Pub Date : 2025-12-05DOI: 10.1016/j.ecoenv.2025.119506
Hui Chang , Huanhuan Zhang , Yuanfang Zhao , Yangyang Yuan , Junze Deng , Jian Jin , Yi Wei , Mingyi Xue , Zengli Yu , Xin Zhao
The association of perinatal exposure to airborne particulate matter (PM) with preterm birth (PTB) remains unclear. This study aimed to investigate possible associations between PM exposure and risk of PTB. There were 61,620 sibling pairs from a retrospective sibling matched cohort study were included. PM exposure was estimated by space-time extremely randomized trees models. Within-group differences in 2.5 and 10 μm particulate (ΔPM2.5 and ΔPM10) maternal exposure levels between corresponding trimesters of two consecutive pregnancies were tested for associations with moderate, very, or all PTB using fixed-effect regression models. Gestational age and difference in gestational age (Δ gestational age) between siblings were treated as secondary outcomes. A total of 1301 (2.1 %) incident PTB cases were confirmed in our study. The exposure-response analyses suggested that each 10 μg/m3 increase in ΔPM2.5 or ΔPM10 were associated with the increased risk of PTB, with significant effect in first trimester (ΔPM2.5 adjusted OR = 1.375, 95 % CI: 1.141, 1.658; ΔPM10 adjusted OR = 1.241, 95 %CI: 1.073, 1.435). Increase in ΔPM2.5 or ΔPM10 in first, second, and third trimester were significantly associated with a shortened gestational age. PTB risk and gestational age shared a near linear exposure-response relationship with increased ΔPM2.5 and ΔPM10 in whole pregnancy. In conclusion, increased ambient PM2.5 exposure is positively associated with reduced gestational age, while increased PM2.5 and PM10 concentration is associated with PTB risk.
{"title":"Association of ambient particulate matter exposure with preterm birth and gestational age in a retrospective sibling-matched Chinese cohort","authors":"Hui Chang , Huanhuan Zhang , Yuanfang Zhao , Yangyang Yuan , Junze Deng , Jian Jin , Yi Wei , Mingyi Xue , Zengli Yu , Xin Zhao","doi":"10.1016/j.ecoenv.2025.119506","DOIUrl":"10.1016/j.ecoenv.2025.119506","url":null,"abstract":"<div><div>The association of perinatal exposure to airborne particulate matter (PM) with preterm birth (PTB) remains unclear. This study aimed to investigate possible associations between PM exposure and risk of PTB. There were 61,620 sibling pairs from a retrospective sibling matched cohort study were included. PM exposure was estimated by space-time extremely randomized trees models. Within-group differences in 2.5 and 10 μm particulate (ΔPM<sub>2.5</sub> and ΔPM<sub>10</sub>) maternal exposure levels between corresponding trimesters of two consecutive pregnancies were tested for associations with moderate, very, or all PTB using fixed-effect regression models. Gestational age and difference in gestational age (Δ gestational age) between siblings were treated as secondary outcomes. A total of 1301 (2.1 %) incident PTB cases were confirmed in our study. The exposure-response analyses suggested that each 10 μg/m<sup>3</sup> increase in ΔPM<sub>2.5</sub> or ΔPM<sub>10</sub> were associated with the increased risk of PTB, with significant effect in first trimester (ΔPM<sub>2.5</sub> adjusted OR = 1.375, 95 % CI: 1.141, 1.658; ΔPM<sub>10</sub> adjusted OR = 1.241, 95 %CI: 1.073, 1.435). Increase in ΔPM<sub>2.5</sub> or ΔPM<sub>10</sub> in first, second, and third trimester were significantly associated with a shortened gestational age. PTB risk and gestational age shared a near linear exposure-response relationship with increased ΔPM<sub>2.5</sub> and ΔPM<sub>10</sub> in whole pregnancy. In conclusion, increased ambient PM<sub>2.5</sub> exposure is positively associated with reduced gestational age, while increased PM<sub>2.5</sub> and PM<sub>10</sub> concentration is associated with PTB risk.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119506"},"PeriodicalIF":6.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-05DOI: 10.1016/j.ecoenv.2025.119513
Hongxia Chen , Hong Cui , Zhongji Meng
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached epidemic proportions, creating a substantial healthcare burden. While traditionally attributed to caloric excess and sedentary lifestyles, the incomplete explanation provided by these factors alone has spurred the investigation of novel etiological agents. There is now compelling evidence that chronic, low-dose exposure to environmental endocrine-disrupting chemicals (EDCs) is a significant and underappreciated risk factor driving MASLD pathogenesis. This review synthesizes the current human epidemiological and mechanistic evidence, focusing on the last five years, to elucidate the role of both established EDCs (e.g., phthalates, bisphenols, PFAS, organochlorine pesticides) and emerging contaminants, notably micro- and nanoplastics (MNPs). We detail how these pervasive pollutants promote hepatic steatosis, inflammation, and fibrosis by disrupting nuclear receptor signaling (e.g., PPARγ), inducing gut dysbiosis and barrier dysfunction, causing mitochondrial and lysosomal impairment, and reprogramming lipid metabolism. The review highlights that MNPs, in particular, represent a frontier in environmental hepatotoxicity, with recent data revealing their ability to bioaccumulate and exacerbate metabolic insults through novel mechanisms. By integrating evidence from population studies and experimental models, this review underscores the necessity of incorporating the “exposome” into the MASLD etiological framework. It concludes that mitigating this public health challenge requires concerted efforts in advancing research on chemical mixtures and critical exposure windows, alongside implementing policies aimed at reducing environmental exposure.
{"title":"The nexus of environmental endocrine-disrupting chemical exposure and metabolic dysfunction-associated steatotic liver disease: An emerging public health challenge","authors":"Hongxia Chen , Hong Cui , Zhongji Meng","doi":"10.1016/j.ecoenv.2025.119513","DOIUrl":"10.1016/j.ecoenv.2025.119513","url":null,"abstract":"<div><div>The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached epidemic proportions, creating a substantial healthcare burden. While traditionally attributed to caloric excess and sedentary lifestyles, the incomplete explanation provided by these factors alone has spurred the investigation of novel etiological agents. There is now compelling evidence that chronic, low-dose exposure to environmental endocrine-disrupting chemicals (EDCs) is a significant and underappreciated risk factor driving MASLD pathogenesis. This review synthesizes the current human epidemiological and mechanistic evidence, focusing on the last five years, to elucidate the role of both established EDCs (e.g., phthalates, bisphenols, PFAS, organochlorine pesticides) and emerging contaminants, notably micro- and nanoplastics (MNPs). We detail how these pervasive pollutants promote hepatic steatosis, inflammation, and fibrosis by disrupting nuclear receptor signaling (e.g., PPARγ), inducing gut dysbiosis and barrier dysfunction, causing mitochondrial and lysosomal impairment, and reprogramming lipid metabolism. The review highlights that MNPs, in particular, represent a frontier in environmental hepatotoxicity, with recent data revealing their ability to bioaccumulate and exacerbate metabolic insults through novel mechanisms. By integrating evidence from population studies and experimental models, this review underscores the necessity of incorporating the “exposome” into the MASLD etiological framework. It concludes that mitigating this public health challenge requires concerted efforts in advancing research on chemical mixtures and critical exposure windows, alongside implementing policies aimed at reducing environmental exposure.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119513"},"PeriodicalIF":6.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-05DOI: 10.1016/j.ecoenv.2025.119516
Gaeun Kim , Jisoo Song , Junho Park , Hojun Lee , Taeyeon Hong , Sunwoo Park , Gwonhwa Song , Whasun Lim
Fenoxycarb is a carbamate pesticide that negatively affects the environment and harms various non-target organisms. Despite its common use in controlling fleas and mosquitoes that are often found in cattle feedlots, the toxic effects of fenoxycarb on cattle have not yet been studied. Considering the pivotal role of cattle in milk production, this study examined the effect of fenoxycarb on bovine mammary epithelial cells (MAC-T) to assess its potential risks for the lactation system. Fenoxycarb reduced cell viability and growth in both 2D and 3D cultures and increased apoptosis. Furthermore, it triggered sub-G1 phase arrest of the cell cycle, accompanied by a pronounced decrease in CCND1 and PCNA expression. Disruption of calcium homeostasis was demonstrated by a marked decline in calcium levels in both the cytosol and the mitochondria. This reduction ultimately led to the collapse of the overall calcium balance, which in turn is closely associated with a decrease in mitochondrial respiration. In addition, fenoxycarb triggered endoplasmic reticulum stress while suppressing the unfolded protein response, especially by inhibiting the EIF2A-GADD153 signaling pathway. Moreover, decreased expression of autophagy-related proteins and diminished formation of acidic vesicular organelles confirmed the occurrence of autophagy. This study highlights the potential adverse effects of fenoxycarb on the dairy industry by elucidating its toxicity mechanisms in bovine mammary glands.
{"title":"Fenoxycarb disrupts calcium homeostasis and impairs unfolded protein response and autophagy, leading to cell death in bovine mammary epithelial cells","authors":"Gaeun Kim , Jisoo Song , Junho Park , Hojun Lee , Taeyeon Hong , Sunwoo Park , Gwonhwa Song , Whasun Lim","doi":"10.1016/j.ecoenv.2025.119516","DOIUrl":"10.1016/j.ecoenv.2025.119516","url":null,"abstract":"<div><div>Fenoxycarb is a carbamate pesticide that negatively affects the environment and harms various non-target organisms. Despite its common use in controlling fleas and mosquitoes that are often found in cattle feedlots, the toxic effects of fenoxycarb on cattle have not yet been studied. Considering the pivotal role of cattle in milk production, this study examined the effect of fenoxycarb on bovine mammary epithelial cells (MAC-T) to assess its potential risks for the lactation system. Fenoxycarb reduced cell viability and growth in both 2D and 3D cultures and increased apoptosis. Furthermore, it triggered sub-G1 phase arrest of the cell cycle, accompanied by a pronounced decrease in CCND1 and PCNA expression. Disruption of calcium homeostasis was demonstrated by a marked decline in calcium levels in both the cytosol and the mitochondria. This reduction ultimately led to the collapse of the overall calcium balance, which in turn is closely associated with a decrease in mitochondrial respiration. In addition, fenoxycarb triggered endoplasmic reticulum stress while suppressing the unfolded protein response, especially by inhibiting the EIF2A-GADD153 signaling pathway. Moreover, decreased expression of autophagy-related proteins and diminished formation of acidic vesicular organelles confirmed the occurrence of autophagy. This study highlights the potential adverse effects of fenoxycarb on the dairy industry by elucidating its toxicity mechanisms in bovine mammary glands.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119516"},"PeriodicalIF":6.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-05DOI: 10.1016/j.ecoenv.2025.119509
Anita Jemec Kokalj , Cene Fišer , Maruša Poje , Igor Zelnik , Ester Premate , Tiziana Di Lorenzo
This study investigates the sensitivity of subterranean amphipods of the genus Niphargus to nitrate pollution, focusing on understanding possible differences between cave-dwelling and spring-dwelling species. Five ecologically distinct subterranean crustacean species of the genus Niphargus were studied, three from springs at the interface between surface and subterranean ecosystems (Niphargus timavi, Niphargus spinulifemur, Niphargus sphagnicolus) and two from cave streams (Niphargus stygius, Niphargus podpecanus), together with Daphnia magna for comparative toxicity assessment. The organisms were exposed to nitrate for 72 h, 96 h and 21 days, followed by a 96-hour recovery period in a nitrate-free medium. In contrast to initial hypothesis, the results showed that nitrate did not induce immobility or mortality to any Niphargus species at concentrations higher than those environmentally relevant. The average 21 d LC50 values determined for different Niphargus sp. were 1735–4266 mg NO3ˉ /L. No significant differences in nitrate sensitivity were found between cave-dwelling and spring-dwelling species. In addition, all species tested showed high recovery rates, regardless of their ecological origin. These results challenge the assumption that subterranean species are inherently more susceptible to chemical stressors due to their lower metabolic rate and lower detoxification capacities. This study highlights the importance of evaluating species-specific traits rather than relying solely on habitat-related generalizations. Although nitrate did not cause toxic effects in this context, potential long-term risks to groundwater ecosystems, such as effects on reproductive success and population dynamics, remain a concern. Comparing the sensitivity of Niphargus and D. magna after 72 h of exposure, N. timavi and N. stygius were more sensitive than D. magna, while N. sphagnicolus was similarly sensitive. These results suggest that tests on subterranean species should be performed to provide a more holistic understanding on the pollutant hazard for subterranean environment.
{"title":"Comparing the toxicity of nitrate between different species of subterranean Niphargus amphipods","authors":"Anita Jemec Kokalj , Cene Fišer , Maruša Poje , Igor Zelnik , Ester Premate , Tiziana Di Lorenzo","doi":"10.1016/j.ecoenv.2025.119509","DOIUrl":"10.1016/j.ecoenv.2025.119509","url":null,"abstract":"<div><div>This study investigates the sensitivity of subterranean amphipods of the genus <em>Niphargus</em> to nitrate pollution, focusing on understanding possible differences between cave-dwelling and spring-dwelling species. Five ecologically distinct subterranean crustacean species of the genus <em>Niphargus</em> were studied, three from springs at the interface between surface and subterranean ecosystems (<em>Niphargus timavi, Niphargus spinulifemur, Niphargus sphagnicolus</em>) and two from cave streams (<em>Niphargus stygius, Niphargus podpecanus</em>), together with <em>Daphnia magna</em> for comparative toxicity assessment. The organisms were exposed to nitrate for 72 h, 96 h and 21 days, followed by a 96-hour recovery period in a nitrate-free medium. In contrast to initial hypothesis, the results showed that nitrate did not induce immobility or mortality to any <em>Niphargus</em> species at concentrations higher than those environmentally relevant. The average 21 d LC<sub>50</sub> values determined for different <em>Niphargus</em> sp. were 1735–4266 mg NO<sub>3</sub>ˉ /L. No significant differences in nitrate sensitivity were found between cave-dwelling and spring-dwelling species. In addition, all species tested showed high recovery rates, regardless of their ecological origin. These results challenge the assumption that subterranean species are inherently more susceptible to chemical stressors due to their lower metabolic rate and lower detoxification capacities. This study highlights the importance of evaluating species-specific traits rather than relying solely on habitat-related generalizations. Although nitrate did not cause toxic effects in this context, potential long-term risks to groundwater ecosystems, such as effects on reproductive success and population dynamics, remain a concern. Comparing the sensitivity <em>of Niphargus</em> and <em>D. magna</em> after 72 h of exposure<em>, N. timavi</em> and <em>N. stygius</em> were more sensitive than <em>D. magna,</em> while <em>N. sphagnicolus</em> was similarly sensitive. These results suggest that tests on subterranean species should be performed to provide a more holistic understanding on the pollutant hazard for subterranean environment.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119509"},"PeriodicalIF":6.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119511
Xiaoran Zhang , Yishuang Duan , Fangyu Liang , Zhen Sun , Pu Wang , Yong Liang , Qunfang Zhou , Guibin Jiang
Flonicamid (FLO), as a novel pyridinecarboxamide insecticide, has attracted wide attention because of its detection in human-derived samples. To evaluate its potential health risk, it is essential to clarify the absorption, distribution, and excretion characteristics of FLO. However, the currently available data are far from sufficient. Moreover, the biotransformation of FLO might cause the generation of bioactive metabolites, which is worthy of high attention. In this study, toxicokinetics and metabolites of FLO were investigated in male Sprague-Dawley rats by a single oral exposure of 5 mg FLO/kg body weight. The results revealed that FLO was rapidly absorbed with the peak plasma concentrations (2.06 ± 0.97 μg/mL) at 2 h post-administration. The half-life of plasma FLO was 7.36 h. FLO was extensively detected in rat heart (2.87 ± 2.16 ng/g), muscle (2.81 ± 2.00 ng/g), and brain (2.53 ± 0.34 ng/g) at 48 h post-administration. Four known metabolites were identified. 4-trifluoromenthylnicotinamide (TFNA-AM) was the only metabolite detected in plasma with the maximum level (102.30 ± 11.12 ng/mL) at 12 h, and a major metabolite in organs and urine. Notably, the detection of FLO and the metabolites in rat brain and testicles may imply their potential neurotoxicity and reproductive toxicity risks. FLO and its metabolites were mostly excreted through urine and feces within 24 h post-administration. Other than acylamino hydrolysis, cyano hydrolysis, and cyano hydration, FLO could be directly transformed to TFNA-AM by decyanomethyl group. These findings help to understand the absorption, distribution, metabolism, and excretion characteristics of FLO and provide reference for its application management in agriculture and risk assessment.
氟虫胺（Flonicamid， FLO）作为一种新型吡啶甲酰胺类杀虫剂，因在人源性样品中检出而受到广泛关注。为了评估其潜在的健康风险，有必要澄清FLO的吸收、分布和排泄特征。然而，目前可获得的数据还远远不够。此外，FLO的生物转化可能会产生生物活性代谢物，值得高度关注。在本研究中，通过单次口服5 mg FLO/kg体重，研究了雄性Sprague-Dawley大鼠FLO的毒性动力学和代谢物。结果表明，FLO吸收迅速，给药后2 h血药浓度达到峰值（2.06 ± 0.97 μg/mL）。血浆FLO的半衰期为7.36 h。弗洛被广泛发现在大鼠心脏(2.87 ±2.16 ng / g),肌肉(2.81 ±2.00 ng / g),和大脑(2.53 ±0.34 ng / g)在48 h post-administration。鉴定出四种已知的代谢物。4-三氟omenthylnicotinamide （TFNA-AM）是唯一在血浆中检测到的代谢物，在12 h时达到最高水平（102.30 ± 11.12 ng/mL），是各器官和尿液中的主要代谢物。值得注意的是，在大鼠脑和睾丸中检测到FLO及其代谢物可能意味着其潜在的神经毒性和生殖毒性风险。给药后24 h内，FLO及其代谢物主要通过尿液和粪便排出体外。除酰基水解、氰基水解和氰基水化外，FLO可通过十氰甲基直接转化为TFNA-AM。这些发现有助于了解FLO的吸收、分布、代谢和排泄特性，为其在农业中的应用管理和风险评估提供参考。
{"title":"Characteristics of toxicokinetics and metabolic transformation of flonicamid in rats","authors":"Xiaoran Zhang , Yishuang Duan , Fangyu Liang , Zhen Sun , Pu Wang , Yong Liang , Qunfang Zhou , Guibin Jiang","doi":"10.1016/j.ecoenv.2025.119511","DOIUrl":"10.1016/j.ecoenv.2025.119511","url":null,"abstract":"<div><div>Flonicamid (FLO), as a novel pyridinecarboxamide insecticide, has attracted wide attention because of its detection in human-derived samples. To evaluate its potential health risk, it is essential to clarify the absorption, distribution, and excretion characteristics of FLO. However, the currently available data are far from sufficient. Moreover, the biotransformation of FLO might cause the generation of bioactive metabolites, which is worthy of high attention. In this study, toxicokinetics and metabolites of FLO were investigated in male Sprague-Dawley rats by a single oral exposure of 5 mg FLO/kg body weight. The results revealed that FLO was rapidly absorbed with the peak plasma concentrations (2.06 ± 0.97 μg/mL) at 2 h post-administration. The half-life of plasma FLO was 7.36 h. FLO was extensively detected in rat heart (2.87 ± 2.16 ng/g), muscle (2.81 ± 2.00 ng/g), and brain (2.53 ± 0.34 ng/g) at 48 h post-administration. Four known metabolites were identified. 4-trifluoromenthylnicotinamide (TFNA-AM) was the only metabolite detected in plasma with the maximum level (102.30 ± 11.12 ng/mL) at 12 h, and a major metabolite in organs and urine. Notably, the detection of FLO and the metabolites in rat brain and testicles may imply their potential neurotoxicity and reproductive toxicity risks. FLO and its metabolites were mostly excreted through urine and feces within 24 h post-administration. Other than acylamino hydrolysis, cyano hydrolysis, and cyano hydration, FLO could be directly transformed to TFNA-AM by decyanomethyl group. These findings help to understand the absorption, distribution, metabolism, and excretion characteristics of FLO and provide reference for its application management in agriculture and risk assessment.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119511"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119515
Weixing Wen , Zhancong Liu , Lingxiao Li , Feipeng Qiu , Hao Zhang , Yue Cao , Jiahuan Li , Xiaohui Huang , Yuli Huang
Background
Di (2-ethylhexyl) phthalate (DEHP), a pervasive environmental plasticizer, is associated with diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD); however, its role in driving Cardiovascular-Kidney-Metabolic (CKM) syndrome remains unconfirmed.
Methods
We employed an integrated approach combining NHANES epidemiological data, network toxicology, computational simulations, and experimental validation. Cytotoxicity was assessed via Lactate Dehydrogenase (LDH) release assays in cardiomyocytes and renal tubular epithelial cells following DEHP exposure (0–150 μM) over 24–48 h.
Results
Urinary DEHP metabolites showed dose-dependent associations with CKM (stages 2–4). Each unit increase in Ln (DEHP) was associated with a 35 % elevated risk of CKM (OR=1.35, 95 % CI: 1.03–1.78). Compared to the lowest exposure tertile, individuals in the highest tertile had a 132 % increased risk (OR=2.32, 95 % CI: 1.18–4.58). Body mass index (BMI) synergistically amplified this association, with obese individuals exhibiting a 2.89-fold higher risk per unit exposure. Network toxicology identified eight core targets, and pathway analysis revealed interconnected metabolic, inflammatory, and fibrotic processes. Molecular docking and dynamics simulations confirmed stable binding with three core targets: PPARG, PTGS2, and MMP2. Furthermore, in vitro experiments showed that DEHP induced concentration- and time-dependent cytotoxicity in both cardiomyocytes and renal tubular epithelial cells.
Conclusions
DEHP exposure promotes CKM syndrome through coordinated disruption of metabolic (PPARG), inflammatory (PTGS2), and fibrotic (MMP2) pathways, with obesity serving as a critical effect modifier. The integrated computational and experimental evidence provides a mechanistic basis for future therapeutic interventions.
{"title":"Multimodal mechanisms of di (2-ethylhexyl) phthalate-induced cardiovascular-kidney-metabolic syndrome: Integrating epidemiology, network toxicology and experimental validation","authors":"Weixing Wen , Zhancong Liu , Lingxiao Li , Feipeng Qiu , Hao Zhang , Yue Cao , Jiahuan Li , Xiaohui Huang , Yuli Huang","doi":"10.1016/j.ecoenv.2025.119515","DOIUrl":"10.1016/j.ecoenv.2025.119515","url":null,"abstract":"<div><h3>Background</h3><div>Di (2-ethylhexyl) phthalate (DEHP), a pervasive environmental plasticizer, is associated with diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD); however, its role in driving Cardiovascular-Kidney-Metabolic (CKM) syndrome remains unconfirmed.</div></div><div><h3>Methods</h3><div>We employed an integrated approach combining NHANES epidemiological data, network toxicology, computational simulations, and experimental validation. Cytotoxicity was assessed <em>via</em> Lactate Dehydrogenase (LDH) release assays in cardiomyocytes and renal tubular epithelial cells following DEHP exposure (0–150 μM) over 24–48 h.</div></div><div><h3>Results</h3><div>Urinary DEHP metabolites showed dose-dependent associations with CKM (stages 2–4). Each unit increase in Ln (DEHP) was associated with a 35 % elevated risk of CKM (OR=1.35, 95 % CI: 1.03–1.78). Compared to the lowest exposure tertile, individuals in the highest tertile had a 132 % increased risk (OR=2.32, 95 % CI: 1.18–4.58). Body mass index (BMI) synergistically amplified this association, with obese individuals exhibiting a 2.89-fold higher risk per unit exposure. Network toxicology identified eight core targets, and pathway analysis revealed interconnected metabolic, inflammatory, and fibrotic processes. Molecular docking and dynamics simulations confirmed stable binding with three core targets: PPARG, PTGS2, and MMP2. Furthermore, <em>in vitro</em> experiments showed that DEHP induced concentration- and time-dependent cytotoxicity in both cardiomyocytes and renal tubular epithelial cells.</div></div><div><h3>Conclusions</h3><div>DEHP exposure promotes CKM syndrome through coordinated disruption of metabolic (PPARG), inflammatory (PTGS2), and fibrotic (MMP2) pathways, with obesity serving as a critical effect modifier. The integrated computational and experimental evidence provides a mechanistic basis for future therapeutic interventions.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119515"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119512
Yilin Zhang , Minhua Li , Shanshan Du , Yifeng Chen , Qingyu Li , Zitong Zhang , Rong Xu , Qing Zu , Zihu Lv , Weimin Ye , Wei Zheng , Jianjun Xiang
Objectives
This study aimed to investigate the pathogenesis of metabolic-associated fatty liver disease (MAFLD) in petrochemical workers chronically exposed to heat and industrial chemicals, using interpretable machine learning to identify synergistic risk factors.
Methods
A nested case-control study was conducted among 1277 petrochemical workers (mean follow-up: 8.20 ± 1.17 years). A total of 347 MAFLD cases were matched with 930 controls (1:4 ratio) by age (± 5 years) and gender. Demographic, occupational, and clinical data were analyzed. After Relief-F feature selection, nine machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Random Forest (RF), Adaptive Boosting (AdaBoost), Gradient Boosting Decision Tree (GBDT), Gaussian Naive Bayes (GNB), Multilayer Perceptron (MLP), Support Vector Machine (SVM), and Decision Tree (DT), were optimized for MAFLD prediction. Model performance was rigorously evaluated using area under the receiver operating characteristic curve (AUC-ROC) analysis with DeLong’s test for statistical comparison. SHAP values were used for model interpretability.
Results
Multivariate analysis revealed that prolonged heat exposure (> 10 years) significantly increased the risk of MAFLD when combined with diesel (OR = 2.31, χ² = 9.407, P = 0.009) or polyethylene dust (OR = 2.78, χ² = 10.645, P = 0.005). Certain socio-demographic factors were also played a significant role: widowed/divorced workers had a 1.89-fold higher risk of MAFLD compared with their married counterparts (χ² = 15.756, P < 0.001), and high-income earners (> $40,000/year) showed a 4.29-fold higher prevalence (χ² = 129.155, P < 0.001). The XGBoost model demonstrated greater stability, achieving a training AUC of 0.919 and maintaining a validation AUC of 0.761. The relatively smaller performance decline observed in XGBoost (ΔAUC = 0.158) reflects better robustness and resistance to overfitting than RF. Shapley value analysis revealed visceral adiposity (0.412), marital status (0.387), and heat-diesel co-exposure (0.218) as primary drivers of MAFLD risk.
Conclusions
Chronic occupational heat exposure is a significant risk factor for MAFLD among petrochemical workers, particularly when combined with chemical exposures.
{"title":"Machine learning-driven analysis of occupational heat exposure and metabolic associated fatty liver disease in petrochemical workers","authors":"Yilin Zhang , Minhua Li , Shanshan Du , Yifeng Chen , Qingyu Li , Zitong Zhang , Rong Xu , Qing Zu , Zihu Lv , Weimin Ye , Wei Zheng , Jianjun Xiang","doi":"10.1016/j.ecoenv.2025.119512","DOIUrl":"10.1016/j.ecoenv.2025.119512","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to investigate the pathogenesis of metabolic-associated fatty liver disease (MAFLD) in petrochemical workers chronically exposed to heat and industrial chemicals, using interpretable machine learning to identify synergistic risk factors.</div></div><div><h3>Methods</h3><div>A nested case-control study was conducted among 1277 petrochemical workers (mean follow-up: 8.20 ± 1.17 years). A total of 347 MAFLD cases were matched with 930 controls (1:4 ratio) by age (± 5 years) and gender. Demographic, occupational, and clinical data were analyzed. After Relief-F feature selection, nine machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Random Forest (RF), Adaptive Boosting (AdaBoost), Gradient Boosting Decision Tree (GBDT), Gaussian Naive Bayes (GNB), Multilayer Perceptron (MLP), Support Vector Machine (SVM), and Decision Tree (DT), were optimized for MAFLD prediction. Model performance was rigorously evaluated using area under the receiver operating characteristic curve (AUC-ROC) analysis with DeLong’s test for statistical comparison. SHAP values were used for model interpretability.</div></div><div><h3>Results</h3><div>Multivariate analysis revealed that prolonged heat exposure (> 10 years) significantly increased the risk of MAFLD when combined with diesel (OR = 2.31, <em>χ²</em> = 9.407<em>, P</em> = 0.009) or polyethylene dust (OR = 2.78, <em>χ²</em> = 10.645<em>, P</em> = 0.005). Certain socio-demographic factors were also played a significant role: widowed/divorced workers had a 1.89-fold higher risk of MAFLD compared with their married counterparts (<em>χ²</em> = 15.756<em>, P</em> < 0.001), and high-income earners (> $40,000/year) showed a 4.29-fold higher prevalence (<em>χ²</em> = 129.155, <em>P</em> < 0.001). The XGBoost model demonstrated greater stability, achieving a training AUC of 0.919 and maintaining a validation AUC of 0.761. The relatively smaller performance decline observed in XGBoost (ΔAUC = 0.158) reflects better robustness and resistance to overfitting than RF. Shapley value analysis revealed visceral adiposity (0.412), marital status (0.387), and heat-diesel co-exposure (0.218) as primary drivers of MAFLD risk.</div></div><div><h3>Conclusions</h3><div>Chronic occupational heat exposure is a significant risk factor for MAFLD among petrochemical workers, particularly when combined with chemical exposures.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119512"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119514
Fiona Traber , Inés Segovia-Campos , Arin Kantarciyan , Vera I. Slaveykova
Silver nanoparticles (AgNPs) are widely used nanomaterials, and understanding their effects on phytoplankton is essential for assessing ecological risks. While AgNP toxicity has been extensively studied in single species, the role of interspecies interactions on toxicity outcomes remains poorly understood. This study investigates the effects of AgNPs and Ag+ on phytoplankton, focusing on species-specific responses and interspecies interactions within artificial assemblages. Monocultures and assemblages of Chlamydomonas reinhardtii, Cyclotella meneghiniana, and Synechocystis sp. were exposed to AgNPs (1–3000 µg L−1) and Ag+ (0.05–300 µg L−1) to assess growth inhibition, photosynthetic efficiency, and pigment fluorescence. Spectral flow cytometry enabled high-resolution, single-cell monitoring of cell abundance and pigment fluorescence in the assemblages. Results revealed species-specific toxicity, with Synechocystis sp. being most affected by AgNPs, while C. meneghiniana showed greater tolerance. Ag+ exposure triggered rapid effects, including reduced photosynthetic efficiency within 2 h, whereas AgNPs caused delayed but persistent toxicity. Experiments with artificial assemblages revealed that interspecies interactions modulated silver toxicity. Co-occurrence of species alleviated AgNP stress, resulting in significantly higher 72h-EC50 for some species and sustained photosynthetic performance in the cohabiting eukaryotes. These findings demonstrated that phytoplankton assemblages’ composition strongly influences AgNP toxicity and highlighted spectral flow cytometry as a powerful tool for resolving species-specific responses within complex assemblages. The study emphasized the importance of integrative, assemblage-based approaches in ecotoxicology to more accurately predict ecosystem-level impacts of pollutants.
{"title":"Artificial phytoplankton assemblages reveal species-specific and interactive responses to silver nanoparticles","authors":"Fiona Traber , Inés Segovia-Campos , Arin Kantarciyan , Vera I. Slaveykova","doi":"10.1016/j.ecoenv.2025.119514","DOIUrl":"10.1016/j.ecoenv.2025.119514","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used nanomaterials, and understanding their effects on phytoplankton is essential for assessing ecological risks. While AgNP toxicity has been extensively studied in single species, the role of interspecies interactions on toxicity outcomes remains poorly understood. This study investigates the effects of AgNPs and Ag<sup>+</sup> on phytoplankton, focusing on species-specific responses and interspecies interactions within artificial assemblages. Monocultures and assemblages of <em>Chlamydomonas reinhardtii</em>, <em>Cyclotella meneghiniana</em>, and <em>Synechocystis</em> sp. were exposed to AgNPs (1–3000 µg L<sup>−1</sup>) and Ag<sup>+</sup> (0.05–300 µg L<sup>−1</sup>) to assess growth inhibition, photosynthetic efficiency, and pigment fluorescence. Spectral flow cytometry enabled high-resolution, single-cell monitoring of cell abundance and pigment fluorescence in the assemblages. Results revealed species-specific toxicity, with <em>Synechocystis</em> sp. being most affected by AgNPs, while <em>C. meneghiniana</em> showed greater tolerance. Ag<sup>+</sup> exposure triggered rapid effects, including reduced photosynthetic efficiency within 2 h, whereas AgNPs caused delayed but persistent toxicity. Experiments with artificial assemblages revealed that interspecies interactions modulated silver toxicity. Co-occurrence of species alleviated AgNP stress, resulting in significantly higher 72h-EC<sub>50</sub> for some species and sustained photosynthetic performance in the cohabiting eukaryotes. These findings demonstrated that phytoplankton assemblages’ composition strongly influences AgNP toxicity and highlighted spectral flow cytometry as a powerful tool for resolving species-specific responses within complex assemblages. The study emphasized the importance of integrative, assemblage-based approaches in ecotoxicology to more accurately predict ecosystem-level impacts of pollutants.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119514"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119510
Jialin Zhang , Xiangru Liu , Shulv Quan , Guihu Luo , Qianyun Chen , Han Zhong , Ying Huang , Yanhua Lin , Xing Li , Bin Yang
The etiology of rheumatoid arthritis (RA) includes environmental factors, and although DINCH (cyclohexane-1,2-diisononyl ester) is considered less toxic than phthalates as a plasticizer, it has been associated with adverse clinical outcomes while its effect on RA remains unknown; this study therefore aimed to evaluate in adults the association between DINCH exposure and RA risk using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2018, applying multivariate logistic regression, trend tests, mediation and subgroup analyses with sensitivity analyses for missing data, and found that among 4263 participants with complete data and 5189 with partial covariate missing data the prevalence of RA was higher in those with urinary DINCH concentrations > 1.0 ng/ml than in those with ≤ 1.0 ng/ml (OR = 1.44, 95 % CI = 1.02–2.03, P = 0.037; trend test P = 0.033), that DINCH may influence RA indirectly via vitamin D (mediation effect 4.7 %), and that this association was more evident in participants with low serum total vitamin D levels (OR 1.79, 95 % CI 1.09–2.94), suggesting that increased urinary DINCH concentration is associated with a higher prevalence of RA, particularly in individuals with low vitamin D.
类风湿性关节炎（RA）的病因包括环境因素，尽管作为增塑剂，DINCH（环己烷-1,2-二异壬基酯）被认为毒性小于邻苯二甲酸盐，但它与不良临床结果有关，而其对RA的影响仍不清楚；因此，本研究旨在利用2013-2018年国家健康与营养检查调查（NHANES）的数据，应用多变量logistic回归、趋势检验、中介和亚组分析以及缺失数据的敏感性分析，评估成年人暴露于DINCH与类风湿性关节炎风险之间的关系。发现在4263名数据完整和5189名部分协变量数据缺失的受试者中，尿中DINCH浓度为>； 1.0 ng/ml的患者RA患病率高于≤ 1.0 ng/ml的患者(OR = 1.44, 95 % CI = 1.02-2.03, P = 0.037；趋势检验P = 0.033)，表明DINCH可能通过维生素D间接影响RA（中介效应4.7 %），并且这种关联在血清总维生素D水平较低的参与者中更为明显（OR 1.79, 95 % CI 1.09-2.94），这表明尿中DINCH浓度升高与RA患病率升高有关，特别是在维生素D水平较低的个体中。
{"title":"Association between urinary DINCH concentration and rheumatoid arthritis: A cross-sectional study","authors":"Jialin Zhang , Xiangru Liu , Shulv Quan , Guihu Luo , Qianyun Chen , Han Zhong , Ying Huang , Yanhua Lin , Xing Li , Bin Yang","doi":"10.1016/j.ecoenv.2025.119510","DOIUrl":"10.1016/j.ecoenv.2025.119510","url":null,"abstract":"<div><div>The etiology of rheumatoid arthritis (RA) includes environmental factors, and although DINCH (cyclohexane-1,2-diisononyl ester) is considered less toxic than phthalates as a plasticizer, it has been associated with adverse clinical outcomes while its effect on RA remains unknown; this study therefore aimed to evaluate in adults the association between DINCH exposure and RA risk using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2018, applying multivariate logistic regression, trend tests, mediation and subgroup analyses with sensitivity analyses for missing data, and found that among 4263 participants with complete data and 5189 with partial covariate missing data the prevalence of RA was higher in those with urinary DINCH concentrations > 1.0 ng/ml than in those with ≤ 1.0 ng/ml (OR = 1.44, 95 % CI = 1.02–2.03, P = 0.037; trend test P = 0.033), that DINCH may influence RA indirectly via vitamin D (mediation effect 4.7 %), and that this association was more evident in participants with low serum total vitamin D levels (OR 1.79, 95 % CI 1.09–2.94), suggesting that increased urinary DINCH concentration is associated with a higher prevalence of RA, particularly in individuals with low vitamin D.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119510"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145658830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2025-12-04DOI: 10.1016/j.ecoenv.2025.119453
Hongmei Duan , Feng Liang , Lin Deng , Shuangmei Liu , Zhaozhou Ren , Jingwu Li
Osteoarthritis (OA) is a multifactorial degenerative joint disease with increasing evidence implicating environmental pollutants as underrecognized contributors to its pathogenesis. This review stematically synthesizes in vitro, animal, computational, and human epidemiological studies to elucidate the mechanistic and population-level effects of chemical exposures on OA. Airborne pollutants, including PM2.5, PM10, NO2, O3, and trihalomethanes, are associated with increased OA incidence, promoting cartilage degradation through oxidative stress, inflammatory cytokine overproduction, and epigenetic or developmental programming. Heavy metals such as cadmium, lead, arsenic, mercury, and copper induce reactive oxygen species (ROS), chondrocyte apoptosis, extracellular matrix (ECM) breakdown, and systemic inflammation, with both experimental and epidemiological studies demonstrating dose-dependent relationships. Persistent organic pollutants, including polychlorinated biphenyls (PCBs) and per-/polyfluoroalkyl substances (PFAS), disrupt autophagy, endocrine signaling, and cartilage homeostasis, with evidence of bioaccumulation in synovial fluid and modulation of gene expression relevant to bone-cartilage metabolism. Endocrine-disrupting chemicals, including phthalates, brominated flame retardants, and acetyl tributyl citrate, further exacerbate OA susceptibility via MAPK and NF-κB pathway activation, ROS generation, and ECM dysregulation. Epidemiological data consistently demonstrate associations between these exposures and OA prevalence, incidence, and symptom severity, often showing additive or synergistic effects for multiple pollutants. Despite these advances, research is limited by cross-sectional designs, high-dose experimental models, incomplete assessment of pollutant mixtures, and geographic and joint-specific biases. Future studies should prioritize longitudinal cohort designs, repeated biomonitoring, mechanistic exploration of mixture effects, and inclusion of emerging pollutants such as microplastics. Integrating environmental exposure assessment with advanced imaging, omics technologies, and computational modeling will enhance understanding of pollutant-induced OA mechanisms. Collectively, this evidence underscores the need for environmental interventions, public health strategies, and preventive approaches aimed at mitigating pollutant-driven joint degeneration, highlighting environmental exposures as a critical, yet modifiable, determinant of OA risk.
{"title":"Environmental pollutants as emerging risk factors in osteoarthritis: Mechanistic and epidemiological evidence","authors":"Hongmei Duan , Feng Liang , Lin Deng , Shuangmei Liu , Zhaozhou Ren , Jingwu Li","doi":"10.1016/j.ecoenv.2025.119453","DOIUrl":"10.1016/j.ecoenv.2025.119453","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a multifactorial degenerative joint disease with increasing evidence implicating environmental pollutants as underrecognized contributors to its pathogenesis. This review <span><math><mrow><mi>Edited</mi><mspace></mspace><mi>by</mi><mspace></mspace><mi>Dr</mi><mo>.</mo><mspace></mspace><mi>Caterina</mi><mspace></mspace><mi>Faggio</mi></mrow></math></span>stematically synthesizes in vitro, animal, computational, and human epidemiological studies to elucidate the mechanistic and population-level effects of chemical exposures on OA. Airborne pollutants, including PM2.5, PM10, NO2, O3, and trihalomethanes, are associated with increased OA incidence, promoting cartilage degradation through oxidative stress, inflammatory cytokine overproduction, and epigenetic or developmental programming. Heavy metals such as cadmium, lead, arsenic, mercury, and copper induce reactive oxygen species (ROS), chondrocyte apoptosis, extracellular matrix (ECM) breakdown, and systemic inflammation, with both experimental and epidemiological studies demonstrating dose-dependent relationships. Persistent organic pollutants, including polychlorinated biphenyls (PCBs) and per-/polyfluoroalkyl substances (PFAS), disrupt autophagy, endocrine signaling, and cartilage homeostasis, with evidence of bioaccumulation in synovial fluid and modulation of gene expression relevant to bone-cartilage metabolism. Endocrine-disrupting chemicals, including phthalates, brominated flame retardants, and acetyl tributyl citrate, further exacerbate OA susceptibility via MAPK and NF-κB pathway activation, ROS generation, and ECM dysregulation. Epidemiological data consistently demonstrate associations between these exposures and OA prevalence, incidence, and symptom severity, often showing additive or synergistic effects for multiple pollutants. Despite these advances, research is limited by cross-sectional designs, high-dose experimental models, incomplete assessment of pollutant mixtures, and geographic and joint-specific biases. Future studies should prioritize longitudinal cohort designs, repeated biomonitoring, mechanistic exploration of mixture effects, and inclusion of emerging pollutants such as microplastics. Integrating environmental exposure assessment with advanced imaging, omics technologies, and computational modeling will enhance understanding of pollutant-induced OA mechanisms. Collectively, this evidence underscores the need for environmental interventions, public health strategies, and preventive approaches aimed at mitigating pollutant-driven joint degeneration, highlighting environmental exposures as a critical, yet modifiable, determinant of OA risk.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119453"},"PeriodicalIF":6.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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