Parabens
Encyclopedia
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....
s in the cosmetic
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
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
Fungicide
Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals...
properties. They can be found in shampoo
Shampoo
Shampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair...
s, commercial moisturizer
Moisturizer
Moisturizers or emollients are complex mixtures of chemical agents specially designed to make the external layers of the skin softer and more pliable, by increasing its hydration by reducing evaporation. Naturally occurring skin lipids and sterols as well as artificial or natural oils,...
s, shaving gels, personal lubricant
Personal lubricant
Personal lubricants are specialized lubricants to reduce friction between body parts, or between body parts and other objects...
s, topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...
/parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
pharmaceuticals, spray tanning solution, makeup, and toothpaste
Toothpaste
Toothpaste is a paste or gel dentifrice used with a toothbrush as an accessory to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it serves as an abrasive that aids in removing the dental plaque and food from the teeth, assists in suppressing...
. They are also used as food additive
Food additive
Food additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...
s.
Their efficacy as preservatives, in combination with their low cost, the long history of their use, and the inefficacy of natural alternatives like grapefruit seed extract
Grapefruit seed extract
Grapefruit seed extract , also known as citrus seed extract, is a liquid derived from the seeds, pulp, and white membranes of grapefruit. Self-made natural GSE processed in the laboratory without solvents or synthetic agents is prepared by grinding the grapefruit seed and juiceless pulp, then...
(GSE), probably explains why parabens are so commonplace. They are becoming increasingly controversial, however, because they have been found in extremely low concentrations in breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
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.
Chemistry
Parabens are esterEster
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s of para-hydroxybenzoic acid
4-Hydroxybenzoic acid
4-Hydroxybenzoic acid is a monohydroxybenzoic acid, a phenolic derivative of benzoic acid. It is a white crystalline solid that is slightly soluble in water and chloroform but more soluble in polar organic solvents such as alcohols and acetone...
, from which the name is derived. Common parabens include methylparaben
Methylparaben
Methylparaben, also methyl paraben, one of the parabens, is a preservative with the chemical formula CH3. It is the methyl ester of p-hydroxybenzoic acid.-Occurrence:...
(E number
E number
E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...
E218), ethylparaben
Ethylparaben
Ethylparaben is the ethyl ester of p-hydroxybenzoic acid. Its formula is HO-C6H4-CO-O-CH2CH3. It is a member of the class of compounds known as parabens.It is used as an antifungal preservative...
(E214), propylparaben (E216) and butylparaben
Butylparaben
Butylparaben, or butyl paraben, is a member of the paraben family, which has the formula C4H9. It is used as an antimicrobial preservative in cosmetics such as eye shadow, foundation, sunscreen, facial moisturizer and skin anti-aging treatment. It is also used in medication suspensions, and as a...
. Less common parabens include isobutylparaben, isopropylparaben, benzylparaben and their sodium salts. The general chemical structure of a paraben is shown at top right, where R symbolizes an alkyl group such as methyl, ethyl
Ethyl group
In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....
, propyl
Propyl
In organic chemistry, propyl is a three-carbon alkyl substituent with chemical formula -C3H7. It is the substituent form of the alkane propane...
or butyl
Butyl
In organic chemistry, butyl is a four-carbon alkyl radical or substituent group with general chemical formula -C4H9, derived from either of the two isomers of butane....
.
Occurrence
Some parabens are found naturally in plant sources. For example, methylparaben is found in blueberriesBlueberry
Blueberries are flowering plants of the genus Vaccinium with dark-blue berries and are perennial...
, where it acts as an antimicrobial agent.
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 acid4-Hydroxybenzoic acid
4-Hydroxybenzoic acid is a monohydroxybenzoic acid, a phenolic derivative of benzoic acid. It is a white crystalline solid that is slightly soluble in water and chloroform but more soluble in polar organic solvents such as alcohols and acetone...
with the appropriate alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
. para-Hydroxybenzoic acid is in turn produced industrially from a modification of the Kolbe-Schmitt reaction
Kolbe-Schmitt reaction
The Kolbe–Schmitt reaction/Kolbe process is a carboxylation chemical reaction that proceeds by heating sodium phenolate with carbon dioxide under pressure , then treating the product with sulfuric acid...
, using potassium phenoxide
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
and carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
.
Toxicology
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 glucuronideGlucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
(M3), and p-carboxyphenylsulfate (M4).
Allergic reactions
In individuals with normal skin, parabens are, for the most part, non-irritating and non-sensitizing. Parabens can, however, cause skin irritation and contact dermatitisContact dermatitis
Contact dermatitis is a term for a skin reaction resulting from exposure to allergens or irritants . Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight....
and rosacea
Rosacea
Rosacea is a chronic condition characterized by facial erythema . Pimples are sometimes included as part of the definition. Unless it affects the eyes, it is typically a harmless cosmetic condition...
in individuals with paraben allergies, a small percentage of the general population.
Breast cancer
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 scientists to conclude that the presence of parabens may be associated with the occurrence of breast cancer, and to call for investigation into whether or not a causal link exists. 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. "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 ToxicologyJournal of Applied Toxicology
The Journal of Applied Toxicology is a bimonthly peer-reviewed scientific journal published since 1981 by John Wiley & Sons. It covers all aspects of toxicology and publishes reviews and research articles on mechanistic, fundamental, and applied research relating to the toxicity of drugs and...
, which published the research. A 2004 study at Northwestern University
Northwestern University
Northwestern University is a private research university in Evanston and Chicago, Illinois, USA. Northwestern has eleven undergraduate, graduate, and professional schools offering 124 undergraduate degrees and 145 graduate and professional degrees....
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.
No direct evidence of a causal link between parabens and cancer, however, 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
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...
in the diet such as the phytoestrogen daidzein
Daidzein
Daidzein belongs to the group of isoflavones. Daidzein and other isoflavone compounds, such as genistein, are present in a number of plants and herbs like the Thai Kwao Krua or Pueraria mirifica, Kudzu or Pueraria lobata, and in food sources such as soybeans and soy products like tofu and textured...
." The American Cancer Society
American Cancer Society
The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
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, but went on to state that "larger studies are needed to find out what effect, if any, parabens might have on breast cancer risk.
While current studies do not causally link parabens with tumors, neither do these studies demonstrate that parabens are safe; the long-term health effects of exposure to parabens are essentially unknown.
A further systematic review in 2008 examined 59 earlier publications (19 in depth) for answers to the questions:
- Are there experimental or biological arguments supporting a potential link between the use of deodorants/antiperspirants and breast cancer?
- Does the use of deodorants/antiperspirants have any effect on the increase in the risk of breast cancer?
- Could a causal relationship between the use of deodorants/antiperspirants and breast cancer be accepted?
They found "no scientific evidence to support the hypothesis was identified and no validated hypothesis appears likely to open the way to interesting avenues of research." They conclude "Au final, il semble possible d’affirmer que cette question ne constitue pas un problème de santé publique et qu’il apparaît donc inutile de poursuivre les recherches sur ce sujet." (Finally, it seems possible to affirm that this question does not constitute a problem of public health and that it appears therefore useless to pursue the research on the subject.)
Estrogenic activity
Animal experiments have shown that parabens have weak estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
ic activity, acting as xenoestrogen
Xenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...
s. In an in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
study, the effect of butylparaben was determined to be approximately 100,000 times weaker than that of estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, 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
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
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
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
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.
Sun exposure
Studies indicate that methylparaben applied on the skin may react with UVBUltraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
leading to increased skin aging and DNA damage.
Regulation
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.Controversy
The above-mentioned studies have resulted in 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 (see also precautionary principle
Precautionary principle
The precautionary principle or precautionary approach states that if an action or policy has a suspected risk of causing harm to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is not harmful falls on those...
). The concerns about endocrine disruptor
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...
s have led consumers and companies to search for paraben free alternatives. Grapefruit seed extract
Grapefruit seed extract
Grapefruit seed extract , also known as citrus seed extract, is a liquid derived from the seeds, pulp, and white membranes of grapefruit. Self-made natural GSE processed in the laboratory without solvents or synthetic agents is prepared by grinding the grapefruit seed and juiceless pulp, then...
that is promoted as a natural preservative was identified as containing artificial preservatives such as methylparaben.
See also
- ButylparabenButylparabenButylparaben, or butyl paraben, is a member of the paraben family, which has the formula C4H9. It is used as an antimicrobial preservative in cosmetics such as eye shadow, foundation, sunscreen, facial moisturizer and skin anti-aging treatment. It is also used in medication suspensions, and as a...
- EthylparabenEthylparabenEthylparaben is the ethyl ester of p-hydroxybenzoic acid. Its formula is HO-C6H4-CO-O-CH2CH3. It is a member of the class of compounds known as parabens.It is used as an antifungal preservative...
- Heptylparaben
- MethylparabenMethylparabenMethylparaben, also methyl paraben, one of the parabens, is a preservative with the chemical formula CH3. It is the methyl ester of p-hydroxybenzoic acid.-Occurrence:...
- Propylparaben