Aug 2026· Environment International· Vol 215, pp.
110445
· 0 citations· 101 references
Medicine
Abstract
Background
The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored.
Methods
We conducted a 1:1 age- and sex-matched case-control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms.
Results
Participants (mean age 45.2 years, 82.3% female) had serum OCPs at 0.007-0.333 ng/mL and SPs at 0.046-0.095 ng/mL. ML algorithms identified fenpropathrin, β-BHC, cyhalothrin, α-BHC, and p,p'-DDD as the top five contributors to TC. Elevated OCPs/SPs exposure was significantly associated with increased TC risk (WQS: adjusted OR = 1.45, 95%CI = 1.34-2.24, P = 0.019; LUCID: OR = 9.33). Fenpropathrin was the primary contributor (BKMR posterior inclusion probability = 1.00; WQS weight = 67.6%). A total of 45 significant differential metabolites (DMs) were identified (VIP ≥1, P < 0.05, and qualitative level 1). LUCID revealed a distinct TC cluster characterized by upregulated S-sulfo-L-cysteine/adenosine and downregulated 2-hydroxycaprylic acid.
Conclusion
OCPs/SPs mixtures, driven by fenpropathrin, disrupt amino acid/nucleotide metabolism while suppressing organic acid metabolism, representing a potential TC-associated metabolic signature.
Exposure to organochlorine pesticides (OCPs) may disrupt adolescent development; however, their precise impacts remain unclear. Using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, we examined associations between OCPs and adolescent body composition indicators, including body mass index (BMI) z_score, appendicular lean mass (ALM), trunk fat (TRF), total fat (TOF), total lean mass (TLM), and total percent fat (TPF). We fitted several statistical models including linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analysis evaluated the effect of serum albumin, while network toxicology and molecular docking identified key targets and pathways. Linear regression showed that OCPs were negatively correlated with BMI z_score, ALM, TRF, TOF, TLM, and TPF in adolescents, particularly in males. The WQS and BKMR revealed a negative relationship between OCPs mixtures and BMI z_score, TRF, TOF, and TPF, with hexachlorobenzene (HCB) as the major contributor. Albumin mediated the negative effects of HCB on all body composition indicators. Preliminary bioinformatics analyses suggested that HCB may influence body composition through inflammation, metabolic regulation, and apoptosis involving the MAPK, PI3K-Akt, and Ras signaling pathways. These findings suggest that HCB exposure may adversely affect adolescent growth and nutritional health, particularly among males.
Background and Objectives: Environmental exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a potential contributor to cancer-related biological variability; however, human biomonitoring data in oncology populations remain limited. The present study aimed to assess urinary concentrations of selected phenolic EDCs and their associations with cardiometabolic, hematological, inflammatory, and survival-related parameters in patients with advanced lung cancer. Materials and Methods: A total of 190 patients diagnosed with stage IIIB/IV lung cancer were included in this study. Urinary concentrations of bisphenol A (BPA), bisphenol S (BPS), triclosan (TCS), and resorcinol (RCO) were determined using validated analytical methods. Associations between exposure biomarkers and clinical laboratory parameters were evaluated using sex-stratified statistical analyses and regression models adjusted for age and body mass index. Results: TCS was the most frequently quantified compound (29.47%), followed by BPS (27.37%), RCO (11.58%), and BPA (7.89%). Higher odds of TCS quantification were observed in patients with lung adenocarcinoma and a higher probability of BPA quantification in patients with squamous-cell carcinoma. Sex-specific exposure patterns were observed, with higher BPA and BPS concentrations measured among female patients. Exposure to phenolic EDCs was associated with alterations in kidney function biomarkers, liver enzyme activity, inflammatory cell profiles, and anthropometric indicators. In particular, BPA and BPS showed associations with renal function markers and systemic inflammatory parameters, while TCS exposure was related to reduced leukocyte subpopulations. Survival analysis demonstrates borderline associations for BPA between exposure groups. Conclusions: These findings provide novel human biomonitoring evidence linking exposure to phenolic endocrine-disrupting chemicals with systemic metabolic and inflammatory variability in patients with advanced lung cancer. The observed associations support the biological plausibility that environmental endocrine disruptors may contribute to interindividual heterogeneity in cancer-related physiological responses.
L. Đurić, N. Milošević, M. Milanović et al.· Medicina· 0 citations
Bisphenol A (BPA) is a ubiquitous environmental endocrine disruptor; its association with pancreatic cancer and its potential mechanisms of action remain unclear. This study established a comprehensive framework integrating population epidemiology, computational toxicology, machine learning, molecular dynamics simulations, and experimental validation to conduct a systematic investigation. Analysis of NHANES 2003-2016 data (N = 11,894 adults) revealed that high urinary BPA exposure (quartile 4 vs. quartiles 1-3) was significantly associated with increased cancer mortality (OR = 1.43, 95% CI: 1.04-1.96, P = 0.027; PAF = 9.51%). Intersection analysis of 597 BPA target genes and 3933 pancreatic cancer-associated genes identified 246 overlapping candidates, from which 14 core genes were prioritized through machine learning screening across 15 algorithms and 175 combinations. A diagnostic nomogram constructed based on these 14 genes achieved AUCs of 0.984 and 0.997 in the GSE15471 and TCGA-PAAD + GTEx datasets, respectively. Molecular dynamics simulations (200 ns × 3 replicates) combined with MM/GBSA binding free energy calculations indicated that the binding affinity of AHR for BPA (-57.55 ± 7.20 kcal/mol) was approximately twice that of GPRC5A (-28.87 ± 12.96) and comparable to that of known AHR ligands. Functionally, BPA exhibited a cell-type-dependent biphasic effect, inhibiting normal pancreatic ductal epithelial cell (hTERT-HPNE) viability while enhancing colony formation in AsPC-1 and MiaPaCa-2 pancreatic cancer cells, with AHR knockdown attenuating this proliferative advantage. Collectively, these findings provide population-level, computational, biophysical, and functional evidence supporting an association between BPA and pancreatic cancer, with AHR identified as a potential key molecular mediator.
Peng Lin, Wei Cheng, Xin Qi et al.· Ecotoxicology and Environmen...· 0 citations
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.
Rifa Tasnia, E. Obeng-Gyasi· Journal of Xenobiotics· 0 citations
Exposure to organophosphate pesticides (OPs) has been associated with increased oxidative stress and a higher risk of attention-deficit/hyperactivity disorder (ADHD). However, metabolic insights underlying ADHD and the potential pathophysiological role of OPs exposure remain limited. This study characterized urinary metabolomic profiles associated with ADHD and examined their associations with OPs exposure and oxidative stress. Urinary metabolites from 67 children with ADHD and 98 controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy and ultra-perforamnce liquid chromatography quadrupole time-of-flight mass spectrometry analysis (UPLC-QTOF-MS). Dimethyl phosphate (DMP) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were used as biomarkers of OPs exposure and oxidative stress, respectively. Children were classified into high- and low-exposure/concentration groups based on DMP or HNE-MA levels. Urinary metabolomic profiles differed significantly between children with ADHD and controls. Several metabolites also differed between children with high and low DMP or HNE-MA levels. Metabolites involved in the tricarboxylic acid cycle were significantly higher in ADHD children and positively correlated with both DMP and HNE-MA. Pathway analysis suggested alterations in energy-related and amino acid metabolic pathways. Stepwise logistic regression and receiver operating characteristic curve analysis identified an 11-compound biomarker panel with good discriminatory performance in the discovery (AUC: 0.8450) and validation (AUC: 0.8748) stages. This metabolomic analysis suggests that OPs exposure and oxidative stress may be associated with metabolic changes in ADHD, particularly in energy metabolism and amino acid pathways. The identified biomarker panel may help distinguish children with ADHD from controls. Larger studies with multiple exposure assessments are warranted.
Hsin-Yun Tseng, C. Lo, Boopathi Subramani et al.· Metabolomics· 0 citations
Organophosphate esters (OPEs) are widely used flame retardants and plasticizers. Given their structural similarity to neurotoxic organophosphorus pesticides, concerns have been raised regarding their potential developmental neurotoxicity. However, epidemiologic evidence remains limited, and the roles of gut microbial and metabolic perturbations in these associations are not well characterized. We analyzed 404 mother-child pairs from the Shanghai Maternal-Child Pairs Cohort. OPE concentrations were quantified in cord serum. Meconium samples were profiled for gut microbiota and metabolomics, and behavioral development at 2 years was assessed using the Strengths and Difficulties Questionnaire. Generalized linear models, negative-binomial hurdle regression, SHapley Additive exPlanations, high-dimensional mediation analysis, metabolome-wide association analysis, meet-in-the-middle analysis, and pathway enrichment analysis were applied. A doubling of cord serum tris(2-butoxyethyl) phosphate (TBEP) concentration was associated with a 0.09-point increase in the conduct problem score at age 2 years (95% confidence interval [CI]: 0.02, 0.16). A doubling of TBEP concentration was also associated with 7.9% higher Chao1 richness (95% CI: 2.8%, 14.1%) and 8.7% higher ACE richness (95% CI: 3.5%, 14.1%). A doubling of Chao1 and ACE richness was associated with 0.27-point (95% CI: 0.12, 0.42) and 0.31-point (95% CI: 0.15, 0.46) increases in conduct problem scores, respectively. Alpha diversity indices and Collinsella were identified as potential mediators of the TBEP-conduct problem association. Integrated metabolomic analyses further implicated five pathways, particularly catecholamine biosynthesis and tyrosine metabolism. Enrichment scores for these pathways were positively associated with Chao1, ACE, and Collinsella. Prenatal TBEP exposure was associated with greater behavioral problems in early childhood. Altered neonatal gut microbiota and related metabolic pathways may partly underlie this association.
Yuhan Zhou, Liyi Zhang, Qiang Li et al.· Environmental Research· 0 citations