Tris(2-ethylhexyl)benzol-1,2,4-tricarboxylat

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Keep in suitable, closed containers for disposal.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a 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.

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.

Waste treatment methods. 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.

Appropriate engineering controls: General industrial hygiene practice.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

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: Impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Workers were exposed to tris(2-ethylhexyl) trimellitate in the atmosphere in a Japanese production site in their occupations of sampling, analysis, and drum filling operations at concentrations of 0.210 mg/cu m, 0.053, and 0.076 mg/cu m, respectively(1). The total daily intake of tris(2-ethylhexyl) trimellitate in a single worker with a body weight of 70 kg, and respiratory volume of 1.25 cu m/hour was 1.77X10-3 mg/kg/day(1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 6.7X10+7(SRC), determined from a structure estimation method(2), indicates that tris(2-ethylhexyl) trimellitate is expected to be immobile in soil(SRC). Volatilization of tris(2-ethylhexyl) trimellitate from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.5X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Tris(2-ethylhexyl) trimellitate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Utilizing the Japanese MITI test, 4.2% 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 6.7X10+7(SRC), determined from a structure estimation method(2), indicates that tris(2-ethylhexyl) trimellitate 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 4.5X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Hydrolysis may be an important environmental fate process based on estimated hydrolysis half-lives of 120 and 12 days at pH 7 and 8(2), respectively. According to a classification scheme(5), BCF values of <1 to 2.7 in carp(7) suggests the potential for bioconcentration in aquatic organisms is low(SRC). Utilizing the Japanese MITI test, 4.2% of the Theoretical BOD was reached in 4 weeks(6) 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), tris(2-ethylhexyl) trimellitate, which has an estimated vapor pressure of 3.8X10-6 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 tris(2-ethylhexyl) trimellitate 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 4 hours(SRC), calculated from its rate constant of 3.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase tris(2-ethylhexyl) trimellitate may be removed from the air by wet and dry deposition(SRC). Tris(2-ethylhexyl) trimellitate contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The CIR Expert Panel concluded that tridecyl trimellitate, tricaprylyl/capryl trimellitate*, triethylhexyl trimellitate, triisodecyl trimellitate, and triisotridecyl trimellitate are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: Tris (2-ethylhexyl) trimellitate (TOTM) is a yellow oily liquid. It is used as a plasticizer. HUMAN EXPOSURE AND TOXICITY: Slight erythema was observed in four individuals exposed to TOTM, two of which resolved within 96 hr and one that occurred only after 96 hr. TOTM was estrogenic in both ERalpha and ERbeta transfected human cells. ANIMAL STUDIES: Slight erythema was seen in all rabbits 30-60 minutes after removal of the occlusive patch. Only one rabbit was affected at 72 hr and no abnormalities were observed at 7 days. In 21 day rat gavage study relative liver weights were significantly increased in female rats at all dose levels (a non-dose related increase) compared to controls. Males in the top dose group showed a slight increase in hepatic peroxisomes compared to controls. Various hepatic enzyme activities (palmitoyl-CoA and lauric acid 12-hydroxylase) were increased in males at 200 mg/kg bw and in females at 2000 mg/kg bw. TOTM was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, TA1537, or TA1538 with or without S-9 metabolic activation systems even at concentrations up to 1.0 mg/plate, and TOTM did not cause mutations in the HGPRT assay in CHO cells with or without S-9 activation. There was no increase in unscheduled DNA synthesis in rat hepatocytes.

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/]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of September 4, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=3319-31-1]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of tris(2-ethylhexyl) trimellitate can be estimated to be 6.7X10+7(SRC). According to a classification scheme(2), this estimated Koc value suggests that tris(2-ethylhexyl) trimellitate is expected to be immobile in soil.

Absorption and metabolism were studied for tri-(2-ethylhexyl)trimellitate (TEHT) mixed with corn oil and administered by gavage in a single dose of 100 mg/kg of body weight in 4 male Sprague Dawley rats. About 75% of the dose was excreted unchanged in the feces, 16% in the urine as metabolites and 1.9% was expired as (14)CO2. Radioactivity was excreted in the feces as unchanged TEHT (85% of the fecal radioactivity), mono- and di-(2-ethylhexyl)trimellitate (MEHT and DEHT, respectively), and as unidentified polar metabolites. Metabolites in the urine were identified as MEHT and metabolites of 2-ethylhexanol. Less than 0.6% of the dose remained in the tissues. Elimination of (14)CO2 was biphasic with half-lives of 4.3 and 31 hrs, and excretion of radioactivity in the urine was biphasic with half-lives of 3.4 hrs and 42 hrs.[Eastman Kodak Company; Absorption and Metabolism of

The rate of hydrolysis of tris(2-ethylhexyl) trimellitate (TEHT) dissolved in methanol and added to intestinal homogenates prepared from Sprague-Dawley rats was determined at 37 degC. There was no evidence for the hydrolysis of TEHT.

The subchronic toxicity of tris(2-ethylhexyl) trimellitate (TOTM) administered orally in the diet to groups of 5 male and 5 female Fischer 344 rats at levels of 0, 0.2, 0.67, 2.0% for 28 days was determined. There were no statistically significant differences in body weights between control and TOTM treated groups. There was a significant difference between control and treated groups in the following: hemoglobin concentration (lower in both sexes, 0.67 or 2.0% TOTM), leucocyte counts (higher in males at 0.67 or 2.0%), hematocrit and mean cell volume (lower in females at 0.2 or 0.67%), absolute and relative liver weights (higher in both sexes at all levels except 0 or 0.2%), serum albumin (higher in both sexes at 0.67 or 2.0%), serum cholesterol levels (higher in males at 0.67 or 2.0%), serum urea (higher in males at 2.0%), serum lipids (decreased in females at 0.2%). Liver biochemistry revealed statistically significant differences between treated and control groups as indicated by palmitoyl CoA oxidation (increased in both sexes at 2.0% and males at all dose levels), and catalase activity (increased in males at 2.0%).

The effects of tris(2-ethylhexyl) trimellitate (TEHT) were examined in the rat primary hepatocyte unscheduled DNA synthesis assay. Based on preliminary toxicity tests, TEHT was tested at concentrations of 250, 500, 1000, 2500, 3000, 4000, and 5000 nl/ml in absolute alcohol vehicle with corresponding relative survival rates ranging from 102.2% to 88.4%. The test material did not induce significant changes in the nuclear labeling and little or no toxicity was observed.

For more TSCA Test Submissions (Complete) data for TRIS(2-ETHYLHEXYL) TRIMELLITATE (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Two hundred and three human volunteers were tested for evidence of sensitization to several plasticizers following 3 weeks of dermal application three times a week. Tris(2-ethylhexyl)mellitate (TOTM; 1%, v/v), 2,2,4-trimethyl-1,3-pentanediol-diisobutyrate (TXIB; 1%, v/v), di(2-ethylhexyl)terephthalate (DEHT; 0.5%, v/v) and diethylphthalate (DEP; 2%, v/v) were applied to the skin of volunteers under semi-occlusive patch for 3 consecutive weeks and the reactions to a challenge application noted following a 2-week rest period. Slight erythema was observed in four individuals exposed to TOTM, two of which resolved within 96 hr and one that occurred only after 96 hr. Slight erythema was noted in three subjects exposed to TXIB, one of which resolved by 96 h and one that occurred only after 96 hr. Two subjects had slight erythema to DEHT, one that resolved by 96 hr and one that occurred only after 96 hr. One reaction occurred with DEP at 96 hr after challenge. Of the positive responses, one subject reacted to all test substances. No subject had a response grade of 1.0 or greater. Because of the low response, the overall conclusion is that none of the plasticizers demonstrated evidence of sensitization or irritation.

/OTHER TOXICITY INFORMATION/ This study presents the estrogenic potency of 21 food-packaging-associated compounds determined for the first time, using two transfected U2-OS (human osteoblasts devoid of endogenous estrogen receptors) estrogen receptor (ER) alpha and beta cell lines. Six plasticizers and three antioxidants were slightly estrogenic in the ERalpha cells. The model compounds bisphenol A and nonylphenol, one plasticizer tris(2-ethylhexyl)trimellitate (TEHTM), and two antioxidants (propyl gallate and butylated hydroxyanisole) were estrogenic in both ERalpha and ERbeta cells. Compared to estradiol (E2), these compounds appeared to be relatively more estrogenic in the ERbeta cells than in the ERalpha cells. Three sorbitol-based plasticizers activated neither ERalpha nor ERbeta and may be good replacements of existing plasticizers. All responses were additive with the response of E2. This indicates that they may contribute to the total effects of the pool of estrogenic compounds humans are exposed to. The estrogenic potencies of these compounds, together with the suggested beneficial effect of ERbeta-mediated responses and adverse ERalpha-mediated effects, support the importance of detecting characteristics for ERalpha and ERbeta response separately in independent models, as done in the present study.

AEROBIC: Tris(2-ethylhexyl) trimellitate, present at 30 mg/L, reached 4.2% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 100 mg/L in the Japanese MITI test(1,2). Tris(2-ethylhexyl) trimellitate, present at 100 mg/L, reached 14% of its theoretical BOD in 4 weeks using an activated sludge inoculum in the Japanese Modified MITI test(3). Tris(2-ethylhexyl) trimellitate, present at 0.26 mg/L related to Dissolved Organic Carbon (DOC), reached 68% after 28 days(3).

ANAEROBIC: Anaerobic biodegradation of tris(2-ethylhexyl) trimellitate is expected to be slow(1).

BCF's of <1 and 2.7 were measured in fish for tris(2-ethylhexyl)trimellitate at concentrations of 2 and 0.2 ppm, respectively, using carp (Cyprinus carpio) which were exposed over a 6-week period(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for tris(2-ethylhexyl) trimellitate is estimated as 4.5X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that tris(2-ethylhexyl) trimellitate is expected to be essentially nonvolatile from water surfaces(2). 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)(2) is estimated as 130 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)(2) is estimated as 1400 days. Tris(2-ethylhexyl) trimellitate's Henry's Law constant indicates that volatilization from moist soil surfaces may not occur(SRC). Tris(2-ethylhexyl) trimellitate is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 3.8X10-6 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Acute Exposure/ /Skin irritation was tested in/ two rabbits/sex ... with 0.5 mL of tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate ... applied along the midline back under ... an occulsive patch. After 4 hr the dressing was removed and the compound residue rinsed from the site. Sites were scored for edema and erythema 30-60 minutes after removal of the dressing, and again at 24, 48 and 72 hr and 7 days. Slight erythema was seen in all rabbits 30-60 minutes after removal of the occlusive patch. Only one rabbit was affected at 72 hr and no abnormalities were observed at 7 days.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /In a 21 day gavage study Fischer 344 rats were given tris(2-ethylhexyl) trimellitate at doses of 0, 200, 700, 2000 mg/kg bw/day./ The groups of 5 males and 5 females were monitored for food intake and body weight throught. On sacrifice, blood samples were taken and liver, kidney and testis were weighed and taken for histological examination. Relative liver weights were significantly increased in female rats at all dose levels (a non-dose related increase) compared to controls. Males in the top dose group ... showed a slight increase in hepatic peroxisomes compared to controls. Various hepatic enzyme activities (palmitoyl-CoA and lauric acid 12-hydroxylase) were increased in males at 200 mg/kg bw and in females at 2000 mg/kg bw.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /In a 28 day repeated dose toxicity study Fischer 344 rats were administered tris(2-ethylhexyl) trimellitate orally at doses of 0, 0.2, 0.67, and 2%./ Groups of 5 males and 5 females were fed diets containing the specified levels of tris(2-ethylhexyl) trimellitate. Body weight and food intake were monitored throughout and preserved tissues from the control and top dose groups were examined histologically. Liver samples from all groups were examined microscopically and with biochemical analyses. Rats of both sexes receiving 0.67% in the diet (approximately 650 mg/kg bw/day) had slightly increased liver weights and increased activities of certain liver enzymes (including palmitoyl CoA and carnitine acetyl transferase). Blood effects including reduced erthrocytes and increased leucocytes, and raised cholesterol levels occurred in treated rats of both sexes at 0.67%. Palmitoyl CoA activity was increased in male rats at the lowest dose (0.2%, ca. 184 mg/kg bw/day). Slight peroxisome proliferation was seen in rats receiving the top dose (2%, ca. 1826 mg/kg bw/day).

/GENOTOXICITY/ TOTM was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, TA1537, or TA1538 with or without S-9 metabolic activation systems even at concentrations up to 1.0 mg/plate, and TOTM did not cause mutations in the HGPRT assay in CHO cells with or without S-9 activation. There was no increase in unscheduled DNA synthesis in rat hepatocytes.

/GENOTOXICITY/ /In an Ames test with Salmonella typhimurium TA97, TA98, TA100, and TA1535 were treated with tris(2-ethylhexyl) trimellitate with and without metabolic activation at concentrations of 0, 100, 333, 1000, 3333, 10000 ug/plate./ ... There was no evidence of any genotoxic activity.

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. Tris(2-ethylhexyl) trimellitate is included on this list. Effective date: 01/03/83; Sunset date: 01/03/93.