2,4-Di-tert-butylphenol

Other Classes -> Phenols

Antioxidant

log Kow = 5.19

5.19

4.74

In water, 35 mg/L at 25 °C

Slightly soluble in carbon tetrachloride; insoluble in alkali

0.035 mg/mL at 25 °C

263.5 °C

263.00 to 264.00 °C. @ 760.00 mm Hg

56.5 °C

56.5 °C

0.0075 [mmHg]

4.77X10-3 mm Hg at 24 °C (extrapolated)

This chemical does not meet GHS hazard criteria for 1.6% (19 of 1181) of reports.

Danger

H302 (36.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1181 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Chemical: Phenol, 2,4-bis(1,1-dimethylethyl)-

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

Status: Active Update: 24-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/14828

2,4-Di-t-butylphenol: Does not have an individual approval but may be used under an appropriate group standard

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] Reported oral LD50 (rat) values of 3,250 and 1,300 mg/kg; A skin and eye irritant in rabbits; Not a skin sensitizer in guinea pig maximization test; Identified in samples of rubber most often used by employees in hydraulic pump manufacturing diagnosed with cutaneous depigmentation (vitiligo); [IUCLID] Histopathological changes of the liver and kidney observed in 28-day oral study of rats; NOEL's of 75 mg/kg/day in males and 20 mg/kg/day in females; [JECDB] An irritant that may cause serious eye injury; [Sigma-Aldrich MSDS] See Clorophene.

2,4-Di-tert-butylphenol

Marine pollutant

Acute Tox. 4 (36.9%)

Acute toxicity (Oral) - Category 4

Acute toxicity (Oral) - Category 4

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.

To fight fire, use foam, CO2, dry chemical.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. 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.

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

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

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.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

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

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

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: Face shield and safety glasses. 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: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

BACKGROUND: In utero exposure to environmental chemicals can adversely impact pregnancy outcomes and childhood health, but minimal biomonitoring data exist on the majority of chemicals used in commerce. OBJECTIVES: We aimed to profile exposure to multiple environmental organic acids (EOAs) and identify novel chemicals that have not been previously biomonitored in a diverse population of pregnant women. METHODS: We used liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a suspect screen for 696 EOAs, (e.g., phenols and phthalate metabolites) on the maternal serum collected at delivery from 75 pregnant women delivering at two large San Francisco Hospitals. We examined demographic differences in peak areas and detection frequency (DF) of suspect EOAs using a Kruskal-Wallis Rank Sum test or Fisher's exact test. We confirmed selected suspects by comparison with their respective reference standards. RESULTS: We detected, on average, 56 [standard deviation (SD)]: 8) suspect EOAs in each sample (range: 32-73). Twelve suspect EOAs with DF=60 were matched to 21 candidate compounds in our EOA database, two-thirds of which are novel chemicals. We found demographic differences in DF for 13 suspect EOAs and confirmed the presence of 6 priority novel chemicals: 2,4-Di-tert-butylphenol, Pyrocatechol, 2,4-Dinitrophenol, 3,5-Di-tert-butylsalicylic acid, 4-Hydroxycoumarin, and 2'-Hydroxyacetophenone (or 3'-Hydroxyacetophenone). The first two are high-production-volume chemicals in the United States. CONCLUSION: Suspect screening in human biomonitoring provides a viable method to characterize a broad spectrum of environmental chemicals to prioritize for targeted method development and quantification.

The oxidized low-density lipoprotein (ox-LDL) plays a critical role at the early stages of atherosclerosis. Thus, the prevention of LDL-oxidation by antioxidants may arrest the progression of atherosclerosis. Two quinoline alkaloids, 3,8-dihydroxyquinoline (1) and 2,8-dihydroxy-3,4-dimethoxyquinoline (3), and 2,4-di-tert-butylphenol (2) were isolated from the dried body of Scolopendra subspinipes. Compounds 1-3 exhibited antioxidant activities on copper-mediated (1: IC50=2.6 microM, 2: IC50=8.2 microM, 3: IC50=63.0 microM), AAPH-mediated oxidation (1: IC50=3.9 microM, 2: IC50=9.9 microM, 3: IC50=71.8 microM), and SIN-1-mediated oxidation (1: 70%, 2: 52%, 3: 29% at 5.0 microM) in the TBARS assay. The antioxidant activities of compounds 1-3 were tested with respect to other parameters, such as the lag time of conjugated diene fromation, relative electrophoretic mobility (REM) of ox-LDL, and apoB-100 fragmentation on copper-mediated LDL-oxidation. In addition, compounds 1-3 showed 1,1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activity and compound 1 also exhibited metal chelating activity.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9000(SRC), determined from a structure estimation method(2), indicates that 2,4-di-tert-butylphenol is expected to be immobile in soil(SRC). Volatilization of 2,4-di-tert-butylphenol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.7X10-5 atm-cu m/mole(SRC), based upon its vapor pressure, 4.77X10-3 mm Hg(3), and water solubility, 35 mg/L(4). However, adsorption to soil is expected to attenuate volatilization(SRC). 2,4-Di-tert-butylphenol 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(4) indicating 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 9000(SRC), determined from a structure estimation method(2), indicates that 2,4-di-tert-butylphenol 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 3.7X10-5 atm-cu m/mole(SRC) derived from its vapor pressure, 4.77X10-3 mm Hg(4), and water solubility, 35 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 1.6 and 16 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 120 months if adsorption is considered(6). According to a classification scheme(7), a BCF range of 128-436(5) suggests that bioconcentration in aquatic organisms is high(SRC). Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 4 weeks(5) indicating 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-di-tert-butylphenol, which has a vapor pressure of 4.77X10-3 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,4-di-tert-butylphenol 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 8 hrs(SRC), calculated from its rate constant of 4.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 2,4-Di-tert-butylphenol 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).

IDENTIFICATION AND USE: 2,4-Di-tert-butylphenol (DTBP) is a solid, which is used as UV stabilizer and an antioxidant for hydrocarbon-based products. HUMAN STUDIES: Occupational vitiligo (cutaneous depigmentation) cases have been reported in workers who handled the rubber containing DTBP. Cytoxicity to multiple human cell lines have been reported. DTBP induces senescence in human gastric adenocarcinoma AGS cells as evidenced by upregulation of p21 and Rb and increased beta-galactosidase activity. DTBP also induces mitotic catastrophe and generates multinucleated cells, which is accompanied by an increase in the proportion of polymerized tubulin, possibly caused by inhibition of HDAC6 enzyme activity. ANIMAL STUDIES: A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to slight edema. Other skin reactions noted were hemorrhage of the dermal capillaries, blanching, light brown discoloration of the epidermis, crust formation and hardened light brown-colored scabs. It was non-sensitizing to guinea pigs. The susceptibility of newborn rats to DTBP was found to be 4-5 times higher than that of young rats. The 1 -generation fertility / Repeated dose toxicity study was carried out in the rat. The parental generation rats were fed diets containing DTBP at dose levels of 50, 150 or 300 mg/kg/day for 4 weeks before mating and throughout mating, gestation and lactation. Groups of 20 generation F1 progeny of each sex were maintained on the experimental diets for 13 weeks after weaning. Reproductive capability of the parental generation animals was unimpaired by the ingestion of DTBP at dose levels of up to 300 mg/kg/d. Ingestion of 300 mg DTBP/kg/d elicited a significant reduction in the mean number of progeny born and reduced the growth rate of the F1 progeny during lactation. The former effect was not apparent at dose levels of 50 and 150 mg/kg/d. The reduced growth rate was also apparent in the progeny of animals treated at 150 mg/kg/d and was associated with a higher average litter number. There were no substance related deaths in any of the experimental groups during the feeding phase. Dietary administration of DTBP at a dose level of 300 mg/kg daily for 13 weeks to rats elicited a primary toxic effect on growth rate, and at dose level of 150 mg/kg/d, elicited growth retardation which was secondary to reduced diet palatability. DTBP was not clastogenic in vivo.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

2,4-Di-tert-butylphenol was detected at a concentration range of 0.5-0.6 ppm in river water collected in the vicinity of an unspecified specialty chemicals manufacturing plant. River samples were collected at intervals from November 1975 to September 1976(1).

2,4-Di-tert-butylphenol occurrence in treated municipal wastewater and river water collected during October 1997 and February/March 1998(1).[Table#8557]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2,4-di-tert-butylphenol can be estimated to be 9000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2,4-di-tert-butylphenol is expected to be immobile in soil(SRC).

/CASE REPORTS/ We investigated the occurrence of cutaneous depigmentation (vitiligo) /SRP: leukoderma/ among employees of a company that manufactured hydraulic pumps. The interiors of these pumps were injection-molded with rubber. We identified a small but significant cluster of vitiligo cases among a group of employees who frequently handled the rubber used in this injection molding process. Although none of the additives specified in the rubber formulations was a phenolic or catecholic derivative, known to be potential causes of chemically induced vitiligo, gas chromatographic analysis identified a para-substituted phenol (2,4-di-tert-butylphenol, DTBP) in solid samples of the most frequently used rubber. Surface wipe analysis confirmed that workers could be exposed to DTBP from simple handling of the rubber. We subsequently established that the solid bulk rubber used as the base in these stock rubber formulations contained both DTBP and smaller quantities of p-tert-butylphenol. Both had formed as unsuspected byproducts during chemical synthesis of two antioxidants added to the solid bulk rubber by a major rubber supplier. We conclude that the unsuspected presence of potential chemical depigmenting agents in solid bulk rubber, from which industrial rubber products are formulated, may contribute to the occurrence of occupational vitiligo, and that a simple review of ingredients in rubber formulations is inadequate to detect their presence.

/ALTERNATIVE and IN VITRO TESTS/ 2,4,6-Tri-tert-butylphenol (TBP)-related compounds are used for stabilizing plastics by making them resistant to oxidation. However, the cytotoxic activity of these compounds has not yet been established. TBP produced phenoxyl radicals at pH >/= 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, using ESR spectroscopy. 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.

/ALTERNATIVE and IN VITRO TESTS/ The natural product 2,4-di-tert-butylphenol (DTBP) has a wide spectrum of biological functions, including anticancer activities, although the underlying mechanisms are poorly understood. Here, we found that DTBP induces senescence in human gastric adenocarcinoma AGS cells as evidenced by upregulation of p21 and Rb and increased beta-galactosidase activity. DTBP also induces mitotic catastrophe and generates multinucleated cells, which is accompanied by an increase in the proportion of polymerized tubulin, possibly caused by inhibition of HDAC6 enzyme activity. In silico docking analysis showed that DTBP docked at the entrance of the ligand-binding pocket of the HDAC6 enzyme. Accordingly, DTBP represents a promising lead structure for the development of HDAC6 inhibitors, with an improvement in specificity conferred by modification of the cap group. We propose for the first time that the underlying mechanism of the anticancer activity of DTBP is attributed to inhibition of HDAC6 activity.

/ALTERNATIVE and IN VITRO TESTS/ The volatile organic compound 2,4-di-tert-butyl phenol (2,4 DTBP) was purified from the cell free supernatant of a newly isolated Lactococcus sp. by solvent extraction and chromatographic techniques. Molecular characterization of the compound by ESI-MS, 1H NMR and FTIR analysis revealed the structure, C14H22O. Fungicidal activity was demonstrated against Aspergillus niger, Fusarium oxysporum and Penicillium chrysogenum by disc diffusion assay. Among the cell lines tested for cytotoxicity of this compound (normal cell line H9c2 and cancer cell lines HeLa and MCF-7), a remarkable cytotoxicity against HeLa cells with an IC50 value of 10 ug/mL was shown. A biocontrol experiment with 2,4 DTBP supplemented fraction prevented growth of the above mentioned fungi on wheat grains. The study further strengthens the case for development of biopreservatives and dietary antioxidants from lactic acid bacteria for food applications.

Studies on the quality of marine environments in Italy have traditionally favoured heavily impacted areas, such as harbours and industrial areas, while there are few investigations aimed at the evaluation of the presence of organic pollutants in the areas of marine reserve. The aim of this study was to determine endocrine-disrupting compounds (EDCs) in the liver of white seabreams (Diplodus sargus sargus) from the Natural Reserve of Torre Guaceto, Italy. Among EDCs, alkyl-phenols 2,6-DTBP, 2,4-DTBP, OP, and BPA were identified and quantified. The mean concentration of 2,6-DTBP, 2,4-DTBP, OP, and BPA were 2.2, 2.0, 1.2 and 3.6 ng/g of liver, respectively, confirming the occurrence and transfer of these organic pollutants in the food web of marine organisms in marine reserves.

Used as an antioxidant; [REPROTOX] Used in the chemical and fuel industries; Used as an intermediate and stabilizer; [IUCLID] Used to make phenolic antioxidants and UV stabilizers; [CPS&Q - Summary Fact Sheet] Used as a stabilizer in manufacture and formulation, fuel additive, and intermediate; [ECHA REACH Registrations]

The main use of 2,4-di-tert-butylphenols is in the manufacture of its triphosphite that is employed as a (co-)stabilizer for poly (vinyl chloride), and of its benzotriazole derivatives that are used as UV absorbers in polyolefins.

... used industrially as UV stabilizer and an antioxidant for hydrocarbon-based products ranging from petrochemicals to plastics. Illustrative of its usefulness, it prevents gumming in aviation fuels.

2023: 10,000,000 - <50,000,000 lb

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Phenol, 2,4-bis(1,1-dimethylethyl)-:

Plastics Product Manufacturing

Phenol, 2,4-bis(1,1-dimethylethyl)-: ACTIVE