Parabens are organic compounds that are commonly used as preservatives in cosmetic and pharmaceutical products. They are esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid).
Chemistry
Structure 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. 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.
Biological 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 more 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.
Applications Parabens are found in shampoos, commercial moisturizers, shaving gels, personal lubricants, topical/parenteral pharmaceuticals, sun-tan products, makeup, and toothpaste. They are also used as food preservatives. Parabens are additionally found in pharmaceutical products such as topical treatments for wounds.
Safety Methylparaben, and implicitly the other esters, is practically non-toxic by both oral and parenteral administration in animals. It is hydrolyzed to p-hydroxybenzoic acid and rapidly excreted in urine without accumulating in the body.
Allergic reactions Parabens are, for the most part, non-irritating and non-sensitizing. Among people with contact dermatitis or eczema, less than 3% of patients were found to have a sensitivity to parabens.
Estrogenic activity Studies in rats have indicated that parabens may mimic the hormone estrogen, raising concerns over possible contributions to breast cancer. However, according to Cancer Research UK, there is no reliable evidence that parabens cause breast cancer in humans. 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 due to estrogenic activity of parabens increasing with the length of the alkyl group.
Controversy Concerns about endocrine disruptors have led consumers and companies to search for paraben-free alternatives. A common alternative has been phenoxyethanol, but this has its own risks and has led to an FDA warning on inclusion in nipple creams.
Regulation The European Scientific Committee on Consumer Safety (SCCS) reiterated in 2013 that methylparaben and ethylparaben are safe at the maximum authorized concentrations (up to 0.4% for one ester or 0.8% when used in combination). The SCCS concluded that the use of butylparaben and propylparaben as preservatives in finished cosmetic products is safe to the consumer, as long as the sum of their individual concentrations does not exceed 0.19%. Isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben were banned by European Commission Regulation (EU) No 358/2014.
Environmental considerations
Release into the environment Paraben discharge into the environment is common due to their ubiquitous use in cosmetic products. A 2010 study on consumer available personal care products revealed that 44% of the tested products contain parabens.
In one New York wastewater treatment plant (WWTP), mass load of all parent paraben derivatives (methylparaben, ethylparaben, propylparaben, butylparaben, etc.) from influent wastewater was found to be 176 mg/day/1000 people. When this value is used to estimate the amount of parabens entering WWTPs from the 8.5 million people currently residing in New York City for an entire year, a value of approximately 546 kg (1,204 lb) of parabens is calculated. Therefore, levels of paraben accumulation prove significant upon long-term observance. WWTPs eliminate between 92–98% of paraben derivatives; however, much of this removal is due to the formation of degradation products. Despite their reputed high elimination through WWTPs, various studies have measured high levels of paraben derivatives and degradation products persisting in the environment.
4-Hydroxybenzoic acid (PHBA)
4-Hydroxybenzoic acid (PHBA) is a significant degradation product . Within WWTPs, some parabens accumulate in the sludge. Enterobacter cloacae, and possibly other organisms, metabolize the sludge parabens into PHBA.
Bioaccumulation of degradation products
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