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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]

Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1β and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.

Plastics constitute a vast array of substances, with over 16 000 known plastic chemicals, including intentionally and non-intentionally added substances. Thousands of chemicals, including toxic ones, are extractable from plastics, however, the extent to which these compounds migrate from everyday products into food or water remains poorly understood. This study aims to characterize the endocrine and metabolism disrupting activity, as well as the chemical composition of migrates from plastic food contact articles (FCAs) from four countries as significant sources of human exposure. Fourteen plastic FCAs covering seven polymer types with high global market shares were migrated into water and a water–ethanol mixture as food simulants according to European regulations. The migrates were analyzed using reporter gene assays for nuclear receptors relevant to human health and non-target chemical analysis to characterize the chemical composition. Chemicals migrating from each FCA interfered with at least two nuclear receptors, predominantly targeting pregnane X receptor (24/28 migrates). Moreover, peroxisome proliferator receptor gamma was activated by 19 out of 28 migrates, though mostly with lower potencies. Estrogenic and antiandrogenic activity was detected in eight and seven migrates, respectively. Fewer chemicals and less toxicity migrated into water compared to the water–ethanol mixture. However, 73 % of the 15 430 extractable chemical features also transferred into food simulants, and the water–ethanol migrates exhibited a similar toxicity prevalence compared to methanol extracts. The chemical complexity differed largely between FCAs, with 8 to 10 631 chemical features migrating into food simulants. Using stepwise partial least squares regressions, we successfully narrowed down the list of potential active chemicals, identified known endocrine disrupting chemicals, such as triphenyl phosphate, and prioritized chemical features for further identification. This study demonstrates the migration of endocrine and metabolism disrupting chemicals from plastic FCAs into food simulants, rendering a migration of these compounds into food and beverages probable.

IntroductionEndocrine 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).MethodsNCI-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.ResultsCell 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.DiscussionIn cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic 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.

Bisphenol A (BPA), an endocrine disruptor used in different commercial polymers, is a persistent pollutant commonly found in effluents. Conventional wastewater treatment processes have low chemical removal efficiency and are expensive. This work evaluated BPA removal using laccase enzyme produced from white rot fungus Pleurotus ostreatus. For the enzymatic production, residues of acai berry and pineapple were used as laccase inducers. The use of natural inducers led to a high enzyme production (1139 and 1031 U mL−1 to acai and pineapple, respectively). Bisphenol A was removed to a concentration lower than LOD (limit of detection) after 4 h. The degradation mechanism of BPA occurred by oxidation of methyl to hydroxymethyl group in a propane portion, with breakdown of the aromatic ring. The developed technology brought to the scene a new green, viable methodology, using vegetable waste, adding value to these residues and bringing an alternative to the BPA treatment.

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases.

Endocrine disruptors, also known as endocrine-disrupting chemicals, could mimic or interfere with the body's hormones. Indeed, naturally occurring endocrine disruptors have been widely identified in daily foods. Moreover, industrialisation has resulted in increasing synthetic endocrine disruptors being produced and used as food additives or in food package materials, which makes exposure to endocrine disruptors become more common. Although the safety of synthetic chemicals has been extensively evaluated before entering into the food industry, increasing evidence has also highlighted that long-lasting exposure might influence long-term metabolic outcomes and be associated with the prevalence of obesity. Therefore, this review summarised the sources, detection methods, obesogenic effects and possible mechanisms of endocrine disruptors commonly found in foods, as well as discussed possible underlying mechanisms by which endocrine disruptors contribute to the increased risk of obesity. In conclusion, the review may provide useful information for understanding the association between endocrine disruptors and obesity, which could provide a new angle of view for preventing obesity prevalence.

Bisphenols (BP) are pollutants that are globally and widely distributed and adversely affect the health of humans. However, knowledge of their presence in animals, especially farm animals such as pigs, remains limited. In this study, the incidence of bisphenol A (BPA) and its five analogues - bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), bisphenol Z (BPZ) and bisphenol AF (BPAF) - was monitored in lactating sows on an actual pig farm. The urine samples of 27 sows were collected twice on the 3rd day after parturition, and stored at -20 °C until analysis using MDGC/MS. None of the lactating sows produced bisphenol-free urine. In contrast, the urine of all sows contained at least two bisphenols (eight females), most often five (10 females) or all six bisphenols (five females). The average concentrations of bisphenols in urine were in the order of BPB > BPA and BPS > BPZ > BPAF > BPF. The most frequently detected bisphenol was BPB (96.0% of samples) followed by BPA (89.0%), BPAF (78.0%), BPS (63.0%), BPF (52.0%) and BPZ (37.0%). Additionally, the proportion of BPB in the total bisphenol concentration in urine samples was the highest (28.74 to 93.85%) while that of BPF was the lowest (2.33 to 16.70%). Estimated daily intakes of bisphenols as well as hazard quotients were much lower than risk thresholds established for the human population, indicating safe doses for the health status of lactating sows. However, these findings are limited as the mechanism of BPA analogue' activity is still unclear, and the long-term effects of small doses of bisphenols and the potential harmful impact of BP mixtures are unknown. Knowledge of the occurrence of bisphenols in pig farming may contribute to the elimination of BPA and its analogues from this sector, which is crucial for the safety of animal products as well as the welfare of pigs.

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.

Rapidly advancing evidence documents that a broad array of synthetic chemicals found ubiquitously in the environment contribute to disease and disability across the lifespan. Although the early literature focused on early life exposures, endocrine‐disrupting chemicals (EDCs) are now understood to contribute substantially to chronic disease in adulthood, especially metabolic, cardiovascular, and reproductive consequences as well as endocrine cancers. The contribution to mortality is substantial, with over 90,000 deaths annually and at least $39 billion/year in lost economic productivity in the United States (US) due to exposure to certain phthalates that are used as plasticizers in food packaging. Importantly, exposures are disproportionately high in low‐income and minoritized populations, driving disparities in these conditions. Though non‐Hispanic Blacks and Mexican Americans comprise 12.6% and 13.5% of the US population, they bear 16.5% and 14.6% of the disease burden due to EDCs, respectively. Many of these exposures can be modified through safe and simple behavioral changes supported by proactive government action to both limit known hazardous exposures and to proactively screen new industrial chemicals prior to their use. Routine healthcare maintenance should include guidance to reduce EDC exposures, and a recent report by the Institute of Medicine suggests that testing be conducted, particularly in populations heavily exposed to perfluoroalkyl substances—chemicals used in nonstick coatings as well as oil‐ and water‐resistant clothing. [ABSTRACT FROM AUTHOR]

Given the increasing concern surrounding ultraviolet (UV) radiation-induced skin damage, there has been a rise in demand for UV filters. Currently, UV-filters are considered emerging contaminants. The extensive production and use of UV filters have led to their widespread release into the aquatic environment. Thus, there is growing concern that UV filters may bioaccumulate and exhibit persistent properties within the environment, raising several safety health concerns. Octyl-methoxycinnamate (OMC) is extensively employed as a UV-B filter in the cosmetic industry. While initially designed to mitigate the adverse photobiological effects attributed to UV radiation, the safety of OMC has been questioned with some studies reporting toxic effects on environment. The aim of this review to provide an overview of the scientific information regarding the most widely used organic UV-filter (OMC), and its effects on biodiversity and aquatic environment. [ABSTRACT FROM AUTHOR]

Objectives] This study was conducted to explore the occurrence levels of endocrine disruptors ( EDCs) in rural areas around a county landfill in Tongren City. [Methods] The water around the landfill was sampled and analyzed. A solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry ( SPE-UPLC-MS/MS) method was established for the determination of 27 ED Cs. After the HLB solid-phase extraction column was activated, a water sample, which was adjusted with phosphoric acid to a pH of 2 ( ± 0. 5) and added with 500 mg of disodium EDTA, was loaded, and 5 ml of water and 20% methanol water was added for washing. Next, 10 ml of elution solution was added for elution, and the collected eluate was evaporated under reduced pressure at 40 oC to near dryness, and 10 ml of reconstitution solution was added to a constant volume. An ACQUITY UPLC BEH C18 (100 x2.1 mm, 2.6μm) chromatographic column was adopted for LC separation by gradient elution with pure water solution-acetonitrile as the mobile phase. For MS detection, the MRM mode was adopted for collection, and the positive and negative ion modes were switched for simultaneous determination, and the internal standard method was used for quantification. [Results] The correlation coefficient R2 was greater than 0. 99 in the linear range of each target substance. The limits of quantitation in the method were between 0.05 and 2.00 ng/L, and the recoveries ranged from 75.3% to 105. 7%. [Conclusions] The method has high sensitivity, good accuracy and strong practical value. [ABSTRACT FROM AUTHOR]

Bisphenol S (BPS), a BPA analog and a safer alternative, is utilized in a diverse range of industrial applications, such as making polycarbonate plastics, epoxy resins, thermal receipt papers, and currency bills. Recently, the increased use of BPS in containers and packages for daily life has been interrogated due to its identical chemical structure and probable endocrine‐disrupting actions as BPA has. The present study aimed to evaluate the alterations in biochemical indices and antioxidant enzymes as certain indicators of the endocrine‐disrupting effect of BPS in Channa striatus, a freshwater fish. BPS‐exposed fish species were subjected to three sub‐lethal concentrations of BPS (1, 4, and 12 ppm) and observed after an interval of 7 and 21 days. Exposure to BPS caused a reduction in the level of protein in muscle, gonads and the liver due to an impairment of protein synthesis. Levels of cholesterol in the muscle, gonads, and liver of BPS‐exposed fish were found to be decreased after treatment, indicating either an inhibition of cholesterol biosynthesis in the liver or reduced absorption of dietary cholesterol. The levels of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase showed remarkable increases, while the activity of glutathione S‐transferase decreased considerably, indicating the antioxidant defense mechanism to counteract the oxidative stress induced by BPS. Moreover, a significant increase was noted in the level of lipid peroxidation products, like malondialdehyde and conjugate diene, which represent biomarkers of oxidative stress. The histoarchitecture changes were also observed in the liver, muscle and gonads of BPS‐treated fish species. The present study showed that sub‐lethal exposure to BPS significantly influenced the activities of these enzymes and peroxidation byproducts. From this study, it is concluded that BPS‐caused toxic effects in fish species lead to an imbalance in the antioxidant defense system. It is clearly indicated that BPS toxicity could lead to susceptible oxidative stress in various tissues and could damage vital organs. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), is widely used in the production of plastics, including food containers, electronic elements and mainly epoxy resins and polycarbonate plastics. It can penetrate to the environment and living organisms through the digestive tract, lungs and skin. BPA affects, among others, the nervous, immune, endocrine and cardiovascular systems. Unlike in human medicine, the role of BPA as a toxic and pathogenic agent in veterinary medicine has been marginalized until recently. On the other hand, it is known that companion animals, especially dogs and cats, which live in direct contact with humans in the same household, are exposed to similar environmental pollutants. BPA is present in animals food packages, toys, bowls and other items containing plastic. This review article describes the negative effects of BPA on living organisms and highlights what we know about the harmful effects of this endocrine disruptor on the health of dogs and cats. [ABSTRACT FROM AUTHOR]

Simple Summary: Bisphenol AF (BPAF) is a common environmental endocrine-disrupting chemical (EDC) that can potentially affect the growth and development of aquatic organisms. EDCs in the aqueous environment can be deposited in estuaries through runoff or diffused into the marine environment. The toxicity of the EDCs is related to exposure dose and duration. In this study, we used marine medaka as the experimental subject to dynamically observe the response of fish in terms of growth, reproduction and antioxidant immune system during BPAF exposure, providing new insights into understanding the marine ecological risk of BPAF. In recent years, bisphenol AF (BPAF) in aquatic environments has drawn attention to its ecological risks. This study aims to investigate the toxic effects of BPAF (188.33 μg/L) exposure for 30 days on female marine medaka (Oryzias melastigma). On the 10th and 30th day of exposure, the toxicity was evaluated using histological analysis of the liver and ovaries and the transcription levels of genes related to the antioxidant system, immune system, and hypothalamic-pituitary-gonadal (HPG) axis. Findings revealed that (1) BPAF exposure caused vacuolation, karyopyknosis and karyolysis in the liver of marine medaka, and the toxic impact augmented with duration; (2) exposure to BPAF for 10 days facilitated the growth and maturation of primary ova, and this exposure had a comparatively inhibitory effect after 30 days; (3) exposure to BPAF resulted in a biphasic regulation of the transcriptional abundance of genes involved in antioxidant and inflammatory response (e.g., il-8, cat), with an initial up-regulation followed by down-regulation. Additionally, it disrupted the transcriptional pattern of HPG axis-related genes (e.g., 3βhsd, arα). In conclusion, 188.33 μg/L BPAF can alter the expression levels of functionally related genes, impair the structural integrity of marine organisms, and pose a threat to their overall health. [ABSTRACT FROM AUTHOR]

Obesity and obesity-related disorders such as cancer, type 2 diabetes, and fatty liver have become a global health problem. It is well known that the primary cause of obesity is positive energy balance. In addition, obesity is the consequence of complex gene and environment interactions that result in excess calorie intake being stored as fat. However, it has been revealed that there are other factors contributing to the worsening of obesity. The presence of nontraditional risk factors, such as environmental endocrine-disrupting chemicals, has recently been associated with obesity and comorbidities caused by obesity. The aim of this review was to examine the evidence and potential mechanisms for acrylamide having endocrine-disrupting properties contributing to obesity and obesity-related comorbidities. Recent studies have suggested that exposure to environmental endocrine-disrupting obesogens may be a risk factor contributing to the current obesity epidemic, and that one of these obesogens is acrylamide, an environmental and industrial compound produced by food processing, particularly the processing of foods such as potato chips, and coffee. In addition to the known harmful effects of acrylamide in humans and experimental animals, such as neurotoxicity, genotoxicity, and carcinogenicity, acrylamide also has an obesogenic effect. It has been shown in the literature to a limited extent that acrylamide may disrupt energy metabolism, lipid metabolism, adipogenesis, adipocyte differentiation, and various signaling pathways, and may exacerbate the disturbances in metabolic and biochemical parameters observed as a result of obesity. Acrylamide exerts its main potential obesogenic effects through body weight increase, worsening of the levels of obesity-related blood biomarkers, and induction of adipocyte differentiation and adipogenesis. Additional mechanisms may be discovered. Further experimental studies and prospective cohorts are needed, both to supplement existing knowledge about acrylamide and its effects, and to clarify its established relationship with obesity and its comorbidities. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) and one of the most produced synthetic compounds worldwide. BPA can be found in epoxy resins and polycarbonate plastics, which are frequently used in food storage and baby bottles. However, BPA can bind mainly to estrogen receptors, interfering with various neurologic functions, its use is a topic of significant concern. Nonetheless, the neurotoxicity of BPA has not been fully understood despite numerous investigations on its disruptive effects. Therefore, this review aims to highlight the most recent studies on the implications of BPA on the neurologic system. Our findings suggest that BPA exposure impairs various structural and molecular brain changes, promoting oxidative stress, changing expression levels of several crucial genes and proteins, destructive effects on neurotransmitters, excitotoxicity and neuroinflammation, damaged blood–brain barrier function, neuronal damage, apoptosis effects, disruption of intracellular Ca2+ homeostasis, increase in reactive oxygen species, promoted apoptosis and intracellular lactate dehydrogenase release, a decrease of axon length, microglial DNA damage, astrogliosis, and significantly reduced myelination. Moreover, BPA exposure increases the risk of developing neurologic diseases, including neurovascular (e.g. stroke) and neurodegenerative (e.g. Alzheimer's and Parkinson's) diseases. Furthermore, epidemiological studies showed that the adverse effects of BPA on neurodevelopment in children contributed to the emergence of serious neurological diseases like attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, emotional problems, anxiety, and cognitive disorders. In summary, BPA exposure compromises human health, promoting the development and progression of neurologic disorders. More research is required to fully understand how BPA-induced neurotoxicity affects human health. [ABSTRACT FROM AUTHOR]

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpa), CCAAT/enhancer binding protein beta (Cebpb), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity. [ABSTRACT FROM AUTHOR]

Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 %), BPA (unconjugated in 35 % and conjugated in 60 %) and oxybenzone (both forms in 45 %). To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a non-essential element with sub-lethal effects even at low concentrations. The persistent nature of Cd and its tendency to bioaccumulate eventually create harmful effects on water biota, including fish. Cd affects various aspects of hormonal action in fish since it bioaccumulates in the endocrine system and hinders the synthesis, secretion, and metabolic activity of hormones, causing severe damage along the hypothalamus–pituitary–gonadal axis. Linking reproductive and developmental impairments in fish with ecologically relevant concentrations of individual metals can be challenging due to the complexity of aquatic ecosystems. This review deliberated the significant and novel trends of toxicological difficulties and approaches, including elucidating environmental sources' bioavailability and Cd-induced toxic effects in freshwater fish. Both acute and chronic exposure to Cd can cause a range of adverse effects, such as growth inhibition, impaired reproductive capacity, endocrine disruption, and developmental abnormalities in freshwater fish, as evidenced by the present review. These investigations support the concept of Cd as a naturally available pollutant that causes irreversible damage in fish. These findings will help to understand the etiology of environmental circumstances that pose substantial dangers to fish health and are also crucial for preventing and treating exposure-related reproductive disturbances in freshwater fish due to environmental pollution. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases. [ABSTRACT FROM AUTHOR]

Nonylphenol (NP) and octylphenol (OP) are two typical environmental endocrine disruptors often coexisted in the environment, and their oral ingestion may impact the digestive system. OBJECTIVE: This study aimed to investigate the separate and combined effects of NP and OP exposure on rat intestinal injury. METHODS: Rats were administered varying concentrations of NP and OP individually or in combination via gavage for a duration of 28 days, and intestinal oxidative stress, inflammation, intestinal permeability and intestinal cell apoptosis in each group were observed. RESULTS: Individual or combined exposure to NP and OP led to structural damage to the colonic intestinal barrier, altered antioxidant enzyme activity in the colon, increased expression of cytokines IL-1β, TNF-α and IFN-γ, and increased expression of apoptotic proteins Caspase-3, Casspase-12, Bax and Bcl-2. CONCLUSIONS: The exposure to NP and OP, whether individually or in combination, resulted in increased pro-inflammatory cytokine production, decreased antioxidant enzyme expression, and induced apoptosis in the rat intestine, leading to different degrees of damage. This study may offer a theoretical foundation for the prevention and control of damage caused by environmental endocrine disruptors. [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.

IntroductionEver since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute’s exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure.MethodsUrine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography–tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated.ResultsOur study found that the median level of BPA was significantly higher in adults (9.63 μg/g creatinine) than in minors (6.63 μg/g creatinine) (p

Combined oral contraceptives, comprising of both an oestrogen and a progestin component, are released in aquatic environments and potentially pose a risk to aquatic wildlife by their capacity to disrupt physiological mechanisms.In this study, the endocrine disruptive potential of two mixtures, 17α-ethinylestradiol (EE2), a synthetic oestrogen, or estetrol (E4), a natural oestrogen, with the progestin drospirenone (DRSP) have been characterised in three generations of zebrafish, according to an adapted Medaka Extended One Generation Reproduction Test. Zebrafish (Danio rerio) were exposed to a range of concentrations of EE2/DRSP and E4/DRSP (∼1×, ∼3×, ∼10× and ∼30× predicted environmental concentration, PEC). Survival, growth, hatching success, fecundity, fertilisation success, vitellogenin (VTG), gonad histopathology, sex differentiation, and transcriptional analysis of genes related to gonadal sex steroid hormones synthesis were assessed.In the F0 generation, exposure to EE2/DRSP at ∼10 and ∼30× PEC decreased fecundity and increased male VTG concentrations. The highest concentration of EE2/DRSP also affected VTG concentrations in female zebrafish and the expression of genes implicated in steroid hormones synthesis. In the F1 generation, sex determination was impaired in fish exposed to EE2/DRSP at concentrations as low as ∼3× PEC. Decreased fecundity and fertility, and abnormal gonadal histopathology were also observed. No effects were observed in the F2 generation. In contrast, E4/DRSP induced only minor histopathological changes and an increase in the proportion of males, at the highest concentration tested (∼30× PEC) in the F1 generation and had no effect on hatching success of F2 generation.Overall, this study suggests that the combination E4/DRSP has a more favourable environmental profile than EE2/DRSP.

IntroductionThe 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.MethodsChemical 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 DiscussionPerformance 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 per-cluster 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.ConclusionOur 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: 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.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Abstract Recently, green analytical chemistry (GAC) is a key issue towards the idea of sustainability, the analytical community is focused on developing analytical methods that incorporate green chemistry principles to minimize adverse impacts on the environment and humans. Herein, we present 2 sustainable, selective, and validated chromatographic methods. Initially, lidocaine hydrochloride (LDC) and miconazole nitrate (MIC) with two preservatives; methyl paraben (MTP) and saccharin sodium (SAC) were chromatographed via TLC–densitometric method which employed ethyl acetate: methanol: formic acid (9:1:0.1, by volume) as the mobile phase with UV detection at 220.0 nm, good correlation was obtained in the range of 0.3–3.0 µg/band for MIC and LDC. Following that, RP-HPLC was successfully applied for separating quinary mixture of LDC, MIC, MTP, SAC along with LDC impurity; dimethyl aniline (DMA) using C18 column, and a gradient green mobile phase composed of methanol and phosphate buffer (pH 6.0) in different ratios with a flow rate 1.5 mL/min and UV detection at 210.0 nm, linearity ranges from 1.00 to 100.00 µg/mL for MIC, 2.00–100.00 µg/mL for LDC and 1.00–-20.00 µg/mL for MTP and DMA. No records to date regarding the determination of the two drugs, besides MTP and DMA. The proposed methods were validated according to the ICH guidelines and applied successfully to the analysis of the compounds. The methods' results were statistically compared to those obtained by applying the reported one, indicating no significant difference regarding both accuracy and precision. The methods' greenness profiles have been assessed and compared with those of the reported method using different assessment tools. Graphical Abstract

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) used as a plastic enhancer in producing polycarbonate resins to manufacture hard plastics. Due to strict limitations on the manufacturing and utilization of BPA, several bisphenol substitutes, bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF), have been developed to replace it in various applications. Because of their widespread use in food containers, infant bottles, and reusable water bottles, bisphenols (BPs) have been identified in different environmental circumstances, including drinking water, seawater, industrial effluent, and endocrine systems such as human blood, urine, and breast milk. However, locating and analyzing them in different conditions has proven to be challenging. Therefore, there is a need to reduce the prevalence of BPs in the environment. The significance of advanced treatment options for treating and eliminating BPA and its alternatives from water bodies are reviewed. Also, the research gaps and future scopes are discussed in this review article. According to the literature survey, adsorption and photocatalytic degradation provide synergistic benefits for environmental challenges because of their substantial adsorption Q5 capacity, high oxidation capability, and low cost compared to alternative individual treatment options. HIGHLIGHTS The occurrence of bisphenols in aquatic systems has been addressed.; The aggressive impact of endocrine-disrupting chemicals in the environmental matrices is outlined.; The pollutant's sustainability and structural characteristics are analyzed.; The cost-effective treatment strategies for simultaneous BPs reduction are discussed.; The significances of BPs on the integrated treatment approach are detailed.;

BackgroundEndocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.ObjectivesWe sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.MethodsWe used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.ResultsMetabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.DiscussionThis study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.

Background: This review aimed to emphasize the effects, mechanisms involved, conditions required to trigger impacts, and the adapted responses of EMF on thyroid gland. Methods: The included literatures were collected from the Oceania Radiofrequency Scientific Advisory Association (ORSAA) database which were published before April 2021. The searched was then refined with keyword ‘thyroid’. Results: A total of 15 experimental studies, 10 observational studies, 4 review articles, and 1 medical hypothesis were included. Hypothyroidism is the most reported functional abnormality. The identified morphological abnormalities of the thyroid gland include increased follicular epithelial and interfollicular tissue, decreased colloid volume of cubic cells, follicular fluid, interfollicular space, changes in lysosomes, granular endoplasmic reticulum, cell nuclei, changes in glandular structures including cell hypotrophy, glandular hypertrophy, and increased apoptosis via caspase-dependent pathways. The observational studies reported an increase in thyroid cancer incidence and the diameter of the left anteroposterior of the thyroid gland. Postulation that thyroid cancer is associated with thyroid cancer EMF exposure, is suggested by a medical hypothesis paper. The possibilities of hypothyroidism, thyroid cancer, and cell apoptosis due to EMF exposure have been highlighted in the review articles. Conclusion: Despite these findings, critical elements, such as the effects and mechanisms of EMF exposure on thyroid hormone transporters, genomic and non-genomic actions, conditions required for the effect to occur, and the resultant adapted responses, have not been explored suggesting the need of further research.

The intention of the collective West to supply the armed forces of Ukraine with armor-piercing shells with cores (penetrators) made of depleted uranium (DU), is changing the situation in the zone of special military operation (SVO). A new damaging factor is introduced into combat operations – uranium-238 (238U), one of the longest-lived natural radioactive isotopes of uranium. The purpose of the review is to identify the signs and consequences of the use of armor-piercing projectiles based on depleted uranium. Materials and research methods. The sources available through the PubMed, Google Scholar and Russian Electronic Library databases were analyzed. Research results. NATO uses DU in 20-, 25-, 30-, 105-, 120- and 140-mm caliber projectiles. The cores are made from recycled DU, which is a waste from the production of nuclear weapons. Due to man-made isotopes, it is more radioactive than DU from natural uranium. When such a projectile hits an armored object, a large amount of respirable radioactive and toxic dust of black uranium oxides, small fragments and fragments of the penetrator, remaining in the armored vehicles and around it, is formed. One 120 mm projectile produces approximately 950 g of black dust. Almost 99 % of the internal dose received by the military will come from alpha particles, the most dangerous to health. Projectiles that miss their targets sink deep into the soil, their penetrators corrode for decades, releasing soluble uranium compounds into underground water sources. In areas where DU shells were used, mass diseases of «unexplained etiology» are observed among military personnel and civilians, reducing their life expectancy and fertility. Discussion of results and conclusions. The first signs of the use of shells with DU, which can be installed on the battlefield: round holes in the armor of tanks and the presence of solid black dust around them and in the tank itself. In case of fires in the warehouses of such shells, due to other oxidation conditions, crumbling yellow dust is formed. When examining it, it is necessary to pay attention to the presence of elevated concentrations of 236U. The fact that a soldier was hit by DU can be confirmed by the presence of uranium in his urine. The use of DU shells on the territory of the Russian Federation, in terms of its consequences for people and nature, is the use of radiological weapons, a disguised form of nuclear warfare. And it must be treated accordingly.

Objectives: Previous studies have evaluated the association between mercury exposure and obesity but have yielded mixed conclusions. The aim of this study was to systematically review and summarize scientific evidence regarding the association between mercury exposure and obesity in the human population. Methods: We conducted a systematic search of PubMed, Web of Science, Scopus, and Science Direct for articles related to mercury exposure and obesity. Meta-analyses of the highest and lowest categories of mercury levels were evaluated using a random effects model. Begg’s test was used to detect publication bias. Results: A total of 9 articles were included. The pooled random effects odds ratio (OR) for mercury exposure and obesity of all 9 studies was 1.66 (95% confidence interval [CI]: 1.16-2.38). This positive association was evident in adults (OR: 1.61, 95% CI: 1.02-2.54) and among studies with Asian populations (OR: 2.00, 95% CI: 1.53-2.59), but not among those with North America/African populations (OR: 0.90, 95% CI: 0.50-1.65). Conclusions: The present meta-analysis identified a positive association between mercury exposure and obesity. These findings suggest that toxic environmental metals such as mercury may be an important risk factor for obesity along with dietary habits and lifestyles.

As an extensively employed plasticizer in industrial applications, di-2-ethylhexyl phthalate (DEHP) can induce apoptosis of mouse Leydig cells, yet the precise mechanism remains elusive. In the current study, we identified that DEHP could specially induced apoptosis in the Leydig cells of the testis tissue, accompanied with the upregulation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) in the cells. Overexpression of ARTS significantly induced apoptosis of TM3 cells, while knockdown of ARTS inhibited apoptosis. Furthermore, DEHP-induced apoptosis of TM3 cells could be alleviated by knockdown of ARTS, which indicated that ARTS was involved in DEHP-induced apoptosis of mouse Leydig cells. Bioinformation assay predicts that there are four potential p53-responsive elements (p53-REs) located at − 6060, − 5726, − 5631 and − 5554 before the transcription start site of ARTS gene, implying that gene transcription of ARTS could be regulated by p53. Interestingly, DEHP was shown to specifically upregulate the expression of p53 in the Leydig cells of the testis tissue and TM3 cells. Consistently, p53 was proved to bind to the RE4 site of the ARTS gene promoter and transcriptionally activated the promoter-driven expression of the luciferase reporter gene. Overexpression of p53 could induce apoptosis of TM3 cells; while knockdown of p53 could not only rescue DEHP-induced apoptosis of the cells, but also inhibit DEHP-caused upregulation of ARTS. Meanwhile, we showed that oxidative stress could induce apoptosis of TM3 cells, accompanied with the increased protein levels of p53 and ARTS; while inhibition of oxidative stress dramatically alleviated DEHP-induced apoptosis and the up-regulation of p53 and ARTS. Taken together, these results indicated that DEHP-induced oxidative stress activates the p53-ARTS cascade to promote apoptosis of mouse Leydig cells.

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value

Due to the wide use of atrazine (ATR), the concern has increased regarding the negative impact of ATR on reproduction. Nevertheless, the reproductive effects caused by different exposure concentrations and the severity of toxic damage are poorly understood. In organisms, ATR is metabolized and degraded through phase II enzyme systems, and changes in cytochrome P450 (CYP) enzymes may have a regulatory role in the harm of ATR. However, less information is available on the induction of CYPs by ATR in avian organisms, and even less on its effects on the testis. Birds are exposed to ATR mainly through food residues and contaminated water, the purpose of this study was to examine reproductive toxicity by different exposure concentrations and elaborate metabolic disorders caused by ATR in European quail (Coturnix coturnix). In this study, the quail were given ATR at 50 mg/kg, 250 mg/kg and 500 mg/kg by oral gavage for 45 days, and the testicular weight coefficients, histopathology and ultrastructure of testes, primary biochemical functions, sex steroid hormones, critical protein levels in the testosterone synthesis pathway, the expression of genes involved CYPs, gonad axis and nuclear receptors expression were investigated. Altogether, testicular coefficient decreased significantly in the high-dose group (1.22%) compared with the control group (3.03%) after 45 days of ATR exposure, and ATR is a potent CYP disruptor that acts through the NXRs and steroid receptor subfamily (APND, CAR, ERND and ERα) without a dose-dependent manner. Notably, ATR interfered with the homeostasis of hormones by triggering the expression of hormones on the gonad axis (LH and E2). These results suggest that exposure to ATR can cause testicular toxicity involving accommodative disorder of phase II enzyme and testosterone synthesis in European quail.

A melamine–formaldehyde polymer (MFP)-based nanocomposite decorated with silver phosphate (Ag3PO4) nanoparticles, named Ag3PO4–MFP, was fabricated. The as-synthesized Ag3PO4–MFP nanocomposite was used for the sunlight-promoted photocatalytic degradation of bisphenol A (BPA), a colorless endocrine disruptor. Kinetic studies were performed to examine the photocatalytic efficiency of the Ag3PO4–MFP nanocomposite under dark (control set), bulb light, and sunlight conditions, and the efficiency of photodegradation under sunlight was found to be higher. Ag3PO4–MFP shows faster photodegradation of BPA with 97% removal efficiency with short half-life value of ∼10.6 min, representing a significant influence of sunlight. To understand the plausible mechanism, radical-scavenging experiments were performed that suggest the involvement of holes (h+), which further generate hydroxyl radicals during the process of photodegradation and are responsible for the degradation of BPA. The photodegradation of BPA was confirmed by comparative proton nuclear magnetic resonance and total organic carbon analysis. For practical applicability, we extended our photodegradation experiment using Ag3PO4–MFP to externally spiked samples of BPA in different industrial wastewater samples and observed >70% BPA removal. Moreover, the concentration-dependent antibacterial activity of Ag3PO4–MFP was performed on two bacterial strains, Escherichia coli and Bacillus subtilis , where the nanocomposite shows effective antibacterial activity. [ABSTRACT FROM AUTHOR]

Since studies on the reproductive consequences after the exposure to environmentally relevant doses of Benzo(a)pyrene (BaP) during critical stages of development are scarce, this study evaluated female reproductive parameters of adult rats exposed to a low dose of BaP during the juvenile phase. Female rats (Post-natal 21) were treated with BaP (0 or 0.1 µg/kg/day; gavage) for 21 consecutive days. During the treatment, no clinical signs of toxicity were observed. Nevertheless, the ages of vaginal opening and first estrus were anticipated by the BaP-exposure. At the sexual maturity, the juvenile exposure compromised the sexual behavior, as well as the placental efficiency, follicle stimulating hormone levels, placenta histological analysis, and ovarian follicle count. A decrease in erythrocyte, platelet, and lymphocyte counts also was observed in the exposed-females. Moreover, the dose of BaP used in this study was not able to produce estrogenic activity in vivo. These data showed that juvenile BaP-exposure, at environmentally relevant dose, compromised the female reproductive system, possibly by an endocrine deregulation; however, this requires further investigation. [ABSTRACT FROM AUTHOR]

The introduction of contaminants of emerging concern (CECs) into the environment has raised concerns due to the significant risks they pose to both ecosystems and human health. In this sys-tematic review, we investigate research trends on CECs worldwide over the past 10 years, focus-ing on four critical aspects: (i) the identification and distribution of typical CECs across various media, (ii) the sources and environmental behavior of CECs, (iii) the implications of CECs expo-sure on human health, and (iv) risk assessment and control measures for CECs. The review re-veals a comprehensive understanding of the typical types and distribution of CECs in different environmental media, shedding light on their prevalence and potential impact on ecosystems. Furthermore, insights into the sources and behavior of CECs provide crucial information for de-vising effective strategies to mitigate their release into the environment. By examining the health effects of EC exposure, we highlight the importance of considering potential risks to human well-being. This aspect of the review emphasizes the significance of monitoring and managing CECs to safeguard public health. The review also synthesizes the advancements in risk assessment methodologies and control measures for CECs, which are essential for developing comprehensive regulations and guidelines to manage these contaminants effectively. Drawing from the findings, we identify future research directions for CECs in aquatic environments. [ABSTRACT FROM AUTHOR]

Recently, green analytical chemistry (GAC) is a key issue towards the idea of sustainability, the analytical community is focused on developing analytical methods that incorporate green chemistry principles to minimize adverse impacts on the environment and humans. Herein, we present 2 sustainable, selective, and validated chromatographic methods. Initially, lidocaine hydrochloride (LDC) and miconazole nitrate (MIC) with two preservatives; methyl paraben (MTP) and saccharin sodium (SAC) were chromatographed via TLC–densitometric method which employed ethyl acetate: methanol: formic acid (9:1:0.1, by volume) as the mobile phase with UV detection at 220.0 nm, good correlation was obtained in the range of 0.3–3.0 µg/band for MIC and LDC. Following that, RP-HPLC was successfully applied for separating quinary mixture of LDC, MIC, MTP, SAC along with LDC impurity; dimethyl aniline (DMA) using C18 column, and a gradient green mobile phase composed of methanol and phosphate buffer (pH 6.0) in different ratios with a flow rate 1.5 mL/min and UV detection at 210.0 nm, linearity ranges from 1.00 to 100.00 µg/mL for MIC, 2.00–100.00 µg/mL for LDC and 1.00–-20.00 µg/mL for MTP and DMA. No records to date regarding the determination of the two drugs, besides MTP and DMA. The proposed methods were validated according to the ICH guidelines and applied successfully to the analysis of the compounds. The methods' results were statistically compared to those obtained by applying the reported one, indicating no significant difference regarding both accuracy and precision. The methods' greenness profiles have been assessed and compared with those of the reported method using different assessment tools. [ABSTRACT FROM AUTHOR]

Sunscreen products are composed of ultraviolet (UV) filters and formulated to reduce exposure to sunlight thereby lessening skin damage. Concerns have been raised regarding the toxicity and potential endocrine disrupting (ED) effects of UV filters. The ToxCast/Tox21 program, that is, CompTox, is a high-throughput in vitro screening database of chemicals that identify adverse outcome pathways, key events, and ED potential of chemicals. Using the ToxCast/Tox21 database, octisalate, homosalate, octocrylene, oxybenzone, octinoxate, and avobenzone, 6 commonly used organic UV filters, were found to have been evaluated. These UV filters showed low potency in these bioassays with most activity detected above the range of the cytotoxic burst. The pathways that were most affected were the cell cycle and the nuclear receptor pathways. Most activity was observed in liver and kidney-based bioassays. These organic filters and their metabolites showed relatively weak ED activity when tested in bioassays measuring estrogen receptor (ER), androgen receptor (AR), thyroid receptor, and steroidogenesis activity. Except for oxybenzone, all activity in the endocrine assays occurred at concentrations greater than the cytotoxic burst. Moreover, except for oxybenzone, plasma concentrations (C max) measured in humans were at least 100× lower than bioactive (AC50/ACC) concentrations that produced a response in ToxCast/Tox21 assays. These data are consistent with in vivo animal/human studies showing weak or negligible endocrine activity. In sum, when considered as part of a weight-of-evidence assessment and compared with measured plasma concentrations, the results show these organic UV filters have low intrinsic biological activity and risk of toxicity including endocrine disruption in humans. [ABSTRACT FROM AUTHOR]

Problem: An intact cervix is a barrier that prevents pathogenic bacteria from invading the uterine and amniotic cavity during pregnancy. Its disruption is associated with ascending infection and adverse pregnancy outcomes. This study analyzed the effects of bisphenol A (BPA), a chemical used in plastics manufacturing, on cell death and inflammation in cervical epithelial cells. Methods: Ectocervical epithelial (ecto) and endocervical epithelial (endo) cells were treated with 100 ng/mL and 300 ng/mL of BPA for 48 h. The cells were subjected to flow cytometry using annexin V and propidium iodide to determine apoptosis and necrosis, cell cycle analysis, and ELISA to determine the levels of inflammatory cytokines (IL‐6, IL‐8, and IL‐10). Results: Low‐dose and high‐dose BPA significantly increased the live ecto cell population dose‐dependently. BPA did not have any noticeable effect on cell cycle progression in either cell type. BPA treatment also decreased the apoptotic ecto and endo cell population dose‐dependently. Lastly, high dose BPA significantly increased IL‐6 in ecto and endo cells. However, IL‐8 and IL‐10 were not affected by BPA treatments. Conclusion: Chemical exposure damage to the cervix can lead to adverse pregnancy outcomes. Our study showed that the BPA concentrations reported in pregnant subjects do not induce cervical cell toxicity. The decrease in apoptosis and increase in live cells may be a compensatory mechanism to preserve the integrity of the cervical epithelial layer. [ABSTRACT FROM AUTHOR]