2,4,6-Tri-tert-butylphenol

log Kow = 6.06

6.3

Soluble in most organic solvents

Insoluble in alkalis; soluble in ethanol, acetone, carbon tetrachloride

In water, 35 mg/L at 25 °C

0.000661 [mmHg]

6.61X10-4 mm Hg at 25 °C

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P270, P272, P280, P301+P317, P302+P352, P318, P319, P321, P330, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 1.6% (11 of 679) of reports.

Danger

H302 (32.7%): Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Phenol, 2,4,6-tris(1,1-dimethylethyl)-

Hazard Traits - Bioaccumulation; Environmental Persistence; Reproductive Toxicity

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

R - indicates a substance that is the subject of a TSCA section 6 risk management rule.

Status: Active Update: 20-04-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/5641

Substance: 2,4,6-tri-tert-butylphenol

Di- and tri-substituted mixed alkylphenols: Category members demonstrate moderate skin irritation; Low acute oral and moderate acute dermal toxicity; Evidence of liver toxicity in repeated-dose oral studies of rats; Developmental toxicity at doses producing marginal systemic toxicity in adults; No evidence of reproductive toxicity, mutagenicity, or carcinogenicity; [EPA ChAMP: Hazard Characterization] May cause irritation; Harmful by ingestion; [Sigma-Aldrich MSDS]

EPA/Office of Pollution Prevention and Toxics; High Production Volume Information System (HPVIS) Detailed Chemical Results for Phenol, 2,4,6-tris(1,1-dimethylethyl)- (732-26-3).[Available from, as of June 8, 2009: http://iaspub.epa.gov/oppthpv/quicksearch.display?pChem=100221]

Acute Tox. 4 (32.7%)

Acute toxicity (Oral) - Category 4

Skin sensitization - Category 1B

Repr. 1B

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

Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation.

Environmental precautions: Do not let product enter drains.

Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

Observe all federal, state, and local environmental regulations.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

In case of skin contact: Wash off with soap and plenty of water. Consult a physician.

In case of eye contact: Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.

Handling: Avoid formation of dust and aerosols.

Hygiene measures: Handle in accordance with good industrial and safety practice. Wash hands before breaks and at the end of workday.

Personal protective equipment: Respiratory protection- Where risk assessment shows air-purifying respirators are appropriate use a dust mask type N95 (US) or type P1 (EN 143) respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Hand protection- Handle with gloves. For prolonged or repeated contact use protective gloves. Eye protection- Safety glasses.

Hand protection: Handle with gloves. For prolonged or repeated contact use protective gloves.

Eye protection: Safety glasses.

Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.

Provide appropriate exhaust ventilation at places where dust is formed. Normal measures fro preventive fire protection.

LC50; Species: Pimephales promelas (Fathead minnow, age 30-31 days, mean length 18.4 mm, mean weight 0.086 g); Conditions: freshwater, flow through, 25.3 °C, pH 7.5, hardness 45.1 mg/L CaCO3, alkalinity 39.6 mg/L CaCO3, dissolved oxygen 6.5 mg/L; Concentration: 60.9 ug/L for 96 hr /97% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 63,000(SRC), determined from a log Kow of 6.06(2) and a regression-derived equation(3), indicates that 2,4,6-tris(1,1-dimethylethyl)phenol is expected to be immobile in soil(SRC). Volatilization of 2,4,6-tris(1,1-dimethylethyl)phenol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.5X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 6.61X10-4 mm Hg(4), and water solubility, 35 mg/L(2). However, adsorption to soil is expected to attenuate volatilization(SRC). 2,4,6-Tris(1,1-methylethyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Utilizing the Japanese MITI test, 0% of the theoretical BOD was reached in 4 weeks using an activated sludge(5), suggesting that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 63,000(SRC), determined from a log Kow of 6.06(2) and a regression-derived equation(3), indicates that 2,4,6-tris(1,1-dimethylethyl)phenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 6.5X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 6.61X10-4 mm Hg(4), and water solubility, 35 mg/L(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 9 and 73 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 440 years if adsorption is considered(5). According to a classification scheme(6), measured BCF values of 4830-16,000 and 4320-23,200 in carp (Cyprinus carpio) exposed to 10 and 1 ppb, respectively(7), suggest bioconcentration in aquatic organisms is very high(SRC). Utilizing the Japanese MITI test, 0% of the theoretical BOD was reached in 4 weeks using an activated sludge(7), suggesting that biodegradation is not an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,4,6-tris(1,1-dimethylethyl)phenol, which has a vapor pressure of 6.61X10-4 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 2,4,6-tris(1,1-dimethylethyl)phenol 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 24 hours(SRC), calculated from its rate constant of 1.6X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 2,4,6-tris(1,1-dimethylethyl)phenol may be removed from the air by wet or dry deposition(SRC). 2,4,6-Tris(1,1-dimethylethyl)phenol does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The Koc of 2,4,6-tris(1,1-dimethylethyl)phenol is estimated as 63,000(SRC), using a log Kow of 6.06(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 2,4,6-tris(1,1-dimethylethyl)phenol is expected to be immobile in soil.

/ALTERNATIVE and IN VITRO TESTS/ 2,4,6-Tri-tert-butylphenol (TBP) ... produced phenoxyl radicals at pH >or= 9.0 and 2,4-di-t-butylphenol (DBP) at pH 12.5, but 3,3',5,5'-tetra-t-butyl-1,1'-biphenyl-2,2'-diol (bisDBP) did not ... . Both superoxide anion radical (O(2)(-)) scavenging activity and reactive oxygen species (ROS) production activity declined in the order of TBP > DBP > bisDBP. The cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) and human gingival fibroblast cells (HGF) declined in the order of DBP >> bisDBP = TBP = TBP-OOH (2,4,6-tri-t-butyl-4-hydroperoxy-2,5-cyclohexadiene-1-one). The cytotoxic activity of TBP, but not of DBP or bisDBP was significantly enhanced after visible light (VL)-irradiation for 10 min. The cytotoxicity of irradiated TBP was significantly higher than that of either original TBP or TBP-OOH, the oxidative metabolite of TBP, possibly due to the formation of TBP stable radical and ROS via oxidation. In contrast, the cytotoxic activity of DBP and bisDBP was independent of radical production, and therefore, may be intrinsic. A non-enzymatic oxidation decomposition of DBP or TBP was estimated from the formation of reaction enthalpy (DeltaH) using a modified neglect of diatomic overlap, parametric method 3 (MNDO-PM3) semi-empirical method, suggesting that O(2) is capable of activating DBP to a reactive quinone or dimer and that TBP phenoxyl radicals via oxidation directly affect extra- or intracellular bioactive materials, resulting in the induction of cytotoxicity.

BCF values of 4,830-16,000 and 4,320-23,200 were measured in carp (Cyprinus carpio) exposed to 10 and 1 ppb, respectively, of 2,4,6-tris(1,1-dimethylethyl)phenol over an 8-week period(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC).

The Henry's Law constant for 2,4,6-tris(1,1-methylethyl)phenol is estimated as 6.5X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 6.61X10-4 mm Hg(1), and water solubility, 35 mg/L(2). This Henry's Law constant indicates that 2,4,6-tris(1,1-dimethylethyl)phenol is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 9 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 73 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 440 years if adsorption is considered(4). 2,4,6-Tris(1,1-dimethylethyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Ten months old beagle males were given a daily dose of 2,4,6-tri-tert-butylphenol mixed with the dog food ... The food consumption rate was reduced in the high dose group. Diarrhea was observed in two animals receiving 173 mg/kg and one receiving 454 mg/kg for 3 to 5 days. Feces of one dog receiving 173 mg/kg and one receiving 454 mg/kg contained blood. Two animals of the high dose group showed signs such as gait abnormality (struggling), blepharoptosia /SRP: drooping of the upper eyelid/, and decreased body temperature. The animals continued showing these signs until the end of dosing. From this observation, it was concluded that TTBP at this dosage has some effect on the central nervous system (apparently autonomic, principally). Hematological examination was conducted on Day 11. Parameters included glutamic-oxalacetic transaminase (GOT), glutamic -pyruvic transaminase (GPT), alkaline phosphatase (ALP), cholinesterase (CHE), total protein (TP), glucose (Glc), total cholesterol (CHO), urea-nitrogen (UN), sodium (Na), potassium (K), calcium (Ca), white blood cells (WBC), red blood cells (RBC), hemoglobin (Hgb) and hematcrit (Hct). GOT, GPT and ALP increased relative to dose levels (marginal at 49.2 mg/kg) ... /It was concluded that/ TTBP did not cause hemorrhage or blood coagulation disorder to dogs. Behavioral abnormalities and increase in GOT, GPT and ALP were observed in animals of the highest dose group. Hematological observations indicated that TTBP might affect the liver parenchymal cells and increase metabolizing enzymes.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In order to study the chronic toxicity of 2, 4, 6-tri-tert-butylphenol (TTBP), groups of 40 Slc: Wistar rats of either sex were fed diet containing 0, 30, 100, 300 or 1000 ppm of TTBP for up to 24 months. Hematological, biochemical and histopathological examinations performed periodically revealed slight microcytic anemia, changes in some biochemical parameters relating to liver function and focal necrosis of liver cells following TTBP administration, and these changes observed in females were severer than those in males. No neoplastic responses following TTBP administration were noted. Noticeable changes were not observed in the 30 ppm group throughout the experimental period. Thus, it was concluded that TTBP causes liver injury characterized by focal necrosis with microcytic anemia and elevations of serum phospholipids and cholesterol levels presumably occurring as secondary effects following the liver injury.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Four-week old Wistar rats were divided into the 5 groups /with 40 males and 40 females per dose/. The animals were fed diet containing the test substance for 24 months. General condition and body weights were observed and recorded throughout the experiment. Hematological and histopathological examinations were performed for all groups. /A/ NOAEL /of/ 30 ppm /was observed with/ slight changes of hemoglobin concentration (Hb), mean corpuscular volume (MCV), blood urea nitrogen (BUN), glutamate oxaloacetate transaminase, phospholipids, total cholesterol (T-Chol) and g-glutamyl transpeptidase (g-GTP) levels, but with liver and kidney weights within normal ranges ... Statistically significant reduction in body weight gain was found in female animals of the 1000 ppm group, 12 months after the start of the experiment and thereafter ... /At/ 6 months statistically significant decreases of Hb and MCV and statistically significant increases of platelet count (except in animals receiving 300 ppm), phospholipids and T-Chol values were observed in male groups receiving 300 and 1000 ppm. Statistically significant decreases of MCV and glutamate oxaloacetate transaminase and statistically significant increases of T-Chol and gamma-GTP values were observed in all treated female groups. Statistically significant decreases of Hb in the 300 and 1000 ppm groups and BUN in the 30 and 1000 ppm groups, and statistically significant increases of platelet count in the 300 and 1000 ppm groups and gamma-GTP in the 1000 ppm group were also found. /At/ 12 months males /presented/ statistically significant decreases of Hb in the 1000 ppm group, MCV in the 30, 300 and 1000 ppm groups and g-GTP in the 30 and 100 ppm groups were observed. Levels of BUN were gamma-GTP in the 100 ppm group were and glutamate oxaloacetate transaminase in the 300 and 1000 ppm groups and phospholipids and T-Chol in the 1000 ppm groups significantly elevated. In females, statistically significant decreases of Hb in the two higher groups, MCV in the three higher groups, glutamate oxaloacetate transaminase in all treated groups and observed. Statistically significant increases of platelet count and phospholipids in the 100, 300 and 1000 ppm groups and T-Chol in all treated groups were found. /At/ 18 months males /presented/ statistically significant decrease of MCV in the 1000 ppm group, and statistically significant increases of BUN in the 100 and 300 ppm groups and gamma-GTP in the 1000 ppm group were observed. In all treated female groups, statistically significant decreases of Hb (except the 100 ppm group) and MCV, and statistically significant increases of phospholipids and T significant decreases of GOT in the 30 and 300 ppm groups and gamma-GTP in the 30 ppm group, and statistically significant increases of platelet count in the 300 and 1000 ppm group were also found. /At/ 24 months males /presented/ statistically significant decreases of MCV in the 1000 ppm group, and statistically significant increases of platelet count in the 1000 ppm group and phospholipids and T-Chol in the 100, 300 and 1000 ppm groups were observed. In females, statistically significant decreases of MCV in the 300 and 1000 ppm groups and g-GTP in the 1000 ppm group, and statistically significant increases of platelet count in the 1000 ppm group and phospholipids and T-Chol in all treated groups were found. Statistically significant increases of relative liver weight in male rats receiving 300 and 1000 ppm and in all female treated groups except the 30 ppm at 12 months were found throughout the study. Statistically significant increases of kidney weights were observed in the animals receiving 1000 ppm at 12 months, in females receiving 1000 ppm at 18 months and in the males receiving 1000 ppm and females receiving 100, 300 and 1000 ppm at 24 months. Statistically significant increases of adrenal weights in the higher dose groups were also observed. In the 300 and 1000 ppm groups, swelling, statistically significant histopathological changes including focal necrosis and vacuolization of liver cells were noted from 6 months after the start. No other neoplastic lesions were observed in other organs throughout the study ... /It was concluded that/ administration of TTBP caused focal necrosis, swelling and vacuolization of liver cells, increases in liver weight, slight microcytic anemia and elevation of serum phospholipid and cholesterol levels, presumably occurring as secondary effects following hepatotoxicity. The changes observed in female rats were more severe than those seen in males. Incidences of tumors in TTBP treated groups were not significantly higher than that of control.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... The /female/ mice, /strain ICR/Ha/ were placed on a diet containing /0.03 mmol/g (= 4,500 ppm in diet)/ test substance or diet without additions (control group) when they were 9 weeks of age. On the eighth day, the mice were given the first of 8 doses (2 times a week for 4 weeks) of 1 mg of BP in 0.2 mL of corn oil. The experimental diets were fed during the entire period of carcinogen administration and were discontinued 3 days after the last dose of carcinogen, at which time the mice were 98 days old. The mice were then fed pellets of rat chow, until they were killed at 211 days old and autopsied. Tumors of the forestomach were counted under a dissecting microscope. Tumors that were 1 mm or larger were recorded and checked histologically ... In the animals given dietary addition of 2,4,6-tri-tert-butylphenol, 93% of animals had neoplasms of the forestomach and there was no reduction in the number of neoplasms per animal. /From the test researchers concluded that the/ substitution of a third tert-butyl group para to the hydroxyl group apparently destroyed any inhibitory activity of 2,4,6-tri-tert-butylphenol in this mouse model, as compared with the di-substituted phenols assessed in this study, which did show inhibitory activity. /Mammalian health effects other/

The rate constant for the vapor-phase reaction of 2,4,6-tris(1,1-dimethylethyl)phenol with photochemically-produced hydroxyl radicals has been estimated as 1.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 24 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 2,4,6-Tris(1,1-dimethylethyl)phenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 2,4,6-Tris(1,1-dimethylethyl)phenol does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Used in Canada as an antioxidant in hydrocarbon fuels (gasoline, jet fuel, diesel, and biodiesel) and formerly as a lubricant additive; [ExPub: Government of Canada: Proposed Risk Management Approach] Also used as a starting material for 2,6-di-tert-butyl-4-methoxyphenol (antioxidant); [HSDB] Used as an intermediate; [ExPub: ECHA REACH Registrations]

2,4,6-Tri-tert-butylphenol is the starting material for the synthesis of 2,6-di-tert-butyl-4-methoxyphenol which is a powerful antioxidant.

Permissible antioxidant for aviation gasolines (when mixed with other butylphenols)

As an additive in fuel, oil, gasoline or lubricants

2023: 500,000 - <1,000,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7391]

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7392]

Phenol, 2,4,6-tris(1,1-dimethylethyl)- 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).

All Other Basic Organic Chemical Manufacturing

Phenol, 2,4,6-tris(1,1-dimethylethyl)-: ACTIVE