エチルバニリン

log Kow = 1.58

1.58

Finer and more intense vanilla

Resembles that of vanillin but approximately 3 times as strong.

Sweet

Finer and more intense taste than vanillin

FLAVORING AGENT OR ADJUVANT, PH CONTROL AGENT -> FDA Substance added to food

Food

Fine, crystalline needles

White or slightly yellowish crystals

Colorless flakes

Slightly soluble (NTP, 1992)

In water, 2,822 mg/L at 25 °C

Slightly soluble in water (1 g in 100 mL at 50 °C)

Soluble in ethanol, ether, benzene, chloroform

Freely soluble in ... solutions of alkali hydroxides; soluble in glycerol, propylene glycol

Solubility in 95% alcohol about 1 g/2 mL

This chemical does not meet GHS hazard criteria for 78.7% (1611 of 2046) of all reports.

Warning

H319 (20.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)

Aggregated GHS information provided per 2046 reports by companies from 15 notifications to the ECHA C&L Inventory.

Warning

Chemical: Benzaldehyde, 3-ethoxy-4-hydroxy-

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Benzaldehyde, 3-ethoxy-4-hydroxy- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzaldehyde, 3-ethoxy-4-hydroxy- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 30-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/13700

Ethylvanillin: Does not have an individual approval but may be used under an appropriate group standard

Synthetic flavoring substances and adjuvants /for human consumption/ that are generally recognized as safe for their intended use, withn the meaning of section 409 of the Act. Ethyl vanillin is included on this list.

Substances migrating to food from paper and paperboard products used in food packaging that are generally recognized as safe for their intended use, within section 409 of the Act. Ethyl vanillin is included on this list.

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Ethyl vanillin is included on this list.

REVIEW WITH 13 REFERENCES.[OPDYKE DL J; FRAGRANCE RAW MATERIALS. ETHYL VANILLIN; FOOD COSMET TOXICOL 13(1) 103 (1975)]

BIBRA working group, Ethyl vanillin, Toxicity profile; The British Industrial Biological Research Association; 4 (1967). In a volunteer study, ethyl vanillin (EV) demonstrated no sensitizing potential but was a skin irritant.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 9/30/91; Reporting date: 11/27/91.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Benzaldehyde, 3-ethoxy-4-hydroxy- is included on this list. Effective date: 9/30/91; Sunset date: 6/30/98.

Protect from light. (NTP, 1992) Aldehydes are readily oxidized to give carboxylic acids. Flammable and/or toxic gases are generated by the combination of aldehydes with azo, diazo compounds, dithiocarbamates, nitrides, and strong reducing agents. Aldehydes can react with air to give first peroxo acids, and ultimately carboxylic acids. These autoxidation reactions are activated by light, catalyzed by salts of transition metals, and are autocatalytic (catalyzed by the products of the reaction). The addition of stabilizers (antioxidants) to shipments of aldehydes retards autoxidation.

A human skin irritant.

... Highly irritating action on the eyes and mucous membranes of the respiratory tract. /Aldehydes/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

EC50; Species: Pimephales promelas (Fathead Minnow) age 28 days, length 14.2 mm; Conditions: freshwater, flow through, 24 (22.7-25.2) °C, pH 7.65 (7.19-8.10), hardness 52.2 (51.4-53.0) mg/L CaCO3, alkalinity 46.6 (46.0-47.0) mg/L CaCO3, dissolved oxygen 77.4 (71.5-90.1) mg/L; Concentration: 90600 ug/L for 24 hr; Effect: behavior, decreased equilibrium /97% purity/

EC50; Species: Pimephales promelas (Fathead Minnow) age 28 days, length 14.2 mm; Conditions: freshwater, flow through, 24 (22.7-25.2) °C, pH 7.65 (7.19-8.10), hardness 52.2 (51.4-53.0) mg/L CaCO3, alkalinity 46.6 (46.0-47.0) mg/L CaCO3, dissolved oxygen 77.4 (71.5-90.1) mg/L; Concentration: 84300 ug/L for 48 hr; Effect: behavior, decreased equilibrium /97% purity/

LC50; Species: Pimephales promelas (Fathead Minnow) age 28 days, length 14.2 mm; Conditions: freshwater, flow through, 24 (22.7-25.2) °C, pH 7.65 (7.19-8.10), hardness 52.2 (51.4-53.0) mg/L CaCO3, alkalinity 46.6 (46.0-47.0) mg/L CaCO3, dissolved oxygen 77.4 (71.5-90.1) mg/L; Concentration: 98000 ug/L for 24 hr /97% purity/

LC50; Species: Pimephales promelas (Fathead Minnow) age 28 days, length 14.2 mm; Conditions: freshwater, flow through, 24 (22.7-25.2) °C, pH 7.65 (7.19-8.10), hardness 52.2 (51.4-53.0) mg/L CaCO3, alkalinity 46.6 (46.0-47.0) mg/L CaCO3, dissolved oxygen 77.4 (71.5-90.1) mg/L; Concentration: 90400 ug/L for 48 hr /97% purity/

LC50; Species: Pimephales promelas (Fathead Minnow) age 28 days, length 14.3 mm. weight 0.034 g; Conditions: freshwater, flow through, 24.1 °C, pH 7.7, hardness 52.2 mg/L CaCO3, alkalinity 46.4 mg/L CaCO3, dissolved oxygen 6.5 mg/L; Concentration: 87600 ug/L for 96 hr (95% confidence limit: 81400-94300 ug/L) /97% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from a log Kow of 1.58(2) and a regression-derived equation(3), indicates that ethyl vanillin is expected to have high mobility in soil(SRC). Volatilization of ethyl vanillin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.1X10-10 atm-cu m/mole(4) derived from its vapor pressure, 1.04X10-5 mm Hg(5), and water solubility, 2,820 mg/L(6). Ethyl vanillin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(5). Utilizing the Japanese MITI test, 88% of the Theoretical BOD was reached in 2 weeks(7) indicating that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from a log Kow of 1.58(2) and a regression-derived equation(3), indicates that ethyl vanillin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 8.1X10-10 atm-cu m/mole(5), derived from its vapor pressure, 1.04X10-5 mm Hg(6), and water solubility, 2,820 mg/L(7). According to a classification scheme(8), an estimated BCF of 5(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Ethyl vanillin contains chromophores that absorb at wavelengths >290 nm(9) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Utilizing the Japanese MITI test, 88% of the Theoretical BOD was reached in 2 weeks(10) indicating that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethyl vanillin, which has a vapor pressure of 1.04X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase ethyl vanillin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1 day(SRC), calculated from its rate constant of 3.3X10-11 cu cm/molecule-sec at 25 °C(SRC). Particulate-phase ethyl vanillin may be removed from the air by wet and dry deposition(SRC). Ethyl vanillin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Ethyl vanillin was detected in artificial vanilla extracts purchased from local and internet retail stores at concentrations ranging from 0.13 to 2.39 ng/mL(1). Ethyl vanillin was detected in samples of 23 domestic and imported vanilla extract products at concentrations ranging from 0.4 to 2.2 mg/g(2).

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.

EPA has released the first beta version (version 0.5) of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The beta version of the iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays; Click on the "Chemical Explorer" button on the tool bar to see the data./[USEPA; ICSS Dashboard Application; Available from, as of April 22, 2015: http://actor.epa.gov/dashboard/]

The Koc of ethyl vanillin is estimated as 60(SRC), using a log Kow of 1.58(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that ethyl vanillin is expected to have high mobility in soil. The pKa of the related compound vanillin is 7.4(3). By analogy, this value suggests that ethyl vanillin will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ ... A maximization test was carried out on 25 volunteers. The material /ethyl vanillin/ was tested at a concentration of 2% in petrolatum and produced no sensitization reactions.

/HUMAN EXPOSURE STUDIES/ ... When tested as 2% in petrolatum, ethyl vanillin produced mild irritation after a 48 hr closed-patch test in 25 human subjects.

/ALTERNATIVE and IN VITRO TESTS/ ... The objective of the present work was to evaluate the impact of vanillin and ethyl vanillin on the activities of CYP2C9, CYP2E1, CYP3A4, CYP2B6 and CYP1A2 in human liver microsomes (HLM) in vitro.... The in vitro results demonstrated that vanillin and ethyl vanillin had no significant effect on the activity of five human CYP450 enzymes with concentration ranged from 8 to 128 uM....

AEROBIC: Ethyl vanillin reached 52.9% of its theoretical BOD in 5 days using an acclimated mixed microbial culture in the Closed Bottle test(1). Ethyl vanillin, present at 100 mg/L, reached 88% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(2).

Synthetic flavoring substances and adjuvants /for human consumption/ that are generally recognized as safe for their intended use, withn the meaning of section 409 of the Act. Ethyl vanillin is included on this list.

Substances migrating to food from paper and paperboard products used in food packaging that are generally recognized as safe for their intended use, within section 409 of the Act. Ethyl vanillin is included on this list.

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Ethyl vanillin is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 9/30/91; Reporting date: 11/27/91.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Benzaldehyde, 3-ethoxy-4-hydroxy- is included on this list. Effective date: 9/30/91; Sunset date: 6/30/98.

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.

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.

Used in perfumes, flavors, and organic synthesis; [HSDB]

In flavoring and perfumery

Used as a chemical intermediate

Flavors, to replace or fortify vanillin.

Reported uses (ppm):

Ethyl vanillin is used extensively in the chocolate industry. It gives a sweet, balsamic note to flowery and fruity perfume compositions.

(1972) 6.93X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1976) 1.06X10+8 GRAMS (PRINCPL CUSTMS DISTS)

2023: 10,000,000 - <25,000,000 lb

(1972) 1.27X10+7 GRAMS

(1975) GREATER THAN 4.5X10+7 GRAMS

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzaldehyde, 3-ethoxy-4-hydroxy-. Aggregated National Production Volume: 1 to < 10 million pounds.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzaldehyde, 3-ethoxy-4-hydroxy-. National Production Volume: 1,000,000 - 10,000,000 lb/yr.

From safrole by isomerization to isosafrole and subsequent oxidation to piperonal; the methylene linkage is then broken by heating piperonal in an alcoholic solution of KOH; finally the resulting protocatechualdehyde is reacted with ethyl alcohol.

From guaethol by condensation with chloral to yield 3-ethoxy-4-hydroxyphenyl trichloromethyl carbinol; this is then boiled with an alcoholic solution of KOH or NaOH, acidified, and extracted with chloroform to yield ethyl vanillin.

By reacting o-ethoxyphenol with formaldehyde and p-nitrosodimethylaniline in the presence of aluminum and water.

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

All Other Chemical Product and Preparation Manufacturing

Benzaldehyde, 3-ethoxy-4-hydroxy-: ACTIVE

The flavoring power is two to four times stronger than vanillin.