Absorption, Distribution and Excretion
Ethyl (14C)-vanillin was administered to male and female Sprague-Dawley CD rats by gavage in polyethylene glycol solution at single doses of 50, 100, or 200 mg/kg bw. Ethyl vanillin was rapidly absorbed and peak plasma radioactivity occurred within 2 hr after dosing at all dose levels, falling rapidly to undetectable levels within 96 hr. Plasma radioactivity tended to be higher in female than male rats and it was postulated that this might reflect a lower metabolic capacity of female rats. Urinary excretion of radioactivity was rapid and more than 94% of the dose was excreted by this route within 24 hr. Only 1-5% of the dose was excreted in faeces. After 5 days, more than 99% of the administered dose was excreted. No radioactivity was detected in expired air, indicating that the aromatic ring was in a metabolically stable position.

---

Metabolism / Metabolites
A healthy adult male volunteer drank a 235 ml aliquot of a liquid dietary supplement containing an unknown quantity of ethyl vanillin. A concentration of 13 mg ethyl vanillic acid/g creatinine was found in a 12-hour urine sample. The compound was not present in urine collected before exposure.
Ethyl vanillic acid was identified by GC/MS in the urine of a 9-year old female patient who had received liquid dietary supplementation flavored with vanilla. Other patients excreting this acid were also known to have consumed foodstuffs flavored with ethyl vanillin. Eight different urine samples containing more than 50 mg ethyl vanillic acid/g creatinine were also found to contain small amounts of vanillylmandelic acid. Unchanged ethyl vanillin was not detected in any of the urine samples.
During urinary organic acid profiling in human subjects, several patients excreted high concentrations of ethyl vanillic acid (3-ethoxy-4-hydroxybenzoic acid) and traces of 3-ethoxy-4-hydroxy- mandelic acid.
Ethyl (14C)-vanillin was administered to male and female Sprague Dawley CD rats at single oral doses of 50, 100, or 200 mg/kg bw. Rapid metabolism occurred and the principal metabolite at all dose levels was ethyl vanillic acid. Analysis of urine after hydrolysis with glucuronidase and/or sulfatase indicated that the major metabolites were glucuronide or sulfate conjugates of ethyl vanillic acid (56-62%), ethyl vanillyl alcohol (15-20%), and ethyl vanillin (7-12%). A minor proportion of the dose (2-8%) was excreted as the glycine conjugate of vanillic acid (ethyl vanilloyl glycine).
Early reports indicated that ethyl vanillin was probably metabolized to glucuroethyl vanillin and ethyl vanillic acid, of which some was conjugated with glucuronic and sulfuric acids.

Toxicity Summary
IDENTIFICATION AND USE: Ethyl vanillin forms fine crystalline needles and is used in fragrances for its vanilla odor. It is also used as a replacement of or to strengthen the flavor of vanilla in a variety of foods. Ethyl vanillin is a widely used food additive and spice in foods, beverages, cosmetics and drugs. HUMAN EXPOSURE AND TOXICITY: Research in humans showed that ethyl vanillin had no significant effect on the activity of five human CYP450 enzymes with concentration ranged from 8 to 128 uM. A 2% concentration of ethyl vanillin caused mild irritation on the skin of humans after 48 hours of direct contact. ANIMAL STUDIES: In animal studies, ethyl vanillin was found to be mostly non-toxic except when given at high doses for longer than 6 weeks. Rabbits were given ethyl vanillin orally in 10% aqueous glycerin 49 mg/kg bw/day for 43 days. At this dose level anemia, diarrhea and lack of weight gain were observed. Rats (20/sex/group) were fed ethyl vanillin of > 99.9% purity (nature of diet e.g., semi-synthetic/chow diet, not specified) at dose levels of 0, 500, 1000 or 2000 mg/kg bw/day for 13 weeks. Clinical biochemistry showed statistically significant higher values in the high-dose group compared to control for ALAT, ALP, cholesterol and total plasma protein. Histological examination revealed a dose-related increased incidence of hepatic peribiliary inflammatory change in both males and females of the intermediate- and high-dose groups, and minor bile duct hyperplasia affecting 1/20 intermediate- and 4/20 high-dose males. There were no changes observed in the liver parenchyma and no degenerative or inflammatory changes of the bile duct epithelium. Increased white pulp cellularity and prominence of germinal centers in the spleen, and increased prominence of germinal centers and lymphoid proliferation in cervical lymph nodes were seen in the intermediate- and high-dose groups. Groups of 12 male and 12 female rats were fed diets containing 0, 0.5, 1 and 2% ethyl vanillin for 2 years or 2% and 5% for one year without any adverse effects on growth, organ weights of major organs, hematology and histology of major tissues. In genotoxicity studies, ethyl vanillin did not induce genetic changes in vitro but was reported to enhance the ability of mitomycin C to cause sister chromatid exchanges. Ethyl vanillin has shown to have anti-angiogenic, anti-inflammatory and anti-nociceptive properties that are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level. The in vivo results revealed that drug interaction between vanillin/ethyl vanillin and drugs metabolized by CYP2E1 or CYP1A2 might be possible, and also suggested that the application of the above additives in foods and drugs should not be unlimited so as to avoid the adverse interaction. The thermal tolerance Cronobacter sakazakii was examined in sterile powdered infant formula (PIF) rehydrated at 58 °C in water or apple juice supplemented with vanillin, ethyl vanillin, or vanillic acid. All three compounds decreased thermal tolerance during-rehydration. Supplementation of PIF with vanillin, ethyl vanillin, or vanillic acid could enhance the safety of PIF or other dehydrated foods contaminated with C. sakazakii.

---

Non-Human Toxicity Values
LD50 Dog iv 760 mg/kg
LD50 Rat sc 1800 mg/kg
LD50 Rabbit oral 3000 mg/kg
LD50 Rat oral >2000 mg/kg
For more Non-Human Toxicity Values (Complete) data for ETHYL VANILLIN (7 total), please visit the HSDB record page.

Ethyl vanillin appears as colorless crystals. More intense vanilla odor and taste than vanillin. (NTP, 1992)
Ethyl vanillin is a member of the class of benzaldehydes that is vanillin in which the methoxy group is replaced by an ethoxy group. It has a role as an antioxidant and a flavouring agent. It is a member of benzaldehydes, a member of phenols and an aromatic ether. It is functionally related to a vanillin.
Ethyl vanillin has been reported in Microtropis japonica and Cornus officinalis with data available.
Ethyl vanillin is a metabolite found in or produced by Saccharomyces cerevisiae.

C9H10O3

166.1739

166.062

121-32-4

Ethylvanillin-d5;1335401-74-5

8467

Fine, crystalline needles
White or slightly yellowish crystals
Colorless flakes

1.2±0.1 g/cm3

295.1±20.0 °C at 760 mmHg

76 °C

119.0±15.3 °C

0.0±0.6 mmHg at 25°C

1.574

1.72

1

3

3

12

147

0

O(C([H])([H])C([H])([H])[H])C1=C(C([H])=C([H])C(C([H])=O)=C1[H])O[H]

CBOQJANXLMLOSS-UHFFFAOYSA-N

InChI=1S/C9H10O3/c1-2-12-9-5-7(6-10)3-4-8(9)11/h3-6,11H,2H2,1H3

3-ethoxy-4-hydroxybenzaldehyde

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

Ethanol :≥ 100 mg/mL (~601.79 mM)
DMSO : ≥ 100 mg/mL (~601.79 mM)
H2O : ~5 mg/mL (~30.09 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (15.04 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (15.04 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (15.04 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.

---

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