Parabens.(Cosmeceutical Critique)

Preservatives are necessary components in most, if not all, cosmetics and skin care products.

Without preservatives these items would, in short order, become infiltrated by various bacteria, molds, and fungi.

Parabens (alkyl esters of p-hydroxybenzoic acid), found naturally in raspberries and blackberries, are common ingredients in food and pharmaceutical products, as well as many skin, hair, and body care products, and can sometimes produce allergic reactions (Cosmetics & Toiletries, January 2005, p. 57; Food Chem. Toxicol. 2005;43:985-1015; "Goodman and Gilman's The Pharmacological Basis of Therapeu tics," 6th ed. New York: Macmillan, 1980, p. 969; Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters Have Been Found to Promote Allergic Sensitization," in Sax's Dangerous Properties of Industrial Materials, 4th ed. New York: Van Nostrand Reinhold, 1975, p. 929).

Nevertheless, parabens are the most widely used preservatives in cosmetics. It is estimated that at least one paraben ingredient is included in about 90% of all cosmetics, because of the strong record of efficacy, safety, and stability exhibited by this group of compounds (Crit. Rev. Toxicol. 2005;35:435-58; Dermatitis 2005;16:57-66).

Parabens, which include butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben (Crit. Rev. Toxicol. 2005;35:435-58), can be absorbed through the skin and migrate into the bloodstream and body tissues. There is no evidence of accumulation of methylparaben, for instance, in body tissue, and acute toxicity studies in animals show that methylparaben is nontoxic via oral and parenteral administration. Furthermore, methylparaben is not carcinogenic, mutagenic, teratogenic, or embryotoxic (Food Chem. Toxicol. 2002;40:1335-73).

Concerns have been raised recently, though, about possible links between some cosmetic products containing parabens and the incidence of breast cancer.

Presence in Cancer Tissue

In a controversial study published in January 2002, high paraben concentrations were found in breast cancer tissue. The investigators identified a weak estrogenic effect exhibited by methylparaben, ethylparaben, n-propylparaben, and n-butylparaben in estrogen-dependent MCF7 human breast cancer cells. They acknowledged that additional research would be needed to ascertain the extent of paraben accumulation in estrogen-sensitive tissues (J. Steroid Biochem. Mol. Biol. 2002;80:49-60; "'Beware of Paraben Preservatives in Body Care Products: Cosmetic Chemicals Found in Breast Tumours," NewScientist.com News Service 2004; Jan. 24).

Rumors that using antiperspirants could cause breast cancer ensued in mainstream circulation over the Internet and beyond during much of the rest of 2002, and may persist in many circles despite the lack of evidence and, in some cases, reports to the contrary.

A population-based case-control study published near the end of 2002 evaluated the relationship between underarm antiperspirant or deodorant use and breast cancer risk in women between the ages of 20 and 74 (813 cases and 793 controls). Breast cancer risk was not found to increase with antiperspirant or deodorant use generally, with use of such products in those who shaved with a razor blade, or with use of such products within 1 hour of shaving. Thus, the investigators concluded that their results did not support the theory that breast cancer risk is increased by the use of antiperspirant products (J. Natl. Cancer Inst. 2002;94:1578-80). In the first study to evaluate the intensity of underarm exposure in breast cancer survivors, results from 437 women revealed that an earlier age of breast cancer diagnosis was associated with frequency and earlier onset of antiperspirant/deodorant use combined with underarm shaving. The investigators concluded that while underarm shaving with use of antiperspirants or deodorants may contribute to breast cancer, case-control studies are necessary to arrive at appropriate recommendations for alternative axillary hygiene (Eur. J. Cancer prev. 2003;12:479-85).

A subsequent review found no reliable data to support the notion that the use of underarm antiperspirant products elevate the risk of human breast cancer (Int. J. Fertil. Womens Med. 2004;49:212). However, a review published more recently avers that while no association between parabens in cosmetics and skin care products has been established, this is because the necessary studies have not yet been conducted, not because some effects have not been identified (Best Pract. Res. Clin. Endocrinol. Metab. 2006;20:121-43).

Furthermore, Dr. Philippa Darbre, who authored the 2006 review, previously stated, in acknowledging the in vitro and in vivo estrogenic effects of paraben, that the potential involvement of these chemical ingredients in endocrine disruption and breast cancer should be amenable to study, measurement, and control, given the large exposed population (J. Appl. Toxicol. 2004;24:167-76). Thus, additional study is feasible and warranted.

Some authors note that the reports citing the presence of parabens in some breast tumor tissue fail to account for the dose-, route-, and species-dependent metabolism and elimination rates of parabens (Food Chem. Toxicol. 2005;43:985-1015). Indeed, as columnist and cosmetics expert Paula Begoun has aptly discussed in her Web site (http://www.cosmeticscop.com) and newsletter, the presence of parabens in these tissue samples does not necessarily mean that the parabens were there from the start or that they engendered the tumors.

Estrogenic Activity

Although parabens have been shown to confer some weak estrogenic effects in vitro and in vivo, such activity has been deemed significantly lower in magnitude than that of estrogen (Crit. Rev. Toxicol. 2005;35:435-58).

In a recent review considering dose and potency in comparing exposure to parabens and estrogen, researchers concluded that it is biologically implausible that parabens could raise the risk of estrogen-mediated end points and that, in the worst-case scenario of daily exposure, parabens would be significantly safer than dietary consumption of the phytoestrogen daidzein (Crit. Rev. Toxicol. 2005;35:435-58).

It is not yet known whether the consumption of parabens or their topical application could be responsible for their presence in human tissue and what the ramifications might be. The Food and Drug Administration is conducting its own research to ascertain the health implications (Endocrine Disruptor Knowledge Base, http://edkb.fda.gov/index.html). Nevertheless, parabens are quickly absorbed, metabolized, and excreted, and they appear to be nontoxic, based on acute, subchronic, and chronic studies in rodents (Food Chem. Toxicol. 2005;43:985-1015).

Effects on the Skin

For dermatologic purposes, it is worth noting that paraben esters are effective against fungi and gram-positive (but not gram-negative) bacteria. Parabens rarely sensitize but may provoke a response when applied to eczematous skin (Food Chem. Toxicol. 2002;40:1335-73). Sensitized patients can often tolerate parabens in cosmetics applied to normal skin, but, understandably, not broken skin (Food Chem. Toxicol. 2005;43:985-1015). Contact dermatitis has been reported in some people after cutaneous exposure to parabens (Food Chem. Toxicol. 2002;40:1335-73).

It is also worth noting that a recent study aimed at identifying and characterizing the toxicology of products from the reaction between p-hydroxybenzoic acid esters (parabens) and singlet oxygen [(1)O(2)] revealed that parabens may engender oxidative stress in the skin after conversion to glutathione conjugates of hydroquinone, through reactions with glutathione and singlet oxygen (Free Radic Res. 2006;40:233-40).

Conclusions

Products containing parabens should be avoided by most people who know they are allergic to parabens, which can be determined by patch testing. There are no convincing data that parabens harm those not allergic to these compounds. Because of some sensationalistic reporting in recent years, however, many people are choosing to avoid products containing this class of preservative ingredients.

Again, for those not allergic to parabens, there are no scientifically established reasons to avoid the plethora of cosmetic and skin care products that contain these preservatives. We can expect to hear much more about this class of frequently used compounds, as research is ongoing. *

BY LESLIE S. BAUMAN. M.D.

DR. BAUMANN is director of cosmetic dermatology at the University of Miami. To respond to this column, or to suggest topics for future columns, write to Dr. Baumann at our editorial offices via e-mail at sknews@elsevier.com.

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