Exposure to bisphenols, parabens, and benzophenones in colostrum breast milk of Panamanian women: A pilot study from the PA-MAMI cohort.

BACKGROUND: Breast milk is the optimal source of nutrition for infants but can also expose them to endocrine-disrupting chemicals (EDCs), among other environmental contaminants. AIM: To determine concentrations of non-persistent phenolic EDCs (three bisphenols, four parabens [PBs], and six benzophenones [BPs]), in colostrum samples from Panamanian mothers and to examine associated reproductive, sociodemographic, and life-style factors. METHODS: Dispersive liquid-liquid microextraction was used to measure concentrations of bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP), and benzophenones BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP in colostrum milk samples from 36 mothers. An ad hoc questionnaire was used to collect data on potential influentially variables, and multiple linear and logistic regression analyses were conducted. RESULTS: Two or more tested EDCs were detected in 36 colostrum samples (100 %), at least four in 14 samples (38.9 %), and at least six in 4 samples (11.1 %). The most frequently detected compounds were BPA (91.7 %), BP-8 (63.9 %), MeP (47.2 %), and BPF (41.7 %). The median concentration was 3.45 ng/mL for BP-8 and 1.37 ng/mL for BPA. No concentrations of n-PrP, BP-1, BP-6, or 4-hydroxy-BP were detected. Associations were observed between phenolic EDC concentrations and maternal place of residence, consumption frequency of poultry, fish, fresh cheese, fruit, yogurt and chocolate, intake of nutritional supplements, and application of some personal care products. CONCLUSIONS: Bisphenols, parabens, and benzophenones were widely present in colostrum milk samples from Panamanian women. Preventive measures are needed to maximize the benefits of breastfeeding.

Exploring the association between urinary bisphenol A, S, and F levels and semen quality parameters: Findings from Led-Fertyl cross-sectional study.

Infertility is recognized as a multifaceted condition affecting approximately 15% of couples globally, influenced by various factors including genetic predisposition and environmental exposures. Among these environmental factors, bisphenol A (BPA) emerges as a prominent Endocrine-disrupting chemical (EDCs) widely distributed, leading to chronic human exposure in daily life. As regulations on BPA became more stringent, alternative substances such as bisphenol S (BPS) and bisphenol F (BPF) have emerged. Animal studies have demonstrated a dose-dependent decline in fertility and embryotoxicity following chronic exposure to BPA. However, literature data on human studies are limited and heterogeneous. Additionally, even less is known about the relationship between exposure to the BPA analogues (BPS and BPF) and sperm quality. Therefore, the present study aimed to examine the association between urinary concentrations of BPA, BPF, and BPS and semen quality parameters among 195 adult Spanish men from the Led-Fertyl study cohort using multiple linear regression models adjusted by potential confounding variables. Our results revealed an inverse association between log-transformed creatinine-adjusted concentration (ng/mg) of BPA and BPF levels and the percentage of sperm vitality (ß: 3.56 %; 95%CI: 6.48 to -0.63 and ß: 4.14 %; 95%CI: 6.97 to -1.31; respectively). Furthermore, participants in the highest quartile of BPA and BPF urinary concentration exhibited lower sperm vitality compared to those in the lowest quartile (ß: 6.90 %; 95%CI: 11.60 to -2.15 and ß: 9.68 %; 95%CI: 14.43 to -4.94; respectively). These results supply epidemiological evidence establishing a relationship between bisphenols urine exposure and sperm quality, suggesting that a re-evaluation of the overall safety of BPA alternatives is warranted.

Plastics in human diets: development and evaluation of the 24-h Dietary Recall - Plastic Exposure and the Dietary Plastics Score.

Background: Humans are commonly exposed to plastic through their dietary intake and food consumption patterns. Plastic-associated chemicals (PAC), such as bisphenols and phthalates, are recognized as endocrine-disrupting and are associated with increased risk of cardiovascular disease and metabolic syndrome. However, accurate methods to assess dietary exposure to plastic products and PAC are inadequate, limiting interrogation of health impacts. Aim: To develop a tool that captures complete dietary exposure to plastics and establish a diet quality score to measure adherence to a low plastic dietary pattern. Methods: We developed the 24-h Dietary Recall - Plastic Exposure (24DR-PE) and administered it to healthy adults (n = 422). This computer-assisted, interviewer-administered tool systematically collects data on food volumes and types, packaging materials, storage, processing, cooking, and consumption methods to assess a food's exposure to plastic. Specifically, the 24DR-PE incorporates predefined criteria for identifying high-risk practices and food characteristics, such as individually packaged items or those microwaved in plastic, enabling the assignment of scores based on a theoretically derived Dietary Plastics Scoring Matrix. Conclusion: The 24DR-PE is the first tool specifically designed to capture detailed data on dietary exposures to plastic products. The next step is to validate the score using laboratory results of urine samples we collected contemporaneous to the dietary information. Once validated, the tool has potential for widespread distribution making it valuable for population monitoring, intervention guidance, and future research investigating the interplay between plastics, diet, and human health.

Development and validation of a green analytical method for determining fourteen bisphenols in bee pollen by ultra-high-performance liquid chromatography-tandem mass spectrometry.

A new analytical method was developed and validated to determine fourteen bisphenols (A, B, C, E, F, M, P, S, Z, AF, AP, BP, FL, PH) in bee pollen using ultra-high-performance liquid chromatography-tandem mass spectrometry. Two different sample treatments were proposed and evaluated: one based on the QuEChERS (quick, easy, cheap, effective, rugged & safe) approach and the other utilizing microextraction with a supramolecular solvent (SUPRAS). In both cases, average analyte recovery ranged between 71 % and 114 %, and the matrix effect was between -45 % and +5 %, although it was not significant when using the QuEChERS-based method (<±20 %). The environmental impact of both sample treatments was assessed using different analytical metrics, with both procedures classified as environmentally friendly, though slightly better results were obtained for SUPRAS. The method was fully validated, showing that the QuEChERS approach had better overall performance, particularly regarding sensitivity and matrix effect. Consequently, the QuEChERS methodology was applied to determine bisphenols in thirty bee pollen samples from different Spanish regions. Residues of three bisphenols (M, P, and S) were detected, although only bisphenol S was quantified in several samples at low concentration levels (<7 µg kg-1), which is below the established specific migration limit (SML; 50 µg kg-1). However, regarding human health, the estimated daily intake, target hazard quotient, and hazard index assessed were higher than acceptable limits, suggesting a potential risk for human consumers.

Toxicological effects, absorption and biodegradation of bisphenols with different functional groups in Chromochloris zofingiensis.

Bisphenols (BPs) are recognized as endocrine disrupting compounds and have garnered increasing attention due to their widespread utilization. However, the varying biological toxicities and underlying mechanisms of BPs with different functional groups remain unknown. In the present study, the toxic effects of four BPs (BPA, BPS, BPAF, and TBBPA) on a photosynthetic microalgae Chromochloris zofingiensis were compared. Results showed that halogen-containing BPs exhibited higher cellular uptake, leading to more severe oxidative stress, lower photosynthetic efficiency, and greater accumulation of starch and lipids. Specifically, TBBPA with bromine groups showed a greater toxicity than BPAF with fluorine groups, possibly due to the incomplete debromination in C. zofingiensis. Transcriptomic analysis revealed that halogen-containing BPs triggered greater number of differentially expressed genes (DEGs), and only 64 common DEGs were found among different BPs, indicating that the effects of BPs with different functional groups varied greatly. Genes involved in endocytosis, peroxisomes, and endoplasmic reticulum protein processing pathways were mostly upregulated across different BPs, while photosynthesis-related genes showed varied expression, possibly due to their distinct functional groups. Additionally, SIN3A, ZFP36L, CHMP, and ATF2 emerged as potential key regulatory genes. Overall, this study thoroughly explained how functional groups impact the toxicity and biodegradation of BPs in C. zofingiensis.

Elucidating the Molecular Interactions and Immune Modulation of Bisphenols Exposure in the Pathogenesis of Polycystic Ovary Syndrome.

Bisphenols (BPs) are known endocrine disruptors potentially contributing to the pathogenesis of Polycystic Ovary Syndrome (PCOS). This study aims to elucidate the molecular interactions between BPs and PCOS-related genes and their combined effects on PCOS development. We identified common genes associated with BPs and PCOS using the CTD. Differential expression analysis was performed on three GEO datasets, leading to the identification of differentially expressed genes (DEGs). Protein-Protein Interaction (PPI) network construction, enrichment analysis, single-gene Gene Set Enrichment Analysis (GSEA), and immune cell infiltration analysis were carried out. A nomogram was developed for PCOS risk prediction, and molecular docking studies were performed using AutoDock Vina, with interaction visualizations via PyMOL. We identified 139 common genes between BPs exposure and PCOS, enrichment analysis highlighted pathways related to hormone metabolism, ovarian steroidogenesis, and p53 signaling. Four hub DEGs (PBK, CCNE2, LPCAT2, S100P) were identified, and a nomogram incorporating these genes demonstrated excellent predictive accuracy. GSEA revealed roles in cell adhesion, immune response, and metabolism. ssGSEA analysis showed significant differences in immune cell infiltration between PCOS and control groups, with notable correlations between hub DEGs and immune cells. Molecular docking indicated strong binding affinities between the hub DEGs and BPAF, suggesting potential disruptions induced by BPs. BPs exposure is associated with significant molecular and immunological changes in PCOS, impacting genes involved in hormone regulation, immune response, and metabolic pathways. The strong binding affinities between BPs and key PCOS-related genes reveal their potential role in exacerbating PCOS, providing insights for targeted therapeutic strategies.

Prenatal co-exposure to phthalate metabolites and bisphenols among non-syndromic cleft lip and/or palate in offspring.

Phthalate metabolites and bisphenols can cause adverse pregnancy outcomes. However, there is no study to evaluate the associations of prenatal exposure to phthalate metabolites and bisphenols with non-syndromic cleft lip and/or palate (NSCL/P) risk in offspring. A population-based case-control study was conducted in a multicenter setting from 2005 to 2021, enrolling 448 pregnant women. Seven phthalate metabolites and six bisphenols were quantified in placenta using liquid chromatography-tandem mass spectrometry. In the logistic regression analysis, high levels of mono-ethyl phthalate, mono-cyclohexyl phthalate, mono-octyl phthalate, bisphenol A, bisphenol AF, bisphenol AP, and fluorene-9-bisphenol were associated with increased NSCL/P risk with odds ratios (95% confidence intervals) of 1.86(1.07,3.25), 6.56(3.47,12.39), 8.49(4.44,16.24), 8.34(4.32,16.08), 3.19(1.81,5.62), 2.78(1.59,4.86), and 5.16(2.82,9.44). The Bayesian kernel machine regression model revealed that co-exposure to phthalate metabolites and bisphenols was associated with increased NSCL/P risk. Similarly, quantile-based g-computation analysis indicated that each quantile increase in mixture concentration was positively related to higher risk for NSCL/P [odds ratio (95% confidence interval) = 2.98(1.97,4.51)]. This study provides novel evidence that prenatal single and co-exposure to phthalate metabolites and bisphenols were associated with increased NSCL/P risk, suggesting that exposure to phthalate metabolites and bisphenols during pregnancy should be minimized to reduce the incidence of NSCL/P in offspring.

Endocrine disrupting chemicals and obesity prevention: scoping review.

INTRODUCTION: Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to highlight the knowledge about EDCs and obesity. METHODS: A scoping review of the electronic literature was performed using PubMed platform for studies on EDCs and obesity published between the years 2013-2023. A total of 10 systematic reviews and meta-analysis studies met our inclusion criteria on more prominent EDCs focusing mainly on bisphenols, including parabens, triclosan, and phthalates, and their association with obesity. DESIGN: Scoping review. RESULTS: EDCs, mostly bisphenols and phthalates, are related to health effects, while there is less information on the impact of parabens and triclosan. A series of negative physiological effects involving obesogenic, diabetogenic, carcinogenic, and inflammatory mechanisms as well as epigenetic and microbiota modulations was related to a prolonged EDCs exposure. A more profound research of particular pollutants is required to illuminate the accelerating effects of particular EDCs, mixtures or their metabolites on the mechanism of the development of obesity. CONCLUSION: Considering the characteristics of EDCs and the heterogeneity of studies, it is necessary to design specific studies of effect tracking and, in particular, education about daily preventive exposure to EDCs for the preservation of long-term public health.

External surface hydrophilic 3D-POSS-COF@GDL for the direct adsorption of bisphenols in milk samples.

In case of organic frameworks (COFs) as adsorbents in the pretreatment of complex food matrices, challenges such as poor dispersion and non-specific adsorption of interfering macromolecules like proteins are often encountered. To address this issue, this work prepared a three-dimensional covalent organic framework (3D-COF) with a novel bcu topology based on polyhedral oligomeric silsesquioxane (POSS). Subsequently, gluconolactone (GDL) was modified onto the external surface of the material via the reaction with the exposed reactive residues. The resulting POSS-COF@GDL adsorbent has an enhanced hydrophilicity in the external surface, thereby significantly improves the dispersion of materials in aqueous solution and reduces the adsorption ability toward protein. Whereas, the inner of material retains hydrophobic pores that exhibit high adsorption efficiency to small hydrophobic molecules. Compared with the traditional pretreatment methods, POSS-COF@GDL can directly extract bisphenols (BPs) in milk samples without any additional treatment. The established sample pretreatment method is coupled with high-performance liquid chromatography-ultraviolet detection (HPLC-UV), resulting in recoveries of 71.8 to 93.6%, intra- and inter-day relative standard deviations (RSDs) of <8.3%, and limits of detection (LODs) of 0.042-0.16 ng∙mL-1 for four BPs.

Evaluation of THP-1 and Jurkat Cell Lines Coculture for the In Vitro Assessment of the Effects of Immunosuppressive Substances.

The strong appeal to reduce animal testing calls for the development and validation of in vitro, in chemico and in silico models that would replace the need for in vivo testing and ex vivo materials. A category that requires such new approach methods is the assessment of immunosuppression that can be induced by chemicals including environmental pollutants. To assess the immunosuppressive action on monocytes and lymphocytes, we mimicked the whole-blood cytokine-release assay by preparing an in vitro coculture of THP-1 and Jurkat cell lines. We optimised its activation and investigated the effects of known immunosuppressive drugs with different mechanisms of action on the release of proinflammatory cytokines. Decreased secretion of IL-8 was achieved by several immunosuppressive mechanisms and was therefore selected as an appropriate marker of immunosuppression. A set of environmentally occurring bisphenols, BPA, BPAP, BPP, BPZ, BPE, TCBPA and BPS-MAE, were then applied to the model and BPP and BPZ were found to act as potent immunosuppressants at micromolar concentrations.

Comparative in silico and in vitro evaluation of possible toxic effects of bisphenol derivatives in HepG2 cells.

Introduction: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and "low dose toxicity". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased. Methods: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-ß) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. In vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects. Conclusion: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) µg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Influence of Genetic Polymorphisms on Cognitive Function According to Dietary Exposure to Bisphenols in a Sample of Spanish Schoolchildren.

BACKGROUND: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure. METHODS: A total of 102 children aged 6-12 years old were included. Ten SNPs in genes involved in brain development, synaptic plasticity, and neurotransmission (BDNF, NTRK2, HTR2A, MTHFR, OXTR, SLC6A2, and SNAP25) were genotyped. Then, dietary exposure to bisphenols (BPA plus BPS) was estimated and cognitive functions were assessed using the WISC-V Spanish form. RESULTS: BDNF rs11030101-T and SNAP25 rs363039-A allele carriers scored better on the fluid reasoning domain, except for those inheriting the BDNF rs6265-A allele, who had lower scores. Secondly, relevant SNP-bisphenol interactions existed in verbal comprehension (NTRK2 rs10868235 (p-int = 0.043)), working memory (HTR2A rs7997012 (p-int = 0.002), MTHFR rs1801133 (p-int = 0.026), and OXTR rs53576 (p-int = 0.030)) and fluid reasoning (SLC6A2 rs998424 (p-int = 0.004)). CONCLUSIONS: Our findings provide the first proof that exploring the synergistic or additive effects between genetic variability and bisphenol exposure on cognitive function could lead to a better understanding of the multifactorial and polygenic aetiology of NDDs.

Application of terpenoids for the remediation of environmental water polluted with bisphenol A and its analogs using an in silico approach.

Nowadays, there is a global concern over water quality and the impact of contamination on both natural ecosystems and human well-being. Plastics, ubiquitous in modern life, may release harmful chemicals when they reach aquatic environments. Among them, bisphenol A (BPA) and its alternatives, such as bisphenol S (BPS), bisphenol F (BPF), and others, are of special concern because their presence in water systems can have detrimental effects on human health and aquatic organisms due to their endocrine-disrupting properties. This study explores the potential of terpenoids, sustainable and environmentally friendly solvents, for efficiently removing bisphenols from contaminated environmental water. Using an in silico approach based on the Conductor-like Screening Model for Realistic Solvents (COSMO-RS) theory, more than 30 terpenoids were screened, and carvone was found to be an excellent candidate due to its high solvent capacity and low toxicity. The impact of pH, temperature, stirring conditions, and sample:extractant phase ratios on the extraction efficiency were investigated. A design of experiments revealed optimal conditions for the extraction process and demonstrated that carvone can effectively extract bisphenols (nearly 100 % for most of them) under a wide range of conditions, showing the robustness and efficiency of the extraction method, even in environmental samples. The paper provides valuable insights into the potential of terpenoids, specifically carvone, as a sustainable and eco-friendly solvent for removing bisphenol contaminants from environmental water bodies. The findings of this study offer a promising solution to address water contamination issues, aligning with the principles of Green Chemistry and contributing to a more environmentally responsible approach to water remediation.

[Determination of ten bisphenols and five parabens in urine by solid supported liquid-liquid extraction and liquid chromatography-tandem mass spectrometry].

Bisphenols (BPs) and parabens (PBs) are of great concern for environmental pollution and human health because of their endocrine-disrupting effects and potential health hazards. Urinary biomonitoring of BPs and PBs can provide basic data for human internal exposure evaluation, which is a prerequisite for accurately assessing their health risks. In this study, we developed a new pretreatment procedure based on solid supported liquid-liquid extraction (SLE) for the simultaneous separation of ten BPs and five PBs in human urine, followed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In the instrumental analysis, the HPLC conditions and MS/MS parameters were comprehensively optimized. Accurate qualitative and quantitative determination of ten BPs and five PBs was achieved by introducing a ternary gradient elution system of water, methanol, and acetonitrile for LC separation. During sample pretreatment, the extraction solvent and elution volume were optimized. Specifically, urine samples were held at room temperature and centrifuged at 3000 r/min for 10 min. The supernatant (2 mL) was then transferred to a glass tube, and the pH was adjusted to 5.0 using HCl (0.5 mL; 0.1 mol/L) and NaAc-HAc buffer (1.5 mL). Thereafter, ß-glucuronidase-arylsulfatase (20 µL) and surrogate standard solutions (10 ng;13C12-BPS,13C12-BPAF,13C6-MeP, and 13C6-BuP) were added, and the mixture was incubated in a shaker bath in the dark at 37 ℃ for 16 h. After incubation, the hydrolyzed sample (4 mL) was loaded onto an SLE cartridge and equilibrated for a minimum of 5 min to ensure the solution was completely absorbed by the packing material. Subsequently, the target chemicals were eluted with a mixed ethyl acetate/n-hexane solution (3∶7, v/v; 15 mL). Separation of the targets was performed on a ZORBAX SB-C18 reversed-phase column (250 mm×4.6 mm, 5 µm) using an acetonitrile-methanol-water system as the mobile phase. The method was verified by spiking mixed urine samples at three levels (1, 5, and 50 µg/L), with the recoveries ranging from 84.3% to 119.8%. Except for bisphenols (BPS), whose matrix effect was calculated as -21.8%, the matrix effects of other analytes were lower than 20%, indicating low matrix interference. The linear ranges of the analytes varied from 0.1-500 µg/L to 1-500 µg/L, with correlation coefficients higher than 0.995. The method limits of quantification for target chemicals ranged from 0.03 to 0.30 µg/L, and the relative standard deviations of intra- and inter-day experiments were 1.4%-8.4% and 5.7%-14.6%, respectively, suggesting high stability and reproducibility. The method was successfully applied to the determination of ten BPs and five PBs in 10 urine samples from a general population. The concentrations of target chemicals in the human urine samples varied. Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and bisphenol A (BPA) were detected in all samples, with median mass concentrations of 1.10, 0.60, 0.21, and 0.55 µg/L, respectively. The detection rates of the other chemicals were less than 50%, which may be related to the production and use of specific chemicals, their bioavailability, and biological metabolism in humans.

An in vitro model system for testing chemical effects on microbiome-immune interactions - examples with BPX and PFAS mixtures.

Introduction: More than 350,000 chemicals make up the chemical universe that surrounds us every day. The impact of this vast array of compounds on our health is still poorly understood. Manufacturers are required to carry out toxicological studies, for example on the reproductive or nervous systems, before putting a new substance on the market. However, toxicological safety does not exclude effects resulting from chronic exposure to low doses or effects on other potentially affected organ systems. This is the case for the microbiome-immune interaction, which is not yet included in any safety studies. Methods: A high-throughput in vitro model was used to elucidate the potential effects of environmental chemicals and chemical mixtures on microbiome-immune interactions. Therefore, a simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species was cultured in vitro in a bioreactor that partially mimics intestinal conditions. The bacteria were continuously exposed to mixtures of representative and widely distributed environmental chemicals, i.e. bisphenols (BPX) and/or per- and polyfluoroalkyl substances (PFAS) at concentrations of 22 µM and 4 µM, respectively. Furthermore, changes in the immunostimulatory potential of exposed microbes were investigated using a co-culture system with human peripheral blood mononuclear cells (PBMCs). Results: The exposure to BPX, PFAS or their mixture did not influence the community structure and the riboflavin production of SIHUMIx in vitro. However, it altered the potential of the consortium to stimulate human immune cells: in particular, activation of CD8+ MAIT cells was affected by the exposure to BPX- and PFAS mixtures-treated bacteria. Discussion: The present study provides a model to investigate how environmental chemicals can indirectly affect immune cells via exposed microbes. It contributes to the much-needed knowledge on the effects of EDCs on an organ system that has been little explored in this context, especially from the perspective of cumulative exposure.

Effect of crosslinker/porogen ratio on sponge-nested polymer monoliths for solid-phase extraction.

Polymer monoliths can be polymerised within different molds, but limited options are available for the preparation of free-standing polymer monoliths for analytical sample preparation, and in particular, solid-phase extraction (SPE). Commercial melamine-formaldehyde sponges can be used as supports for the preparation of polymer monoliths, due its flexibility, giving various shapes to monoliths. Herein, the crosslinker/porogen ratio of highly porous sponge-nested divinylbenzene (DVB) polymer monoliths has been evaluated. Monoliths prepared using different crosslinker/porogen ratios were applied to the extraction of bisphenol F, bisphenol A, bisphenol AF, and bisphenol B. Monoliths containing 50 wt % DVB and 50 wt % porogens presented the highest recovery of bisphenols. Under the optimised conditions, the developed method showed a linear range between 2.5 µg L-1 and 150 µg L-1 for BPA and BPAF, and between 5 µg L-1 and 150 µg L-1 for BPB and BPF. The limits of detection (LOD, S/N = 3) and limits of quantification (LOQ, S/N = 10) ranged from 0.36 µg L-1 to 1.09 µg L-1, and from 1.20 µg L-1 to 3.65 µg L-1, respectively. The recoveries for spiked bisphenols (10 µg L-1) in tap water and water contained in a polycarbonate containers were between 82 % and 114 %.

Maternal bisphenols exposure and thyroid function in children: a systematic review and meta-analysis.

Background: Evidence from animal experiments and epidemiological studies has reported controversial results about the effects of prenatal bisphenols (BPs) exposure on childhood thyroid function. This study aims to explore the associations of prenatal exposure to BPs with thyroid-related hormones (THs) in newborns and early childhood, with a particular focus on the sex-dependent and exposure level effects. Methods: Correlated studies were systematically searched from PubMed, Web of Science, Medline, Cochrane, and Embase until February 21, 2024. The exposures assessed include bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and tetrachlorobisphenol A (TCBPA). THs measured were thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), free tri-iothyronine (FT3), and free thyroxine (FT4). Effect estimates were quantified using coefficients from multivariable regression models. Statistical analyses were completed using Stata 16.0. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Eleven cohort studies comprising 5,363 children were included in our meta-analysis. Prenatal bisphenol concentrations were statistically significant related to alterations in thyroid hormones in children, exclusively in female offspring, including reduced TSH (ß = -0.020, 95% CI: -0.036, -0.005) and increased TT3 levels (ß = 0.011, 95% CI: 0.001, 0.021), and exposure to high concentration of bisphenols (>1.5 ug/g creatinine) significantly reduced FT3 levels in children (ß = -0.011, 95% CI: -0.020, -0.003). Conclusion: Prenatal bisphenol exposure is linked to alterations in thyroid hormone levels in girls, necessitating enhanced measures to control bisphenol exposure levels during pregnancy for child health protection. Systematic Review Registration: https://inplasy.com, identifier INPLASY202450129.

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells.

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

The mediating role of steroid hormones in the relationship between bisphenol A and its alternatives bisphenol S and F exposure and preeclampsia.

Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17 % of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion, maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE.