QSAR: Using the Past to Study the Present.

Quantitative structure-activity relationships (QSAR) is a method for predicting the physical and biological properties of small molecules; it is in use in industry and public services. However, as any scientific method, it is challenged by more and more requests, especially considering its possible role in assessing the safety of new chemicals. To answer the question whether QSAR, by exploiting available knowledge, can build new knowledge, the chapter reviews QSAR methods in search of a QSAR epistemology. QSAR stands on tree pillars, i.e., biological data, chemical knowledge, and modeling algorithms. Usually the biological data, resulting from good experimental practice, are taken as a true picture of the world; chemical knowledge has scientific bases; so if a QSAR model is not working, blame modeling. The role of modeling in developing scientific theories, and in producing knowledge, is so analyzed. QSAR is a mature technology and is part of a large body of in silico methods and other computational methods. The active debate about the acceptability of the QSAR models, about the way to communicate them, and the explanation to provide accompanies the development of today QSAR models. An example about predicting possible endocrine-disrupting chemicals (EDC) shows the many faces of modern QSAR methods.

Leveraging new approach methodologies: ecotoxicological modelling of endocrine disrupting chemicals to Danio rerio through machine learning and toxicity studies.

New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown endocrine-disrupting chemicals (EDCs) against zebrafish. EDCs are a diverse group of toxic substances that disrupt the endocrine system of humans and animals. The q-RASAR model was constructed and verified using validation metrics (R2 = 0.886 and Q2 = 0.814) which found to be more reliable model compare to QSAR model. The substructure fingerprint was well-fitted for the classification model and it was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew's correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity based on q-RASAR model. The docking and simulation study indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L-1 was very close to the predicted value of 0.763 mg L-1, which provides high confidence to the developed model.

Ultrasonic decomposition of endocrine disrupting Compounds - A review.

Endocrine disrupting compounds (EDCs) need to be removed by efficient treatment methods as they are a major concern for both human and environmental health. To reduce the impact of EDCs in water, this review examines the use of ultrasonic degradation processes. Following an overview of EDCs and their origins, the basic concepts of sonochemistry are examined, highlighting the potential of ultrasound in chemical reactions. An in-depth analysis of the variables that affect the ultrasonic degradation of EDCs, such as frequency, intensity/power, temperature and solution chemistry, prepares the reader for a case study investigation focusing on specific EDCs. The study also looks at synergistic methods, emphasizing how hybrid ultrasonic systems can improve removal efficiency. The study provides a comprehensive overview of the use of sonochemistry in the treatment of EDCs by addressing current issues and suggesting future research directions. The aim of this review paper is to provide insightful analysis and useful suggestions for scientists working on EDC remediation projects.

Historical sedimentary and evolutionary characteristics of POPs and EDCs in typical regions of the three Gorges reservoir, China.

The historical sedimentary and evolutionary characteristics of persistent organic pollutants and endocrine disruptors in typical regions of the Three Gorges Reservoir are scarcely studied. Herein, the 96-year data on contaminated sediment history were reconstructed using Caesium 137 isotope dating. Polychlorinated biphenyl concentrations in the involved sediment cores ranged from non-detected (ND) to 11.39 ng/g. The concentrations of polycyclic aromatic hydrocarbons ranged from ND to 2075.20 ng/g and peaked in the 1970s owing to natural, agricultural and human activities. Further, phthalate esters (PAEs) and heavy metals (HMs) were detected at concentrations ranging from ND to 589.2 ng/g and 12.10-93.67 µg/g, respectively, with highest values recorded in the 1980s owing to rapid industrialisation and insufficient management during China's early reform and development stages. PAE and HM concentrations have increased in recent years, suggesting the need to focus on industrial and agricultural activities that have caused this impact. Although current pollutant concentrations in sediments do not pose a risk to the aquatic ecosystem, they should be continuously monitored.

Occurrence and risks of pharmaceuticals, personal care products, and endocrine-disrupting compounds in Chinese surface waters.

The continuous and rapid increase of chemical pollution in surface waters has become a pressing and widely recognized global concern. As emerging contaminants (ECs) in surface waters, pharmaceutical and personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have attracted considerable attention due to their wide occurrence and potential threat to human health. Therefore, a comprehensive understanding of the occurrence and risks of ECs in Chinese surface waters is urgently required. This study summarizes and assesses the environmental occurrence concentrations and ecological risks of 42 pharmaceuticals, 15 personal care products (PCPs), and 20 EDCs frequently detected in Chinese surface waters. The ECs were primarily detected in China's densely populated and highly industrialized regions. Most detected PPCPs and EDCs had concentrations between ng/L to µg/L, whereas norfloxacin, caffeine, and erythromycin had relatively high contamination levels, even exceeding 2000 ng/L. Risk evaluation based on the risk quotient method revealed that 34 PPCPs and EDCs in Chinese surface waters did not pose a significant risk, whereas 4-nonylphenol, 4-tert-octylphenol, 17α-ethinyl estradiol, 17ß-estradiol, and triclocarban did. This review provides a comprehensive summary of the occurrence and associated hazards of typical PPCPs and EDCs in Chinese surface waters over the past decade, and will aid in the regulation and control of these ECs in Chinese surface waters.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

The association between endocrine disrupting chemicals and nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg's test, and Egger's test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of "elevated alanine aminotransferase". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

Maternal pre-pregnancy BMI influences the associations between bisphenol and phthalate exposures and maternal weight changes and fat accumulation.

BACKGROUND: Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes. METHODS: This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects. RESULTS: Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain. CONCLUSION: In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed.

Endocrine disruption and male reproductive disorders: unanswered questions.

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women.

BACKGROUND: Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). OBJECTIVE: We estimated associations between hair product use and EDC biomarker concentrations. METHODS: We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23-34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. RESULTS: Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. CONCLUSION: Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women.

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Microplastics and Endocrine Disruptors in Typical Wastewater Treatment Plants in Megacity Shanghai.

The fast development of China's urbanization has led to a notable release of emerging pollutants, including microplastics (MPs) and endocrine disruptors (EDCs). Generally, these pollutants enter the coastal environment through the discharge of wastewater treatment plants (WWTPs) and finally threaten the organisms in the receiving waterbody. The study investigated the environmental behavior of MPs and EDCs in two typical WWTPs in one of the megacities in China, Shanghai. The abundance of MPs in the influent ranged from 321 to 976 items/L. Four shapes (films, fragments, fibers, and microbead) were found, while fibers and films dominated. Transparent (31-63%) and white (20-47%) MPs were more frequently observed, while polyethylene terephthalate, cellulose, and cellophane were the main polymetric materials. The size of the MPs fell between 15.8 µm and 2220 µm, and the smaller one (<500 µm) dominated. The removal efficiencies of the two WWTPs for MPs ranged from 64% to 92%, and both WWTPs performed better for large pieces of MPs (>500 µm). For EDCs, total concentrations in the influent were detected, ranging from 113 to 2780 ng/L. Two groups, including phenolic estrogens (PEs) and steroid estrogens (SEs), were detected, and PEs, especially bisphenol A (BPA), were the predominant individuals among the studied EDCs. Specifically, PEs ranged from 82.8 to 2637 ng/L, while SEs ranged from 27.3 to 143 ng/L. The removal efficiencies of the WWTPs for EDCs varied (82.8-100%) as well, possibly due to the different treatment compartments and contamination load in the influent. Seasonal variations for both MPs and EDCs were observed. Specifically, concentrations of MPs and EDCs in WWTPs influent were higher in the wet season, as well as the removal efficiency. Furthermore, there was a correlation observed between the concentrations of MPs and EDCs, suggesting that MPs and EDCs may originate from the same source and that EDCs released by MPs cannot be ignored during treatment. Finally, the study evaluated the environmental risk of the effluents. MPs led to a minor risk (Level I), while EDCs might lead to an adverse impact on algae (RQs = 0.0014-0.024) and fish (RQs = 3.4-30.2). In summary, WWTPs received considerable amounts of MPs and EDCs. Although the WWTPs removed the contaminants efficiently, the environmental risk of the effluent needs to be noted.

Endocrine disrupting chemicals in children's and their parents' urine: Is the exposure related to the Chinese and Western lifestyle?

Children are known to be more vulnerable to exposure to endocrine-disrupting chemicals (EDCs) compared to adults, but evaluating the exposure pathways can be challenging. This research employed target and non-target analysis (NTA) to examine the exposure characteristics of EDCs in spot urine samples collected from 46 children's (aged 3-12 years) and their parents in Hong Kong (Chinese/Western lifestyle) and Guangzhou (mainly Chinese lifestyle). The results revealed that the geometric mean concentrations of phthalate esters metabolites (mPAEs) and bisphenols (BPs) in children's urine were 127.3 µg/gcrea and 2.5 µg/gcrea in Guangzhou, and 93.7 µg/gcrea and 2.9 µg/gcrea in Hong Kong, respectively, which were consistent with global levels. NTA identified a total of 1069 compounds, including 106 EDCs, commonly detected in food, cosmetics, and drugs. Notable regional differences were observed between Guangzhou and Hong Kong with potential sources of EDCs including dietary and cosmetic additives, toys, flooring and dust, as well as differences in lifestyles, diet, and living environment. However, age was found to significantly impact EDC exposure. The quantified EDCs (mPAEs and BPs) posed possible health risks to 60% of the children. Moreover, the presence of caffeine in children's urine, which exhibited higher detection rates in children from Hong Kong (95.6%) and Guangzhou (44.4%), warrants further attention. The sources of EDCs exposure in these regions need to be fully confirmed.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes. OBJECTIVE: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. METHODS: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. RESULTS: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (ß = 0.03; 95 % CrI = 0.20, 0.25), 50th (ß = 0.02; 95 % CrI = -0.16, 0.19), and 90th (ß = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture. CONCLUSION: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women.

OBJECTIVE: To evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. RESULTS: Overall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). CONCLUSION: Increased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.

The Interplay between Endocrine-Disrupting Chemicals and the Epigenome towards Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), described as the most prominent cause of chronic liver disease worldwide, has emerged as a significant public health issue, posing a considerable challenge for most countries. Endocrine-disrupting chemicals (EDCs), commonly found in daily use items and foods, are able to interfere with nuclear receptors (NRs) and disturb hormonal signaling and mitochondrial function, leading, among other metabolic disorders, to MASLD. EDCs have also been proposed to cause transgenerationally inherited alterations leading to increased disease susceptibility. In this review, we are focusing on the most prominent linking pathways between EDCs and MASLD, their role in the induction of epigenetic transgenerational inheritance of the disease as well as up-to-date practices aimed at reducing their impact.

Endocrine disrupting chemicals: gestational diabetes and beyond.

Gestational Diabetes Mellitus (GDM) has been on the rise for the last two decades along with the growing incidence of obesity. The ubiquitous use of Endocrine-Disrupting Chemicals (EDCs) worldwide has been associated with this increase in GDM incidence. Epigenetic modifications such as DNA methylation, histone acetylation, and methylation have been associated with prenatal exposure to EDCs. EDC exposure can also drive a sustained disruption of the hypothalamus-pituitary-thyroid axis and various other signaling pathways such as thyroid signaling, PPARγ signaling, PI3K-AKT signaling. This disruption leads to impaired glucose metabolism, insulin resistance as well as ß-cell dysfunction, which culminate into GDM. Persistent EDC exposure in pregnant women also increases adipogenesis, which results in gestational weight gain. Importantly, pregnant mothers transfer these EDCs to the fetus via the placenta, thus leading to other pregnancy-associated complications such as intrauterine growth restriction (IUGR), and large for gestational age neonates. Furthermore, this early EDC exposure of the fetus increases the susceptibility of the infant to metabolic diseases in early life. The transgenerational impact of EDCs is also associated with higher vascular tone, cognitive aberrations, and enhanced susceptibility to lifestyle disorders including reproductive health anomalies. The review focuses on the impact of environmental toxins in inducing epigenetic alterations and increasing the susceptibility to metabolic diseases during pregnancy needs to be extensively studied such that interventions can be developed to break this vicious cycle. Furthermore, the use of EDC-associated ExomiRs from the serum of patients can help in the early diagnosis of GDM, thereby leading to triaging of patients based on increasing risk factor of the clinicopathological condition.

Enhanced Detection of Estrogen-like Compounds by Genetically Engineered Yeast Sensor Strains.

The release of endocrine-disrupting compounds (EDCs) to the environment poses a health hazard to both humans and wildlife. EDCs can activate or inhibit endogenous endocrine functions by binding hormone receptors, leading to potentially adverse effects. Conventional analytical methods can detect EDCs at a high sensitivity and precision, but are blind to the biological activity of the detected compounds. To overcome this limitation, yeast-based bioassays have previously been developed as a pre-screening method, providing an effect-based overview of hormonal-disruptive activity within the sample prior to the application of analytical methods. These yeast biosensors express human endocrine-specific receptors, co-transfected with the relevant response element fused to the specific fluorescent protein reporter gene. We describe several molecular manipulations of the sensor/reporter circuit in a Saccharomyces cerevisiae bioreporter strain that have yielded an enhanced detection of estrogenic-like compounds. Improved responses were displayed both in liquid culture (96-well plate format) as well as in conjunction with sample separation using high-performance thin-layer chromatography (HPTLC). The latter approach allows for an assessment of the biological effect of individual sample components without the need for their chemical identification at the screening stage.

Influence of microplastic contamination on the dissipation of endocrine disrupting chemicals in soil environment.

Microplastic (MP) contamination is in the spotlight today, yet knowledge of their interaction with other organic contaminants in the soil environment is limited. Concerns extend to endocrine disrupting chemicals (EDCs), known for their potential to interfere with the hormonal systems of organisms and for their persistence and widespread presence in the environment. In this study, the most frequently occurring EDCs were monitored both in alluvial soil and in soil contaminated with different MPs commonly found in soil media, polyethylene, polyamide, and polystyrene. Bisphenol A and parabens were the most rapidly dissipating compounds, followed by triclosan and triclocarban, with the latter showing poor degradation. Per- and polyfluoroalkyl substances (PFAS) showed high persistence as concentrations remained nearly constant throughout the experiment. Although they fitted well with first-order dissipation kinetics, most showed biphasic behavior. The co-occurrence of MPs in the soil influenced the kinetic behavior in most cases although the differences were not very marked. MPs could impact sorption-desorption processes, affecting contaminant mobility and bioavailability to organisms in soil. These findings strengthen evidence for the influence of MPs on the behavior of soil contaminants such as EDCs, not only as vectors or sources of contaminants but by affecting dissipation kinetics.