Bisphenol S (BPS), a widely used bisphenol analogue, has been increasingly detected in aquatic environments, raising concerns about its potential neurotoxic effects. However, the mechanism underlying the neurotoxicity induced by BPS remains elusive. In this context, our present study was aimed to investigate the impact of temporal BPS exposure towards precocious development of neurobehavioral transformation and neurodegeneration in zebrafish brain. Heightened monoamine oxidase (MAO) activity is associated with induction of aggressive behavioural response. In line with earlier report, our findings following mirror biting test advocated that temporal BPS exposure is associated with gradual genesis of aggressive neurobehavioral response and is correlated with augmented MAO activity and downregulation of tyrosine hydroxylase (TH) expression in zebrafish brain. Our further observation towards native neurobehavioral response as regulated by periventricular grey zone (PGZ) of optic tectum (TeO) of brain showed that duration dependent exposure to BPS is associated with gross transformation in scototaxis and explorative behaviour of zebrafish. Concurrently, our objective was also predestined to emphasize the detrimental effect of BPS on brain biochemistry and neuromorphology. In this line, our findings showed that BPS-persuaded heightened oxidative stress is linked with augmented chromatin condensation and apoptotic cell death as depicted through cleaved caspase-3 expression in zebrafish brain. To understand neuromorphological integrity of PGZ region through expression of NeuN, our findings advocated a significant downregulation following temporal exposure to BPS. In a nutshell, the gross observation delineates the strong neurodegenerative potential of BPS coupled through neurobehavioral transformation, oxidative stress and neuromorphological alteration in zebrafish brain.

Endocrine disrupting-chemicals (EDCs) are chemical compounds found in the environment that can have adverse impacts on human health. Among these agents are tributyltin (TBT) and bisphenol S (BPS). TBT is used in anti-fouling paints, and its indiscriminate use has health repercussions. BPS is found in plastic products and marketed as a safe alternative to bisphenol A (BPA). Little is known about the effects resulting from interactions between different EDCs on the organisms. The aim of this study was to analyze changes induced by exposure to these compounds in hypothalamic-pituitary-gonadal (HPG) axis and uterus. We divided four groups: Control, TBT 100 ng kg-1.day-1, BPS 50 μg kg-1.day-1, and the group simultaneously exposed to TBT and BPS. Rats were gavaged for 15 days and euthanized in the estrus phase. All EDCs groups showed uterus with cellular hyperplasia, glandular degeneration, increased epithelial thickness, and vacuolization. In the ovaries, there was an increase in atretic follicles in all EDCs groups. In the hypothalamus, the group exposed to the mixture showed an increase in the GnRH gene. In the blood, all EDCs groups had reduced levels of FSH and LH. Additionally, the BPS and mixture groups exhibited reduced levels of prolactin. Therefore, we suggest that exposure to these agents may contribute to damage to the female reproductive system, and that doses considered safe by regulatory agencies need to be reassessed.

Bisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the hepatotoxicity of BPF and its effects on glucose and lipid metabolism remain unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE staining, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100 mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.

Currently, there is limited information regarding the presence of chemicals in female underwear and the potential risks involved. This study investigated the levels of ten bisphenols in brassieres and briefs made in China, revealing total concentrations ranging from 13.9 to 52,967 ng/g. Bisphenol S (BPS), bisphenol F (BPF), and bisphenol A (BPA) made up a median of 53.2 %, 24.4 %, and 22.2 % of the total concentrations, respectively. The concentrations of bisphenols were significantly higher in darker samples compared to most other colors. When compared to previous reports on other textiles, this study found similar levels of BPA but higher concentrations of BPF and BPS. Furthermore, the median migration rates of BPF (39.1 %) and BPS (25.2 %) in artificial sweat were significantly greater than that of BPA (6.58 %), leading to higher exposure levels for BPF and BPS. The estimated non-carcinogenic risks associated with the three primary bisphenols in the underwear were deemed acceptable. However, the estimated exposure to BPS and BPF from this source represented about 2.53-12.0 % and 11.8-38.2 % of total human exposure, respectively, suggesting that the contamination of these chemicals in underwear is a concern that should not be overlooked.

Natural organic matter (NOM) has an important impact on the environmental behaviors of iron minerals, such as green rust (GR), however, NOM with different types and concentrations on these phenomena and mechanisms are still limited. This study explored effects of two common NOM (humic acid (HA) and fulvic acid (FA)) on the physicochemical properties of GR as well as the catalytic degradation of Bisphenol F (BPF). Results indicated that both HA and FA had a critical impact on the mineralization process and catalytic performance of GR, and the impact was concentration-dependent. High concentration of NOM inhibited the GR crystallization, accompanied by changing the surface structure from lamellar to porous, while reducing the degradation efficiency of BPF. Low concentration of NOM modified the morphology of GR into a petal-like shape, which increased surface oxygen vacancies and charge transfer, more importantly, facilitated the reduction of Fe(III) in GR. As a result, the production of reactive oxygen species, such as hydroxyl radicals (•OH), superoxide anions (O2•-), and singlet oxygen (1O2) was increased. O2•- and •OH were identified as the primary ROS for enhancing the degradation of BPF. Humic-like substances and tyrosine of NOM played an important role in promoting the reduction of Fe(III).

Bisphenols, particularly BPA, are ubiquitous environmental contaminants known to affect male reproductive health. However, their specific impacts on sperm function and subsequent embryo development remain understudied especially for BPA's commonly used replacements, BPS and BPF. This study investigated the effects of direct sperm exposure to BPA, BPS, and BPF on fertilization capacity and embryo development using a bovine model, as translational for humans. Sperm samples were exposed to 0.05 mg/mL of each bisphenol in vitro. Parameters, including hyperactivity and acrosome reaction, as well as fertilization outcomes, such as developmental rates and blastocyst quality, were further evaluated following IVF. miRNA profiles were also analyzed in sperm and embryos to detect potential biomarkers of bisphenol exposure. We found that BPF significantly increased sperm hyperactivity, and BPA decreased acrosome reaction levels (p < 0.05). Cleavage and blastocyst rates were also notably decreased in embryos derived from BPA-exposed sperm (p < 0.05). Furthermore, blastocysts produced from BPA, BPS and BPF treated sperm all had significantly lower cell counts and increased DNA fragmentation (p < 0.05). Although no statistically significant changes in miRNA levels were observed, this study highlights some of the detrimental effects of bisphenols on bovine sperm and subsequent embryo development, with potential implications for human reproductive health.

As a major substitute for the bisphenol A (BPA), the use of the bisphenol F (BPF) has increased dramatically in recent years. Growing evidence suggest that BPF shares numerous toxicological properties with BPA, raising the concerns about its potential impact on the health of organisms. However, the developmental toxicity of BPF remains poorly understood. In this study, we conducted a 5-day BPF exposure experiment on zebrafish (Danio rerio) from blastula stage at concentrations of 2, 20, 200, and 2000 µg/L. Our results demonstrated a significant increase in hatching rates across all treatment groups at 2 days post-fertilization (dpf). The esr1 was significantly upregulated at 2000 µg/L by 5 dpf, while no significant change was observed in ar. The frequency of operculum loss significantly increased at exposure concentrations of 20, 200, and 2000 µg/L, and a notable increase in notochord loss was observed at 2000 µg/L. To explore the underlying mechanisms, transcriptomic analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analysis revealed that the toxic effects of BPF were closely associated with osteoclast differentiation, the FoxO signaling pathway, and the MAPK signaling pathway. These pathways influenced critical biological processes, including response to stimuli, animal organ morphogenesis, detoxification, and biomineralization. This study provides evidence that BPF exposure at environmentally relevant concentrations (2 µg/L) is harmful to hatching, concentrations above 20 µg/L exhibit estrogenic-disrupting activity and exert toxicological effects on the development of the head skeleton in zebrafish. These effects are particularly linked to disruptions in osteoclast differentiation.

Bisphenol compounds (BPs), particularly bisphenol A (BPA), are chemicals that are widely used in various industrial sections and come into contact with humans via different routes of exposure. Documented toxic effects of BPs include androgenicity, estrogenecity, cytotoxicity, neurotoxicity, etc. As a well-known member of bisphenols, BPA is an endocrine disruptor chemical (EDC) that has been the subject of safety regulations. Monitoring infants' exposure to BPs via consumption of breast milk and infant formula is essential as they are at critical stages of development and are potentially more vulnerable. Following a systematic search in databases PubMed and Scopus, out of 44 studies included in the present work, 27 and 13 analyzed breast milk and infant formula samples, respectively. In addition, 4 studies reported BPs levels in both matrices. BPA is the most frequently detected BP with concentrations in breast milk reaching up to 112.44 ng/g in samples from Taiwan and as high as 262 ng/g in formula samples from Canada. For breast milk and formula samples, Liquid Chromatography coupled with Tandem Mass Spectrometry (HPLC-MS/MS) and Gas Chromatography Mass Spectrometry (GC-MS) were the most frequently employed methods of detection, respectively. Our review indicates scarcity of data on BPA analogs such as bisphenol S (BPS) and bisphenol F (BPF), highlighting the necessity for assessment of the occurrence of all BPA analogs in these matrices.

Bisphenol A (BPA) is a type of endocrine-disrupting chemical utilized in the production of plastics like epoxy resins and polycarbonate polymers. BPA exhibits weak estrogenic and potent anti-androgenic effects, and prior research has linked it to disturbances in thyroid function. This study aims to assess the potential association between early childhood exposure to urinary bisphenol A and thyroid hormone levels in pubertal children from Korea.

Participants were drawn from the Ewha Birth and Growth Cohort Study, encompassing individuals who visited Ewha Women's Mokdong Hospital between 2001 and 2005. The concentration of urinary BPA was repeatedly measured for each subject at ages 3-5 years and 7-9 years. Serum levels of free triiothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) were measured at ages 10-12 years in a subgroup of 128 out of 164 subjects who had undergone repeated BPA concentration measurements. We utilized the SAS program to analyze possible links between childhood exposure to BPA and thyroid hormone function in adolescence. Additionally, we explored how exposure to BPA during two specific periods influenced changes in thyroid hormone levels.

The study observed that urinary BPA levels at ages 3-5 years were not notably linked to thyroid hormone levels in adolescents aged 10-12 years. However, BPA levels at ages 7-9 years were significantly associated with free T3 levels in girls aged 10-12 years. Conversely, exposure to BPA did not result in significant differences in thyroid hormone levels among boys. The study did not find statistically significant connections between levels of urinary BPA and the other thyroid hormones, specifically TSH and free T4. There was a significant decrease in the concentration of free T3 in girls with higher BPA concentrations.

BPA exposure in childhood affects thyroid function in adolescent girls. This relationship may contribute to an increased prevalence of thyroid disorders in adolescents due to environmental influences.

This study investigated the relationship between maternal behaviours, environmental exposures, and the levels of melamine and bisphenols (BPs), including bisphenol F (BPF), bisphenol A-F (BPAF), and bisphenol S (BPS), in breast milk. Mothers provided information on cosmetic use, food packaging, and dietary habits, while breast milk samples were analyzed using high-performance liquid chromatography. BPAF, BPS, and BPF were detected in 32.3%, 33.8%, and 20% of samples, respectively, while melamine was present in all samples (mean: 32.3 ± 16.7 ng/mL). Seven samples (10.8%) contained all three BPs, while 49.2% had none. Higher BPAF and BPF levels were observed in breast milk from mothers aged 30-34. Makeup use was associated with elevated BPAF levels (p = 0.013), while sunscreen use was correlated with increased BPF (p = 0.040) and melamine (p = 0.010) levels. Storing oil in plastic containers was linked to higher BPS levels. These findings suggest that maternal exposure to personal care products and food packaging materials significantly influences BPs and melamine levels in breast milk. The results highlight the importance of considering both behavioural and environmental factors when assessing chemical exposure during breastfeeding. Further research is needed to understand the long-term effects of these exposures on infant health.

Aquatic ecosystems face ever increasing threats from pollutants, including those derived from exposure to bisphenol compounds (BPs). Bisphenols are endocrine disruptors with significant neurotoxic effects. This review examines the neurobehavioural impacts of bisphenol A (BPA) and its analogues (e.g. BPS, BPF, BPAF, and others) in zebrafish (Danio rerio), a widely used model organism in environmental and regulatory toxicology. Behavioural endpoints such as locomotor activity, anxiety, shoaling, and cognitive functions can be measured in zebrafish, providing insight into the potential neurotoxicity of chemicals. Bisphenols disrupt neural processes through mechanisms involving oxidative stress, endocrine disruption, neurotransmitter dysfunction, and altered gene expression related to neurodevelopment. Specific behavioural disruptions include impaired locomotor activity, heightened anxiety, altered social behaviours, and visual disturbances, often linked to structural damage in the nervous system. While BPA remains the most studied compound, evidence suggests other BPA analogues may have comparable or greater neurobehavioural toxicity. Implicated mechanisms underlying bisphenol-mediated behavioural events in zebrafish include cortisol metabolism, antioxidant defence, serotoninergic receptor signaling, and glutamate receptor signaling, revealing complex interactions that require further investigation. In addition, emerging studies point to the transgenerational effects of these compounds on neurobehavioural functions, necessitating further exploration of behaviour. This comprehensive review underscores the need for expanded research into the molecular pathways underlying BPs-induced neurotoxicity to help formulate better mitigation strategies and regulatory policies.

Several adverse outcome pathways (AOPs) describe the effects of endocrine disrupting compounds on estrogen signaling. Substantial data support an AOP related to estrogen receptor (ER) antagonism, leading to decreased fecundity in fish. In this study, data were generated for an ER agonism AOP leading to reduced fecundity in avian species (AOP537). Chicken embryos and the chicken leghorn male hepatoma cell line, LMH, were used to elucidate key events associated with estrogen signaling following exposure to 17α-ethinylestradiol (EE2) and bisphenol A (BPA). Embryos were exposed via egg injection. Viability and hepatic estrogen-responsive gene expression data were collected at midincubation (embryonic day [ED] 11). Changes in plasma vitellogenin (VTG), gonad morphology and growth were evaluated prior to pipping (ED20). Both chemicals dysregulated estrogen-responsive genes in hepatic tissue and increased plasma VTG concentrations. In LMH spheroids, EE2 and BPA altered estrogen-responsive genes and VTG concentrations at 24 and 48 h, respectively. Gonadal histology revealed oocyte-type cells and loss of testicular cords in male embryos exposed to EE2 and BPA. Overall, EE2 and BPA upregulated VTG mRNA expression, increased plasma VTG, and caused impairments in gonadal development. These results contribute avian-specific evidence to support an endocrine disruption AOP describing the relationship between disrupted VTG synthesis and impaired reproduction.

Bisphenol S (BPS) and Bisphenol F (BPF), as alternatives to bisphenol A (BPA), are recognized for their endocrine-disrupting properties, but their combined immune toxicity mechanisms remain poorly understood. This study systematically evaluates the individual and joint immune toxicity effects of BPS and BPF through ADMET predictions, transgenic zebrafish models, and molecular docking analyses. The results indicate that equal effect concentration BPS and BPF act through distinct immune pathways: BPS primarily targets macrophages to mediate immune responses, while BPF significantly stimulates neutrophil proliferation and induces a stronger inflammatory response through chemokine signaling. Molecular docking studies show that BPF binds more stably to pro-apoptotic protein Mapk8 and oxidative stress-related protein Hsp90aa1, leading to significantly higher levels of apoptosis and reactive oxygen species (ROS) compared to BPS. The similarity of modes of action (MOA)between BPS and BPF based on relevant immune indicators calculated and experimentally is about 0.3; this quantitative result also proves that modes of action differ widely. Nonetheless, most of the indicators showed superimposed effects in the combined experiments, and it is noteworthy that the oxidative stress indicators (SOD, MDA) showed synergistic effects, suggesting that BPS and BPF, which have very different modes of action, are able to be risk assessed using an additive model with respect to immunity, but may exhibit synergistic risks with respect to oxidative stress. This research demonstrates that BPS and BPF induce immune toxicity via different molecular targets and pathways and highlights the need to account for their synergistic effects in risk assessments. These findings provide important insights into the immune toxicity mechanisms of BPA substitutes and the potential risks of combined exposures.

We conducted pioneering research evaluating Akkermansia muciniphila and Faecalibacterium prausnitzii as next-generation probiotics (NGPs) for removing bisphenol A (BPA) analogues, such as bisphenol F (BPF) and tetramethylbisphenol F (TMBPF). Chronic exposure to these under-researched compounds through contaminated food poses a risk to health by promoting gut microbiota imbalances and inflammation. In our experiments, pasteurized F. prausnitzii removed up to ∼87 % of TMBPF after 48 h (from 9,976 ± 0,790 μg/mL to 1,350 ± 0,330 μg/mL μg/mL, p < 0.0001) through bioadsorption. Meanwhile, A. muciniphila achieved ∼48 % removal of BPF (from 10,33 ± 0,96 μg/mL to 5,33 ± 0,62 μg/mL, p < 0.0001) via biotransformation also after 48 h. Bioadsorption and biotransformation mechanisms were compared across conditions, with significant differences (p < 0.01) observed only for A. muciniphila with BPF and F. prausnitzii with TMBPF after 48 h. No cytotoxic effects of raw bisphenols were seen in Caco-2 cells, although the post-fermentation supernatant from A. muciniphila reduced cell viability to 68 % (p < 0.001). Notably, TMBPF showed no estrogenic activity, while BPF exhibited strong estrogenicity, which decreased following incubation with both strains. These findings confirm both NGPs reduce bisphenol concentrations, supporting their use in detoxification and functional food development. Implementing NGP-based strategies in food production and supplementation could lower human exposure to harmful bisphenols. This approach underscores the promise of advanced probiotics in mitigating foodborne chemical risks and aligns with evolving regulations and public health efforts to protect consumers.

This review's main purpose is to draw attention to the possible influence of widely used bisphenols on the inflammatory process. Bisphenols are endocrine-disrupting chemicals that are produced worldwide in great quantities. From this point of view, it is very important to clarify their influence on innate immune reactions, which protect the integrity of the body against the action of various pathogens on a daily basis. The inflammation process consists of several key factors that are produced at different levels of this reaction. Each of these levels can be affected by endocrine disruptors, from the point of view of modifying either the immune system cells that intervene in this process or the way in which they produce inflammatory mediators. The development of new recommendations for the use of bisphenols is a complex issue given their influence on inflammatory processes. Because the immune system and immune response are so intricate, bisphenols may pose more risk to humans than is presently recognized. This paper discusses the classification of bisphenols, the fundamental mechanism of inflammation, the characterization of inflammatory mediators, and the current knowledge of the molecular mechanisms behind the impact of bisphenols on the inflammatory response.

Chemical pollution is one of today's most significant threats to the developmental potential of children worldwide. Maternal exposure to toxicants can perturb sensitive windows of fetal development, indirectly through promoting antenatal disorders, abnormal placental adaptation, or directly through maternal-fetal transport. Current evidence clearly shows that persistent organic chemicals promote hypertensive disorders of pregnancy, placental abnormalities, and fetal growth restriction, whereas findings are less consistent for phthalates and bisphenols. Prospective birth cohorts strongly support a link between adverse neurodevelopmental outcomes and prenatal exposure to flame retardants and organophosphate pesticides. Emerging evidence reveals a potential association between in utero exposure to bisphenols and childhood behavioral disorders, while childhood metabolic health is more consistently associated with postnatal exposure to phthalates and bisphenols. IMPACT: Synthesizes emerging evidence linking modern forms of chemical pollution to antenatal disorders, fetal growth restriction and childhood disorders. Highlights potential developmental impacts of emerging pollutants of concern now ubiquitous in our environment but without regulatory restrictions.

Novel bisphenol S (BPS) derivatives are being increasingly utilized as substitutes to bisphenol A (BPA) and BPS in thermal receipts and other industrial or commercial products. In recent years, the environmental occurrence, human exposure, and toxicity of non-chlorinated and chlorinated BPS derivatives have been investigated in numerous studies. This review summarizes the state-of-art and new knowledge on these aspects and provides recommendations for future research directions. The environmental analysis showed that BPS derivatives have been widely detected in paper products, water, indoor dust, sediment, and municipal sewage sludge. Recent studies have also reported the presence of non-chlorinated BPS derivatives, such as benzenesulfonylbenzene (DDS) and 4-(4-propan-2-yloxyphenyl)sulfonylphenol (BPSIP), in human breast milk, urine, and the maternal-fetal-placental unit. Toxicological studies suggest that BPS derivatives may cause a series of toxic effects, including endocrine-disrupting effects, cytotoxicity, hepatotoxicity, developmental toxicity, and neurotoxicity, some of which have been shown to exhibit adverse effects similar to or even greater than those of BPS. Future studies should focus on elucidating environmental occurrences, half-lives, sources for human exposure, and potential transformation pathways of BPS derivatives, as well as their toxic effects and underlying mechanisms.

Bisphenol S (BPS) has become extensively used in the manufacturing of consumer products. BPS mainly enters the body through food and water, with oral exposure targeting the gastrointestinal tract. However, its safety profile remains contentious and warrants further investigation. In this study, we aimed to assess whether BPS exerts harmful effects on the body in the absence of overt pathological damage. Our results revealed that although BPS did not lead to significant histopathological damage, it induced intestinal barrier dysfunction. Additionally, in vitro investigations utilizing NCM460 cells and human-derived colorectal organoids demonstrated that BPS exposure induced mitochondrial reactive oxygen species (ROS) levels in intestinal endocrine cells (EECs), upregulating the expression of inflammatory mediators TNF-α and CXCL10. Using a DSS-induced colitis mouse model, it was found that BPS exposure exacerbates the progression of intestinal inflammatory diseases. Analysis of single-cell databases demonstrated a significant reduction in the expression of CHGA, a functional protein of enteroendocrine cells (EECs), in patients with inflammatory bowel disease (IBD). The expression of CHGA showed a significant negative correlation with the expression of IL17. Notably, supplementation with 3-Indoleglyoxylic acid effectively mitigates the intestinal damage induced by BPS. These findings highlight the role of mitochondrial oxidative stress and IL-17/CXCL10/TNF-α signaling in BPS-induced intestinal damage and demonstrate the therapeutic potential of 3-Indoleglyoxylic acid in mitigating these effects.

Bisphenol S (BPS), as an environmental pollutant, is known to reduce brain lipid levels and induce neurotoxicity. However, whether brain lipid imbalance can induce neurotoxicity has not yet been clarified. Here, wild-type zebrafish and apoEb mutant zebrafish were used to investigate the effect of BPS on the macrophages proliferation and microglia mobilization caused by the decrease of cerebral lipids and its potential neurotoxic effects. The zebrafish exposed to BPS (1, 10, or 100 μg/L) from 2 hours after fertilization (hpf) to 3 days after fertilization (dpf) displayed microglial aggregation, as well as a decrease in brain lipid content. Lipidomic analyses of the brains and plasma of 50 dpf zebrafish exposed to BPS were used to identify key lipids, including lysophosphatidylcholine and phosphatidylcholine in brain and phosphatidylcholine in plasma. The apoEb mutant zebrafish as a hyperlipidemia model was used to further demonstrate that BPS-induced lipid reduction increased the number of microglia in the brain. Our data provide new insight into the mechanism by which pollutants cause neurotoxicity.

Bisphenol analogs, structurally similar to bisphenol A (BPA), are widely used in various industries as a safer alternative to BPA. However, these alternatives also present risks, such as inflammation and potential connections to chronic diseases like cancer and diabetes, highlighting the need for further research into their toxicity mechanisms. Building on our previous cytotoxicity research, this study delves into the mechanisms of toxicity associated with bisphenol analogs (bisphenol AF, bisphenol AP, bisphenol E, and bisphenol P) on human in vitro cell models (HepaRG, Caco-2, HMC3, and HMEC-1). In this study, we assessed the impact of these compounds on key cellular stress markers: reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), and mitochondrial calcium levels. Results revealed dose-dependent increases in oxidative stress and decrease in mitochondrial membrane potential (ΔΨm), with Caco-2 cells (enterocytes) exhibiting the highest sensitivity, indicating tissue-specific vulnerability. Notably, bisphenol AF, bisphenol AP and bisphenol P were identified as the most potent analogs in inducing ROS, affecting mitochondrial integrity and calcium homeostasis among all cell models. This research highlights the importance of understanding analog-specific and cell-specific responses to bisphenol compounds, providing a foundation for improved regulatory strategies to mitigate health risks associated with their exposure.

Neurodevelopmental disorders have complex etiologies, stemming both from genetic and environmental risk factors, including gestational exposure to bisphenol A (BPA). BPA is an endocrine-disrupting chemical widely used in the synthesis of plastics and epoxy-resins. In 2012, the Food and Drug Administration issued a ban on the use of BPA in certain baby and childhood products, which contributed to the proliferation of BPA-free products. To make products without BPA, plastic and epoxy manufacturers often use chemical analogs, including bisphenol F (BPF) and bisphenol S (BPS). However, the structural and biochemical similarities BPF and BPS share with BPA suggest they may have similar molecular and cellular impacts on the developing nervous system, despite consumers generally regarding BPA-free products as safer alternatives. In this review, we synthesized all available peer-reviewed primary literature to date reporting on the neurodevelopmental impacts of BPF and/or BPS in animal models. In total, 61 papers were identified as relevant to the topic, including evaluation of BPF- and BPS-associated neurodevelopmental phenotypes such as changes in neurodevelopmental gene expression, the proliferation and differentiation of neural stem cells, synaptogenesis, central nervous system morphology, neuronal cell death, and behavior. Though less extensively studied than BPA, the collective works described here indicate that BPF and BPS can act as developmental neurotoxicants in animal models, urging further mechanistic and epidemiological analyses of these bisphenol analogs, as well as a reconsideration by regulatory agencies of policies surrounding their usage.

The in silico assessment of chemical toxicity is crucial for regulatory frameworks like REACH, which support the use of QSAR models and read-across techniques to predict the properties of compounds. This study addresses the challenge of evaluating bisphenol A (BPA) alternatives, for which specific predictive models are often lacking. Utilizing VEGA software, we examined three ecotoxicological endpoints: toxicity in Daphnia magna (Daphnia magna Acute (EC50) Toxicity model (IRFMN)), Pimephales promelas (Fathead Minnow LC50 96 h toxicity (EPA)), and Oryzias latipes (Fish Acute (LC50) toxicity model (IRFMN)). We employed Self-Organizing Maps (SOM) to cluster bisphenol compounds based on similarities to experimental data from model training sets. Principal Component Analysis (PCA) was used to reduce dimensionality and visualize data, with color-coding to indicate predicted properties. Our results reveal that while BPA is often a cluster indicator due to its extensive inclusion in training sets, BPA alternatives frequently exhibit similar toxicological concerns. The clustering approach provides a nuanced understanding of the potential risks associated with BPA alternatives, suggesting that many may not offer significant safety improvements over BPA itself.

Bisphenol A (BPA), a common endocrine disrupting chemical (EDC), has shown detrimental effects on sperm quality and function in experimental models. However, epidemiological evidence is inconsistent and also there exists a notable lack of data on its analogues, such as bisphenol F (BPF) and bisphenol S (BPS). To investigate the relationships between BPA, BPF and BPS exposures and sperm DNA damage, we conducted a cross-sectional study recruiting 474 Chinese men from an infertility clinic in Wuhan, China. We repeated measurements of urinary BPA, BPF and BPS concentrations to enhance the exposure assessments and evaluated sperm DNA damage using three comet assay indicators: tail length (TL), tail distributed moment (TDM) and percentages of tail DNA (Tail%). We observed positive associations of BPA exposure with TL and TDM (both P for trends < 0.05) and an association of elevated BPF exposure with increased Tail% (P for trend = 0.066). Furthermore, BPA exposure in relation to increased TL and TDM were more pronounced in men with body mass index (BMI) below 24 kg/m2 and non-smokers (all P for interactions < 0.05). Our findings strengthened human evidence that BPA and its analogue BPF exposures were in relation to increased sperm DNA damage.

Bisphenols can enter the body, where they have potential adverse effects on human health, via different routes such as inhalation, dermally or orally. They are known as endocrine disrupting chemicals that activate signaling pathways by mimicking the estrogen actions. In this study, we aimed to investigate effects of bisphenol A (BPA), and its analogues bisphenol F (BPF) and bisphenol S (BPS) on MCF-10A cells and their impact mechanisms on autophagy, apoptosis and reduced glutathion levels. In comparison of the cytotoxic effects, while BPF and BPS showed dose-dependent high toxicity on MCF-10A cells, BPA exerted cytotoxic effects only at the highest doses. Caspase 3 and LC3B are strongly and positively correlated with BPF exposures while significant changes were not detected in the BPA and BPS applied groups. It was clearly observed that BPF and BPS displayed more toxic effects than BPA on human breast cells that are important targets for the bisphenols. These findings provide data for understanding the mechanisms for BPA, BPF and BPS-induced toxicity on human breast cells.

Bisphenol analogues have been shown to have similar estrogenic activity to that of BPA and may affect fetal development. However, no human studies have examined the effects of perinatal exposure to emerging bisphenol alternatives [bisphenol G, bisphenol M, and bisphenol BP (BPBP)] on small for gestational age (SGA) and how placental function may mediate the relationship. Here, 13 urinary bisphenol analogues were detected in 1054 contemporary pregnant women, and BPA was still the most dominant congener. Logistic regressions identified BPA and its traditional alternatives [bisphenol B (BPB), bisphenol E (BPE), bisphenol Z, and bisphenol AP (BPAP)] as being associated with an elevated risk of SGA (all ORs > 1.80, P < 0.05). In contrast, the emerging substitutes, despite high occurrences, all showed much attenuated risk. Mixture effect models Bayesian kernel machine regression and quantile-based g-computation demonstrated that coexposure to bisphenols was strongly correlated with SGA risk (OR = 2.70, P < 0.001), with BPA and the conventional substitutes (BPB, BPE, and BPAP) as primary effect drivers, outweighing the effect from emerging substitutes. Finally, mediation analysis revealed that the placental function index estriol mediated the relationship between exposure and SGA, dominated by BPBP (25.4%). Our findings provide new epidemiological evidence that early BPA alternatives may pose a higher risk for offspring development than those emerging alternatives, potentially via mediation by compromised placental function. Future toxicity assessments and validation studies in other settings on these emerging bisphenols are needed.

Bisphenol S (BPS) is extensively utilized in personal care products, foods, and paper products, raising growing concerns about its potential environmental hazards. However, few studies have reported the effects of BPS exposure on bone homeostasis. In this study, using data from the National Health and Nutrition Examination Survey, we found a negative correlation between urinary BPS and bone mineral density (BMD). To further investigate the underlying mechanisms, C57BL/6 mice were exposed to a human-equivalent dose of BPS for 6 months. Micro-CT analysis demonstrated reduced femoral BMD in the mice, indicating that osteoporosis was caused by chronic exposure. RNA-seq analysis showed that BPS activated PPARγ in human primary mesenchymal stem cells (MSCs). Additionally, 3D molecular docking confirmed a direct interaction between BPS and PPARγ. Bioinformatics analysis identified SMAD6 as a downstream target of PPARγ. Mechanistically, the BPS-PPARγ interaction activated PPARγ, promoting SMAD6 transcription, which inhibited the osteogenic differentiation of MSCs. High-throughput virtual screening further revealed that olodanrigan effectively blocked the BPS-PPARγ interaction, and in vitro assays revealed that olodanrigan blocked the inhibition of osteogenic differentiation of MSCs induced by BPS. Additionally, olodanrigan supplementation inhibited PPARγ levels, thereby reversing BPS-induced osteoporosis. In summary, this study elucidates the role of the PPARγ-SMAD6 axis in mediating BPS-induced osteoporosis and highlights olodanrigan as a promising therapeutic intervention, offering new insights into the health risks posed by BPS and potential targets for treatment.

Substantial amounts of nitrogenous (N) compounds, as well as bisphenol A (BPA) and bisphenol S (BPS), contribute to the impurities of pharmaceutical contamination (PC) in wastewater, which have detrimental effects on the environment, humans, and aquaculture. The anammox processes is primarily used to treat wastewater contamination, in which certain microbial communities play a crucial role. In this regard, the present study focuses on microbial communities and the functional genes involved in the anammox process. Further, the current study highlights the secondary (biological) and tertiary (advanced) methods; these techniques are more effective solutions for PC treatment. Anammox bacteria are the primary drivers of the wastewater's ammonium and nitrite removal process. However, overall, 25 anammox species have been recognized between five important genera, including Anammoxoglobus, Anammoximicrobium, Brocadia, Kuenenia, and Jettenia, which are mainly found in activated sludge and marine environments. The group of bacteria called anammox has genes that encode enzymes such as hydrazine synthase (HZS), hydrazine dehydrogenase (HDH), nitrite oxidoreductase reductase (NIR), hydroxylamine oxidoreductase (HAO), and ammonium monooxygenase (AMO). The anammox process is responsible for developing about 30% to 70% N gases worldwide, making it a critical component of the nitrogen cycle as well. Therefore, this review paper also investigates the pathways of hydrazine, an intermediate in the anammox process, and discusses the potential way to significantly decrease the N-compound contamination from wastewater systems and the environmental effects of determined organic contaminants of BPA and BPS.

The introduction of bisphenol-S (BPS) in substitution of bisphenol-A (BPA) has become argumentative owing to their endocrine destructive properties and insufficient comparative ecotoxicity assessments. Thus, comparative effects of long-term, low-dose BPA and BPS exposure on the development of juvenile zebrafish (Danio rerio) were investigated. Juvenile zebrafish (age: 21 days; weight: ~ 61.5 mg; length: ~ 7.56 mm) were exposed to environmentally-relevant 50 µg/L of BPA, BPS, and control for ~ 60 days in triplicate. Both BPA and BPS significantly increased length (p = 0.00), weight (p = 0.00), specific growth rate (p = 0.00), female preponderance (p = 0.003), mortality (p = 0.017), ammonia excretion (p = 0.00), and aggression (p = 0.00) in zebrafish compared to control. Both bisphenols significantly reduced fish swimming speed in a comparable manner (p = 0.001). A notably higher female-biased-sex ratio was observed in BPS than in BPA (p = 0.003). The length gain (p = 0.014) and aggression (p = 0.032) were higher in BPA-treated fish than in BPS. However, a significant difference was not shown in body mass index (p = 0.295) and condition factor (p = 0.256) between bisphenols and control (p < 0.05). BPA and BPS exposure led to hyperplasia, mucous secretion, aneurism in fish gills, vacuolization and necrosis in liver. Therefore, BPS (~ 50 µg/L) also imposes noteworthy threats to aquatic wildlife, emphasizing the necessity of toxicity assessments and regular monitoring aiming at bespoken environmental standards for freshwater.

As substitutes for bisphenol A (BPA), bisphenol analogs (BPs) have raised concerns due to their frequent environmental detection and unclear safety. Here, the cytotoxicity, endocrine disruption, neurotoxicity, aryl hydrocarbon receptor (AhR) activity, and genotoxicity of nine BPs and BPA were evaluated in three types of cell lines. Over half of the tested BPs exhibited greater cytotoxicity than BPA, with IC50 values showing a linear correlation with LogKow (R²=0.69). All tested BPs exhibited at least one endocrine-disrupting effect, notably estrogenic, which was observable even at 0.01-0.1 μM. Importantly, BPAF and BPAP exposure had widespread endocrine-suppressing effects. Moreover, all BPs (except BPP) and BPA increased SH-SY5Y cells apoptosis at 1-10 μM. Only BPF and BPP significantly increased 7-ethoxyresorufin-O-deethylase levels, highlighting their notable effects on AhR activity. BPAF significantly induced DNA damage at 1.25 μM, whereas BPA, BPF, and BPP induced damage at 20, 25, and 25 μM, respectively. Finally, ToxPi, a weighted scoring system, was used to rank the comprehensive toxicity of BPs, with 7 of 9 BPs showing higher scores than BPA. Collectively, BPs generally exhibited stronger comprehensive toxicity compared with BPA, emphasizing the urgent need for further research to confirm their potential health implications.

BPF is a ubiquitous environmental chemical that has been shown to affect neurodevelopmental toxicity from animals to humans. Whether BPF exposure affects neural stem cell proliferation and differentiation is unknown. Here, we utilized a method of permeabilization of Drosophila embryos to analyze the effects of exposure to 0.5 mM, 1 mM, and 2 mM BPF on the proliferation and differentiation of neural stem cells. Our results showed that BPF exposure reduced the number of neuroblasts and intermediate neural progenitors during the embryonic stage, which caused the neuron/glial cell ratio to be out of balance, with a decrease in the number of neurons and an increase in the number of glial cells. BPF exposure caused neurotoxicity by reducing the activities of the antioxidant enzymes CAT and SOD, the downregulation of the transcriptional levels of oxidative stress-related genes, which triggered oxidative damage. As a result, embryonic BPF exposure affected the development of the neuromuscular junctions (NMJs) by reducing the number of axon branches and synaptic buttons, decreasing the number of peristaltic contractions, and reducing larval locomotion. In conclusion, our results demonstrate that embryonic BPF exposure disrupts neural stem cell proliferation, causing neurodevelopmental toxicity and abnormal larval behavior.

The effects of bisphenol A (BPA), a highly diffused endocrine-disrupting chemical found mainly in plastics, on neural circuits and behaviors are well-known. However, the effects of its substitutes have not been fully investigated. Thus, in the present study, we compare the effects of perinatal exposure to bisphenol A or S (BPS) on reproductive behaviors and related hypothalamic kisspeptin system in mice. C57BL/6J dams were orally treated with 4 μg/kg body weight/day of BPA, BPS, or vehicle from mating until the weaning of the offspring. In the adult offspring, we performed the two-bedding T-Maze test, and we observed the spontaneous sexual behavior. Exposure to BPA caused a delay in puberty onset in females, while BPS caused anticipation in males, and both altered the estrous cycle in females. The sexual and sexual-related behaviors were partially altered in males, especially in the BPA-exposed ones. Regarding the kisspeptin immunoreactivity in the analyzed hypothalamic nuclei, in BPA- or BPS-treated females, we observed an increase within the rostral periventricular area, while BPA led to an increase in the paraventricular nucleus, and BPS induced a reduction compared to control females. Among males, we observed a significant increase in the arcuate nucleus of BPA-treated males and a significant decrease in the paraventricular nucleus of BPS-treated ones. These results support the idea that perinatal exposure to low doses of either BPA or BPS is altering, in a sexually differentiated way, some reproductive-relevant parameters, sexual behaviors, and kisspeptin hypothalamic nuclei.

Two new diacid monomers containing either fluorene or sulfone moieties polymerize via step-growth polymerization in the presence of their diol counterparts or alkyl diols (ethylene glycol and 1,6-hexanediol), forming eight new cardo structure polyesters. The polymers exhibit high optical transparency in the thin-film form with refractive indices ranging from 1.56 to 1.69, tunable glass transition temperatures from ca. 40 to 116 °C with no melting temperature, and resistance to thermal degradation in a nitrogenous atmosphere, reaching 350-398 °C before observing 10% weight loss. Their molecular weights, M w , range from ca. 17 to 77 kDa, with an average polydispersity, Đ, of 1.5, and average purified yields of 82%. The polymers absorb light primarily in the UV region from ca. 228 to 320 nm with no absorption from 320 to 800 nm. A critical finding is that some of the fluorene and sulfone monomers induce negative bioactivity and even cell death in T47D-KBLuc cells, a breast cancer cell line, at high concentrations. This report details the project inspiration, monomer synthesis, polymerization steps, structural confirmation, material characterization, and the impact of the new monomer's estrogenic and antiestrogenic bioactivity.

Increasing levels of infertility in Western countries has drawn ever more scientific attention to the role in this trend of endocrine disruptors, such as bisphenol A, a substance now banned in some cases and some countries. Because this substance has been replaced by the structurally similar bisphenol S (BPS), this study focused on the effects of the latter on early mice embryo development.

Cultures of CD1 mice embryos with varying concentrations of BPS were compared with control blank cultures in order to examine the survival rate of embryos according to BPS concentration and culture day.

The administration of BPS at any dose (1, 10, and 100 pg/ml) in cultures of mice embryos led to a significant decrease in their survival rate. The negative effect of BPS was seen to start early (day 1 of experiment), even with the lowest employed dose (1 pg/ml).

This is, to the best of our knowledge, the first study to investigate the impact of BPS on the survival rate of mice embryos. In this study, potential adverse effects of BPS on early CD1 mice embryo development with regard to survival rate have been identified. Dose of BPS, timing of BPS administration, and time duration of exposure play a critical role in the decrease of mice embryo survival rate as compared to control cultures. These findings raise concerns regarding the safety of BPS and highlight the need for further research into the effect of this substance on human embryos.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is widely used in consumer products, increasing the potential for environmental exposure. Our study investigated the reproductive effects of BPF on adult male zebrafish and explored its toxicological mechanisms, as well as its intergenerational effects.

Adult male zebrafish were exposed to BPF concentrations of 0, 50, 500, 2500, and 5000 nM for 21 days. We evaluated sperm cell quantity and quality, hormonal markers testosterone (T) and vitellogenin (VTG), gene expression profiles related to hormone synthesis, metabolism, apoptosis, cell cycle, sexual behavior, and offspring health metrics including survival, development and locomotion.

BPF exposure did not significantly affect body weight or gonadal index. However, at 500 and 2500 nM, a significant reduction in sperm count was observed. BPF exposure led to decreased serum T and increased hepatic VTG levels, indicating hormonal disruption. At 50 nM, BPF initiated sperm apoptosis, and at higher doses, it disrupted sperm meiosis, affecting cell distribution. This exposure negatively impacted sperm quality, reduced offspring survival rates, and altered sperm motility in adult fish. Offspring from BPF-exposed groups showed developmental issues, including increased mortality, delayed developmental stages, abnormal tail coiling and heart rate, which correlated with paternal sperm count and quality changes, alterations in T and VTG levels, and cell cycle phase distributions.

Our study demonstrated that BPF exposure significantly impacted sperm quality, characterized by reduced sperm count and altered motility patterns, leading to developmental anomalies in offspring. These novel findings highlight the need for further research into BPF's reproductive and developmental toxicity, emphasizing the potential risks to aquatic ecosystems and human health. The observed effects on sperm quality, hormonal balance, and offspring development provide new insights into the reproductive toxicity profile of BPF.

Endocrine Disrupting Chemicals (EDCs) are ubiquitously found as low-level contaminants and pose serious threat to women's health. EDCs may result in various reproductive disorders, fetal birth and developmental abnormalities, and endocrine and metabolic disorders. EDCs can be detected in body fluids of exposed individuals including blood and urine. This study aimed to detect four EDCs - Methyl Paraben (MP), 2,4-Dichlorophenoxyacetic acid (2,4-D), Monobutyl Phthalate (MBP), and Bisphenol A (BPA) in urine samples of women using Ultra-Performance Liquid Chromatography - Quadrupole Time-of-Flight (UPLC-QTOF) mass spectrometry.

Sequential steps of enzymatic deconjugation, liquid-liquid extraction, solid phase extraction, and liquid chromatography separation and mass spectrometry detection were optimized in urine samples. The method was used to analyze 70 urine samples from women of reproductive age.

The sample preparation method showed a recovery ranging from 86.6% (MBP) to 100 % (2,4-D). The method demonstrated limits of quantitation ranging from 1.52 ng/m(MP) to 6.46 ng/mL(2,4D). Intra-day precisions expressed as relative standard deviation were all below 15% while accuracy was shown to range from 67.10% (2,4-D) to 102.39% (MBP). MP was detected in nine samples (12.86%) with a geometric mean value of 10.15 ng/ml (range: 3.62-52.39 ng/ml). MBP was detected in 68 samples (97.14%) with a geometric mean value of 97.62 ng/ml (range: 15.32-698.18 ng/ml). BPA was detected only once (9.58 ng/ml) while 2, 4-D was not detected in all samples.

A UPLC-QTOF mass spectrometry method to detect four EDCs at parts per billion level (ng/ml) was adapted and applied for analysis of urine samples. This method can find applicability in routine testing of clinical specimens as well as surveillance and other epidemiological studies.

Bisphenol A (BPA) is a pollutant that has gained the attention of scientists globally because of its ubiquity in environmental matrices as well as its toxicity in the environment. It is listed as a priority pollutant in South Africa, capable of health risk impacts, which, according to the European Union, should not exceed 2.5 μg/L in water. In South Africa, historical data on its environmental occurrence is sparingly available, although research on BPA and other endocrine disruptors is currently gaining momentum. Surface, ground, and wastewater constitute the major proportion of the water sources that are prone to contamination by emerging pollutants such as BPA. In order to gain a holistic perspective of this chemical, a detailed review was carried out using over five hundred peer-reviewed articles that investigated the occurrence of BPA in South African aquatic systems. This study shows that Gauteng and Western Cape are the Provinces with the highest reported number of BPA occurrences in water. The data also shows that surface water constitutes 41% of all BPA articles while matrices like ponds and lagoons have no recorded studies. Its presence was attributed to anthropogenic activities such as the generation of domestic, agricultural, and industrial waste. Local application of removal techniques such as adsorption and photocatalysis on laboratory and field samples has shown good prospects (especially photocatalysis) in mitigating current challenges related to the occurrence of BPA. However, there is room for more innovative initiatives. Although there is a ban on the use of BPA for making baby bottles, additional regulations can be put in place regarding the use of BPA in making plastics or other packaging materials from which BPA can leach.

Early-life exposure to short half-life chemicals may influence adiposity growth, a precursor to obesity. Previous studies often relied on limited urine samples that inadequately represent exposure during pregnancy or infancy. Additionally, childhood adiposity is commonly estimated using body mass index, which does not accurately reflect body composition. We aimed to investigate associations between early-life exposures to phenols, parabens, phthalates and fat mass percent at 3 years of age among 341 mother-child couple from the SEPAGES cohort. We further assessed potential effect modification by sex.

We measured 8 phenols, 4 parabens, 13 phthalates and 2 non-phthalate plasticizer metabolites from weekly pooled urine sample collected from mothers during pregnancy (three urine samples a day, median 18 and 34 gestational weeks), and from their infant (one urine sample a day, at 2 and 12 months). Clinical examinations at 3 years included standardized skinfold thickness measurements and bioelectrical impedance analysis to calculate fat mass percentage.

Positive associations were identified between prenatal exposures to bisphenol S, mono-benzyl phthalate (MBzP), monoethyl phthalate (MEP), and mono-n-butyl phthalate and fat mass percentage at 3 years, while triclosan showed a negative association. MBzP and MEP showed effect modification by sex, with stronger associations among females. No significant associations were detected for postnatal exposures.

This study suggests associations between prenatal exposures to short half-life chemicals and percent fat mass in preschool children. Furthermore, this study is the first investigating the impact of prenatal bisphenol S exposure, highlighting the need for investigation of this overlooked compound.

Bisphenol F (BPF) is an environmental endocrine disruptor capable of crossing the placental barrier and affecting the growth and development of offspring. Despite its potential impact, systematic research about effects of BPF on the reproductive function of male offspring remains limited. In this study, pregnant female mice were exposed to BPF at doses of 40, 400, and 4000 μg/kg during gestation and lactation, respectively, to evaluate its impact on testicular damage, testosterone levels, and spermatogenesis of male offspring (F1 generation), and further explore the mechanisms using transcriptomics. First, the study demonstrated that BPF induces testicular damage in F1 generation mice, leading to decreased testosterone levels and sperm quality. Second, transcriptomic analysis revealed that BPF affected spermatogenesis in F1 generation mice by disrupting retinol metabolism. Third, transcriptomic analysis revealed that BPF reduce the capacity for testosterone synthesis in F1 generation mice by diverting the testosterone precursor dehydroepiandrosterone (DHEA) towards the synthesis of 16α-hydroxydehydroepiandrosterone rather than testosterone. Finally, it was confirmed that BPF hinder cholesterol transport to mitochondria by inhibiting the cAMP signaling pathway, thereby impacting testosterone synthesis. In summary, the results of this study suggest that gestational exposure to BPF can lead to reproductive dysfunction in F1 generation male mice.

Exposures to endocrine disrupting chemicals (EDCs) in early life have demonstrable adverse implications on child health and development. Yet, there is a dearth of studies evaluating the potential exposures to EDCs, such as bisphenols, parabens, phthalates, and volatile organic compounds (VOCs), in hospital-based settings among children who are critically ill and/or particularly vulnerable. This narrative review seeks to provide up-to-date evidence on the sources and magnitude of exposure to EDCs in neonatal-, pediatric-, and cardiac intensive care units (NICUs/PICUs/CICUs) as well as resulting health impacts.

Thirty-three studies were included in this review. The most frequently studied and characterized EDCs in NICUs/PICUs/CICUs were phthalates followed by terephthalates and alternative plasticizers. Evaluations of health outcomes resulting from such exposures were scarce, and few studies assessed health outcomes after hospital discharge. EDCs are pervasive in NICU/PICU/CICU settings and pediatric exposure levels are much higher than in other environments. However, the existing evidence has multiple limitations that should be addressed in future work. Specifically, studies evaluating a more expansive array of chemicals, including contemporary and emerging replacements for legacy compounds, are needed, as are studies that consider chemical mixtures. Additionally, few studies evaluated the health impacts of chemical exposures, and their mixtures, in NICU/PICU/CICU settings, especially long-term health outcomes observed after hospital discharge. Such studies could be invaluable in supporting policy as well as development of medical products without toxic chemicals.

Infertility affects 8-12% of couples worldwide, and 30-75% of preclinical pregnancy losses are due to a failure during the implantation process. Exposure to endocrine disruptors, like bisphenols, among others, has been associated with the increase in infertility observed in the past decades. An increase in infertility has correlated with exposure to endocrine disruptors like bisphenols. The uterus harbors its own microbiota, and changes in this microbiota have been linked to several gynecological conditions, including reproductive failure. There are no studies on the effects of bisphenols on the uterine-microbiota composition, but some inferences can be gleaned by looking at the gut. Bisphenols can alter the gut microbiota, and the molecular mechanism by which gut microbiota regulates intestinal permeability involves Toll-like receptors (TLRs) and tight junction (TJ) proteins. TJs participate in embryo implantation in the uterus, but bisphenol exposure disrupts the expression and localization of TJ proteins. The aim of this review is to summarize the current knowledge on the microbiota of the female reproductive tract (FRT), its association with different reproductive diseases-particularly reproductive failure-the effects of bisphenols on microbiota composition and reproductive health, and the molecular mechanisms regulating uterine-microbiota interactions crucial for embryo implantation. This review also highlights existing knowledge gaps and outlines research needs for future risk assessments regarding the effects of bisphenols on reproduction.

Bisphenol A (BPA) is an organic synthetic chemical used worldwide. Billions of pounds of BPA are produced annually through industrial processes to be used in commercial products, making human exposure to BPA ubiquitous. Concerns have been raised due to the potential adverse health effects of BPA, specifically in vulnerable populations, such as pregnant persons and children. BPA is an endocrine-disrupting chemical, and through this function has been linked to reproductive toxicity. We review BPA's historical and current use, health and safety concerns and regulations, sources of exposure, and evidence for male and female reproductive toxicity. Evidence from epidemiological and animal studies idenfity that low- and high-exposure levels of BPA (prenatal, postnatal and adulthood exposure) can adversely affect male and female fertility and reproductive organs. While the cause of BPA-induced reproductive toxicity is not fully understood, we discuss BPA's estrogenic and androgenic activity, and its ability to disrupt the hypothalamic-pituitary-gonadal axis as a potential associated mechanism. There are significant differences in tolerable daily intakes of BPA set by global agencies, making interpretation of previous and emerging research findings challenging and inconsistent. Although BPA is deemed toxic by some government agencies, most do not currently consider it a health risk due to low populational exposure levels. However, we highlight evidence that even at acute, low exposure, BPA can adversely affect reproductive function. We recommend continuing research into the adverse effects of BPA on human health and revisiting the regulatory measures of BPA to limit exposure and promote public awareness of its potential to cause reproductive toxicity.