Pub Date : 2026-10-12DOI: 10.1016/j.envint.2026.110546
Nobuhisa Morimoto, Yukiko Nishihama, Kazunari Onishi, Shoji F Nakayama
{"title":"Corrigendum to \"Association between blood lipid levels in early pregnancy and urinary organophosphate metabolites in the Japan Environment and Children's Study\" [Environ. Int. 190 (2024) 108932].","authors":"Nobuhisa Morimoto, Yukiko Nishihama, Kazunari Onishi, Shoji F Nakayama","doi":"10.1016/j.envint.2026.110546","DOIUrl":"https://doi.org/10.1016/j.envint.2026.110546","url":null,"abstract":"","PeriodicalId":308,"journal":{"name":"Environment International","volume":" ","pages":"110546"},"PeriodicalIF":10.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163487","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}
Pub Date : 2026-10-04DOI: 10.1016/j.envint.2026.110548
Leonardo Trasande, Morgan E. Nelson, Akram Alshawabkeh, Emily S. Barrett, Jessie P. Buckley, Dana Dabelea, Anne L. Dunlop, Julie B. Herbstman, John D. Meeker, Mrudula Naidu, Craig Newschaffer, Amy M. Padula, Megan E. Romano, Douglas M. Ruden, Sheela Sathyanarayana, Susan L. Schantz, Anne P. Starling, Taylor M. Etzel, for the ECHO Cohort Consortium
A large body of evidence has documented the effects of ortho-phthalates, additives to soft plastic used in food packaging, on premature birth. Ortho-phthalates are increasingly replaced with alternatives including tere-phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH). A limited toxicological literature suggests that DINCH metabolites disrupt sex hormones and promote oxidant stress known to contribute to adverse birth outcomes, and epidemiologic studies have also been limited in sample size, inclusivity of different populations and measurements at different time points in pregnancy.
{"title":"Prenatal exposure to di(isononyl) cyclohexane-1,2-dicarboxylate and adverse birth outcomes in the USA: a prospective analysis of births in a large American birth cohort","authors":"Leonardo Trasande, Morgan E. Nelson, Akram Alshawabkeh, Emily S. Barrett, Jessie P. Buckley, Dana Dabelea, Anne L. Dunlop, Julie B. Herbstman, John D. Meeker, Mrudula Naidu, Craig Newschaffer, Amy M. Padula, Megan E. Romano, Douglas M. Ruden, Sheela Sathyanarayana, Susan L. Schantz, Anne P. Starling, Taylor M. Etzel, for the ECHO Cohort Consortium","doi":"10.1016/j.envint.2026.110548","DOIUrl":"https://doi.org/10.1016/j.envint.2026.110548","url":null,"abstract":"A large body of evidence has documented the effects of ortho-phthalates, additives to soft plastic used in food packaging, on premature birth. Ortho-phthalates are increasingly replaced with alternatives including tere-phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH). A limited toxicological literature suggests that DINCH metabolites disrupt sex hormones and promote oxidant stress known to contribute to adverse birth outcomes, and epidemiologic studies have also been limited in sample size, inclusivity of different populations and measurements at different time points in pregnancy.","PeriodicalId":308,"journal":{"name":"Environment International","volume":"33 1 1","pages":"110548"},"PeriodicalIF":11.8,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123672","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}
Pub Date : 2026-10-01Epub Date: 2026-09-28DOI: 10.1016/j.envint.2026.110540
Tess Goessens, Yasmine Bader, Febe Vertriest, Kokeb Tesfamariam, Sarah De Saeger, Carl Lachat, Marthe De Boevre
Background
Mycotoxins, toxic fungal metabolites present in food, are an increasing global health concern expected to intensify with climate change and shifting dietary patterns.
Aim
This review systematically identified, appraised, and synthesized primary research on human health effects associated with exposure to single and multiple mycotoxins, aiming to clarify current evidence, uncertainties, and research gaps.
Methods
Following the PECO framework, Embase, Cochrane Library, PubMed, Web of Science, and Scopus were searched from inception to May 2025 for studies reporting measured or modelled mycotoxin exposure and human health outcomes. Non-human, mechanistic, review, and grey literature were excluded. Three reviewers independently screened studies, with duplicate full-text assessment. Risk of bias was evaluated using OHAT and certainty of evidence with GRADE. Sensitivity analyses, publication bias assessment, and non-quantitative evidence were synthesized using Cochrane effect-direction plots. Random-effects meta-analyses assessed associations between aflatoxin exposure and seven health outcomes.
Results
Of 55,342 records, 268 studies met inclusion criteria, covering 17 mycotoxin groups and 71 health outcomes. Liver disease, particularly hepatocellular carcinoma, and kidney disease were the most frequently investigated outcomes, with most studies conducted in Africa and Asia. Qualitative synthesis demonstrated predominantly positive associations between mycotoxin exposure and neurological, metabolic, oncological, renal, reproductive, and developmental disorders. Certainty of evidence was very low for all 21 assessed outcomes, reflecting the predominance of cross-sectional designs and substantial between-study inconsistency. Quantitative meta-analyses of 42 studies identified associations between aflatoxin exposure and hepatocellular carcinoma, liver cirrhosis, elevated ALT, and gallbladder cancer.
Conclusion
Evidence supports associations between mycotoxin exposure and multiple health risks; however, heterogeneity in study design, exposure assessment, and outcome reporting highlights the need for more rigorous and harmonized research across diverse populations.
背景：真菌毒素，即存在于食物中的有毒真菌代谢物，是一个日益严重的全球健康问题，预计将随着气候变化和饮食模式的转变而加剧。目的：本综述系统地识别、评价和综合了与暴露于单一和多种真菌毒素有关的人类健康影响的初步研究，旨在澄清当前的证据、不确定性和研究空白。方法：根据PECO框架，检索Embase、Cochrane图书馆、PubMed、Web of Science和Scopus，从建立到2025年5月，报告测量或模拟霉菌毒素暴露和人类健康结果的研究。非人类、机械、综述和灰色文献被排除在外。三位审稿人独立筛选研究，并进行重复的全文评估。偏倚风险采用OHAT评估，证据确定性采用GRADE评估。敏感性分析、发表偏倚评估和非定量证据采用Cochrane效应方向图进行综合。随机效应荟萃分析评估了黄曲霉毒素暴露与七种健康结果之间的关系。结果：在55,342项记录中，268项研究符合纳入标准，涵盖17个霉菌毒素组和71个健康结局。肝脏疾病，特别是肝细胞癌和肾脏疾病是最常见的调查结果，大多数研究在非洲和亚洲进行。定性合成证明真菌毒素暴露与神经、代谢、肿瘤、肾脏、生殖和发育障碍之间存在显著正相关。所有21个评估结果的证据确定性都很低，反映了横断面设计的优势和研究之间的大量不一致。42项研究的定量荟萃分析确定了黄曲霉毒素暴露与肝细胞癌、肝硬化、ALT升高和胆囊癌之间的关联。结论：有证据支持霉菌毒素暴露与多种健康风险之间存在关联；然而，研究设计、暴露评估和结果报告的异质性突出了在不同人群中进行更严格和协调的研究的必要性。
{"title":"Systematic review and meta-analysis of adverse health effects associated with mycotoxin exposure","authors":"Tess Goessens, Yasmine Bader, Febe Vertriest, Kokeb Tesfamariam, Sarah De Saeger, Carl Lachat, Marthe De Boevre","doi":"10.1016/j.envint.2026.110540","DOIUrl":"10.1016/j.envint.2026.110540","url":null,"abstract":"<div><h3>Background</h3><div>Mycotoxins, toxic fungal metabolites present in food, are an increasing global health concern expected to intensify with climate change and shifting dietary patterns.</div></div><div><h3>Aim</h3><div>This review systematically identified, appraised, and synthesized primary research on human health effects associated with exposure to single and multiple mycotoxins, aiming to clarify current evidence, uncertainties, and research gaps.</div></div><div><h3>Methods</h3><div>Following the PECO framework, Embase, Cochrane Library, PubMed, Web of Science, and Scopus were searched from inception to May 2025 for studies reporting measured or modelled mycotoxin exposure and human health outcomes. Non-human, mechanistic, review, and grey literature were excluded. Three reviewers independently screened studies, with duplicate full-text assessment. Risk of bias was evaluated using OHAT and certainty of evidence with GRADE. Sensitivity analyses, publication bias assessment, and non-quantitative evidence were synthesized using Cochrane effect-direction plots. Random-effects <em>meta</em>-analyses assessed associations between aflatoxin exposure and seven health outcomes.</div></div><div><h3>Results</h3><div>Of 55,342 records, 268 studies met inclusion criteria, covering 17 mycotoxin groups and 71 health outcomes. Liver disease, particularly hepatocellular carcinoma, and kidney disease were the most frequently investigated outcomes, with most studies conducted in Africa and Asia. Qualitative synthesis demonstrated predominantly positive associations between mycotoxin exposure and neurological, metabolic, oncological, renal, reproductive, and developmental disorders. Certainty of evidence was very low for all 21 assessed outcomes, reflecting the predominance of cross-sectional designs and substantial between-study inconsistency. Quantitative <em>meta</em>-analyses of 42 studies identified associations between aflatoxin exposure and hepatocellular carcinoma, liver cirrhosis, elevated ALT, and gallbladder cancer.</div></div><div><h3>Conclusion</h3><div>Evidence supports associations between mycotoxin exposure and multiple health risks; however, heterogeneity in study design, exposure assessment, and outcome reporting highlights the need for more rigorous and harmonized research across diverse populations.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110540"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01Epub Date: 2026-09-21DOI: 10.1016/j.envint.2026.110535
Joshua D. Preston, Yongliang Liang, Thomas Szabo Yamashita, Sami Teeny, Jaclyn Weinberg, William J. Crandall, Zachery R. Jarrell, Xin Hu, Susan A. Safley, Jennifer M. Robertson, ViLinh Tran, Anee S. Jackson, Snehal G. Patel, Logan D. Glosser, Collin J. Weber, Jyotirmay Sharma, Neil D. Saunders, Young-Mi Go, Dean P. Jones, M. Ryan Smith
Differentiated thyroid cancer (DTC) incidence has increased over recent decades. Environmental risk factors may contribute, but little information is available on cumulative exposures to environmental chemicals in human thyroid tumors. This pilot study screened for and characterized environmental chemicals in DTC and non-cancer cadaver thyroid tissues, and explored differences in chemical profiles between tumor types as a secondary goal. Surgical samples from patients undergoing total or subtotal thyroidectomy for thyroid cancer in Atlanta, GA (USA) were procured from a biorepository (N = 60 representing three types: papillary thyroid carcinoma [PTC], follicular thyroid carcinoma [FTC], and invasive encapsulated follicular variant of PTC [IEFVPTC]; n = 20/type), along with cadaveric non-cancer thyroids for comparison (n = 8). An exposomics analysis was performed using gas chromatography–mass spectrometry to screen for chemicals from a library of 709 xenobiotic compounds. Overall, 442 environmental chemicals were annotated, including insecticides, herbicides, chemical synthesis intermediates, dye intermediates, flavoring or fragrance agents, plasticizers, solvents, combustion byproducts, fungicides, flame retardants, preservatives, polychlorinated biphenyls, lubricants, and per- and polyfluoroalkyl substances. Of these, 40 % were potential endocrine-disrupting chemicals. Twenty-nine identified chemicals differed between types; PTC samples in particular had higher levels of several combustion byproducts, insecticides and pesticides, and herbicides, many of which were known, likely, or possible carcinogens. However, no type-specific differences remained significant following correction for multiple comparisons. Two IARC Group 1 carcinogens, o-toluidine and 4-aminobiphenyl, were higher in tumors than in non-cancer thyroids. This study provides evidence for accumulation of environmental chemicals in human DTC and posits that specific pollutants may influence type-specific carcinogenesis. Larger and more geographically diverse cohorts are needed to determine the generalizability of these findings.
分化型甲状腺癌（DTC）的发病率在近几十年来有所增加。环境风险因素可能起作用，但关于人类甲状腺肿瘤中环境化学品累积暴露的信息很少。这项初步研究筛选和表征了DTC和非癌尸体甲状腺组织中的环境化学物质，并探索肿瘤类型之间化学特征的差异作为次要目标。来自美国乔治亚州亚特兰大接受甲状腺癌全切除术或次全切除术患者的手术样本来自生物库（N = 60，代表三种类型：乳头状甲状腺癌[PTC]、滤泡性甲状腺癌[FTC]和侵袭性囊泡性甲状腺癌[IEFVPTC]； N = 20/型），以及尸体非癌性甲状腺（N = 8）进行比较。利用气相色谱-质谱联用技术对709种外源性化合物进行了暴露组学分析。总共注释了442种环境化学品，包括杀虫剂、除草剂、化学合成中间体、染料中间体、调味剂或芳香剂、增塑剂、溶剂、燃烧副产物、杀菌剂、阻燃剂、防腐剂、多氯联苯、润滑剂以及全氟烷基和多氟烷基物质。其中40%是潜在的干扰内分泌的化学物质。29种已确定的化学物质在不同类型之间存在差异；特别是PTC样品中几种燃烧副产物、杀虫剂和除草剂的含量较高，其中许多是已知的、可能的或可能的致癌物质。然而，在多次比较校正后，没有类型特异性差异仍然显著。两种IARC 1组致癌物，邻甲苯胺和4-氨基联苯，在肿瘤中的含量高于非癌性甲状腺。本研究为环境化学物质在人类DTC中的积累提供了证据，并假设特定污染物可能影响特定类型的致癌作用。为了确定这些发现的普遍性，需要更大、地理上更多样化的队列。
{"title":"Environmental chemical burden in differentiated thyroid cancer","authors":"Joshua D. Preston, Yongliang Liang, Thomas Szabo Yamashita, Sami Teeny, Jaclyn Weinberg, William J. Crandall, Zachery R. Jarrell, Xin Hu, Susan A. Safley, Jennifer M. Robertson, ViLinh Tran, Anee S. Jackson, Snehal G. Patel, Logan D. Glosser, Collin J. Weber, Jyotirmay Sharma, Neil D. Saunders, Young-Mi Go, Dean P. Jones, M. Ryan Smith","doi":"10.1016/j.envint.2026.110535","DOIUrl":"10.1016/j.envint.2026.110535","url":null,"abstract":"<div><div>Differentiated thyroid cancer (DTC) incidence has increased over recent decades. Environmental risk factors may contribute, but little information is available on cumulative exposures to environmental chemicals in human thyroid tumors. This pilot study screened for and characterized environmental chemicals in DTC and non-cancer cadaver thyroid tissues, and explored differences in chemical profiles between tumor types as a secondary goal. Surgical samples from patients undergoing total or subtotal thyroidectomy for thyroid cancer in Atlanta, GA (USA) were procured from a biorepository (<em>N</em> = 60 representing three types: papillary thyroid carcinoma [PTC], follicular thyroid carcinoma [FTC], and invasive encapsulated follicular variant of PTC [IEFVPTC]; <em>n</em> = 20/type), along with cadaveric non-cancer thyroids for comparison (<em>n</em> = 8). An exposomics analysis was performed using gas chromatography–mass spectrometry to screen for chemicals from a library of 709 xenobiotic compounds. Overall, 442 environmental chemicals were annotated, including insecticides, herbicides, chemical synthesis intermediates, dye intermediates, flavoring or fragrance agents, plasticizers, solvents, combustion byproducts, fungicides, flame retardants, preservatives, polychlorinated biphenyls, lubricants, and per- and polyfluoroalkyl substances. Of these, 40 % were potential endocrine-disrupting chemicals. Twenty-nine identified chemicals differed between types; PTC samples in particular had higher levels of several combustion byproducts, insecticides and pesticides, and herbicides, many of which were known, likely, or possible carcinogens. However, no type-specific differences remained significant following correction for multiple comparisons. Two IARC Group 1 carcinogens, <em>o</em>-toluidine and 4-aminobiphenyl, were higher in tumors than in non-cancer thyroids. This study provides evidence for accumulation of environmental chemicals in human DTC and posits that specific pollutants may influence type-specific carcinogenesis. Larger and more geographically diverse cohorts are needed to determine the generalizability of these findings.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110535"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01Epub Date: 2026-10-05DOI: 10.1016/j.envint.2026.110552
Fengyi Zhang, Rongke Hu, Wenqi Sun, Bendong Shi, Yujie Yao
Deoxynivalenol (DON) is a widespread mycotoxin contaminating cereal grains and animal feed, posing significant risks to livestock health and food safety. However, the molecular mechanisms underlying DON-induced nephrotoxicity remain poorly understood. In this study, we identify cuproptosis as a critical driver of DON-induced nephrotoxicity in chickens and investigate the protective role of nano-selenium (Nano-Se). DON exposure disrupted copper homeostasis and induced cuproptosis, as evidenced by dysregulation of FDX1, LIAS, and DLAT, resulting in mitochondrial oxidative damage and electron transport chain (ETC) dysfunction. Excessive mitochondrial reactive oxygen species (mtROS) further impaired lysosomal acidification, resulting in lysosomal membrane permeabilization (LMP) and blockade of mitophagic flux, ultimately triggering a robust inflammatory response. Nano-Se supplementation effectively mitigated DON-induced renal injury by suppressing cuproptosis, restoring mitochondrial redox balance, preserving ETC function, rescuing lysosomal function, re-establishing mitophagic flux, and attenuating inflammatory responses in vivo and in vitro. Mechanistically, pharmacological modulation targeting copper levels, mtROS generation, or mitophagic flux abolished the protective effects of Nano-Se. Collectively, these findings reveal that DON induces nephrotoxicity via the cuproptosis-mtROS-mitophagy axis and that Nano-Se ameliorates DON-induced renal inflammation by suppressing cuproptosis, reducing mtROS accumulation, and restoring mitophagic flux. This study provides a mechanistic basis for the use of Nano-Se as a potential therapeutic agent against mycotoxin-associated renal injury, with implications for environmental health risk assessment and livestock production.
{"title":"Nano-selenium suppresses cuproptosis to restore mitophagic flux and alleviate deoxynivalenol-induced renal inflammation","authors":"Fengyi Zhang, Rongke Hu, Wenqi Sun, Bendong Shi, Yujie Yao","doi":"10.1016/j.envint.2026.110552","DOIUrl":"10.1016/j.envint.2026.110552","url":null,"abstract":"<div><div>Deoxynivalenol (DON) is a widespread mycotoxin contaminating cereal grains and animal feed, posing significant risks to livestock health and food safety. However, the molecular mechanisms underlying DON-induced nephrotoxicity remain poorly understood. In this study, we identify cuproptosis as a critical driver of DON-induced nephrotoxicity in chickens and investigate the protective role of nano-selenium (Nano-Se). DON exposure disrupted copper homeostasis and induced cuproptosis, as evidenced by dysregulation of FDX1, LIAS, and DLAT, resulting in mitochondrial oxidative damage and electron transport chain (ETC) dysfunction. Excessive mitochondrial reactive oxygen species (mtROS) further impaired lysosomal acidification, resulting in lysosomal membrane permeabilization (LMP) and blockade of mitophagic flux, ultimately triggering a robust inflammatory response. Nano-Se supplementation effectively mitigated DON-induced renal injury by suppressing cuproptosis, restoring mitochondrial redox balance, preserving ETC function, rescuing lysosomal function, re-establishing mitophagic flux, and attenuating inflammatory responses in vivo and in vitro. Mechanistically, pharmacological modulation targeting copper levels, mtROS generation, or mitophagic flux abolished the protective effects of Nano-Se. Collectively, these findings reveal that DON induces nephrotoxicity via the cuproptosis-mtROS-mitophagy axis and that Nano-Se ameliorates DON-induced renal inflammation by suppressing cuproptosis, reducing mtROS accumulation, and restoring mitophagic flux. This study provides a mechanistic basis for the use of Nano-Se as a potential therapeutic agent against mycotoxin-associated renal injury, with implications for environmental health risk assessment and livestock production.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110552"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01Epub Date: 2026-10-10DOI: 10.1016/j.envint.2026.110559
Tong An, Guohuan Zhang, Nian Liu, Bin Liang, Ziyi Song, Lei Fu, Xueyan Bai, Shuo Han, Qun Lu, Ligang Hu
The oocyte microenvironment, comprising ovarian granulosa cells (GCs) and follicular fluid (FF), sustains oocyte development with nutrients and regulatory signals but may also transfer heavy metals to the oocyte. While high concentrations of heavy metals in FF and blood have been associated with impaired oocyte development, the effect of low-level exposure on the oocyte remains unclear, partly due to the analytical challenges in measuring low-level heavy metals in biological fluids. Here, we investigated the associations between low-level heavy metal exposure and oocyte development. Using a highly sensitive single-cell metallomic technique, we analyzed ovarian GCs collected from women undergoing in vitro fertilization and embryo transfer (IVF-ET) to serve as a biomarker of intracellular heavy metal burden in the peri-oocyte microenvironment. The associations between heavy metals in GCs and reproductive outcomes across multiple key reproductive stages were analyzed. Our results showed that the heavy metals content in GCs were generally below 0.5 fg/cell. Higher mean intensities and prevalence of several metals in GCs were significantly associated with reduced oocyte maturation rate, normal fertilization rate, and good-quality embryo rate (all adjusted P < 0.05). Elevated intracellular levels of lead and mercury were also associated with adverse reproductive outcomes and increased risk of early miscarriage. In contrast, higher heterogeneity of Hg within GCs was associated with reduced miscarriage risk (OR = 0.37 [0.04, 0.92], P = 0.034). Notably, these associations are significantly contributed by intercellular heterogeneity of metal accumulation within the GC population. Our study demonstrates the feasibility of applying single-cell metallomic technique to ovarian GCs to assess the reproductive risk associated with low-level intracellular heavy metal burden in ovarian follicles, and underscores the need for further reducing environmental heavy metal exposure to protect female reproductive health.
{"title":"Single-Cell Metallomics of ovarian granulosa cells enables assessment of Low-Level heavy metal exposure associated with impaired human oocyte development","authors":"Tong An, Guohuan Zhang, Nian Liu, Bin Liang, Ziyi Song, Lei Fu, Xueyan Bai, Shuo Han, Qun Lu, Ligang Hu","doi":"10.1016/j.envint.2026.110559","DOIUrl":"10.1016/j.envint.2026.110559","url":null,"abstract":"<div><div>The oocyte microenvironment, comprising ovarian granulosa cells (GCs) and follicular fluid (FF), sustains oocyte development with nutrients and regulatory signals but may also transfer heavy metals to the oocyte. While high concentrations of heavy metals in FF and blood have been associated with impaired oocyte development, the effect of low-level exposure on the oocyte remains unclear, partly due to the analytical challenges in measuring low-level heavy metals in biological fluids. Here, we investigated the associations between low-level heavy metal exposure and oocyte development. Using a highly sensitive single-cell metallomic technique, we analyzed ovarian GCs collected from women undergoing <em>in vitro</em> fertilization and embryo transfer (IVF-ET) to serve as a biomarker of intracellular heavy metal burden in the <em>peri</em>-oocyte microenvironment. The associations between heavy metals in GCs and reproductive outcomes across multiple key reproductive stages were analyzed. Our results showed that the heavy metals content in GCs were generally below 0.5 fg/cell. Higher mean intensities and prevalence of several metals in GCs were significantly associated with reduced oocyte maturation rate, normal fertilization rate, and good-quality embryo rate (all adjusted <em>P</em> < 0.05). Elevated intracellular levels of lead and mercury were also associated with adverse reproductive outcomes and increased risk of early miscarriage. In contrast, higher heterogeneity of Hg within GCs was associated with reduced miscarriage risk (<em>OR</em> = 0.37 [0.04, 0.92], <em>P</em> = 0.034). Notably, these associations are significantly contributed by intercellular heterogeneity of metal accumulation within the GC population. Our study demonstrates the feasibility of applying single-cell metallomic technique to ovarian GCs to assess the reproductive risk associated with low-level intracellular heavy metal burden in ovarian follicles, and underscores the need for further reducing environmental heavy metal exposure to protect female reproductive health.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110559"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01Epub Date: 2026-10-12DOI: 10.1016/j.envint.2026.110562
Jing Shang, Lin Pei, Shiguang Miao, Xiya Zhang, Jingjing Dou, Chunchun Meng, Wenjia Cai, Zhaobin Sun
Driven by climate change, extreme heat events pose growing health threats across China. Although infrastructure-based urban cooling strategies have been promoted, the regional disparities in their cooling efficacy and health benefits remain insufficiently quantified. Using the WRF-SLUCM and regional temperature-mortality exposure–response relationships, this study simulated four typical cooling measures (Green Roof, Cool Roof, Street Tree, and Full Adaptation) across 319 Chinese cities during summer 2022 and quantified heat-related mortality reductions. Results show that Full Adaptation reduces heat mortality by 18.8 % (95 % CI: 12.7 %–24.5 %), while Cool Roof, Green Roof, and Street Tree achieve 11.2 % (95 % CI: 7.6 %–14.6 %), 11.0 % (95 % CI: 7.4 %–14.3 %) and 5.5 % (95 % CI: 3.3 %–7.5 %) reductions, respectively. Beyond regional differences in cooling efficacy, variation in dRR/dT is another key determinant of overall effectiveness. This study emphasizes that the deployment of infrastructure‑based strategies at the regional level should balance both efficiency and equity principles. East China, with its large exposed urban population, delivers the greatest total health benefits. Regions with higher temperature sensitivity, such as Southwest and Northwest China, achieve larger per‑capita mortality reductions per unit temperature drop. In regions such as South China, where populations have developed substantial heat acclimatization, the mortality mitigation effect of cooling interventions is comparatively limited. These findings confirm the effectiveness of infrastructure‑based urban cooling strategies in reducing heat‑related mortality risk across China, while also revealing substantial regional heterogeneity, suggesting that priority should be balanced between areas of high temperature sensitivity and those with large population exposure.
{"title":"Regional heterogeneity in heat mortality reduction by urban cooling strategies across Chinese cities","authors":"Jing Shang, Lin Pei, Shiguang Miao, Xiya Zhang, Jingjing Dou, Chunchun Meng, Wenjia Cai, Zhaobin Sun","doi":"10.1016/j.envint.2026.110562","DOIUrl":"10.1016/j.envint.2026.110562","url":null,"abstract":"<div><div>Driven by climate change, extreme heat events pose growing health threats across China. Although infrastructure-based urban cooling strategies have been promoted, the regional disparities in their cooling efficacy and health benefits remain insufficiently quantified. Using the WRF-SLUCM and regional temperature-mortality exposure–response relationships, this study simulated four typical cooling measures (Green Roof, Cool Roof, Street Tree, and Full Adaptation) across 319 Chinese cities during summer 2022 and quantified heat-related mortality reductions. Results show that Full Adaptation reduces heat mortality by 18.8 % (95 % CI: 12.7 %–24.5 %), while Cool Roof, Green Roof, and Street Tree achieve 11.2 % (95 % CI: 7.6 %–14.6 %), 11.0 % (95 % CI: 7.4 %–14.3 %) and 5.5 % (95 % CI: 3.3 %–7.5 %) reductions, respectively. Beyond regional differences in cooling efficacy, variation in dRR/dT is another key determinant of overall effectiveness. This study emphasizes that the deployment of infrastructure‑based strategies at the regional level should balance both efficiency and equity principles. East China, with its large exposed urban population, delivers the greatest total health benefits. Regions with higher temperature sensitivity, such as Southwest and Northwest China, achieve larger per‑capita mortality reductions per unit temperature drop. In regions such as South China, where populations have developed substantial heat acclimatization, the mortality mitigation effect of cooling interventions is comparatively limited. These findings confirm the effectiveness of infrastructure‑based urban cooling strategies in reducing heat‑related mortality risk across China, while also revealing substantial regional heterogeneity, suggesting that priority should be balanced between areas of high temperature sensitivity and those with large population exposure.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110562"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Widespread atmospheric pollutants such as benzo[a]pyrene (BaP) and bisphenol A (BPA) persistently coexist, yet their combined risks to the respiratory system remain largely overlooked. In this study, C57BL/6J mouse and A549 cell models were employed to investigate the combined pulmonary toxicity induced by BaP and BPA, with an integrated transcriptomic-metabolomic framework established to characterize their response patterns. Combined exposure to BaP and BPA caused pathological damage in mouse lung tissue and specifically induced a broader spectrum of adverse effects. In vitro experiments demonstrated that combined exposure induced cytotoxicity, including FOXM1-mediated changes in cell survival and EGFR/AKT pathway-mediated alterations in the invasive phenotype. Transcriptomic and metabolomic analyses indicated that combined exposure suppressed immune cell populations, especially CD8 T cells, and disrupted glycerophospholipid metabolism. We further categorized these outcomes into four interaction response patterns, which may facilitate the more precise identification of target information within specific interaction contexts. In addition, glycerophosphocholine (GPC) was found to mediate the overall immunosuppressive effects caused by combined exposure, while had a limited effect on changes in lung cell populations. We suggest that greater attention be paid to the interaction characteristics between mixed pollutants and their molecular targets within the framework of joint health risk assessment, to improve the mechanistic understanding of complex combined toxic effects.
{"title":"Benzo[a]pyrene and bisphenol A interact to induce combined pulmonary toxicity through an integrated transcriptomic-metabolomic network","authors":"Guangchao Yang, Xiaoyan Jiang, Liuhong Wang, Ying Peng, Wu Wen, Qile Fang, Yunjiang Yu, Qian Yang, Jining Liu","doi":"10.1016/j.envint.2026.110557","DOIUrl":"10.1016/j.envint.2026.110557","url":null,"abstract":"<div><div>Widespread atmospheric pollutants such as benzo[a]pyrene (BaP) and bisphenol A (BPA) persistently coexist, yet their combined risks to the respiratory system remain largely overlooked. In this study, C57BL/6J mouse and A549 cell models were employed to investigate the combined pulmonary toxicity induced by BaP and BPA, with an integrated transcriptomic-metabolomic framework established to characterize their response patterns. Combined exposure to BaP and BPA caused pathological damage in mouse lung tissue and specifically induced a broader spectrum of adverse effects. <em>In vitro</em> experiments demonstrated that combined exposure induced cytotoxicity, including FOXM1-mediated changes in cell survival and EGFR/AKT pathway-mediated alterations in the invasive phenotype. Transcriptomic and metabolomic analyses indicated that combined exposure suppressed immune cell populations, especially CD8 T cells, and disrupted glycerophospholipid metabolism. We further categorized these outcomes into four interaction response patterns, which may facilitate the more precise identification of target information within specific interaction contexts. In addition, glycerophosphocholine (GPC) was found to mediate the overall immunosuppressive effects caused by combined exposure, while had a limited effect on changes in lung cell populations. We suggest that greater attention be paid to the interaction characteristics between mixed pollutants and their molecular targets within the framework of joint health risk assessment, to improve the mechanistic understanding of complex combined toxic effects.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110557"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01Epub Date: 2026-10-05DOI: 10.1016/j.envint.2026.110554
Yanyan Zhou, Alemseged Tamiru Haile, Mulugeta Kibret, Hu Li, Mihret Mersha Haileselassie, Tilaye Worku Bekele, Jemila Mohammed Kassa, Kirubel Demissie, Ethan R. Wyrsch, Steven P. Djordjevic, Kelly Jobling, Marcos Quintela-Baluja, Jian-Qiang Su, Javier Mateo-Sagasta, David W Graham
Rapid urbanization in the Global South consistently outpaces sanitation infrastructure, transforming urban rivers into AMR reservoirs. Yet watershed-scale quantification of resistomes in such settings remains scarce, limiting exposure risk assessment and intervention planning. Here we present the most detailed spatial baseline for waterborne AMR in sub-Saharan Africa, using the Akaki River (Addis Ababa, Ethiopia) as a model system for rapidly urbanizing megacity watersheds with inadequate sanitation. We sampled 38 sites across an extreme pollution gradient during the dry season, when low flow produces maximum pollutant concentrations and the highest resident exposure risk. Water quality, microbiome marker data, 309 antibiotic resistance genes (ARGs), and 57 mobile genetic elements (MGEs) were quantified by high-throughput quantitative PCR. ARG and MGE abundances in central urban reaches exceeded 1010 gene copies L-1, indistinguishable from untreated sewage. Critically, clinically important ARGs co-occurred widely with broad-host-range MGEs, including the IncP-1α plasmid backbone, IS26, ISEcp1, IS6100, and class 1 integron integrase genes, indicating that ARGs are primed for potential horizontal gene transfer in waters where hundreds of thousands of Addis residents bathe, wash, and irrigate food crops. Dissolved oxygen depletion and elevated NH4-N correlated significantly with resistome expansion (p < 0.01), serving as robust chemical proxies for diffuse, system-wide raw sewage inputs that carry the actual mechanistic AMR drivers (e.g., heavy metals, antibiotic residues, and resistant hosts). The 38-site spatial design and dry-season worst-case conditions together provide a replicable model for AMR exposure assessment in comparable Global South cities.
{"title":"Inadequate waste management drives the spread of antimicrobial resistance across the watershed of a large African city","authors":"Yanyan Zhou, Alemseged Tamiru Haile, Mulugeta Kibret, Hu Li, Mihret Mersha Haileselassie, Tilaye Worku Bekele, Jemila Mohammed Kassa, Kirubel Demissie, Ethan R. Wyrsch, Steven P. Djordjevic, Kelly Jobling, Marcos Quintela-Baluja, Jian-Qiang Su, Javier Mateo-Sagasta, David W Graham","doi":"10.1016/j.envint.2026.110554","DOIUrl":"10.1016/j.envint.2026.110554","url":null,"abstract":"<div><div>Rapid urbanization in the Global South consistently outpaces sanitation infrastructure, transforming urban rivers into AMR reservoirs. Yet watershed-scale quantification of resistomes in such settings remains scarce, limiting exposure risk assessment and intervention planning. Here we present the most detailed spatial baseline for waterborne AMR in sub-Saharan Africa, using the Akaki River (Addis Ababa, Ethiopia) as a model system for rapidly urbanizing megacity watersheds with inadequate sanitation. We sampled 38 sites across an extreme pollution gradient during the dry season, when low flow produces maximum pollutant concentrations and the highest resident exposure risk. Water quality, microbiome marker data, 309 antibiotic resistance genes (ARGs), and 57 mobile genetic elements (MGEs) were quantified by high-throughput quantitative PCR. ARG and MGE abundances in central urban reaches exceeded 10<sup>10</sup> gene copies L<sup>-1</sup>, indistinguishable from untreated sewage. Critically, clinically important ARGs co-occurred widely with broad-host-range MGEs, including the IncP-1α plasmid backbone, IS<em>26</em>, IS<em>Ecp1</em>, IS<em>6100</em>, and class 1 integron integrase genes, indicating that ARGs are primed for potential horizontal gene transfer in waters where hundreds of thousands of Addis residents bathe, wash, and irrigate food crops. Dissolved oxygen depletion and elevated NH<sub>4</sub>-N correlated significantly with resistome expansion (<em>p</em> < 0.01), serving as robust chemical proxies for diffuse, system-wide raw sewage inputs that carry the actual mechanistic AMR drivers (e.g., heavy metals, antibiotic residues, and resistant hosts). The 38-site spatial design and dry-season worst-case conditions together provide a replicable model for AMR exposure assessment in comparable Global South cities.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"216 ","pages":"Article 110554"},"PeriodicalIF":10.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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