Absorption, Distribution and Excretion
Ethyl (14C) vanillin was dissolved in polyethylene glycol and administered by gavage to male and female Sprague-Dawley CD rats at single doses of 50, 100, or 200 mg/kg body weight. Ethyl vanillin was rapidly absorbed, with peak plasma radioactivity occurring within 2 hours of administration in all dose groups, rapidly decreasing to undetectable levels within 96 hours. Plasma radioactivity was consistently higher in female rats than in male rats, presumably reflecting a lower metabolic capacity in females. The radioactive material was rapidly excreted in the urine, with over 94% of the dose excreted within 24 hours. Only 1–5% of the dose was excreted in the feces. After 5 days, over 99% of the administered dose was excreted. No radioactivity was detected in exhaled breath, indicating that the aromatic ring was in a metabolically stable state. Metabolism/Metabolites A healthy adult male volunteer consumed 235 ml of a liquid dietary supplement containing an unknown amount of ethyl vanillin. Ethyl vanillic acid was detected at a concentration of 13 mg/g creatinine in a 12-hour urine sample. This compound was not detected in urine collected prior to exposure. Ethyl vanillic acid was identified in the urine of a 9-year-old female patient who had taken a vanilla-flavored liquid dietary supplement by gas chromatography-mass spectrometry (GC/MS). Other patients known to excrete this acid have also consumed foods containing ethyl vanillin. Trace amounts of vanillylmandelic acid were also found in eight urine samples with ethyl vanillic acid concentrations exceeding 50 mg/g creatinine. Unaltered ethyl vanillin was not detected in any urine samples. In human subjects, urinary organic acid analysis revealed that some patients excreted high concentrations of ethyl vanillic acid (3-ethoxy-4-hydroxybenzoic acid) and trace amounts of 3-ethoxy-4-hydroxymandelic acid. Ethyl(14C)-vanillin was administered orally to male and female Sprague Dawley CD rats at single doses of 50, 100, or 200 mg/kg body weight. The substance is rapidly metabolized, with ethylvanillin being the major metabolite at all dose levels. Following hydrolysis by glucuronidase and/or sulfatase, urinary analysis revealed that the major metabolites were glucuronide or sulfate conjugates of ethylvanillin (56-62%), ethylvanillyl alcohol (15-20%), and ethylvanillin (7-12%). A small amount (2-8%) was excreted as a glycine conjugate of vanillic acid (ethylvanillyl glycine). Previous reports suggested that ethylvanillin may be metabolized to ethylvanillin glucuronide and ethylvanillic acid, a portion of which is conjugated with glucuronic acid and sulfate.

Toxicity Summary
Identification and Uses: Ethyl vanillin forms small, needle-like crystals and is used in flavorings for its vanilla aroma. It is also used as a vanilla substitute or to enhance the flavor of vanilla in various foods. Ethyl vanillin is a widely used food additive and flavoring in food, beverages, cosmetics, and pharmaceuticals. Human Exposure and Toxicity: Human studies have shown that concentrations of ethyl vanillin ranging from 8 to 128 μM have no significant effect on the activity of five human CYP450 enzymes. A 2% concentration of ethyl vanillin caused mild skin irritation in humans after 48 hours of direct exposure. Animal Studies: Animal studies have shown that ethyl vanillin is mostly non-toxic except when administered at high doses for more than 6 weeks. Rabbits were orally administered ethyl vanillin dissolved in a 10% glycerol aqueous solution at a dose of 49 mg/kg body weight/day for 43 consecutive days. At this dose level, anemia, diarrhea, and insufficient weight gain were observed. Rats (n=20 per group, half male and half female) were fed ethyl vanillin with a purity >99.9% (diet type, e.g., semi-synthetic/standard diet, not specified) at doses of 0, 500, 1000, or 2000 mg/kg body weight/day for 13 weeks. Clinical biochemical examinations showed significantly elevated ALAT, ALP, cholesterol, and total plasma protein levels in the high-dose group compared to the control group. Histological examination revealed perihepatic and bile duct inflammation in both male and female rats in the medium-dose and high-dose groups, positively correlated with dose. Furthermore, mild bile duct hyperplasia was observed in 1 of the 20 male rats in the medium-dose group and 4 of the 20 male rats in the high-dose group. No changes were observed in the liver parenchyma, and no degenerative or inflammatory changes were seen in the bile duct epithelium. Increased white pulp cells and significantly enlarged germinal centers were observed in the spleen in both the medium-dose and high-dose groups; significantly enlarged germinal centers and enhanced lymphocyte proliferation were also observed in the cervical lymph nodes. Twelve male and twelve female rats were fed diets containing 0%, 0.5%, 1%, and 2% ethyl vanillin for two years, or diets containing 2% and 5% ethyl vanillin for one year. No adverse effects on growth, major organ weight, hematology, or major histology were observed. In genotoxicity studies, ethyl vanillin did not induce genetic alterations in vitro, but it has been reported to enhance the ability of mitomycin C to induce sister chromatid exchange. Ethyl vanillin has been shown to possess anti-angiogenic, anti-inflammatory, and analgesic properties, and its mechanism of action may be through inhibiting nitric oxide production, thereby reducing reactive oxygen species levels. In vivo experiments indicate that there may be drug interactions between vanillin/ethyl vanillin and drugs metabolized by CYP2E1 or CYP1A2, suggesting that the use of these additives in food and pharmaceuticals should not be unrestricted to avoid adverse interactions. This study tested the heat resistance of Cronobacter sakazakii after rehydration in water or apple juice at 58°C, with the addition of vanillin, ethyl vanillin, or vanillic acid, respectively. The results showed that all three compounds reduced the heat resistance of Cronobacter sakazakii during rehydration. Adding vanillin, ethyl vanillin, or vanillic acid to PIF can improve the safety of PIF or other dehydrated foods contaminated with Cronobacter sakazakii.

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Non-human toxicity values
Canine intravenous LD50: 760 mg/kg
Rat subcutaneous LD50: 1800 mg/kg
Rabbit oral LD50: 3000 mg/kg
Rat oral LD50: >2000 mg/kg
For more complete non-human toxicity data on ethyl vanillin (7 compounds), please visit the HSDB record page.

Ethyl vanillin is a colorless crystal with a stronger vanilla aroma and flavor than vanillin. (NTP, 1992)
Ethyl vanillin belongs to the benzaldehyde class of compounds and is a derivative of vanillin, in which the methoxy group is replaced by an ethoxy group. It has antioxidant and flavoring properties. Ethyl vanillin belongs to the benzaldehyde, phenol, and aromatic ether class of compounds, and its functions are related to vanillin.
Ethyl vanillin has been reported to be found in Japanese Cornus officinalis (Microtropis japonica) and Cornus officinalis, and relevant data exist.
Ethyl vanillin is a metabolite of 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.

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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.

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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.

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