BACKGROUNDA large proportion of global population use solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function.OBJECTIVESTo investigate the association between household use of different types of fuels and kidney disease-related mortality.METHODSWe 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. The outcome of interest was death due to any kidney disease, excluding kidney cancer (ICD-10 codes: N00-N19, N25-N29).RESULTSDuring 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 increasing 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 increased 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]; Pdifference=0.025).DISCUSSIONThe findings of our study suggest that burning biomass for household purposes under poor ventilating conditions is associated with kidney disease-related mortality. https://doi.org/10.1289/EHP15629.
{"title":"Household fuel use and kidney disease-related mortality: the Golestan Cohort Study.","authors":"Michele Sassano,Monireh Sadat Seyyedsalehi,Sudabeh Alatab,Hossein Poustchi,Mahdi Sheikh,Arash Etemadi,Reza Malekzadeh,Paolo Boffetta","doi":"10.1289/ehp15629","DOIUrl":"https://doi.org/10.1289/ehp15629","url":null,"abstract":"BACKGROUNDA large proportion of global population use solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function.OBJECTIVESTo investigate the association between household use of different types of fuels and kidney disease-related mortality.METHODSWe 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. The outcome of interest was death due to any kidney disease, excluding kidney cancer (ICD-10 codes: N00-N19, N25-N29).RESULTSDuring 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 increasing 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 increased 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]; Pdifference=0.025).DISCUSSIONThe findings of our study suggest that burning biomass for household purposes under poor ventilating conditions is associated with kidney disease-related mortality. https://doi.org/10.1289/EHP15629.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"15 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065854","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}
BACKGROUNDThe 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.OBJECTIVEWe created the Food Systems-related GHGE Factor Database (FS-GHGEF-D) to cover an entire food system and estimate per-capita GHGEs for Korea.METHODSWe include GHGE factors for 3,894 food items derived from 24-hour-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.RESULTSThe FS-GHGEF-D covered 96.6% of food items. A total of 265 food items, primarily alcoholic and non-alcoholic 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 non-alcoholic). The average daily diet-related GHGEs per capita in Korea, as calculated using FS-GHGEF-D, was 5.08 kgCO2eq. 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.DISCUSSIONThis 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.
{"title":"Development of the Food Systems-related Greenhouse Gas Emissions Factor Database using the Korea National Health and Nutrition Examination Survey (2016-2018).","authors":"Jee Yeon Hong,Mi Kyung Kim","doi":"10.1289/ehp15534","DOIUrl":"https://doi.org/10.1289/ehp15534","url":null,"abstract":"BACKGROUNDThe 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.OBJECTIVEWe created the Food Systems-related GHGE Factor Database (FS-GHGEF-D) to cover an entire food system and estimate per-capita GHGEs for Korea.METHODSWe include GHGE factors for 3,894 food items derived from 24-hour-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.RESULTSThe FS-GHGEF-D covered 96.6% of food items. A total of 265 food items, primarily alcoholic and non-alcoholic 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 non-alcoholic). The average daily diet-related GHGEs per capita in Korea, as calculated using FS-GHGEF-D, was 5.08 kgCO2eq. 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.DISCUSSIONThis 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.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"121 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991942","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}
BACKGROUNDOvarian 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.OBJECTIVESUsing 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.METHODSWild-type (WT) and three different genotypes of female zebrafish (amh+/-;bmpr2a+/+, amh+/+;bmpr2a+/-, amh+/-;bmpr2a+/-) 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).RESULTSAfter neburon exposure, only four metabolites of neburon were detected but not itself, and all these metabolites had AHR agonistic activity, indicating the persistent toxicity of neburon. Neburon exposure altered 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, amh+/-;bmpr2a+/- zebrafish showed a rescued phenotype with regard to these neburon-associated outcomes. Moreover, AHR exhibited specific binding to the Amh promoter in KK1 cells, and neburon treatment enhanced their interaction.DISCUSSIONIn zebrafish, AMH was identified as a critical target for reproductive disorders following neburon exposure. Despite the short half-lives of currently used pesticides, their metabolites might still have significant toxicological risks. This study provides a novel insight into how one AHR agonistic pollutant affects female zebrafish reproduction. https://doi.org/10.1289/EHP15372.
{"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":"10.1289/ehp15372","DOIUrl":"https://doi.org/10.1289/ehp15372","url":null,"abstract":"BACKGROUNDOvarian 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.OBJECTIVESUsing 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.METHODSWild-type (WT) and three different genotypes of female zebrafish (amh+/-;bmpr2a+/+, amh+/+;bmpr2a+/-, amh+/-;bmpr2a+/-) 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).RESULTSAfter neburon exposure, only four metabolites of neburon were detected but not itself, and all these metabolites had AHR agonistic activity, indicating the persistent toxicity of neburon. Neburon exposure altered 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, amh+/-;bmpr2a+/- zebrafish showed a rescued phenotype with regard to these neburon-associated outcomes. Moreover, AHR exhibited specific binding to the Amh promoter in KK1 cells, and neburon treatment enhanced their interaction.DISCUSSIONIn zebrafish, AMH was identified as a critical target for reproductive disorders following neburon exposure. Despite the short half-lives of currently used pesticides, their metabolites might still have significant toxicological risks. This study provides a novel insight into how one AHR agonistic pollutant affects female zebrafish reproduction. https://doi.org/10.1289/EHP15372.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"36 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065855","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}
Jesse D Rogers,Joseph L Bundy,Joshua A Harrill,Richard J Judson,Katie Paul-Friedman,Logan J Everett
BACKGROUNDWith thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted in vitro 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.OBJECTIVESWe 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.METHODSTranscriptomic profiles generated via TempO-Seq in U-2 OS and HepaRG cell lines were used to develop signatures comprised of genes uniquely responsive to reference chemicals for distinct molecular targets. These signatures were applied to 75 reference and 1,126 non-reference chemicals screened via HTTr in both cell lines. Selective bioactivity towards 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 US EPA's 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.RESULTSOf the 1,126 non-reference 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.DISCUSSIONOur 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/EHPXXXXX.
{"title":"Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.","authors":"Jesse D Rogers,Joseph L Bundy,Joshua A Harrill,Richard J Judson,Katie Paul-Friedman,Logan J Everett","doi":"10.1289/ehp16024","DOIUrl":"https://doi.org/10.1289/ehp16024","url":null,"abstract":"BACKGROUNDWith thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted in vitro 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.OBJECTIVESWe 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.METHODSTranscriptomic profiles generated via TempO-Seq in U-2 OS and HepaRG cell lines were used to develop signatures comprised of genes uniquely responsive to reference chemicals for distinct molecular targets. These signatures were applied to 75 reference and 1,126 non-reference chemicals screened via HTTr in both cell lines. Selective bioactivity towards 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 US EPA's 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.RESULTSOf the 1,126 non-reference 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.DISCUSSIONOur 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/EHPXXXXX.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"25 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945264","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}
BACKGROUNDDeveloping 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 co-exposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation.OBJECTIVEThis study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether co-exposure to BPA and exogenous RA could potentiate HOX gene expression and exert pleiotropic effects on RA signaling.METHODSHuman iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, or 12.5 nM) or BPA (20 µM) alone or co-exposed to BPA (2 nM-20 µM) and exogenous RA (7.5-100 nM). Post-exposure changes in HOX 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, spacial expression of fgf8a and hoxb1a was evaluated by whole-mount in situ 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 biologic processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish.RESULTSIn both iPSCs and zebrafish, RA/BPA co-exposure had higher expression of 3' HOX genes compared to RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA co-exposure, compared to RA alone, resulted in a significant rostral shift in hoxb1a 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.CONCLUSIONOur findings suggested a mechanistic link between chemical exposure and neurodevelopmental impairments, and demonstrated 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 co-exposure. https://doi.org/10.1289/EHP15574.
{"title":"Effects of Bisphenol A and Retinoic Acid Exposure on Neuron and Brain Formation: a Study in Human Induced Pluripotent Stem Cells and Zebrafish Embryos.","authors":"Tomomi Nishie,Tomoki Taya,Shunichi Omori,Kenya Ueno,Yoshinori Okamoto,Shogo Higaki,Marina Oka,Yachiyo Mitsuishi,Taiga Tanaka,Mana Nakamoto,Hideaki Kawahara,Natsuki Teraguchi,Tomoyuki Kotaka,Misaki Sawabe,Miu Takahashi,Shoko Kitaike,Minori Wada,Keiko Iida,Akihiro Yamashita,Hideto Jinno,Atsuhiko Ichimura,Ikuo Tooyama,Noriyoshi Sakai,Masahiko Hibi,Akira Hirasawa,Tatsuyuki Takada","doi":"10.1289/ehp15574","DOIUrl":"https://doi.org/10.1289/ehp15574","url":null,"abstract":"BACKGROUNDDeveloping 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 co-exposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation.OBJECTIVEThis study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether co-exposure to BPA and exogenous RA could potentiate HOX gene expression and exert pleiotropic effects on RA signaling.METHODSHuman iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, or 12.5 nM) or BPA (20 µM) alone or co-exposed to BPA (2 nM-20 µM) and exogenous RA (7.5-100 nM). Post-exposure changes in HOX 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, spacial expression of fgf8a and hoxb1a was evaluated by whole-mount in situ 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 biologic processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish.RESULTSIn both iPSCs and zebrafish, RA/BPA co-exposure had higher expression of 3' HOX genes compared to RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA co-exposure, compared to RA alone, resulted in a significant rostral shift in hoxb1a 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.CONCLUSIONOur findings suggested a mechanistic link between chemical exposure and neurodevelopmental impairments, and demonstrated 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 co-exposure. https://doi.org/10.1289/EHP15574.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"4 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945266","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}
BACKGROUNDPhysiological heat strain induced by extreme temperature 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.OBJECTIVESWe 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.METHODSThe 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, temperature and population data to generate future heat-related deaths with 1 km resolution and conducted 5,000 Monte Carlo simulations for uncertainty analysis.RESULTSOur analyses estimated that heat-related mortality will increase from 136.5±16.5 deaths per million in 2016 to 175.7±27.5 deaths per million in 2055 under SSP2-RCP4.5 (shared socioeconomic pathways-representative concentration pathways) scenario and from 140.0±21.4 deaths per million to 230.2±38.7 deaths per million under SSP5-RCP8.5 scenario, despite socioeconomic adaptation and landscape level strategies. Socioeconomic adaptation (reducing deaths by 18.4-64.1 per million) and landscape level strategies (reducing deaths by 45.6-51.3 per million) 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 lead to an additional reduction up to 4.9-6.8 death•km-2 compared to surrounding areas.DISCUSSIONOur 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.
{"title":"Projections of heat-related mortality in Chinese cities: The roles of climate change, urbanization, socioeconomic adaptation, and landscape level strategies.","authors":"Xue Liu,Ming Hao,Yuyu Zhou,Yue Zhang,Ziheng Xu,Xiaojuan Liu,Yukun Gao,Rui Li,Han Zhang,Xia Li,Xiaoping Liu,Yuanzhi Yao","doi":"10.1289/ehp15010","DOIUrl":"https://doi.org/10.1289/ehp15010","url":null,"abstract":"BACKGROUNDPhysiological heat strain induced by extreme temperature 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.OBJECTIVESWe 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.METHODSThe 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, temperature and population data to generate future heat-related deaths with 1 km resolution and conducted 5,000 Monte Carlo simulations for uncertainty analysis.RESULTSOur analyses estimated that heat-related mortality will increase from 136.5±16.5 deaths per million in 2016 to 175.7±27.5 deaths per million in 2055 under SSP2-RCP4.5 (shared socioeconomic pathways-representative concentration pathways) scenario and from 140.0±21.4 deaths per million to 230.2±38.7 deaths per million under SSP5-RCP8.5 scenario, despite socioeconomic adaptation and landscape level strategies. Socioeconomic adaptation (reducing deaths by 18.4-64.1 per million) and landscape level strategies (reducing deaths by 45.6-51.3 per million) 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 lead to an additional reduction up to 4.9-6.8 death•km-2 compared to surrounding areas.DISCUSSIONOur 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.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"81 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945265","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}
Carolyn J Reuland,Laura Nicolaou,Maureen M Black,Mingling Yang,Ryan McCord,Milagros Alvarado,Fiorella Arana,Paola S Sanchez,Kendra N Williams,Shakir Hossen,Marilú Chiang,Stella M Hartinger,William Checkley
BACKGROUNDBurning 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 (PM2.5) during pregnancy and infancy.OBJECTIVEWe sought to evaluate the effects of the intervention on neurodevelopment among pre-school aged offspring.METHODSWe 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 PM2.5 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 pre-natal and post-natal PM2.5 exposures and Bayley-III scores.RESULTSA total of 301 children (mean age 29.0 ± 3.5 months; 47.8% girls; and 54.8% in intervention) were visited. Mean cognitive, language and motor scores were 90.8 ± 11.0, 89.0 ± 10.8, and 95.3 ± 12.9, respectively. On intention-to-treat, the adjusted differences between intervention and control arms were -1.9 (98.3% CI -4.9 to 1.2), -2.9 (-6.0 to 0.1), and -1.4 (-5.0 to 2.3) for the composite cognitive, language, and motor scores, respectively. We did not identify associations between PM2.5 exposures during the 18-month intervention and any of the Bayley-III scores, or when the personal exposures to PM2.5 were separated as either prenatal or post-natal.DISCUSSIONThe LPG intervention did not improve neurodevelopment in Peruvian children. We also did not find an association between prenatal or post-natal PM2.5 exposures and neurodevelopment. https://doi.org/10.1289/EHP15500.
燃烧生物质燃料烹饪是一种广泛的环境暴露，可能对儿童健康产生不利影响。我们在秘鲁普诺进行了一项为期18个月的随机现场试验，比较了液化石油气（LPG）炉子、从怀孕到婴儿开始的连续燃料输送和行为信息干预，以及使用生物质燃料的常规烹饪方法。总共有800名孕妇参加了这项研究。干预措施成功地降低了孕期和婴儿期个人接触细颗粒物（PM2.5）的风险。目的探讨干预对学龄前儿童神经发育的影响。方法我们对试验期间出生的秘鲁儿童进行了一项纵向随访研究，并评估了24至36个月大的神经发育情况。训练有素的工作人员使用Bayley婴幼儿发展量表第三版（Bayley- iii）测量神经发育。贝利- iii神经发育评估测试分别给出了认知、语言和运动的分数。我们在怀孕期间和婴儿期分别测量了三次个人接触PM2.5的情况。我们对干预对Bayley-III评分的影响进行了修改意向治疗分析，并对产前和产后PM2.5暴露与Bayley-III评分之间的暴露反应进行了分析。结果共301例患儿(平均年龄29.0±3.5个月；47.8%的女孩;干预组（54.8%）。平均认知、语言和运动得分分别为90.8±11.0、89.0±10.8和95.3±12.9。在意向治疗方面，干预组和对照组的综合认知、语言和运动评分调整后的差异分别为-1.9 （98.3% CI -4.9至1.2）、-2.9（-6.0至0.1）和-1.4（-5.0至2.3）。我们没有发现18个月干预期间PM2.5暴露与任何Bayley-III评分之间的关联，也没有发现个人PM2.5暴露在产前或产后分开时的关联。LPG干预并没有改善秘鲁儿童的神经发育。我们也没有发现产前或产后PM2.5暴露与神经发育之间的联系。https://doi.org/10.1289/EHP15500。
{"title":"Effects of cooking with liquefied petroleum gas or biomass fuels on neurodevelopmental outcomes in pre-school aged children living in Puno, Peru.","authors":"Carolyn J Reuland,Laura Nicolaou,Maureen M Black,Mingling Yang,Ryan McCord,Milagros Alvarado,Fiorella Arana,Paola S Sanchez,Kendra N Williams,Shakir Hossen,Marilú Chiang,Stella M Hartinger,William Checkley","doi":"10.1289/ehp15500","DOIUrl":"https://doi.org/10.1289/ehp15500","url":null,"abstract":"BACKGROUNDBurning 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 (PM2.5) during pregnancy and infancy.OBJECTIVEWe sought to evaluate the effects of the intervention on neurodevelopment among pre-school aged offspring.METHODSWe 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 PM2.5 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 pre-natal and post-natal PM2.5 exposures and Bayley-III scores.RESULTSA total of 301 children (mean age 29.0 ± 3.5 months; 47.8% girls; and 54.8% in intervention) were visited. Mean cognitive, language and motor scores were 90.8 ± 11.0, 89.0 ± 10.8, and 95.3 ± 12.9, respectively. On intention-to-treat, the adjusted differences between intervention and control arms were -1.9 (98.3% CI -4.9 to 1.2), -2.9 (-6.0 to 0.1), and -1.4 (-5.0 to 2.3) for the composite cognitive, language, and motor scores, respectively. We did not identify associations between PM2.5 exposures during the 18-month intervention and any of the Bayley-III scores, or when the personal exposures to PM2.5 were separated as either prenatal or post-natal.DISCUSSIONThe LPG intervention did not improve neurodevelopment in Peruvian children. We also did not find an association between prenatal or post-natal PM2.5 exposures and neurodevelopment. https://doi.org/10.1289/EHP15500.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"39 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945189","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}
Nan Lin,Zengwei Li,Ning Ding,Sung Kyun Park,Stuart Batterman,Wei Du,Jiayin Dai,Ying Zhu
BACKGROUNDIncreasing studies have informed noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs).OBJECTIVESThis study is 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.METHODSWe 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 thermal desorption system coupled with gas chromatography-mass spectrometer. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females.RESULTSVia 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, p-cymene was estimated to reach approximately 2.23 ng/mL in adipose tissue before decreasing over several hours due to efficient excretion pathways, including liver metabolism and exhalation. The model estimated that while the majority of absorbed VOCs (78.9%) were eliminated via liver metabolism, exhalation, and urine excretion, VOCs with logKow higher than 3.5, such as p-cymene, hexane, and n-nonane, exhibited a potential cumulative trend in adipose tissue. This resulted in the estimated VOC concentrations in adipose tissue being 1 to 4 orders of magnitude higher than those estimated in other tissues. Notably, in certain cases, n-nonane posed a potential non-cancer risk (up to 0.07), and benzene presented a notable cancer risk (up to 1.82 × 10-7), primarily attributed to wash and moisturizer, respectively.DISCUSSIONThese 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 solely measuring solely one type of biomarkers, to illustrate exposure variances and ensure accurate risk assessment.. https://doi.org/10.1289/EHP15418.
{"title":"Estimation of Dermal Exposure to Volatile Organic Compounds (VOCs) from Feminine Hygiene Products: Integrating Measurement Data and Physiologically Based Toxicokinetic (PBTK) Model.","authors":"Nan Lin,Zengwei Li,Ning Ding,Sung Kyun Park,Stuart Batterman,Wei Du,Jiayin Dai,Ying Zhu","doi":"10.1289/ehp15418","DOIUrl":"https://doi.org/10.1289/ehp15418","url":null,"abstract":"BACKGROUNDIncreasing studies have informed noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs).OBJECTIVESThis study is 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.METHODSWe 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 thermal desorption system coupled with gas chromatography-mass spectrometer. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females.RESULTSVia 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, p-cymene was estimated to reach approximately 2.23 ng/mL in adipose tissue before decreasing over several hours due to efficient excretion pathways, including liver metabolism and exhalation. The model estimated that while the majority of absorbed VOCs (78.9%) were eliminated via liver metabolism, exhalation, and urine excretion, VOCs with logKow higher than 3.5, such as p-cymene, hexane, and n-nonane, exhibited a potential cumulative trend in adipose tissue. This resulted in the estimated VOC concentrations in adipose tissue being 1 to 4 orders of magnitude higher than those estimated in other tissues. Notably, in certain cases, n-nonane posed a potential non-cancer risk (up to 0.07), and benzene presented a notable cancer risk (up to 1.82 × 10-7), primarily attributed to wash and moisturizer, respectively.DISCUSSIONThese 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 solely measuring solely one type of biomarkers, to illustrate exposure variances and ensure accurate risk assessment.. https://doi.org/10.1289/EHP15418.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"2 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932392","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}
Emily Floess,Ayse Ercumen,Angela R Harris,Andrew P Grieshop
BACKGROUNDBillions 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.OBJECTIVESThis modeling study explores the tradeoff of increased air pollution from boiling drinking water under multiple contamination and fuel use scenarios typical of low-income settings.METHODSWe 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.RESULTSBoiling drinking water reduced the diarrhea disease burden by a mean of 1100 DALYs and 367 DALYs per 10,000 people for those under and over 5 years 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 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.DISCUSSIONBoiling 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.
{"title":"Health Trade-offs of Boiling Drinking Water with Solid Fuels: A Modeling Study.","authors":"Emily Floess,Ayse Ercumen,Angela R Harris,Andrew P Grieshop","doi":"10.1289/ehp15059","DOIUrl":"https://doi.org/10.1289/ehp15059","url":null,"abstract":"BACKGROUNDBillions 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.OBJECTIVESThis modeling study explores the tradeoff of increased air pollution from boiling drinking water under multiple contamination and fuel use scenarios typical of low-income settings.METHODSWe 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.RESULTSBoiling drinking water reduced the diarrhea disease burden by a mean of 1100 DALYs and 367 DALYs per 10,000 people for those under and over 5 years 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 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.DISCUSSIONBoiling 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.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"50 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932393","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}
Wei-Chun Chou,J William Gaynor,Eric M Graham,Brenna Klepczynski,Tia Walker,Eric S Coker,Richard F Ittenbach,Zhoumeng Lin
BACKGROUNDPlastic-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.OBJECTIVESThis 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 peri-operative period.METHODWe collected daily urine samples from infants with CHD undergoing cardiac surgery during the peri-operative period (from birth to 21 days) and measured BPA, 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 (UHPLC-MS/MS). Machine learning-based cluster analysis was utilized to analyze these time-dependent data.RESULTSUtilizing 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.DISCUSSIONOur 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.
{"title":"A Machine Learning-Based Clustering Analysis to Explore Bisphenol A and Phthalate Exposure from Medical Devices in Infants with Congenital Heart Defects.","authors":"Wei-Chun Chou,J William Gaynor,Eric M Graham,Brenna Klepczynski,Tia Walker,Eric S Coker,Richard F Ittenbach,Zhoumeng Lin","doi":"10.1289/ehp15034","DOIUrl":"https://doi.org/10.1289/ehp15034","url":null,"abstract":"BACKGROUNDPlastic-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.OBJECTIVESThis 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 peri-operative period.METHODWe collected daily urine samples from infants with CHD undergoing cardiac surgery during the peri-operative period (from birth to 21 days) and measured BPA, 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 (UHPLC-MS/MS). Machine learning-based cluster analysis was utilized to analyze these time-dependent data.RESULTSUtilizing 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.DISCUSSIONOur 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.","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"68 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921024","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}
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