Objective: Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured ...unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women. Methods: Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography-mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered ³H-BPA at doses ranging from 2 to 100,000 μg/kg. Results: In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice. Conclusions: BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.
It is already known that bisphenol S (BPS) has been used as a substitute for BPA in thermal papers in recent years. It is not clear, however, if BPS has also been used to replace BPA in can coatings ...as currently being speculated due to a lack of credible studies on migration of BPS from can coatings and occurrence data of BPS in foods. In this study, an LC-MS/MS method was developed for the analysis of BPS, along with several other bisphenols, and method detection limits for BPS varied from 0.0017 to 3.1 ng/g depending on the type of sample matrix and the amount of sample analysed. This method was used to analyse 159 different food composite samples from a recent Canadian total diet study. Bisphenol E (BPE), bisphenol B (BPB), and bisphenol AF (BPAF) were not detected in any of the 159 food composite samples, bisphenol F (BPF) was detected in only three samples (25-2360 ng/g), and bisphenol A (BPA) was detected in 10 samples (5.3-41 ng/g) which were all prepared from canned foods. BPS was not detected in any of the canned food composite samples but was detected in nine food composite samples prepared from meat and meat products (1.2-35 ng/g), indicating sources for BPS other than can coatings may be possible, which will be investigated in future studies.
Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results ...have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25–9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03–7.67) in comparison with girls with a BMI lower than 25 kg/m2. Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.
Objective: We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of ...several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices. Measurements: We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben. Results: The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of use of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001). Conclusion: BPA geometric mean urinary concentration (30.3 μg/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA.
Although the increasing prevalence of thyroid nodular disease (TND) has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to ...thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (ClxBPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter >3mm), and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and ClxBPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression. Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%), the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified.
The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in ...Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 μg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose-response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease.
Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption.
We compared the percutaneous absorption and biotransformation of ...BPS and BPA in vitro and in a controlled human trial.
Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0-48 h) and serum (0-7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA (Formula: see text) in the same participants.
At doses of 1.5 and Formula: see text applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and Formula: see text, respectively) was significantly lower than for BPA (0.036 and Formula: see text, respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and Formula: see text on hands was significantly correlated with maximum urinary event flux (Formula: see text), but the slope was lower for BPS than BPA (Formula: see text and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS Formula: see text: Formula: see text was higher than for free BPA (Formula: see text). Postexposure maximum urinary BPS concentrations (0.93 to Formula: see text; Formula: see text) were in the 93-98th percentile range of BPS in background Canadians (Formula: see text; Formula: see text).
Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044.
Bisphenol A (BPA: 2,3-bis (4-hydroxyphenyl) propane) is an environmental chemical widely used in the manufacturing of epoxy polymers and many thermoplastic consumer products. Serious concerns about ...its safety led to the development of analogs, such as BPS (4-hydroxyphenyl sulfone). Very limited studies about BPS's impact on reproduction, specifically in spermatozoa, exist in comparison with BPA. Therefore, this work aims to study the in vitro impact of BPS in pig spermatozoa in comparison with BPA, focusing on sperm motility, intracellular signaling pathways and functional sperm parameters. We have used porcine spermatozoa as an optimal and validated in vitro cell model to investigate sperm toxicity. Pig spermatozoa were exposed to 1 and 100 μM BPS or BPA for 3 and 20 h. Both bisphenol S and A (100 μM) significantly reduce pig sperm motility in a time-dependent manner, although BPS exerts a lower and slower effect than BPA. Moreover, BPS (100 μM, 20 h) causes a significant increase in the mitochondrial reactive species, whereas it does not affect sperm viability, mitochondrial membrane potential, cell reactive oxygen species, GSK3α/β phosphorylation or phosphorylation of PKA substrates. However, BPA (100 μM, 20 h) leads to a decrease in sperm viability, mitochondrial membrane potential, GSK3β phosphorylation and PKA phosphorylation, also causing an increase in cell reactive oxygen species and mitochondrial reactive species. These intracellular effects and signaling pathways inhibited might contribute to explaining the BPA-triggered reduction in pig sperm motility. However, the intracellular pathways and mechanisms triggered by BPS are different, and the BPS-caused reduction in motility can be only partially attributed to an increase in mitochondrial oxidant species.
Bisphenols threaten human health and sensitive detection is crucial. The present study aims to develop ternary composites of copper metal-organic framework (Cu-MOF) with AuAg microstructures. The ...composite structure was formed by a galvanic displacement reaction and confirmed using SEM. A binder-free catalyst was used to study the electrochemical redox reaction of bisphenol A (BPA) and bisphenol S (BPS); an irreversible cyclic voltammetric signal at +0.70 V and + 0.91 V (vs. Ag/AgCl), in the dynamic range of 20 nM to 2.0 mM, and 10 nM to 1.0 mM, with limits of detection of 2.9 nM, and 3.2 nM (S/N = 3) was obtained. Practical analysis was applied to frozen tomatoes, tuna fish, milk powder, PET bottles, raw milk, and urine samples with a recovery rate of 94.00–100.80% (n = 3). Voltammetric results were validated using HPLC detection with high precision. The sensor is a promising alternative platform for measuring BPA in food samples.
Morphologically designed ternary hybrid composite material enables sensitive and selective detection of bisphenol A and bisphenol S in food samples. Display omitted
•Ultra-sensitive BPA and BPS sensors were developed based on Cu-MOF and their nanocomposites•Designed composite surface exhibits a superior anti-passivation effect with a highly stable signal•Morphologically tuned sensor substrate exhibits wide linearity concentrations and nanomolar LOD•The developed electrode surface had a reliable interference-free sensor and was highly reproducible•The platform was designed for practical application in PET bottles, frozen foods, and milk samples
BACKGROUND: Various lines of evidence have shown that bisphenol A BPA;$HO-C_{6}H_{4};-C(CH_{3})_{2}- C_{6}H&_{4}-OH$ acts as an endocrine disruptor when present in very low doses. We have recently ...demonstrated that BPA binds strongly to human estrogen-related$receptor-\gamma$($ERR-\gamma$) in a binding assay using$^{3}H4-hydroxytamoxifen$($^{3}H4-OHT$). We also demonstrated that BPA inhibits the deactivation activity of 4-OHT. OBJECTICES: In the present study, we intended to obtain direct evidence that BPA interacts with$ERR-\gamma$as a strong binder, and also to clarify the structural requirements of BPA for its binding to$ERR-\gamma$. METHODS: We examined$^{3}HBPA$in the saturation binding assay using the ligand binding domain of$ERR-\gamma$and analyzed the result using Scatchard plot analysis. A number of BPA derivatives were tested in the competitive binding assay using$^{3}HBPA$as a tracer and in the luciferase reporter gene assay. RESULTS:$^{3}HBPA$showed a KDof 5.50 nM at a Bmaxof 14.4 nmol/mg. When we examined BPA derivatives to evaluate the structural essentials required for the binding of BPA to$ERR-\gamma$, we found that only one of the two phenol-hydroxyl groups was essential for the full binding. The maximal activity was attained when one of the methyl groups was removed. All of the potent BPA derivatives retained a high constitutive basal activity of$ERR-\gamma$in the luciferase reporter gene assay and exhibited a distinct inhibitory activity against 4-OHT. CONCLUSION: These results indicate that the phenol derivatives are potent candidates for the endocrine disruptor that binds to$ERR-\gamma$.
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