Paraben

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

Parabens are a class of chemicals widely used as preservatives in the cosmetic and pharmaceutical industries. Parabens are effective preservatives in many types of formulas. These compounds, and their salts, are used primarily for their bacteriocidal and fungicidal properties. They can be found in shampoos, commercial moisturizers, shaving gels, personal lubricants, topical/parenteral pharmaceuticals, spray tanning solution and toothpaste. They are also used as food additives.

Their efficacy as preservatives, in combination with their low cost, their long history of safe use and the unproven efficacy of natural ingredients like grapefruit seed extract (GSE),^[1] probably explains why parabens are so commonplace. They are becoming increasingly controversial, however, and some organizations which adhere to the precautionary principle object to their everyday use.^[2]

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) and butylparaben. Less common parabens include isobutylparaben, isopropylparaben, benzylparaben and their sodium salts. The general chemical structure of a paraben is shown at top right, where R symbolizes an alkyl group such as methyl, ethyl, propyl or butyl.

Occurrence

Some parabens are found naturally in plant sources. For example, methylparaben is found in blueberries,^[3][4][5] where it acts as an antimicrobial agent. However, when parabens are eaten, they are metabolised and lose the ester group, making them less strongly estrogen-mimicking.^[6]

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. para-Hydroxybenzoic acid is in turn produced industrially from a modification of the Kolbe-Schmitt reaction, using potassium phenoxide and carbon dioxide.

Toxicology

Parabens are considered to be safe because of their low toxicity profile and their long history of safe use. Studies on the acute, subchronic, and chronic effects in rodents indicate that parabens are practically non-toxic.^[7][8] Parabens are rapidly absorbed, metabolized, and excreted.^[7] The major metabolites of parabens are p-hydroxybenzoic acid (pHBA), p-hydroxyhippuric acid (M1), p-hydroxybenzoyl glucuronide (M3), and p-carboxyphenylsulfate (M4).^[9]

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.^[10]

Breast cancer

One scientific study reports that parabens were found in samples of breast tumors.^[11] While not entirely conclusive, this study has resulted in a call for further research.^[12] Nevertheless, this same study has fueled the belief that parabens in underarm deodorants or other cosmetics may migrate into breast tissue and contribute to the development of tumors. However, no causal link with cancer has ever been proven and so far there is no scientific evidence to support any link with any form of cancer. Some scientists believe that it may be correlated with breast cancer, based on a study by UK scientists in which preservative chemicals were found in samples of breast tumors.^[6] Their analysis of 20 breast tumors found high concentrations of parabens in 18 samples.^[13] What supports this argument is based on the ability of parabens to mimic the hormone estrogen, which is known to play a role in the development of breast cancers.^[13]

A recent review of the available data^[14] has 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 (EACs) in the diet such as the phytoestrogen daidzein."^[15] In addition, the American Cancer Society has concluded that there is no good scientific evidence to support a claim that use of cosmetics such as antiperspirants increase an individual's risk of developing breast cancer.^[16]

Even though it is impossible to link parabens directly with tumors based on the current studies, it is also impossible to say parabens are safe since their long-term health effects of exposure are essentially unknown.^[17] "From this research it is not possible to say whether parabens actually caused these tumors, but they may certainly be associated with the overall rise in breast cancer cases. Given that breast cancer is a large killer of women and a very high percentage of young women use underarm deodorants, I think we should be carrying out properly funded, further investigations into parabens and where they are found in the body," says Dr.Philip Harvey, an editor of the Journal of Applied Toxicology, which published the research.^[6] Molecular biologist Philippa Darbre at the University of Reading says that the ester-bearing form of parabens found in the tumors indicates it came from something applied to the skin, such as an underarm deodorant, cream or body spray.^[6]

Estrogenic activity

Animal experiments have shown that parabens have weak estrogenic activity, acting as xenoestrogens.^[18] In an in vivo study, the effect of butylparaben was determined to be approximately 100,000 times weaker than estradiol, although this effect was only observed when employing a dose level which was 25,000 times higher than is actually used to preserve products.^[19] As the estrogenic effect is dose-related, it may be calculated that the estrogenic effect at normal use concentrations of butylparaben is 100,000 x 25,000, i.e. 2,500,000,000 times weaker than estradiol. In the same study it was shown that the in vivo estrogenic activity of parabens is reduced by about three orders of magnitude compared to in vitro activity probably through the rapid metabolism of the parabens to the non-estrogenic metabolites. In vivo data are accepted as being more relevant than in vitro data.

The estrogenic activity of parabens increase with the length of the alkyl group. It is believed that propylparaben is estrogenic to a certain degree as well,^[20] 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.

Some estrogens are known to drive the growth of tumors; however the estrogenic activity and mutagenic activity of estrogens are not the same, with the latter dependent on free radical chemistry and not estrogen receptor activity.^[21] Nonetheless, this study has elicited some concern about the use of butylparaben, and to a lesser extent other parabens as well, in cosmetics and antiperspirants. However, there is no evidence that any cosmetics containing parabens pose a health risk, because of the low doses involved and the fact that parabens are unlikely to penetrate into the tissue, remain intact, and to accumulate there.^[7]

Nevertheless, 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.^[22]

Controversy

The above-mentioned studies have resulted in scientific debate that in turn led to popular controversy largely propagated by mass e-mail.^[23][24] The controversy has led to some concerns (both over possible carcinogenicity^[25] as well as estrogenic effects^[26]) being expressed over the continued use of parabens as preservatives, although the scientific community has found no correlation with cancer and mostly agree that any causation is improbable.^{[12][27][24][28]} There has been consensus that any estrogenic effect caused by the doses of parabens received from consumer products are insignificant compared to natural estrogens and other xenoestrogens.^[18]

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.^[28] Public interest organizations which raise awareness about cosmetic ingredients believe that further research is necessary to determine the safety of parabens (see also precautionary principle).^[25] The concerns have led to a significant minority shift from their usage by natural personal care companies seeking alternatives.^[29] The ingredient grapefruit seed extract that is promoted as a natural preservative was identified with the preservative methylparaben.^[1]

See also

• Butylparaben
• Ethylparaben
• Methylparaben
• Propylparaben

References