2,2',6,6'-Tetrabrom-4,4'-isopropylidendiphenol

2.2 kg/L at 4 °C

Relative density = 2.12, 2.18

Crystals from isopropyl alcohol

White, crystalline powder

Insoluble (<1 mg/ml) (NTP, 1992)

In water, 0.171 mg/L at 25 °C (non-ionic form, pH 3.05); 4.15 mg/L at 25 deg (pH 7.56); 30.5 mg/L at 25 deg (pH 7.99); 228 mg/L at 25 °C (pH 8.48); 1510 mg/L at 25 °C (pH 8.91)

In water, 0.148 mg/L at pH 5; 1.26 mg/L at pH 7; 2.34 mg/L at pH 9, at 25 °C. In pure water, 0.063 mg/L at 21 °C; 0.24 mg/L at 25 °C

Soluble in ethanol, ether, benzene and chloroform

Soluble in oxygenated solvents.

356 to 363 °F (NTP, 1992)

179 °C

Bromine content = 58.4%; specific gravity = 2.17; melting point = 179-181 °C /Commercial product/

Tetrabromobisphenol a is a white powder. A monomer for flame-retardant epoxy, polyester and polycarboante resins.

Dry Powder; CBI; Large Crystals; Liquid

Off-white solid; [HSDB] White powder; [MSDSonline]

Danger

H350: May cause cancer [Danger Carcinogenicity]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P203, P273, P280, P318, P391, P405, and P501 (click each P-code to see the statement)

Warning

Chemical: Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo-；Specific Information Requirement: Obligations to provide information apply. You must tell us within 28 days if the circumstances of your importation or manufacture (introduction) are different to those in our assessment.

Hazard Traits - Bioaccumulation; Carcinogenicity; Endocrine Toxicity; Environmental Persistence; Neurotoxicity; Reproductive Toxicity；Authoritative List - CECBP - Priority Chemicals; EC Annex VI CMRs - Cat. 1B; IARC Carcinogens - 2A; OSPAR Priority Action Part A; Prop 65; US EPA TRI PBTs; WA PBTs；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo- 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)

T - indicates a substance that is the subject of a final TSCA section 4 test rule.

Status: Active Update: 09-09-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/14760

See Carcinogenicity of some industrial chemicals, Volume 115. [IARC, News Release, 23 Feb. 2016] Not embryotoxic in rats and mice at dose that causes reduction in offspring weight; [REPROTOX] Reproductive effector; Causes hepatitis, evidence of kidney injury, and weight loss in feeding studies of mice and rats; Causes somnolence and dyspnea in lethal-dose inhalation studies of rats; [RTECS] An irritant; [MSDSonline]

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Tetrabromobisphenol A is included on this list. Effective date: 6/20/85; Sunset date: 6/20/95.

Special hazards arising from the substance or mixture: Carbon oxides, hydrogen bromide gas.

When tetrabromobisphenol A was pyrolyzed in open quartz tubes for 10 min, brominated dibenzo p dioxins and dibenzofurans were generated at 700 °C and increased at 800 °C; at 900 °C a decrease in levels of these combustion products was found.

Carc. 2 (21.2%)；Aquatic Acute 1 (99.7%)；Aquatic Chronic 1 (100%)

Hazardous to the aquatic environment (acute) - category 1；Hazardous to the aquatic environment (chronic) - category 1

Acute toxicity (Inhalation: Dusts and mists) - Category 4；Carcinogenicity - Category 1B；Reproductive toxicity - Category 1B, Additional category: Effects on or via lactation；Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Acute toxicity (Inhalation: Dusts and mists) - Category 4；Carcinogenicity - Category 2；Reproductive toxicity - Category 1B, Additional category: Effects on or via lactation；Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 2

Carc. 1B；Aquatic Acute 1；Aquatic Chronic 1

EYES: Check for contact lenses and remove them at once if present. You should then immediately flush eyes with water from any source for 15 minutes. Do not use oil or ointment in eyes. Arrange immediate transportation to a medical facility.；SKIN: You should remove all contaminated clothing and flood skin with water. Wash all affected skin areas thoroughly with soap and water and seek immediate medical attention.；INGESTION: If the exposed person is convulsing or unconscious, you should not attempt first aid. Transport immediately to a hospital emergency room or poison control center. If the victim is conscious, administer large volumes of liquid then immediately induce vomiting. Transport at once to a medical facility. (NTP, 1992)

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

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. 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.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, dampen the solid spill material with toluene, then transfer the dampened material to a suitable container. Use absorbent paper dampened with toluene to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash all contaminated surfaces with toluene followed by washing with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: 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: 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: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Composite samples of human hair collected from barber shops in El Dorado and Magnolia, Arkansas contained 2,2',6,6'-tetrabromobisphenol A at concentrations of up to 2 to 5 ug/kg(1). A French monitoring study conducted during 2004-2006 analyzed samples of maternal and cord serum, adipose tissue and breast milk of 93 women during caesaren births(2); 2,2',6,6'-tetrabromobisphenol A was detected 44% breast milk samples at concentrations of 0.06 to 37.34 ng/g lipid wt, but no detections in adipose tissue(2); positive detections were made in serum samples with average concentrations of 154-199 pg/g fresh wt(2).

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

Combined toxicity and oxidative stress biomarker responses were determined for tetrabromobisphenol A (TBBPA) and sulfadiazine (SDZ) to the unicellular green alga Scenedesmus obliquus. Concentration-response analyses were performed for single toxicants and for mixtures containing TBBPA and SDZ with two different mixture ratios. The effect concentrations and the observed effects of the mixtures were compared to the predictions of the joint toxicity by the concentration addition (CA) model and independent action (IA) model. Results showed that the observed joint toxicity was within the scope of the highest (TBBPA) and lowest (SDZ) toxicity observed for the individual components. Furthermore, co-exposure of S. obliquus to TBBPA and SDZ provided preliminary evidence that the mixtures induced oxidative stress leading to cell damage. The CA and IA models proved to be valid for the prediction of the joint toxicity of TBBPA and SDZ. This study highlights a combined environmental risk assessment for two emerging pollutants.

BACKGROUND: Humans are commonly exposed to multiple environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antimicrobial agent), and bisphenol A (BPA; polycarbonate plastics). These chemicals are readily absorbed and may interact with each other. OBJECTIVES: We sought to determine whether TBBPA, given alone or in combination with triclosan, can modulate the concentrations of BPA and 17beta-estradiol (E2). METHODS: Female and male CF-1 mice were each given a subcutaneous injection of 0-27 mg TBBPA, with or without concurrent 0.33 mg triclosan, followed by dietary administration of 50 ug/kg body weight (14)C-BPA. Radioactivity was measured in blood serum and tissues through liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were each given a subcutaneous injection of 0 or 1mg TBBPA and E2 was measured in urine 2-12 hr after injection. RESULTS: Doses as low as 1 mg TBBPA significantly elevated (14)C-BPA concentrations in the uterus and ovaries of females; in the testes, epididymides, vesicular-coagulating glands, and preputial glands of males; and in blood serum, heart, lungs, and kidneys of both sexes; urinary E2 concentrations were also elevated. Lower doses of TBBPA or triclosan that had no effects on their own elevated (14)C-BPA concentrations when the two substances were given concurrently. CONCLUSION: These data indicate that TBBPA, triclosan, and BPA interact in vivo, consistent with evidence that TBBPA and triclosan inhibit enzymes that are critical for BPA and E2 metabolism.

Cadmium (Cd) and tetrabromobisphenol A (TBBPA) are two prevalent contaminants in e-waste recycling facilities. However, the potential adversely health effect of co-exposure to these two types of pollutants in an occupational setting is unknown. In this study, we investigated co-exposure of these two pollutants on hepatic toxicity in CD-1 male mice through a whole-body aerosol inhalation route. Specifically, mice were exposed to solvent control (5% DMSO), Cd (8 ug/cu m), TBBPA (16 ug/cu m) and Cd/TBBPA mixture for 8 hr/day and 6 days a week for 60 days. Hepatic changes include increased organ weight, focal necrosis, and elevated levels of liver enzymes in serum. These changes were most severe in mice exposed to TBBPA, followed by Cd/TBBPA mixture and Cd. These chemicals also led to suppressed antioxidant defensive mechanisms and increased oxidative stress. Further, these chemicals induced gene expression of apoptosis-related genes, activated genes encoding for phase I detoxification enzymes and inhibited genes encoding for phase II detoxification enzymes. These findings indicate that the hepatic damages induced by subchronic aerosol exposure of Cd and TBBPA may result from the oxidative damages caused by excessive ROS production when these chemicals were metabolized in the liver.

Bromine vapour causes irritation and direct damage to the mucous membranes. Elemental bromine also burns the skin. The bromide ion is a central nervous system depressant and chronic exposure produces neuronal effects. This is called bromism and can result in central reactions reaching from somnolence to coma, cachexia, exicosis, loss of reflexes or pathologic reflexes, clonic seizures, tremor, ataxia, loss of neural sensitivity, paresis, papillar edema of the eyes, abnormal speech, cerebral edema, delirium, aggressiveness, and psychoses. (L625, L626, L627)

LC50; Species: /Lepomis macrochirus/ (Bluegill sunfish); Concentration: 0.51 mg/L for 96 hr /Conditions of bioassay not specified in source examined/

LC50; Species: /Oncorhynchus mykiss/ (rainbow trout); Concentration: 0.40 mg/L for 96 hr /Conditions of bioassay not specified in source examined/

EC50; Species: Thalassiosira pseudonana (Diatom) 4.7X10+4 cells/mL; Conditions: saltwater, static, pH 8.2; Concentration: 1000 ug/L for 72 hr; Effect: population change /formulation/

EC50; Species: Thalassiosira pseudonana (Diatom) 4.7X10+4 cells/mL; Conditions: saltwater, static, pH 7.6; Concentration: 110 ug/L for 72 hr; Effect: population change /formulation/

For more Ecotoxicity Values (Complete) data for 2,2',6,6'-Tetrabromobisphenol A (21 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.7X10+5(SRC), determined from a structure estimation method(2), indicates that 2,2',6,6'-tetrabromobisphenol A is expected to be immobile in soil(SRC). The pKa1 and pKa2 of 2,2',6,6'-tetrabromobisphenol A are 7.5 and 8.5 respectively(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). Volatilization of 2,2',6,6'-tetrabromobisphenol A from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 4.68X10-8 mm Hg(5), and water solubility, 0.171 mg/L(6). 2,2',6,6'-Tetrabromobisphenol A is not expected to volatilize from dry soil surfaces based upon its vapor pressure(SRC). Anaerobic biodegradation of 2,2',6,6'-tetrabromobisphenol A has been shown to occur in soil and sediment studies with primary degradation being nearly complete within 10-64 days in some tests(7-9). Anaerobic biodegradation occurs through a biodehalogenation through tri- and dibromobisphenol A with a final product of bisphenol A(8,9). Aerobic biodegradation in soil can also occur(10,11). Aerobic degradation in a Chinese sandy soil under static incubation for 143 days resulted in a half-life of 14.7 days(10). Other studies in aerobic soils have reported half-lives ranging from 9 to 93 days(11). Results of aqueous photolysis studies(12) suggest that direct photolysis may occur on soil surfaces exposed to sunlight(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.7X10+5(SRC), determined from a structure estimation method(2), indicates that 2,2',6,6'-tetrabromobisphenol A 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 2.0X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 4.68X10-8 mm Hg(4) and water solubility, 0.171 mg/L(5). According to a classification scheme(6), BCF values ranging from 30 to 485(7,8) suggest the potential for bioconcentration in aquatic organisms is moderate to high. Anaerobic biodegradation of 2,2',6,6'-tetrabromobisphenol A has been shown to occur in sediment studies with primary degradation being nearly complete within 55 days(9) and 80% degradation in 10 days of incubation(10). Other studies in anaerobic sediments have reported half-lives ranging from 5 to >130 days(11). Anaerobic biodegradation occurs through a biodehalogenation through tri- and dibromobisphenol A with a final product of bisphenol A(9-11). Aerobic biodegradation may also occur based on a sediment/water study reporting half-lives from 48 to 84 days(12). Phototransformation studies of 2,2',6,6'-tetrabromobisphenol A in aqueous solution determined a UV absorption maximum at 310 nm, a quantum yield of 0.042 and decomposition rates ranging from 3.3X10-5 (at pH 5.5) to 6.8X10-4 (at pH 9) per second which correspond to a half-life range 17 minutes to 5.8 hours(13). 2,2',6,6'-Tetrabromobisphenol A is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Phenols can undergo sensitized photo-oxidation in surface waters exposed to sunlight via reaction with hydroxyl (OH), peroxy (RO2) radicals and singlet oxygen with a half-live on the order of weeks at the water surface(14); therefore, photo-oxidation may have some importance as a fate process for 2,2',6,6'-t

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,2',6,6'-tetrabromobisphenol A, which has a vapor pressure of 4.68X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 2,2',6,6'-tetrabromobisphenol A 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 5.4 days(SRC), calculated from its rate constant of 3.0X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 2,2',6,6'-tetrabromobisphenol A may be removed from the air by wet and dry deposition(SRC). 2,2',6,6'-Tetrabromobisphenol A absorbs UV light at wavelengths >290 and is susceptible to direct photolysis by sunlight(4).

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.

2,2',6,6'-Tetrabromobisphenol A concentrations varying from 0.06 to 37.34 ng/g were detected in breast milk samples collected from 93 volunteers in France between 2004 and 2006(1); 44% of all samples collected contained detectable levels(1). Breast milk samples collected from 10 volunteers in Birmingham, UK during 12 months of lactation (2010 to 2011) had a detection frequency of 61% with concentrations of 0.03-0.17 ng/g lipid wt (5th to 95th percentile) and an average concentration of 0.06 ng/g(2). A few studies demonstrate the presence of TBBPA in breast milk, with average levels between 0.06 and 4.11 ng/g fat, suggesting that milk represents a substantial route of excretion for TBBPA in humans(3).

IDENTIFICATION AND USE: 2,2',6,6'-Tetrabromobisphenol A (TBBPA) is a white crystalline powder. It is primarily used as a reactive flame retardant in epoxy resin circuit boards and more recently in electronic enclosures made of polycarbonate-acrylonitrile-butadiene-styrene (PC-ABS); approximately 90% is used in the manufacture of the resins. HUMAN STUDIES: TBBPA did not produce skin irritation nor contact sensitization. TBBPA was negative for the induction of structural and numerical chromosome aberrations in the in vitro chromosome aberration test using human peripheral lymphocytes. ANIMAL STUDIES: In a 90-day oral study, no toxicity was found in rats treated with up to 100 mg/kg in the feed. A study performed in 3 week old mice treated with a single oral dose (gavage) of 0.1, 5 or 250 mg TBBPA/kg bw showed behavioral alterations in the open field, contextual fear conditioning and Y maze tests 3 hours after dosing. Effects were observed at the two lower doses and not at the highest dose. In a two generation study, rats were administered TBBPA by gavage at 10, 100 or 1,000 mg/kg bw per day from pre-mating until the end of the lactation. The behavioral testing included locomotor activity (horizontal and vertical), and learning and memory tests in the Morris water maze and passive avoidance test. There were no differences in the F2 pups between exposed and control animals. In Xenopus laevis metamorphosis TBBPA exhibits an antagonistic activity at the developmental stages when animals have high endogenous thyroid hormone (TH) levels, whereas it acts as an agonist at the developmental stages when animals have low endogenous TH levels. Some oral toxicity studies in rodents with TBBPA reported changes in thyroid hormone levels and a carcinogenicity study with TBBPA showed increased incidences of uterine tumors in rats. TBBPA may increase levels of circulating estrogens by a competitive inhibition of estrogen conjugation. TBBPA was examined for mutagenic activity at concent

Bromine is a powerful oxidizing agent and is able to release oxygen free radicals from the water in mucous membranes. These free radicals are also potent oxidizers and produce tissue damage. In additon, the formation of hydrobromic and bromic acids will result in secondary irritation. The bromide ion is also known to affect the central nervous system, causing bromism. This is believed to be a result of bromide ions substituting for chloride ions in the in actions of neurotransmitters and transport systems, thus affecting numerous synaptic processes. (L626, L627, A543)

Based on the 5th Chinese Total Diet Study (TDS) carried out in 2011, the average estimated daily intake of 2,2',6,6'-tetrabromobisphenol A via food consumption for a "standard Chinese man" was 1.34 ng/kg bw/day(1); meat and meat products were found to be the major contributor to the daily dietary intake because the consumption of meat and meat products were significantly higher than that of other food groups in China(1).

Chemical: Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo-；Specific Information Requirement: Obligations to provide information apply. You must tell us within 28 days if the circumstances of your importation or manufacture (introduction) are different to those in our assessment.

Hazard Traits - Bioaccumulation; Carcinogenicity; Endocrine Toxicity; Environmental Persistence; Neurotoxicity; Reproductive Toxicity；Authoritative List - CECBP - Priority Chemicals; EC Annex VI CMRs - Cat. 1B; IARC Carcinogens - 2A; OSPAR Priority Action Part A; Prop 65; US EPA TRI PBTs; WA PBTs；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo- 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)

T - indicates a substance that is the subject of a final TSCA section 4 test rule.

Status: Active Update: 09-09-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/14760

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Tetrabromobisphenol A is included on this list. Effective date: 6/20/85; Sunset date: 6/20/95.

TBBPA is a non-genotoxic flame retardant used to improve fire safety in a wide variety of consumer products. Estimated human exposures to TBBPA are very low (<0.000084 mg/kg-day), relative to the doses (500 and 1000 mg/kg-day of TBBPA) administered in a recent bioassay that resulted in uterine tumors in Wistar Han rats following chronic exposure. As part of an effort to characterize the relevance of the uterine tumors to humans, data and biological knowledge relevant to the progression of events associated with TBBPA-induced uterine tumors in female rats were organized in an adverse outcome pathway (AOP) framework. Based on a review of possible MOAs for chemically induced uterine tumors and available TBBPA data sets, a plausible molecular initiating event (MIE) was the ability of TBBPA to bind to and inhibit estrogen sulfotransferases, the enzymes responsible for sulfation of estradiol. Subsequent key events in the AOP, including increased bioavailability of unconjugated estrogens in uterine tissue, would occur as a result of decreased sulfation, leading to a disruption in estrogen homeostasis, increased expression of estrogen responsive genes, cell proliferation, and hyperplasia. Available data support subsequent key events, including generation of reactive quinones from the metabolism of estrogens, followed by DNA damage that could contribute to the development of uterine tumors. Uncertainties associated with human relevance are highlighted by potential strain/species sensitivities to development of uterine tumors, as well as the characterization of a dose-dependent MIE. For the latter, it was determined that the TBBPA metabolic profile is altered at high doses (such as those used in the cancer bioassay), and thus an MIE that is only operative under repeated high dose, administration. The MIE and subsequent key events for the development of TBBPA-induced uterine tumors are not feasible in humans given differences in the kinetic and dynamic factors associated with

Due to potential consumer exposures, the toxicity of tetrabromobisphenol A (TBBPA) has been extensively studied. Reviews of TBBPA concluded no concerns regarding human health risks. The low toxicity of TBBPA is consistent with low bioavailability. However, some oral toxicity studies in rodents with TBBPA reported changes in thyroid hormone levels and a carcinogenicity study with TBBPA showed increased incidences of uterine tumors in rats. This review analyzes several modes of action (MoA) that may account for the observed thyroxine hormone changes and the uterine tumors. It concludes that the potential modes of action for thyroid changes induced by TBBPA are expected to exhibit a threshold for adverse effects due to the ability of the mammalian organism to compensate small changes in thyroid hormone levels. Regarding MoAs for the uterine tumors, TBBPA does not exert genotoxic or estrogenic effects. Available evidence suggests that TBBPA may increase levels of circulating estrogens by a competitive inhibition of estrogen conjugation and produce uterine tumors by promoting pre-existing Tp53-mutations due to increased estrogen levels resulting in increased cell proliferation.

... To investigate the nephrotoxic potential of Tetrabromobisphenol A (TBBPA) and its toxicokinetic profile in rats, single-dose and daily 14-day repeated-dose toxicity studies at 200, 500, or 1000 mg/kg were performed. ... Toxicokinetic studies indicated that TBBPA shows relatively a short half-life (7-9 hr) ... .

Ten female Sprague-Dawley rats received a single gavage dose of (14)C labelled TBBP-A in corn oil (average dose 7 mg/kg) (the position of the label was not stated). ... The half-life in the blood was calculated ... to be approximately 20 hours. The maximum half-life of radioactivity in any tissue was estimated to be 71 hours (for fat).

... The disposition of (14)C-TBBPA /was studied/ after a single dose (250 or 1,000 mg/kg b.w.) administered intraperitoneally to rats. ...The half-life in plasma, based on radioactivity measurement was found to be 230 hr.

The half-life of TBBPA in blood serum from 4 employees working in an electronics equipment dismantling plant in Sweden /was calculated/. Samples were collected just before the summer vacation and at various times during the vacation. The concentration of TBBPA in serum was found to decrease during the vacation period and a half-life of 2.2 days was estimated.

Rats received by gavage a single oral dose of TBBPA (300 mg/kg b.w.). TBBPA plasma concentration peaked at 103 umol/L 3 hours after administration, and thereafter declined with a half-life of 13 hours.

Tetrabromobisphenol A (TBBPA), a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA) for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES), the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA) and TBBPA-sulfate (S) conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg) for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC-MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28) as well as liver and uterus tissue (day 28) at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA associated with the induction

The comparative in vitro metabolism of the flame retardant tetrabromo-bisphenol A was studied in rat and human using a ((14)C)-radio-labelled molecule. Tetrabromo-bisphenol A is metabolized into the corresponding glucuronide (liver S9 fractions) and several other metabolites produced by cytochrome P450 dependent pathways (liver microsomes and liver S9 fractions). No major qualitative differences were observed between rat and human, regardless of the selected concentration, within the 20-200 uM range. Tetrabromo-bisphenol A undergoes an oxidative cleavage near the central carbon of the molecule, that leads to the production of hydroxylated dibromo-phenol, hydroxylated dibromo-isopropyl-phenol and glutathione conjugated dibromo-isopropyl-phenol. The main metabolites of tetrabromo-bisphenol A are two molecules of lower polarity than the parent compound, characterized as a hexa-brominated compound with three aromatic rings and a hepta-brominated dimer-like compound, respectively. Both structures, as well as the lower molecular weight metabolites resulting from the breakdown of the molecule, suggest the occurrence of chemically reactive intermediates formed following a first step oxidation of tetrabromo-bisphenol A.

(14)C-TBBP-A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane) was administered orally to the conventional and bile-duct cannulated male Sprague-Dawley rat (2.0 mg/kg body weight). ... Three metabolites were characterized in 0-24 hr bile samples. Glucuronic acid and sulfate ester conjugates were characterized by mass spectrometry. More than 95% of the extractable fecal (14)C was identified as parent TBBP-A. Negligible amounts of TBBP-A-derived (14)C were associated with carrier proteins in the urine and bile.

The metabolic fate of (14)C-TBBPA in pregnant rats dosed daily by gavage (190 ug/kg per day) from GD16 to GD19. Animals were killed at GD20. Total radioactivity measured in animals accounted for less than 0.5% of the administered dose, the highest levels being found in intestine and liver, and the amount found in fetuses representing less than 0.01% of the dose, suggesting minor trans-placental transfer. The major part of the radioactivity present in the intestine was found to be due to sulfate and glucuronide conjugates of TBBPA, but these metabolites were not formally identified by LC-MS.

For more Metabolism/Metabolites (Complete) data for 2,2',6,6'-Tetrabromobisphenol A (6 total), please visit the HSDB record page.

Bromine is mainly absorbed via inhalation, but may also enter the body through dermal contact. Bromine salts can be ingested. Due to its reactivity, bromine quickly forms bromide and may be deposited in the tissues, displacing other halogens. (L626)

Tetrabromobisphenol A (TBBPA), one of the most widely used global brominated flame retardants, is used to improve fire safety of laminates in electrical and electronic equipment. To investigate the nephrotoxic potential of TBBPA and its toxicokinetic profile in rats, single-dose and daily 14-day repeated-dose toxicity studies at 200, 500, or 1000 mg/kg were performed. Several biochemical parameters were analyzed to evaluate nephrotoxicity of TBBPA. High-dose 1000 mg/kg TBBPA significantly elevated renal thiobarbituric acid-reactive substance (TBARS) levels, and superoxide dismutase (SOD) activity was increased at all 3 doses administered. This was associated with no change in the activity of catalase (CAT). Our results suggest that acute 1-d high-dose administration of TBBPA produced transient renal changes at 5 h. Subsequently, TBBPA in serum, urine, and kidney was determined by liquid chromatography-mass spectroscopy (LC/MS). Toxicokinetic studies indicated that TBBPA shows relatively a short half-life (7-9 hr) and was eliminated almost completely in feces by 2 day. Based on the results from the 14-day repeated-dose study, TBBPA did not accumulate in the rat, and was eliminated in feces. The present results suggested that TBBPA may not be toxic to kidney, as the chemical is not bioavailable and is not present in renal tissue.

In the rat, tetrabromobisphenol A (TBBPA) was readily absorbed, metabolized and eliminated within 72 hours after oral dosing. Recovery of (14)C-activity in the conventional and bile-cannulated rat administered a single oral dose of (14)C-TBBPA was 92 and 98.5% of the dose, respectively, by 72 hours post-dosing. Owing to the extensive elimination, total tissue retention at 72 hours was limited. In the conventional rat, 2% of the dose was retained in the tissues, but <1 % in the cannulated rat at 72 hours. Essentially no deposition of TBBPA was detected in adipose tissue, heart, spleen, testis or thymus < 0.0005% of dose). The primary route of elimination was the feces; only negligible amounts were detected in urine. Glucuronic acid and sulfate ester conjugates were detected in bile; however the parent molecule was the predominant form found in species due to deconjugation by intestinal bacteria.

TBBP-A (14)C was administered intraperitoneally to 60 female Wistar rats in a single dose of 250 or 1,000 mg/kg in an olive oil vehicle; the site of the (14)C label was not stipulated. The animals were housed in metabolism cages. Urine and fecal samples were collected throughout the 72-hour study. Sixteen blood samples per animal were collected from the tail vein; sampling time was not reported. At 1, 4, 12, 24, 48 and 72 hours after exposure 4 animals from each dose group were decapitated and tissues (liver, kidneys, spleen, brain, fat, muscles, adrenals and sciatic nerve) were extracted. The amount of (14)C in the red blood cells, plasma, feces, tissue extracts and urine was determined. Samples of feces collected over the first 48 hours were analyzed and metabolites were identified via gas chromatography/mass spectrometry. At 24, 48 and 72 hours, the /researchers/ report the fate of the radioactivity in urine, feces and various tissues at both dose levels (results from 4 rats/timepoint). Irrespective of dose, the majority of the radioactivity detected was found in the feces. At 24 hours, 37 +/- 34% and 25 +/- 24% of administered radioactivity was eliminated in feces in the 250 and 1,000 mg/kg groups, respectively; at 48 hours, 61 +/- 25% and 43 +/- 19% of the administered radioactivity was eliminated, respectively; and at 72 hours, 65 +/- 24% and 51 +/- 17% of the administered radioactivity was eliminated, respectively. The urine represented a minor route of excretion; for both doses approximately 0.3% of the administered radioactivity was eliminated by this route by 72 hours. Radioactivity in the blood of the 250 mg/kg animals was reported to be 1.8 0.3%, 4 +/- 0.4% and 3.8 +/- 0.7% at 24, 48 and 72 hours, respectively (it was not determined in the 1,000 mg/kg group). At 72 hours, post-administration there was some retention in fat (approximately 3-6%) and muscle (approximately 11-14%); the deposition of (14)C within the tissues did not appear to be dose-dependen

Pregnant Wistar rats were orally dosed with 0 or 5 mg/kg (14)C-ring labelled TBBP-A in corn oil daily on days 10-16 of gestation (the number of animals/group was not documented). Feces and urine were collected daily from day 10 of gestation. On gestational day 20, rats were sacrificed via ether anesthesia, and a number of tissues from the dams and the fetuses (liver, skeletal muscle, abdominal fat, placenta, total plasma, forebrain, kidney, lungs, spleen, heart, cerebellum, pancreas and thymus) and the carcasses were collected for radioactivity measurements, assessed by liquid scintillation counting. The majority of the radioactivity (79.8%) was excreted in the feces by 48 hours after the final dose, with limited amounts reported to be excreted in the urine (<0.2% of the administered radioactivity). The tissues of the dams and fetuses between them contained 1.2% of the dosed radioactivity; of this, the highest levels in maternal tissues were detected in the carcass (0.37% of the dose) and the liver (0.26% of the dose). The total amount of radioactivity in the fetus was approximately 0.34% of the administered dose); the highest levels in the fetal tissues were detected in the carcass (0.07% of the dose) and liver (0.06% of the dose). The nature of the labelled substance detected in the tissue was not verified in this study; it may have been a metabolite of TBBP-A rather than TBBP-A itself.

For more Absorption, Distribution and Excretion (Complete) data for 2,2',6,6'-Tetrabromobisphenol A (15 total), please visit the HSDB record page.

Used as a flame retardant additive to plastics (ABS, phenolic, unsaturated polyester resins, and epoxy resin circuit boards), paper, and textiles; Also used as a plasticizer and chemical intermediate; [HSDB]

Semiconductor Manufacturing [Category: Industry]；Pulp and Paper Processing [Category: Industry]；Textiles (Printing, Dyeing, or Finishing) [Category: Industry]

Primarily used as a reactive flame retardant in epoxy resin circuit boards and more recently in electronic enclosures made of polycarbonate-acrylonitrile-butadiene-styrene (PC-ABS); approximately 90% is used in the manufacture of the resins. In encapsulations for integrated circuit chips, 2,2',6,6'-tetrabromombisphenol A (TBBPA) is incorporated into the epoxy polymer structure after curing, resulting in no free TBBPA in the finished product. In addition to its use in polymers, general applications include its use as a flame retardant for plastics, paper, and textiles; as a plasticizer; in adhesives and coatings; and as a chemical intermediate for the synthesis of other flame retardants. It has also been used as a fire-retardant additive and as a fire-retardant polycarbonate comonomer. Additionally, TBBPA is applied to carpeting and office furniture.[NIEHS; Tetrabromobisphenol A

Reproductive effector.

TBBPA and its derivatives are a widely used group of flame retardants. TBBPA is primarily used as a reactive flame retardant, covalently bound to epoxy and polycarbonate resins. It is also used as an additive flame retardant in the manufacture of acrylonitrile butadiene styrene (ABS) resins, high impact polystyrene (HIPS) and phenolic resins. TBBPA derivatives may be used as either reactive or additive intermediates in polymer manufacture.

Used as a chemical intermediate for the synthesis of: tetrabromobisphenol A allyl ether; tetrabromobisphenol A bis(2-hydroxyethyl ether); tetrabromobisphenol A carbonate oligomer; tetrabromobisphenol A diglycidyl ether.

2023: 10,000,000 - <50,000,000 lb；2022: 10,000,000 - <50,000,000 lb；2021: 10,000,000 - <50,000,000 lb；2020: 10,000,000 - <50,000,000 lb

2,2',6,6'-Tetrabromobisphenol A is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#5296]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: 2,2',6,6'-Tetrabromobisphenol A. Aggregated National Production Volume: 100 to < 500 million pounds.

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 2,2',6,6'-Tetrabromobisphenol A:；Table: National Aggregate Production Volume (pounds) [Table#5297]

TBBPA is produced by the bromination of bisphenol-A in the presence of a solvent. This reaction may be conducted in the presence of a hydrocarbon solvent only or with water, 50% hydrobromic acid or aqueous alkyl mono ethers. When methanol is used as the solvent, methyl bromide is formed as a by-product. The production process is largely conducted in closed systems.

In the typical batch reaction, bromine in slight excess is added to a stirred bisphenol-A solution in methanol in a suitable reactor at 25-30 °C. The exothermic reaction is controlled by the rate of bromine addition, which is dependent on the refrigeration capacity of the reactor cooling system. After bromine addition, the contents of the reactor are heated to reflux (65 °C) for a short period to allow the slower reaction between methanol and dissolved HBr to occur. During this postreaction period, methyl bromide and some HBr are vented through the overhead condenser system into a series of scrubbers that neutralize and dry methyl bromide, which is produced in about 60% yield based on byproduct HBr. Water is then added to precipitate TBBPA and the resulting slurry is cooled, filtered, washed, and dried. The yield of TBBPA is generally 94-97% based on bisphenol-A.

Commercial TBBPA is available in two grades, an epoxy resin grade and a higher quality polycarbonate grade.

The purity of commercial TBBPA is 98.5% containing 0.1% water, a maximum of 60 mg hydrolysable bromine/kg, and a maximum of 100 mg ionic bromide/kg.

Trade Names: Great Lakes BA-59P; Saytex RB-100; Saytex RB-100 ABS; FR-1524; Bromdian; FG 2000; Fire Guard 2000; Firemaster BP 4A; Tetrabrom

Plastics -> Polymer Type -> Polyolefin-I; Polyolefin-II; ABS

Plastics -> Flame retardants

Adhesive Manufacturing；Plastics Material and Resin Manufacturing；Paint and Coating Manufacturing；Plastics Product Manufacturing

Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo-: ACTIVE

Tetrabromobisphenol-A is produced in the USA, Israel and Japan but not in the EU.