Parabens is a term used within the vernacular of the specialty chemicals industry to describe a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid). Parabens are widely used as preservatives by cosmetic and pharmaceutical industries. 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. They are becoming increasingly controversial, however, because they have been found in breast cancer tumors (an average of 20 nanograms/g of tissue). Parabens have also displayed the ability to slightly mimic estrogen (a hormone known to play a role in the development of breast cancer). No effective direct links between parabens and cancer have been established, however. Another concern is that the estrogen-mimicking aspect of parabens may be a factor in the increasing prevalence of early puberty in girls.
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.
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.
Studies on the acute, subchronic, and chronic effects in rodents indicate that parabens are practically non-toxic. Parabens are rapidly absorbed, metabolized, and excreted. The major metabolites of parabens are p-hydroxybenzoic acid (pHBA), p-hydroxyhippuric acid (M1), p-hydroxybenzoyl glucuronide (M3), and p-carboxyphenylsulfate (M4).
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.
Average levels of 20 nanograms/gram of parabens have been detected in a small sample of 20 breast tumors. These findings, along with the demonstrated ability of some parabens to partially mimic estrogen, a hormone known to play a role in the development of breast cancers, have led some people to conclude that the presence of parabens may be associated with the occurrence of breast cancer, though scientists say no link can be determined from current studies and that more research called for.
The lead researcher of the UK study, molecular biologist Philippa Darbre, reported that the ester-bearing form of the parabens found in the tumors indicate that they came from something applied to the skin, such as an underarm deodorant, cream or body spray, and stated that the results helped to explain why up to 60% of all breast tumors are found in just one-fifth of the breast - the upper-outer quadrant, nearest the underarm (though this is controversial). "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 Philip Harvey, an editor of the Journal of Applied Toxicology, which published the research. A 2004 study at Northwestern University found that an earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving. "I personally feel there is a very strong correlation between the underarm hygiene habits and breast cancer," said immunologist Dr. Kris McGrath, the author of the study.
This research has fueled a popular belief that the parabens in underarm deodorants and other cosmetics can migrate into breast tissue and contribute to the development of tumors.
However, no direct evidence of a causal link between parabens and cancer has been shown. A 2005 review of the data available at that time 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." The American Cancer Society also concluded that there was insufficient scientific evidence to support a claim that use of cosmetics such as antiperspirants increase an individual's risk of developing breast cancer.
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.
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. 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. A 2005 safety assessment of parabens concluded that cosmetics containing parabens do not, on the basis of currently available evidence, pose a health risk; because of the low doses involved and the low probability that parabens will penetrate into the tissue, remain intact, and accumulate there.
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.
The above-mentioned studies have sparked scientific debate that in turn led to popular controversy, largely propagated by mass e-mail. Darbre's paper led to further 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 that is promoted as a natural preservative was identified as containing artificial preservatives such as methylparaben.
- von Woedtke T, Schluter B, Pflegel P, Lindequist U, Julich WD (June 1999). "Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained". Pharmazie (Greifswald, Germany: Institute of Pharmacy, Ernst Moritz Arndt University,) 54 (6): 452–6. PMID 10399191.
- Harvey PW, Everett DJ (Jan 2004). "Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours". Journal of Applied Toxicology 24 (1): 1–4. doi:10.1002/jat.957. PMID 14745840.
- Golden R, Gandy J, Vollmer G (2005). "A review of the endocrine activity of parabens and implications for potential risks to human health". Critical Reviews in Toxicology 35 (5): 435–58. doi:10.1080/10408440490920104. PMID 16097138.
- Weil, Elizabeth (March 30, 2012). "Puberty Before Age 10: A New 'Normal'?". The New York Times.
- Al-Shamma A, Drake S, Flynn DL, Mitscher LA, Park YH, Rao GSR, Simpson A, Swayze JK, Veysoglu T, Wu STS (1981). "Antimicrobial Agents From Higher Plants. Antimicrobial Agents From Peganum harmala Seeds". J Nat Prod 44 (6): 745–747. doi:10.1021/np50018a025. PMID 7334386.
- Bais HP, Vepachedu R, Vivanco JM, (1 April 2003). "Root specific elicitation and exudation of fluorescent beta-carbolines in transformed root cultures of Oxalis tuberosa". Plant Physiology and Biochemistry 41 (4): 345–353. doi:10.1016/S0981-9428(03)00029-9.
- "In Vitro Cellular and Developmental Biology". Plant 37 (6): 730–741. 2001. doi:10.1007/s11627-001-0122-y.
- Soni MG, Carabin IG, Burdock GA (2005). "Safety assessment of esters of p-hydroxybenzoic acid (parabens)". Food and Chemical Toxicology 43 (7): 985–1015. doi:10.1016/j.fct.2005.01.020. PMID 15833376.
- Soni MG, Taylor SL, Greenberg NA, Burdock GA (2002). "Evaluation of the health aspects of methyl paraben: a review of the published literature". Food and Chemical Toxicology 40 (10): 1335–73. doi:10.1016/S0278-6915(02)00107-2. PMID 12387298.
- Elder RL (1984). "Final report on the safety assessment of methylparaben, ethylparaben, propylparaben, and butylparaben". J Am Coll Toxicol 3: 147–209. doi:10.3109/10915818409021274.
- Nagel JE, Fuscaldo JT, Fireman P. Paraben allergy (April 11, 1977). "Paraben allergy.". J Am Med Assoc 237 (15): 1594–5. doi:10.1001/jama.237.15.1594. PMID 576658.
- Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS (Jan–Feb 2004). "Concentrations of parabens in human breast tumours". J Appl Toxicol 24 (1): 5–13. doi:10.1002/jat.958. PMID 14745841.
- Vince G (12 January 2004). "Cosmetic chemicals found in breast tumours". New Scientist.
- Lagorio, Christine (Dec 5, 2005). "The Cancer-Antiperspirant "Myth": Could Shaving And Antiperspirant Be Related To Breast Cancer?". CBS News. Retrieved 2 Jan 2009.
- Harvey PW, Darbre P (2004). "Endocrine disruptors and human health: Could estrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research". Journal of Applied Toxicology 24 (3): 167–76. doi:10.1002/jat.978. PMID 15211609.
- Ed Friedlander MD (2 March 2010). "Anti-Perspirants -- Not a Breast Cancer Risk".
- McGrath, Kris (December 2003). "An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving" (PDF). European Journal of Cancer Prevention 12 (6): 479–85. doi:10.1097/00008469-200312000-00006. PMID 14639125.
- The American Cancer Society Antiperspirants and Breast Cancer Risk
- Byford JR, Shaw LE, Drew MG, Pope GS, Sauer MJ, Darbre PD (January 2002). "Oestrogenic activity of parabens in MCF7 human breast cancer cells". J Steroid Biochem Mol Biol 80 (1): 49–60. doi:10.1016/S0960-0760(01)00174-1. PMID 11867263.
- Edwin J. Routledge, et al. (1998). "Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic". Toxicology and Applied Pharmacology 153 (1): 12–19. doi:10.1006/taap.1998.8544. PMID 9875295.
- Cashman AL, Warshaw EM (June 2005). "Parabens: a review of epidemiology, structure, allergenicity, and hormonal properties". Dermatitis 16 (2): 57–66. doi:10.1097/01206501-200506000-00001. PMID 16036114.
- Fernandez SV, Russo IH, Russo J (2006-04-15). "Estradiol and its metabolites 4-hydroxyestradiol and 2-hydroxyestradiol induce mutations in human breast epithelial cells". Int J Cancer 118 (8): 1862–8. doi:10.1002/ijc.21590. PMID 16287077.
- Osamu Handa, Satoko Adachi, Tomohisa Takagi et al. (3 October 2006). "Methylparaben potentiates UV-induced damage of skin keratinocytes". Toxicology 227 (1-2): 62–72. doi:10.1016/j.tox.2006.07.018. PMID 16938376.
- Yoshinori Okamoto, Tomohiro Hayashi, Shinpei Matsunami, Koji Ueda, Nakao Kojima (July 26, 2008). "Combined activation of methyl paraben by light irradiation and esterase metabolism toward oxidative DNA damage". Chemical Research in Toxicology 21 (8): 1594–9. doi:10.1021/tx800066u. PMID 18656963.
- SCCP: Opinion on Parabens. Colipa No P82 10 Oct 2006.
- Jones J (September 20, 2000). "Can rumors cause cancer?". Journal of the National Cancer Institute 92 (18): 1469–71. doi:10.1093/jnci/92.18.1469. PMID 10995800.
- "Antiperspirants do NOT cause breast cancer". Breastcancer.org. August 15, 2008. Retrieved April 15, 2010.; "Link between antiperspirants and breast cancer?". Breastcancer.org. October 2, 2008. Retrieved May 3, 2012.; "Common Fears With No Evidence: Antiperspirants and Bras". Breastcancer.org. March 20, 2012. Retrieved May 3, 2012.
- Harvey, PW; Everett, DJ (2004). "Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours.". Journal of applied toxicology : JAT 24 (1): 1–4. doi:10.1002/jat.957. PMID 14745840.
- Rita Arditti (June 9, 2004). "Cosmetics, parabens, and breast cancer". Organic Consumers Association.
- "The truth about antiperspirants and breast cancer". Unilever.
- "Underarm Hygiene Does Not Cause Breast Cancer". ChemistryViews.
- Lebovits SC (May 26, 2008). "Cosmetics firms heed calls for organics". The Boston Globe.