2,2-비스(4-하이드록시페닐)헥사플루오로프로판

PFAS -> PFAS identified in REACH Regulation EC No. 1272/2008

PFAS -> Identified in migrating and extractable food contact chemical data

PFAS -> Intentionally added food contact chemicals

PFAS -> Other/unspecified

PFAS -> Suspected persistent, mobile, toxic (PMT) PFAS or PFAS-like compounds

165.6 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID7037717]

230.13 Ų [2M-H]-

Danger

H360F: May damage fertility [Danger Reproductive toxicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Danger

H315 (56%): Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P318, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Chemical: Phenol, 4,4′-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis-

Hazard Traits - Endocrine Toxicity; Reproductive Toxicity

Phenol, 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 16-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/23236

Substance: 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol (Bisphenol AF)

Phenol, 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis-: Does not have an individual approval but may be used under an appropriate group standard

Skin Irrit. 2 (56%)

Serious eye damage/eye irritation - Category 1

Repr. 1B

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. 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 soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Exposure to xenoestrogens occurs against a backdrop to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in early childhood to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with endogenous estrogens. The current study was designed to characterize the individual dose-response curves of estradiol-17beta (E(2)), bisphenol A (BPA), tetrabromo-bisphenol A (TBBPA), and bisphenol AF (BPAF, 4,4'-hexafluoroisopropylidene diphenol) on estrogen-dependent luciferase expression in T47D-KBluc cells and to determine how binary (8 x 8 factorial) and ternary (4 x 4 x 4 factorial) mixtures of an endogenous estrogen (E(2)) interact with BPA and/or BPAF. Log EC(50) and hillslope values with SEs, respectively, for individual compounds were as follows: E(2), -12.10M +/- 0.06071, 0.7702 +/- 0.1739; BPA, -6.679M +/- 0.08505, 1.194 +/- 0.2137; and BPAF, -7.648M +/- 0.05527, 1.273 +/- 0.1739. TBBPA was not evaluated in mixture studies because of its minimally estrogenic response at 3 x10(-5)M and elicited cytotoxicity at higher concentrations. Both the binary mixtures of E(2) with BPA and BPAF and the ternary mixture of E(2), BPA, and BPAF behaved in an additive manner. For binary mixtures, as E(2) concentration increased, higher concentrations of BPA and BPAF were necessary to induce a significant increase in the estrogenic response. Understanding the behavior of mixture interactions of xenoestrogens, like BPA and BPAF, with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals, individually or as mixtures.

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 x L(-1), 7.44 x 10(-7) mol x L(-1), 1.43 x 10(-5) mol x L(-1), 7.52 x 10(-6) mol x L(-1) 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. It reveals that the combined ratios of the components may affect the combined effect. The dose addition model and the independent action model are used to identify the combined effect. They are testified to be more intuitionistic and more comprehensive than other joint effect indices.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 7.6X10+5(SRC), determined from a structure estimation method(2), indicates that bisphenol AF is expected to be immobile in soil(SRC). The estimated pKa of bisphenol AF is 9.2(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of bisphenol AF from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.7X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Bisphenol AF is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 7.6X10+5(SRC), determined from a structure estimation method(2), indicates that bisphenol AF 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 5.7X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 420(SRC), from an estimated log Kow of 4.47(2) and a regression-derived equation(2). 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(5); therefore, photo-oxidation may have some importance as a fate process for bisphenol AF in natural water(SRC). Bisphenol AF is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2012).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bisphenol AF, which has an estimated vapor pressure of 5.4X10-7 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 AF 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 1.6 hours(SRC), calculated from its rate constant of 8.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase bisphenol AF may be removed from the air by wet and dry deposition(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bisphenol AF can be estimated to be 7.6X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that bisphenol AF is expected to be immobile in soil. The estimated pKa of bisphenol AF is 9.2(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/ENDOCRINE MODULATION/ /The researchers/ aimed to determine the relative preference of bisphenol AF for the human nuclear estrogenic receptors ERalpha and ERbeta and the bisphenol A-specific estrogen-related receptor ERRgamma, and to clarify structural characteristics of receptors that influence bisphenol AF binding. /The researchers/ examined receptor-binding activities of bisphenol AF relative to [(3)H]17beta-estradiol (for ERalpha and ERbeta) and [(3)H]bisphenol A (for ERRgamma). Functional luciferase reporter gene assays were performed to assess receptor activation in HeLa cells. /The researchers/ found that bisphenol AF strongly and selectively binds to ERs over ERRgamma. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ERbeta [IC50 (median inhibitory concentration) = 18.9 nM] than for ERalpha. When examined using a reporter gene assay, bisphenol AF was a full agonist for ERalpha. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ERbeta. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ERbeta agonist 17beta-estradiol. ... Results suggest that bisphenol AF could function as an endocrine-disrupting chemical by acting as an agonist or antagonist to perturb physiological processes mediated through ERalpha and/or ERbeta.

An estimated BCF of 420 was calculated in fish for bisphenol AF(SRC), using an estimated log Kow of 4.47(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

The Henry's Law constant for bisphenol AF is estimated as 5.7X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bisphenol AF is expected to be essentially nonvolatile from water surfaces(2). Bisphenol AF's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Bisphenol AF is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-7 mm Hg(SRC), determined from a fragment constant method(1).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In this study, the effects of Bisphenol AF (BPAF) exposure on the testis and the related mechanisms of toxicity were investigated. Sprague-Dawley (SD) male rats were exposed to BPAF (0, 2, 10, 50 and 200 mg/kg/d) for 14 days. Total cholesterol levels in serum were decreased in rats given a dose of 50 and 200 mg/kg/d. BPAF concentration in the testes increased with increasing doses of BPAF. Reduced serum testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were observed in rats in the higher dose groups. Furthermore, BPAF exposure resulted in a dramatic decline in genes and protein involved in cholesterol biosynthesis, transport and steroid biosynthesis. Similarly, the testicular mRNA levels of inhibin B, estrogen receptor (ERa) and luteinizing hormone receptor (LHR) also decreased in rats given a dosage of 200 mg/kg/d BPAF. Together, these data demonstrate that BPAF-induced inhibition of testosterone production primarily resulted from the alteration of genes and proteins in the testosterone biosynthesis pathway.

/LABORATORY ANIMALS: Neurotoxicity/ Bisphenol AF (BPAF), a newly introduced chemical structurally related to bisphenol A, is used extensively in fluoroelastomers and polyesters, and has been known to induce estrogen-dependent responses. However, the toxicity of BPAF is largely unknown except for its endocrine-related effects. In this study, /the researchers/ investigated the neurotoxicity of BPAF and underlying mechanisms of action using hippocampal cell line (HT-22) and mouse primary neuronal cells. We found that BPAF induced apoptosis in both HT-22 and primary neuronal cells. In order to clarify the underlying mechanisms of BPAF-induced apoptosis, various signaling molecules were evaluated. BPAF increased the level of intracellular calcium, followed by the generation of reactive oxygen species (ROS). BPAF upregulated the phosphorylation of mitogen-activated protein kinase: extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-kappa B. Using specific inhibitors, we confirmed that calcium, ROS, p38, and JNK mediated the BPAF-induced apoptosis. In addition, BPAF inhibited microglial activation in a microglia/neuroblastoma coculture model by the reduction of nitric oxide production. We found that BPAF interrupted the normal physiologic functions of microglia at non-toxic levels. Taken together, ... results suggest that BPAF, the substitute of BPA, also have neurotoxic properties.

/ENDOCRINE MODULATION/ Route: oral via stomach tube (Hershberger assay). Species: rat, Brl Han:WIST Jcl (GALAS), males. Dose/Duration: 50, 200, or 600 (reduced to 400 due to toxicity) mg/kg/day for 10 consecutive days beginning on postnatal day 56 Observation Time: not provided. Effects: decreased body weight gain and decreased spontaneous locomotion at 200 and 600 mg/kg; decreased bulbocavernosus/levator ani muscle weights at 200 mg/kg; increased relative glans penis weight at 600 mg/kg and at 50 mg/kg and 600 mg/kg in the presence of testosterone propionate (TP); significantly increased relative seminal vesicle weight at 50 mg/kg and 600 mg/kg + TP; significantly increased relative Cowper's gland at 600 mg/kg + TP.

/ENDOCRINE MODULATION/ The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA, and tetramethylbisphenol A (TMBPA); 2,2-bis(4-hydroxyphenyl)-1-propanol, 1,1-bis(4-hydroxyphenyl)propionic acid and 2,2-diphenylpropane showed little or no activity. Anti-estrogenic activity against 17beta-estradiol was observed with TMBPA and tetrabromobisphenol A (TBBPA). TCBPA, TBBPA, and BPA gave positive responses in the in vivo uterotrophic assay using ovariectomized mice. In contrast, BPA and some related compounds showed significant inhibitory effects on the androgenic activity of 5alpha-dihydrotestosterone in mouse fibroblast cell line NIH3T3. TMBPA showed the highest antagonistic activity, followed by bisphenol AF, bisphenol AD, bisphenol B, and BPA. However, TBBPA, TCBPA, and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA, and 3,3'-dimethylbisphenol A exhibited significant thyroid hormonal activity towards rat pituitary cell line GH3, which releases growth hormone in a thyroid hormone-dependent manner. However, BPA and other derivatives did not show such activity. The results suggest that the 4-hydroxyl group of the A-phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.

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

The rate constant for the vapor-phase reaction of bisphenol AF with photochemically-produced hydroxyl radicals has been estimated as 8.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Bisphenol AF is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Phenols can undergo sensitized photo-oxidation in surface waters exposed to sunlight via reaction with hydroxyl and peroxy (RO2) radicals with half-lives on the order of days to weeks at the water surface(3); therefore, photo-oxidation may have some importance as a fate process for bisphenol AF in natural water(SRC).

According to the 2006 TSCA Inventory Update Reporting data, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of bisphenol AF is 1000 or greater; the data may be greatly underestimated(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 4388 workers (1460 of these were female) were potentially exposed to bisphenol AF in the US(1). Occupational exposure to bisphenol AF may occur through inhalation and dermal contact with this compound at workplaces where bisphenol AF is produced or used(2). The general population may be exposed to bisphenol AF via dermal contact with this compound from consumer products containing polymers made from bisphenol AF(2). Contact via food and cosmetics may be possible since the tubing and seals in the food and pharmaceutical industry are made from bisphenol AF polymers(2). Monitoring data indicate that the general population may be exposed to bisphenol AF via inhalation of indoor dust(3).[(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Nov 5, 2012: http://www.cdc.gov/noes/ (2) NTP; Chemical Information Profile for Bisphenol AF

The presence of bisphenol AF in dust samples from New York (Albany, n = 38), China (n = 55), Japan (n = 22), and Korea (n = 41) was monitored in 2006 and 2010. Bisphenol AF was not detected in dust samples from New York or China(1); bisphenol AF was detected in 76% of dust samples from Korea, with a maximum level of 0.091 ug/g, and 9% of dust samples from Japan, with a maximum level of 0.011 ug/g(1).

Bisphenol AF's production and use as a cross-linking agent in fluorocarbon elastomers and specialty polymers may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 5.4X10-7 mm Hg at 25 °C indicates bisphenol AF will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase bisphenol AF will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 1.6 hours. Particulate-phase bisphenol AF will be removed from the atmosphere by wet and dry deposition. If released to soil, bisphenol AF is expected to have no mobility based upon an estimated Koc of 7.6X10+5. The estimated pKa of bisphenol AF is 9.2, indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5.7X10-10 atm-cu m/mole. Bisphenol AF is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, bisphenol AF is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 420 suggests the potential for bioconcentration in aquatic organisms is high. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Sensitized photo-oxidation may have some importance as a fate process for Bisphenol AF in sunlit natural water. Occupational exposure to bisphenol AF may occur through inhalation and dermal contact with this compound at workplaces where Bisphenol AF is produced or used. The general population may be exposed to bisphenol AF via dermal contact with this compound from consumer products containing polymers made from bisphenol AF. Contact via food and cosmetics may be possible since the tubing and seals in the food and pharmaceutical industry are made from bisphenol AF polymers. Monitoring data indicate that the general population may be exposed to bisphenol AF via inhalation of indoor dust. (SRC)

Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. /The researchers/ used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) alpha and ERbeta. /The researchers/ used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERalpha and ERbeta. Ishikawa/ERa stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. The three EDCs showed strong estrogenic activity as agonists for ERalpha in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERalpha in Ishikawa cells and BPAF acted as an antagonist for ERbeta in HeLa cells, whereas Zea was only a partial antagonist for ERalpha. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERalpha, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERalpha target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. BPA and BPAF can function as EDCs by acting as cell type-specific agonists (= 10 nM) or antagonists (= 10 nM) for ERalpha and ERbeta. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ERalpha. In addition, all three compounds induced the rapid action-mediated response for ERalpha.

/The researchers/ report that the mechanisms by which biphenol A (BPA) and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) alpha and beta differ from that used by 17beta-estradiol. /The researchers/ show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17beta-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor gamma and androgen receptor, which are two known main targets of bisphenols. ...

Exogenous agents, synthetic and naturally occurring, which are capable of disrupting the functions of the ENDOCRINE SYSTEM including the maintenance of HOMEOSTASIS and the regulation of developmental processes. Endocrine disruptors are compounds that can mimic HORMONES, or enhance or block the binding of hormones to their receptors, or otherwise lead to activating or inhibiting the endocrine signaling pathways and hormone metabolism.

... Crosslinking agent for certain fluoroelastomers and as a monomer for polyimides, polyamides, polyesters, polycarbonate copolymers and other specialty polymers

Synthesis of various polycarbonate polymers and specialty polymers for high heat applications

Bisphenol AF is used to cross-link and cure fluoroelastomers, often along with an accelerator such as triphenyl benzyl phosphonium chloride. When used as a curing agent it produces elastomers with excellent chemical resistance and thermal stability. Bisphenol AF is also used as a monomer in the synthesis of specialty polymers. Polymers containing Bisphenol AF are useful in high temperature composites, in electronic materials and other specialty applications.

2023: 250,000 - <400,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#8069]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Phenol, 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis-. Aggregated National Production Volume: < 500,000 pounds.[US EPA; Non-Confidential 2006 Inventory Update Reporting. National Chemical Information. Phenol, 4,4'-

Produced from hexafluoropropanone-2 and phenol as the starting materials. In general, fluorinated bisphenols can be made from the reaction of a phenol and a fluorinated precursor consisting of a fluorinated aldehyde or a fluorinated ketone in the presence of an organic sulfonic acid catalyst.

All Other Chemical Product and Preparation Manufacturing

Phenol, 4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis-: ACTIVE