Absorption, Distribution and Excretion
To assess the toxicological behavior of triethyl citrate, we evaluated existing experimental and projected physicochemical data. The substance is expected to be well absorbed. Absorption of any metabolite of the target substance is rapid and complete. Regarding absorption after inhalation exposure, its bioavailability is expected to be low due to the low vapor pressure of this chemical. Given its lipophilicity (LogPow 1.17), if absorbed, it is expected to be absorbed directly through the respiratory epithelial cells. Due to its molecular weight and LogPow value, absorption in the stratum corneum and epidermis after skin exposure is also expected to be low. Furthermore, systemic toxicity via the skin route is considered low, as confirmed by the results of an acute skin study of triethyl citrate, in which an LD50 of 5000 mg/kg body weight was determined. Regarding its distribution in the body, triethyl citrate is expected to be primarily distributed in the circulatory system (due to its water solubility). Experimental measurements of LogPow values, water solubility, and predictions of triethyl citrate absorption behavior indicate that this substance is unlikely to accumulate.
Metabolism/Metabolites

Triethyl citrate is hydrolyzed in vivo to citric acid and ethanol. The hydrolysis rate of triethyl citrate in human serum appears to be slower compared to rat serum.
Freshly collected rat or human serum samples were added to triethyl citrate, and the disappearance of triethyl citrate was measured over 4 hours.
Triethyl citrate is rapidly hydrolyzed in rat serum (15 minutes), but the hydrolysis rate in human serum is much slower, and it is still not completely hydrolyzed at the end of the 4-hour test.
Rat, mouse, and human liver homogenates and serum enzymes all hydrolyze triethyl citrate to 1 mole of citric acid and 3 moles of ethanol/mol of ester.
Triethyl citrate is expected to be extensively metabolized by esterases and cytochrome P450 enzymes, and broken down in β-oxidation or the citric acid cycle, or in some cases by subsequent glucuronidation. This substance is thought to be excreted primarily in urine as a metabolite (i.e., a substance bound to glucuronic acid) if it is not completely metabolized in the β-oxidation and citric acid cycles, with a small amount excreted in bile.

Toxicity Summary
Identification and Uses: Triethyl citrate is a colorless, oily liquid with a bitter taste. It can be used as a solvent and plasticizer for nitrocellulose and natural resins, a softener, a paint remover, an adhesive, a fragrance base, a food additive (not exceeding 0.25%), an emulsifier, and a preservative. Human Exposure and Toxicity: In human studies, a 20% triethyl citrate petrolatum solution did not show a major irritant or sensitizer. Animal Studies: In the maximum sensitization test in guinea pigs, undiluted triethyl citrate showed a strong sensitizing effect during epidermal induction. 33.3% triethyl citrate irritated the eyes of rabbits. Intravenous injection of 100 mg/kg body weight of triethyl citrate significantly increased the kinetic activity and respiratory rate of rabbits. A group of 20 mice that received intraperitoneal injections of 350 mg/kg body weight of triethyl citrate daily for 14 consecutive days showed a slightly lower average growth rate than the control group. There were no differences in red blood cell and white blood cell counts, clotting time, and hemoglobin levels between the two groups of mice. Autopsies were performed on both mice, examining their liver, lung, and kidney tissues; no pathological cytological changes were found. Triethyl citrate showed no teratogenic effects on chicken embryos within a dose range of 0.5–10 mg/kg body weight. Ames tests using triethyl citrate (0.4%–1.6%) against Salmonella Typhimurium TA1535, TA1537, and TA1538 were negative, regardless of whether metabolic activation was performed.

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Toxicity Data
LC50 (Rat) = 1,300 ppm/6hNon-human Toxicity Values
LD50 Guinea Pig Dermal Administration >10 mL/kg
LD50 Mouse Intraperitoneal Injection 1750 mg/kg
LD50 Rabbit Dermal Administration >5 g/kg
LD50 Rat Inhalation 3500 ppm For more non-human toxicity values (complete data) for triethyl citrate (out of 11), please visit the HSDB records page.

Triethyl citrate is a carbonyl compound. It is used in food as a flavoring agent, solvent, and surfactant. Triethyl citrate is a citrate ester. It is a colorless and odorless liquid used as a food additive (E-number E1505) to stabilize foam, particularly for whipping egg whites. It is also used in pharmaceutical coatings and plastics. Triethyl citrate belongs to the family of tricarboxylic acids and their derivatives. These are organic compounds containing three carboxylic acid groups (or their salts/ester derivatives). Mechanism of Action: There is evidence that some of its effects may be due to the release of citrate ions that bind to calcium, leading to hypocalcemia. Therapeutic Uses: /Exploratory Treatment/ This study aims to evaluate the efficacy and tolerability of a novel emulsion containing triethyl citrate and ethyl linoleate for the treatment of mild to moderate acne vulgaris. This was a double-blind, placebo-controlled, randomized study comparing the efficacy of an active emulsion containing triethyl citrate and ethyl linoleate with its excipients (as a placebo control). Patients were assessed using the modified Liz Acne Grading System at weeks 0, 4, 8, and 12, and inflammatory and non-inflammatory facial lesions were counted. Sebum secretion was assessed using the sebum tape method at weeks 0 and 12. All adverse events were recorded. A total of 40 patients were enrolled, of whom 33 completed the study. The active treatment was superior to the placebo group in reducing Liz grade, as well as the total number of lesions, inflammatory lesions, and non-inflammatory lesions. The active emulsion had a rapid onset of action, with significant reductions in both the number of lesions and acne grade within 4 weeks. Sebum secretion was significantly reduced in the active treatment group, with a mean reduction of 53% compared to baseline. One patient withdrew from the study due to an irritant reaction to the active emulsion. This novel emulsion, containing triethyl citrate and ethyl linoleate, has been proven effective in treating mild to moderate acne, showing efficacy against both inflammatory and non-inflammatory acne lesions. The emulsion is rapid-acting and well-tolerated. A surprising finding is its significant effect on sebum secretion, suggesting potential efficacy for patients with seborrheic dermatitis.
Medication (Veterinary): ...Oral administration for the treatment of flatulence in ruminants.

C12H20O7

276.29

276.12

77-93-0

6506

Oily liquid
Colorless, mobile liquid

1.2±0.1 g/cm3

294.0±0.0 °C at 760 mmHg

-46 °C

95.4±11.7 °C

0.0±1.3 mmHg at 25°C

1.462

1.49

1

7

11

19

304

0

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

DOOTYTYQINUNNV-UHFFFAOYSA-N

InChI=1S/C12H20O7/c1-4-17-9(13)7-12(16,11(15)19-6-3)8-10(14)18-5-2/h16H,4-8H2,1-3H3

triethyl 2-hydroxypropane-1,2,3-tricarboxylate

NSC-8907; NSC 8907; Triethyl citrate

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 : ~100 mg/mL (~361.94 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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