Search Results (855)

Three-dimensional (3D) printing and bioprinting technologies are increasingly used in tissue engineering and in the development of personalized medical devices with tailored biological and mechanical properties. Despite their advantages, these technologies may involve exposure to chemical compounds with uncertain biological effects, including potential endocrine-disrupting activity. This study aims to evaluate the hormonal activity and cytotoxicity of various materials commonly used for 3D printing technologies, including thermoplastics and synthetic materials (PLA, ABS, PCL, b-TPUe, PVA, PEGDA), and biomaterials (collagen, alginate, hyaluronic acid, agarose, silk fibroin, GelMA, HAMA). Hormonal activity was evaluated using the E-screen assay for estrogenic and anti-estrogenic activity, and the PALM assay for androgenic and anti-androgenic activity. Cytotoxic effects are evaluated by assessing cellular metabolic viability using the MTT assay. No detectable estrogenic, anti-estrogenic, androgenic, or anti-androgenic activity, nor any signs of cytotoxicity, were observed within the experimental conditions analysed. This study represents the first analysis of some specific endocrine-related endpoints of a wide range of 3D printing and bioprinting materials, and should not be interpreted as definitive proof of the complete absence of endocrine activity. Further studies addressing additional toxicological parameters and long-term assessments are required to comprehensively characterize their safety and suitability. Full article

Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate in both aquatic and terrestrial ecosystems. As a xenoestrogenic compound, NP can bind steroid receptors, including estrogen receptors (ERs), thereby activating ER-dependent pathways. In this work, we investigated the effects of NP alone and in combination with the endogenous hormones 17β-oestradiol (E2) and/or testosterone (T) on a human non-tumoral prostate cell line (PNT1A). Cell viability and migration assays, together with analysis of ER expression and localization, were carried out to assess the xenoestrogenic activity of NP, particularly in the presence of E2 and T. Our results showed that NP retained its endocrine-disrupting features in the mixtures, positively affecting cell viability, except for the NP+E2 mixture, in which cell viability did not significantly differ from control, suggesting an antagonistic interaction between NP and E2. The mixtures also interfered with steroid receptor dynamics, affecting receptor expression and delaying receptor localization and activation kinetics. Moreover, all mixtures negatively affected cell migration compared with treatment with endogenous hormones alone. In conclusion, our results demonstrate that NP retains its xenoestrogenic behavior in mixture, inducing a significant alteration in prostate cell homeostasis. Full article

The personal care product market has expanded rapidly in recent years, along with growing consumer awareness of chemical exposures and increasing demand for “clean” products. Consumer perceptions of product safety and potential health impacts are commonly based on ingredient labels, intended use, and certifications, rather than the full chemical composition of finished products. In this study, we conducted a targeted review of certification and ingredient-evaluation programs in the United States and European markets. Eighteen programs were identified and characterized based on their evaluation approaches, data sources, and whether they incorporate analytical measurement of finished products. We also evaluated the current U.S. and EU regulatory frameworks. Across both certification and regulatory systems, evaluation was found to rely primarily on ingredient-based approaches and supporting documentation, with limited incorporation of analytical measurement. As a result, contaminants, impurities, and incidentals/non-intentionally added substances (which have previously been identified in many consumer products) may not be consistently identified or evaluated for safety. These findings highlight a fundamental gap between intended formulation and actual product composition. Incorporating analytical measurement, particularly non-targeted approaches, provides a complementary groundwork for identifying previously unrecognized chemical exposures and improving the accuracy of product safety certification programs and hazard assessments. Aligning evaluation with measured chemical composition may enhance transparency and better reflect real-world exposure, support more credible sustainability claims, enhance consumer trust, support growing market demand, support consumer safety, and contribute to more effective regulation in the personal care industry. Full article

Atherosclerosis is a complex, multifactorial disease and the leading underlying cause of cardiovascular morbidity and mortality worldwide. Beyond traditional risk factors, growing evidence highlights the critical role of environmental exposures in modulating atherogenesis. In real-world scenarios, individuals are exposed to complex mixtures of contaminants, including particulate matter, toxic metals, pesticides, polycyclic aromatic hydrocarbons, and endocrine-disrupting chemicals. These combined exposures may exert additive, synergistic or antagonistic effects, resulting in biological responses that cannot always be predicted from single-agent exposures. At the cellular and molecular level, both chemical mixtures and environmental co-exposures converge on key pathogenic pathways, including oxidative stress, endothelial dysfunction, chronic inflammation, and lipid dysregulation. These processes may favor monocyte recruitment, foam cell formation, vascular smooth muscle cell remodeling, and plaque instability. Moreover, cumulative exposures are associated with epigenetic alterations, such as dysregulation of DNA methylation and non-coding expression patterns, which may influence long-term susceptibility to atherosclerosis. This structured narrative review synthesizes evidence from 37 studies investigating the cellular and molecular mechanisms underlying the impact of environmental mixtures and multipollutant co-exposures on atherosclerosis. By integrating evidence from epidemiological, toxicological, experimental, bioinformatics and multi-omics studies, while recognizing the predominantly associative nature of the available human evidence, we highlight emerging mechanistic insights and discuss the relevance of mixture-based approaches for improving risk assessment and informing future preventive strategies. Full article

Bisphenol A (BPA) is a non-persistent industrial chemical widely used in the production of polycarbonate plastics and epoxy resins. Due to its mass production and versatility, BPA is ubiquitous in environmental matrices, leading to human exposure through ingestion, dermal contact, and inhalation. As a known endocrine-disrupting chemical (EDC) with estrogenic activity, BPA exposure has been associated with reproductive, metabolic, immune, oncogenic, and developmental effects. Mechanistically, BPA is reported to exert its toxic effects via multiple pathways, including alterations in epigenetic microRNA (miRNA) expression. miRNAs are endogenous non-coding RNA molecules that regulate gene expression by targeting mRNAs, thereby influencing a wide range of cellular and metabolic pathways involved in development and disease. Importantly, this review consolidates evidence suggesting that the biological effects of BPA may, in part, be mediated through miRNA-driven epigenetic modifications, affecting numerous downstream proteins and signaling pathways. Altered miRNA expression induced by BPA exposure is implicated in diverse health outcomes, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental abnormalities. Notably, BPA exposure predominantly results in the upregulation of specific miRNAs, such as miR-21 and miR-146a, although tissue-specific and sex-dependent variations are evident. In this review, we provide a comprehensive overview of human, in vivo, and in vitro studies investigating BPA-induced miRNA dysregulation and its associated biological effects. Full article

Background–Aim: Children represent a particularly susceptible population to endocrine-disrupting chemical (EDC) exposure; however, biomonitoring data in this population remain limited. To the best of our knowledge, this is the first study using hair biomonitoring to simultaneously assess the concentrations of phthalate metabolites (PMs), triclosan (TCS) and triclocarban (TCC) in children with obesity (OB), type 1 diabetes mellitus (T1D), and hypothalamic–pituitary-related diseases (HPRD), through hair biomonitoring. Methods: Liquid chromatography–mass spectrometry (LC-MS) was used to measure TCS, TCC and PM levels in head hair samples from 212 children, categorized into control, T1D, HPRD and OB groups. PMs and TCS levels were compared across groups and evaluated in relation to health issues, cosmetics exposure, dietary habits, cardiometabolic, and somatometric parameters. Results: Our hair biomonitoring results showed that the most commonly detected EDCs were MEHP, MBP, MiBP, and TCS, with detection frequencies of samples 95.3%, 84.4%, 79.7%, and 60.8%, respectively. Children with T1D had statistically significantly higher mean MEHP concentrations than the control group. Children with HPRD exhibited higher PM concentrations, primarily driven by elevated mean MEHP and MBP levels compared with the control group. In contrast, mean MiBP levels were lower in the OB group than in the control group. Regarding TCS levels, no statistically significant differences were observed across the disease groups compared with controls. TCS was inversely associated with somatometric parameters in the OB group. Subgroup analyses by age, sex, residence area, and maternal education were conducted to assess statistically significant differences in concentrations of PM and TCS. Conclusions: Overall, our biomonitoring results indicate group-specific concentration patterns of PMs and TCS among children with T1D, HPRD and OB groups compared to the control group. In particular, PM levels were higher in children with T1D and HPRD and lower in those with OB groups compared to the control group. As a result, this is the first study to assess PM and TCS concentrations in children across clinical groups, using hair matrix. Full article

Numerous types of environmental toxicants alter human metabolomics, directly or indirectly, through gut microbial dysbiosis, upsetting immune homeostasis. Environmental toxicants capable of these direct and indirect effects have included heavy metals, pesticides, herbicides, polychlorinated biphenyl (PCB) congeners, and endocrine-disrupting chemicals. The cell and molecular events induced by some diverse toxicants are reviewed, along with their potential additive, synergistic, and antagonistic effects on immune homeostasis (increasing proinflammatory immune cell activation and suppressing immunoregulation), which leads to systemic oxidative stress (OS). As people are exposed in varying degrees to countless chemicals and environmental factors over a lifetime, it is challenging to correlate specific diagnoses to any single toxicant or exposure, which is often a key challenge in linking environmental exposure to health outcomes. However, many toxicants have the common mechanistic effect of OS. The effects of toxicants are more pronounced with aging due to cumulative exposures and immunoaging (immunosenescence), with chronic low-grade inflammation referred to as “inflammaging”. The cell and molecular mechanisms of toxicants include altered calcium flux, mitochondrial dysfunction, and increased levels of damage-associated molecular patterns (alarmins) that trigger an inflammatory response and possibly promote autoimmune and neurological disorders. OS skews type-1 immunity for defenses against pathogens and cancers more toward type-2 immune responses to self-antigens (autoimmunity). The toxicants may directly affect the innate and adaptive immune cells inducing this skewing, or they may modify portions of gut microbial species and strains and their production of metabolites that indirectly affect systemic immunity. These latter toxicant influences require metabolomic analysis of the differential structures and activities of the microbial metabolites. The damaging effects of OS and inflammation disrupting immune homeostasis and leading to disorders are reviewed and discussed. The need for well-designed studies that allow for standardized comparison of exposures and related effects are emphasized, and their real-world limitations noted. Full article

Objectives: The present study evaluated the association between plasma concentrations of selected endocrine-disrupting chemicals (EDCs)—bisphenol A (BPA), methylparaben (MeP), propylparaben (PrP), 4-nonylphenol (4-NP), 4-octylphenol (4-OP), bis(2-ethylhexyl) phthalate (DEHP), and imazalil (IMZ)—and prior coronavirus disease 2019 (COVID-19) status. Methods: Plasma EDC levels were quantified via gas chromatography–mass spectrometry in 262 voluntary blood donors (121 convalescents and 141 controls) at the Regional Centre for Transfusion Medicine in Bialystok, Poland. Results: The cohort exhibited widespread environmental exposure to all selected EDCs (BPA: 1.14 ng/mL, MeP: 1.20 ng/mL, PrP: 1.38 ng/mL, 4-NP: 1.90 ng/mL, 4-OP: 0.57 ng/mL, DEHP: 49.68 ng/mL, IMZ: 20.06 ng/mL). Convalescents had significantly higher concentrations of MeP, PrP, 4-OP, and 4-NP. Logistic regression revealed that MeP, PrP, and 4-NP were significantly associated with prior COVID-19 status, increasing infection odds by 80%, 70%, and 63%, respectively. While 4-OP was strongly associated with prior COVID-19 status (odds ratio > 300 per unit change and 1.79 per 0.1 unit change), the wide confidence interval for the unit change estimate requires cautious interpretation. Conclusions: These findings suggest a strong link between selected paraben and alkylphenol exposure and prior COVID-19 status in blood donors. Additionally, the high IMZ levels highlight the need for urgent evaluation of its safety and environmental prevalence. Full article

Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H₂DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H₂DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings. Full article

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: Over the past decades, the global onset of menarche has progressively advanced, driven by complex interactions between metabolic, psychosocial, and environmental factors. Beyond its reproductive significance, menarche represents a critical developmental milestone that coincides with increased vulnerability to mental health difficulties. Contemporary determinants such as childhood obesity, early-life adversity, and exposure to endocrine-disrupting chemicals (EDCs) may accelerate pubertal timing while simultaneously shaping adverse psychological trajectories during adolescence. Objectives: This review aims to provide a translational and clinically oriented synthesis of modern determinants of earlier menarche and their associations with mental health outcomes in girls and adolescents, highlighting implications for early identification, prevention, and integrated clinical care. Methods: We conducted a narrative review mapping a scoping literature search conducted using PubMed/Medline, Scopus, and PsycINFO, focusing on literature from the last decade (2016–2026), with emphasis on systematic reviews, meta-analyses, and longitudinal cohort studies. Evidence was synthesized across biological, psychosocial, and environmental domains. Results: Accumulating evidence indicates that higher childhood adiposity, psychosocial stress, and EDC exposure are consistently associated with advanced pubertal timing. Earlier menarche correlates with an elevated risk of depressive symptoms, anxiety, self-harm, and body image-related distress, although effect sizes vary across populations. Emerging longitudinal data suggest that the peri-menarcheal period represents a critical window for symptom exacerbation. These associations appear to be mediated by biological mechanisms (e.g., hormonal shifts, hypothalamic–pituitary–adrenal (HPA) axis reactivity) and social processes including peer-comparison dynamics and premature sexualization. Conclusions: Earlier menarche acts as a biopsychosocial sentinel event rather than an isolated gynecological milestone. Integrating mental health screening and anticipatory guidance into pediatric and gynecological care is essential for early risk detection. A multidisciplinary, equity-oriented approach is required to address both individual vulnerability and broader environmental determinants. Full article

Endocrine-disrupting compounds (EDCs) are frequently detected in wastewater and aquatic environments because of their incomplete removal in conventional wastewater treatment plants. Evaluating alternative treatment technologies, including microalgae-based systems, requires analytical methods suitable for low-volume samples. In this work, a solid-phase extraction (SPE) procedure coupled with high-performance liquid chromatography with diode array detection (HPLC-DAD) was developed for the simultaneous determination of methylparaben (MeP), propylparaben (PrP), butylparaben (BuP), benzophenone (BP), bisphenol A (BPA) and estrone (E). The method combines relatively low sample volume and limited eluent consumption with the analysis of six chemically diverse EDCs in biomass-containing samples using accessible HPLC-DAD instrumentation. Sorbent mass, sample volume, elution volume, and pH were evaluated experimentally, with Random Forest used for exploratory multivariable interpretation. Selected conditions were a 500 mg cartridge, 30 mL of sample volume at pH 7 and 2 mL methanol elution volume. The method showed satisfactory linearity (R² ≥ 0.98), limits of quantification between 1.67 and 6.67 ppb, and stable recoveries across the evaluated concentration range. Applicability was demonstrated in a Scenedesmus sp.-based system. AGREEprep assessment yielded a score of 0.34. The developed SPE method provides a low-volume approach for monitoring EDCs in microalgae-based wastewater treatment systems. Full article

Background/Objectives: Chronic exposure to endocrine-disrupting chemicals has been increasingly recognized as a potential contributor to cancer progression. Monobutyl phthalate (MBP), a major metabolite of dibutyl phthalate, is widely detected in human biological samples, yet its long-term impact on anaplastic thyroid cancer (ATC) has not been systematically investigated. Methods: CAL-62 cells were continuously exposed to an environmentally relevant concentration of MBP (10 nM) over 3 months to establish a chronic exposure model that mimics long-term environmental exposure. Transcriptomic profiling was integrated with network toxicology to identify key molecular pathways and hub genes, followed by molecular docking and Western blot validation. Results: Chronic MBP exposure significantly enhanced cell viability, proliferation, colony formation, and tumorsphere formation, indicating promotion of malignant phenotypes. Transcriptomic profiling revealed extensive molecular remodeling characterized by activation of inflammation-associated pathways, including cytokine–cytokine receptor interaction, IL-17, TNF, and JAK–STAT signaling, accompanied by suppression of p53- and mTOR-related pathways. Integrated analysis identified 57 overlapping KEGG pathways, with IL6 and CSF2 emerging as central hub genes. Molecular docking demonstrated favorable binding affinities between MBP and representative target proteins, including IL6, TP53, CASP3, BCL2, and PPARG. Western blot analysis further confirmed increased IL6 and BCL2 expression together with decreased TP53, CASP3, and PPARG expression following chronic MBP exposure. Conclusions: Chronic environmentally relevant MBP exposure promotes ATC malignant progression through coordinated inflammation-associated molecular network remodeling accompanied by suppression of apoptosis-related signaling. Integrating network toxicology with transcriptomic profiling provides an effective systems-level strategy for identifying biologically relevant molecular networks underlying chronic environmental toxicant exposure. Full article

Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes. Full article