2,4,6-Tri-(dimethylamino-methyl)phenol

2,4,6-tridimethylaminomethyl phenol appears as an amber to red-brown liquid with an amine odor. Less dense than water. Vapors heavier than air. Corrosive to the eyes, skin, mouth, stomach and throat. Vapors may irritate the eyes and corrode the upper respiratory tract.

Liquid

Liquid; [IUCLID] Clear, light yellow viscous liquid; [Aldrich MSDS]

Warning

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

P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P337+P317, P362+P364, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.1% (2 of 1578) of reports.

Danger

H302 (91.3%): Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Phenol, 2,4,6-tris[(dimethylamino)methyl]-

Phenol, 2,4,6-tris[(dimethylamino)methyl]- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 2,4,6-tris[(dimethylamino)methyl]- 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: 11-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/13928

2,4,6-Tris(dimethylaminomethyl) phenol: Does not have an individual approval but may be used under an appropriate group standard

European Chemicals Agency (ECHA); REACH Registration for 2,4,6-tris(dimethylaminomethyl)phenol; This is unique source of information on the chemicals manufactured and imported in Europe. It covers their hazardous properties, classification and information on how to use them safely. It is generated by industry in line with their responsibilities under the EU chemicals legislation. This information is a valuable resource for advancing the safe use of chemicals and for the replacement of the most hazardous ones by safer alternatives.[European Chemicals Agency (ECHA); REACH Registration for 2,4,6-tris(dimethylaminomethyl)phenol; Available from, as of May 29, 2014: http://echa.europa.eu/]

Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. TOXICITY - Variable. Some are very poisonous; others are only slightly toxic. Many amines are skin irritants, and some are sensitizers.

3 - Materials that, under emergency conditions, can cause serious or permanent injury.

0 - Materials that will not burn under typical fire conditions, including intrinsically noncombustible materials such as concrete, stone, and sand.

0 - Materials that in themselves are normally stable, even under fire conditions.

Storage temperature: 2-8 °C

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.

Accidental Release Measures. Personal precautions: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. 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 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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits 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.

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

Avoid contact with skin and eyes. Avoid inhalation of vapor or mist.

0.60 [mg/m3]

6.6 [mg/m3]

40 [mg/m3]

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Hand protection: Handle with gloves

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multi-purpose combination (US) or type ABEK (EN 14387) 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).

Eye protection: Tightly fitting safety goggles. Faceshield (8-inch minimum). Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin and 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.

LC50; Species: Oncorhynchus mykiss (Rainbow trout); Conditions: static; Concentration: >180 mg/L but <240 mg/L for 96 hr[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

LC50; Species: Oncorhynchus mykiss (Rainbow trout); Conditions: static; Concentration: 222 mg/L for 24 hr[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

LC50; Species: Cyprinus carpio (Carp); Conditions: static; Concentration: 249 mg/L for 24 hr[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

LC50; Species: Cyprinus carpio (Carp); Conditions: static; Concentration: 175 mg/L for 96 hr[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

For more Ecotoxicity Values (Complete) data for 2,4,6-tris(dimethylaminomethyl)phenol (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1480(SRC), determined from a structure estimation method(2), indicates that 2,4,6-tris(dimethylaminomethyl)phenol is expected to have low mobility in soil(SRC). Estimated pKa values of 8.41, 9.12 and 9.75 for the three amine groups(3), indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of 2,4,6-tris(dimethylaminomethyl)phenol from moist soil surfaces is not expected to be an important fate process(SRC) based on the estimated pKa values(3). 2,4,6-Tris(dimethylaminomethyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2014).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1480(SRC), determined from a structure estimation method(2), indicates that 2,4,6-tris(dimethylaminomethyl)phenol is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 8.41, 9.12 and 9.75 for the three amine groups(3), indicate 2,4,6-tris(dimethylaminomethyl)phenol will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9)(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.77(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2014).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,4,6-tris(dimethylaminomethyl)phenol, which has an estimated vapor pressure of 1.6X10-6 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 2,4,6-tris(dimethylaminomethyl)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 1.4 hours(SRC), calculated from its rate constant of 2.5X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase 2,4,6-tris(dimethylaminomethyl)phenol may be removed from the air by wet and dry deposition(SRC). 2,4,6-Tris(dimethylaminomethyl)phenol does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 2,4,6-tris(dimethylaminomethyl)phenol (tris-DMP) is a clear, light yellow, viscous liquid. It is used as a catalyst and co-curing agent for room temperature cure of epoxides and as a paint hardener. HUMAN EXPOSURE AND TOXICITY: A group of industrial painters was followed to assess the incidence of allergic contact dermatitis (ACD) caused by exposure to epoxy resin systems. The study lasted for 4 years and included 2236 workers, contributing 5113 person years. Of 57 patch-tested workers, 23 with ACD caused by epoxy resin systems were found, indicating an incidence rate of 4.5/1000 person years. 4 workers (17%) were identified solely by patch tests to tris-DMP, m-xylene-alpha, alpha-diamine (XAD), and/or 2,2,4 trimethylhexamethylenediamine. Positive patch tests to tris-DMP were seen in 7 workers indicating that this chemical is an important sensitizer in industrial painters. Tris-DMP was non-clastogenic to human lymphocytes in vitro. ANIMAL STUDIES: Rats were exposed dermally to tris-DMP at dose levels of 0, 5, 25, and 125 mg/kg/day, 5 days/week for 4 weeks. Treatment-related signs and symptoms included slight to moderate excitability and/or hypertonicity in the 25- and 125-mg/kg dose groups. Slight to moderate erythema, occasionally accompanied by edema and necrosis, was observed in the 125- mg/kg dose group. Histopathology revealed moderate to marked hydropic change and slight parakeratosis in the epidermis in the 125-mg/kg dose group. Slight hydropic change without parakeratosis was noted in the 25-mg/kg dose group. In developmental study, rats were exposed via oral gavage to tris-DMP at dose levels of 0, 15, 50, and 150 mg/kg/day for two weeks prior to mating, during gestation and for 4 days postpartum. There were no unscheduled deaths during the study and no clinical signs of toxicity were observed. No adverse effect on mating performance, fertility, or gestation length was detected. Litter data at 15 mg/kg/day were unaffected by treatment. There were no adverse effects of maternal treatment on offspring growth or development including pinna unfolding and surface righting reflex. No treatment-related macroscopic abnormalities were detected in the offspring of all treatment groups.There were no treatment-related changes observed in the reproductive or accessory reproductive organs for parental rats of either sex. At 50 and 150 mg/kg/day treatment appeared to be associated with a higher level of preimplantation loss although there was no subsequent effect on post-natal survival, growth or development. Tris-DMP diluted in sterile water was not mutagenic in a Salmonella typhimurium-Escherichia coli direct plate incorporation assay performed using S. typhimurium strains TA1535, TA1537, TA98, and TA100 and E. coli strain WP2uvrA- over a dose range of 50 to 5,000 ug/plate in both the presence and absence of a metabolic activation system. Tris-DMP was considered to be non-mutagenic to L5178Y cells under the conditions of the test with and without activation. ECOTOXICITY STUDIES: Tris-DMP is practically nontoxic to fish and aquatic invertebrates.

EPA has released the first beta version (version 0.5) of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The beta version of 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; See the data in Chemical Explorer/[USEPA; ICSS Dashboard Application; Available from, as of June 27, 2014: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2,4,6-tris(dimethylaminomethyl)phenol can be estimated to be 1480(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2,4,6-tris(dimethylaminomethyl)phenol is expected to have low mobility in soil. The estimated pKa's of 2,4,6-tris(dimethylaminomethyl)phenol are estimated as 8.41, 9.12 and 9.75 for the three amine groups and 10.4 for the hydroxyl group(3), indicating that this compound will exist almost entirely in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/CASE REPORTS/ Epoxy resin compounds (ERC) include a large number of sensitizing chemicals such as epoxy resins (ER), hardeners (curing agents), and reactive diluents. Allergic contact dermatitis (ACD) caused by ERCS is often occupational. The study reports a patient, sensitized to a hardener of a two-component epoxy paint. Three conventional patch test sessions were performed to diagnose the causative chemical. Lliterature on sensitizing epoxy-resin hardeners is also reviewed. A 47-year-old nonatopic woman developed dermatitis from a two-component epoxy paint. Patch testing with epoxy resin was negative, but 2,4,6-tris(dimethylaminomethyl)phenol (tris-DMP), used in the paint hardener, induced an allergic patch test reaction. ... No one chemical can be used to screen for sensitization to the many different epoxy hardeners. Extensive patch testing may be required to reveal the hardener that has caused the allergy. The hardener, 2,4,6-tris-(dimethylaminomethyl)phenol (tris-DMP), is a new sensitizer. To verify ACD caused by tris-DMP, patch-testing at 1% in petrolatum is suggested.

/SURVEILLANCE/ A group of industrial painters employed in 6 companies of the Norwegian oil industry was followed to assess the incidence of allergic contact dermatitis (ACD) caused by exposure to epoxy resin systems. The study lasted from 1 September 1997 to 31 August 2001 and included 2236 workers, contributing 5113 person years. Commercially available patch test series were supplemented with a special study series based on known or suspected sensitizers present at the workplaces. Of 57 patch-tested workers, 23 with ACD caused by epoxy resin systems were found, indicating an incidence rate of 4.5/1000 person years. In /this/ study patch test series, 4 workers (17%) were identified solely by patch tests to 2,4,6-tris-(dimethylaminomethyl)phenol (tris-DMP), m-xylene-alpha,alpha-diamine (XAD), and/or 2,2,4 trimethylhexamethylenediamine. Positive patch tests to tris-DMP and XAD were seen in 7 and 8 workers, respectively, indicating that the 2 chemicals are important sensitizers in industrial painters. They are, however, not classified as skin sensitizers according to the European regulations on the classification and labelling of dangerous chemicals. The results show the usefulness of including patch tests based on an investigation of known and suspected skin sensitizers present at the workplaces.

/GENOTOXICITY/ Duplicate cultures of human lymphocytes, treated with the test material, were evaluated for chromosome aberrations at up to four dose levels, together with vehicle and positive controls. In Experiment 1, cells were treated for 4 hours in the presence of an induced rat liver homogenate metabolizing system (S9) at a 2% final concentration with cell harvest after a 20-hour expression period and a second group of cells were treated for 4 hours in the absence of metabolic activation (S9) with a 20-hour expression period. In Experiment 2, the 4-hour exposure with addition of S9 was repeated (using a 1% final S9 concentration), whilst in the absence of metabolic activation the exposure time was increased to 24 hours. The test material did not induce a statistically significant increase in the numbers of polyploid cells or a statistically significant increase in the frequency of cells with chromosome aberrations in either the absence or presence of a liver enzyme metabolising system at any dose level in either of two separate experiments. Using a dose range that included a dose level that induced mitotic inhibition, 2,4,6-tris[(dimethylamino)methyl]phenol was non-clastogenic to human lymphocytes in vitro.

An estimated BCF of 3 was calculated in fish for 2,4,6-tris(dimethylaminomethyl)phenol(SRC), using an estimated log Kow of 0.77(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The pKa's of 2,4,6-tris(dimethylaminomethyl)phenol are estimated as 8.41, 9.12 and 9.75 for the three amine groups and 10.4 for the hydroxyl group(1), indicating that this compound will exist almost entirely in cation form in the environment. Volatilization from moist soil and water surfaces is not expected because cations do not volatilize. 2,4,6-Tris(dimethylaminomethyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Acute Exposure/ Groups of ten Sprague-Dawley rats (five male and five female) were orally administered undiluted phenol, 2,4,6-tris[(dimethylamino)methyl]- at dose levels of 1333, 2000 and 3000 mg/kg body weight. Surviving animals were observed daily post-dose for 14 days. All animals in the low dose group survived. Three out of ten animals in the mid-dose group died. All animals in the high-dose group died. All surviving animals appeared normal within three days or less of dosing, gained weight, and the only findings seen at necropsy in the survivors were abnormalities of the nonglandular stomach epithelium. Since this material is corrosive, the stomach findings were not unusual. The oral LD50 for phenol, 2,4,6-tris[(dimethylamino)methyl]- in rats was 2169 mg/kg body weight[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats were exposed dermally to tris(dimethylaminomethyl)phenol at dose levels of 0, 5, 25, and 125 mg/kg/day, 5 days/week for 4 weeks. Treatment-related signs and symptoms included slight to moderate excitability and/or hypertonicity in the 25- and 125-mg/kg, dose groups. Slight to moderate erythema, occasionally accompanied by edema and necrosis, was observed in the 125- mg/kg, dose group. Histopathology revealed moderate to marked hydropic change and slight parakeratosis in the epidermis in the 125-mg/kg, dose group. Slight hydropic change without parakeratosis was noted in the 25-mg/kg, dose group. The no observed effect level (NOEL) was 5 mg/kg/day[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ As part of an OECD 422 study, rats were exposed via oral gavage to 2,4,6-tris[(dimethylamino)methyl]phenol at dose levels of 0, 15, 50, and 150 mg/kg/day for two weeks prior to mating, during gestation and for 4 days post partum. There were no unscheduled deaths during the study and no clinical signs of toxicity were observed. No adverse effect on mating performance, fertility, or gestation length was detected. While not statistically significant, at 150 mg/kg/day there was a lower corpora lutea count and a higher pre-implantation loss compared with the controls and at 50 mg/kg/day, pre-implantation loss was again higher than controls. Resultant litter size at this dosage was lower than the control but offspring survival was unaffected by treatment. Litter data at 15 mg/kg/day were unaffected by treatment. There were no adverse affects of maternal treatment on offspring growth or development including pinna unfolding and surface righting reflex. No treatment-related macroscopic abnormalities were detected in the offspring of all treatment groups. There were no treatment-related changes observed in the reproductive or accessory reproductive organs for parental rats of either sex. At 50 and 150 mg/kg/day treatment appeared to be associated with a higher level of preimplantation loss although there was no subsequent effect on post-natal survival, growth or development. The NOEL for reproductive (fertility) toxicity was therefore, considered to be 15 mg/kg/day.

/GENOTOXICITY/ Phenol, 2,4,6-tris[(dimethylamino)methyl]- diluted in sterile water was examined for mutagenic activity in a Salmonella typhimurium-Escherichia coli direct plate incorporation assay. The assay was performed using S. typhimurium strains TA1535, TA1537, TA98, and TA100 and E. coli strain WP2uvrA- over a dose range of 50 to 5,000 ug/plate in both the presence and absence of a rat-liver S9 metabolic activation system. OECD guideline 471 was followed. Phenol, 2,4,6-tris[(dimethylamino)methyl]- was not mutagenic under the test conditions used in this bacterial assay.[US EPA; High Production Volume (HPV) Challenge Program Data Analysis and Test Plan For Phenol, 2,4,6-tris

For more Non-Human Toxicity Excerpts (Complete) data for 2,4,6-tris(dimethylaminomethyl)phenol (8 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of 2,4,6-tris(dimethylaminomethyl)phenol with photochemically-produced hydroxyl radicals has been estimated as 2.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9)(2). 2,4,6-Tris(dimethylaminomethyl)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).

Permitted for use as an inert ingredient in non-food pesticide products; [EPA] Used in the chemical and polymers industries; Used as an adhesive and binding agent, construction materials additive, catalyst for epoxy resins, and curing agent for polyurethane; [IUCLID] Used as a catalyst for rigid foams and as a curing agent (tertiary amine activator) for epoxy resins; [EPA ChAMP] A promoter factor for spreading circular DNA, linear DNA, and DNA-protein complexes. [ChemIDplus]

Working with Glues and Adhesives [Category: Other]

Catalyst and co-curing agent for room temperature cure of epoxides

Used in the presence of high levels of MDI /4,4'-methylenediphenyl diisocyanate/ to promote trimerization of the isocyanate and ... form isocyanate ring structures.

Catalyst and hardener in epoxy resins

Paint hardener

2023: 1,000,000 - <5,000,000 lb

Phenol, 2,4,6-tris[(dimethylamino)methyl]- 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).[EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program. Phenol, 2,4,6-tris

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#8188]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Phenol, 2,4,6-tris[(dimethylamino)methyl]-. Aggregated National Production Volume: 1 to < 10 million pounds.[US EPA; Non-Confidential 2006 Inventory Update Reporting. National Chemical Information. Phenol, 2,4,6-tris

Non-confidential 2014 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Phenol, 2,4,6-tris[(dimethylamino)methyl]-. National Production Volume: 1,000,000 - 10,000,000 lb/yr.[USEPA/Pollution Prevention and Toxics; 2014 Chemical Data Reporting Database. Phenol, 2,4,6-tris

Adhesive Manufacturing

Phenol, 2,4,6-tris[(dimethylamino)methyl]-: ACTIVE