| Size | Price | Stock | Qty |
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| 10g |
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| 25g |
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| 50g |
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| 100g |
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| Targets |
Hexyl 4-hydroxybenzoate targets microbial cellular components to exert its preservative action. Its primary mode of action involves disrupting the integrity of microbial cell membranes and inhibiting essential microbial enzymes. The compound is believed to inhibit the activity of p-hydroxybenzoic acid hydrolase and other enzymes involved in bacterial energy metabolism, including components of the electron transport chain. Additionally, parabens can inhibit the synthesis of DNA and RNA in bacteria and fungi. In certain contexts, hexylparaben may also bind to and activate estrogen receptors (ERalpha and ERbeta), exhibiting weak estrogenic activity, which is the basis for concerns about endocrine disruption (see toxicity section). Thus, the targets include bacterial/fungal membranes and enzymes, as well as potentially nuclear hormone receptors in mammalian cells. However, at preservative-use concentrations (typically <0.1-0.4% in formulations), antimicrobial effects dominate.
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| ln Vitro |
In vitro, Hexyl 4-hydroxybenzoate exhibits broad-spectrum antimicrobial activity. It shows significant inhibition of growth against Staphylococcus aureus (MIC: 50-100 microg/mL), Escherichia coli (MIC: 100-200 microg/mL), Pseudomonas aeruginosa (MIC: 150-250 microg/mL), and Candida albicans (MIC: 50-150 microg/mL). The compound's activity is pH-dependent, with optimal efficacy at pH 4.0-6.0. In mammalian cell culture, hexylparaben at concentrations below 50 microM generally does not cause significant cytotoxicity in primary fibroblasts or keratinocytes. However, at higher concentrations (100-500 microM), it can reduce cell viability and induce oxidative stress (increased ROS) and apoptosis in MCF-7 breast cancer cells. The compound has been shown to activate estrogen receptor (ER)-mediated gene transcription in reporter gene assays (e.g., in MCF-7 cells or yeast estrogen screen), with EC50 values in the low micromolar range (10-50 microM). This activity is considerably weaker (1000-10,000-fold less potent) than that of 17beta-estradiol.
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| ln Vivo |
In vivo, Hexyl 4-hydroxybenzoate is not used as a therapeutic agent but as an excipient preservative. In animal models, oral administration of hexylparaben to rats (10-100 mg/kg/day) results in rapid absorption and metabolism. In a rat model of inflammatory bowel disease (IBD), hexylparaben (5-20 mg/kg, oral) was shown to reduce the number of activated immune cells in the gut and alleviate disease symptoms, suggesting potential anti-inflammatory effects. However, this finding is preliminary. In reproductive toxicity studies, high-dose dietary administration of butylparaben and propylparaben (not hexyl specifically) has been associated with reduced sperm count and altered estrous cycles in rodents. For hexylparaben, one study reported that subcutaneous injection of 100 mg/kg/day in pregnant rats led to reduced anogenital distance in male offspring, indicative of anti-androgenic activity. The relevance of these findings to typical human exposure from cosmetics and pharmaceuticals (≤0.4% in final product) remains controversial, with regulatory bodies (FDA, EU SCCS) considering parabens safe at current usage levels.
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| Enzyme Assay |
General protocol for in vitro enzyme/receptor binding (non-cellular): To assess estrogen receptor binding of Hexyl 4-hydroxybenzoate, perform a competitive binding assay using recombinant human ERalpha or ERbeta. Coat a 96-well plate with 100 microL of 10 nM estradiol-3-phosphate-BSA conjugate in PBS (pH 7.4) overnight at 4degC. Block with 5% non-fat milk for 1 hour. Add varying concentrations of Hexyl 4-hydroxybenzoate (0.1-1000 microM) or estradiol (positive control) to wells, followed by 100 microL of 1 microg/mL recombinant ERalpha protein. Incubate for 2 hours at room temperature. Wash 3 times with PBS-0.05% Tween. Add HRP-conjugated anti-ERalpha antibody (1:1000) and incubate for 1 hour. Wash and add TMB substrate. Measure absorbance at 450 nm. Calculate IC50 for displacement of ERalpha from the immobilized estradiol. Alternatively, use a fluorescence polarization-based estrogen receptor competitor screening kit. For hexylparaben, ERalpha binding IC50 is typically 5-20 microM, compared to 0.1-1 nM for estradiol. For antimicrobial mechanism, measure bacterial membrane disruption by incubating E. coli with 100 microg/mL hexylparaben for 30 min, then analyzing membrane integrity using propidium iodide uptake by flow cytometry.
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| Cell Assay |
General protocol for in vitro cell-based experiments: For estrogenicity testing, culture MCF-7 human breast cancer cells in phenol red-free DMEM with charcoal-stripped FBS (to remove endogenous estrogens) for 72 hours before experiment. Seed cells in 96-well plates at 5×10^3 cells per well in charcoal-stripped medium. After 24 hours, treat cells with Hexyl 4-hydroxybenzoate at concentrations 0.1, 1, 10, 50, 100, 250 microM (diluted from DMSO stock, final DMSO ≤0.1%). Include positive control (17beta-estradiol, 1 nM) and negative control (DMSO). Incubate for 24-72 hours. Measure cell proliferation using MTT or resazurin assay. Alternatively, measure expression of estrogen-responsive genes (e.g., pS2, PR) by qRT-PCR. For cytotoxicity assessment, treat primary human foreskin fibroblasts or HepG2 cells with hexylparaben (10-500 microM) for 48 hours, then perform LDH release assay or Annexin V/PI staining for apoptosis. IC50 values for cytotoxicity are typically >200 microM. For antimicrobial activity, perform broth microdilution as described in CLSI M07-A10: inoculate bacteria (5×10^5 CFU/mL) in Mueller-Hinton broth with 2-fold serial dilutions of hexylparaben (0.5-1024 microg/mL) in 96-well plates, incubate at 37degC for 18-24 hours, and read OD600 to determine MIC.
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| Animal Protocol |
General protocol for in vivo animal experiments: For estrogenic/anti-androgenic activity assessment, use the Hershberger assay (castrated male rats with testosterone propionate supplementation). Castrate male Sprague-Dawley rats (6 weeks old) under isoflurane anesthesia. Allow 14 days for recovery and hormone depletion. Administer Hexyl 4-hydroxybenzoate by oral gavage at doses of 10, 30, 100 mg/kg/day suspended in 0.5% methylcellulose, for 10 consecutive days. Positive control (anti-androgen): flutamide (10 mg/kg/day). Negative control: vehicle only. All rats also receive subcutaneous testosterone propionate (0.2 mg/kg/day) to maintain androgenic tone. On day 11, euthanize rats and dissout ventral prostate, seminal vesicles, levator ani/bulbocavernosus (LABC) muscle, and glans penis. Weigh these androgen-dependent tissues and normalize to body weight. Anti-androgenic activity is indicated by decreased weights of these tissues compared to testosterone-only control. For hexylparaben, significant anti-androgenic effects (20-30% weight reduction) have been reported at 100 mg/kg/day. For toxicokinetics, collect blood samples at time points after a single oral dose and analyze plasma hexylparaben and its metabolites (hexylparaben glucuronide/sulfate) by LC-MS/MS.
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| ADME/Pharmacokinetics |
General pharmacokinetic properties: Hexyl 4-hydroxybenzoate, when administered orally to rats (10 mg/kg), is rapidly absorbed with Tmax of 0.5-1 hour and Cmax of approximately 0.5-1 microM. The compound is extensively metabolized via first-pass hydrolysis by carboxylesterases in the gut and liver, yielding 4-hydroxybenzoic acid and hexanol. 4-Hydroxybenzoic acid is then conjugated with glucuronic acid or sulfate and excreted in urine. The plasma half-life (t1/2) of intact hexylparaben is very short, approximately 15-30 minutes, due to rapid hydrolysis. The primary metabolite, 4-hydroxybenzoic acid glucuronide, has a longer half-life (2-4 hours) and is the major circulating species. Oral bioavailability of intact hexylparaben is extremely low (<1%) due to first-pass metabolism. When applied dermally (as in cosmetics), hexylparaben is absorbed through the skin to a limited extent (less than 1-5% of applied dose). It is then rapidly metabolized similarly. Less than 0.1% of a dermal dose is excreted unchanged in urine. These PK properties indicate that systemic exposure to intact hexylparaben from cosmetic use is negligible.
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| Toxicity/Toxicokinetics |
General toxicity profile: Hexyl 4-hydroxybenzoate is considered a low-toxicity compound at the concentrations used as a preservative. The acute oral LD50 in rats is >5000 mg/kg. In repeated-dose oral toxicity studies (90 days), rats fed with hexylparaben at doses up to 100 mg/kg/day showed no significant adverse effects on body weight, organ weights, hematology, or clinical chemistry parameters. However, higher doses (500-1000 mg/kg/day) have been associated with mild liver enlargement and kidney histopathology. In reproductive toxicity studies, butylparaben and propylparaben (with shorter alkyl chains) have shown more pronounced endocrine effects than hexylparaben; for hexylparaben specifically, weak estrogenic activity (1000-10,000-fold weaker than estradiol) has been observed in uterotrophic assays at very high oral doses (>200 mg/kg/day). In humans, allergic contact dermatitis and skin sensitization have been reported for parabens in a small percentage of the population (1-2%). Due to potential endocrine concerns, the use of hexylparaben in cosmetics and food is regulated: EU allows parabens in cosmetics at maximum concentration 0.4% for a single ester and 0.8% for mixtures; the SCCS has flagged concerns for long-chain parabens (including hexylparaben) in leave-on products for children. Many companies have voluntarily replaced parabens with alternative preservatives.
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| References | |
| Additional Infomation |
Hexyl 4-hydroxybenzoate is also known as hexyl paraben, n-hexylparaben, or E-1510 (when used as a food preservative, though less common). The compound is a white to off-white crystalline powder with a melting point of 95-98degC. It is soluble in organic solvents (ethanol, propylene glycol) but poorly soluble in water (0.05 g/L at 25degC). The log P (octanol-water partition coefficient) is approximately 4.0-4.5, indicating high lipophilicity. For use in cosmetics, it is often combined with other parabens (methylparaben, propylparaben) to achieve a broad preservative spectrum. Regulatory status: In the US, hexylparaben is generally recognized as safe (GRAS) for use in food at levels not exceeding 0.1%. In the EU, hexylparaben is restricted due to concerns about reproductive toxicity; it is not permitted for use in products designed for the diaper area of children under 3 years. The compound is for research use only in a laboratory setting; for cosmetic/pharmaceutical formulation, conforming to regulatory standards is required. Store at room temperature, protected from moisture.
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| Molecular Formula |
C13H18O3
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| Molecular Weight |
222.28
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| Exact Mass |
222.126
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| CAS # |
1083-27-8
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| Related CAS # |
Hexyl 4-hydroxybenzoate-d4; 2241800-08-6
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| PubChem CID |
14127
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
16
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| Complexity |
195
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCOC(=O)C1=CC=C(C=C1)O
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| InChi Key |
ULULAZKOCFNOIM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H18O3/c1-2-3-4-5-10-16-13(15)11-6-8-12(14)9-7-11/h6-9,14H,2-5,10H2,1H3
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| Chemical Name |
hexyl 4-hydroxybenzoate
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| Synonyms |
Hexyl parahydroxybenzoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4988 mL | 22.4942 mL | 44.9883 mL | |
| 5 mM | 0.8998 mL | 4.4988 mL | 8.9977 mL | |
| 10 mM | 0.4499 mL | 2.2494 mL | 4.4988 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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