Name: Ethylparaben
CAS No: Ethyl-4-hydroxybenzoate [120-47-8]
BP: Ethyl Hydroxybenzoate JP: Ethyl Parahydroxybenzoate PhEur: Ethyl Parahydroxybenzoate USP-NF: Ethylparaben
Aethylum hydrobenzoicum; CoSept E; E214; ethylis parahydroxybenzoas; ethyl p-hydroxybenzoate; Ethyl parasept; 4-hydroxybenzoic acid ethyl ester; Nipagin A; Solbrol A; Tegosept E; Uniphen P23.
Ethyl-4-hydroxybenzoate [120-47-8]
C9H10O3 ,166.18
Ethylparaben is widely used as an antimicrobial preservative in cosmetics,(1) 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; see Section 10. 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. See Methylparaben for further information.
Ethylparaben occurs as a white, odorless or almost odorless, crystalline powder.
See Table I
Antimicrobial activity Ethylparaben exhibits antimicrobial activity from pH 4–8. Preservative efficacy decreases with increasing pH owing to the formation of the phenolate anion. Parabens are more active against yeasts and molds than against bacteria. They are also more active against Gram-positive than against Gram-negative bacteria. The activity of the parabens increases with increasing chain length of the alkyl moiety, but solubility decreases. Activity may be improved by using combinations of parabens since synergistic effects occur. Ethylparaben is commonly used with methylparaben and propylparaben in oral and topical formulations (such mixtures are commercially available; for example, Nipasept (Nipa Laboratories Inc.). Activity has also been reported to be improved by the addition of other excipients; see Methylparaben for further information. See Table II for minimum inhibitory concentrations of ethylparaben.(2) Boiling point 297–2988C with decomposition. Melting point 115–1188C NIR spectra see Figure 1. Partition coefficient The values for different vegetable oils vary considerably and are affected by the purity of the oil; see Table III.(3) Solubility see Table IV.
Aqueous ethylparaben solutions at pH 3–6 can be sterilized by autoclaving, without decomposition.(4) 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).(5) Ethylparaben should be stored in a well-closed container in a cool, dry place.
The antimicrobial properties of ethylparaben are considerably reduced in the presence of nonionic surfactants as a result of micellization.(6) 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.(7) Yellow iron oxide, ultramarine blue, and aluminum silicate extensively absorb ethylparaben in simple aqueous systems, thus reducing preservative efficacy.(8,9) Ethylparaben is discolored in the presence of iron and is subject to hydrolysis by weak alkalis and strong acids.
Ethylparaben is prepared by the esterification of p-hydroxybenzoic acid with ethanol (95%).
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.(11) LD50 (mouse, IP): 0.52 g/kg(12) LD50 (mouse, oral): 3.0 g/kg
Observe normal precautions appropriate to the circumstances and quantity of material handled. Ethylparaben may be irritant to the skin, eyes, and mucous membranes, and should be handled in a well ventilated environment. Eye protection, gloves, and a dust mask or respirator are recommended.
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.
Butylparaben; ethylparaben potassium; ethylparaben sodium; methylparaben; propylparaben. Ethylparaben potassium Empirical formula C9H9KO3 Molecular weight 204.28 CAS number [36547-19-9] Synonyms Ethyl 4-hydroxybenzoate potassium salt; potassium ethyl hydroxybenzoate. Ethylparaben sodium Empirical formula C9H9NaO3 Molecular weight 188.17 CAS number [35285-68-8] Synonyms E215; ethyl 4-hydroxybenzoate sodium salt; sodium ethyl hydroxybenzoate.
Ethylparaben is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. See Methylparaben for further information. The EINECS number for ethylparaben is 204-399-4. The PubChem Compound ID (CID) for ethylparaben is 8434.