Methyl 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate and hygrine are important biosynthetic intermediates for tropane alkaloids. We have developed a concise method to synthesize these two compounds from ...the key intermediate N-methylpyrrolinium cation. Methyl 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate and hygrine were obtained in four and six steps from commercially available 4,4-diethoxybutylamine with overall yields of 42% and 25%, respectively. Mots-cles : 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate de methyle, hygrine, intermediaire biosynthetique, alcaloide tropanique, cation N-methylpyrrolinium.
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•Bisphenol F (BPF) and S (BPS) have been suggested to have neurotoxic effects.•We examined exposure to bisphenols and attention-deficit hyperactivity symptoms (ADHD).•The detection ...frequency of BPF and BPS increased greatly from age 6 to age 8.•Exposure to BPF and BPS were associated with greater ADHD symptoms at age 6.•Bisphenol A (BPA) showed nonlinear relationships with ADHD symptoms.•The association of BPA and ADHD was pronounced above a threshold of 3.0 μg/g creatinine.
Bisphenol A (BPA) has been linked to attention-deficit/hyperactivity disorder (ADHD) symptoms, but the neurotoxic effects of bisphenol substitutes such as bisphenol F (BPF) and S (BPS) have not been well investigated. We investigated the associations between BPA, BPF, and BPS with ADHD symptoms at multiple time points in children.
The levels of BPA (at ages 4, 6, and 8), BPF (at ages 6 and 8), and BPS (at ages 6 and 8) were measured in 619 children. Because of the low detection frequency of BPF and BPS levels, participants were divided into categories (<or ≥ limit of detection (LOD) for BPF; < LOD, ≥ LOD and < median, or ≥ median for BPS). ADHD symptoms were assessed using the ADHD Rating Scale IV (ARS). The relationship between bisphenols and ARS scores was analyzed using Poisson regression models, and generalized additive models and piecewise regression models were further explored for BPA.
BPA was detected in most participants (>97%), whereas BPF and BPS were less frequently detected (age 6: 17.5% for BPF and 42.0% for BPS; age 8: 51.6% for BPF and 73.3% for BPS). Doubling in BPA levels was associated with increased ARS scores by 4.7% (95% confidence intervals CI: 0.5, 9.2) at age 6. The association was greater with BPA levels higher than 3.0 μg/g creatinine (24.2% 95% CI: 15.5, 33.6 increase). The BPF ≥ LOD group had 10.8% (95% CI: 1.2, 21.4) higher ARS scores than the BPF < LOD group. The BPS ≥ median group had 11.4% (95% CI: 2.0, 21.7) higher ARS scores than the BPS < LOD group.
All bisphenols, in particular those at or above the LOD or median levels, were associated with ADHD symptoms at age 6. Further prospective studies are warranted to determine causal inference.
Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical, and one of the major new issues is the safe replacement of this commonly used compound. Bisphenol S (BPS) and bisphenol F ...(BPF) are already or are planned to be used as BPA alternatives. With the use of a culture system that we developed (fetal testis assay FeTA), we previously showed that 10 nmol/L BPA reduces basal testosterone secretion of human fetal testis explants and that the susceptibility to BPA is at least 100-fold lower in rat and mouse fetal testes. Here, we show that addition of LH in the FeTA system considerably enhances BPA minimum effective concentration in mouse and human but not in rat fetal testes. Then, using the FeTA system without LH (the experimental conditions in which mouse and human fetal testes are most sensitive to BPA), we found that, as for BPA, 10 nmol/L BPS or BPF is sufficient to decrease basal testosterone secretion by human fetal testes with often nonmonotonic dose-response curves. In fetal mouse testes, the dose-response curves were mostly monotonic and the minimum effective concentrations were 1,000 nmol/L for BPA and BPF and 100 nmol/L for BPS. Finally, 10,000 nmol/L BPA, BPS, or BPF reduced Insl3 expression in cultured mouse fetal testes. This is the first report describing BPS and BPF adverse effects on a physiologic function in humans and rodents.
Bisphenols: More unnecessary surprises Thayer, Kristina A.; Pelch, Katie E.; Birnbaum, Linda S. ...
Endocrine disruptors (Austin, Tex.),
20/4/1/, Volume:
4, Issue:
1
Journal Article
Peer reviewed
Open access
A recent biomonitoring study "Bisphenol A, Bisphenol S, and 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) in Urine and Blood of Cashiers" reported on levels of BPA, BPS, and a novel BPS-derivative ...(BPSIP) in cashiers compared to non-cashiers. Our study was the first to detect BPSIP in humans. In this commentary we discuss our findings in the context of considering bisphenols as a class in health assessments and how technological advances in exposure assessment could be utilized to more efficiently identify emerging chemicals of interest.
ABSTRACT Background Bisphenol A (BPA) and other related chemical compounds may be components used in the manufacturing process of resin-based composite dental restorative material. The purpose of the ...authors study was to assess salivary and urinary concentrations of BPA and other compounds before and after placement of resin-based composite dental restorations. Methods The authors collected saliva and urine from 172 participants receiving composite restorations before and as long as 30 hours after placement of composite restorations. The authors analyzed saliva specimens from 151 participants and urine specimens from 171 participants for concentrations of BPA and five related compounds by using liquid chromatography/mass spectrometry (LC/MS). Results Salivary concentrations of BPA and some related compounds increased immediately (within one hour) after composite placement. Salivary concentrations of BPA and most study compounds returned to prerestoration levels within eight hours after composite placement. With the exception of a 43 percent increase in BPA, concentrations of the study compounds in urine returned to prerestoration levels nine to 30 hours after restoration placement. Concentrations in saliva were lower when a rubber dam was used; however, rubber dam use appeared to have no effect on urinary concentrations of the measured compounds during the study period. The authors observed similar changes in study compound levels in both saliva and urine between participants who received anterior restorations and those who received posterior restorations. Conclusions Placement of resin-based composite restorations was associated with detectable increases in saliva of BPA and other study compounds within one hour after restoration placement and an increased concentration of BPA in urine nine to 30 hours after restoration placement. Rubber dam use did not reduce the absorption of BPA (measured as BPA level in urine) during the study. Clinical Implications Additional studies are needed to address how long BPA levels in urine associated with composite placement remain elevated to aid in better understanding of the clearance rates of BPA and other study compounds.
In this work, degradation of bisphenol F (BPF), bisphenol AF (BPAF) and bisphenol S (BPS) by peroxymonosulfate (PMS) with TiO2 nano-tubes arrays (TiO2NTAs) under simulated sunlight irradiation was ...investigated and compared for the first time. All three bisphenols exhibited appreciable degradation following the order of BPS < BPAF < BPF, and acidic conditions were more conducive to their degradation. The SO4•-, ·OH, h+ and •O2- were all identified in three bisphenols degradation processes. Among these, SO4•- and •O2- were proven to play a dominant role in BPF oxidation process, but SO4•- and h+ were confirmed as the main reactive species for BPAF and BPS removal. Owing to the different reactive species worked in different bisphenols degradation processes, the influences of inorganic anions on three bisphenols degradation were also different. By analyzing the oxidation intermediates of the three bisphenols, it was found that there were some common degradation pathways including bond-cleavage and hydroxylation of the benzene ring shared by three bisphenols. Besides, some specific degradation pathways were also identified, for example, the self-coupling was found in BPF and BPS degradation process, while the benzene ring splitting was occurred only in BPAF transformation process
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•TiO2NTAs were employed to activate PMS for bisphenols removal in simulated sunlight.•In this study, BPF was more easily oxidized than BPAF and BPS over a wide pH range.•Bond-cleavage and benzene ring hydroxylation occurred in all bisphenols degradation.•Self-coupling was found both in BPF and BPS degradation process.•Benzene ring splitting occurred only in BPAF transformation process.
Background: Bisphenol A (BPA) is a ubiquitous and known endocrine disrupting chemical (EDC), however the effects of perinatal exposure to BPA on offspring of metabolically chalanged population are ...under-investigated. Upon oral exposure BPA is metabolaized in liver, which is the primary metabolic gland of mammalian body.The purpose of this study was to analyze the transgenerational hepatic effects of BPA on offspring of obese parents.Methods: Obese Wistar rats (6M/6F) were given 10ppm BPA in drinking water for 180 days and crossed to obtain offspring. Pups (6M/6F) were analyzed for hallmarks of NAFLD, including birth weight, progressive weight gain, lipid homeostasis, liver specific enzymes, hepatic glutathione reserve, lipid preoxidation, inflammatory marker C-reactive protein (CRP) along with enzymatic antioxident acivity and histological changes. Male and female pups were assessed separately to undertand if effects are sex dependent. Data were analyzed using GraphPad Prism 6.0.Results: Compared to unexposed offspring controls, pups of BPA exposed obese rats (p = 0.0462) had increased body weight and progressive weight gain until 21 days after birth, along with elevated cholesterol (p < 0.001),triglycerides (p < 0.001), Low-density lipoproteins (p < 0.001),serum CRP (p < 0.01), aspartate aminotransferases (p = 0.0020), and alkaline phosphatase (p = 0.0030). They also had decreased levels of High-density lipoproteins, hepatic glutathione reserve ( (p < 0.001), loss of enzymatic antioxidant activity along with increased lipid peroxidation (p < 0.001). Preseence of high lipid vacuolization, inflammatory and apoptotic cells along with peribiliary infiltration in histology studies of liver tissue confirmed the onset of NAFLD.Conclusions: Pups with perinatal BPA exposure and obese parentage are highly predisposed to oxidative stress leading to hepatotoxicity. Combined parental BPA and obesity exposure exerts transgenerational toxic effects in weanling offspring. Offspring of BPA-exposed obese Wistar rats exhibited early onset of NAFLD. Even after ban for use, BPA is present on environment and poese serious threat to future generations. Further studies are needed to assess effects in humans.
There is increasing concern regarding human exposure to bisphenol analogues (BPs) due to their widespread use and potentially adverse effects. Nevertheless, information on the occurrence of BPs in ...pregnant women is limited. In this study, BPs were detected in 181 serum samples from pregnant Chinese women. Ten BPs, including bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AP (BPAP), tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), and tetrachlorobisphenol A (TCBPA), were positively identified and quantified in serum samples with total BP concentrations (sum of bisphenols: ∑BPs) of 0‐144 ng/mL. Concentrations of the two frequently detected compounds, TBBPS and BPS, were 0.593 and 0.113 ng/mL, respectively. The results were also compared with the geographic distributions of the BPs. To our knowledge, this is the first time that TBBPS and TCBPA have been detected in serum samples of pregnant women. These findings suggest that additional studies are urgently needed to identify the risk of maternal and fetal exposure to these compounds.
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•Ten BPs were detected in serum samples from pregnant Chinese women.•TBBPS and BPS were frequently detected compounds.•The results were compared with the geographic distributions of the BPs.•This is the first report of TBBPS and TCBPA detection in serum of pregnant women.
In this work, transformation of bisphenol A (BPA) alternatives bisphenol AF (BPAF) and bisphenol S (BPS) by manganese dioxide (MnO2) and the effect of iodide (I−) during these processes were ...investigated in comparison with BPA for the first time. These three bisphenols showed appreciable reactivity towards MnO2 with the half-lives of their loss following the order of BPA < BPAF < BPS under similar conditions, and a higher transformation efficiency was generally obtained at a lower pH. The presence of I− apparently accelerated the transformation of BPAF and BPS by MnO2 at pH ≤ 7 but negligibly affected BPA transformation over the pH range of 5–9. This discrepancy could be well explained by the relative contribution of hypoiodous acid (HOI) in situ formed from I− oxidation by MnO2. Polymers, hydroxylated derivatives, and bond-cleavage products were detected from BPAF and BPS treated by MnO2, where a series of reactions of BPAF/BPS radicals formed from one-electron oxidation of BPAF/BPS were likely involved, similar to the case of BPA reported in literature. A group of iodinated aromatic products were additionally identified from BPAF/BPS treated by MnO2 in the presence of I− (e.g., iodinated BPAF/BPS and iodinated BPAF/BPS dimers), and they could be further transformed. This study suggests that naturally occurring manganese oxides play a significant role in the attenuation of bisphenols released into the environment and the presence of I− can display a great effect on their transformation.
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•MnO2 showed considerable reactivity towards bisphenols following the order of BPA > BPAF > BPS.•I− significantly enhanced the transformation of BPAF and BPS by MnO2 at pH ≤ 7.•Polymeric, hydroxylated, and bond-cleavage products were detected from BPAF/BPS treated by MnO2.•Iodinated aromatic products were generated from MnO2/BPAF(BPS)/I− systems.
Bisphenol A (BPA) is gradually being replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), due to its toxic, endocrine disrupting and possible ...carcinogenic effects. Although these bisphenols are widely used to produce a variety of everyday household items, the effects of BPA and its analogues on oxidative stress and cellular energy metabolism of the female reproductive system are still poorly understood. The aim of this study was to evaluate the oxidative stress, biomacromolecular damage and changes in calcium ion (Ca2+) levels induced by BPA and its substitutes on KGN cells, which are maintain physiological characteristics of ovarian granulosa cells. We have observed that BPA and BPAF significantly reduced the viability of KGN cells, while BPS and BPF exhibited a slight toxic effect on the cells. The levels of intracellular ROS production and antioxidant capacity were significantly increased and decreased, respectively, in KGN cells after treatment with high concentrations of BPA and its analogues. In addition, we found that the damage to biomacromolecules, which are the main targets of oxidative stress was significantly increased after treatment with BPA, BPS, BPF, and BPAF. The intracellular Ca2+ levels in KGN cells were significantly increased after exposure to high concentrations of BPA and BPAF, respectively. These results suggest that BPA and its analogues may play different roles in regulating the biologic functions of granulosa cells and the process of ovarian follicular development.
•BPA and BPAF significantly reduced the viability of KGN cells.•BPA and its analogues exposure break the balance of antioxidant system in KGN cells.•BPAF induced the strongest oxidative damage to KGN cells.•BPA and BPAF significantly increase intracellular calcium levels in KGN cells.
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