Absorption, Distribution and Excretion
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.

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Metabolism / Metabolites
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.

Toxicity Summary
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.

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Non-Human Toxicity Values
LD50 Rat oral 31.4 g/kg
LD50 Mouse ip >4 g/kg
LD50 Cat oral >50 mL/kg

Acetyl tributyl citrate is an organooxygen compound. It is functionally related to a tetracarboxylic acid.
Acetyl tributyl citrate is a flavouring ingredient and plasticiser used in packaging films for food.

C20H34O8

402.4792

402.225

77-90-7

Tributyl 2-acetoxypropane-1,2,3-tricarboxylate-d3;1794753-49-3

6505

Colorless liquid

1.1±0.1 g/cm3

418.1±40.0 °C at 760 mmHg

-59 °C

175.1±27.4 °C

0.0±1.0 mmHg at 25°C

1.458

6.92

0

8

19

28

476

0

O(C(C([H])([H])[H])=O)C(C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])(C([H])([H])C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])C([H])([H])C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]

QZCLKYGREBVARF-UHFFFAOYSA-N

InChI=1S/C20H34O8/c1-5-8-11-25-17(22)14-20(28-16(4)21,19(24)27-13-10-7-3)15-18(23)26-12-9-6-2/h5-15H2,1-4H3

tributyl 2-acetyloxypropane-1,2,3-tricarboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)