Parabens: A Review of Epidemiology, Structure, Allergenicity, and Hormonal Properties

Allison L. Cashman; Erin M. Warshaw

Disclosures

Dermatitis. 2005;16(2):57-66. 

In This Article

Structure, Formulation, and Metabolism

The term 'paraben' is an abbreviation for para-hydroxybenzoic acid. Parabens are a family of alkyl esters of para-hydroxybenzoic acid that differ at the para position of the benzene ring by various chemical substitutions.[1,8] There are five widely marketed para-hydroxybenzoic acid esters: methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben (fig1). The chemical substitutions provide each paraben ester with a different solubility and spectrum of antimicrobial activity. As the alkyl chain length increases, water solubility decreases and oil solubility increases.[15] The greater the paraben's lipid solubility, the greater the penetration through the epidermis. Therefore, penetration increases with ester chain length.[15,16]

Structure of the parabens.

In the United States, the average total paraben exposure per individual is estimated to be approximately 76 mg per day (1.3 mg/kg/d for a person weighing 70 kg). Cosmetics and personal products provide the bulk of exposure at 50 mg per day, drugs supply 25 mg per day, and food accounts for approximately 1 mg per day.[17] The concentration of parabens in foods is usually less than 1%.[17] In the past, concentrations of parabens in topical over-the-counter products were as high as 5% in the United States.[17] Currently, however, the concentrations of parabens in cosmetics are generally less than 0.3% but may range up to a total concentration of 1%.[11,18,19] The bioavailability of all parabens is greater in oil-in-water preparations than in petrolatum.[8,20] The potential for the percutaneous absorption of parabens is influenced by the relative distribution of the oil/water phases of formulation, and this is further altered by the addition of various surfactants.[21,22] All parabens partition into the oil phase, but those with longer chains are more soluble in oil, and those with shorter chains are more soluble in water. Therefore, in oil-based formulations, methylparaben requires a higher concentration to maintain effectiveness.[23] The effect of variable concentrations of parental formulations on the development of paraben hypersensitivity reactions has not been examined.

Parabens applied to skin are partially metabolized by four carboxyl esterases found in skin and subcutaneous fat. These esterases hydrolyze the parabens to para-hydroxybenzoic acid and their respective side chains.[24] The carboxyl esterases found in the subcutaneous fat are more active against parabens with short chains whereas esterases localized to keratinocytes are more active against parabens with longer chains.[24] Parabens absorbed by the body were once thought to be fully metabolized by esterases in the liver and kidney, excreted in the urine, and not to accumulate in the body; however, recent evidence points to the contrary. Nakazawa and colleagues found that individual parabens were not detected in human blood and milk but that para-hydroxybenzoic acid, the main metabolite of parabens, was detected in all patient blood and milk samples tested.[25] In addition, a study by Oishi demonstrated that a portion of parabens can be absorbed and retained in human body tissues without hydrolysis by tissue esterases.[14]

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