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Home > Encyclopedia > Acetyl tributyl citrate

Acetyl tributyl citrate

pharmaceutical raw materials
Acetyl tributyl citrate structure

Acetyl tributyl citrate 

structure
  • CAS No:

    77-90-7

  • Formula:

    C20H34O8

  • Chemical Name:

    Acetyl tributyl citrate

  • Synonyms:

    1,2,3-Propanetricarboxylic acid,2-(acetyloxy)-,1,2,3-tributyl ester;Citric acid,tributyl ester,acetate;1,2,3-Propanetricarboxylic acid,2-(acetyloxy)-,tributyl ester;2-Acetoxy-1,2,3-propanetricarboxylic acid tributyl ester;Acetyl tributyl citrate;Citroflex A 4;Tributyl 2-acetoxy-1,2,3-propanetricarboxylate;Citroflex A;Tributyl acetylcitrate;Tributyl citrate acetate;Tributyl 2-(acetyloxy)-1,2,3-propanetricarboxylic acid;Tributyl O-acetylcitrate;Blo-trol;Acetylcitric acid tributyl ester;Acetyl butyl citrate;ATBC;Estaflex ATC;Citroflex 4A-S;Sansocizer ATBC;NSC 3894;Monocizer ATBC;Morflex ATBC;Citrofol BII;Acetyl tris-n-butyl citrate;Pacizer 6412;Tributyl 2-acetyl citrate;Scandinol SP 22;Acetyl tri-n-butyl citrate;Kanatol 3400AC;ADK Cizer PN 6810;Citrofol B 2;LC 18;LC 18 (plasticizer);FF 454;Proviplast 2624;Plasticizer 40T;37070-91-0;791812-73-2

  • Categories:

    Cosmetic Ingredient  >  Perfuming

Description

clear colorless liquid Acetyltributyl citrate is a clear, odorless, practically colorless, oily liquid. Tributyl acetylcitrate has a very faint, sweet, herbaceous odor. At high levels (e.g., 1000 ppm emulsion in water), it has a mild, fruity, nondescript flavor. Acetyl tributyl citrate (ATBC) is a colorless, odorless liquid. Its water solubility is less than 0.002 g/100 mL, but it is soluble in organic solvents.


DryPowder; Liquid|Liquid|colourless, slightly viscous liquid with very faint sweet herbaceous odour


Acetyl tributyl citrate is an organooxygen compound. It derives from a tetracarboxylic acid.

Acetyl tributyl citrate Basic Attributes

402.479

402.48

201-067-0

0ZBX0N59RZ

3894

DTXSID2026446

Colorless liquid

2918150000

Characteristics

105.2

3.3

Transparent viscous liquid

1.046 g/cm3 @ Temp: 25 °C

-80 °C

172-174 °C @ Press: 1 Torr

>230 °F

n20/D 1.443(lit.)

H2O: <0.1 g/100 mL

Keep in a well ventilated area. Keep container tightly closed. Keep awaw from moisture.

0.26 psi ( 20 °C)

14.1 (Air = 1; 20 deg C)

Very faint sweet, herbaceous odor

At high levels (e.g., 1000 ppm emulsion in water) it has a mild, fruity, non-descript flavor.

Henry's Law constant = 3.8X10-10 atm-cu m/mole at 25 °C /Estimated/

199.82 Ų [M+H]+

When heated to decomposition it emits acrid smoke and irritating fumes.|Hydroxyl radical reaction rate constant = 1.4X10-11 cu cm/molec-sec at 25 °C /Estimated/

Safety Information

NONH for all modes of transport

3

S24/25

TZ8330000

Stable under recommended storage conditions.

P201, P202, P210, P264, P273, P280, P281, P302+P352, P305+P351+P338, P308+P313, P321, P332+P313, P337+P313, P362, P377, P381, P403, P405, P501

H220

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

Strong oxidizing agents

Food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part. Tributyl acetylcitrate is included on this list.|Acetyl tributyl citrate is an indirect food additive for use only as a component of adhesives.|Prior-sanctioned food ingredients. Substances classified as plasticizers, when migrating from food packaging material. Acetyl tributyl citrate is included on this list.

The U.S. high production volume (HPV) chemicals are those which are manufactured in or imported into the United States in amounts equal to or greater than one million pounds per year. Robust Summaries include health effects, ecotoxicity data, and environmental fate information for selected chemicals. EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans.[Available from, as of November 28, 2015: http://www.epa.gov/hpv/pubs/hpvrstp.htm]

Not Classified

Skin protection: Handle with gloves.|Eye/face protection: Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose 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).|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.

Wear self contained breathing apparatus for fire fighting if necessary.|Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures. Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. 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.

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.|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.

... Migration /citric acid, acetyl tributyl ester/ plasticizer from plasticized polyvinylidene chloride-polyvinyl chloride ...films into both olive oil and distilled water during microwave heating was studied. The amount of /citric acid, acetyl tributyl ester/ migrating into olive oil after heating for 10 min was 73.9 mg/L, into distilled water it was 4.1 mg/L after heating for 8 min.|Food-grade polyvinyl chloride (PVC) cling-film containing 5.3% (w/w) di(2-ethylhexyl) adipate (DEHA) and 3.0% (w/w) acetyltributyl citrate (ATBC) plasticizers was used to wrap halawa tehineh (halva) samples. Samples were split into two groups and stored at 25+/-1 degrees C. One group was analyzed for DEHA and ATBC content at intervals between 0.5 and 240hr of contact (kinetic study) and a second group was cut into slices (1.5mm thick) after 240hr of halva/PVC contact and was analyzed for DEHA and ATBC content (penetration study). Determination of both plasticizers was performed using a direct gas chromatographic (GC) method after extraction of DEHA from halva samples. DEHA readily migrated into halva samples: the equilibrium amount of DEHA in halva (3.31mg/sq dm film or 81.4mg/kg halva) corresponding to a loss of 54.7% (w/w) DEHA from PVC film. This value is slightly higher than the limit of 3mg/ sq dm of film surface set by the European Union for DEHA. The equilibrium amount of ATBC in halva was 1.46mg/sq dm (36.1mg/kg) corresponding to a loss of 42.7% ATBC from PVC film. With regard to the penetration of both placticizers into halva samples, migration of DEHA was detectable up to the 7th slice beneath the surface of halva (total depth 10.5mm) while the migration of ATBC was detectable up to the 5th slice (total depth 7.5mm).

Toxicity

IDENTIFICATION AND USE: Acetyl tributyl citrate (ATBC) is a colorless liquid. It is the most widely used phthalate substitute plasticizer. It is used in products such as food wrap, vinyl toys, and pharmaceutical excipients. It is also used as a flavor ingredient in non-alcoholic beverages. HUMAN EXPOSURE AND TOXICITY: The skin irritation potential of acetyl tributyl citrate was evaluated using 59 men and women, all of whom had history of diabetes, psoriasis, or active dermatoses. ATBC was nonirritating to the skin, and reactions suggestive of contact sensitization were not observed during the study. In vitro ATBC increased CYP3A4 messenger RNA (mRNA) levels and enzyme activity in the human intestinal cells but not in human liver cells. ANIMAL STUDIES: Acute oral toxicity of ATBC in cats and rats is low. CYP3A1 mRNA levels were increased in the intestine but not the liver of ATBC-treated rats. In a 90-day repeated-dose oral dietary study in rats, decreased body weight and organ weight changes were observed at 1000 mg/kg-bw/day. In a combined repeated dose/reproductive/developmental toxicity study in rats, organ weight and histopathological changes were observed in adults at 1000 mg/kg-bw/day. In a 2-generation reproductive toxicity study in rats, reduced body weight was observed in F1 males at 300 mg/kg-bw/day. In the same study, no other treatment related effects were observed. In the combined repeated dose/reproductive/developmental toxicity study in rats previously described, histopathological changes were observed in the liver of adult males at 300 mg/kg-bw/day. In the same study, decreased litter size and decreased number of implantations were observed at 1000 mg/kg-bw/day. ATBC did not induce gene mutations in bacteria or mammalian cells in vitro and did not induce chromosomal aberrations in mammalian cells in vitro. ECOTOXICITY STUDIES: For acetyl tributyl citrate, the 96-hr LC50 values for fish range from 38 to 60 mg/L, the 48-hr EC50 value for aquatic invertebrates is 7.8 mg/L and the 72-hr EC50 values for aquatic plants are 11.5 mg/L for biomass and 74.4mg/L for growth rate, respectively.

LD50 Rat oral 31.4 g/kg|LD50 Mouse ip >4 g/kg|LD50 Cat oral >50 mL/kg

/AQUATIC SPECIES/ The study measured the acute toxicity of the test substance to locally obtained bluegill sunfish during a 96-hr exposure period in flow-through systems. Fish were acclimated to laboratory conditions for >1 month before use in this study. Following 96-hr exposure, observation for mortality and behavioral effects were monitored for an additional 96 hours. Experimental conditions during this study were as follows: flow through tanks delivered 4.8 volume replacements/day; the pH ranged from 6.5-7.6; the dissolved oxygen concentration was 70-95% saturation; temperature was maintained at approximately 23-24 °C; and fish were not fed during the first 96 hours of an extended exposure period. ...The fish exposed to low concentrations of the test substance appeared to be more excitable than usual, while activity was greatly reduced in fish exposed to the higher concentrations. Loss of equilibrium was observed and, at higher concentrations, a marked loss of equilibrium and fine fin movements was observed. Gill motion was irregular and shallow. All fish reportedly recovered from treatment-related effects within 48 hours of cessation of exposure to the test substance.|/AQUATIC SPECIES/ The study measured the acute toxicity of the test substance to locally obtained mummichogs during a 96-hr exposure period in flow-through tanks. Fish were acclimated to laboratory conditions for several weeks before use in this study. Following 96-hr exposure, observation for mortality and behavioral effects were monitored for an additional 96 hours. Experimental conditions during this study were as follows: flow through tanks delivered 4.8 volume replacements/day; the dilution water was synthetic seawater (25%); the pH ranged from 6.5-7.6; the dissolved oxygen concentration was 70-95% saturation; temperature was maintained at approximately 23-24 °C; and fish were not fed during the first 96 hours of an extended exposure period. Mummichogs were 3.5-8.5 inches in length. ...Behavioral effects were observed in fish exposed to 50 mg/L of the test substance in <48 hours. Some survival was seen at 100 mg/L after 96 hours of exposure. The fish exposed to low concentrations of the test substance appeared to be more excitable than usual, while activity was greatly reduced in fish exposed to the higher concentrations. Loss of equilibrium was observed and, at higher concentrations, a marked loss of equilibrium and fine fin movements (especially pectoral fins) was observed. Gill motion was irregular and shallow. ... Two severely affected fish were transferred from test solutions to fresh water, one of which fully recovered from exposure to a 120 mg/L test solution for 7.5 hours and the other recovered from exposure to an 80 mg/L test solution after 24 hours. All surviving fish reportedly recovered from treatment-related effects within 48 hours of cessation of exposure to the test substance. /Citroflex-A4 (O-acetyl-tributyl citrate)/

Acetyl tributyl citrate is not reported as found in nature.

Acetyl tributyl citrate's production and use as a plasticizer for vinyl and other resin(1,2), as a solvent and functional fluid in adhesives, paints, coating and inks(2) as a flavor ingredient(3) and in nail enamel(4) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3280(SRC), determined from a log Kow of 4.90(2) and a regression-derived equation(3), indicates that acetyl tributyl citrate is expected to have slight mobility in soil(SRC). Volatilization of acetyl tributyl citrate from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.2X10-5 atm-cu m/mole(SRC), derived from its estimated vapor pressure, 3X10-4 mm Hg(3), and water solubility, 5 mg/L(4). However, adsorption to soil is expected to attenuate volatilization(SRC). Acetyl tributyl citrate is not expected to volatilize from dry soil surfaces(SRC) based upon its estimated vapor pressure of 3X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). An 82% of theoretical BOD using activated sludge in the Japanese MITI test(5) suggests that biodegradation is an important environmental fate process in soil(SRC). Acetyl tributyl citrate was shown to biodegrade extensively in several other biodegradation studies and simulation tests(6,7). Two soil degradation studies observed rapid biomineralization of acetyl tributyl citrate(7).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,280(SRC), determined from a log Kow of 4.92(2) and a regression-derived equation(3), indicates that acetyl tributyl citrate is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 3.2X10-5 atm-cu m/mole(SRC), derived from its estimated vapor pressure, 3X10-4 mm Hg(3), and water solubility, 5 mg/L(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 2.6 and 25 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 335 days if adsorption is considered(6). According to a classification scheme(7), an estimated BCF of 35(SRC), from its log Kow and a regression-derived equation(3) suggests the potential for bioconcentration in aquatic organisms is moderate. An 82% of theoretical BOD using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in water(SRC). Acetyl tributyl citrate was shown to biodegrade extensively in several other biodegradation studies and simulation tests(9,10). A base-catalyzed second-order hydrolysis rate constant of 5.8X10-2 L/mole-sec(SRC) was estimated using a structure estimation method(3); this corresponds to half-lives of 3.8 years and 140 days at pH values of 7 and 8, respectively(3). [|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acetyl tributyl citrate, which has an estimated vapor pressure of 3X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase acetyl tributyl citrate 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 27 hours(SRC), calculated from its rate constant of 1.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase acetyl tributyl citrate may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of acetyl tributyl citrate with photochemically-produced hydroxyl radicals has been estimated as 1.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 27 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 5.8X10-2 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 3.8 years and 140 days at pH values of 7 and 8, respectively(1).

An estimated BCF of 35 was calculated in fish for acetyl tributyl citrate(SRC), using a log Kow of 4.92(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of acetyl tributyl citrate is estimated as 3280(SRC), using a log Kow of 4.92(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that acetyl tributyl citrate is expected to have slight mobility in soil.

The Henry's Law constant for acetyl tributyl citrate is estimated as 3.2X10-5 atm-cu m/mole(SRC) derived from its estimated vapor pressure, 3.0X10-4 mm Hg(1), and water solubility, 5 mg/L(2). This Henry's Law constant indicates that acetyl tributyl citrate 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 2.6 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 25 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 335 days if adsorption is considered(4). Acetyl tributyl citrate's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur, but the rate may be attenuated by adsorption to soil(SRC). Acetyl tributyl citrate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

SURFACE WATER: Acetyl tributyl citrate was identified in 2 water samples taken from the River Lee, Great Britain at trace levels(1).

Acetyl tributyl citrate is reportedly used as a flavor ingredient in nonalcoholic beverages at a concentration of 1.0 ppm(1). A monitoring study of hospital diets in Japan for plasticizers in hospital food detected acetyl tributyl citrate at levels (in one hospital) that corresponded to a daily intake of 1228 ug/day(2); the source of the acetyl tributyl citrate in the food was suspected to be cling-film wrapping or other packaging(2). Monitoring tests determined that acetyl tributyl citrate plasticizer in plastic films migrated from the film into cooked poultry meat during microwave cooking(3).

According to the 2012 TSCA Inventory Update Reporting data, 6 reporting facilities estimate the number of persons reasonably likely to be exposed in their respective industrial use in the United States manufacturing, processing, or use of acetyl tributyl citrate (77-90-7) may be as low as <10 workers up to the range of 50-99 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 106,672 workers (98,182 of these are female) are potentially exposed to acetyl tributyl citrate in the US(1). Occupational exposure to acetyl tributyl citrate may occur through inhalation and dermal contact with this compound at workplaces where acetyl tributyl citrate is produced or used(SRC). Use data indicate that the general population may be exposed to acetyl tributyl citrate via inhalation of ambient air, ingestion of food containing this compound, and dermal contact with consumer products (such as cosmetics, paints and inks) containing acetyl tributyl citrate(SRC).

Drug Information

The metabolism of acetyl tributyl citrate was evaluated using groups of male rats (number of animals, weights, and strain not stated). Each animal received a single oral dose of 14C-acetyl tributyl citrate (dose not stated). At 48 hr post dosing, approximately 99% of the administered dose had been excreted either in urine (59% to 70%), feces (25% to 36%), or in the expired air (2%). Only 0.36% to 1.26% of the dose remained in the tissues or carcass.

The metabolism of acetyl tributyl citrate was evaluated using groups of male rats (number of animals, weights, and strain not stated). ... Both the absorption and metabolism of 14C-Acetyl tributyl Citrate proceeded rapidly, and the following metabolites were identified: acetyl citrate, monobutyl citrate, acetyl monobutyl citrate, dibutyl citrate, and acetyl dibutyl citrate.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ The skin irritation potential of acetyl tributyl citrate was evaluated using 59 men and women (age range = 21-60 years), all of whom had history of diabetes, psoriasis, or active dermatoses. ... Occlusive patches moistened with 0.4 mL of acetyl tributyl citrate were applied to the upper arm of each subject on Mondays, Wednesdays, and Fridays for 3 consecutive weeks. Each patch was removed 24 hours post application. Induction reactions were scored prior to patch applications (second through ninth visits) and at the time of the tenth visit. Duplicate challenge of the test material was made after a two-week non-treatment period. ... One challenge patch was applied to the original test site, and , another, to an adjacent site. Challenge reactions were scored at 48 and 96 hours post application. /Acetyl tributyl citrate/ was nonirritating to the skin, and reactions suggestive of contact sensitization were not observed during the study.|/ALTERNATIVE and IN VITRO TESTS/ The cytotoxicity of acetyl-tributyl-citrate and dibutyl-sebacate was studied in cultured mammalian cells. The impetus for the study was a report that acetyl-tributyl-citrate and dibutyl-sebacate, which were plasticizers found in polyvinylidene-chloride film used for packaging food, could leach out and diffuse into the foods. Human KB cells, monkey Vero cells, and canine MDCK cells were incubated with acetyl-tributyl-citrate or dibutyl sebacate over a range of concentrations for 72 hours. Cytotoxicity was evaluated by determining the extent of growth inhibition. Doses of acetyl-tributyl-citrate and dibutyl-sebacate that inhibited growth by 50% were calculated from the data. Both compounds inhibited the growth of all cells in a dose dependent manner. The inhibited growth by 50% of acetyl-tributyl-citrate in the various types were: 44.7 ug/mL in KB cells; 39.9 ug/mL in Vero cells; and 42.1 ug/mL in MDCK cells. The inhibited growth by 50% of dibutyl-sebacate in these cells were: KB cells, 1,549 ug/mL; Vero cells, 1,510 ug/mL; and MDCK cells, 1,549 ug/mL. /It was/ concluded that when comparing the results of this study with those obtained previously using tricresyl-phosphate,triphenyl-phosphate (TPP), butylated-hydroxyanisole, and butylated-hydroxytoluene in human KB cells, acetyl-tributyl-citrate is more toxic than TCP and more toxic than TPP. Acetyl-tributyl-citrate is less toxic than BHA, but shows toxicity similar to that of BHT. DBS is much less toxic than either BHT or BHA. KB, Vero, and MDCK cells show similar sensitivity to acetyl-tributyl-citrate and DBS.|/ALTERNATIVE and IN VITRO TESTS/ The in vitro cytotoxicity of acetyl tributyl citrate in HeLa cell cultures (human cell line) was evaluated using the metabolic inhibition test, supplemented by microscopy of cells after 24 hours of incubation (the MIT-24 test system). ... After 24 hours, cell viability was determined by microscopy. Two endpoints of cytoinhibition (total and partial inhibition) were estimated after 24 hours, based on the absence or scarcity of spindle-shaped cells, and, after 7 days.... The following values for minimal inhibitory concentration were reported for acetyl tributyl citrate: 13 mg/mL (for total inhibition at 24 hours), 3.8 mg/mL (for partial inhibition at 24 hours), and 5.7 mg/mL (for total and partial inhibition at 7 days). Acetyl tributyl citrate caused little toxicity in HeLa cell cultures.|/ALTERNATIVE and IN VITRO TESTS/ The effects of polyvinyl-chloride (PVC) tubing extracts were investigated in isolated ileum of guinea-pigs. Ileum were isolated and mounted in tissue baths. Tubing ingredients from PVC or tubing extracts of the plasticizer acetyl-N-tributyl-citrate (ATBC) were added to the bath for 15 minutes. Contractions or modifications of methacholine responses were measured. ...A significant and characteristic effect was seen for ATBC in ileum, consisting of rapid contractions and relaxations which were dependent on concentrations. The spasms were unaffected by tetrodotoxin. No spasmogenic effect was seen for ATBC in human small intestine or colon. None of the other tubing ingredients had any spasmogenic action, including PVC extracts. No methacholine contractions occurred with the other ingredients. Tubing extracts containing ATBC produced spasms similar to chemical ATBC.|/ALTERNATIVE and IN VITRO TESTS/ Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chemicals including steroids, bile acids, and prescription drugs. SXR is highly expressed in the liver and intestine, where it regulates cytochrome P450 3A4 (CYP3A4), which in turn controls xenobiotic and endogenous steroid hormone metabolism. However, it is unclear whether Food and Drug Administration (FDA)-approved plasticizers exert such activity. ...We found that four of eight FDA-approved plasticizers increased SXR-mediated transcription. In particular, acetyl tributyl citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated human and rat SXR. ATBC increased CYP3A4 messenger RNA (mRNA) levels and enzyme activity in the human intestinal cells but not in human liver cells.

2-acetyltributylcitrate

Acetyl tributyl citrate Use and Manufacturing

Methods of Manufacturing

Citric acid and butanol esterification; and then acetic anhydride in sulfuric acid catalyzed by acetylation, vacuum distillation, washing and neutralization in the system.

Uses

1. Labelled Tributyl O-Acetylcitrate (T772950). Topical pharmaceutical formulation anesthetic surfactant ester.
2. Plasticizer flavoring agent


Intermediates


Adhesives and sealants

Production

1,000,000 - 10,000,000 lb|(1976) GREATER THAN 2X10+6 GRAMS|1,2,3-Propanetricarboxylic acid, 2-(acetyloxy)-, tributyl ester 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).|Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 1,2,3-Propanetricarboxylic acid, 2-(acetyloxy)-, 1,2,3-tributyl ester. National Production Volume: 4,669,244 lb/yr.

Grade: Technical

Adhesive manufacturing|1,2,3-Propanetricarboxylic acid, 2-(acetyloxy)-, 1,2,3-tributyl ester: ACTIVE

Food additives -> Flavoring Agents|Flavoring Agents -> JECFA Flavorings Index|Cosmetics -> Film forming; Plasticiser

Flavoring Agents

Computed Properties

Molecular Weight:402.5
XLogP3:3.3
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:19
Exact Mass:402.22536804
Monoisotopic Mass:402.22536804
Topological Polar Surface Area:105
Heavy Atom Count:28
Complexity:476
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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