Production Methods

Ethylparaben is prepared by the esterification of p-hydroxybenzoic acid with ethanol (95%).

Synthesis Reference(s)

The Journal of Organic Chemistry, 39, p. 3343, 1974 DOI: 10.1021/jo00937a007

Pharmaceutical Applications

Ethylparaben is widely used as an antimicrobial preservative in cosmetics,food products, and pharmaceutical formulations. It may be used either alone or in combination with other paraben esters or with other antimicrobial agents. In cosmetics it is one of the most frequently used preservatives. 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. Owing to the poor solubility of the parabens, paraben salts, particularly the sodium salt, are frequently used. However, this may cause the pH of poorly buffered formulations to become more alkaline.

Safety

Ethylparaben and other parabens are widely used as antimicrobial preservatives in cosmetics, food products, and oral and topical pharmaceutical formulations. Systemically, no adverse reactions to parabens have been reported, although they have been associated with hypersensitivity reactions. Parabens, in vivo, have also been reported to exhibit estrogenic responses in fish.(10) The WHO has set an estimated total acceptable daily intake for methyl-, ethyl-, and propylparabens at up to 10 mg/kg body-weight.LD50 (mouse, IP): 0.52 g/kg LD50 (mouse, oral): 3.0 g/kg

storage

Aqueous ethylparaben solutions at pH 3–6 can be sterilized by autoclaving, without decomposition. At pH 3–6, aqueous solutions are stable (less than 10% decomposition) for up to about 4 years at room temperature, while solutions at pH 8 or above are subject to rapid hydrolysis (10% or more after about 60 days at room temperature). Ethylparaben should be stored in a well-closed container in a cool, dry place.

Incompatibilities

The antimicrobial properties of ethylparaben are considerably reduced in the presence of nonionic surfactants as a result of micellization. Absorption of ethylparaben by plastics has not been reported, although it appears probable given the behavior of other parabens. Ethylparaben is coabsorbed on silica in the presence of ethoxylated phenols. Yellow iron oxide, ultramarine blue, and aluminum silicate extensively absorb ethylparaben in simple aqueous systems, thus reducing preservative efficacy. Ethylparaben is discolored in the presence of iron and is subject to hydrolysis by weak alkalis and strong acids.

Regulatory Status

Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral, otic, and topical preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Definition

ChEBI: Ethylparaben is an ethyl ester resulting from the formal condensation of the carboxy group of 4-hydroxybenzoic acid with ethanol, It has a role as an antimicrobial food preservative, an antifungal agent, a plant metabolite and a phytoestrogen. It is a paraben and an ethyl ester.