Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome.

SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.

Plastic compounds and liver diseases: Whether bisphenol A is the only culprit.

Plastics, while providing modern conveniences, have become an inescapable source of global concern due to their role in environmental pollution. Particularly, the focus on bisphenol A (BPA) reveals its biohazardous nature and association with liver issues, specifically steatosis. However, research indicates that BPA is just one facet of the problem, as other bisphenol analogues, microplastics, nanoplastics and additional plastic derivatives also pose potential risks. Notably, BPA is implicated in every stage of non-alcoholic fatty liver disease (NAFLD) onset and progression, surpassing hepatitis B virus as a primary cause of chronic liver disease worldwide. As plastic contamination tops the environmental contaminants list, urgent action is needed to assess causative factors and mitigate their impact. This review delves into the molecular disruptions linking plastic pollutant exposure to liver diseases, emphasizing the broader connection between plastics and the rising prevalence of NAFLD.

Sex-Specific and Trimester-Specific Associations of Prenatal Exposure to Bisphenols, Parabens, and Triclosan with Neonatal Birth Size and Gestational Age.

Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (ß = -39.9, 95% CI: -73.8, -6.1), birth length (ß = -0.19, 95% CI: -0.34, -0.04), head circumference (ß = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (ß = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (ß = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.

New Mechanism for the Apoptosis of Human Neuroblastoma Cells by the Interaction between Fluorene-9-Bisphenol and the G Protein-Coupled Estrogen Receptor 1.

Fluorene-9-bisphenol (BHPF) is an emerging contaminant. Presently, there is no report on its interaction with G protein-coupled estrogen receptor 1 (GPER). By using an integrated toxicity research scenario that combined theoretical study with experimental methods, BHPF was found to inhibit the GPER-mediated effect via direct receptor binding. Molecular dynamics simulations found that Trp2726.48 and Glu2756.51 be the key amino acids of BHPF binding with GPER. Moreover, the calculation indicated that BHPF was a suspected GPER inhibitor, which neither can activate GPER nor is able to form water channels of GPER. The role of two residues was successfully verified by following gene knockout and site-directed mutagenesis assays. Further in vitro assays showed that BHPF could attenuate the increase in intracellular concentration of free Ca2+ induced by G1-activated GPER. Besides, BHPF showed an enhanced cytotoxicity compared with G15, indicating that BHPF might be a more potent GPER inhibitor than G15. In addition, a statistically significant effect on the mRNA level of GPER was observed for BHPF. In brief, the present study proposes that BHPF be a GPER inhibitor, and its GPER molecular recognition mechanism has been revealed, which is of great significance for the health risk and assessment of BHPF.

New analytical method for the determination of endocrine disruptors in human faeces using gas chromatography coupled to tandem mass spectrometry.

Endocrine-disrupting chemicals are environmental pollutants that can enter our bodies and cause diverse pathologies. Some bisphenols and parabens have been shown to be capable of modifying proper functioning of the endocrine system. Among other dysfunctions, endocrine-disrupting chemicals can cause changes in intestinal microbiota. Faeces are a convenient matrix that can be useful for identifying the quantity of endocrine disruptors that reach the intestine and the extent to which the organism is exposed to these pollutants. The present work developed a new analytical method to determine 17 compounds belonging to the paraben and bisphenol families found in human faeces. The extraction method was optimized using an ultrasound-assisted extraction technique followed by a clean-up step based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) technique. Optimization was performed using the design of experiments technique. In validation analysis, the method was proven to be linear over a wide range. R-squared outcomes were between 95 and 99%. Selectiveness and sensitivity outcomes were acceptable, with detection limits being between 1 and 10 ng g-1 in all cases, whilst quantification limits were between 3 and 25 ng g-1 in all instances, with the exception of bisphenol AF. The method was deemed accurate, with recovery values being close to 100% and relative standard deviations being lower than 15% in all cases. Applicability was examined by analysing 13 samples collected from volunteers (male and female). All samples were contaminated with at least one of the analytes studied. The most commonly found compounds were methylparaben and bisphenol A, which were detected in almost all samples and quantitatively determined in 11 and 12 samples, respectively. Of the 17 compounds analysed, 11 were found in at least one sample. Outcomes demonstrate that faeces can be a good matrix for the determination of exposure to contaminants of interest here.

Biochemical responses and antioxidant defense mechanisms in Channa Striatus exposed to Bisphenol S.

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.

Exposure to endocrine-disrupting plasticisers and lung function in children and adolescents: A systematic review and meta-analysis.

Exposure to endocrine-disrupting plasticisers (EDPs), such as phthalates and bisphenols, has been associated with reduced lung function in children and adolescents. However, the existing literature yields conflicting results. This systematic review and meta-analysis aimed to assess the epidemiologic evidence investigating the association between EDP exposure and lung function in children and adolescents. A comprehensive search of five databases identified 25 relevant studies. We employed a random-effects meta-analysis on spirometry measures. The effect size of interest was the change in lung function in standard deviation (SD) units resulting from a two-fold increase in exposure levels. We found that certain phthalates marginally reduced lung function in children. Forced expiratory volume in 1 s (FEV1) was reduced by a two-fold increase in mono-benzyl phthalate (MBzP) (ß = -0.025 SD, 95%CI: 0.042, -0.008), mono-ethyl-oxo-hexyl phthalate (MEOHP) (ß = -0.035 SD, 95%CI: 0.057, -0.014) and mono-carboxy-nonyl phthalate (MCNP) (ß = -0.024 SD, 95%CI: 0.05, -0.003). Forced vital capacity (FVC) was decreased by a two-fold increase in MBzP (ß = -0.022 SD, 95%CI: 0.036, -0.008) and MEOHP (ß = -0.035 SD, 95%CI: 0.057, -0.014) levels. A two-fold increase in MCNP levels was associated with lower FEV1/FVC (ß = -0.023 SD, 95%CI: 0.045, -0.001). Furthermore, a two-fold increase in MEOHP levels reduced forced mid-expiratory flow (FEF25-75) (ß = -0.030 SD, 95%CI: 0.055, -0.005) and peak expiratory flow (PEF) (ß = -0.056 SD, 95%CI: 0.098, -0.014). Notably, associations were more pronounced in males. Given the potential for reverse causation bias, the association between childhood exposure to EDPs and lung function remains uncertain. Overall, our meta-analysis showed small reductions in lung function with higher phthalate exposure. However, future studies are warranted in younger age groups.

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.

In situ growth of imine-based covalent organic framework as stationary phase for open-tubular capillary electrochromatographic separation.

Designing advanced stationary phases to improve separation efficiency is essential in capillary electrochromatography. Due to their outstanding performance, covalent organic frameworks have recently demonstrated considerable promise in the field of separation science. Herein, an open-tubular capillary electrochromatography method was reported using porous imine-based covalent organic framework with sufficiently available interaction sites as stationary phase. The imine-based covalent organic framework coated capillary was easily prepared via an in situ growth method at room temperature, and its separation performance was evaluated, indicating the high separation efficiency for three types of analytes, including herbicides, polybrominated dibenzofurans, and bisphenols. Moreover, the imine-based covalent organic framework coated capillary showed good reproducibility and stability, with intraday (n = 3), interday (n = 3), and column-to-column (n = 3) relative standard deviations of retention time and peak areas of less than 5%. The separation efficiency of the coated capillary remained unchanged even after 200 runs and the maximum theoretical plates reached up to 85 595 N/m for 4,4'-ethylidenebisphenol. It was predicted that the imine-based covalent organic framework stationary phase would be a strong contender for chromatographic separation with high efficiency.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Halogenated bisphenol A derivatives potently inhibit human and rat 11ß-hydroxysteroid dehydrogenase 1: Structure-activity relationship and molecular docking.

Chlorinated bisphenol A (BPA) derivatives are formed during chlorination process of drinking water, whereas bisphenol S (BPS) and brominated BPA and BPS (TBBPA and TBBPS) were synthesized for many industrial uses such as fire retardants. However, the effect of halogenated BPA and BPS derivatives on glucocorticoid metabolizing enzyme 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) remains unclear. The inhibitory effects of 6 BPA derivatives in the inhibition of human and rat 11ß-HSD1 were investigated. The potencies for inhibition on human 11ß-HSD1 were TBBPA (IC50, 3.87 µM) = monochloro BPA (MCBPA, 4.08 µM) = trichloro BPA (TrCBPA, 4.41 µM) > tetrachloro BPA (TCBPA, 9.75 µM) > TBBPS (>100 µM) = BPS (>100 µM), and those for rat 11ß-HSD1 were TrCBPA (IC50, 2.76 µM) = MCBPA (3.75 µM) > TBBPA (39.58 µM) > TCBPA = TBBPS = BPS. All these BPA derivatives are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that MCBPA, TrCBPA, TCBPA, and TBBPA all bind to the active site of human 11ß-HSD1, forming hydrogen bonds with catalytic residue Ser170 except TCBPA. Regression of the lowest binding energy with IC50 values revealed a significant inverse linear regression. In conclusion, halogenated BPA derivatives are mostly potent inhibitors of human and rat 11ß-HSD1, and there is structure-dependent inhibition.

[Determination of six bisphenols in human urine by ultra-high performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To develop and validate a solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of six bisphenols(bisphenol S, bisphenol F, bisphenol A, 2, 2'-methylenediphenol, bisphenol AF, bisphenol AP) in urine. METHODS: After enzymolysis of urine sample, the target substances were quickly purified and extracted by WAX solid phase extraction column. On ACQUITY BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), the mobile phase of water and methanol was used to separate. Finally, multi-reaction detection was carried out under electrospray negative ion scanning, and quantification was carried out by internal standard method. RESULTS: The correlation coefficients(r) of the target compounds were all more than 0.998 in the range of 0.1-50.0 ng/mL, the linearity was good, and the detection limits were all lower than 0.1 ng/mL. The recoveries of the three standard concentrations(0.5, 5.0 and 50.0 ng/mL) were all between 80% and 120%, and the relative standard deviation was less than 20%(n=5). The standard reference material was detected and the concentration was within the reference range. CONCLUSION: This method can be used to detect six bisphenols in urine quickly and accurately, is suitable for the trace analysis of bisphenol compounds in human urine.

Reproductive toxicity of emerging plasticizers, flame retardants, and bisphenols, using culture of the rat fetal testis†.

The use of bis (2-ethylhexyl) phthalate (DEHP), 2,2'4,4'-tetrabromodiphenyl ether (BDE47), and bisphenol A (BPA), as plasticizers, flame retardants, and epoxy resins, respectively, has been regulated due to their endocrine disrupting activities. Replacements for these chemicals are found in human matrices, yet the endocrine disrupting potential of these emerging contaminants is poorly characterized. We compared the effects of legacy chemicals with those of their replacements using fetal rat testis organ culture. Fetal testes sampled at gestation day 15 were grown ex vivo, and the impact was evaluated after a 3-day exposure to 10 µM of each legacy chemical; two BPA analogs (bisphenol M and bisphenol TMC); three replacements for DEHP/MEHP (2,2,4-trimethyl-1,3-pentanediol diisobutyrate, diisononyl-phthalate, and diisodecyl adipate); or two replacements for BDE47 (tributoxyethyl phosphate and isopropylated triphenyl phosphate). We showed that only BPA and MEHP significantly decrease testosterone secretions after 24 h, while BPM and BPTMC have the opposite effect. Luteinizing hormone-stimulated testosterone was reduced by BPA and MEHP but was increased by BPTMC. After exposure, testes were used for immunofluorescent staining of germ cells, Sertoli cells, and Leydig cells. Interestingly, exposures to BPM or BPTMC induced a significant increase in the Leydig cell density and surface area. A decrease in germ cell density was observed only after treatment with MEHP or BDE47. MEHP also significantly decreased Sertoli cell proliferation. These studies show that some replacement chemicals can affect testicular function, while others appear to show little toxicity in this model. These findings provide essential information regarding the need for their regulation.

Chemical contaminants in canned food and can-packaged food: a review.

Canning, as a preservation technique, is widely used to extend the shelf life as well as to maintain the quality of perishable foods. During the canning process, most of the microorganisms are killed, reducing their impact on food quality and safety. However, the presence of a range of undesirable chemical contaminants has been reported in canned foods and in relation to the canning process. The present review provides an overview of these chemical contaminants, including metals, polymeric contaminants and biogenic amine contaminants. They have various origins, including migration from the can materials, formation during the canning process, or contamination during steps required prior to canning (e.g. the disinfection step). Some other can-packaged foods (e.g. beverages or milk powder), which are not canned foods by definition, were also discussed in this review, as they have been frequently studied simultaneously with canned foods in terms of contamination. The occurrence of these contaminants, the analytical techniques involved, and the factors influencing the presence of these contaminants in canned food and can-packaged food are summarized and discussed.

Role of Gastrointestinal Microbiota from Crucian Carp in Microbial Transformation and Estrogenicity Modification of Novel Plastic Additives.

Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.

Impact of Extended and Combined Exposure of Bisphenol Compounds on Their Chromosome-Damaging Effect─Increased Potency and Shifted Mode of Action.

Bisphenol (BP) compounds are important environmental pollutants and endocrine disruptors. BPs are capable of inducing DNA/chromosome breaks (clastogenesis, involved in carcinogenesis), which requires activation by human CYP1A1. We hypothesized that combined BPs and extended (from the standard two-cell cycle) exposure may enhance their genotoxicity via modulating CYP enzymes. In this study, individual and combined BPA/BPF/BPS/BPAF and a human hepatoma (HepG2) cell line were used for testing several genotoxicity end points. Exposing for a two-cell cycle period (48 h), each BP alone (0.625-10 µM) was negative in the micronucleus test, while micronucleus was formed under three- (72 h) and four-cell cycle (96 h) exposure; BP combinations further elevated the potency (with nanomolar thresholds). Immunofluorescence analysis of the centromere with formed micronucleus indicated that 48 h exposure produced centromere-negative micronucleus and phosphorylated histone H2AX (γ-H2AX) (evidencing clastogenesis), while extended (72 and 96 h) exposure formed centromere-positive micronucleus and phosphorylated histone H3 (p-H3) (indicating chromosome loss, i.e., aneugenesis); moreover, 1-aminotriabenzotriazole (CYP inhibitor) selectively blocked the formation of centromere-negative micronucleus and γ-H2AX, without affecting that of centromere-positive micronucleus and p-H3. This study suggests that the genotoxicity of BPs is potentiated by combined and extended exposure, the latter being specific for aneuploidy formation, a CYP activity-independent effect.

Endocrine-disrupting compounds and metabolomic reprogramming in breast cancer.

Endocrine-disrupting chemicals pose a growing threat to human health through their increasing presence in the environment and their potential interactions with the mammalian endocrine systems. Due to their structural similarity to hormones like estrogen, these chemicals can interfere with endocrine signaling, leading to many deleterious effects. Exposure to estrogenic endocrine-disrupting compounds (EDC) is a suggested risk factor for the development of breast cancer, one of the most frequently diagnosed cancers in women. However, the mechanisms through which EDCs contribute to breast cancer development remain elusive. To rapidly proliferate, cancer cells undertake distinct metabolic programs to utilize existing nutrients in the tumor microenvironment and synthesize macromolecules de novo. EDCs are known to dysregulate cell signaling pathways related to cellular metabolism, which may be an important mechanism through which they exert their cancer-promoting effects. These altered pathways can be studied via metabolomic analysis, a new advancement in -omics technologies that can interrogate molecular pathways that favor cancer development and progression. This review will summarize recent discoveries regarding EDCs and the metabolic reprogramming that they may induce to facilitate the development of breast cancer.

Prenatal bisphenol A and S exposure and atopic disease phenotypes at age 6.

BACKGROUND: Atopic disease may be influenced by prenatal and early life exposure to endocrine disrupting chemicals, including bisphenols, but results from epidemiological studies have been mixed. This study aimed to extend the epidemiological literature, hypothesizing that children with higher prenatal bisphenol exposure are more likely to have childhood atopic disease. METHODS: Urinary bisphenol A (BPA) and S (BPS) concentrations were measured in each trimester from 501 pregnant women in a multi-center, prospective pregnancy cohort. Ever asthma, current asthma, wheeze, and food allergy) were assessed at age six via standardized ISAAC questionnaire. We constructed generalized estimating equations to examine BPA and BPS exposure jointly at each trimester for each atopy phenotype. BPA was modeled as a log-transformed continuous variable, whereas BPS was modeled as detected versus not detected. We also modeled pregnancy-averaged BPA values and a categorical indicator for number of detectable BPS values over pregnancy (0-3) in logistic regression models. RESULTS: First trimester BPA was associated with inverse odds of food allergy among the entire study sample (OR = 0.78, 95% CI = 0.64-0.95, p = 0.01) and females only (OR = 0.69, 95% CI = 0.52-0.90, p = 0.006). The inverse relationship persisted in pregnancy-averaged models of BPA among females (OR = 0.56, 95% CI = 0.35-0.90, p = 0.006). Second trimester BPA was associated with greater odds of food allergy in the entire sample (OR = 1.27, 95% CI = 1.02-1.58, p = 0.03) and among males only (OR = 1.48, 95% CI = 1.02-2.14, p = 0.04). Odds of current asthma increased among males in the pregnancy-averaged BPS models (OR = 1.65, 95% CI = 1.01-2.69, p = 0.045). CONCLUSION: We saw opposite effects of BPA on food allergy that were trimester- and sex-specific. These divergent associations warrant further investigation. There is some evidence to suggest that prenatal BPS is associated with asthma among males, but further research is required in cohorts with a greater proportion of prenatal urine samples with detectable BPS to validate these results.

Bisphenols and perfluoroalkyls alter human stem cells integrity: A possible link with infertility.

Bisphenols and Perfluoroalkyls are chemical compounds widely used in industry known to be endocrine disruptors (EDs). Once ingested through contaminated aliments, they mimic the activity of endogenous hormones leading to a broad spectrum of diseases. Due to the extensive use of plastic in human life, particular attention should be paid to antenatal exposure to Bisphenols and Perfluoroalkyls since they cross the placental barrier and accumulates in developing embryo. Here we investigated the effects of Bisphenol-A (BPA), Bisphenol-S (BPS), perfluorooctane-sulfonate (PFOS) and perfluorooctanoic-acid (PFOA), alone or combined, on human-induced pluripotent stem cells (hiPSCs) that share several biological features with the stem cells of blastocysts. Our data show that these EDs affect hiPSC inducing a great mitotoxicity and dramatic changes in genes involved in the maintenance of pluripotency, germline specification, and epigenetic regulation. We also evidenced that these chemicals, when combined, may have additive, synergistic but also negative effects. All these data suggest that antenatal exposure to these EDs may affect the integrity of stem cells in the developing embryos, interfering with critical stages of early human development that might be determinant for fertility. The observation that the effects of exposure to a combination of these chemicals are not easily foreseeable further highlights the need for wider awareness of the complexity of the EDs effects on human health and of the social and economic burden attributable to these compounds.

Fulvic acid enhanced peroxymonosulfate activation over Co-Fe binary metals for efficient degradation of emerging bisphenols.

Bisphenol F (BPF) and bisphenol S (BPS) are emerging bisphenols, which have become the main substitutes for bisphenol A (BPA) in industrial production and are also considered as new environmental pollution challenges. Thus, the necessity for an effective approach to remove BPF and BPS is essential. In this study, fulvic acid (FA) was used to modify Co-Fe binary metals (CFO) for peroxymonosulfate (PMS) activation. The characterization results demonstrated that CFO changed significantly in morphology after compounding with FA, with smaller particle size and 5.6 times larger specific surface area, greatly increasing the active sites of catalyst; Moreover, humic acid-like compounds increased the surface functional groups of CFO, especially phenolic hydroxyl, which could effectively prolong the PMS activation. The concentration of all reactive species, such as SO4•-, •OH, O2•-, and 1O2 increased in FA@CFO/PMS system. As a result, the degradation efficiency of CFO for both BPF and BPS was significantly improved after compounding FA, which also had a wide range of pH applications. The degradation pathways of both BPF and BPS were proposed based on liquid chromatography-mass spectrometry (LC-MS) analysis and the density functional theory (DFT) calculations. Our findings are expected to provide new strategies and methods for remediation of environmental pollution caused by emerging bisphenols.