User:Mgattar/Paraben

Parabens are chemicals that are commonly used as preservatives in cosmetic and pharmaceutical products. Chemically, they are a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid). Research is being conducted to evaluate the potential negative health implications of paraben usage. Certain parabens have been linked to cancer.

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. 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.

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, 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.

General Uses
Parabens are effective preservatives in many types of formulas. These compounds, and their salts, are used primarily for their bactericidal and fungicidal properties. They 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. These treatments work to help wounds heal by keeping the skin moist, and to also help prevent infection. The antimicrobial properties of parabens play a role in the effectiveness of the treatment. This application is helpful for those who have chronic wounds, and need to prevent infections as much as possible. I reorganized paragraphs and added information on paraben use in wound care. Mgattar (talk)

Health considerations
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. FDA states that they have no information that use of parabens in cosmetics has any effect on health. They continue to consider certain questions and evaluate data about parabens' possible health effects.

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. At least one case has been reported of an allergic reaction to parabens.

Breast cancer
The American Cancer Society mentioned a 2004 study that found parabens in the breast tissue of mastectomy patients but did not find parabens to be a cause of the cancers. Michael Thun of ACS stated that the effects of parabens would be minuscule compared to other risks "such as taking hormones after menopause and being overweight". 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."

Estrogenic activity
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 about 1/100,000th that of estradiol, and was observed only at a dose level around 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 due to estrogenic activity of parabens increasing with the length of the alkyl group.

Birth Size
The paraben n-butylparaben has been linked to decreased birth size of female babies. This study evaluated the urine of pregnant mothers to measure the concentrations of several different parabens such as methylparaben, ethylparaben, iso-propylparaben, n-propylparaben, and benzylparaben. When birth sizes of their children were correlated to paraben concentration of the mother, n-butylparaben was shown to be associated with smaller sizes of female children at birth. The males were not affected, and the other parabens studied did not hold this association either.