Search Results (84)

Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic–pituitary–gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods. Full article

Environmental chemical exposures are increasingly recognized as contributors to metabolic dysfunction, particularly when they occur as chronic, low-dose mixtures rather than as isolated high-dose toxicants. However, current approaches often focus on exposure intensity, single-compound hazard or isolated biomarker associations, and provide limited explanation for why individuals with comparable exposure profiles may develop markedly different metabolic outcomes. This semi-systematic review proposes an Exposure–Adaptive Capacity (EAC) framework to interpret the metabolic consequences of environmental chemical mixtures through the interaction between exposure burden and host adaptive capacity. A structured literature search covered PubMed/MEDLINE, Scopus and Web of Science records published through 30 June 2026; a reviewer-triggered PubMed/MEDLINE update was executed on 30 July 2026 using harmonized British and American dyslipidaemia/dyslipidemia terms, explicit eligibility domains and evidence-mapping procedures. The review integrates epidemiological, mechanistic, toxicological and translational evidence related to environmental chemicals, metabolic dysfunction, mitochondrial impairment, oxidative stress, inflammation, endocrine disruption, metabolic resilience and biomarkers. The evidence indicates that several chemical classes, including per- and polyfluoroalkyl substances, bisphenols, phthalates, pesticides, persistent organic pollutants and selected metals, converge on mitochondrial bioenergetics, redox regulation, inflammatory signalling, endocrine and nuclear receptor activity, nutrient-sensing networks and adipose tissue function. The EAC framework defines exposure burden as the cumulative biological pressure imposed by chemical mixtures and adaptive capacity as the organism’s functional ability to buffer, compensate for or recover from exposure-induced metabolic stress. To make the framework empirically testable, we specify measurable domains for exposure burden, adaptive capacity and EAC mismatch, and distinguish biomarkers of exposure, early biological effect, adaptive capacity, metabolic dysfunction and vulnerability. A quotient-based expression is retained only as a heuristic representation, while empirical testing is proposed through exposure-by-adaptive-capacity interaction models and complementary multidimensional approaches. The framework provides a structured basis for future exposomic, epidemiological and translational studies by shifting attention from exposure alone to the balance between environmental pressure and biological resilience. Full article

Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes—bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances—demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform. Full article

Background: Human exposure to environmental endocrine-disrupting chemicals (EDCs) rarely occurs in isolation, yet most epidemiological research has assessed chemicals individually. PFASs, toxic metals, phthalates, and VOCs are ubiquitous contaminants with well-documented reproductive toxicity. Objective: The aim of this study was to investigate the joint and individual effects of 28 EDCs spanning four chemical classes on six reproductive hormone biomarkers in a nationally representative U.S. population—using an innovative approach that simultaneously characterizes nonlinear mixture effects and chemical interactions across multiple exposure domains. Methods: This cross-sectional study used NHANES 2017–2018 data (n = 9254). Multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) characterized individual and mixture associations, respectively. Missing data were handled using multiple imputations by chained equations. Survey design weights were applied in linear regression models. Results: Linear regression revealed heterogeneous associations across chemical classes and hormones. PFOA was positively associated with SHBG (β = 12.35; 95% CI: 8.33, 16.38) and LH (β = 6.91; 95% CI: 1.44, 12.38), while mercury was inversely associated with estradiol (β = −3.38; 95% CI: −5.12, −1.65). BKMR analyses identified pronounced non-monotonic dose–response relationships and emergent mixture effects not predictable from single-chemical analyses for all six hormones. Posterior inclusion probabilities identified cadmium, PFOA, MEHP, and MBzP as the most influential predictors across hormone endpoints. Conclusions: Concurrent real-world exposure to PFASs, toxic metals, phthalates, and VOCs is associated with measurable, nonlinear alterations in reproductive hormone profiles. Chemical mixture effects cannot be reliably predicted from single-pollutant analyses, underscoring the necessity of mixture-based methodologies in environmental reproductive epidemiology. Prospective studies are needed to establish causal temporality and identify critical windows of susceptibility. Full article

Nowadays, technology is developing so rapidly that it implicitly drives economic growth by increasing the productivity of artificial products. Endocrine disruptors (EDs) are increasingly recognized as emerging contaminants in cosmetic formulations, raising concerns about their ability to alter hormonal homeostasis through long-term, low-dose exposure. The objective of this systematic review is to synthesize current evidence on the presence, mechanisms of action, and health effects of endocrine-disrupting chemicals commonly found in cosmetic formulations, as well as existing regulatory frameworks and gaps in consumer protection. A systematic search across major scientific databases for studies published between 2000 and March 2026 was conducted in accordance with PRISMA guidelines, yielding 102 eligible studies. The most commonly identified endocrine disruptors were parabens, phthalates, benzophenones, and triclosan. Evidence shows that these compounds can mimic or block endogenous hormones, disrupt estrogenic, androgenic, and thyroid pathways, and contribute to reproductive, metabolic, and developmental disturbances. Several studies reported bioaccumulation in human tissues and measurable internal exposure with higher vulnerability in pregnant women and adolescents. Current evidence supports a biologically plausible and clinically relevant association between exposure to cosmetic-derived endocrine disruptors and adverse health outcomes. Despite regulatory progress, major gaps persist in long-term exposure assessment, mixture toxicity, and cumulative real-world risk. Strengthening surveillance, harmonizing international regulations, and encouraging safer cosmetic formulations remain essential to reducing population exposure. Although regulatory measures have been introduced, comprehensive protocols for the use of endocrine disruptors in cosmetics are still under development; additional targeted research is required to refine health risk assessments and strengthen regulatory frameworks. Full article

Paint manufacturing wastewater contains complex mixtures of solvents, resins, surfactants, pigments, and polymeric additives that result in high chemical oxygen demand (COD), toxicity, and poor biodegradability. Conventional physicochemical treatment provides limited removal of dissolved organics, and the pollutant-level behavior of paint effluents during biological treatment remains insufficiently characterized. This study addresses this gap by evaluating a sequential anaerobic–aerobic batch process treating three distinct synthetic paint wastewater samples. This study is a comparative investigation of sequential biological treatment across multiple paint wastewater variants, combined with high-resolution LC–MS to track compound-level transformations. Treatment performance was assessed through COD removal, biogas generation, pH and redox behavior, and LC–MS profiling of organic contaminants. The anaerobic stage achieved 70–95% COD removal depending on wastewater type. Aerobic polishing increased overall removal efficiencies, while PWW3 exhibited reduced stability during extended operation. LC–MS analysis showed substantial decreases in the number and intensity of chromatographic peaks and demonstrated degradation of phthalates, glycol ethers, organophosphate plasticizers, and solvent-derived compounds. The study provides integrated performance- and pollutant-level assessment of sequential anaerobic–aerobic treatment of paint wastewater and demonstrates the influences of wastewater heterogeneity in biological degradation pathways. Full article

Solar energy, as a clean and renewable resource, plays a pivotal role in advancing sustainable energy technologies. The efficiency of front-side silver paste is critical for the photovoltaic performance of Tunnel Oxide Passivated Contact (TOPCon) solar cells. In this study, we comprehensively investigated how the composition of organic vehicles in conductive pastes influences both printing rheological properties and electrical performance. Through rheological characterization, contact angle measurements, and Three-Interval Thixotropy Tests (3ITT), we examined the effects of varying solvent, binder, and thixotropic agent ratios on paste properties. The optimized formulation—a solvent mixture of lauryl alcohol ester (TE), butyl carbitol (DGME), butyl carbitol acetate (BCA), and dibutyl phthalate (DBP) in a 3:4:2:1 ratio, with ethyl cellulose (EC) STD10 as the binder and a polyamide wax (PAW)–hydrogenated castor oil (HCO) thixotropic agent at a 3:1 mass ratio—demonstrated superior viscosity control and rapid structural recovery. Printed grid lines achieved a height-to-width ratio (H/W) of 0.35 and a sheet resistance (Rs) of 1.43 Ω/□. These findings reveal direct relationships between organic vehicle composition, paste rheology, and functional performance, providing practical guidance for the design and optimization of high-performance conductive pastes for c-Si solar cells. This work establishes a foundation for improving both the efficiency and reliability of next-generation silver paste formulations in photovoltaic applications. Full article

Intercellular communication is mediated by extracellular vesicles (EVs), particles released by all cell types that transfer bioactive cargo (proteins, lipids, nucleic acids) to recipient cells, influencing their function. Furthermore, the human population is simultaneously exposed to mixtures of endocrine-disrupting chemicals (EDCs), capable of altering hormonal homeostasis. Epidemiological and experimental evidence, in animal and cellular models, show that EDCs can contribute to the initiation, development, and progression of carcinogenesis. This review analyzes the EDC–EV–Cancer axis, connecting the biology of EVs to environmental toxicology and the processes that lead to tumor development. It has been examined how specific pollutants—arsenic, polycyclic aromatic hydrocarbons, bisphenol A, phthalates, particulate matter 2.5, and cigarette smoke—modify the secretion and content of EVs. These altered EVs may subsequently trigger critical oncogenic mechanisms in recipient cells, including proliferation, angiogenesis, migration, immunosuppression, and metastasis. Specific mechanisms, pathways, miRNAs, and proteins have been identified, following exposure to various EDCs that are capable of modulating cells and the tumor microenvironment to induce carcinogenesis and tumor progression. Therefore, EVs represent a promising platform for investigating the role of exposome in tumor development, serving as a real-time monitoring system that would allow tracking of combined and dynamic human environmental exposure and help in cancer prevention. Full article

Environmental pollutants are persistent chemicals that pose substantial risks to human health, contributing to global mortality and economic burden. In real-world situations, exposure rarely occurs to single compounds; instead, people are chronically exposed to complex mixtures at low concentrations. However, most regulatory frameworks still rely on single-substance risk assessments, potentially underestimating the hazards associated with combined exposures. This study investigated the cytotoxic interactions of binary mixtures of five environmentally relevant pollutants: bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), and perfluorooctanoic acid (PFOA), using the human lymphoblast cell line NALM-6. Cells were exposed for 72 h to each compound individually and to all possible binary combinations, reflecting concentrations reported in human plasma or serum. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and interactions were analyzed using the Bliss model of independence and two-way analysis of variance (ANOVA). Intracellular reactive oxygen species were measured using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) probe to explore the involvement of oxidative stress. Synergistic interactions were observed under specific conditions, although not all statistically identified interactions corresponded to biologically significant effects. The BPA-DBP combination produced the highest cytotoxicity when both pollutants were present at 100 nM (31%), consistent with a strong synergistic effect. A similar pattern was observed for BADGE-BPA. ROS production was partially associated with cytotoxicity in these selected mixtures. Overall, these findings highlight the importance of distinguishing statistical synergy from toxicological relevance. Full article

Depression is a major public health concern, and evidence continues to show that environmental toxicants may contribute to its development. This study evaluated the association between depressive symptoms and per- and polyfluoroalkyl substances (PFAS), heavy metals, phthalates, and organophosphate metabolites using data from NHANES 2017–2018. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Environmental exposure variables were analyzed using multivariable linear regression and Bayesian Kernel Machine Regression (BKMR). All models adjusted for demographic, socioeconomic, behavioral, and clinical covariates. In multivariable linear regression models adjusted for demographic, socioeconomic, behavioral, and clinical covariates, higher urinary dimethylphosphate concentrations were significantly associated with increased depressive symptom scores (β = 0.15; 95% CI: 0.04, 0.27; p = 0.0098). Mono-(2-ethylhexyl) phthalate (MEHP) was also positively associated with PHQ-9 scores (β = 0.001; 95% CI: 0.0003, 0.0019; p = 0.0043). Because environmental mixtures tend to follow non-linear patterns, BKMR analysis was run. BKMR analyses indicated that organophosphate metabolites exhibited the greatest overall contribution to depressive symptoms (group posterior inclusion probability = 0.7875), with diethylphosphate emerging as the most influential individual exposure within the group (conditional PIP = 0.7211). Exposure–response functions suggested non-linear and threshold relationships for several metabolites. These findings identify specific organophosphate and phthalate metabolites as potential contributors to depressive symptoms and support the importance of evaluating chemical mixtures rather than single exposures. Additional longitudinal studies are needed to clarify temporal relationships and to inform public health efforts aimed at reducing exposure to organophosphate pesticides and endocrine-disrupting chemicals. Full article

(1) Background: Hot pot bases are susceptible to phthalate (PAE) contamination due to their high lipid content. Standard risk models often fail to capture extreme values, leading to biased exposure estimates. This study characterized dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) contamination using a hybrid modeling framework to ensure precise risk profiling. (2) Methods: A total of 91 samples were analyzed via GC-MS. Concentration data were fitted using traditional parametric, extreme value mixture (EVMM), and finite mixture models. Probabilistic dietary risks were assessed for Chinese demographic groups using 10,000-iteration Monte Carlo simulations. (3) Results: DEHP (detection rate: 55%) and DBP (32%) were best modeled by a two-component Gamma mixture and a Lognormal–Generalized Pareto distribution, respectively. These advanced models significantly outperformed conventional distributions in capturing upper-tail extremes. Crucially, all hazard quotients (HQs) remained below the safety threshold of 1, indicating acceptable risk, although children aged 7–13 exhibited the highest calculated risk (Max DEHP HQ = 0.68). (4) Conclusions: Although current exposure levels are within safe limits, the heavy-tailed distributions identify potential sporadic high-exposure events that traditional models overlook, specifically highlighting the relative vulnerability of children aged 7–13. This study validates that hybrid statistical approaches offer superior precision for analyzing skewed contamination data. Consequently, these findings provide a critical scientific basis for refining regulatory monitoring and implementing targeted source-tracking measures to mitigate long-tail food safety risks. Full article

Over the last 15 years, mixture risk assessment for food xenobiotics has evolved from conceptual discussions and simple screening tools, such as the Hazard Index (HI), towards operational, component-based and probabilistic frameworks embedded in major food-safety institutions. This review synthesizes methodological and regulatory advances in cumulative risk assessment for dietary “cocktails” of pesticides, contaminants and other xenobiotics, with a specific focus on food-relevant exposure scenarios. At the toxicological level, the field is now anchored in concentration/dose addition as the default model for similarly acting chemicals, supported by extensive experimental evidence that most environmental mixtures behave approximately dose-additively at low effect levels. Building on this paradigm, a portfolio of quantitative metrics has been developed to operationalize component-based mixture assessment: HI as a conservative screening anchor; Relative Potency Factors (RPF) and Toxic Equivalents (TEQ) to express doses within cumulative assessment groups; the Maximum Cumulative Ratio (MCR) to diagnose whether risk is dominated by one or several components; and the combined Margin of Exposure (MOET) as a point-of-departure-based integrator that avoids compounding uncertainty factors. Regulatory frameworks developed by EFSA, the U.S. EPA and FAO/WHO converge on tiered assessment schemes, biologically informed grouping of chemicals and dose addition as the default model for similarly acting substances, while differing in scope, data infrastructure and legal embedding. Implementation in food safety critically depends on robust exposure data streams. Total Diet Studies provide population-level, “as eaten” exposure estimates through harmonized food-list construction, home-style preparation and composite sampling, and are increasingly combined with conventional monitoring. In parallel, human biomonitoring quantifies internal exposure to diet-related xenobiotics such as PFAS, phthalates, bisphenols and mycotoxins, embedding mixture assessment within a dietary-exposome perspective. Across these developments, structured uncertainty analysis and decision-oriented communication have become indispensable. By integrating advances in toxicology, exposure science and regulatory practice, this review outlines a coherent, tiered and uncertainty-aware framework for assessing real-world dietary mixtures of xenobiotics, and identifies priorities for future work, including mechanistically and data-driven grouping strategies, expanded use of physiologically based pharmacokinetic modelling and refined mixture-sensitive indicators to support public-health decision-making. Full article

Associations between prenatal exposure to phthalates, bisphenols and their mixtures and early childhood allergic conditions and asthma were examined. Five hundred and fifty-six mother–child pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort participated. Urine samples collected from mothers during the second trimester of pregnancy were analyzed for phthalates and bisphenols. A child health questionnaire, completed by mothers when children were 12, 24, and 36 months, asked whether children had experienced allergic conditions (i.e., food allergies, eczema, rash) or asthma. In single-chemical models, associations varied with child age. Higher prenatal concentrations of mono-benzyl phthalate (MBzP) were associated with lower odds of eczema at 12 months. At 36 months, higher mono-methyl phthalate (MMP) was associated with increased odds of eczema, whereas higher mono-carboxy-octyl phthalate (MCOP) was associated with reduced odds. Higher prenatal MCOP was also associated with higher odds of rash at 12 months, and higher MMP was associated with higher odds of rash at 36 months. Higher bisphenol S (BPS) was associated with increased odds of asthma at 12 months but decreased odds of eczema and rash at 36 months. Sex-specific effects were also noted. In multi-chemical exposure least absolute shrinkage and selection operator (LASSO) models, several phthalate metabolites and BPS were selected as the best predictors of eczema and rash at 36 months of age. Bayesian kernel machine regression (BKMR) mixture models suggested that BPS was the most important chemical in predicting eczema in children at 36 months, while MMP and BPS were the most important chemicals in predicting rash at 36 months. Prenatal exposure to certain phthalate metabolites and BPS predicted allergic conditions and asthma in young children, with patterns varying by age and sex. Prenatal exposure to these chemicals may differentially influence immune development and contribute to the development of early-life allergic conditions, with potentially sex-specific susceptibility. Full article

Phthalic acid esters (PAEs) are ubiquitous pollutants with reported endocrine-disruption and multiplex toxic activities in a wide range of invertebrate and vertebrate animals. In the present review, the molecular and physiological effects of phthalate exposure on invertebrates, as well as less characterized vertebrates such as amphibians, reptiles, and mammals, are thoroughly examined. PAEs induce a series of adverse effects, such as reproductive toxicity, oxidative stress, immune system impairment, and neuroendocrine disruption. The effects can extensively vary depending on the species, developmental stage, and environmental conditions, ranging from impaired hormone signaling, developmental malformations, and thyroid impairment in amphibians and reptiles to lipid metabolism disturbances and epigenetic changes in mammals. This review will place particular emphasis on transgenerational effects, mixture toxicity, and chronic low-level exposure. By integrating evidence from in vivo, in vitro, and omics studies, this review defines areas of knowledge gaps and the necessity to integrate these taxa in integrated ecological risk assessments, as well as regulatory policy. Full article

Microplastics harbor chemical additives and absorb pollutants from the environment. Microplastics pose a human health threat and have been found in nearly all human tissues. The toxicological pathways and physiological effects of microplastic-mediated chemical exposure following ingestion remain unknown. Here we use Caenorhabditis elegans to investigate the effects of di-butyl phthalate and polystyrene microplastic mixtures on fertility and lifespan. Our studies demonstrate that 1 µm microplastics at 1 mg/L exposure levels result in decreased brood size, whereas 1000 times fewer microplastics (1 µg/L) did not affect the number of eggs laid. While there was no change in brood size at 1 µg/L microplastic exposure levels, there was an increase in embryonic lethality. Microplastics-mediated delivery of di-butyl phthalate to C. elegans significantly reduced brood size and increased embryonic lethality compared to exposure to microplastics alone. This reproductive toxicity is potentially due to a stress response via DAF-16, as observed with microplastics and di-butyl phthalate co-exposure. Furthermore, chronic exposure (from hatching onward) to microplastics shortened the lifespan of C. elegans, which was further reduced with di-butyl phthalate co-exposure. The exacerbated defects observed with co-exposure to phthalate-containing microplastics underscore the risks associated with microplastics releasing the additives and/or chemicals that they have absorbed from the environment. Full article