... The metabolism of bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites were isolated and characterized using HPLC and mass spectrometry. Many of these metabolites were characterized for the first time in mammals, namely isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers.
... In this study, bisphenol A (BPA) levels in 30 healthy Koreans (men, N=15, 42.6 +/- 2.4 years; women, N=15, 43.0 +/- 2.7 years) were analyzed from urine treated with/without beta-glucuronidase and/or sulfatase by an RP-HPLC with fluorescence detection. The total BPA concentrations including free BPA and the urinary conjugates were similar in men and women (2.82 +/- 0.73 and 2.76 +/- 0.54 ng/mL, respectively), but gender differences were found in the levels of urinary BPA conjugates. Men had significantly higher levels of BPA-glucuronide (2.34 +/- 0.85 ng/mL) than women (1.00 +/- 0.34 ng/mL), whereas women had higher levels of BPA-sulfate (1.20 +/- 0.32 ng/mL) than men (0.49 +/- 0.27 ng/mL).
... The objective of this study was to determine if a route dependency exists in the pharmacokinetics and metabolism of (14)C-labeled bisphenol A (BPA) following single oral (po), intraperitoneal (ip), or subcutaneous (sc) doses of either 10 or 100 mg/kg to Fischer 344 rats. Results indicated a marked route dependency in the pharmacokinetics of BPA. The relative bioavailability of BPA and plasma radioactivity was markedly lower following oral administration as compared to sc or ip administration. The major fraction of plasma radioactivity following oral dosing was the monoglucuronide conjugate of BPA (68-100% of plasma radioactivity). BPA was the major component in plasma at Cmax following sc or ip administration exceeded only by BPA-monoglucuronide in females dosed ip. Up to four additional unidentified metabolites were present only in the plasma of animals dosed ip or sc. One of these, found only following ip administration, was tentatively identified as the monosulfate conjugate of BPA. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA was the principal component excreted in feces. ...
Previous studies demonstrated the rapid clearance of bisphenol A (BPA) from blood following oral administration to adult rats with the principal metabolite being BPA-monoglucuronide (BPA-glucuronide). Since the ontogeny of glucuronyl transferases (GT) differs with age, the pharmacokinetics of BPA were studied in neonatal animals. (14)C-BPA was administered via gavage at 1 or 10 mg/kg body weight to rats at postnatal day (pnd) 4, pnd 7, pnd 21, or to 11 week old adult rats (10 mg/kg dose only). Blood (neonates and adults) and selected tissues (neonates) were collected at 0.25, 0.75, 1.5, 3, 6, 12, 18, and 24 hr postdosing. BPA and BPA-glucuronide in the plasma were quantified by high-performance liquid chromatography; radioactivity in the plasma and tissues was quantified by liquid scintillation spectrometry. The data indicate that neonatal rats at all three ages metabolized BPA to BPA-glucuronide, although an age dependency in the number and concentration of plasma metabolites was observed, consistent with the ontogeny of GT. BPA-glucuronide and BPA concentrations in the plasma were greater in neonates than in adults, except at 24 hr postdosing, suggesting an immaturity in the development of hepatic excretory function in neonatal rats. ... A dose dependency in the metabolism and pharmacokinetics of BPA administered to neonates was also observed with nearly complete metabolism of BPA to BPA-glucuronide (94-100% of the plasma radioactivity) at a dose of 1 mg/kg. This was in contrast to finding up to 13 different plasma metabolites observed at the 10 mg/kg dose. ...
来源:Hazardous Substances Data Bank (HSDB)
代谢
Bisphenol A 已知的人类代谢物包括 (2S,3S,4S,5R)-3,4,5-三羟基-6-[4-[2-(4-羟基苯基)丙烷-2-基]苯氧基]氧杂环己烷-2-羧酸。
Bisphenol A has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[4-[2-(4-hydroxyphenyl)propan-2-yl]phenoxy]oxane-2-carboxylic acid.
IDENTIFICATION AND USE: Bishphenol A (BPA) is a solid. It is used in the manufacture of epoxy resins and polycarbonates for food packaging. HUMAN STUDIES: Allergic contact dermatitis caused by polyvinyl chloride gloves is rarely reported, and in only 2 cases was BPA considered to be the responsible sensitizer. A clinical report describes photoallergic contact dermatitis to BPA in a group of eight outdoor workers. Urinary BPA may be associated with declined semen quality and increased sperm DNA damage. A correlation was observed between environmental exposure to BPA and the genesis of fetal malformations. Maternal conjugated BPA was also associated with a higher risk of aneuploid and euploid miscarriage. BPA is an endocrine disruptor with estrogenic properties that can adversely affect meiotic spindle assemblies. Data indicate that BPA exposure in female patients may interfere with oocyte quality during in vitro fertilization (IVF). Male BPA exposure may affect embryo quality during IVF. BPA was found to be cytotoxic, but not genotoxic in human cell lines. ANIMAL STUDIES: BPA caused serious damage to the eyes of rabbits, but demonstrated negligible skin irritation potential in rabbits. The effect of BPA on fertility was evaluated in an extensive oral two generation reproduction toxicity study in rats. No clinical signs of toxicity or effects on body weight gain during lactation were observed in F1 and F2 pups. No treatment-related changes were seen in the litter size, survival, sex ratio, anogenital distance and reflex ontogeny. BPA significantly accelerated mammary tumorigenesis in a transgenic mouse model that spontaneously develops tumors. In mice, exposure to a low dose of BPA, only during gestation, had immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Prenatal exposure to BPA mainly affected male rats and abolished sex differences in rearing behavior in the open-field test and struggling behavior in the forced swimming test. In mice, prenatal exposure to BPA affected pituitary gonadotroph development in females. BPA was not mutagenic using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolic activation. However, in vivo BPA exposure in rats caused a significant increase in the frequency of micronucleus in polychromatic erythrocytes, structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. Exposure to BPA in rodents was shown to induce obesity. Furthermore, feeding Drosophila melanogaster males with BPA significantly inhibited the expression of insulin-like peptides. ECOTOXICITY STUDIES: BPA demonstrated sex reversal effects on the gonads in F1 Japanese quail (Coturnix japonica) embryos. Vitellogenin induction in rainbow trout described after intraperitoneal injection of BPA. Japanese medaka (Oryzias latipes) was exposed to BPA at the sublethal concentrations of 2.28, 13.0, 71.2, 355, and 1,820 ug/L in the early life stage from fertilized eggs to 60-days posthatch. When observed for their external secondary sex characteristics, no males were identified in the 1,820-ug/L treatment. In addition, histological examination showed that 32% of fish in the 1,820-ug/L group had testis-ova composed of both testicular germ cells and oocytes. The effect of BPA on gene expression in Arabidopsis thaliana was determined using microarray analysis and quantitative gene PCR. Many hormone responsive genes showed changes in expression after BPA treatment. BPA disrupted flowering by a mechanism that may involve disruption of auxin signaling.
Bisphenol is an endocrine disruptor. Low doses of bisphenol A can mimic the body's own hormones, possibly causing negative health effects. There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans (L705).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Permanent changes to genital tract, changes in breast tissue that predispose cells to hormones and carcinogens, increased prostate weight 30%, lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus, decline in testicular testosterone, breast cells predisposed to cancer, prostate cells more sensitive to hormones and cancer, decreased maternal behaviors, reversed the normal sex differences in brain structure and behavior, U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA). (L953)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其气溶胶被吸收进入人体。
The substance can be absorbed into the body by inhalation of its aerosol.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
This research examined the distribution of low dietary doses of bisphenol A (BPA). When female rats received 50 ug/kg (14)C-BPA orally, radioactivity was distributed throughout the body, with especial presence in the uterus. Pre-treatment with estradiol or the estrogen antagonist ICI 182,780 significantly reduced radioactivity in the uterus. The majority of BPA at the uterus was determined to be aglycone (receptor-active) via GC-MS. Subsequently, mice given 0.5, 5, or 50 ug/kg (14)C-BPA showed more radioactivity in the uterus than in other non-metabolic tissues. When female mice received 1, 7, or 28 daily doses of 50 ug/kg (14)C-BPA, then were measured 24 hr after the last dose, significantly more radioactivity was detected in the uterus, liver, and kidney following repeated doses. Collectively, these data provide evidence for the in vivo interaction of BPA with estrogen receptors. They also indicate elevated presence of BPA in reproductive tissues after repeated low doses.
The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.
When administered as a single dose by gavage to male CFE rats, 28% of the (14)C-labeled bisphenol A was excreted in the urine (primarily as the glucosamide) and 56% in the feces (20% as free bisphenol A, 20% as a hydroxylated bisphenol A, and the rest as an unidentified conjugate). No carbon-labeled residues were detected in animals killed after 8 days.
Toxicokinetics of radiolabeled (14C) bisphenol A was studied in the common frog (Rana temporaria) at two experimental temperatures (7 and 19 °C). The growth rate of the tadpoles during the 96-hr experiment was very slow at 7 °C, but the weight of tadpoles almost tripled at 19 °C. At all tested exposure concentrations (0.2, 1.5, 10, and 100 ug/L), conditional uptake rate constants (ku) were 69 to 82%, and elimination rates (ke) 79 to 90% lower, at 7 °C than at 19 °C. On the contrary, bioconcentration factors (BCFs) were higher at 7 °C than at 19 °C. Total accumulated bisphenol A per individual was higher at 19 °C, which is in agreement with higher ku at 19 °C. Exposure concentrations did not have any constant effect on BCFs at the two temperatures. The results of the current experiment suggest that higher temperature increases uptake and total amount of chemical in frog tadpoles but does not necessarily lead to higher BCFs. High temperature may have increased the growth rate more than the uptake rate, resulting in a net dilution of bisphenol A in tadpole tissues. The observed difference in BCFs also could be a result of temperature-induced changes in allometric relationships (increased surface area to volume ratio) and/or more effective elimination in more developed tadpoles at high temperature.
1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
PHOTOSENSITIVE RESIN COMPOSITION, OXIME SULFONATE COMPOUND, METHOD FOR FORMING CURED FILM, CURED FILM, ORGANIC EL DISPLAY DEVICE, AND LIQUID CRYSTAL DISPLAY DEVICE
申请人：FUJIFILM Corporation
公开号：US20130171415A1
公开（公告）日：2013-07-04
Disclosed is a photosensitive resin composition comprising: (Component A) an oxime sulfonate compound represented by Formula (1); (Component B) a resin comprising a constituent unit having an acid-decomposable group that is decomposed by an acid to form a carboxyl group or a phenolic hydroxy group; and (Component C) a solvent
wherein in Formula (1) R
1
denotes an alkyl group, an aryl group, or a heteroaryl group, each R
2
independently denotes a hydrogen atom, an alkyl group, an aryl group, or a halogen atom, Ar
1
denotes an o-arylene group or an o-heteroarylene group, X denotes O or S, and n denotes 1 or 2, provided that of two or more R
2
s present in the compound, at least one denotes an alkyl group, an aryl group, or a halogen atom.
ENZYMATICALLY AND HYDROLYTICALLY STABLE RESINS, RESIN MONOMERS, AND RESIN COMPOSITES FOR USE IN DENTAL PREVENTIVE AND RESTORATIVE APPLICATIONS
申请人：ADA Foundation
公开号：US20150257986A1
公开（公告）日：2015-09-17
A composition of matter includes one or more functionalized vinylbenzyl components of the formula
covalently connected to one or more R functional components; the one or more R functional groups selected from a group including one or more hydroxyl methyl (—CHOH—) moieties and/or derivatives thereof, one or more ethoxy (—CH
2
—CH
2
—O—) moieties and/or derivatives thereof, and one or more benzene (C
6
H
6
) and/or derivatives thereof; and ether links that connect the functionalized vinylbenzyl components and the R functional components.
Diamine Compound Having Phosphorylcholine Group, Polymer Thereof, and Process for Producing the Polymer
申请人：Nagase Yu
公开号：US20100036081A1
公开（公告）日：2010-02-11
Highly polymerizable diamine compounds having a phosphorylcholine group are disclosed. High-molecular weight polymers are obtained from the highly polymerizable diamine compound having a phosphorylcholine group as a monomer, and the polymers have improved mechanical strength, water resistance and heat resistance while maintaining excellent biocompatibility and processability of MPC polymers. Processes for producing the polymers are disclosed. The diamine compounds having a phosphorylcholine group are represented by Formula (I). The polymers contain at least 1 mol % of a specific structural unit with a phosphorylcholine group represented by Formula (II) and have a number average molecular weight of not less than 5,000. In the processes, the diamine compound is used as a monomer.
The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.
The present application relates to encapsulates, compositions, products comprising such encapsulates, and processes for making and using such encapsulates. Such encapsulates comprise a core comprising a perfume and a shell that encapsulates said core, such encapsulates may optionally comprise a parametric balancing agent, such shell comprising one or more azobenzene moieties.
