a database of compounds classified according to their developmental toxicity potential, use this database to develop and validate QSAR models for predicting prenatal developmental toxicity, and implement models via a user-friendly online platform to support regulatory assessments of drug candidates. METHODS: We compiled and curated data from the FDA and Teratogen Information System (TERIS) databases and validated annotations with rigorous literature searches. The database was leveraged to create QSAR models using machine learning algorithms (RF, SVM, LightGBM) with Bayesian hyperparameter optimization. These models were implemented into a web tool. RESULTS: We built a binary classification QSAR model for overall pregnancy risk, and separate QSAR models for trimester-specific risk, exhibiting correct classification rates of and 76% (overall), 80% (1 trimester), 95% (2 trimester), and 95% (3 trimester). Models showed a sensitivity between 53% and 90%, specificity between 46% and 100%, and coverage of 76% assessed using a five-fold external validation protocol. We established a publicly accessible web portal (https://detox.mml.unc.edu/) for developmental toxicity prediction of both overall and trimester-specific toxicity predictions. CONCLUSIONS: DeTox can be employed to support regulatory assessment of pharmaceutical and cosmetic products aligned with the 3Rs of animal testing and to guide the development of safer drugs for pregnant populations. The curated dataset of developmental toxicants is publicly available, and all models are implemented in a public, user-friendly web tool, DeTox (velopmental icity), at https://detox.mml.unc.edu/. https://doi.org/10.1289/EHP15307.
Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy.
Chiang YF, Chen YC, Huang KC … +2 more , Ali M, Hsia SM
Environ Health Perspect · 2025 May · PMID 40378307 · Publisher ↗
BACKGROUND: The impact of non-nutritive sweeteners on male reproductive health, particularly at the cellular level, remains insufficiently explored. Sucralose's high stability and resistance to degradation during wastewa...
BACKGROUND: The impact of non-nutritive sweeteners on male reproductive health, particularly at the cellular level, remains insufficiently explored. Sucralose's high stability and resistance to degradation during wastewater treatment raises concerns about its long-term environmental and health impacts. Whether sucralose consumption correlates with reduced reproductive hormone levels and testicular damage remains unclear, and the underlying mechanisms require further investigation. OBJECTIVES: This study aims to investigate the influence of sucralose on cell damage and reproductive health in male. METHODS: The male mouse Leydig cell line TM3 and Sertoli cell line TM4 were used to evaluate sucralose-associated cellular damage. In vitro experiments assessed cell survival rates and the potential disruption of autophagy. Additionally, male SD rats were exposed to sucralose via oral gavage for two months at doses reflecting the acceptable daily intake (ADI) to evaluate sperm viability and reproductive health. RESULTS: In vitro experiments demonstrated cells exposed to sucralose had significantly lower cell survival rates. Sucralose exposure significantly reduced cell viability in TM3 and TM4 cells, induced oxidative stress, and disrupted autophagic flux by impairing autophagosome-lysosome fusion. Additionally, sucralose downregulated T1R3 protein expression, suggesting a role for sweet taste receptor signaling in testicular cell regulation. In vivo, chronic oral exposure to sucralose led to decreased sperm viability and dysregulated reproductive function, including altered testicular morphology and suppressed steroidogenesis. DISCUSSION: These findings provide new insights into the adverse effects of sucralose on male reproductive physiology, highlighting its role in disrupting autophagy, inducing oxidative stress, and impairing reproductive function. The environmental persistence of sucralose and its potential leakage into wastewater systems present broader implications for public health and ecological stability. This study underscores the importance of carefully evaluating non-nutritive sweeteners in the diet and calls for stricter food safety regulations and wastewater management practices to mitigate potential risks.. https://doi.org/10.1289/EHP15919.
Household fuel use and kidney disease-related mortality: the Golestan Cohort Study.
Sassano M, Seyyedsalehi MS, Alatab S … +5 more , Poustchi H, Sheikh M, Etemadi A, Malekzadeh R, Boffetta P
Environ Health Perspect · 2025 May · PMID 40373289 · Publisher ↗
BACKGROUND: A large proportion of global population uses solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function. OBJECTIVES: To inv...
BACKGROUND: A large proportion of global population uses solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function. OBJECTIVES: To investigate the association between household use of different types of fuels and kidney disease-related mortality. METHODS: We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study conducted in northeastern Iran, with 50,045 individuals aged 40-75 years enrolled in the period 2004-2008 and followed through April 2023. Information on household fuel use was collected using validated questionnaires. We estimated adjusted hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox proportional hazards models with age as the time scale. The outcome of interest was death due to any kidney disease, excluding kidney cancer (ICD-10 codes: N00-N19, N25-N29). RESULTS: During 724,063.62 person-years of follow-up, 262 participants died due to kidney disease. The risk of kidney disease-related mortality was higher with longer duration of biomass use for cooking or house heating (HR for every 10-year increase: 1.20; 95% CI: 1.04-1.37), while it was not associated with longer duration of using kerosene (10-y HR: 1.09; 95% CI: 0.95-1.24), or gas (10-y HR: 1.00; 95% CI: 0.86-1.16). Estimates for lifetime duration of fuel burning for both cooking and house heating (exclusive fuel use) did not differ according to whether used heating stoves were chimney-equipped or not for kerosene, while they differed for biomass (10-y HR, chimney-equipped: 1.06 [95% CI: 0.95-1.18]; 10-y HR, not chimney-equipped: 1.19 [95% CI: 1.06-1.34]; =0.025). DISCUSSION: The findings of our study suggest that burning biomass for household purposes with poor ventilation is associated with kidney disease-related mortality. Interventions fostering the adoption of chimney-equipped stoves should be considered to reduce mortality due to use of solid fuels. https://doi.org/10.1289/EHP15629.
Development of the Food Systems-Related Greenhouse Gas Emissions Factor Database Using the Korea National Health and Nutrition Examination Survey (2016-2018).
Hong JY, Kim MK
Environ Health Perspect · 2025 Jun · PMID 40372422 · Full text
BACKGROUND: The increase in the frequency and scale of climate-related disasters is closely linked to greenhouse gas emissions (GHGEs) from food systems. Due to a lack of a comprehensive emission database that covers ent...
BACKGROUND: The increase in the frequency and scale of climate-related disasters is closely linked to greenhouse gas emissions (GHGEs) from food systems. Due to a lack of a comprehensive emission database that covers entire food systems, data on per capita dietary GHGEs are limited. OBJECTIVE: We created the Food Systems-related GHGE Factor Database (FS-GHGEF-D) to cover an entire food system and estimate per capita GHGEs for Korea. METHODS: We include GHGE factors for 3,894 food items derived from 24-h recall data of the seventh Korea National Health and Nutrition Examination Survey (2016-2018). We extracted these factors from 920 articles, excluding studies that focused only on specific GHG types or single-system boundaries and used a Monte Carlo Markov chain simulation to assess uncertainty of estimates. RESULTS: The FS-GHGEF-D covered 96.6% of food items. A total of 265 food items, primarily alcoholic and nonalcoholic beverages, were characterized by high degrees of uncertainty. However, removing these foods did not significantly alter the average GHGE factor across all food groups or affect coverage significantly, with the exception of the beverage category (both alcoholic and nonalcoholic). The average daily diet-related GHGEs per capita in Korea, as calculated using FS-GHGEF-D, were . Among food groups, meats contributed the most to the total variation in dietary GHGEs in the Korea population (75.7%). Men generally emitted more GHGEs than did women, with men in their 30s being the highest emitters. DISCUSSION: This study highlights the utility of a full-system GHGE database that addresses prior limitations in global estimates. Korean dietary patterns exceed climate-compatible thresholds, with substantial variation by demographic groups. These findings support the need for equity-focused strategies and integration of environmental considerations into national dietary guidelines for sustainable and climate-resilient food systems. https://doi.org/10.1289/EHP15534.
Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.
Rogers JD, Bundy JL, Harrill JA … +3 more , Judson RJ, Paul-Friedman K, Everett LJ
Environ Health Perspect · 2025 Jun · PMID 40366647 · Full text
BACKGROUND: With thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted assays, such as high-throughput tr...
BACKGROUND: With thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted assays, such as high-throughput transcriptomics (HTTr) and receptor screening assays, could improve identification of chemicals that perturb key molecular targets associated with adverse outcomes. OBJECTIVES: We aimed to link transcriptomic readouts to individual molecular targets and integrate transcriptomic predictions with orthogonal receptor-level assays in a proof-of-concept framework for chemical hazard prioritization. METHODS: Transcriptomic profiles generated via TempO-Seq in U-2 OS and HepaRG cell lines were used to develop signatures composed of genes uniquely responsive to reference chemicals for distinct molecular targets. These signatures were applied to 75 reference and 1,126 nonreference chemicals screened via HTTr in both cell lines. Selective bioactivity toward each signature was determined by comparing potency estimates against the bulk of transcriptomic bioactivity for each chemical. Chemicals predicted by transcriptomics were confirmed for target bioactivity and selectivity using available orthogonal assay data from the US Environmental Protection Agency ToxCast program. A subset of 37 selectively acting chemicals from HTTr that did not have sufficient orthogonal data were prospectively tested using one of five receptor-level assays. RESULTS: Of the 1,126 nonreference chemicals screened, 201 demonstrated selective bioactivity in at least one transcriptomic signature and 57 were confirmed as selective nuclear receptor agonists. Chemicals bioactive for each signature were significantly associated with orthogonal assay bioactivity, and signature-based points-of-departure were equally or more sensitive than biological pathway altering concentrations in 95.4% of signature-prioritized chemicals. Prospective profiling found that 18 of 37 (49%) chemicals without prior orthogonal assay data were bioactive against the predicted receptor. DISCUSSION: Our work demonstrates that integrating transcriptomics with targeted orthogonal assays in a tiered framework can support Next Generation Risk Assessment by informing putative molecular targets and prioritizing chemicals for further testing. https://doi.org/10.1289/EHP16024.
Projections of Heat-Related Mortality in Chinese Cities: The Roles of Climate Change, Urbanization, Socioeconomic Adaptation, and Landscape-Level Strategies.
Liu X, Hao M, Zhou Y … +9 more , Zhang Y, Xu Z, Liu X, Gao Y, Li R, Zhang H, Li X, Liu X, Yao Y
Environ Health Perspect · 2025 Jun · PMID 40359307 · Full text
BACKGROUND: Physiological heat strain induced by extreme temperatures in cities has led to significant heat-related deaths. Although socioeconomic adaptation is suggested to mitigate this issue, its effectiveness is limi...
BACKGROUND: Physiological heat strain induced by extreme temperatures in cities has led to significant heat-related deaths. Although socioeconomic adaptation is suggested to mitigate this issue, its effectiveness is limited. Conversely, there is a lack of comprehensive evaluation on the effectiveness of landscape-level strategies for mitigating heat-related deaths. OBJECTIVES: We developed a comprehensive modeling framework to estimate the impacts of environmental stresses and mitigating strategies on heat-related deaths in China's cities from 2016 to 2055. METHODS: The framework assesses future heat-related deaths through five experiments considering the influences of climate change, urbanization, socioeconomic adaptation, and landscape-level strategies. We used extrapolated region-specific exposure-response functions (ERF) and recent advancement of geo-statistics for public health to generate urban patch level ERF curves. We used these curves and temperature and population data to generate future heat-related deaths with a resolution and conducted 5,000 Monte Carlo simulations for uncertainty analysis. RESULTS: Our analyses estimated that heat-related mortality will increase from deaths per million in 2016 to deaths per million in 2055 under SSP2-RCP4.5 (shared socioeconomic pathways-representative concentration pathways) scenario and from deaths per million to deaths per million under SSP5-RCP8.5 scenario, despite socioeconomic adaptation and landscape-level strategies. Socioeconomic adaptation (reducing deaths by ) and landscape-level strategies (reducing deaths by ) significantly mitigate heat-related deaths with varying effectiveness across different income levels. Specifically, in high-income cities with dense populations, landscape-level strategies are 2.2-4.3 times more effective than socioeconomic adaptation. Within these cities, implementing the same landscape-level strategies in the high-density urban centers led to an additional reduction up to in comparison with surrounding areas. DISCUSSION: Our framework helps to systematically understand the effectiveness of landscape-level strategies in reducing heat-related mortality. Future sustainable city management should prioritize landscape-level strategies along with socioeconomic adaptation to support healthy and comfortable communities. https://doi.org/10.1289/EHP15010.
Effects of Bisphenol A and Retinoic Acid Exposure on Neuron and Brain Formation: A Study in Human Induced Pluripotent Stem Cells and Zebrafish Embryos.
Nishie T, Taya T, Omori S … +23 more , Ueno K, Okamoto Y, Higaki S, Oka M, Mitsuishi Y, Tanaka T, Nakamoto M, Kawahara H, Teraguchi N, Kotaka T, Sawabe M, Takahashi M, Kitaike S, Wada M, Iida K, Yamashita A, Jinno H, Ichimura A, Tooyama I, Sakai N, Hibi M, Hirasawa A, Takada T
Environ Health Perspect · 2025 Jun · PMID 40359302 · Full text
BACKGROUND: Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and...
BACKGROUND: Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and is essential for organ development, including the brain. We previously reported that RA/BPA coexposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation. OBJECTIVE: This study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether coexposure to BPA and exogenous RA could potentiate gene expression and exert pleiotropic effects on RA signaling. METHODS: Human iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, 12.5, 100, 200 or ) or BPA () alone or coexposed to BPA () and exogenous RA (). Postexposure changes in genes were assessed by quantitative polymerase chain reaction and/or transcriptome analyses. RA receptor antagonists were used to identify the receptor responsible for signaling. In zebrafish, spatial expression of and was evaluated by whole-mount hybridization. Mauthner cell and craniofacial cartilage anomalies were studied by immunostaining and Alcian blue staining, respectively. Transcriptome was compared between iPSCs and zebrafish to identify alterations of common biological processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish. RESULTS: In both iPSCs and zebrafish, RA/BPA coexposure had higher expression of 3' genes in comparison with RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA coexposure, in comparison with RA alone, resulted in a significant rostral shift in expression and increased rate of anomalies in Mauthner cells and craniofacial cartilage. Transcriptome comparison and correlations between the experimental results and gradient curve simulations strengthened these observations. CONCLUSION: Our findings suggest a mechanistic link between chemical exposure and neurodevelopmental impairments and demonstrate involvement of exogenous RA signaling in endocrine disruption. Further investigation is needed to explore why BPA alone did not affect endogenous RA signaling, whereas exogenous RA signaling was potentiated with RA/BPA coexposure. https://doi.org/10.1289/EHP15574.
Effects of Cooking with Liquefied Petroleum Gas or Biomass Fuels on Neurodevelopmental Outcomes in Preschool-Age Children Living in Puno, Peru.
Reuland CJ, Nicolaou L, Black MM … +10 more , Yang M, McCord R, Alvarado M, Arana F, Sanchez PS, Williams KN, Hossen S, Chiang M, Hartinger SM, Checkley W
Environ Health Perspect · 2025 Jun · PMID 40354572 · Full text
BACKGROUND: Burning biomass fuels for cooking is a widespread environmental exposure that may adversely affect child health. We conducted an 18-month randomized field trial comparing a liquefied petroleum gas (LPG) stove...
BACKGROUND: Burning biomass fuels for cooking is a widespread environmental exposure that may adversely affect child health. We conducted an 18-month randomized field trial comparing a liquefied petroleum gas (LPG) stove, continuous fuel delivery, and behavioral messaging intervention starting in pregnancy through infancy with usual cooking practices using biomass fuels in Puno, Peru. A total of 800 pregnant women were enrolled. The intervention successfully lowered personal exposures to fine particulate matter with aerodynamic diameter () during pregnancy and infancy. OBJECTIVE: We sought to evaluate the effects of the intervention on neurodevelopment among preschool-age offspring. METHODS: We conducted a longitudinal follow-up study in a subset of Peruvian children born during the trial and assessed neurodevelopment between 24 and 36 months of age. Trained staff measured neurodevelopment using the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III). The Bayley-III neurodevelopmental assessment test yields separate cognition, language, and motor scores. We measured personal exposures to three times during pregnancy and three times in infancy. We conducted modified intention-to-treat analyses of the intervention on Bayley-III scores and exposure-response analyses between prenatal and postnatal exposures and Bayley-III scores. RESULTS: A total of 301 children (mean age months, 47.8% girls, and 54.8% in intervention) were visited. Mean cognitive, language, and motor scores were , , and , respectively. On intention-to-treat, the adjusted differences between intervention and control arms were [98.3% confidence interval (CI): , 1.15], (, 0.1), and (, 2.29) for the composite cognitive, language, and motor scores, respectively. We did not identify associations between exposures during the 18-month intervention and any of the Bayley-III scores or when the personal exposures to were separated as either prenatal or postnatal. DISCUSSION: The LPG intervention did not improve neurodevelopment in Peruvian children. We also did not find an association between prenatal or postnatal exposures and neurodevelopment. https://doi.org/10.1289/EHP15500.
Estimation of Dermal Exposure to Volatile Organic Compounds (VOCs) from Feminine Hygiene Products: Integrating Measurement Data and Physiologically Based Toxicokinetic (PBTK) Model.
Lin N, Li Z, Ding N … +5 more , Park SK, Batterman S, Du W, Dai J, Zhu Y
Environ Health Perspect · 2025 Jun · PMID 40344599 · Full text
BACKGROUND: An increasing number of studies have reported noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs). OBJECTIVES: This study sought...
BACKGROUND: An increasing number of studies have reported noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs). OBJECTIVES: This study sought to address the gap in understanding the absorption, distribution, metabolism, and excretion dynamics of dermal exposure to VOCs from FHPs and to identify chemicals and products that could cause significant body burden. METHODS: We used measured contents of eight widely present VOCs across five categories of FHPs to estimate dermal exposure, and applied a physiologically based toxicokinetic (PBTK) modeling approach to elucidate VOC toxicokinetics in human body tissues. Inhalation exposure estimates were derived from 20 air samples collected via passive sampling and analyzed using a thermal desorption system coupled with gas chromatography-mass spectrometry. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females. RESULTS: Via skin absorption, the estimated levels of most target VOCs in nearly all tissues, except adipose and the rest of the body, rapidly peaked within an hour of product use. Specifically, -cymene was estimated to reach in adipose tissue before decreasing over several hours due to efficient excretion pathways, including liver metabolism and exhalation. The model estimated that although the majority of absorbed VOCs (78.9%) were eliminated via liver metabolism, exhalation, and urine excretion, VOCs with higher than 3.5, such as -cymene, hexane, and -nonane, exhibited a potential cumulative trend in adipose tissue. This trend resulted in the estimated VOC concentrations in adipose tissue being 1 to 4 orders of magnitude higher than those estimated in other tissues. In certain cases, -nonane posed a potential noncancer risk (up to 0.07), and benzene presented a notable cancer risk (up to ), primarily attributed to washes and moisturizers, respectively. DISCUSSION: These findings reveal potential significant body burden and health risks associated with dermal exposure to VOCs from FHPs, warranting further research and regulatory measures. Comprehensive assessment of internal exposure by integrating with toxicokinetic modeling to elucidate chemical distribution in various tissues is recommended, rather than by measuring only one type of biomarker, to illustrate exposure variances and ensure accurate risk assessment. https://doi.org/10.1289/EHP15418.
Health Trade-Offs of Boiling Drinking Water with Solid Fuels: A Modeling Study.
Floess E, Ercumen A, Harris AR … +1 more , Grieshop AP
Environ Health Perspect · 2025 Jun · PMID 40344151 · Full text
BACKGROUND: Billions of the world's poorest households are faced with the lack of access to both safe drinking water and clean cooking. One solution to microbiologically contaminated water is boiling, often promoted with...
BACKGROUND: Billions of the world's poorest households are faced with the lack of access to both safe drinking water and clean cooking. One solution to microbiologically contaminated water is boiling, often promoted without acknowledging the additional risks incurred from indoor air degradation from using solid fuels. OBJECTIVES: This modeling study explores the trade-off of increased air pollution from boiling drinking water under multiple contamination and fuel use scenarios typical of low-income settings. METHODS: We calculated the total change in disability-adjusted life years (DALYs) from household air pollution (HAP) and diarrhea from fecal contamination of drinking water for scenarios of different source water quality, boiling effectiveness, and stove type. We used Uganda and Vietnam, two countries with a high prevalence of water boiling and solid fuel use, as case studies. RESULTS: Boiling drinking water reduced the diarrhea disease burden by a mean of 1,100 DALYs and 367 DALYs per 10,000 people for those under and over 5 y of age in Uganda, respectively, for high-risk water quality and the most efficient (lab-level) boiling scenario, with smaller reductions for less-contaminated water and ineffective boiling. Similar results were found in Vietnam, though with fewer avoided DALYs in children under 5 y of age due to different demographics. In both countries, for households with high baseline HAP from existing solid fuel use, adding water boiling to cooking on a given stove was associated with a limited increase in HAP DALYs due to the log-linear exposure-response curves. Boiling, even at low effectiveness, was associated with net DALY reductions for medium- and high-risk water, even with unclean stoves/fuels. Use of clean stoves coupled with effective boiling significantly reduced total DALYs. DISCUSSION: Boiling water generally resulted in net decreases in DALYs. Future efforts should empirically measure health outcomes from HAP vs. diarrhea associated with boiling drinking water using field studies with different boiling methods and stove types. https://doi.org/10.1289/EHP15059.
A Machine Learning-Based Clustering Analysis to Explore Bisphenol A and Phthalate Exposure from Medical Devices in Infants with Congenital Heart Defects.
Chou WC, Gaynor JW, Graham EM … +5 more , Klepczynski B, Walker T, Coker ES, Ittenbach RF, Lin Z
Environ Health Perspect · 2025 Jun · PMID 40338266 · Full text
BACKGROUND: Plastic-containing medical devices are commonly used in critical care units and other patient care settings. Patients are often exposed to xenobiotic agents that are leached out from plastic-containing medica...
BACKGROUND: Plastic-containing medical devices are commonly used in critical care units and other patient care settings. Patients are often exposed to xenobiotic agents that are leached out from plastic-containing medical devices, including bisphenol A (BPA) and phthalates. Given the potential health implications, there is an urgent need for a comprehensive understanding of this exposure. OBJECTIVES: This multi-institutional study aimed to determine the time-dependent concentrations and analyze the exposure patterns of bisphenol A (BPA) and phthalate metabolites in urine obtained from infants with congenital heart defects (CHD) undergoing cardiac surgery during the perioperative period. METHODS: We collected daily urine samples from infants with CHD undergoing cardiac surgery during the perioperative period (from birth to 21 d) and measured BPA, di(2-ethylhexyl)phthalate (DEHP) metabolites (MEHP, MEHHP, MEOHP, MECPP), and non-DEHP phthalate metabolites (MBP, MBzP, MMP, MEP, MCPP) using ultra-high-performance liquid chromatography-tandem mass spectrometry. Machine learning-based cluster analysis was utilized to analyze these time-dependent data. RESULTS: Utilizing a machine learning-based clustering approach, six distinct clustering groups were identified among infants exhibiting similar time-series toxicokinetic exposure patterns. These distinct clustering groups correlated with the utilization of extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), as well as the intensity of medical care. Notably, clustering groups associated with ECMO use demonstrated elevated levels of urinary BPA and DEHP metabolites compared to those without ECMO use, a trend not observed with non-DEHP metabolites. Moreover, peak concentrations in toxicokinetic profiles were associated with intensity of medical care. DISCUSSION: Our findings suggest that dynamic changes of urinary BPA and DEHP metabolites corresponded to the type and number of medical devices used in infants. Further studies are needed to investigate the potential toxicological risks of infants with CHD undergoing cardiac surgery exposed to these chemicals in medical devices. https://doi.org/10.1289/EHP15034.
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