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

Allison L. Cashman; Erin M. Warshaw


Dermatitis. 2005;16(2):57-66. 

In This Article

The Paraben Paradox and Suggested Hypotheses

The term 'paraben paradox' was first used by Fisher in 1973 to describe two phenomena. The first paradox is that paraben-containing personal products, which are the cause of an allergic contact dermatitis, often produce false-negative patch-test reactions when applied to the skin of the back.[84] The second paradox is that paraben-sensitive persons, who react to parabens on patch testing and develop a dermatitis when paraben-containing products are used on compromised skin, may continue to use paraben-containing products on other areas of the body that have intact uninvolved skin, without any adverse reactions. Fisher provided two explanations for these paradoxes: (1) the patch testing is being performed on normal skin and (2) the concentration of the vehicle ingredient is too low.[84]

While these hypotheses provide partial explanations for these phenomena, other factors may play a role. We propose two additional hypotheses for the 'paraben paradox,' namely, the 'esterase' and the 'microbial metabolite' hypotheses.

Long-chain parabens (eg, butylparaben) are metabolized by esterases in the subcutaneous tissue and are the least reactive. Short-chain parabens (methylparaben and propylparaben) are metabolized by esterases in keratinocytes and are the most reactive. Damaged epithelium could adversely affect the metabolism of parabens by esterases in this layer, thereby altering the final concentration of parabens that reach the dermis. It is possible that the short-chain highly reactive parabens, therefore, can penetrate damaged skin more readily because of impaired metabolism by keratinocyte esterases. It is also possible (as has been proposed for other antigens in dermatitic or traumatized skin where the stratum corneum barrier is impaired) that this disruption alone may allow greater absorption and penetration of all paraben esters. Either impaired metabolism of short-chain highly allergenic parabens by damaged keratinocytes and/or greater penetration of all paraben esterases by a disrupted stratum corneum could play a role in the development or elicitation of allergic contact dermatitis.

Most reports of allergic contact dermatitis from parabens describe the development of an allergic reaction in damaged skin after repeated applications of a paraben-containing therapeutic agent. It is possible that repeated applications produce or allow the cultivation of paraben-resistant microbes on the skin. These paraben-resistant organisms hydrolyze parabens to hydroxybenzoic acid and their respective side chains, which could in turn induce or accentuate sensitization. To our knowledge, the role of paraben-resistant microbial breakdown products in causing an allergic reaction to chemicals or in enhancing sensitization to the parent paraben has not been evaluated.