Absorption, Distribution and Excretion
Triacetin was absorbed from the gastrointestinal tract faster than other fats tested within 3 hours. Studies have shown that triacetin is a source of liver glycogen and its utilization efficiency is as high as glucose when fed in amounts equivalent to the caloric value of 15% glucose. This study used mongrel dogs to determine the absorption of acetate in the whole body, hind limbs, intestines, liver, and kidneys during infusion of a 5% (v/v) triacetin aqueous solution. Ten animals were continuously infused with a pre-prepared [1-(14)C]-acetate for 7 hours. Three hours after the start of tracer infusion, triacetin was infused into the animals for 4 hours at a rate of 47 μmol/kg/min. Blood and respiratory samples were collected every 15 minutes during the last 30 minutes. Plasma acetate concentration, specific activity, and exhaled [(14)-CO2] reached steady state. Plasma acetate concentrations in the aorta, renal vein, portal vein, femoral vein, and hepatic vein were 1180, 935, 817, 752, and 473 μmol/L, respectively (all values are approximate). The acetate turnover rate during triacetin infusion was 2214 μmol/min; the systemic acetate turnover rate accounted for 68% of the triacetin-derived acetate.

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Metabolism/Metabolites
Triacetin was administered intravenously to mongrel dogs. Most of the infused triacetin underwent intravascular hydrolysis, and the resulting acetate was largely oxidized. Studies have shown that triacetin can be hydrolyzed by human intestinal lipases.
…Triacetin can be rapidly hydrolyzed in vitro by all biological tissues, including the gastrointestinal tract.
This study used female mongrel dogs to investigate the metabolic effects of isothermal and hypercaloric infusions of a 5% (v/v) triacetin aqueous solution. First, animals were continuously infused with 5 μmol/kg (0.3 μCi/kg/min) [(13)C]-acetoacetic acid and 1.0 μCi/kg (0.01 μCi/kg/min) [(3)H]-glucose for 6 hours. Three hours after the start of isotope infusion, triacetin was administered. Six animals received triacetin at a rate of 47 μmol/kg/min, and seven animals received triacetin at a rate of 70 μmol/kg/min for 3 hours. Blood and respiratory samples were collected every 15 to 30 minutes. Four other animals received glycerol at a rate of 70 μmol/kg/min as a control group for high-calorie infusion. During isothermal triacetin infusion, plasma acetate and free fatty acid concentrations significantly increased at 30 and 60 minutes, respectively, and remained at high levels. During high-calorie infusion, plasma acetate concentration continuously increased throughout the study, while plasma free fatty acid concentration remained unchanged. During isothermal and hypercaloric infusions, plasma pyruvate and lactate concentrations decreased significantly at 30 and 90 minutes, respectively, and throughout the study. Both infusion methods resulted in a slight increase in plasma insulin concentration. Plasma glucose concentration decreased significantly during isothermal triacetyl infusion; a slight but significant increase was observed during hypercaloric infusion. Glucose clearance was significantly reduced in both groups during the last hour of triacetyl infusion. Plasma ketone body concentration increased significantly at 60 minutes and remained elevated during isothermal infusion, while continuing to rise during hypercaloric triacetyl infusion; the increase was due to increased ketone body production. During the last hour of infusion, isothermal triacetyl infusion significantly increased resting energy expenditure. Esterases in fungi or serum exert their effects at pH > 4, slowly releasing acetic acid in situ. The degree of hydrolysis is automatically limited by increasing acidity and decreasing pH. …The antibacterial activity of triacetyl (glycerol triacetate) derives from its hydrolysis to acetic acid by fungal esterases.

Toxicity Summary
Identification and Uses: Triacetate, also known as glyceryl triacetate (GTA), is a colorless liquid. It has been reported as a bactericide, plasticizer, and solvent in cosmetic formulations. Triacetate is also used as a cellulose plasticizer in the manufacture of cigarette filters, a carrier for bactericide compositions, and a raw material for removing carbon dioxide from natural gas. The U.S. Food and Drug Administration (FDA) has designated triacetate as a GRAS (Generally Recognized As Safe) human food ingredient. Triacetate has been used to treat canavan disease, a fatal genetic disorder of myelin dysplasia associated with aspartic acid deficiency, which leads to reduced acetic acid levels and decreased myelin lipid synthesis in the developing brain. Human Exposure and Toxicity: In humans, commercially available triacetate causes eye irritation but no damage. In clinically maximized studies, triacetate did not show irritation or sensitization, with only very mild reactions observed in a 50% dilution Durin chamber test. It may cause mild irritation in sensitive individuals. Animal Studies: Triacetate is moderately toxic via intraperitoneal, subcutaneous, and intravenous administration. The main symptoms of triacetate toxicity are weakness and ataxia. Dying animals typically develop severe respiratory distress, muscle tremors, and occasional seizures 2–22 minutes after injection. In addition, varying degrees of pulmonary hemorrhage have been observed. Triacetate does not appear to affect the liver, spleen, heart, or kidneys. In short-term feeding studies, triacetate affected weight gain. Rats fed 30% triacetate as a starch substitute for 3–4 weeks or 12–13 weeks showed relatively poor growth and development. Hepatomegaly was observed in all animals. Short-term studies indicate that triacetate administered by inhalation or parenteral administration is non-toxic; subchronic studies indicate that triacetate administered by feed or inhalation is also non-toxic. Triacetate causes at most mild skin irritation in guinea pigs. However, in one study, it caused erythema, mild edema, hair loss, and desquamation. Triacetate has no sensitizing effect on guinea pigs. Triacetate is somewhat irritating to the eyes of rabbits. A study in dogs found that intragastric administration of 1.0%–2.0% triacetate could delay gastric emptying by increasing proximal gastric volume, temporarily inhibiting antral contractions, and promoting duodenal contractions. Another study using triacetate as a method for delivering metabolizable acetates into the brains of rats with traumatic brain injury found that triacetate administration significantly increased NAA (N-acetylaspartate) and ATP levels in the damaged hemisphere at 4 and 6 days post-injury, and significantly improved motor function in rats at 3 days post-injury. Regardless of metabolic activation, triacetate did not show mutagenicity in Ames assays using Salmonella Typhimurium strains TA98, TA100, TA1535, and TA153. In vivo assays in Drosophila also showed no mutagenicity.

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Toxicity Data
LC50 (Rat)> 1,721 mg/m3/4h

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Interactions
This study investigated the effects of intravenous administration of the short-chain triglyceride triacetate on canine leucine metabolism. Animals received infusions of triacetate at 1.0 times the estimated resting energy expenditure (REE), high-energy triacetate at 1.5 times the REE, glycerol, or saline, simultaneously with infusion of [(1-14)C]leucine. Plasma α-ketoisocaproic acid concentrations increased during both triacetate infusions (p < 0.05). During the 1.5 times REE triacetate infusion, plasma leucine concentrations decreased (p < 0.05), and the leucine incidence decreased by approximately 19% (p < 0.05); this change was significantly greater than the changes during the 1.0 times REE triacetate and glycerol infusions (p < 0.05). There was no difference in leucine oxidation rate between dogs given a 1.0-fold REE dose and the control group; however, during triacetylene infusion at a 1.5-fold REE dose, the leucine oxidation rate decreased by 53% (p < 0.05). The rate of disappearance of non-oxidized leucine (an indicator of protein synthesis) remained unchanged in all studies.

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Non-human toxicity values
Rabbit intravenous LD50: 750 mg/kg
Dog intravenous LD50: 1500 mg/kg
Mouse subcutaneous LD50: 2300 mg/kg
Mouse intraperitoneal LD50: 1400 mg/kg
For more non-human toxicity values (complete data) for triacetylene (13 in total), please visit the HSDB record page.

Triacetin is a triglyceride formed by the acetylation of three hydroxyl groups of glycerol. It has antibacterial activity (based on the release of acetic acid) and has been used topically to treat minor dermatophyte infections. It is used as a plant metabolite, solvent, fuel additive, adjuvant, food additive carrier, food emulsifier, food humectant, and antifungal agent. Its function is related to acetic acid.
Triacetin has been reported to be found in grapes (Vitis vinifera), and relevant data are available.
A triglyceride used as an antifungal agent.
See also: Tobacco leaves (partial).

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Therapeutic Uses
/EXPL THER/ Canavan disease (CD) is a fatal inherited disorder of myelination associated with a deficiency of aspartate, leading to reduced acetic acid levels and decreased myelin lipid synthesis in the developing brain. This study tested the tolerability of low doses of a potent acetate precursor, glycerotriacetate (GTA), in two CD infants aged 8 months and 13 months, respectively. Subsequently, the toxicity of higher doses of GTA was evaluated in a CD tremor rat model. GTA was administered orally to children at a dose of 25 mg/kg twice daily for 4.5 months and 6 months, with the dose doubling weekly until a maximum dose of 250 mg/kg was reached. GTA treatment did not cause detectable toxicity, nor did it worsen the children's clinical condition. No GTA toxicity was observed in two children with CD in the low-dose trial, suggesting the need for studies at higher effective doses in CD patients. Solvent/EXPL THER/ FDA-approved food additive triacetin (glycerotriacetate, GTA) has been safely used as acetate supplementation therapy for canavan disease (a leukodystrophy caused by an aspartate aminotransferase (ASPA) mutation). This study aimed to elucidate the effects of GTA on the proliferation and differentiation of six glioblastoma stem cell-like cells (GSCs) derived from primary glioblastoma (GBM), and to compare them with established U87 and U251 GBM cell lines, normal human cortical astrocytes, and mouse neural stem cells. GTA showed a stronger inhibitory effect on GSC proliferation than on established GBM cell lines. Furthermore, GTA exhibits stronger growth inhibition on the more aggressive mesenchymal GSCs than on anterior neural GSCs. While sodium acetate can dose-dependently inhibit GSC growth, it also reduces cell viability. GTA-mediated growth inhibition is independent of differentiation but increases protein acetylation levels. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy for inhibiting GSC growth. Canavan disease (CD) is a rare autosomal recessive neurodegenerative disorder that typically manifests in early infancy. The course of the disease varies but is ultimately fatal. CD is caused by a mutation in the ASPA gene, which encodes aspartic acid acylase (ASPA), an enzyme that breaks down N-acetylaspartate (NAA) into acetate and aspartate. A deficiency in NAA-degrading enzyme activity leads to excessive NAA accumulation in the brain, while acetate, required for myelin lipid synthesis, is lacking. Glyceryl triacetate (GTA) is a short-chain triglyceride with three acetate groups attached to its glycerol backbone and has been shown to be a potent acetate precursor. Intragastric instillation of GTA in tremor mice significantly increased intracranial acetate levels and improved motor function. Treatment of infants with CD with low-dose (maximum 0.25 g/kg/day) GTA did not show improvement in clinical symptoms, nor were any toxic reactions detected. We report for the first time the safety of high-dose GTA (4.5 g/kg/day) in two CD patients. We treated two CD infants, one 8 months old and the other 1 year old, with high-dose GTA for 4.5 months and 6 months, respectively. No significant side effects or toxic reactions were observed. Although the treatment did not improve motor function, the infants tolerated it well. The main reason for the lack of improvement in clinical symptoms may be the late initiation of treatment, at which point significant brain damage had already occurred. Larger-scale studies in CD patients under 3 months of age are needed to examine the long-term efficacy of this drug. For more complete data on the therapeutic uses of TRIACETIN (9 types), please visit the HSDB records page.

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Drug Warnings
For external use only: Do not use in the eyes.
>If irritation or allergic reaction occurs: Discontinue use and inform your doctor.
>In patients with diabetes or circulatory disorders: Use the spray with caution.

C9H14O6

218.2039

218.079

102-76-1

Triacetin-d5;159510-46-0;Glyceryl Triacetate-d9

5541

Colorless to light yellow liquid

1.2±0.1 g/cm3

258.0±0.0 °C at 760 mmHg

3 °C(lit.)

148.9±0.0 °C

0.0±0.5 mmHg at 25°C

1.435

-0.24

0

6

8

15

229

0

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

URAYPUMNDPQOKB-UHFFFAOYSA-N

InChI=1S/C9H14O6/c1-6(10)13-4-9(15-8(3)12)5-14-7(2)11/h9H,4-5H2,1-3H3

2,3-diacetyloxypropyl acetate

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)

DMSO : ≥ 2.3 mg/mL (~10.54 mM)

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.)