4,4'-메틸렌비스페놀

Bisphenol

Other emerging contaminant and(or) Hormone

log Kow = 2.91

2.91

153.6 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID9022445]

155.05 Ų [M-H]-

This chemical does not meet GHS hazard criteria for 3.8% (5 of 130) of reports.

Danger

H315 (80.8%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P272, P273, P280, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 130 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Hazard Traits - Hazard Trait Undefined

Phenol, 4,4'-methylenebis-: Does not have an individual approval but may be used under an appropriate group standard

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Bisphenol F was detected in 60% of human breast milk samples collected from 20 healthy voluntary donors living in Hunan Province, China, at 0.010-0.166 ug/L. In 116, 22 and 20 urine samples collected July-August 2014 from people living in an electronic waste dismantling, rural reference and urban reference areas of China, respective bisphenol F concentrations were <LOQ-8.68, <LOQ-0.855 and <LOQ-3.04 ng/mL(2).

Urine samples collected from adult volunteers in Atlanta, GA contained bisphenol F at the following concentrations(1).[Table#8071]

The estrogenic activities of BPA, BPAF, BPAP, BPF were tested based on recombinant gene yeast assay. Six mixtures were designed based on the result of the test,each of which had an equitoxic ratio ray (EC10 or EC50). The EC50 values are 6.81 x 10(-6) mol/L, 7.44 x 10(-7) mol/L, 1.43 x 10(-5) mol/L, 7.52 x 10(-6) mol/L for BPA, BPAF, BPAP and BPF respectively,which reveals that the estrogenic activities order among the four bisphenols was BPAF> BPA> BPF> BPAP. The experiment shows that when BPA mixes with BPAF, BPAP and BPF in different ratios individually, different combination effects are produced. ...

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 15,000(SRC), determined from a structure estimation method(2), indicates that bisphenol F is expected to be immobile in soil(SRC). Volatilization of bisphenol F from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 5.2X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Bisphenol F is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). A 1% of theoretical BOD using activated sludge in the Japanese MITI test(3) suggests that biodegradation is not an important environmental fate process in soil(SRC). In contrast, bisphenol F was readily biodegradable in modified river and seawater die-away tests(4-5) including complete mineralization within 22 days in various microcosms(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 15,000(SRC), determined from a structure estimation method(2), indicates that bisphenol F is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.2X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Bisphenol F is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), BCFs of 3.8-18 measured in carp(5), suggest bioconcentration in aquatic organisms is low. Phenols can undergo sensitized photo-oxidation in surface waters exposed to sunlight via reaction with hydroxyl and peroxy radicals with half-lives on the order of days to weeks at the water surface(6); therefore, photo-oxidation may have some importance as a fate process for Bisphenol F in natural water(SRC). In 22-day aerobic river die-away tests using river water samples, bisphenol F showed complete degradation or complete primary degradation(7). Biodegradation of bisphenol F was 8-58% after 30 days using an aerobic degradation test and seawater microcosms following a 6-12 day lag period(8); biodegradation of bisphenol F was >92% after 60 days(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bisphenol F, which has an estimated vapor pressure of 3.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase bisphenol F is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 5 hours(SRC), calculated from its rate constant of 8.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase bisphenol F may be removed from the air by wet or dry deposition(SRC).

Bisphenol F was detected in two of eleven canned beverages purchased in Barcelona supermarkets; concentration in a sample of orange soda was 0.218 g/L and concentration in a sample of lemon soda was 0.141 ug/L(1). Bisphenol F was not detected in beverages packaged in poly(ethylene terephthalate) containers, but was detected in the same beverages packaged in cans at <LOQ-0.39 ng/mL; it was also detected in canned foods at <LOQ-35 ng/g, beverage and food products were purchased Feb 2014 from a supermarket in Beijing, China(2). Bisphenol F was detected in 6 of 36 honey samples purchased 2015 and 2016 from supermarkets from various European and non-European countries at 1.69-31.6 ng/g(3). Bisphenol F has been detected in prepared mustards containing ground white mustard (Sinapis alba) seeds, mustards containing only brown (Brassica juncea) or black (Brassica nigra) seeds did not contain bisphenol F(4).

In 267 food samples divided into nine categories collected 2008, 2011 and 2012 from retail grocery stores in Albany, NY, bisphenol F was detected at the following concentrations(1):[Table#8072]

IDENTIFICATION AND USE: Bisphenol F is a mixture of isomeric and oligomeric products. Bisphenol F is used to make epoxy resins and coatings for various applications, such as lacquers, varnishes, liners, adhesives, plastics, water pipes, dental sealants, and food packaging. HUMAN STUDIES: Retrospective review of results of patch-testing with plastics and glues allergens was conducted. In total, 444 patients were patch-tested with up to 56 plastics and glues allergens in the specialized series and up to five plastics and glues allergens in a baseline series. Positive-reaction rates were compared to other patch testing reports. Of patients, 97 (22%) had irritant reactions, and 201 (45%) had at least one allergic reaction. Bis(2-dimethylaminoethyl) ether 1%, benzoyl peroxide 1%, epoxy resin, bisphenol F 0.25%, 2-hydroxyethyl methacrylate 2%, and 2-hydroxyethyl acrylate 0.1% had the highest allergy reaction rates. Testing with specialized series identified 193 patients with plastics and glues allergy, of whom 162 were not identified by testing with baseline series alone. Occupational exposure to bisphenol F may occur through inhalation of dust and dermal contact with this compound at workplaces where it is produced or used. Monitoring data indicate that the general population is exposed to bisphenol F via inhalation of house dust, ingestion of soda, and possibly dermal contact with consumer products containing resins and coatings made with bisphenol F. Bisphenol F caused mainly necrotic changes in in human peripheral blood mononuclear cells. Bisphenol F was anti-androgenic in the human cell lines. Bisphenol F was effective on HepG2 cell DNA fragmentation at non-cytotoxic concentrations, but it did not induced a positive response in the micronucleus assay. ANIMAL STUDIES: Bisphenol F was orally administered to young rats for at least 28 days. No clear endocrine mediated changes were detected, and it was concluded bisphenol F had no endocrine mediated effects. The main effect of the chemical was liver toxicity based on clinical biochemical parameters and liver weight, but without histopathological changes. Decreased body weight accompanied by decreased serum total cholesterol, glucose, and albumin values were observed in the female rats given bisphenol F. When estrogenic activities of bisphenols were tested using recombinant gene yeast assay, bisphenol F was the most potent of the group. Bisphenol F did not induce any genic mutation in bacteria in the Ames test.

The average daily intake (ADI) of bisphenol F for different age groups was calculated using food concentrations from a survey collected 2008, 2011 and 2012 in Albany, NY(1).[Table#8070]

The average intake of the sum of 9 bisphenols (including bisphenol F) by the mouthing of baby teeters for 1 hour by 12 month old infants is reported as 1.40-1.51 ng/kg body weight/day(1).

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of November 16, 2017: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bisphenol F can be estimated to be 15,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that bisphenol F is expected to be immobile in soil.

/HUMAN EXPOSURE STUDIES/ Retrospective review of results of patch-testing with plastics and glues allergens at our institution between 2000 and 2007. In total, 444 patients were patch-tested with up to 56 plastics and glues allergens in the specialized series and up to five plastics and glues allergens in a baseline series. Positive-reaction rates were compared to other patch testing reports. Of patients, 97 (22%) had irritant reactions, and 201 (45%) had at least one allergic reaction. Bis(2-dimethylaminoethyl) ether 1%, benzoyl peroxide 1%, epoxy resin, bisphenol F 0.25%, 2-hydroxyethyl methacrylate 2%, and 2-hydroxyethyl acrylate 0.1% had the highest allergy reaction rates. Testing with specialized series identified 193 patients with plastics and glues allergy, of whom 162 were not identified by testing with baseline series alone.

/ENDOCRINE MODULATION/ Concerning endocrine activities, /bisphenol F/ BPF increased the luciferase activity in HepG2 cells transiently transfected with a concentration dependant pattern, dihyroxybenzophenone (DHB) also induced a positive response but at highest concentrations. Estrogenic responses in the HepG2 cells differed with the estrogen receptor (ER) involved. Using MDA-kb2 cell line stably transfected with pMMTV-neo-Luc, only BPF was anti-androgenic at the highest concentration (1.0x10-5 M). /Investigators/ demonstrated using human cell lines, especially HepG2, /that/ BPF was the most toxic compound in term of ... endocrine activities compared to DHB and BPF-OH, the free metabolites identified in rat urine when BPF was administrated to rats.

/ENDOCRINE MODULATION/ Bisphenol F, bisphenol A, fluorine-containing bisphenol A (bisphenol AF), and other diphenylalkanes were found to be estrogenic in a bioassay with MCF7 human breast cancer cells in culture (E-SCREEN assay). Bisphenols promoted cell proliferation and increased the synthesis and secretion of cell type-specific proteins. When ranked by proliferative potency, the longer the alkyl substituent at the bridging carbon, the lower the concentration needed for maximal cell yield; the most active compound contained two propyl chains at the bridging carbon. Bisphenols with two hydroxyl groups in the para position and an angular configuration are suitable for appropriate hydrogen bonding to the acceptor site of the estrogen receptor. Our data suggest that estrogenicity is influenced not only by the length of the substituents at the bridging carbon but also by their nature. ...

/GENOTOXICITY/ Bisphenol A (BPA) and bisphenol F (BPF) are widely used to manufacture plastics and epoxy resins. Both compounds have been shown to be present in the environment and are food contaminants, with, as a result, a low but chronic exposure of humans. However, the fate and possible bioactivation of these compounds at the level of human cell lines was not completely elucidated yet. In this study, /the researchers/ investigated the ability of human cells (intestinal cell line: LS174T, hepatoma cell line: HepG2, and renal cell line: ACHN) to biotransform BPA and BPF, and focused on the cytotoxicity and genotoxicity of these two bisphenols, through the use of a novel and efficient genotoxic assay based on the detection of histone H2AX phosphorylation. BPA and BPF were extensively metabolized in HepG2 and LS174T cell lines, with stronger biotransformation capabilities in intestinal cells than observed in liver cells. Both cell lines produced the glucuronide as well as the sulfate conjugates of BPA. Conversely, the ACHN cell line was found to be devoid of any metabolic capabilities for the two examined bisphenols. Cytotoxicity was tested for BPA, BPF, as well as one metabolite of BPF produced in vivo in rat, namely dihydroxybenzophenone (DHB). In the three cell lines used, /the researchers/ observed similar ranges of toxicity, with DHB being weakly cytotoxic, BPF exhibiting an intermediary cytotoxicity, and BPA being the most cytotoxic compound tested. BPA and DHB were not found to be genotoxic, whatever the cell line examined. BPF was clearly genotoxic in HepG2 cells. These results demonstrate that some human cell lines extensively metabolize bisphenols and establish the genotoxic potential of bisphenol F.

For more Human Toxicity Excerpts (Complete) data for Bisphenol F (7 total), please visit the HSDB record page.

Bisphenol F's production and use in making epoxy resins and coatings for various applications such as lacquers, varnishes, liners, adhesives, plastics, water pipes, dental sealants and food packaging(1) may result in its release to the environment through various waste streams(SRC).

Bisphenol F [4,4'-dihydroxydiphenyl-methane] (BPF) has a broad range of applications in industry (liners lacquers, adhesives, plastics, coating of drinks and food cans). Free monomers of this bisphenol can be released into the environment and enter the food chain, very likely resulting in the exposure of humans to low doses of BPF. This synthetic compound has been reported to be estrogenic. A study of BPF distribution and metabolism in rats has demonstrated the formation of many metabolites, with multiple biotransformation pathways. In the present work we investigated the in vitro biotransformation of radio-labeled BPF using rat and human liver subcellular fractions. BPF metabolites were separated, isolated by high-performance liquid chromatography (HPLC), and analysed by mass spectrometry (MS), MS(n), and nuclear magnetic resonance (NMR). Many of these metabolites were characterized for the first time in mammals and in humans. BPF is metabolized into the corresponding glucuronide and sulfate (liver S9 fractions). In addition to these phase II biotransformation products, various hydroxylated metabolites are formed, as well as structurally related apolar metabolites. These phase I metabolic pathways are dominant for incubations carried out with liver microsomes and also present for incubations carried out with liver S9 fractions. The formation of the main metabolites, namely meta-hydroxylated BPF and ortho-hydroxylated BPF (catechol BPF) is P450 dependent, as is the formation of the less polar metabolites characterized as BPF dimers. Both the formation of a catechol and of dimeric metabolites correspond to biotransformation pathways shared by BPF, other bisphenols and estradiol.

Bisphenol A (BPA) and bisphenol F (BPF) are widely used to manufacture plastics and epoxy resins. Both compounds have been shown to be present in the environment and are food contaminants, with, as a result, a low but chronic exposure of humans. However, the fate and possible bioactivation of these compounds at the level of human cell lines was not completely elucidated yet. In this study, /the researchers/ investigated the ability of human cells (intestinal cell line: LS174T, hepatoma cell line: HepG2, and renal cell line: ACHN) to biotransform BPA and BPF, and focused on the cytotoxicity and genotoxicity of these two bisphenols, through the use of a novel and efficient genotoxic assay based on the detection of histone H2AX phosphorylation. BPA and BPF were extensively metabolized in HepG2 and LS174T cell lines, with stronger biotransformation capabilities in intestinal cells than observed in liver cells. Both cell lines produced the glucuronide as well as the sulfate conjugates of BPA. Conversely, the ACHN cell line was found to be devoid of any metabolic capabilities for the two examined bisphenols. Cytotoxicity was tested for BPA, BPF, as well as one metabolite of BPF produced in vivo in rat, namely dihydroxybenzophenone (DHB). In the three cell lines used, /the researchers/ observed similar ranges of toxicity, with DHB being weakly cytotoxic, BPF exhibiting an intermediary cytotoxicity, and BPA being the most cytotoxic compound tested. BPA and DHB were not found to be genotoxic, whatever the cell line examined. BPF was clearly genotoxic in HepG2 cells. These results demonstrate that some human cell lines extensively metabolize bisphenols and establish the genotoxic potential of bisphenol F.

Bisphenol F (BPF) is present in the environment and as a contaminant of food. Humans may, therefore, be exposed to BPF, and an assessment of this risk is required. BPF has been shown to have genotoxic and endocrine-disruptor properties in a human hepatoma cell line (HepG2), which is a model system for studies of xenobiotic toxicity. In this study, we investigated the ability of HepG2 cells to biotransform BPF, because metabolism may affect the observed effects of BPF, and we compared this metabolic capacity with that of human hepatocytes. Cells were incubated for 24 hours with (3)H-BPF. The culture medium was then concentrated and its metabolites were isolated by high-performance liquid chromatography and identified by mass spectrometry. BPF was largely metabolized into the corresponding sulfate by the HepG2 cell line. BPF was metabolized into both sulfate and glucuronide by human hepatocytes, but with differences between individuals. The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway. Thus, these two cell models differ in metabolic capacity. It is, therefore, very important, when assessing the toxic effects of substances in vitro, to determine, in parallel, the biotransformation capacities of the model used to extrapolate in vivo.

Bisphenol F (BPF) as an endocrine disrupting compounds (EDCs) pollutant in the environment poses a great threat to human health. To evaluate the toxicity of BPF at the protein level, the effects of BPF on human serum albumin (HSA) were investigated at three temperatures 283, 298, and 308 K by multiple spectroscopic techniques. The experimental results showed that BPF effectively quenched the intrinsic fluorescence of HSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and the binding subdomain were measured, and indicated that BPF could spontaneously bind with HSA on subdomain IIA through H-bond and van der Waals interactions. Furthermore, the conformation of HSA was demonstrably changed in the presence of BPF. The work provides accurate and full basic data for clarifying the binding mechanisms of BPF with HSA in vivo and is helpful for understanding its effect on protein function during its transportation and distribution in blood.

The distribution of bisphenol F (4,4'-dihydroxydiphenyl-methane, BPF) was studied in female Sprague-Dawley rats. Pregnant and nonpregnant animals were gavaged with a single dose of 7 or 100 mg/kg [(3)H]BPF and were kept for 96 hr in metabolic cages. The excretion of BPF residues occurred mainly in urine (43-54% of the administered dose), which was found to contain at least six different metabolites, and to a lesser extent in feces (15-20% of the administered dose). Sulfatase treatment and subsequent high-performance liquid chromatography analyses suggest that the major urinary metabolite (more than 50% of the radioactivity present in urine) is a sulfate conjugate of BPF. At 96 hr, BPF residues were detectable in all tissues examined with the largest amounts in the liver (0.5% of the dose). In pregnant rats dosed at day 17 of gestation, BPF residues were detected in the uterus, placenta, amniotic fluid, and fetuses (0.9-1.3% of the administered dose). Large amounts of radioactivity (8-10% of the dose) were still located in the digestive tract lumen at the end of the study. After administration of a single oral dose of [(3)H]BPF, 46% of the distributed radioactivity was excreted in bile over a 6 hr period. In rats, BPF and/or its metabolites very likely undergo enterohepatic cycling, which could be responsible for the relatively high amounts of residues still excreted 4 days after BPF administration. This bisphenol is efficiently absorbed and distributed to the reproductive tract in female rats, and its residues pass the placental barrier at a late stage of gestation in rats.

Bisphenol F is used to make epoxy resins and coatings for various applications, such as lacquers, varnishes, liners, adhesives, plastics, water pipes, dental sealants, and food packaging.

Epoxy resins based on bisphenol F are used primarily as functional diluents in applications requiring a low viscosity, high performance resin system (e.g., solvent-free coatings). ... Bisphenol F epoxy resins are used in high solids, high build systems such as tank and pipe linings, industrial floors, road and bridge deck toppings, structural adhesives, grouts, coatings, and electrical varnishes.

Phenol, 4,4'-methylenebis-: ACTIVE

In 2005 the European Union banned the production of bisphenol F diglycidyl ether as a food packaging material. /Bisphenol F diglycidyl ether/