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.
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.
||This section needs more medical references for verification or relies too heavily on primary sources. (October 2015)|
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.
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.
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."
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.
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 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, but this has its own risks and has led to an FDA warning on inclusion in nipple creams.
- Nutrition, Center for Food Safety and Applied. "Ingredients - Parabens in Cosmetics". www.fda.gov. Retrieved 2016-11-01.
- von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD (1999). "Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained". Die Pharmazie. 54 (6): 452–6. PMID 10399191.
- 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. PMID 16097138. doi:10.1080/10408440490920104.
- Freese, E; Sheu, CW; Galliers, E (2 February 1973). "Function of lipophilic acids as antimicrobial food additives.". Nature. 241 (5388): 321–5. PMID 4633553. doi:10.1038/241321a0.
- Nes, IF; Eklund, T (April 1983). "The effect of parabens on DNA, RNA and protein synthesis in Escherichia coli and Bacillus subtilis.". The Journal of applied bacteriology. 54 (2): 237–42. PMID 6189812. doi:10.1111/j.1365-2672.1983.tb02612.x.
- Ma, Y; Marquis, RE (November 1996). "Irreversible paraben inhibition of glycolysis by Streptococcus mutans GS-5.". Letters in applied microbiology. 23 (5): 329–33. PMID 8987716. doi:10.1111/j.1472-765x.1996.tb00201.x.
- Valkova N, Lépine F, Villemur R (2001). "Hydrolysis of 4-Hydroxybenzoic Acid Esters (Parabens) and Their Aerobic Transformation into Phenol by the Resistant Enterobacter cloacae Strain EM". Applied and Environmental Microbiology. 67 (6): 2404–09. PMC . PMID 11375144. doi:10.1128/AEM.67.6.2404-2409.2001.
- "Parabens: A Review of Epidemiology, Structure, Allergenicity, and Hormonal Properties". Medscape. Retrieved Feb 29, 2016.
- Karpuzoglu E, Holladay SD, Gogal RM (2013). "Parabens: potential impact of low-affinity estrogen receptor binding chemicals on human health". Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 16 (5): 321–35. PMID 23909435. doi:10.1080/10937404.2013.809252.
- Nagel JE, Fuscaldo JT, Fireman P (1977). "Paraben allergy". JAMA. 237 (15): 1594–5. PMID 576658. doi:10.1001/jama.237.15.1594.
- "Parabens in Breast Tissue not Limited to Women who Have Used Underarm Products". Wiley. Retrieved 31 December 2015.
- "Parabens". U.S. Food and Drug Administration. Retrieved 31 December 2015.
- 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. PMID 11867263. doi:10.1016/S0960-0760(01)00174-1.
- Edwin J. Routledge; et al. (1998). "Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic". Toxicology and Applied Pharmacology. 153 (1): 12–19. PMID 9875295. doi:10.1006/taap.1998.8544.
- Cashman AL, Warshaw EM (2005). "Parabens: a review of epidemiology, structure, allergenicity, and hormonal properties". Dermatitis. 16 (2): 57–66; quiz 55–6. PMID 16036114. doi:10.1097/01206501-200506000-00001.
- Handa O, Kokura S, Adachi S, Takagi T, Naito Y, Tanigawa T, Yoshida N, Yoshikawa T (2006). "Methylparaben potentiates UV-induced damage of skin keratinocytes". Toxicology. 227 (1-2): 62–72. PMID 16938376. doi:10.1016/j.tox.2006.07.018.
- Okamoto Y, Hayashi T, Matsunami S, Ueda K, Kojima N (2008). "Combined activation of methyl paraben by light irradiation and esterase metabolism toward oxidative DNA damage". Chemical Research in Toxicology. 21 (8): 1594–9. PMID 18656963. doi:10.1021/tx800066u.
- SCCP: Opinion on Parabens. Colipa No P82 10 Oct 2006.
- Harvey PW, Everett DJ (2004). "Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours". Journal of Applied Toxicology. 24 (1): 1–4. PMID 14745840. doi:10.1002/jat.957.
- 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.
- Commissioner, Office of the. "2008 - FDA Warns Consumers Against Using Mommy's Bliss Nipple Cream". www.fda.gov. Retrieved 2015-10-31.