Absorption, Distribution and Excretion
... When vanillin was fed to rats at doses of 100 mg/kg most metabolites were excreted in the urine within 24 hr....

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Metabolism / Metabolites
... Vanillin administered intraperitoneally to rats gave rise to a number of urinary products; chief among these was vanillic acid in both free and conjugated forms. Other metabolites were conjugated vanillin, conjugated vanillyl alcohol, and catechol.
YIELDS PROTOCATECHUALDEHYDE PROBABLY BY MICROORGANISMS; VANILLIN-4-BETA-D-GLUCOSIDE IN BEAN & JAPONICA; VANILLIN-4-BETA-D-GLUCURONIDE IN RABBITS. /FROM TABLE/
... When vanillin was fed to rats at doses of 100 mg/kg most metabolites were excreted in urine within 24 hr, chiefly as glucuronide and/or sulfate conjugates, although the acids formed were also excreted free and as their glycine conjugates. In 48 hr 94% of the dose was accounted for, 7% as vanillin, 19% as vanillyl alcohol, 47% as vanillic acid, 10% as vanilloyglycine, 8% as catechol, 2% as 4-methylcatechol, 0.5% as guaiacol , and 0.6% as 4-methylguaiacol.
YIELDS VANILLIC ACID IN MAN. /FROM TABLE/

Toxicity Summary
IDENTIFICATION: Small quantities of vanillin are used in perfumery to round and fix sweet, balsamic fragrances. Vanillin is also used as a brightener in galvanotechnical processes and is an important intermediate in, for example, the production of pharmaceuticals such as l-3,4-dihydroxyphenylalanine (l-DOPA) and methyldopa. For vanillin (USEPA/OPP Pesticide Code: 115801) there are 0 labels match. /Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./ Pharmaceutic aid (flavor). As a flavoring agent in confectionery, beverages, foods and animal feeds. Fragrance and flavor in cosmetics. Reagent for synthesis. HUMAN EXPOSURE AND TOXICITY: In closed-patch tests on human skin vanillin caused no primary irritation when tested at concentrations of 20% on 29 normal subjects, at 2% on 30 normal subjects, and at 0.4% on 35 subjects with dermatoses. Maximization tests were conducted on groups of 25 volunteers. The material was tested at concentrations of 2 and 5% in petrolatum and produced no sensitization reactions. Vanillin was considered to be a secondary allergen because sensitivity was found only in patients sensitive to vanilla, isoeugenol, and coniferyl benzoate. Drug interaction between vanillin/ethyl vanillin and drugs metabolized by CYP2E1/CYP1A2 might be possible. ANIMAL STUDIES: Vanillin injected intraperitoneally into strain A mice in total doses of 3.6-18.0 g/kg over a period of 24 weeks produced no excesses of lung tumors and was not considered to be carcinogenic. Groups of 16 rats were fed diets containing vanillin at levels to provide 20 mg/kg body weight/day for 18 week without any adverse effects, but 64 mg/kg/day for 10 week caused growth depression and damage to myocardium, liver, kidney, lung, spleen, and stomach. In experiments with yeast, vanillin acted as a co-mutagen. The modifying effects of vanillin on the cytotoxicity and 6-thioguanine (6TG)-resistant mutations induced by two different types of chemical mutagens, ethyl methanesulfonate (EMS) and hydrogen peroxide (H2O2), were examined using cultured Chinese hamster V79 cells. The effects of vanillin on H2O2-induced chromosome aberrations were also examined. Vanillin had a dose-dependent enhancing effect on EMS-induced cytotoxicity and 6TG-resistant mutations, when cells were simultaneously treated with vanillin. The post-treatment with vanillin during the mutation expression time of cells after treatment with EMS also showed an enhancement of the frequency of mutations induced by EMS. However, vanillin suppressed the cytotoxicity induced by H2O2 when cells were post-treated with vanillin after H2O2 treatment. Vanillin showed no change in the absence of activity of H2O2 to induce mutations. Post-treatment with vanillin also suppressed the chromosome aberrations induced by H2O2. The differential effects of vanillin were probably due to the quality of mutagen-induced DNA lesions and vanillin might influence at least two different kinds of cellular repair functions. Vanillin (200 ug/culture) was found to directly suppress the in vitro anti-sheep RBC antibody response at noncytotoxic doses.

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Toxicity Data
LC (rat) > 41.7 mg/m3/4hr

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Interactions
Methotrexate (MTX), a chemotherapeutic agent used to treat cancer, produces cytogenetic damage and has a cytostatic effect in a variety of test systems. Several antigenotoxic agents have been studied in various in vitro and in vivo systems. However, data are limited regarding their ability to modulate MTX-induced genotoxicity. In the present study, vanillin (VA) and chlorophyllin (CHL) were used as antigenotoxic agents to study their ability to minimize the DNA damage caused by MTX. Exponentially growing V79 Chinese hamster lung cells were treated with MTX at five different concentrations (5-100 ug/mL) with S9 activation for 6 h and post-treated with two concentrations of either VA (50 or 100 ug/mL) or CHL (50 or 100 ug/mL) for 40 h. Cytochalasin B was added for the micronucleus (MN) assay along with antigenotoxic agents to evaluate MN in binucleated cells. Chromosomal aberrations were also evaluated in parallel cultures. Results indicate that MTX alone induced a dose-dependent decrease in the nuclear division index (NDI) and the mitotic index (MI). A significant increase in percent micronucleated binucleated cells (MNBN) and percent aberrant cells (Abs) was observed. Studies using VA as an antigenotoxic agent showed a decrease in the number of MNBN (26.3-83.1%) and Abs (16.0-87.5%) with the addition of either 50 or 100 micrograms VA/ml. The addition of CHL also significantly reduced the number of MNBN (53.0-91.5%) at both concentrations tested. Chromosomal aberrations were also significantly reduced (41.0-83.0). These studies indicate that both VA and CHL are capable of effectively minimizing MTX-induced chromosomal damage.
Vanillin (VA), an anticlastogen, has been demonstrated to inhibit gene mutations in both bacterial and mammalian cells. However, the data on its effect against radiation-induced cytogenetic damage are limited. The aim of this study was to investigate the protective effect of on radiation-induced chromosomal damage in V79 cells. Exponentially growing cells were exposed to five doses of X-rays (1-12 Gy) and UV radiation (50-800 x 10(2)uJ/sq cm and posttreated with 3 concentrations of VA (5, 50 or 100 ug/mL for 16 hr for micronucleus (MN) and 18 h for structural chromosomal aberration (SCA) analyses. MN and SCA assays were performed concurrently according to standard procedures. Results indicate that there was a dose related increase in the percent of micronucleated binucleated cells (MNBN) (5.6 to 79.6) and percent of aberrant cells (Abs) (12 to 98) with X-ray treatment alone. Inhibition studies showed that the addition of VA at 100 VA ug/mL significantly reduced the percent of micronucleated binucleated cells (21 to 48) induced by X-ray at 1, 2, and 4 Gy. There was a slight decrease in percent micronucleated binucleated cells at 5 and 50 VA ug/mL. All three concentrations of VA decreased percent Abs (15.7 to 57.1) induced by X-rays at all doses. UV radiation alone significantly increased percent micronucleated binucleated cells (3.5 to 14.8) and percent Abs (17 to 29). Addition of 50 or 100 VA ug/mL, significantly decreased percent micronucleated binucleated cells (31.7 to 86.2) and percent Abs (54.5 to 90.9) at all doses of UV radiation. A decrease in percent micronucleated binucleated cells (2.8 to 72.4) and percent Abs (34.8 to 66.7) was also noted at 5 VA ug/mL. These data clearly indicate the protective effect of VA on radiation-induced chromosomal damage, suggesting that VA is an anticlastogenic agent.
The effects of dietary bioantimutagens (compounds which have been shown to inhibit mutagenesis via interaction with DNA repair processes) on spontaneous and heterocyclic amine (HCA)-induced micronucleus (MN) frequencies were studied in metabolically competent human hepatoma (Hep-G2) cells. All the compounds tested (coumarin, vanillin, caffeine, tannic acid and cinnamaldehyde) caused a moderate increase of micronucleus numbers in Hep-G2 cells at high concentrations (500 ug/ml); only tannic acid was also active at lower dose levels. In combination experiments with the heterocyclic amine 2-amino-3-methylimidazo-[3,4-f]quinoline (IQ), post-treatment of the cells with bioantimutagens resulted in a pronounced (75-90%) decrease in micronucleus. The most drastic effects were seen with vanillin, coumarin and caffeine which were active at concentrations < or = 5 ug/ml. Further experiments indicated that these compounds also attenuate the mutagenic effects of other HCAs (PhIP, MeIQ, MeIQx, Trp-P-1).
N-Methylnitrosourea (MNU) administered to pregnant mice at the stage of blastogenesis induces congenital anomalies probably by direct affection to the embryos. In this study, we examined whether several antimutagens, such as vanillin (VA) and CoCl2, modify the developmental toxicity of N-Methylnitrosourea given to pregnant mice at the preimplantation stage. ICR mice were treated with N-Methylnitrosourea at a single IP dose of 20 mg/kg on day 2.5 of gestation. A single IP dose of 50 mg/kg of vanillin or single IV dose of 10 mg/kg of CoCl2 was administered 1 hour after N-Methylnitrosourea treatment. Embryotoxicity and teratogenicity were examined on day 18 of gestation. N-Methylnitrosourea-induced embryonic/fetal mortality was remarkably decreased by CoCl2 and the incidence of N-Methylnitrosourea-induced external malformations was obviously decreased. These suppressing effects of vanillin and CoCl2 support the idea that embryotoxicity of N-Methylnitrosourea is caused by the direct action on embryos. Furthermore, the effects of vanillin and CoCl2 is considered to be a direct modifying action into the affected embryos after N-Methylnitrosourea treatment. ...
The modifying effects of vanillin on the cytotoxicity and 6-thioguanine (6TG)-resistant mutations induced by two different types of chemical mutagens, ethyl methanesulfonate (EMS) and hydrogen peroxide (H2O2), were examined using cultured Chinese hamster V79 cells. The effects of vanillin on hydrogen peroxide-induced chromosome aberrations were also examined. Vanillin had a dose-dependent enhancing effect on ethyl methanesulfonate-induced cytotoxicity and 6TG-resistant mutations, when cells were simultaneously treated with vanillin. The post-treatment with vanillin during the mutation expression time of cells after treatment with ethyl methanesulfonate also showed an enhancement of the frequency of mutations induced by ethyl methanesulfonate. However, vanillin suppressed the cytotoxicity induced by hydrogen peroxide when cells were post-treated with vanillin after hydrogen peroxide treatment. Vanillin showed no change in the absence of activity of hydrogen peroxide to induce mutations. Post-treatment with vanillin also suppressed the chromosome aberrations induced by hydrogen peroxide. The differential effects of vanillin were probably due to the quality of mutagen-induced DNA lesions and vanillin might influence at least two different kinds of cellular repair functions. The mechanisms by which vanillin enhances or suppresses chemical-induced cytotoxicity, mutations and chromosome aberrations are discussed.

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Non-Human Toxicity Values
LD50 Rat oral 1580 mg/kg
LD50 Rat ip 1160 mg/kg
LD50 Rat sc 1500 mg/kg
LD50 Mouse ip 475 mg/kg
For more Non-Human Toxicity Values (Complete) data for VANILLIN (11 total), please visit the HSDB record page.

Vanillin appears as white or very slightly yellow needles.
Vanillin is a member of the class of benzaldehydes carrying methoxy and hydroxy substituents at positions 3 and 4 respectively. It has a role as a plant metabolite, an anti-inflammatory agent, a flavouring agent, an antioxidant and an anticonvulsant. It is a member of phenols, a monomethoxybenzene and a member of benzaldehydes.
Vanilla allergenic extract is used in allergenic testing.
Vanillin has been reported in Humulus lupulus, Ficus erecta var. beecheyana, and other organisms with data available.
Vanillin is the primary component of the extract of the vanilla bean. Synthetic vanillin, instead of natural vanilla extract, is sometimes used as a flavouring agent in foods, beverages, and pharmaceuticals. It is used by the food industry as well as ethylvanillin.Artificial vanilla flavoring is a solution of pure vanillin, usually of synthetic origin. Because of the scarcity and expense of natural vanilla extract, there has long been interest in the synthetic preparation of its predominant component. The first commercial synthesis of vanillin began with the more readily available natural compound eugenol. Today, artificial vanillin is made from either guaiacol or from lignin, a constituent of wood which is a byproduct of the paper industry. (Wiki).
Vanillin is a metabolite found in or produced by Saccharomyces cerevisiae.
See also: Oils, vanilla (annotation moved to).

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Therapeutic Uses
EXPL THER THE CHOLERETIC PROPERTIES & MECHANISM OF COUMARIN COMPD & PHENOLIC COMPD WERE STUDIED BY EXAMINING THEIR EFFECTS ON PARAMETERS SUCH AS BILE FLOW, BILE ACIDS, ELECTROLYTES, & BILIARY METABOLITES. VANILLIN ACCELERATED BILE SECRETION.
VET: ...AS AN AEROSOLED AID IN GETTING EWES TO SUCKLE ORPHAN LAMBS.
EXPL THER Methotrexate (MTX), a chemotherapeutic agent used to treat cancer, produces cytogenetic damage and has a cytostatic effect in a variety of test systems. Several antigenotoxic agents have been studied in various in vitro and in vivo systems. However, data are limited regarding their ability to modulate MTX-induced genotoxicity. In the present study, vanillin (VA) and chlorophyllin (CHL) were used as antigenotoxic agents to study their ability to minimize the DNA damage caused by MTX. Exponentially growing V79 Chinese hamster lung cells were treated with MTX at five different concentrations (5-100 ug/mL) with S9 activation for 6 h and post-treated with two concentrations of either VA (50 or 100 ug/mL) or CHL (50 or 100 ug/mL) for 40 h. Cytochalasin B was added for the micronucleus (MN) assay along with antigenotoxic agents to evaluate MN in binucleated cells. Chromosomal aberrations were also evaluated in parallel cultures. Results indicate that MTX alone induced a dose-dependent decrease in the nuclear division index (NDI) and the mitotic index (MI). A significant increase in percent micronucleated binucleated cells (MNBN) and percent aberrant cells (Abs) was observed. Studies using VA as an antigenotoxic agent showed a decrease in the number of MNBN (26.3-83.1%) and Abs (16.0-87.5%) with the addition of either 50 or 100 micrograms VA/ml. The addition of CHL also significantly reduced the number of MNBN (53.0-91.5%) at both concentrations tested. Chromosomal aberrations were also significantly reduced (41.0-83.0). These studies indicate that both VA and CHL are capable of effectively minimizing MTX-induced chromosomal damage.
EXPL THER Vanillin is a well-known food and cosmetic additive and has antioxidant and antimutagenic properties. It has also been suggested to have antifungal activity against major human pathogenic fungi, although it is not very effective. In this study, the antifungal activities of vanillin and 33 vanillin derivatives against the human fungal pathogen Cryptococcus neoformans, the main pathogen of cryptococcal meningitis in immunocompromised patients, were investigated. We found a structural correlation between the vanillin derivatives and antifungal activity, showing that the hydroxyl or alkoxy group is more advantageous than the halogenated or nitrated group in benzaldehyde. Among the vanillin derivatives with a hydroxyl or alkoxy group, o-vanillin and o-ethyl vanillin showed the highest antifungal activity against C. neoformans. o-Vanillin was further studied to understand the mechanism of antifungal action. We compared the transcriptome of C. neoformans cells untreated or treated with o-vanillin by using RNA sequencing and found that the compound caused mitochondrial dysfunction and triggered oxidative stress. These antifungal mechanisms of o-vanillin were experimentally confirmed by the significantly reduced growth of the mutants lacking the genes involved in mitochondrial functions and oxidative stress response.

C8H8O3

152.15

152.047

121-33-5

1183

White to off-white solid powder

1.2±0.1 g/cm3

282.6±20.0 °C at 760 mmHg

81-83 °C(lit.)

117.6±15.3 °C

0.0±0.6 mmHg at 25°C

1.588

1.19

1

3

2

11

135

0

MWOOGOJBHIARFG-UHFFFAOYSA-N

InChI=1S/C8H8O3/c1-11-8-4-6(5-9)2-3-7(8)10/h2-5,10H,1H3

4-hydroxy-3-methoxybenzaldehyde

NSC-15351; NSC 15351; Vanillin

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 (~657.25 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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