| Identification | More | [Name]
Methylparaben | [CAS]
99-76-3 | [Synonyms]
4-(carbomethoxy)phenol
4-HYDROXYBENZOIC ACID METHYL ESTER
4-HYDROXYBENZOIC ACID METYL ESTER
4-(methoxycarbonyl)phenol
AKOS BBS-00004393
FEMA 2710
metaben
methaben
METHYL 4-HYDROXYBENZOATE
methyl butex
METHYLIS PARAHYDROXYBENZOAS
METHYLPARABEN
Methyl parasept
METHYL P-HYDROXYBENZOATE
NIPAGIN
NIPAGIN PLAIN
P-HYDROXYBENZOIC ACID METHYL ESTER
RARECHEM AL BF 0098
4-hydroxy-benzoicacimethylester
Abiol | [EINECS(EC#)]
202-785-7 | [Molecular Formula]
C8H8O3 | [MDL Number]
MFCD00002352 | [Molecular Weight]
152.15 | [MOL File]
99-76-3.mol |
| Chemical Properties | Back Directory | [Appearance]
white crystalline powder | [Melting point ]
125-128 °C(lit.)
| [Boiling point ]
298.6 °C
| [density ]
1,46g/cm | [vapor pressure ]
0.000005 hPa (20 °C) | [FEMA ]
2710 | [refractive index ]
1.4447 (estimate) | [Fp ]
280°C | [storage temp. ]
0-6°C | [solubility ]
ethanol: soluble0.1M, clear, colorless | [form ]
Crystalline Powder | [pka]
pKa 8.15(H2O,t =20.0) (Uncertain) | [color ]
White to almost white | [Odor]
odorless or faint char. odor, sl. burning taste | [PH]
5.8 (H2O, 20°C) (saturated solution) | [Stability:]
Stable. Incompatible with strong oxidizing agents, strong bases. | [Water Solubility ]
Slightly soluble in water. | [FreezingPoint ]
131℃ | [Merck ]
14,6107 | [BRN ]
509801 | [Contact allergens]
This substance is one of the parabens family. Parabens are esters formed by p-hydroxybenzoic acid
and an alcohol. They are largely used as biocides in
cosmetics and toiletries, medicaments, or food. They
have synergistic power with other biocides. Parabens
can induce allergic contact dermatitis, mainly in
chronic dermatitis and wounded skin. | [InChIKey]
LXCFILQKKLGQFO-UHFFFAOYSA-N | [LogP]
1.98 at 20℃ | [Uses]
parabens is one of the most commonly used group of preservatives in the cosmetic, pharmaceutical, and food industries. Parabens provide bacteriostatic and fungistatic activity against a diverse number of organisms, and are considered safe for use in cosmetics, particularly in light of their low sensitizing potential. An evaluation of preservatives for use in leave-on cosmetic preparations lists parabens among the least sensitizing. The range of concentrations used in cosmetics varies between 0.03 and 0.30 percent, depending on the conditions for use and the product to which the paraben is added. | [CAS DataBase Reference]
99-76-3(CAS DataBase Reference) | [NIST Chemistry Reference]
Benzoic acid, 4-hydroxy-, methyl ester(99-76-3) | [EPA Substance Registry System]
99-76-3(EPA Substance) |
| Hazard Information | Back Directory | [Uses]
It is used as preservative in foods, beverages and cosmetics. | [Definition]
ChEBI: A 4-hydroxybenzoate ester resulting from the formal condensation of the carboxy group of 4-hydroxybenzoic acid with methanol. It is the most frequently used antimicrobial preservative in cosmetics. It occurs naturally in several fruits, particularly in blu
berries. | [Uses]
As preservative in foods, beverages and cosmetics. | [Hazard]
Toxic. Use in foods restricted to 0.1%. | [Occurrence]
Reported present in cloudberry, yellow passion fruit juice, white wine, botrytised wine and Bourbon vanilla. | [Production Methods]
Methylparaben is prepared by the esterification of p-hydroxybenzoic
acid with methanol. | [Aroma threshold values]
Detection: 2.6 ppm. | [General Description]
Methyl paraben is basically a methyl ester of p-hydroxybenzoic acid. It is non-toxic, and non-carcinogenic in nature. It is a stable, non-volatile compound and finds application as an anti-microbial preservative in foods, drugs and cosmetics. It is readily absorbed through the skin and gastrointestinal tract. Upon hydrolyzation, it is hydrolyzed to p-hydroxybenzoic acid, and the conjugates formed get rapidly excreted in the urine. | [Flammability and Explosibility]
Nonflammable | [Pharmaceutical Applications]
Methylparaben is widely used as an antimicrobial preservative in
cosmetics, food products, and pharmaceutical formulations; see
Table I. It may be used either alone or in combination with other methylparaben is the most frequently used antimicrobial preservative.
The parabens are effective over a wide pH range and have a
broad spectrum of antimicrobial activity, although they are most
effective against yeasts and molds. Antimicrobial activity increases
as the chain length of the alkyl moiety is increased, but aqueous
solubility decreases; therefore a mixture of parabens is frequently
used to provide effective preservation. Preservative efficacy is also
improved by the addition of propylene glycol (2–5%), or by using
parabens in combination with other antimicrobial agents such as
imidurea;
Owing to the poor solubility of the parabens, paraben salts
(particularly the sodium salt) are more frequently used in
formulations. However, this raises the pH of poorly buffered
formulations.
Methylparaben (0.18%) together with propylparaben (0.02%)
has been used for the preservation of various parenteral pharmaceutical
formulations; | [Biochem/physiol Actions]
Methyl 4-hydroxybenzoate, also called methyl paraben or nipagin, comprises the ester of p-hydroxybenzoic acid. It is present naturally in cloudberry, white wine and bourbon vanilla. Methyl 4-hydroxybenzoate has antimicrobial and antifungal functionality and is commercially used as a preservative in the food, cosmetic and pharmaceutical industry. Methyl 4-hydroxybenzoate has cytotoxic effects on keratinocytes in the presence of sunlight. Methyl 4-hydroxybenzoate upon solar irradiation mediates DNA damage and modulates esterase metabolism resulting in skin damage and favors cancer progression. Methyl 4-hydroxybenzoate has estrogenic functionality and upregulates estrogen-related genes. | [Safety]
Methylparaben and other parabens are widely used as antimicrobial
preservatives in cosmetics and oral and topical pharmaceutical
formulations. Although parabens have also been used as preservatives
in injections and ophthalmic preparations, they are now
generally regarded as being unsuitable for these types of formulations
owing to the irritant potential of the parabens. These
experiences may depend on immune responses to enzymatically
formed metabolites of the parabens in the skin.
Parabens are nonmutagenic, nonteratogenic, and noncarcinogenic.
Sensitization to the parabens is rare, and these compounds do
not exhibit significant levels of photocontact sensitization or
phototoxicity.
Hypersensitivity reactions to parabens, generally of the delayed
type and appearing as contact dermatitis, have been reported.
However, given the widespread use of parabens as preservatives,
such reactions are relatively uncommon; the classification of overstated.
Immediate hypersensitivity reactions following injection of
preparations containing parabens have also been reported.
Delayed-contact dermatitis occurs more frequently when parabens
are used topically, but has also been reported to occur after oral
administration.
Unexpectedly, preparations containing parabens may be used by
patients who have reacted previously with contact dermatitis
provided they are applied to another, unaffected, site. This has
been termed the paraben paradox.
Concern has been expressed over the use of methylparaben in
infant parenteral products because bilirubin binding may be
affected, which is potentially hazardous in hyperbilirubinemic
neonates.
The WHO has set an estimated total acceptable daily intake for
methyl-, ethyl-, and propylparabens at up to 10 mg/kg bodyweight.
LD50 (dog, oral): 3.0 g/kg
LD50 (mouse, IP): 0.96 g/kg
LD50 (mouse, SC): 1.20 g/kg | [Carcinogenicity]
The carcinogenic potential of
methyl paraben has been studied in rodents. Several studies
are available, but none that expose animals via oral or dermal
routes. No evidence of a carcinogenic effect was observed
following intravenous or subcutaneous injection . | [storage]
Aqueous solutions of methylparaben at pH 3–6 may be sterilized by
autoclaving at 120°C for 20 minutes, without decomposition.
Aqueous solutions at pH 3–6 are stable (less than 10%
decomposition) for up to about 4 years at room temperature, while
aqueous solutions at pH 8 or above are subject to rapid hydrolysis
(10% or more after about 60 days storage at room temperature);
Methylparaben should be stored in a well-closed container in a
cool, dry place. | [Purification Methods]
Fractionally crystallise the ester from its melt, and recrystallise it from *benzene, then from *benzene/MeOH and dry it over CaCl2 in a vacuum desiccator. [Beilstein 10 IV 360.] | [Incompatibilities]
The antimicrobial activity of methylparaben and other parabens is
considerably reduced in the presence of nonionic surfactants, such
as polysorbate 80, as a result of micellization.However,
propylene glycol (10%) has been shown to potentiate the
antimicrobial activity of the parabens in the presence of nonionic
surfactants and prevents the interaction between methylparaben
and polysorbate 80.
Incompatibilities with other substances, such as bentonite,
magnesium trisilicate,talc,tragacanth,sodium alginate,
essential oils,sorbitol,and atropine,have been reported. It
also reacts with various sugars and related sugar alcohols.
Absorption of methylparaben by plastics has also been reported;
the amount absorbed is dependent upon the type of plastic and the
vehicle. It has been claimed that low-density and high-density
polyethylene bottles do not absorb methylparaben.
Methylparaben is discolored in the presence of iron and is
subject to hydrolysis by weak alkalis and strong acids. | [Regulatory Status]
Methylparaben and propylparaben are affirmed GRAS Direct Food
Substances in the USA at levels up to 0.1%. All esters except the
benzyl ester are allowed for injection in Japan. In cosmetics, the EU
and Brazil allow use of each paraben at 0.4%, but the total of all
parabens may not exceed 0.8%. The upper limit in Japan is 1.0%.
Accepted for use as a food additive in Europe. Included in the
FDA Inactive Ingredients Database (IM, IV, and SC injections;
inhalation preparations; ophthalmic preparations; oral capsules,
tablets, solutions and suspensions; otic, rectal, topical, and vaginal
preparations). Included in medicines licensed in the UK. Included in
the Canadian List of Acceptable Non-medicinal Ingredients. | [References]
The Protective Effect of Rosmarinic Acid against Unfavorable Influence of Methylparaben and Propylparaben on Collagen in Human Skin Fibroblasts DOI:10.3390/nu12051282
https://www.byrdie.com/methylparaben-for-skin-4779820
https://pubchem.ncbi.nlm.nih.gov/compound/Methylparaben
Handa O, et al. (2006). Methylparaben potentiates UV-induced damage of skin keratinocytes. DOI: 10.1016/j.tox.2006.07.018
Parabens in Cosmetics https://www.fda.gov/cosmetics/productsingredients/ingredients/ucm128042.htm
Okamoto T, et al. (2008). Combined activation of methyl paraben by light irradiation and metabolism toward oxidative DNA damage. DOI:10.1021/tx800066u |
| Safety Data | Back Directory | [Hazard Codes ]
Xi,Xn | [Risk Statements ]
R36/37/38:Irritating to eyes, respiratory system and skin .
R20/21/22:Harmful by inhalation, in contact with skin and if swallowed . | [Safety Statements ]
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S36:Wear suitable protective clothing .
S24/25:Avoid contact with skin and eyes . | [RIDADR ]
UN 2769 | [WGK Germany ]
1
| [RTECS ]
DH2450000
| [Autoignition Temperature]
>600 °C | [TSCA ]
Yes | [HS Code ]
29182930 | [Hazardous Substances Data]
99-76-3(Hazardous Substances Data) |
| Questions And Answer | Back Directory | [Chemical properties]
Methylparaben is a colorless crystalline powder with a faint characteristic odor and a slight burning taste. It is slightly soluble in water but easily dissolves in ethanol, ether, acetone, and other organic solvents. One gram can dissolve in 2.5 ml of ethanol, approximately 4 ml of propylene glycol, or 400 ml of water at 25°C or about 50 ml of water at 80°C. It is commonly used as a fungistat in soft drinks, non-leavened bakery products, and other products, with a permissible level of up to 0.1%. To inhibit Gram-positive bacteria, 1000 to 4000 ppm are required, and its effectiveness increases with decreasing pH, similar to benzoates.
 | [Uses]
Methylparaben is the ester of methyl alcohol and p-hydroxybenzoic acid, It is a bacteriostatic agent and preservative that was added to local anesthetic agents without vasoconstrictors before 1984 to prevent bacterial growth. Allergic reactions developed from repeated exposures to parabens led to the removal of this agent from dental anesthetic solutions. Similar products produced by similar production methods, like ethyl p-hydroxybenzoate (paraben B) and propyl p-hydroxybenzoate (Nepalese c), are also disinfectant preservatives. The products are irritating to the skin. | [Content analysis]
Method one: determinate according to the content analysis method in "butyl p-hydroxybenzoate (07002)". Per mL 1 mol/L sodium hydroxide is equivalent to the product (C8H8O3) 152.2mg.
Method two: Take 0.1 g (accurate to 1 mg) of the sample previously dried on silica gel for 5 h and move into a 300 ml flask with a glass plug. Plus l mol/L sodium hydroxide 10ml, heated in the water bath for 15min. After cooling, add 0.1mol/L potassium bromate 0.00ml, potassium bromide 5.0g and l mol/L hydrochloric acid 30ml. Put 15min in the dark room after sealing. Add potassium iodide 1 g, shake the flask vigorously, with 0.1mol/L sodium thiosulfate titration, with starch test solution (TS-235) as an indicator. Per ml 0.1mol/L potassium bromate is equivalent to the product (C8H8O3) 25.36mg. | [Toxicity]
ADI 0～10mg/kg(FAO/WHO,2001).
GRAS(FDA,§184．1490，2000).
LD503000mg/kg(Dog, mouth) | [Utilization limitation]
FAO/WHO (1984): Jam, jelly, 1000mg/kg (single or with benzoate, sorbic acid and potassium sorbate).
EEC(1990,mg/kg): For use in pigment solutions, flavor syrups, coffee extracts, frozen drinks, fruit, glucose and soft drinks, pickled fish, salad, sauce, snack food, concentrated soup and so on, limited to GMP; Beer 70; Snack cereals and soup concentrate 175, the same as "07018 p-hydroxybenzoate".
HACSG is listed as a restricted list.
FDA,§184.1490(2000):0.1%. | [Preparation]
To prepare the drug, p-hydroxybenzoic acid, and methanol were esterified. First, excess methanol was added to p-hydroxybenzoic acid and stirred to dissolve. Concentrated sulfuric acid was then slowly added while stirring. The mixture was heated and refluxed for 10 hours, before being poured into water to precipitate crystallization. The crude product was then washed with water, sodium carbonate solution, and water, and recrystallized from water or 25% ethanol to obtain the finished product. The yield of the drug was 85%. Raw material consumption for each tonne of product included 1200 kg of p-hydroxybenzoic acid and 1000 kg of methanol. |
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