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.
;