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The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1 , both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα. [ABSTRACT FROM AUTHOR]

Bisphenol AF (BPAF) is increasingly used and now found in products intended for human consumption. The protective effect of 1,8-cineole (CIN) against BPAF-induced reproductive toxicity was investigated. Four groups were created, with each group consisting of eight rats: control, BPAF (200 mg/kg), CIN (200 mg/kg), and BPAF + CIN groups. The results demonstrated that the BPAF group exhibited a decline in testosterone levels and a decrease in sperm parameters compared with the control. Additionally, higher levels of MDA were observed, along with lower levels of GSH and GPx activity. CAT activity also decreased slightly. Tnf-α, Nf-κB levels were significantly higher, and caspase-3 expression was elevated, while PCNA expression decreased. BPAF significantly increased tissue degeneration compared with the control. However, the BPAF + CIN group showed statistically significant improvements in sperm parameters, except for concentration. They also exhibited an increase in testosterone levels and an improvement in MDA and GSH levels compared with the BPAF group. However, GPx activity partially enhanced. Tnf-α and Nf-κB levels were significantly reduced, and caspase-3 levels declined while PCNA and Bcl-2 levels increased. The Johnsen Testicular Biopsy score showed a substantial increase. Overall, these results suggest that CIN co-treatment in rats enhanced reproductive health and exhibited antioxidant, antiapoptotic, and anti-inflammatory properties against BPAF-induced testicular damage. [ABSTRACT FROM AUTHOR]

Introduction: Triclosan is an antibacterial and antifungal compound that is frequently found in personal care and consumer products, and its its impact on male reproductive health is a growing concern. Despite existing experimental studies demonstrating its potential threats to male fertility, reports on its effects on human semen quality remains limited and inconsistent. Therefore, this study presents a systematic review and meta-analysis assessing the relationship between triclosan exposure and semen quality. Methods: This study was registered with PROSPERO (CRD42024524192) and adhered to PRISMA guidelines. Results: The study analyzed 562 screened studies, out of which five articles including 1,312 male subjects were finally included in the study. The eligible studies were geographically diverse, with three from China, one from Belgium, and one from Poland. More so, the eligible studies were both case-control and cross-sectional. The meta-analysis revealed that triclosan exposure significantly reduced sperm concentration (Standard Mean Difference (SMD) -0.42 [95% CI: -0.75, -0.10], P = 0.01) and sperm total motility (SMD -1.30 [95% CI: -2.26, -0.34], P = 0.008). Mechanistic insights from animal and in vitro studies showed that oxidative stress may mediate the adverse effects of triclosan on semen quality. Discussion: This meta-analysis is the first comprehensive evaluation of the impact of triclosan on human semen quality, highlighting its potential to impair male fertility through reductions in sperm concentration and motility. However, the high heterogeneity among the included studies underscores the need for further high-quality research to establish more definitive conclusions regarding the effects of triclosan exposure on human reproductive health. [ABSTRACT FROM AUTHOR]

In the era dominated by plastic, the widespread use of plastic in our daily lives has led to a growing accumulation of its degraded byproducts, such as microplastics and plastic additives like Bisphenol A (BPA). BPA is recognized as one of the earliest man-made substances that exhibit endocrine-disrupting properties. It is frequently employed in the manufacturing of epoxy resins, polycarbonates, dental fillings, food storage containers, infant bottles, and water containers. BPA is linked to a range of health issues including obesity, diabetes, chronic respiratory illnesses, cardiovascular diseases, and reproductive abnormalities. This study examines the bacterial bioremediation of the BPA, which is found in many sources and is known for its hazardous effects on the environment. The metabolic pathways for the breakdown of BPA in important bacterial strains were hypothesized based on the observed altered intermediate metabolites during the degradation of BPA. This review discusses the enzymes and genes involved in the bacterial degradation of BPA. The utilization of naturally occurring microorganisms is the most efficient and cost-effective method due to their selectivity of strains, ensuring sustainability. [ABSTRACT FROM AUTHOR]

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defects in liganded estrogen receptor (ER) signaling, demonstrating its role in genomic instability and cancer initiation. 2. In breast tumors, the increased expression of special receptor family maybe an effort for self-directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER-positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast cancers non-responsive to antiestrogen treatment exhibit HER2-overexpression for compensating the complete inhibition of hormonal ER activation. 5. In breast tumors, somatic mutations serve upregulation of ER activation via liganded or unliganded pathway helping genome stabilization and apoptotic death. 6. The mutual communication between breast cancer and its inflammatory environment is a wonderful partnership among cells fighting for genome stabilization and apoptotic death of tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather, the nonresponsive tumor cells exhaust all compensatory possibilities against therapeutic damages. Conclusions: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying supportive care instead of genotoxic measures. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are a group of 209 highly stable molecules that were used extensively in industry. Although their commercial use ceased in 1979, they are still present in many aquatic ecosystems due to improper disposal, oceanic currents, atmospheric deposition, and hydrophobic nature. PCBs pose a significant and ongoing threat to the development and sustainability of aquatic organisms. In areas with PCB exposure high mortality rates of organisms inhabiting them are still seen today, posing a significant threat to local species. Zebrafish were exposed to a standard PCB mixture (Aroclor 1254) for the first 5 days post fertilization, as there is a gap in knowledge during this important developmental period for fish (i.e., organization of the body). This PCB mixture was formally available commercially and has a high prevalence in PCB-contaminated sites. We tested for the effects of PCB dosage (control (embryo water only; 0 mg/L), methanol (solvent control; 0 mg/L); PCB 1 (0.125 mg/L), PCB 2 (0.25 mg/L), PCB 3 (0.35 mg/L), and PCB 4 (0.40 mg/L)) on zebrafish survival, rate of metamorphosis, feeding efficiency, and growth. We found significant, dose-dependent effects of PCB exposure on mortality, feeding efficiency, and growth, but no clear effect of PCBs on the rate of zebrafish metamorphosis. We identified a concentration in which there were no observable effects (NOEC), PCB concentration above the NOEC had a significant impact on life-critical processes. This can further inform local management decisions in environments experiencing PCB contamination. [ABSTRACT FROM AUTHOR]

One of the factors associated with increased morbidity of malignant neoplasms is environmental pollution with cancerogenic compounds including pesticides. Until recently, stable organic pollutant insecticide dichlorodiphenyltrichloroethane (DDT) was the single tool for fighting malaria carriers. Despite vast evidence of its negative effect on human health, DDT is still used in some countries.Aim. To perform a comprehensive analysis of the dynamics of DDT pesticide use and the consequences of its use on the global healthcare as well as to investigate the mechanism of its action on the human body including the endocrine system and cancerogenic effects.The review was composed using the PubMed (2853 publications), Elsevier (3139 publications), eLibrary (784 publications) biomedical literature databases. Full-text articles were retrieved through PubMed Central (PMC), Science Direct, Research Gate, CyberLeninka electronic resources.

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defects in liganded estrogen receptor (ER) signaling, demonstrating its role in genomic instability and cancer initiation. 2. In breast tumors, the increased expression of special receptor family maybe an effort for self-directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER-positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast cancers non-responsive to antiestrogen treatment exhibit HER2-overexpression for compensating the complete inhibition of hormonal ER activation. 5. In breast tumors, somatic mutations serve upregulation of ER activation via liganded or unliganded pathway helping genome stabilization and apoptotic death. 6. The mutual communication between breast cancer and its inflammatory environment is a wonderful partnership among cells fighting for genome stabilization and apoptotic death of tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather, the nonresponsive tumor cells exhaust all compensatory possibilities against therapeutic damages. Conclusions: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying supportive care instead of genotoxic measures.

Milk can be contaminated with organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs), which are known as endocrine disruptors (EDCs). However, the relationship between the lactation period of cows and the residues of EDCs is unknown. The aim of this study was to determine the relationship between the lactation period in cows and EDCs residues such as OCPs, PCBs, PBDEs, and PAHs. Milk collected from cows during each lactation period was analyzed in terms of fat content and EDC residues. One or more contaminants were detected in almost all (98%) of the milk taken in three lactation periods. Three PCBs and 11 PAHs were found together in 1st lactation period, and one more PAH was added to them in other periods. However, the sample rate exceeded the maximum residue limit of 48%, 10%, and 16% in the first, second and third lactation periods, respectively. Also, it was seen that the riskiest period was the first lactation period, followed by the third and second periods. The same ranking is valid for the fat content in milk. Thus, it was concluded that the excretion of lipophilic EDCs in milk is related to the fat content in milk, and the higher the fat content in milk, the more lipophilic EDCs are excreted in milk.

Diabetes and its complications significantly affect individuals' quality of life. The etiology of diabetes mellitus and its associated complications is complex and not yet fully understood. There is an increasing emphasis on investigating the effects of endocrine disruptors on diabetes, as these substances can impact cellular processes, energy production, and utilization, ultimately leading to disturbances in energy homeostasis. Mitochondria play a crucial role in cellular energy generation, and any impairment in these organelles can increase susceptibility to diabetes. This review examines the most recent epidemiological and pathogenic evidence concerning the link between endocrine disruptors and diabetes, including its complications. The analysis suggests that endocrine disruptor-induced mitochondrial dysfunction--characterized by disruptions in the mitochondrial electron transport chain, dysregulation of calcium ions (Ca2+), overproduction of reactive oxygen species (ROS), and initiation of signaling pathways related to mitochondrial apoptosis--may be key mechanisms connecting endocrine disruptors to the development of diabetes and its complications. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the bisphenol A (BPA) release from four CAD/CAM splint materials: three polycarbonate‐based (DD BioSplint C, Splint Plus Biostar, Temp Premium Flexible) and one polymethylmethacrylate‐based (Temp Basic) material. From each material, ten cylindrical samples (n = 40) were immersed in high‐performance liquid chromatography (HPLC) grade water following ISO 10993‐12 and incubated for 24 h in an incubation shaker at 37°C and 112 rpm. Following BPA derivatization, analysis was performed by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). After 24 h of incubation, all investigated materials released significant amounts of BPA compared to water blanks. The material‐dependent elution increased in the following order: DD BioSplint C < Splint Plus Biostar < Temp Basic < Temp Premium Flexible. Subtracting extraneous BPA, the concentrations ranged between 2.27 ng/mL and 12.65 ng/mL. After extrapolating the concentrations in relation to the average surface area of occlusal splints, the amount of BPA per mL exceeded the Tolerable Daily Intake (TDI) set by the European Union for a person weighing 70 kg by 1.32–6.16 times. Contrary to the release from previously investigated materials, BPA elution from CAD/CAM splint materials was highly elevated. Considering the increasing adaptation of CAD/CAM techniques, elution from them may represent a relevant BPA source in daily dental practice. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a compound known for its direct action on the prostate. Prostatic morphogenesis is a critical period when interference by any compound could permanently damage the organ. As such, the present study evaluated the morphological aspects resulting from gestational and lactational administration of BPA, indole-3-carbinol (I3C) and genistein (GEN) in prepubescent male rats. Pregnant Sprague Dawley females were allocated into 4 experimental groups and received the following: C: Control (no treatment); B: BPA (10 µg/Kg); BG: BPA+GEN (5 mg/Kg); BI: BPA+I3C (20 mg/Kg) from gestation day (GD) 17 to postnatal day (PND) 21. After euthanasia on PND22, the prostate was collected and processed. When administered alone, BPA reduced the stromal compartment when compared to group C (P = 0.039). This decline was reversed in the groups submitted to GEN (P = 0.019) or I3C (P = 0.017). The groups treated with BPA (P < 0.0001) and the phytoestrogens (P < 0.0001) exhibited decreased epithelial height in relation to the control group. These changes were observed in stereological and morphometric analyses, but not in fractal analysis (P = 0.569). The area occupied by collagen increased in groups treated with BPA (P < 0.0001) and phytoestrogens (P < 0.0001) in relation to controls, while collagen distribution values were higher in all the treated groups (P < 0.0001), according to fractal analysis. Thus, BPA induced prostrate stroma remodeling with no influence from the phytoestrogens, which may affect glandular development and cause histopathological changes in adulthood. [ABSTRACT FROM AUTHOR]

Simple Summary: Females prenatally exposed to diethylstilbestrol have an elevated risk of severe cervical dysplasia and some cancers, while testicular cancer is increased in males. We assessed these associations in the prenatally exposed female's offspring (third generation). Based on third-generation females' self-reports, diethylstilbestrol exposure was not associated with risks of overall cancer, breast cancer, or severe cervical dysplasia. Borderline ovarian cancer risk in exposed vs. unexposed was elevated but compatible with chance. Based on mothers' reports, diethylstilbestrol exposure did not increase the risk of overall or other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated but compatible with chance. Testicular cancer risk was not elevated in exposed males, and there were no prostate cancers reported. These data do not provide evidence that diethylstilbestrol is associated with cancer risk in third-generation females or males. The third generation is relatively young and requires follow-up to assess risk as the cohort ages. Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. [ABSTRACT FROM AUTHOR]

Bisphenol A diglycidyl ether (BADGE), a derivative of the well-known endocrine disruptor Bisphenol A (BPA), is a potential threat to long-term environmental health due to its prevalence as a micropollutant. This study addresses the previously unexplored area of BADGE toxicity and removal. We investigated, for the first time, the biodegradation potential of laccase isolated from Geobacillus thermophilic bacteria against BADGE. The laccase-mediated degradation process was optimized using a combination of response surface methodology (RSM) and machine learning models. Degradation of BADGE was analyzed by various techniques, including UV-Vis spectrophotometry, high-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). Laccase from Geobacillus stearothermophilus strain MB600 achieved a degradation rate of 93.28% within 30 min, while laccase from Geobacillus thermoparafinivorans strain MB606 reached 94% degradation within 90 min. RSM analysis predicted the optimal degradation conditions to be 60 min reaction time, 80°C temperature, and pH 4.5. Furthermore, CB-Dock simulations revealed good binding interactions between laccase enzymes and BADGE, with an initial binding mode selected for a cavity size of 263 and a Vina score of -5.5, which confirmed the observed biodegradation potential of laccase. These findings highlight the biocatalytic potential of laccases derived from thermophilic Geobacillus strains, notably MB600, for enzymatic decontamination of BADGE-contaminated environments. [ABSTRACT FROM AUTHOR]

BPA is a multifunctional endocrine disruptor with ubiquitous presence in aquatic ecosystems. The Mexican Central Plateau is an area severely impacted by pollution, inhabited by endemic viviparous fish. However, efforts to understand the effects of BPA on native species such as Goodea atripinnis are non-existent. This study focused on providing in vivo evidence of alterations in the testes of G. atripinnis males due to acute exposure to BPA at test concentrations of 1 mg/L, 10 mg/L, and 50 mg/L for 96 h. BPA exposition 1 mg/L and 10 mg/L showed degeneration and disorganization in germinal tissue. Furthermore, there was a notable decrease in sperm within the seminiferous tubules of males exposed to 10 mg/L of BPA. In all treatments, somatic cells had alterations by connective tissue thickening and an increase in collagen fibers. Additionally, inflammation and bleeding occurred in the testes of males exposed to 1 and 10 mg/L BPA. The alterations in the testes of G. atripinnis are related to BPA toxicity, which can lead to apoptosis in germ cells increasing connective tissue. Finally, even though the changes produced by BPA became evident in acute exposure (96 h), its effects are probably irreversible, compromising the reproduction of G. atripinnis. [ABSTRACT FROM AUTHOR]

Milk can be contaminated with organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs), which are known as endocrine disruptors (EDCs). However, the relationship between the lactation period of cows and the residues of EDCs is unknown. The aim of this study was to determine the relationship between the lactation period in cows and EDCs residues such as OCPs, PCBs, PBDEs, and PAHs. Milk collected from cows during each lactation period was analyzed in terms of fat content and EDC residues. One or more contaminants were detected in almost all (98%) of the milk taken in three lactation periods. Three PCBs and 11 PAHs were found together in 1st lactation period, and one more PAH was added to them in other periods. However, the sample rate exceeded the maximum residue limit of 48%, 10%, and 16% in the first, second and third lactation periods, respectively. Also, it was seen that the riskiest period was the first lactation period, followed by the third and second periods. The same ranking is valid for the fat content in milk. Thus, it was concluded that the excretion of lipophilic EDCs in milk is related to the fat content in milk, and the higher the fat content in milk, the more lipophilic EDCs are excreted in milk. [ABSTRACT FROM AUTHOR]

Resin composites may release bisphenol A (BPA) due to impurities present in the monomers. However, there is a lack of knowledge regarding the leaching characteristics of BPA from resin composites. Therefore, experimental resin composites were prepared with known amounts of BPA. The objective of this study was (1) to determine which amount of BPA initially present in the material leaches out in the short term and, (2) how this release is influenced by the resin composition. BPA (0, 0.001, 0.01, or 0.1 wt%) was added to experimental resin composites containing 60 mol% BisGMA, BisEMA(3), or UDMA, respectively, as base monomer and 40 mol% TEGDMA as diluent monomer. Polymerized samples (n = 5) were immersed at 37 °C for 7 days in 1 mL of water, which was collected and refreshed daily. BPA release was quantified with UPLC-MS/MS after derivatization with pyridine-3-sulfonyl chloride. Between 0.47 to 0.67 mol% of the originally added BPA eluted from the resin composites after 7 days. Similar elution trends were observed irrespective of the base monomer. Two-way ANOVA showed a significant effect of the base monomer on BPA release, but the differences were small and not consistent. The released amount of BPA was directly proportional to the quantity of BPA present in the resin composite as an impurity. BPA release was mainly diffusion-based, while polymer composition seemed to play a minor role. Our results underscore the importance for manufacturers only to use monomers of the highest purity in dental resin composites to avoid unnecessary BPA exposure in patients. [ABSTRACT FROM AUTHOR]

During the process of decidualization, the stromal cells of the endometrium change dynamically to create a favorable environment for embryo implantation. Lysosome activity has often been associated with physiological changes in the endometrium during the preimplantation period and early pregnancy. In this study, the effect of para-nonylphenol (p-NP), an endocrine disruptor, on human immortalized endometrial stromal cells (tHESCs) was investigated. After exposure to p-NP (1 nM and 1 pM), the cells were examined for the decidualization markers connexin-43, insulin like growth factor binding protein 1 (IGFBP1), and prolactin. In addition, the effect of p-NP on lysosome biogenesis and exocytosis was investigated by examining the expression and localization of the transcription factor EB (TFEB) and that of the lysosomal-associated membrane protein 1 (LAMP-1). Finally, we evaluated the effect of p-NP on extracellular matrix (ECM) remodeling using a fibronectin assay. Our results showed that p-NP reduced the expression of prolactin protein, increased the nuclear localization of TFEB, and induced the increase and translocation of the lysosomal protein LAMP-1 to the membrane of tHESCs. The data indicate an impairment of decidualization and suggest an increase in lysosomal biogenesis and exocytosis, which is supported by the higher release of active cathepsin D by tHESCs. Given the importance of cathepsins in the processing and degradation of the ECM during trophoblast invasiveness and migration into the decidua, our results appear to be clear evidence of the negative effects of p-NP on endometrial processes that are fundamental to reproductive success and the establishment of pregnancy. NEW & NOTEWORTHY: Endocrine disruptors, such as para-nonylphenol, affect the decidualization of human endometrial stromal cells with an impact on decidualization itself, lysosome biogenesis and exocytosis, and extracellular matrix remodeling. All these alterations may negatively impact embryo implantation with the success of reproduction and the establishment of pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Endocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS). Methods: NCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR. Results: Cell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65 ±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11- deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11- deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix. Discussion: In cell culture, bisphenols interfere with steroidogenesis at noncytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality. [ABSTRACT FROM AUTHOR]

The environmental spread of pollutants has led to a persistent exposure of living beings to multiple chemicals, by now become ubiquitous in the surrounding environment. Environmental exposure to these substances has been reported to cause multi- and/or transgenerational health effects. Per- and Polyfluorinated Substances (PFAS) raise great concern, given their known effects both as endocrine disruptors and potential carcinogens. The multi/trans-generational effects of different endocrine disruptors have been investigated by several studies, and harmful effects observed also for PFAS. This review examines the current data on the multi-trans-generational effects of PFAS, with a focus on their impact on the thyroid axis. The aim is to determine if there is evidence of potential multi-trans-generational effects of PFAS on the thyroid and/or if more research is needed. PFAS exposure impacts thyroid homeostasis and can cross the placental barrier. In addition PFAS have shown multi-transgenerational effects in laboratory experiences and animal models, but thyroid disruptive effects of PFAS were also investigated only in a small number of these studies. Efforts are needed to study the adverse effects of PFAS, as not all PFAS are regulated and removal strategies are still being developed. [ABSTRACT FROM AUTHOR]

Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid‐stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six‐week‐old male and female Sprague–Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the ≥1 mg/kg PTU and ≥3 mg/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3 mg/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67‐positive thyroid follicular cell counts, and TSH‐positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements. In rats treated with PTU and MMI for 28 days, histopathological and immunohistochemical findings and serum hormone levels were compared to establish a simplified method for detecting antithyroid chemicals. The results demonstrated that histopathological analysis and T4 immunostaining in the thyroid gland were more sensitive parameters than blood hormone levels and that immunohistochemistry for thyroid Ki67 and pituitary TSH may also be useful for evaluation. [ABSTRACT FROM AUTHOR]

Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is an endocrine disruptor pesticide that induces breast cancer cell proliferation through Estrogen receptor alpha pathway in humans. It also has toxic effects on some beneficial insects like bees, wasps, and arthropods, even low levels of CP can kill fish in water. Thus, it is important to efficiently remove this compound from wastewaters to get rid of its hazardous effects. Al2O3 supported ZnO.MoO3 composite was prepared as an efficient material for photo‐degradation of chlorpyrifos under UV irradiation and characterized by SEM‐EDX, XRD and TG techniques. The XRD analysis showed the orthorhombic structures with band gap of 2.86 eV for ZnO.MoO3/Al2O3 which was 2.96 eV for MoO3/Al2O3. The kinetics of degradation depicted that ZnO.MoO3/Al2O3 afforded a complete degradation of chlorpyrifos with half life of only 3 minutes which otherwise was 24 minutes in the presence of MoO3/Al2O3. The complete mineralization of chlorpyrifos was confirmed by GC/MS analysis, where no peaks of intermediates were recorded. The prepared material also exhibited good recyclability without any leaching of Zn and Mo metals. Thus, ZnO.MoO3/Al2O3 is an efficient and cost effective material for removal of chlorpyrifos. Its potential may also be explored for the removal of other hazardous organic pollutants. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is an endocrine disruptor pesticide that induces breast cancer cell proliferation through Estrogen receptor alpha pathway in humans. It also has toxic effects on some beneficial insects like bees, wasps, and arthropods, even low levels of CP can kill fish in water. Thus, it is important to efficiently remove this compound from wastewaters to get rid of its hazardous effects. Al2O3 supported ZnO.MoO3 composite was prepared as an efficient material for photo‐degradation of chlorpyrifos under UV irradiation and characterized by SEM‐EDX, XRD and TG techniques. The XRD analysis showed the orthorhombic structures with band gap of 2.86 eV for ZnO.MoO3/Al2O3 which was 2.96 eV for MoO3/Al2O3. The kinetics of degradation depicted that ZnO.MoO3/Al2O3 afforded a complete degradation of chlorpyrifos with half life of only 3 minutes which otherwise was 24 minutes in the presence of MoO3/Al2O3. The complete mineralization of chlorpyrifos was confirmed by GC/MS analysis, where no peaks of intermediates were recorded. The prepared material also exhibited good recyclability without any leaching of Zn and Mo metals. Thus, ZnO.MoO3/Al2O3 is an efficient and cost effective material for removal of chlorpyrifos. Its potential may also be explored for the removal of other hazardous organic pollutants. [ABSTRACT FROM AUTHOR]

Morphogenesis of the spleen during the neonatal period in rats exposed in prenatal and postnatal development to low doses of dichlorodiphenyltrichloroethane (DDT), a persistent universal pollutant with endocrine disrupting properties, was studied. More intensive formation of periarterial lymphoid sheaths and marginal zone and a simultaneously decreased rate of B-cell differentiation in the spleen were revealed. A higher content of differentiating T-cells and a lower number of cytotoxic T-lymphocytes by the end of the first week of life indicates a decrease in the differentiation of the latter. A lower content of neutrophils in the marginal zone also indicates a delay in the rate of functional development of lymphoid tissue, as opposed to morphological, in rats developing under exposure to low doses of DDT. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (TBBPA), due to its recognized harmful effects on the endocrine system, has drawn particular attention from scientists. Its presence in the environment has been proven in general, particularly in surface and groundwater. This study aims to eliminate TBBPA in batch mode in an aqueous medium using activated carbon based on a puck shell. The activated carbon (CRP) was characterized by advanced techniques such as EDX mapping, FT-IR, FE-SEM, XRD and N2 adsorption/desorption. The results revealed a high carbon content in the activated carbons with a surface of acidic functional groups. In addition, the Activated carbon (AC) exhibited an amorphous phase consisting of mesopores and micropores. The specific surface area obtained from the BET was 502 m2/g. Optimum conditions for TBBPA adsorption obtained from response surface methodology using Box-Behnken design were 200 mg for activated carbon, 15mg/L for TBBPA concentration at pH 7.6, a stirring time of 89 minutes, with a retention percentage of 87.9% corresponding to an absorbed quantity of 4,1 mg/g. Adsorption isotherms and kinetics showed a multilayer and favorable adsorption involving π-π interactions, the possibility of ion exchange, Van der Waals and hydrogen bonds. Computational modeling was carried out through functional density theory and Monte Carlo molecular modeling. These confirmed the experimental results, indicating a strong affinity between CRP and TBBPA in a slightly basic medium with an adsorption energy of -135.25 kcal/mol. The results of the desorption process using sodium hydroxide, water and ethanol as desorbing agents show that the CRP is reusable. [ABSTRACT FROM AUTHOR]

Background Bisphenol A (BPA) is an endocrine disrupter affecting glucose homeostasis. Objectives This study aimed to investigate BPA's relationship with Type 1 Diabetes Mellitus (T1DM) in Dakahlia Governorate's children, in Egypt. Subjects, materials and methods The study had two parts: clinical and experimental. Clinical Study was conducted on 200 children, equally divided into control and T1DM groups. They underwent: demographic data, height, weight, body mass index, glycosylated HbA1C, random blood glucose, and urinary BPA measurements. Experimental Study was conducted on 60 adult albino rats. Rats were randomly divided into three equal groups: control group: received 0.5 mL of pure olive oil, group 1: received 20 mg/kg/day BPA, and group 2: received 100 mg/kg/day BPA orally for 6 weeks. Fasting and two hours postprandial glucose levels were measured at the beginning and end of the study. Histopathological examination and imaging study of the pancreas were done. Results In clinical study: HbA1C and random blood glucose levels in diabetic children showed a significant increase compared to control. Children in control group showed controlled HbA1C, while the T1DM group showed 86% with poor diabetic control. There was a significant increase in BPA level in the T1DM group compared to the control. Rats that received BPA showed a marked increase in fasting and two hours postprandial glucose levels, histopathological changes in the pancreas with more changes determined in the high dose group, and a significant decrease in the islets of Langerhans diameters with group 2 more affected. Conclusion So, BPA exposure could be considered a risk factor for T1DM in children. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an anthropogenic chemical compound utilized to manufacture a wide range of consumer products, such as polycarbonate, polyvinyl chloride (PVC), food packages, and thermal papers. Because of its extensive worldwide use, BPA is pervasive in the environment, negatively affecting aquatic life. Therefore, we studied the occurrence, persistence, and ecological risk of BPA in surface water receiving raw leachate from a municipal solid waste (MSW) open dump in Kerawalapitiya, Sri Lanka. Our findings corroborate that the BPA average concentrations in the canal network were 0.4–42.6 µg/L during the wet season and 0.2–4.9 µg/L during the dry season. The levels of BPA at 11 locations (out of 16) during both seasons differed significantly from the upstream sample, where there was no impact from the dump site (p < 0.05), indicating the ubiquitous occurrence and persistence of BPA in the canal network. BPA levels in the waterbodies are greater in the wet period than in the dry period because of the continuous ingress of run‐off‐driven leachate to the canal network. Our study infers that pH and salinity correlate positively with BPA, while temperature, DO, and TSS are negatively correlated with BPA. BPA levels in five locations during the wet season and one during the dry season surpassed the tolerable level of BPA stipulated by the Canadian Federal Environmental Quality Guidelines to safeguard aquatic life, which is 3.5 µg/L. The findings of the acute ecological risk assessment articulate that during the wet season, Mozambique tilapia (Oreochromis mossambicus) and orange chromide (Etroplus maculatus) constitute a high acute risk, while they pose a medium acute risk during the dry season. Our study suggests that the relevant authorities must prevent the ingress of runoff rich with BPA onto the canal network to protect aquatic life. [ABSTRACT FROM AUTHOR]

ABSTRACT: Glyphosate-based herbicides (GBH) are the most extensively used herbicides worldwide. Despite a presumed nondangerousness for animals, several studies reported negative effects after a GBH exposure in several animal models including birds, notably on reproductive functions. Several studies concerning the advantages of Vitamin E (VE) for antioxidant activity but also growth and reproduction have been reported in birds. However, it remains unclear whether VE could alleviate the negative effect of GBHs on chicken ovarian cells. Here we exposed chicken primary granulosa cells (GCs) from F1 and F3/4 follicles to growing doses of GBH (0.036, 0.36, 3.6, and 36 gly eq/L), with or without VE supplementation (1 mg/L) and investigated cell viability, proliferation, oxidative stress and steroidogenesis. GBH exposure did not affect F1 and F3 GCs viability but it increased cell proliferation only in F1 GCs and this effect was not altered by VE. In both F1 and F3/4 GCs, GBH exposure increased total oxidant status (TOS), reduced total antioxidant status (TAS) and consequently increased index of oxidative stress (OSI) in dose dependent manner. This latter effect for GBH 36 mg eq gly/L was totally abolished in response to VE. In both F1 and F3/4 GCs, GBH exposure reduced progesterone secretion in a dose dependent manner and this effect with GBH 0.36 and 1.8 mg eq glyphosate/L was alleviated by VE. However, we did not observe any effect of GBH and VE on the gene expression of several components of the steroidogenesis process. Taken together, these results show that GBH may have endocrine disruptor effects, and that these effects might be alleviated by antioxidant VE supplementation.

The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1, both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα.

IntroductionTriclosan is an antibacterial and antifungal compound that is frequently found in personal care and consumer products, and its its impact on male reproductive health is a growing concern. Despite existing experimental studies demonstrating its potential threats to male fertility, reports on its effects on human semen quality remains limited and inconsistent. Therefore, this study presents a systematic review and meta-analysis assessing the relationship between triclosan exposure and semen quality.MethodsThis study was registered with PROSPERO (CRD42024524192) and adhered to PRISMA guidelines.ResultsThe study analyzed 562 screened studies, out of which five articles including 1,312 male subjects were finally included in the study. The eligible studies were geographically diverse, with three from China, one from Belgium, and one from Poland. More so, the eligible studies were both case-control and cross-sectional. The meta-analysis revealed that triclosan exposure significantly reduced sperm concentration (Standard Mean Difference (SMD) −0.42 [95% CI: −0.75, −0.10], P = 0.01) and sperm total motility (SMD −1.30 [95% CI: −2.26, −0.34], P = 0.008). Mechanistic insights from animal and in vitro studies showed that oxidative stress may mediate the adverse effects of triclosan on semen quality.DiscussionThis meta-analysis is the first comprehensive evaluation of the impact of triclosan on human semen quality, highlighting its potential to impair male fertility through reductions in sperm concentration and motility. However, the high heterogeneity among the included studies underscores the need for further high-quality research to establish more definitive conclusions regarding the effects of triclosan exposure on human reproductive health.

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.

This study examines the concentrations and population-normalized mass loads (PNML) of five phthalate esters (PAEs) and four metabolites (mPAEs) in 390 sewage sludge samples collected from two municipal wastewater treatment plants in Beijing between July 2020 and June 2023, amidst the COVID-19 pandemic. Through GC/MS analysis, the compounds were simultaneously quantified, with peak concentrations in 2020. Bis(2-ethylhexyl) phthalate (DEHP) and mono(2-ethyl-5-oxohexyl) phthalate emerged as predominant PAE and mPAE congeners with concentrations of 78.7 µg/g dw and 259 µg/g dw, respectively. DEHP and monobenzyl phthalate had the highest median PNML among PAEs and mPAEs, respectively, at 128 µg/inhabitant/day and 798 µg/inhabitant/day. Linear regression models revealed a positive association between PNML of PAEs and five public health and social measures aimed at mitigating the COVID-19 pandemic. This research contributes to the expanding body of literature by emphasizing the role of wastewater-based epidemiology as a vital tool for monitoring community-level exposure to environmental contaminants.

The molecular pathways involved in oviductal adenogenesis are highly conserved among vertebrates. In this work, we study the histomorphological changes and molecular pathways involved in Caiman latirostris oviductal adenogenesis and the effects of in ovo exposure to environmentally relevant doses of endosulfan (END) and atrazine (ATZ) on these processes. To this end, the histomorphological changes at epithelial and subepithelial compartments, the protein expressions of β-catenin and Wnt-7a, and the gene expression of metalloproteinases (MMPs) and its inhibitors (TIMPs) were evaluated as biomarkers of oviductal adenogenesis in prepubertal juvenile C. latirostris. Exposure to END altered adenogenesis-related epithelium characteristics and mRNA expression of MMP2, MMP9, and TIMP1. Exposure to ATZ increased the width of the subepithelial stroma with loosely arranged collagen fibers and increased β-catenin expression in buds (invaginated structures that precede glands). The results demonstrate that in ovo exposure to ATZ and END alters oviductal adenogenesis at tissue, cellular, and molecular levels. An altered oviductal adenogenesis could impair fertility, raising concern on the effects of pesticide pollution in wildlife and domestic animals. [ABSTRACT FROM AUTHOR]

The effects of endocrine disruptors including phenols and phthalates on adult lung function remain unclear. In the present study, data from 2007–2012 National Health and Nutrition Examination Survey (NHANES) were extracted, and 4338 participants were included in the final analyses. The associations of three phenols and four phthalate metabolites with six lung function parameters were investigated. In generalized linear regression models (GLM) and restricted cubic spline (RCS) analyses, bisphenol A (BPA) was associated with decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), and 2,5-dichlorophenol (DCP) was associated with reduced FEV1, FVC and peak expiratory flow rate (PEF), and increased prevalence of restrictive lung function (RLF) in adults. Furthermore, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models demonstrated that mixed exposures to phenols and phthalates were linked to reduced FEV1, FVC and PEF and increased prevalence of RLF, and these associations were mainly driven by BPA and 2,5-DCP. In conclusion, mixed exposure to phenols and phthalates was linked to compromised and a restrictive pattern of lung function. The mechanisms of the effects of phenol and phthalate exposures on lung function and respiratory diseases need to be further investigated. [ABSTRACT FROM AUTHOR]

Background: Investigation into environmental chemicals and their impact on human health is a topic of great interest. It is essential to understand the relationship between the quantity of chemical substances involved and the prevalence of particular diseases. Bisphenol-A (BPA) is a disrupting agent to human endocrine health. Human exposure to BPA is on the rise due to the widespread use of this agent, particularly in manufacturing industries. This study aimed to investigate the concentrations of BPA in the Iraqi population. Methods: This study aimed to determine the amount of BPA in the urine samples of 100 adults residing in the three cities of Diyalah, Kirkuk, and Solaymania in northeastern Iraq. After the subjects' urine samples were collected, the overall, free, and conjugated BPA contents of the samples were measured using high-performance liquid chromatography and mass spectroscopy (HPLC/MS). The data were adjusted based on the precalculated creatinine levels in the subjects. Results: Urine samples were collected from 100 individuals residing in three different cities in Iraq, comprising 47 men and 53 women. The concentrations of BPA in all participants' urine samples ranged from greater than the limit of quantification to 80.24 µg/g creatinine, with a calculated geometric mean of 4.17 µg/g creatinine. Conclusion: The findings of this preliminary study indicated that the Iraqi population's level of BPA exposure falls within an acceptable range. To provide a more accurate estimate of BPA exposure nationwide, further investigations on larger sample sizes are required across a wider range of age and gender distributions. [ABSTRACT FROM AUTHOR]

Introduction: The U. S. Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP) Tier 1 assays are used to screen for potential endocrine system-disrupting chemicals. A model integrating data from 16 high-throughput screening assays to predict estrogen receptor (ER) agonism has been proposed as an alternative to some low-throughput Tier 1 assays. Later work demonstrated that as few as four assays could replicate the ER agonism predictions from the full model with 98% sensitivity and 92% specificity. The current study utilized chemical clustering to illustrate the coverage of the EDSP Universe of Chemicals (UoC) tested in the existing ER pathway models and to investigate the utility of chemical clustering to evaluate the screening approach using an existing 4-assay model as a test case. Although the full original assay battery is no longer available, the demonstrated contribution of chemical clustering is broadly applicable to assay sets, chemical inventories, and models, and the data analysis used can also be applied to future evaluation of minimal assay models for consideration in screening. Methods: Chemical structures were collected for 6,947 substances via the CompTox Chemicals Dashboard from the over 10,000 UoC and grouped based on structural similarity, generating 826 chemical clusters. Of the 1,812 substances run in the original ER model, 1,730 substances had a single, clearly defined structure. The ER model chemicals with a clearly defined structure that were not present in the EDSP UoC were assigned to chemical clusters using a k-nearest neighbors approach, resulting in 557 EDSP UoC clusters containing at least one ER model chemical. Results and Discussion: Performance of an existing 4-assay model in comparison with the existing full ER agonist model was analyzed as related to chemical clustering. This was a case study, and a similar analysis can be performed with any subset model in which the same chemicals (or subset of chemicals) are screened. Of the 365 clusters containing >1 ER model chemical, 321 did not have any chemicals predicted to be agonists by the full ER agonist model. The best 4-assay subset ER agonist model disagreed with the full ER agonist model by predicting agonist activity for 122 chemicals from 91 of the 321 clusters. There were 44 clusters with at least two chemicals and at least one agonist based upon the full ER agonist model, which allowed accuracy predictions on a percluster basis. The accuracy of the best 4-assay subset ER agonist model ranged from 50% to 100% across these 44 clusters, with 32 clusters having accuracy =90%. Overall, the best 4-assay subset ER agonist model resulted in 122 false-positive and only 2 false-negative predictions compared with the full ER agonist model. Most false positives (89) were active in only two of the four assays, whereas all but 11 true positive chemicals were active in at least three assays. False positive chemicals also tended to have lower area under the curve (AUC) values, with 110 out of 122 false positives having an AUC value below 0.214, which is lower than 75% of the positives as predicted by the full ER agonist model. Many false positives demonstrated borderline activity. The median AUC value for the 122 false positives from the best 4-assay subset ER agonist model was 0.138, whereas the threshold for an active prediction is 0.1. Conclusion: Our results show that the existing 4-assay model performs well across a range of structurally diverse chemicals. Although this is a descriptive analysis of previous results, several concepts can be applied to any screening model used in the future. First, the clustering of the chemicals provides a means of ensuring that future screening evaluations consider the broad chemical space represented by the EDSP UoC. The clusters can also assist in prioritizing future chemicals for screening in specific clusters based on the activity of known chemicals in those clusters. The clustering approach can be useful in providing a framework to evaluate which portions of the EDSP UoC chemical space are reliably covered by in silico and in vitro approaches and where predictions from either method alone or both methods combined are most reliable. The lessons learned from this case study can be easily applied to future evaluations of model applicability and screening to evaluate future datasets. [ABSTRACT FROM AUTHOR]

Detergents are highly produced pollutants with environmental problems like foam generation and toxic effects in biota. Nonylphenol ethoxylates (NPEs) are efficient, economical, and versatile surfactants, used in detergents for more than 40 years due to their detergency capacity. In the environment, NPE biodegrades into the metabolite nonylphenol (NP), classified as an endocrine disruptor. The identification and quantification of 4-NP in a designed detergent and 30 commercially available detergents were performed to prove the degradation of NPE into 4-NP during storage time. This investigation introduces the first evidence of NPE degradation during storage in commercially available detergents, demonstrating a novel exposure pathway in humans that has not been explored before, representing potential human health risks. Therefore, simple, easy, low-cost, and available approaches to remove and substitute NP is paramount. Alkyl polyglucoside (APG) was assessed as a substitute, and the feasibility of this substitution was proven according to physical and chemical properties, cleaning performance, and antimicrobial properties. NPE substitution in detergents is demonstrated as a viable strategy to minimize exposure risks in humans and the environment. [ABSTRACT FROM AUTHOR]

Simple Summary: This work challenges the traditional principles of cancer therapy: simply targeting and blocking the regulatory pathways of rapidly proliferating tumors is a serious mistake. Since tumor initiation and growth may be attributed to a patient's genomic instability and damage, genotoxic medications are inappropriate as they cause additional genomic damage in both patients and their cancers. Tumor cells are not enemies to be killed, but rather they are ill human cells which have the remnants of same genome stabilizer pathways like healthy cells. Within tumors, there is a combat for the improvement of their genomic defects. Moreover, tumors ask for help in their kamikaze action by recruiting immune competent cells into their environment. We should learn by watching the genome repairing activities within tumors, in the peritumoral region and in the whole body, and may follow them with supportive care. Successful cancer therapy does not remain a dream to be realized in the far future, but we should set about a cancer cure without delay. Background: In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors.Purpose: Justifying that cancer cells are not enemies to be killed, but rather that they are ill human cells which have the remnants of physiologic regulatory pathways. Results: 1. Genomic instability and cancer development may be originated from a flaw in estrogen signaling rather than excessive estrogen signaling; 2. Healthy cells with genomic instability exhibit somatic mutations, helping DNA restitution; 3. Somatic mutations in tumor cells aim for the restoration of DNA damage, rather than further genomic derangement; 4. In tumors, estrogen signaling drives the pathways of DNA stabilization, leading to apoptotic death; 5. In peritumoral cellular infiltration, the genomic damage of the tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, an increased growth factor receptor (GFR) signaling confers the unliganded activation of estrogen receptors (ERs); 6. In breast cancer cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signaling and consequential apoptosis. In breast tumors non-responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathways are exhausted, leading to farther genomic instability and unrestrained proliferation. Conclusions: Understanding the real character and behavior of human tumors at the molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy, rather than provoking additional genomic damages. [ABSTRACT FROM AUTHOR]

Nonylphenol ethoxylate (NPE) is an endocrine-disrupting chemical that has bioaccumulative, persistent and toxic characteristics in different environmental matrices and is difficult to remove in sewage treatment plants. In this study, the effects of the initial concentration of NPE (0.2 ± 0.03 - 3.0 ± 0.02 mg. L−1) and ethanol (73.9 ± 5.0-218.6 ± 10.6 mg. L−1) were investigated using factorial design. Assays were carried out in anaerobic batch reactors, using the Zinder basal medium, yeast extract (200 mg. L−1), vitamin solution and sodium bicarbonate (10% v/v). The optimal conditions were 218.56 mg.L−1 of ethanol and 1596.51 µg.L−1 of NPE, with 92% and 88% of NPE and organic matter removal, respectively, and methane yield (1689.8 ± 59.6 mmol) after 450 h of operation. In this condition, bacteria potentially involved in the degradation of this surfactant were identified in greater relative abundance, such as Acetoanaerobium (1.68%), Smithella (1.52%), Aminivibrio (0.91%), Petrimonas (0.57%) and Enterobacter (0.47%), as well as archaea Methanobacterium and Methanoregula, mainly involved in hydrogenotrophic pathway. [ABSTRACT FROM AUTHOR]

In this study, a new biosensor was designed to the determination of Bisphenol A (BPA), an endocrine disruptor. First, poly(amidoamine) salicylidenimine Pd(II)-loaded PAMAM dendrimer was synthesized and characterized. Then, a modified carbon paste electrode was prepared with this Pd(II)-loaded PAMAM dendrimer. The biosensor was prepared by immobilizing the tyrosinase enzyme on the modified carbon paste electrode surface by the cross-linking method in the presence of glutaraldehyde. BPA determination was made by measuring the cathodic currents of the quinone compound formed due to this enzymatic reaction at − 0.10 V. In order to determine the best working conditions of the prepared BPA biosensor, linear operating range, polymer amount, glutaraldehyde amount, pH, temperature, BPA concentration effect, reproducibility, and shelf-life studies were performed. The prepared biosensor with a wide operating range (0.001–0.05 μM and 0.1–1.0 μM, (R2 = 0.9530 and R2 = 0.9765)), a very low detection limit (0.001 µM) and good reproducibility was prepared (relative standard deviation of 9.43% after 18 measurements). The effects of species that may interfere with BPA determination on real samples were investigated. The prepared biosensor was used to detect BPA leakage from plastic food storage containers and plastic water bottles. [ABSTRACT FROM AUTHOR]

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Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with ingested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant referred to as HydroRenewable Jet (HRJ) fuel, to help evaluate potential effects of ingested jet fuel. The results of the in vivo study provide evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated that JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while HRJ was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid receptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action. [ABSTRACT FROM AUTHOR]

Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition of their impact on human health and the environment has stimulated attention and research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, and industry representatives, are collaborating to develop robust methodologies and guidelines for assessing these disruptors. A key aspect of these efforts is the development of standardized testing protocols and guidelines that aim to provide consistent and reliable methods for identifying and characterizing endocrine disruptors. When evaluating the potential endocrine-disrupting activity of chemicals, no single test is capable of detecting all relevant endocrine-disrupting agents. The test battery approach is designed to reduce the risk of false negative results for compounds with toxic potential. A weight-of-evidence approach is therefore necessary for endocrine disruptor evaluation. This approach considers various types of data from multiple sources, assessing the overall strength, consistency, and reliability of the evidence. OECD guidelines are highly regarded for their scientific rigor, transparency, and consensus-based development process. It is crucial to explore and develop new methodologies that can effectively evaluate the risks associated with potential endocrine disruptors. Integrating these methods into a comprehensive weight-of-evidence framework will enhance risk assessments and facilitate informed decisions regarding the regulation and management of these substances, ensuring the protection of human health and the environment from their adverse effects. [ABSTRACT FROM AUTHOR]