By Ted Waszkuc, Ph.D., Methods Development Scientist, NOW Foods
A growing body of evidence suggests that parabens are estrogenic has convinced many manufacturers to reduce their use in topically applied products. Parabens comprise a group of alkyl esters of p-hydroxybenzoic acid widely used as synthetic antimicrobial preservatives in cosmetics, pharmaceutical products and food. Although most effective against molds and yeasts, parabens exert a broad spectrum of antimicrobial activity over a wide pH range.
Parabens in Cosmetics
Parabens individually, or in combination, are employed in all cosmetic product categories, with reported use in over 13,000 formulations.3 Products containing parabens may contact the skin, hair and scalp, lips and nails. Parabens are non-irritating and non-sensitizing when applied to normal skin. However, application to damaged or broken skin may result in sensitization. Parabens formulate well because they have no perceptible odor or taste, do not produce discoloration, and are practically pH neutral.
Parabens in Pharmaceuticals
Parabens were first used in pharmaceuticals in the mid-1900’s and a variety of drug formulations - including pills, syrups, injectable solutions and contraceptives - are known to contain them since. The concentration of parabens used varies from product to product, but seldom exceeds 1%. Combinations of methyl and propyl parabens are often used in aqueous formulations, due to observed synergistic effects.4 Methyl and propyl parabens have been classified as inactive ingredients in several over-the-counter (OTC) drugs.5 However, the FDA has determined that parabens are not suitable as preservatives in OTC ophthalmic products, because they may be irritating to the eyes. 6
Parabens in Food
Parabens have been added to food for more than 50 years and their usage steadily increased to include more food categories, like soft drinks and frozen dairy products. Methyl and propyl are the most extensively used in foods, and FDA has affirmed them as Generally Recognized as Safe (GRAS) for direct addition to food at concentrations below 0.1%.7 A 30-fold increase in use of parabens was noted from 1960 to 1970.
Paraben absorption, Metabolism and Excretion
Parabens are rapidly absorbed through the intact skin and partially hydrolyzed by specific enzymes in subcutaneous fat tissue.8 Ingested parabens undergo complete hydrolysis to p-hydroxybenzoic acid, which shows little preservative action.9 Final metabolites are excreted in the urine as glycine, glucuronic or sulfuric acid conjugates. 10,11 Some studies have shown no evidence of accumulation of parabens or their metabolites in the body, but others have shown accumulation in breast tissue. Are parabens toxic? In the past, parabens were considered to be practically non-toxic by various routes of administration, based on acute and chronic animal studies.3,10 However, some studies have shown accumulation of parabens in breast tissue and leading to cancer in long term use. The popular use of parabens as preservatives arises from their low acute toxicity, broad spectrum of activity, inertness, stability over the pH 4.5 – 7.5 range, biodegradability, low cost and worldwide regulatory acceptance.13
How much is considered to be safe?
The total consumption of parabens from all sources (via cosmetics and personal care products, food and pharmaceuticals) is estimated as about 77.5mg/day, with food accounting for approximately 2.5mg/day, cosmetics and personal care products 50mg/day and drugs 25mg/day. For an individual weighing 60kg (132lb) it correlates as about 1.29mg/kg/day.14 The recommended Acceptable Daily Intake (ADI) for methyl-, ethyl-, and propyl parabens combined is up to 10mg/kg body weight/day.3
Recent Safety Concerns
In recent years there has been a growing concern about human exposure to synthetic estrogens from the environment, including chemical exposure from body-care cosmetics (lotions, moisturizers, deodorants, sun screens).15 Several studies on the estrogenic activity of parabens have been published, which generated a debate on the role of parabens in the increased incidence of breast cancer.16, Detection of parabens in breast tumor tissue samples has provoked controversy over the continued use of these substances.17 Because of their good skin-permeability and reasonable lipid solubility (especially the higher esters) parabens from body-care products applied to the underarm as deodorants undergo direct dermal absorption and may concentrate in the skin fat tissue before being metabolized. The term of “endocrine disrupters” - embracing parabens and other environmental estrogens – was coined to refer to synthetic chemicals that mimic or block hormones and affect the functions these hormones control.18
In a very recently published report, parabens are shown to elevate estrogen levels through inhibition of estrogen-metabolizing enzymes in the skin.19 Although the assessment of possible paraben estrogenic hazards on the basis of current studies is still equivocal and more research is needed, it seems to be an intelligent choice to avoid parabens by choosing paraben-free personal care products.
1 Sottofattori, E., et al., Simultaneous HPLC determination of multiple components in a commercial cosmetic cream. J. Pharm. Biomed. Anal. 18, 213-217 (1998)
2 Labat, L., et al., Comparison of High-Performance Liquid Chromatography and capillary zone electrophoresis for the determination of parabens in a cosmetic products. J. Pharm. Biomed. Anal. 23, 763-769 (2000)
3 Soni, M.G., et al. Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food and Chemical Toxicology 43, 985-1015 (2005) and references cited therein.
4 Gilliland, D., et al., Kinetic evaluation of claimed synergistic paraben combinations using a factorial design. Journal of Applied Bacteriology 72, 258-261 (1992)
5 FDA. Monograph on OTC topical analgesics. Federal Register 44, 69790 (1979)
6 FDA. Monograph on OTC ophthalmic ingredients. Federal Register 45,20669 (1980)
7 FDA. Methyl paraben and propyl paraben. Affirmation of GRAS status of direct human food ingredients. Federal Register 38, 20048-200050 (1973)
8 Lobemeier, C., et al. Hydrolysis of parabens by extracts from differing layers of human skin. Biological Chemistry 377(10), 647-651 (1996)
9 Soni, M.G., et al., Safety assessment of propyl paraben: a review of the published literature. Food and Chemical Toxicology 39, 513-532 (2001) and references cited therein
10 Elder, R.L., Final report on the safety assessment of methyl paraben, ethyl paraben, propyl paraben and butyl paraben. Journal of the American College of Toxicology 3, 147-209 (1984)
11 Hindmarsh, K.W., et al., Urinary excretion of methyl paraben and its metabolites. Journal of Pharmaceutical Sciences. 72, 1039-1041 (1983)
12 Nakagawa, Y., Mechanism of p-hydroxybenzoate ester-induced mitochondrial dysfunction and cytotoxicity in isolated rat hepatocytes. Biochemical Pharmacology 55, 1907-1914 (1998)
13 FDA. Inactive Ingredient Guide. Center for DrugEvaluation and Research, Office of Management, Food and Drug Administration, Rockville, MD
14 Soni, M.G., et al., Evaluation of the health aspects of methyl paraben: a review of the published literature. Food and Chemical Toxicology 40, 1335-1375 (2002) and references cited therein
15 Darbre, P.D., Environmental oestrogens, cosmetics and brest cancer. Best Practice and Research Clinical Endocrinology and Metabolism, 20 (1) 121-143 (2006)
16 Darbre,P.D. Underarm cosmetics are a cause of brest cancer. European Journal of Cancer Prevention 10, 389-393 (2001)
17 Darbre. P.D., et al., Concentration of parabens in human breast tumors. J. Appl. Toxicol. 24, 5-13 (2004)
18 Harvey, P.W., et al., Endocrine disrupters and human health: could oestrogenic chemicals in bodycare cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research. J. Appl. Toxicol. 24, 167-176 (2004)
19 Prusakiewicz, J.J, et al., Parabens inhibit human skin estrogen sulfotransferase activity: Possible link to paraben estrogenic effects. Toxicology, In press, available on line 19 January, 2007
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