Absorption, Distribution and Excretion
In order to assess the toxicological behavior of triethyl citrate, the available experimental and predicted physico-chemical data have been evaluated. The substance is expected to be absorbed very well. The absorption of any metabolite of the substances of interest is fast and complete. Concerning the absorption after exposure via inhalation, as the chemical has a low vapor pressure, it is clear, that the substance is poorly available after inhalation. Given its lipophilicity (LogPow 1.17) - if absorbed - it is expected to be absorbed directly across the respiratory tract epithelium. The substance is expected to be also poorly absorbed following dermal exposure into the stratum corneum and to a certain extent into the epidermis, due to its molecular weight and its LogPow. In addition, the systemic toxicity via the skin is assumed to be low and this has been proven with the results of the acute dermal study with triethyl citrate, in which a LD50 of 5000 mg/kg bw has been obtained. Concerning the distribution in the body, triethyl citrate is expected to be mainly available in the circulatory system (due to its water solubility). The experimentally determined LogPow value, the water solubility and predicted behavior concerning absorption of the substance triethyl citrate do not indicate a potential for accumulation.

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Metabolism / Metabolites
Triethyl citrate is hydrolyzed in vivo to citric acid and ethanol. Triethyl citrate appeared to be hydrolyzed at a slower rate with human serum compared to rat serum.
Samples of freshly collected rat or human serum were spiked with triethyl citrate and the disappearance of the triethyl citrate measured over a 4 hr period. Triethyl citrate was rapidly hydrolysed by rat serum (15 min), but hydrolysisoccurred at a much slower rate in human serum and was not complete at the end of the 4 hr test period.
Rat-, mouse- and human-liver homogenates as well as serum enzymes hydrolyse triethyl citrate to 1 mol citric acid and 3 mol ethanol/mol ester.
/Triethyl citrate/ is expected to be extensively metabolized by esterases and cytochrome P450 enzymes and break-down in the beta-oxidation or citric acid cycle or in cases subsequent glucuronidation. The substance is assumed to be excreted (if not metabolized completely in beta-oxidation and citric cycle) as metabolites (i.e. conjugates with glucuronic acid) via urine and to a lower extent via bile.

Toxicity Summary
IDENTIFICATION AND USE: Triethyl citrate is a colorless, oily liquid with bitter taste. It is used as solvent and plasticizer for nitrocellulose and natural resins, softener, paint removers, agglutinant, perfume base, food additive (not over 0.25%) as an emulsifier and as a flavor-preserving agent. HUMAN EXPOSURE AND TOXICITY: Triethyl citrate 20% in petrolatum was not a primary irritant or sensitizer in human studies. ANIMAL STUDIES: Triethyl citrate, applied undiluted during epidermal induction, was a strong sensitizer in a guinea pig maximization test. Triethyl citrate 33.3% produced irritation in rabbit eyes. Intravenous administration of a 100 mg/kg bw dose of triethyl citrate to rabbits produced a marked increase in motor activity and respiration. A group of 20 mice given intraperitoneal doses of 350 mg/kg bw of triethyl citrate daily for 14 days had a slightly lower mean growth rate than control animals. No differences were seen in the two groups in erythrocyte and leucocyte blood cell count, clotting time and hemoglobin levels. Examination of the liver, lung and kidney tissues of two animals at necropsy revealed no pathological cellular changes. At doses ranging from 0.5 to 10 mg/kg b.w. triethyl citrate was nonteratogenic in the chicken embryo. Ames test using triethyl citrate (0.4%-1.6%) on Salmonella typhimurium TA1535, TA1537, TA1538 was negative with and without metabolic activation.

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Toxicity Data
LC50 (rat) = 1,300 ppm/6h

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Non-Human Toxicity Values
LD50 Guinea pig dermal >10 mL/kg
LD50 Mouse ip 1750 mg/kg
LD50 Rabbit dermal >5 g/kg
LD50 Rat inhalation 3500 pppm
For more Non-Human Toxicity Values (Complete) data for TRIETHYL CITRATE (11 total), please visit the HSDB record page.

Triethyl citrate is a carbonyl compound.
Triethyl citrate is used in foods as a flavouring agent, solvent and surface-active agent Triethyl citrate is an ester of citric acid. It is a colorless, odorless liquid used as a food additive (E number E1505) to stabilize foams, especially as whipping aid for egg white. In pharmaceutical coatings and plastics.
Triethyl citrate belongs to the family of Tricarboxylic Acids and Derivatives. These are organic compounds containing three carboxylic acid groups (or salt/ester derivatives thereof).

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Mechanism of Action
There was some evidence that type of effects produced may have resulted from binding of calcium by release of citrate ion with resultant hypocalcemia.

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Therapeutic Uses
/EXPL THER/ The objective of this study was/ to evaluate the efficacy and tolerability of a novel lotion containing triethyl citrate and ethyl linoleate in the treatment of mild to moderate acne vulgaris. This was a double-blind, placebo-controlled, randomized study comparing the active lotion containing triethyl citrate and ethyl linoleate with its vehicle as a placebo control. Patients were assessed by the modified Leeds acne grading system as well as by counting inflammatory and noninflammatory lesions on the face at weeks 0, 4, 8 and 12. Sebum production was assessed by the Sebutape method at weeks 0 and 12. All adverse events were recorded. Forty patients were recruited into the study, of whom 33 completed the study. Active treatment was statistically superior to placebo in reduction of Leeds grading and total, inflammatory and noninflammatory lesion counts. The active lotion showed a rapid response with obvious reduction in lesion counts and acne grading by 4 weeks. Sebum production was significantly reduced in the actively treated group, with a mean reduction of 53% in sebum production compared with baseline. One patient developed irritation to the active lotion and withdrew from the study. The new lotion containing triethyl citrate and ethyl linoleate has been shown to be an effective treatment for mild to moderate acne, with an effect on both inflammatory and noninflammatory acne lesions. The new lotion worked quickly and was generally well tolerated. A surprising finding was the significant impact the new lotion has on sebum production, suggesting a role in patients with seborrhea.
MEDICATION (VET): ... Orally, in treating bloat 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.)