Journal of Xenobiotics最新文献

{"title":"Emerging Environmental Toxicants Undermine Reproductive Success in Aquatic Animals: A Narrative Review.","authors":"Yuchen Du, Hua Chang, Qiuyue Wang, Yaqin Liang, Liqian Shang, Chun Yang, Ling Li, Xun Xiang","doi":"10.3390/jox16040137","DOIUrl":"10.3390/jox16040137","url":null,"abstract":"<p><p>Aquatic animals are increasingly exposed to complex mixtures of emerging environmental toxicants, including microplastics, nanoplastics, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs). This raises serious concerns for reproductive health, offspring survival rates, and long-term population stability. This narrative review synthesizes the available peer-reviewed evidence on the reproductive and developmental effects of these contaminant groups in aquatic animals. Growing evidence indicates that these contaminants adversely affect reproductive processes, impair offspring development, and reduce survival and fitness across a wide range of aquatic species. Their effects are mediated through interconnected pathways involving oxidative stress, endocrine disruption, inflammation, mitochondrial dysfunction, and epigenetic alterations, ultimately leading to reproductive and developmental abnormalities. These changes may weaken wild fish populations, reduce aquaculture productivity, and compromise aquatic biodiversity. However, interpretation of the available evidence is constrained by substantial heterogeneity in species, contaminant properties and concentrations, exposure durations, and reproductive endpoints, together with the predominance of laboratory-based single-contaminant studies. This review integrates current knowledge on the reproductive and developmental impacts of emerging contaminants by connecting mechanistic toxicity pathways with population-level and ecosystem consequences. Overall, this review emphasizes that protecting aquatic reproductive health requires an integrated framework linking contaminant monitoring, mechanistic biomarkers, reproductive performance, and ecosystem-level risk assessment.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled Micro- and Nanoplastics as Environmental Modifiers of Lung Carcinogenesis: Mechanistic Insights and Evidence Synthesis.","authors":"Chrysa Andrikopoulou, Nikolaos E Koletsis, Vasileios Leivaditis, Francesk Mulita, Sofoklis Mitsos, Periklis Tomos, Ioannis Panagiotopoulos, Vasiliki Androutsopoulou, Marios G Kostakis, Nikolaos S Thomaidis, Efstratios Koletsis","doi":"10.3390/jox16040136","DOIUrl":"10.3390/jox16040136","url":null,"abstract":"<p><p>The exponential rise in global plastic production has resulted in the widespread environmental dissemination of micro- and nanoplastics (MNPs) across air, water, and biological systems. Inhalation of airborne MNPs represents a biologically plausible pathway of pulmonary exposure, particularly within indoor and occupational environments. Experimental evidence indicates that inhaled MNPs deposit within distal lung compartments, where their small aerodynamic diameter and surface reactivity may favor cellular uptake, oxidative stress induction, inflammatory activation, and prolonged biopersistence. Experimental studies further indicate that MNP exposure may induce DNA damage, chromosomal instability, and the dysregulation of signaling pathways involved in genomic integrity, thereby providing additional mechanistic support for their potential role in carcinogenesis. Chronic redox imbalance, macrophage dysfunction, inflammasome activation, epithelial-mesenchymal transition, and dysregulated cell adhesion collectively resemble mechanisms implicated in inflammation-associated carcinogenesis. Emerging in vitro and in vivo data further suggest that nanoplastics may function as tumor promoters or co-carcinogenic modifiers, particularly under chronic low-dose exposure or in combination with other airborne toxicants. However, human epidemiological evidence remains limited, and causality has not been established. This review synthesizes current mechanistic evidence regarding inhaled MNPs as potential modifiers of lung carcinogenesis, compares them with established inhaled carcinogens, and outlines critical research priorities necessary to clarify exposure-response relationships and clinical relevance. Current evidence supports biological plausibility rather than confirmed carcinogenic classification.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidental Changes in Urinary Lead Excretion Following Intra-Venous Ca-DTPA Administration in Patients Treated Primarily for Gadolinium Exposure.","authors":"Richard C Semelka, Miguel Ramalho","doi":"10.3390/jox16040135","DOIUrl":"10.3390/jox16040135","url":null,"abstract":"<p><p>Lead is a prevalent environmental pollutant and the heavy metal most frequently associated with toxic effects in humans. This study aimed to evaluate changes in urinary lead excretion following intravenous Ca-DTPA administration. We retrospectively included all patients treated at a medical clinic between January 2023 and March 2025 for suspected symptoms associated with gadolinium exposure who underwent intravenous Ca-DTPA chelation and had both pre- and post-chelation 24 h urine testing for 20 heavy metals. Urinary lead excretion was summarized using mean, standard deviation, median, and interquartile range, and non-parametric testing was applied because values were not normally distributed. A total of 63 participants were included, of whom 37 were female, with a mean age of 48.6 ± 12.5 years, ranging from 15 to 78 years. Median urinary lead excretion increased from 0.283 µg/24 h (IQR, 0.183-0.421) before treatment to 3.22 µg/24 h (IQR, 1.87-5.28) afterward (<i>p</i> < 0.001), corresponding to a median 11.8-fold increase. Participants aged ≥50 years had a higher median fold increase than younger participants (14.0 vs. 9.8; <i>p</i> = 0.003). All participants had detectable urinary lead levels, and intravenous Ca-DTPA administration was associated with a significant increase in urinary lead excretion. Older participants demonstrated greater lead mobilization and excretion than younger participants. These findings suggest that Ca-DTPA may reveal a mobilizable body burden of lead under the tested conditions, but they do not establish lead poisoning, reduction in total-body lead burden, symptom improvement, or long-term clinical benefit.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A DFT Perspective on Cd²⁺ Removal by CaCO₃/FAU Zeolite Frameworks: Bridging Theory and Experiment.","authors":"Ramon S da Silva, Mendelssolm K Pietre, Rodrigo G Amorim","doi":"10.3390/jox16040133","DOIUrl":"10.3390/jox16040133","url":null,"abstract":"<p><p>The efficient removal of toxic heavy metals from wastewater remains a critical environmental challenge. Faujasite (FAU) zeolite is highly effective for this purpose due to its high surface area, microporous structure, and exceptional ion exchange capacity. This study employs density functional theory (DFT) calculations to investigate the thermodynamics and geometry of Cd2+ capture by two distinct processes: (i) ion exchange and (ii) CaCO3/FAU adsorption. We systematically identify preferential binding sites and calculate binding energies for Cd2+ within the FAU framework. As a key result, the current theoretical modeling confirms previous experimental observations that dispersed CaCO3 units on the surface of faujasite enhance Cd2+ adsorption compared to aggregated units. The computed binding energies for the dispersed configuration range from -54 kcal/mol to -60 kcal/mol, depending on the number of CaCO3 units. These findings provide a fundamental theoretical perspective and represent a first step toward understanding Cd2+ removal by modified zeolites.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated Sludge in the Bioremediation of Water Containing SARS-CoV-2 Antivirals.","authors":"Dora Lastovčić, Ivona Zirn, Tijana Jezerčić, Kristina Bule Možar, Luka Večenaj, Matija Cvetnić, Magdalena Ujević Bošnjak, Marinko Markić, Tomislav Bolanča, Šime Ukić, Dajana Kučić Grgić","doi":"10.3390/jox16040134","DOIUrl":"10.3390/jox16040134","url":null,"abstract":"<p><p>The increasing presence of SARS-CoV-2 antivirals (SASs) in wastewater threatens aquatic ecosystems, making it necessary to better understand their removal efficiency during biological treatment. This study evaluates the removal percentages, kinetic mechanisms, and toxicity profiles of six SASs, daclatasvir (DCV), darunavir (DRV), favipiravir (FAV), lopinavir (LOP), remdesivir (REM), and ritonavir (RIT), using activated sludge. A full factorial design combined with response surface methodology (RSM) was used to assess the impact of pH, temperature (<i>T</i>), and mixed liquor suspended solids (MLSS) on SAS removal and microbial stability. The results distinguished two dominant removal pathways. DCV and LOP were primarily removed by adsorption, whereas DRV, FAV, REM and RIT were predominantly removed through biodegradation involving enzymatic transformation and bacterial co-metabolism. RSM achieved a desirability score of 0.772 and identified the optimal operating conditions (pH = 6.08, MLSS = 4.41 g/L, and <i>T</i> = 44.99 °C), resulting in removal efficiencies above 93% for all compounds except DRV, which remained the limiting compound with a maximum removal efficiency of 66%. Perturbation analysis showed that all tested factors have a distinct influence on process performance. These established kinetic trends should support further investigations into advanced biological wastewater treatment methods and precise ecotoxicity profiling of emerging biotransformation products.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic Trace Element Levels in Maternal and Cord Blood Worldwide and Their Impact on Pregnancy: A Narrative Review.","authors":"Radomir Aničić, Dejan Mihajlović, Jovana Kocić, Aleksandar Stojsavljević","doi":"10.3390/jox16040132","DOIUrl":"10.3390/jox16040132","url":null,"abstract":"<p><strong>Background: </strong>This up-to-date narrative review examines the associations of low environmental exposure to toxic trace elements-arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg)-on pregnancy. While high levels are known to be harmful, the impact of low levels has not been fully analyzed. The aim was to summarize global data on As, Cd, Pb, and Hg levels in maternal and cord blood of healthy pregnant women, compare their distribution, and assess associations with demographic factors, lifestyle, and pregnancy outcomes.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Cochrane Library, and Scopus for studies published between 1 January 1990 and 14 May 2025. The review was conducted in accordance with PRISMA 2020 guidelines. A total of 824 records were assessed for eligibility, and 656 were excluded based on predefined criteria. Exclusion criteria encompassed in vivo or in vitro studies, non-English written publications, treatment-based studies, and studies involving occupationally exposed pregnant women. Inclusion criteria included original full-length research papers with cross-sectional, prospective cohort, or case-control designs; studies measuring As, Cd, Pb, and/or Hg in maternal and/or cord blood; and studies examining associations with demographic, lifestyle, and pregnancy outcomes. The review was not registered, and no external funding was received. Given the narrative synthesis approach of the review, a formal risk-of-bias assessment was not undertaken.</p><p><strong>Results: </strong>A total of 168 studies were included: 32 reported findings on As, 55 on Cd, 78 on Pb, and 64 on Hg, with 26 addressing all four elements. No meta-analysis was performed; results were summarized narratively. Results show that As and Cd levels are higher in maternal blood, whereas Pb and Hg, including methylmercury, are higher in cord blood. Key factors include smoking, rural residence, and fish or seafood consumption, linked to higher Cd, Pb, and Hg levels, respectively.</p><p><strong>Interpretation: </strong>Low Pb levels show the strongest associations with adverse pregnancy outcomes, while As shows the weakest. Pb's effects may relate to passive placental diffusion, unlike other elements. Further studies are needed.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro- and Nanoplastics as Emerging Cardiovascular Risk Factors: A Systematic Review.","authors":"Dominika Kaczyńska, Emilia Malik, Kamil Szemik, Szymon Pokrzywiński, Wiktoria Nowojewska, Adam Mitręga, Jakub Kufel","doi":"10.3390/jox16040131","DOIUrl":"10.3390/jox16040131","url":null,"abstract":"<p><strong>Background: </strong>Micro- and nanoplastics (MNPs) are emerging contaminants increasingly detected in human tissues and biological fluids. Their presence in blood, vascular tissues, thrombi, and atherosclerotic plaques raises concern about their possible association with cardiovascular disease. This systematic review synthesized evidence on associations between MNPs and cardiovascular pathology.</p><p><strong>Methods: </strong>A systematic search was conducted in October 2025 in PubMed, Scopus, Web of Science, and Embase according to PRISMA guidelines and a PICOS-based strategy. Original human studies from the last 10 years were eligible. Fourteen studies were included. Due to methodological heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using ROBINS-E, and certainty of evidence was evaluated using a GRADE-informed approach.</p><p><strong>Results: </strong>MNPs were detected in multiple cardiovascular-related matrices. Included studies suggested possible associations with major adverse cardiovascular events, acute coronary syndrome, myocardial infarction, arterial stenosis, vascular calcification, thromboembolic disease, hypertension, inflammatory markers, coagulation-related parameters, and lipid profiles. However, the certainty of evidence was very low, and most studies had a high or very high risk of bias.</p><p><strong>Conclusions: </strong>Current evidence suggests a possible association between MNPs and cardiovascular pathology, but causality remains unproven. Larger prospective studies using standardized detection protocols, rigorous contamination control, and adjustment for confounders are needed.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A SAR-Based Classification Model for Assessing Pesticide Toxicity to <i>Apis mellifera</i>.","authors":"Nadia Iovine, Anna Lombardo, Alessandra Roncaglioni, Emilio Benfenati","doi":"10.3390/jox16040130","DOIUrl":"10.3390/jox16040130","url":null,"abstract":"<p><p>Pollinators are essential for maintaining ecosystem stability and agricultural productivity, yet their populations are in decline due to various stressors, including parasites, pathogens, climate change and pesticide exposure. Protecting pollinators has become a priority for environmental safety and food security. Regulatory authorities, including the European Food Safety Authority (EFSA), the Environmental Protection Agency (EPA) and the Organisation for Economic Co-operation and Development (OECD), have guidelines for pesticide risk assessment, but conventional testing methods are costly and time-consuming, limiting their applicability to large chemical datasets. Computational approaches, such as Structure-Activity Relationship (SAR) models, offer efficient alternatives by enabling the rapid screening of pesticides for potential toxicity to pollinators. In this study, we used a dataset of 357 compounds to develop a classification model based on structural alerts to predict oral acute toxicity in <i>Apis mellifera</i>. The model showed a higher Matthews Correlation Coefficient in the training set (0.82), with a moderate decay in the test set (0.56) likely due to applicability domain limits. Despite this, high balanced accuracy (0.80) and sensitivity (0.79) in the test set confirm the model as a reliable tool for the toxicological screening of pesticides.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Toxic Elements in Farm Soils and Vegetables of Northern Bangladesh: Impact on Soil Health and Human Safety.","authors":"Aninda Sarker, Supti Mallick, Minhaj Uddin, Ronzon Chandra Das, Md Harun Rashid, Md Shohidul Alam, Quazi Forhad Quadir, Md Zakir Hossen","doi":"10.3390/jox16040127","DOIUrl":"10.3390/jox16040127","url":null,"abstract":"<p><p>Intensive vegetable production can increase the transfer of persistent toxic trace elements from agricultural soils into the food chain, particularly where agrochemical use, irrigation inputs, and local geochemical conditions are insufficiently characterized. This study was undertaken to assess toxic trace-metal contamination levels in soils and vegetables from two renowned vegetable-producing subdistricts-Shibganj and Kahaloo-in the Bogra district, Bangladesh. The study also estimated potential human health risks by evaluating the dietary intake of these elements. It measured Pb, Ni, Cd, and Cr content in six vegetables and their respective farm soils using an atomic absorption spectrophotometer (AAS). The average concentrations of Pb, Ni, Cd, and Cr in farm soils of Shibganj and Kahaloo subdistricts were 158.3 ± 8.83, 31.5 ± 5.25, 0.43 ± 0.08, and 14.1 ± 2.16 µg g^-1 and 164.1 ± 4.60, 35.7 ± 6.91, 0.53 ± 0.14, and 9.37 ± 2.87 µg g^-1, respectively. Soils collected from all locations in both subdistricts of Bogra fall under 'moderate' ecological risk. Regarding the pollution load index (PLI), 66.7% of Shibganj and 75.0% of Kahaloo sampling sites had a PLI > 1.0, confirming that 'metal pollution exists.' Based on the calculated bioconcentration factors (BCFs), Cr and Cd show a high tendency to migrate from soil to various vegetables in the study area, though the mean Cd BCF for brinjal in Shibganj exceeded 1.0 due to a single high observation. The results demonstrated that the edible parts of potatoes, onions, and chilies accumulate significant amounts of toxic trace elements. The calculated mean daily intake of Pb and Cr in all vegetables ranged from 0.33 to 1.21 mg person^-1 day^-1 and from 0.10 to 0.64 mg person^-1 day^-1, respectively, exceeding the upper tolerable intake limits. Similarly, dietary intake of potatoes showed both non-carcinogenic and carcinogenic risks, while brinjal showed only carcinogenic risks for adults. Redundancy analysis (RDA) indicates that the measured soil parameters are strong predictors of the response variables (trace element content in various vegetables). Overall, the results identified Pb-dominated soil contamination and human exposure to Pb and Cr associated with vegetables as the principal concerns. To address these issues, priority actions should be given to source apportionment and testing of various agricultural inputs. Additionally, before implementing site-specific remediation or issuing consumption advisories, these risks should be validated through metal speciation and bioaccessibility analyses.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Effects of Metals and PFAS Exposure on Prevalent Diabetes.","authors":"Rifa Tasnia, Emmanuel Obeng-Gyasi","doi":"10.3390/jox16040128","DOIUrl":"10.3390/jox16040128","url":null,"abstract":"<p><p>Human per- and polyfluoroalkyl substances (PFAS) and metal exposures occur as mixtures, but most studies evaluate them independently. Using data from adults in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) with directly measured PFAS and blood metals (N = 1648), we assessed joint associations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), lead, cadmium, and mercury with prevalent diabetes via survey-weighted logistic regression, Weighted Quantile Sum (WQS) regression, quantile g-computation, and design-aware and naïve Bayesian Kernel Machine Regression (BKMR). Survey-weighted diabetes prevalence was 11.4%. Lead and PFOS emerged as the dominant contributors to the exposure mixture in the BKMR model, with posterior inclusion probabilities of 1.00 and 0.997, respectively. In the WQS model, PFOS and PFOA were the primary drivers of the positive mixture index, consistent with their proposed roles in endocrine disruption and insulin resistance. BKMR exposure-response functions were non-monotonic, indicating that lead and cadmium associations with diabetes are nonlinear rather than uniformly directional across the exposure range, a structure that conventional logistic regression cannot capture. Overall, restricting to directly measured exposures, incorporating the full NHANES design in the primary regression, and triangulating across complementary mixture frameworks provide a more rigorous platform than prior single-pollutant or design-naive approaches.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}