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排序方式: 共有255条查询结果,搜索用时 15 毫秒
1.
Bisphenol A is a commercially important chemical used to make polycarbonate plastic, epoxy resins, and other specialty products. Despite an extensive body of in vitro, animal and human observational studies on the effects of exposure to bisphenol A, no authoritative bodies in the U.S. have adopted or recommended occupational exposure limits for bisphenol A. In 2017, the National Institute for Occupational Safety and Health published a Draft process for assigning health-protective occupational exposure bands, i.e., an airborne concentration range, to chemicals lacking an occupational exposure limit. Occupational exposure banding is a systematic process that uses both quantitative and qualitative toxicity information on selected health effect endpoints to assign an occupational exposure band for a chemical. The Draft process proposes three methodological tiers of increasing complexity for assigning an occupational exposure band. We applied Tier 1 (based on the Globally Harmonized System of Classification and Labelling) and Tier 2 (based on authoritative sources/reviews) to assign an occupational exposure band to bisphenol A. Under both Tier 1 and 2, the occupational exposure band for bisphenol A was “E” (<0.01?mg/m3), an assignment based on eye damage. “E” is the lowest exposure concentration range, reserved for chemicals with high potential toxicity. If eye damage was excluded in assigning an air concentration exposure range, then bisphenol A would band as “D” (>0.01 to 0.1?mg/m3) under Tier 1 (based on reproductive toxicity and respiratory/skin sensitization) and under Tier 2 (based on specific target organ toxicity-repeated exposure). In summary, Tiers 1 and 2 gave the same occupational exposure band for bisphenol A when eye damage was included (“E”) or excluded (“D”) as an endpoint.  相似文献   
2.
目的:探讨外源性双酚A(BPA)调控MCF-7乳腺癌细胞迁移的分子机制?方法:通过划痕实验和Transwell实验检测MCF-7乳腺癌细胞迁移能力,并以黏附实验反向辅助验证;通过质粒转染干扰Snail蛋白表达水平,进一步研究外源性BPA调控MCF-7乳腺癌细胞迁移的分子机制?结果:外源性BPA能上调细胞中Snail的表达水平,从而下调E-cadherin的表达并促进MCF-7乳腺癌细胞迁移;siRNA干扰Snail表达后MCF-7乳腺癌细胞迁移减慢?此外,BPA刺激能降低MCF-7乳腺癌细胞黏附能力?结论:外源性BPA可通过上调Snail表达水平,促进MCF-7乳腺癌细胞的迁移,为进一步阐明乳腺癌细胞侵袭与转移的分子调控机制提供了新线索?  相似文献   
3.
Bisphenol A (BPA) is a high‐production chemical used in a variety of applications worldwide. While BPA has been documented as an endocrine‐disrupting chemical (EDC) having adverse health‐related outcomes in multiple studies, risk assessment for BPA has lagged due to reliance on guideline toxicology studies over academic ones with end‐points considered more sensitive and appropriate. To address current controversies on BPA safety, the United States National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and the Food and Drug Administration (FDA) established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY‐BPA) using the NCTR Sprague‐Dawley rats. The goal of CLARITY‐BPA is to perform a traditional regulatory toxicology study (Core study) in conjunction with multiple behavioural, molecular and cellular studies by academic laboratories focused on previously identified BPA‐sensitive organ systems (Academic studies). Combined analysis of the data from both study types will be undertaken by the NTP with the aim of resolving uncertainties on BPA toxicity. To date, the Core study has been completed and a draft report released. Most of the academic studies have also been finalized and published in peer‐reviewed journals. In light of this important milestone, the PPTOX‐VI meeting held in the Faroe Islands, 27‐30 May 2018 devoted a plenary session to CLARITY‐BPA with presentations by multiple investigators with the purpose of highlighting key outcome. This MiniReview synthesizes the results of three academic studies presented at this plenary session, evaluates recently published findings by other CLARITY‐BPA academic studies to provide an early combined overview of this emerging data and places this in the context of the Core study findings. This co‐ordinated effort revealed a plethora of significant BPA effects across multiple organ systems and BPA doses with non‐monotonic responses across the dose range utilized. Remarkably consistent across most studies, including the Core study, are low‐dose effects (2.5, 25 and 250 μg BPA/kg body‐weight). Collectively, the findings highlighted herein corroborate a significant body of evidence that documents adverse effects of BPA at doses relevant to human exposures and emphasizes the need for updated risk assessment analysis.  相似文献   
4.
Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats.Hyperactivity of the hypothalamic-pituitary-adrenal(HPA) axis is one of the most consistent biological findings in anxiety- and depression-related disorders.The HPA axis is reported to be susceptible to developmental reprogramming.The present study focused on HPA reactivity in postnatal day(PND) 80 male rats exposed perinatally to environmental-dose BPA.When female breeders were orally administered 2 μg/(kg.day) BPA from gestation day 10 to lactation day 7,their offspring(PND 80 BPA-exposed rats)showed obvious anxiety/depression-like behaviors.Notably,significant increase in serum corticosterone and adrenocorticotropin,and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor.Additionally,the level of glucocorticoid receptor mRNA in the hippocampus,but not the hypothalamus,was decreased in BPA-exposed rats.The levels of hippocampal mineralocorticoid receptor mRNA,neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats.In addition,the testosterone level was in BPA-exposed rats.The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.  相似文献   
5.
《Radiotherapy and oncology》2014,110(2):193-197
Background and purposeThe aim of this study was to compare the accumulation of 4-borono-2-18F-fluoro-phenylalanine (18F-BPA) with that of 18F-fluorodeoxyglucose (18F-FDG) in head and neck cancers, and to assess the usefulness of 18F-FDG PET for screening candidates for boron neutron capture therapy (BNCT).Material and methodsTwenty patients with pathologically proven malignant tumors of the head and neck were recruited from March 2012 to January 2014. All patients underwent both whole-body 18F-BPA PET/CT and 18F-FDG PET/CT within 2 weeks of each other. The uptakes of 18F-BPA and 18F-FDG at 1 h after injection were evaluated using the maximum standardized uptake value (SUVmax).ResultsThe accumulation of 18F-FDG was significantly correlated with that of 18F-BPA. The SUVmax of 18F-FDG ⩾5.0 is considered to be suggestive of high 18F-BPA accumulation.Conclusions18F-FDG PET might be an effective screening method performed prior to 18F-BPA for selecting patients with head and neck cancer for treatment with BNCT.  相似文献   
6.
The endocrine disruptor bisphenol A (BPA) is a frequently used chemical in the manufacture of consumer products. In humans, BPA is extensively metabolized to BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms. The study has been performed with the intention to improve the accuracy of published physiologically based pharmacokinetic models and to improve regulatory risk assessments of BPA. In order to gain insight into intestine, kidney, liver, and lung glucuronidation of BPA, human microsomes of all tested organs were used. BPAG formation followed Michaelis-Menten kinetics in the intestine and kidney, but followed substrate inhibition kinetics in the liver. Human lung microsomes did not show glucuronidation activity towards BPA. While the liver intrinsic clearance was very high (857 mL min(-1)kg body weight(-1)), the tissue intrinsic clearances for the kidney and intestine were less than 1% of liver intrinsic clearance. Since BPA is a UGT1A1 substrate, we postulated that the common UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min(-1)kg body weight(-1), respectively. Prior to microsomal experiments, the bioproduction of BPAG and stable isotope-labeled BPAG (BPAG(d16)) was performed for the purpose of the reliable and accurate quantification of BPAG. In addition, a sensitive LC-MS/MS analytical method for the simultaneous determination of BPA and BPAG based on two stable isotope-labeled internal standards was developed and validated. In conclusion, our in vitro results show that the liver is the main site of BPA glucuronidation (K(m) 8.9 μM, V(max) 8.5 nmol min(-1) mg(-1)) and BPA metabolism may be significantly influenced by a person's genotype (K(m) 10.0-13.1 μM, V(max) 3.4-16.2 nmol min(-1) mg(-1)). This discovery may be an important fact for the currently on-going worldwide BPA risk assessments and for the improvement of physiologically based pharmacokinetic models.  相似文献   
7.
Bisphenol A (BPA), an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA (2 µg/kg) for consecutive 14 days in adult rats (BPA rats) significantly reduced the sperm count and the number of germ cells compared to controls. The serum levels of testosterone and follicle-stimulating hormone (FSH), as well as the level of GnRH mRNA in BPA rats were lower than those of control rats. Testosterone treatment could partially rescue the reduction of germ cells in BPA rats. Notably, the number of apoptotic germ cells was significantly increased in BPA rats, which was insensitive to testosterone. Furthermore, the levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased in comparison with controls. These results indicate that exposure to a low dose of BPA impairs spermatogenesis through decreasing reproductive hormones and activating the Fas/FasL signaling pathway.  相似文献   
8.
Many people are repeatedly exposed to both bisphenol A (BPA) and diethylhexyl phthalate (DEHP), but there has been little research concerning their effects in combination. Both can disrupt blastocyst implantation in inseminated females, albeit at high doses. We exposed mice on gestation days (GD) 1–4 to combinations of BPA and DEHP in doses below the threshold necessary to disrupt implantation on their own. On GD 6, there were fewer normally-developed implantation sites and more underdeveloped implantation sites in females given the combined subthreshold doses. Uterine epithelial cadherin (e-cadherin), a protein that assists in blastocyst adhesion to the uterine epithelium, was significantly reduced by these combined doses, but not by the individual doses. A similar trend was seen in integrin αvβ3, another uterine adhesion molecule. Cadherin-11 was disrupted by BPA but not DEHP. These data are consistent with competition of BPA and DEHP for conjugating enzymes.  相似文献   
9.

Objectives

Bisphenol A (BPA) exposure may promote obesity, but its effect on bone mineral density (BMD) has not been reported in humans. We aimed to examine the relationships between BPA exposure, body composition, serum estradiol, leptin, osteocalcin levels and BMDs in healthy premenopausal women.

Design and methods

In this cross-sectional study, a total of 246 healthy premenopausal women aged 20 years and older with regular menstrual cycles were investigated. Body mass index (BMI), fat mass, fat-free mass and BMDs were measured by DXA. Serum estradiol, leptin, osteocalcin, urinary BPA and NTx levels were also tested.

Results

Urinary BPA levels were positively associated with fat mass (r = 0.193, p = 0.006) and leptin (r = 0.236, p = 0.001) but not with fat-free mass after adjusting for age and BMI. BPA was not associated with serum estradiol levels, BMDs, or bone resorption marker NTx and bone formation parameter osteocalcin, either. A multivariate stepwise regression analysis confirmed that serum leptin levels were positively influenced by fat mass (β = 0.746, p < 0.001) and BPA (β = 0.127, p = 0.01) but negatively correlated with fat-free mass (β = − 0.196, p < 0.001). However, the changes of BMDs at the lumbar spine (β = 0.298, p < 0.001) and femoral neck (β = 0.305, p < 0.001) were primarily explained by fat-free mass, and were irrelevant of the fat mass, leptin or BPA exposure.

Conclusions

Although BPA exposure is related with increased amount of fat mass and elevated serum leptin levels, it has neutral effect on BMDs in premenopausal women, possibly due to the exclusive role of fat-free mass, which is unrelated to BPA in determining BMDs.  相似文献   
10.
In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.  相似文献   
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