Paraben

General chemical structure of a paraben
(a para-hydroxybenzoate)
where R = an alkyl group

Parabens are a class of widely used preservatives in cosmetic and pharmaceutical products. Chemically, they are a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid). Parabens are effective preservatives in many types of formulas. These compounds, and their salts, are used primarily for their bactericidal and fungicidal properties. They can be found in shampoos, commercial moisturizers, shaving gels, personal lubricants, topical/parenteral pharmaceuticals, spray tanning solution, makeup, and toothpaste. They are also used as food additives.

Their efficacy as preservatives, in combination with their low cost, the long history of their use, and the inefficacy of some natural alternatives like grapefruit seed extract (GSE), probably explains why parabens are so commonplace. No effective direct links between parabens and cancer have been established.

Mode of Action

Parabens are active against a broad spectrum of microorganisms. However, their antibacterial mode of action is not well understood. They are thought to act by disrupting membrane transport processes or by inhibiting synthesis of DNA and RNA or of some key enzymes, such as ATPases and phosphotransferases, in some bacterial species. Propylparaben is considered more active against most bacteria than methylparaben. The stronger antibacterial action of propylparaben may be due to its greater solubility in the bacterial membrane, which may allow it to reach cytoplasmic targets in greater concentrations. However, since a majority of the studies on the mechanism of action of parabens suggest that their antibacterial action is linked to the membrane, it is possible that its greater lipid solubility disrupts the lipid bilayer, thereby interfering with bacterial membrane transport processes and perhaps causing the leakage of intracellular constituents.

Chemistry

Parabens are esters of para-hydroxybenzoic acid, from which the name is derived. Common parabens include methylparaben (E number E218), ethylparaben (E214), propylparaben (E216), butylparaben and heptylparaben (E209). Less common parabens include isobutylparaben, isopropylparaben, benzylparaben and their sodium salts. The general chemical structure of a paraben is shown at the top right of this page, where R symbolizes an alkyl group such as methyl, ethyl, propyl or butyl.

Synthesis

All commercially used parabens are synthetically produced, although some are identical to those found in nature. They are produced by the esterification of para-hydroxybenzoic acid with the appropriate alcohol, such as methanol, ethanol, or n-propanol. para-Hydroxybenzoic acid is in turn produced industrially from a modification of the Kolbe-Schmitt reaction, using potassium phenoxide and carbon dioxide.

Health aspects

Most of the available paraben toxicity data are from single-exposure studies, meaning one type of paraben in one type of product. According to paraben research this is relatively safe, posing only a negligible risk to the endocrine system. However, since many types of parabens in many types of products are used commonly, further assessment of the additive and cumulative risk of multiple paraben exposure from daily use of multiple cosmetic and/or personal care products is needed.

Allergic reactions

In individuals with normal skin, parabens are, for the most part, non-irritating and non-sensitizing. Parabens can, however, cause skin irritation and contact dermatitis and rosacea in individuals with paraben allergies, a small percentage of the general population.

Breast cancer

While even small amounts of parabens introduced in vitro stimulate breast cancer cell proliferation, there is no evidence that application of consumer products containing parabens cause cancer. Investigations by the American Cancer Society and FDA found that current levels of parabens in consumer products were not dangerous. A 2005 review concluded "it is biologically implausible that parabens could increase the risk of any estrogen-mediated endpoint, including effects on the male reproductive tract or breast cancer" and that "worst-case daily exposure to parabens would present substantially less risk relative to exposure to naturally occurring endocrine active chemicals in the diet such as the phytoestrogen daidzein."

Estrogenic activity

Animal experiments have shown that parabens have weak estrogenic activity, acting as xenoestrogens. In an in vivo study, the effect of butylparaben was determined to be approximately 100,000 times weaker than that of estradiol, and was only observed at a dose level approximately 25,000 times higher than the level typically used to preserve products. The study also found that the in vivo estrogenic activity of parabens is reduced by about three orders of magnitude compared to in vitro activity.

The estrogenic activity of parabens increases with the length of the alkyl group. It is believed that propylparaben is estrogenic to a certain degree as well, though this is expected to be less than butylparaben by virtue of its less lipophilic nature. Since it can be concluded that the estrogenic activity of butylparaben is negligible under normal use, the same should be concluded for shorter analogs.

Sun exposure

Studies indicate that methylparaben applied on the skin may react with UVB leading to increased skin aging and DNA damage.

Regulation

The European Scientific Committee on Consumer Products (SCCP) stated in 2006 that the available data on parabens do not enable a decisive response to the question of whether propyl, butyl and isobutyl paraben can be safely used in cosmetic products at individual concentrations up to 0.4%, which is the allowed limit in the EU.

Controversy

A 2004 paper led to discussion over possible carcinogenicity and estrogenic effects being expressed over the continued use of parabens as preservatives.

The mainstream cosmetic industry believes that parabens, like most cosmetic ingredients, are safe based on their long term use and safety record and recent scientific studies. Public interest organizations which raise awareness about cosmetic ingredients believe that further research is necessary to determine the safety of parabens, under the precautionary principle. The concerns about endocrine disruptors have led consumers and companies to search for paraben-free alternatives. Grapefruit seed extract is promoted as a natural preservative, but in a study, five out of six commercial products tested were found to contain artificial preservatives such as methylparaben and benzethonium chloride. A common alternative has been phenoxyethanol, however this has its own risks and led to an FDA warning on inclusion in nipple creams.