Bisphenol P Research Articles

Cytotoxic impacts of seven alternative bisphenols on human in vitro cellular models

Bisphenols (BPs), common in plastics, coatings, and resins, are under scrutiny for potential endocrine disruption. Despite banning bisphenol A (BPA), its perceived safer alternatives may still pose health risks, urging thorough studies on their toxicity mechanisms. This study aimed to investigate the cellular toxicity of the top seven most commonly used BPs, bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol P (BPP), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol E (BPE) in eight different relevant human in vitro cell models: liver (HepaRG), intestinal (Caco-2), breast (T47D), brain (HMC-3), lungs (MRC-5), kidney (HEK293), endothelial (HMEC-1), and skin (HEK-001) cell lines. BPE manifested the highest cytotoxicity in Caco-2 cells, presenting an EC50 value of roughly 0.2 μM (95% confidence interval). In contrast, HEK293 and HepaRG cells demonstrated significant resilience to BPS (EC50 > 1000 μM). BPAF, BPP, and BPAP had consistently low EC50 values across cell lines (6–27.9 μM, 0.6–134.7 μM, and 3.6–178.8 μM), indicating elevated toxicity. After 24 h, all bisphenols adhered to nominal concentrations except BPAF, BPP, and BPS. BPP's concentration notably decreased (30.82 ± 5.53% of nominal value). The results revealed diverse effects of bisphenol analogs on different cell types. These findings emphasized the considerable cytotoxic potential of specific bisphenol analogs across various human cell models, underlining the necessity for a re-evaluation of their safety and regulatory standards.

Parabens, bisphenols, and triclosan in coral polyps, algae, and sediments from sanya, China: Occurrence, profiles, and environmental implications

Parabens, bisphenols (BPs), and triclosan (TCS) are common environmental phenols widely applied in industrial products, pharmaceuticals, and personal care products. They are endocrine disruptors and pervade the natural environment, causing significant detrimental impacts on ecosystems, including marine habitats. Therefore, in this study, 40 samples comprising coral polyps, algae, and sediments were collected from Sanya, Hainan Province, China, in which the presence and compositional profiles of parabens, BPs, and TCS were examined to identify their fate in the oceans. The results unveiled the ubiquitous occurrence of at least one paraben or bisphenol in all samples, with TCS detected in over 80% of cases. Notably, coral samples contained the most contaminants (median concentration: 9.42 ng/g dry weight-dw), followed by sediment samples (5.95 ng/g dw) and algal samples (3.58 ng/g dw). Attributed to their broadest application, methylparaben (MeP) and propylparaben (PrP) emerged as the primary paraben constituents. MeP displayed the highest median concentration in coral samples (4.42 ng/g dw), probably related to its high-water solubility and the filtration mechanism employed by the coral polyps during seawater intake. Intriguingly, bisphenol P (BPP) superseded bisphenol A (BPA) as the dominant bisphenol, especially in the algal samples, probably owing to the lipophilic character of BPP and the enhanced biodegradability of BPA within aquatic environments. The highest concentration of TCS (3.44 ng/g dw) was found in the sediment samples, associated with its long half-life in the sediments. Furthermore, the correlation between multiple parabens and TCS implies their co-use to augment antimicrobial efficacy. Future research should prioritize the examination of these phenols in diverse marine environmental media. Corresponding toxicological experiments should be conducted to visualize their transport dynamics, degradation byproducts, and toxicity to marine biota to gain insights into the risks they pose to the marine ecosystem.

Associations of Bisphenols Exposure and Hyperuricemia Based on Human Investigation and Animal Experiments.

Hyperuricemia is characterized by elevated blood uric acid (UA) levels, which can lead to certain diseases. Epidemiological studies have explored the association between environmental contaminant exposure and hyperuricemia. However, few studies have investigated the role of chemical exposure in the development of hyperuricemia. Here, we sought to investigate the effects of bisphenol exposure on the occurrence of hyperuricemia. Fifteen bisphenol chemicals (BPs) were detected in human serum and urine samples collected from an area with a high incidence of hyperuricemia in China. Serum UA levels positively correlated with urinary bisphenol S (BPS), urinary bisphenol P (BPP), and serum bisphenol F (BPF). The effects of these three chemicals on UA levels in mice were explored at various exposure concentrations. An increase in serum UA levels was observed in BPS- and BPP-exposed mice. The results showed that BPS exposure increased serum UA levels by damaging the structure of the kidneys, whereas BPP exposure increased serum UA levels by disturbing purine metabolism in the liver. Moreover, BPF did not induce an increase in serum UA levels owing to the inhibition of guanine conversion to UA. In summary, we provide evidence of the mechanisms whereby exposure to three BPs disturbs UA homeostasis. These findings provide new insights into the risks of exposure to bisphenol chemicals.

Bisphenols in Aquatic Products from South China: Implications for Human Exposure.

In this study, 245 representative samples of aquatic products were selected from local markets in Shenzhen by stochastic sampling. The samples comprised eight species and fell into three aquatic product categories: fish, crustaceans, and bivalves. A total of eight BPs were determined by liquid chromatography coupled with mass spectrometry, namely, bisphenol A (BPA), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol S (BPS), bisphenol P (BPP), bisphenol Z (BPZ), and bisphenol F (BPF). All BPs were detected in aquatic products, except for BPAF, indicating pervasive contamination by BPs in aquatic products. BPS demonstrated the highest detection rate both before and after enzymatic hydrolysis, whereas BPAP exhibited the lowest detection rate before enzymatic hydrolysis and BPB displayed the lowest detection rate after enzymatic hydrolysis. The concentration difference before and after enzymatic hydrolysis proved to be statistically significant. Moreover, 49-96% of BPs in aquatic products were found in the combined state, underscoring the essentiality of conducting detections on aquatic product samples following enzymatic hydrolysis. While the health risks associated with ingesting BPs residues through aquatic product consumption were found to be minimal for residents at risk of exposure, the results suggest the necessity for more stringent regulations governing the consumption of aquatic products.

A biochemical and histological evaluation of in vivo exposure of bisphenol P for multi-organ toxicity and pathology in rats.

Bisphenol P (BPP) is a structural analog of bisphenol A (BPA) and is increasingly used as a substitute of BPA in commercial and household applications. In recent years, BPP has been frequently detected in terrestrial and aquatic ecosystems. Very little epidemiological and experimental information are available on the toxicity potential of BPP in human and animal systems, which is very concerning in view of its increasing use. The current study evaluated the biochemical and histopathological effects of BPP in rats. The seven experimental groups (n = 5 rats/group) included BPA5 (5mg), BPA50 (50mg), BPA100 (100mg), BPP5 (5mg), BPP50 (50mg), and BPP100 (100mg) while the remaining one group served as untreated control. At the end of treatment, the organs (liver, kidney, heart, and lung) of rats were harvested for oxidative stress and histopathological analyses. A significant (p < .05) decrease was observed in the weight of the liver, lungs, and kidneys in the BPP100 group similar to the BPA100 group compared with the control group. Further, a significant (p < .05) decrease was also observed for concentrations of antioxidant enzymes (catalase, peroxidase, superoxide dismutase, and glutathione peroxidase) in the liver, lungs, kidneys, and heart at the highest two doses of BPP similar to the respective BPA groups compared with the control group. The two highest doses of BPP induced histopathological changes in the liver such as nuclei distortion, excessive necrosis of hepatocytes, nuclei shrinkage and pyknosis of cells with disrupted cell structure (BPP100), and cellular congestion and degeneration of hepatocytes (BPP50) similar to the two respective doses of BPA. The BPP treated groups also showed varying histopathological changes in kidney tissue, heart tissue, and lung tissue similar to BPA treated rats. In conclusion, the present study indicated that BPP has the potential to induce oxidative stress and alter the histomorphological architecture of different organs and is as deleterious as BPA.

Alternatives Exert Higher Health Risks than Bisphenol A on Indo-Pacific Humpback Dolphins.

The detrimental effects of bisphenol (BP) exposure are a concern for vulnerable species, Indo-Pacific humpback dolphins (Sousa chinensis). To investigate the characteristics of BP profiles and their adverse impact on humpback dolphins, we assessed the concentrations of six BPs, including bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol P (BPP) in blubber (n = 26) and kidney (n = 12) of humpback dolphins stranded in the Pearl River Estuary, China. BPS accounted for the largest proportion of the total bisphenols (∑BPs) in blubber (55%) and kidney (69%). The concentration of ∑BP in blubber was significantly higher than that in the kidney and liver. The EC50 values of five BPA alternatives were lower than those of BPA in humpback dolphin skin fibroblasts (ScSF) and human skin fibroblasts (HSF). ScSF was more sensitive to BPS, BPAF, BPB, and BPP than HSF. The enrichment pathway of BPA was found to be associated with inflammation and immune dysregulation, while BPP and BPS demonstrated a preference for genotoxicity. BPA, BPP, and BPS, which had risk quotients (RQs) > 1, were found to contribute to subhealth and chronic disease in humpback dolphins. According to the EC50-based risk assessment, BPS poses a higher health risk than BPA for humpback dolphins. This study successfully evaluated the risks of bisphenols in rare and endangered cetacean cell lines using a noninvasive method. More in vivo and in field observations are necessary to know whether the BPA alternatives are likely to be regrettable substitutions.

Levels of organic pollutants and metals/metalloids in infant formula marketed in Brazil: Risks to early-life health

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI – 3.57 and 0.36 μg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Association of urinary bisphenols with thyroid function in the general population: a cross-sectional study of an industrial park in China.

Bisphenols (BPs) are potential thyroid disruptors that are widely used in many consumer products, leading to their widespread exposure in the general population. Current cross-sectional and case-control studies have found associations between exposure to BPs and serum thyroid function, but the results were contradictory. The objectives of this study are to describe demographic characteristics, BP exposure levels, and thyroid function measurements in potentially exposed and control districts and to investigate the association of urinary BPs with thyroid function. Data were collected from a general population aged 3-79 years (N = 281) recruited by the Zhejiang Human Biomonitoring Program (ZJHBP). The concentrations of 10 kinds of BPs in urine and serum free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyrotropin receptor antibody (TRAb) in serum were measured. Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the relationship between single and mixed exposure of BPs and thyroid function. Bisphenol A (BPA), bisphenol S (BPS), and bisphenol P (BPP) were detected, respectively, in 82.73%, 94.24%, and 55.40% of the population in the exposed area and 81.69%, 61.27%, and 43.66% of the population in the control area. Among adult females, serum TT3 was negatively associated with urinary BPA (β = -0.033, 95% CI = -0.071, -0.008, P = 0.021). Among minor females, FT4 and Tg levels were negatively associated with the urinary BPA (β = -0.026, 95% CI = -0.051, -0.002, P = 0.032 for FT4; β = -0.129, 95% CI = -0.248, -0.009, P = 0.035 for Tg), and TPOAb was positively associated with urinary BPA (β = 0.104, 95% CI = 0.006, 0.203, P = 0.039). In WQS models, BPs mixture was positively associated with FT3 (βWQS = 0.022, 95% CI = 0.002, 0.042) and TT3 (βWQS = 0.033, 95% CI = 0.004, 0.062), and negatively associated with FT4 (βWQS = -0.024, 95% CI = -0.044, 0.004). We found widespread exposure to BPA, BPS, and BPP in the general population of Zhejiang province and found an association between BPA and thyroid hormones. This association is gender- and age-dependent and needs to be confirmed in further studies.

Associations of exposure to bisphenol A and its substitutes with neurodevelopmental outcomes among infants at 12 months of age: A cross-sectional study

BackgroundBisphenol A (BPA) exposure has been linked to adverse childhood neurodevelopment, but little is known about whether BPA substitutes exposures are also related to childhood neurodevelopment. ObjectivesTo investigate the associations of exposure to BPA and its substitutes with infant neurodevelopment at 12 months. MethodsA total of 420 infants at 12 months were included from the Laizhou Wan (Bay) Birth Cohort in Shandong, China. Urinary concentrations of BPA and its substitutes including bisphenol S (BPS), bisphenol B (BPB), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol P (BPP) and bisphenol Z (BPZ) were measured. Developmental quotient (DQ) scores based on the Gesell Development Schedules (GDS) were used to evaluate infant neurodevelopment. The multivariable linear regression and weighted quantile sum (WQS) regression were applied to estimate the associations of exposure to individual bisphenols and their mixtures with DQ scores, respectively. Sex-stratified analyses were also performed. ResultsBPA was detected in most infants (89.05%) and had the highest median concentration (0.709 ng/mL) among all bisphenols. BPA substitutes except BPZ were ubiquitous in infants’ urine samples (>70%), and BPS showed the highest median concentration (0.064 ng/mL) followed by BPAP (0.036 ng/mL), BPAF (0.028 ng/mL), BPP (0.015 ng/mL) and BPB (0.013 ng/mL). In multivariable linear regression, only BPAF exposure was inversely associated with social DQ scores among all infants (β = −0.334; 95% CI: −0.650, −0.019). After sex stratification, this inverse association was significant in girls (β = −0.605; 95% CI: −1.030, −0.180). Besides, BPA exposure was negatively related to gross motor DQ scores in boys (β = −1.061; 95% CI: −2.078, −0.045). WQS analyses confirmed these results. ConclusionsOur study suggests that bisphenol exposure during infancy may be associated with poor infant neurodevelopment, and BPAF as a commonly used BPA substitute contributing the most to this adverse association deserves more attention.

Association of parabens and bisphenols with lung function in children aged 5-12 years from Shanghai, China.

Epidemiological studies have reported potential effects of individual paraben or bisphenol exposure on lung function, but few studies have estimated their joint effects. We conducted a cross sectional survey to investigate the associations of parabens and bisphenols exposure with lung function in 205 children aged 5-12 years from Shanghai, China. Urinary concentrations of six parabens [methyl-, ethyl-, propyl-, butyl-, benzyl-, and heptyl-paraben (MeP, EtP, PrP, BuP, BzP, and HeP)] and seven bisphenols [bisphenol A (BPA), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol P (BPP), bisphenol S (BPS), and bisphenol Z (BPZ)] were assessed by the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Lung function, including forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), was further measured. Linear regression, bayesian kernel machine regression (BKMR), and weighted quantile sum regression (WQS) evaluated the individual and joint relationships of the parabens and bisphenols with the lung function parameters. Further, the analysis was stratified by child sex. Parabens (MeP, EtP, PrP, and BuP) and bisphenols (BPA, BPAP, BPB, and BPS) with detection rates >75% were included for analyses. In linear regressions, parabens (MeP, PrP, and BuP) were generally negatively associated with FEV1, FVC, PEF, and FEF25-75%, but no associations for bisphenols were found. The association of parabens with lung function was more pronounced in girls. The aforementioned negative associations between parabens and lung function were confirmed by both the BKMR and WQS, with MeP being considered most heavily weighing chemical. Our findings suggested that exposure to parabens, either individuals or as a mixture, were associated with decreased lung function in children aged 5-12 years, and these associations were stronger among girls. Considering the cross-sectional study design, large longitudinal studies are warranted to confirm our findings.

Bisphenol P and bisphenol M promote triple-negative breast cancer metastasis through activation of AKT pathways

Bisphenol P (BPP) and bisphenol M (BPM) are increasing in our living environment as analogues of bisphenol A (BPA), but little is known about their biological effect. In this study, we investigated the effects of low to medium dose exposure of BPP and BPM on triple negative breast cancer (TNBC). We found that BPP and BPM exposure didn't affect proliferation of TNBC cell lines MDA-MB-231 and 4 T1, but significantly promoted cells migration and invasion. The effect of BPP and BPM on promoting TNBC metastasis was further confirmed in mouse models. Low concentrations of BPP and BPM significantly increased the expression of epithelial-mesenchymal transition (EMT) marker and related proteins such as N-cadherin, MMP-9, MMP-2 and Snail, and also enhanced phosphorylation of AKT both in vitro and in vivo. When PI3K inhibitor wortmannin was applied to specifically inhibit phosphorylation of AKT, the expression of target genes markedly decreased, and the TNBC metastasis induced by low-concentration BPP and BPM were reversed. In conclusion, these results showed that PI3K/AKT signaling regulate BPP/BPM-induced metastasis of TNBC by triggering EMT. This study provides insights into the effects and the potential mechanisms of BPP and BPM on TNBC, raising concerns about the risk of using these two bisphenols as the alternative of BPA.

Bisphenol A substitutes and childhood obesity at 7years: a cross-sectional study in Shandong, China.

Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010-2013 participated in the 2019-2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75%) in children's urine samples. A positive association with obesity measures was consistently observed for urinary BPS and BPAF, i.e., BMI z-score, waist circumference, and overweight/obesity. Further analysis from the WQS regression model demonstrated a positive association between bisphenol mixtures and all measures of obesity, with BPAF contributing the greatest weighing to the observed associations. Sex difference might exist as the positive associations were only significant in boys. No significant association was found between obesity and BPA or other BPA substitutes. Our study adds to mounting evidence that BPA substitutes BPS and BPAF are linked to obesity in children, especially in boys. Further longitudinal studies with larger sample size with continued biomonitoring these chemicals and their obesogenic effects are necessary.

Bisphenol P exposure in C57BL/6 mice caused gut microbiota dysbiosis and induced intestinal barrier disruption via LPS/TLR4/NF-κB signaling pathway

Despite being one of the most world's widely used and mass-produced compounds, bisphenol A (BPA) has a wide range of toxic effects. Bisphenol P (BPP), an alternative to BPA, has been detected in many foods. The effects of BPP dietary exposure on gut microbiota and the intestinal barrier were unclear. We designed three batches of animal experiments: The first studied mice were exposed to BPP (30 µg/kg BW/day) for nine weeks and found that they gained weight and developed dysbiosis of the gut microbiota. The second, using typical human exposure levels (L, 0.3 µg/kg BW/day BPP) and higher concentrations (M, 30 µg/kg BW/day BPP; H, 3000 µg/kg BW/day BPP), caused gut microbiota dysbiosis in mice, activated the Lipopolysaccharide (LPS) /TLR4/NF-κB signaling pathway, triggered an inflammatory response, increased intestinal permeability, and promoted bacterial translocation leading to intestinal barrier disruption. The third treatment used a combination of antibiotics and alleviated intestinal inflammation and injury. This study demonstrated the mechanism of injury and concentration effects of intestinal damage caused by BPP exposure, providing reference data for BPP use and control and yielding new insights for human disease prevention.

Obesogenic effect of Bisphenol P on mice via altering the metabolic pathways

Bisphenol P (BPP), structurally similar to bisphenol A, is commonly identified in the samples of environment, food, and humans. Unfortunately, very little information is currently available on adverse effects of BPP. The obesogenic effects and underlying mechanisms of BPP on mice were investigated in this study. Compared with the control, high-resolution microcomputed tomography (micro-CT) scans displayed that the visceral fat volume of mice was significantly increased at a dose of 5 mg/kg/day after BPP exposure for 14 days, whereas the subcutaneous fat volume remained unchanged. Nontargeted metabolomic analysis revealed that BPP significantly perturbed the metabolic pathways of mouse livers, and acetyl-CoA was identified as the potential key metabolite responsible for the visceral fat induced by BPP. These findings recommend that a great deal of attention should be paid to the obesogenic properties of BPP as a result of its widely utilized and persistence in the environment.

Antagonistic mechanisms of bisphenol analogues on the estrogen receptor α in zebrafish embryos: Experimental and computational studies

Bisphenol A (BPA) can disturb the estrogen receptor α (ERα)-mediated signaling pathway, which results in endocrine-disrupting effects and reproductive toxicity. Most BPA analogues as alternatives were evidenced to generate estrogenic activity as agonists or partial agonists of ERα. Recent studies indicated that certain BPA analogues, such as bisphenol M (BPM), bisphenol P (BPP), and bisphenol FL (BPFL), exhibited strong anti-estrogenic effects comparable with the typical antagonist 4-hydroxytamoxifen. However, conflicting findings were also observed for the compounds in different in vitro assays, and whether these BPA analogues can elicit an in vivo effect on ERα at environmentally relevant concentrations remains unknown. The underlying structural basis of estrogenic/anti-estrogenic activity should be further elucidated at the atomic level. To address these issues, we combined zebrafish-based in vivo and in silico methods to assess the effects of the compounds on ERα. The results show that the expressions of ERα-mediated downstream related genes in zebrafish embryos decreased after exposed to the compounds. Further molecular dynamics simulations were used to probe the antagonistic mechanisms of the compounds on ERα. The key H-bonding interactions were identified as important ligand recognition by ERα in the analysis of binding modes and binding free energy calculations. In summary, the current study provides preliminary in vivo evidence of fish species for the anti-estrogenic activity of certain BPA analogues.

Exposure to bisphenol A and its analogs and polycystic ovarian syndrome in women of childbearing age: A multicenter case-control study

Background/objectivesIn recent years, the reproductive toxicity of new bisphenol analogs has garnered much interest, but it remains to be determined whether bisphenol analogs affect polycystic ovarian syndrome (PCOS). MethodsThis study utilized data from a multicenter hospital-based case-control study conducted in 2014–2016 to examine the association between endocrine-disrupting chemicals and infertility in China. 321 PCOS cases and 412 controls were included in the current analysis. We quantified seven bisphenol analogs in urine samples, including bisphenol A (BPA), bisphenol AP (BPAP), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol S (BPS), bisphenol P (BPP), and bisphenol Z (BPZ). Spearman correlation and generalized linear regression were used in assessing the relationship between bisphenol analogs and hormonal parameters. To examine the association of bisphenol analogs with odds of PCOS, multiple logistic regression, and two multi-pollutant models [quantile-based g-computation (QGC) and extreme gradient boosting (XGBoost) methods] were used. ResultsAfter covariates adjustment, BPA, BPS, and BPAF were positively correlated with testosterone (T) in the control group (P < 0.05). Dose-response relationships were discovered between BPA, BPS, BPZ, and BPAF quartiles and PCOS. Mixed exposure to seven bisphenol analogs was found to be positively associated with the odds of PCOS (adjusted odds ratio = 1.26; 1.12–1.45), which was primarily driven by BPS (weight = 0.51), BPZ (weight = 0.26), and BPAF (weight = 0.23). Women who were overweight or obese tended to have a stronger association between bisphenol analogs and PCOS than normal-weight women. ConclusionsEnvironmental exposure to bisphenol analogs was associated with increased odds of PCOS in this case-control study. This association was stronger among obese and overweight women.

Cross-Generational Impacts of Diet Shift on Bisphenol Analogue Loads in Indo-Pacific Humpback Dolphins (Sousa chinensis).

Bisphenol analogues (BPs) are ubiquitous pollutants to marine organisms as endocrine disruptive chemicals. However, the residue contamination and the trophic transfer of BPs in the apex predator nearshore dolphins are poorly studied. Here, we measured the concentrations of six BPs, including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol F (BPF), bisphenol P (BPP), and bisphenol S (BPS) in the liver of Indo-Pacific humpback dolphin (Sousa chinensis) (n = 75) collected from the Pearl River Estuary during a period with significant dietary changes (2004-2020). BPA and BPAF were the dominant components of the residue ∑BPs in the liver, with a proportion of 80%. Sex, maturity, and stranding location had no significant effects on BP levels. The generalized additive models indicated that BPA levels in juveniles and adults decreased from 2004 to 2013 while increasing from 2013 to 2020. The temporal trend of BPA levels was likely driven by the shift of the dominant diet from Harpadon nehereus to Thryssa spp. The concurrent increase of BPA loads in calves and juveniles and adults over the recent decades suggested that the diet-mediated variations of maternal BPA levels could be redistributed to their offspring.

Cytotoxicity, redox and immune status in African catfish, Clarias gariepinus (Burchell, 1822) exposed to bisphenol A (BPA) and its analogues.

The objective of the study was to determine the comparative toxicities and immune dysfunction in the African catfish, Clarias gariepinus, exposed to bisphenol A (BPA) and its two analogues: bisphenol AP (BPAP) and bisphenol P (BPP). Juveniles of C. gariepinus were exposed to sublethal concentrations (70 and 140 μg/L) of BPA, BPAP and BPP for 7, 14 or 21 days after which various endpoints which are indicative of cytotoxicity, oxidative stress and haematological and innate immune parameters were determined in the liver homogenates or blood plasma. The exposure of C. gariepinus to BPA and its analogues caused significant increased activities of lactate dehydrogenase, catalase and superoxide dismutase. The exposed fish had increased levels of DNA fragmentation, lipid peroxidation, white blood cells, nitric oxide and respiratory burst, while the red blood cell counts and the percentage packed cell volume decreased significantly in the exposed fish compared to control. The toxic effects elicited by the bisphenols were both concentration- and duration-dependent. Generally, BPA exerted the most toxic effects on the fish, followed by BPAP, while BPP exerted the least toxic effects to C. gariepinus. Summarily, the findings indicated that BPA and its two analogues studied in the research are capable of causing cytotoxicity, oxidative stress and immune dysfunction in C. gariepinus.

New method for the determination of endocrine disrupting chemicals in Mediterranean mussel (Mytilus galloprovincialis) using ultra-high performance liquid chromatography–tandem mass spectrometry

There are numerous types of contaminants that pose a health risk to aquatic organisms and consequently also to humans through consumption. Endocrine disrupting compounds are found in daily-use products and have the potential to mimic natural hormones. The main objective of this work is to optimize and validate a method for the determination of bisphenols, parabens and triclocarban in natural samples of Mediterranean mussel (Mytilus galloprovincialis). The procedure involves ultrasound-assisted extraction (UAE), and a subsequent clean-up of the extracts using dispersive solid phase extraction (d-SPE) with C18 adsorbent, and analysis by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sensitivity, accuracy (trueness and precision), linearity and selectivity of the method were studied. The limits of detection ranged from 0.2 ng g−1 to 1.5 ng g−1 dry weight. The trueness of the method (estimation of recovery) was between 90 % for TCC (triclocarban) and 109.6 % for BPP (bisphenol P), with an estimated precision lower than 12.6 % for all the investigated analytes. The application of the method was to specimens of Mytilus galloprovincialis collected along the Mediterranean coast of Granada (South Spain), where the species is abundant. The study conducted in different sample sites revealed EDCs presence in this aquatic species.

A mutispectroscopic study on the structure–affinity relationship of the interactions of bisphenol analogues with bovine serum albumin

Bisphenol A (BPA) is a recognized endocrine-disrupting chemical (EDC), and its analogues also exert negative effects on health. The structure–affinity relationship between the structures of nine bisphenol (BP) analogues and the conformational changes of bovine serum albumin (BSA) was studied by various characterization methods and molecular docking. BPs including BPA and its analogues, bisphenol B (BPB), bisphenol C (BPC), bisphenol AP (BPAP), bisphenol M (BPM), bisphenol P (BPP), bisphenol Z (BPZ), diethylstilbestrol (DES) and dienestrol (DS) interacted with BSA. At the concentration of 3.85 × 10−5 mol l−1, DS was found to lead to 64% quenching, while BPAP, BPM and DES quenched 60%, 59% and 55% of BSA fluorescence, respectively. The values of ΔH (−19.31–135.42 kJ mol−1) and ΔS (12.52–495.63 J mol−1 K−1) indicated that hydrophobic interactions and hydrogen bonds played important roles in the binding process. The binding constants of DS (8.87 × 104 l mol−1), DES (3.05 × 104 l mol−1), BPAP (1.52 × 104 l mol−1), BPC (1.16 × 104 l mol−1) and BPM (1.10 × 104 l mol−1) to BSA were greater than that of BPA (1.18 × 103 l mol−1) to BSA, indicating that they may exert more negative effects than BPA. The molecular structure differences of these BPs partly affected their ability to bind to BSA. The binding constants of BPB/BPP to BSA were smaller due to the steric hindrance of ethyl and benzene ring. BPs with conjugated double bond structures (DS and DES) and benzene ring structures (BPM, BPP, BPAP) had a greater influence on the conformation of BSA.