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Parabens: Potential impact of Low-Affinity Estrogen receptor Binding chemicals on Human health a


Ebru Karpuzoglu , Steven D. Holladay & Robert M. Gogal Jr.



Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine , University of Georgia , Athens , Georgia , USA Published online: 02 Aug 2013.

To cite this article: Ebru Karpuzoglu , Steven D. Holladay & Robert M. Gogal Jr. (2013) Parabens: Potential impact of LowAffinity Estrogen receptor Binding chemicals on Human health, Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 16:5, 321-335, DOI: 10.1080/10937404.2013.809252 To link to this article:

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Journal of Toxicology and Environmental Health, Part B, 16:321–335, 2013 Copyright © Taylor & Francis Group, LLC ISSN: 1093-7404 print / 1521-6950 online DOI: 10.1080/10937404.2013.809252


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Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA Parabens, alkyl esters of p-hydroxybenzoic acid, are widely used in cosmetics, pharmaceuticals, personal care products and as food additives to inhibit microbial growth and extend product shelf life. Consumers of these compounds are frequently exposed via the skin, lips, eyes, oral mucosa, nails, and hair. Parabens are estrogenic molecules but exert weaker activity than natural estrogens, which would imply a low risk. Consistent with this idea, a number of recent commission reports from different countries suggested that parabens pose a negligible endocrine-disrupting risk at the recommended doses. However, individuals are not routinely exposed to a single paraben, and most of the available paraben toxicity data, reviewed in these reports, are from single-exposure studies. Further, assessing the additive and cumulative risk of multiple paraben exposure from daily use of multiple cosmetic and/or personal care products is presently not possible based on current studies. In this review, current and recent studies of paraben exposure and public health policies as well as critical gaps in the knowledge are discussed and new research directions regarding multiple exposures and novel target cohorts are recommended.

Parabens are alkyl esters of p-hydroxybenzoic acid widely used in cosmetics, including foundations, powders, eye shadows, mascara, lip glosses, lipsticks, and nail polishes, and in pharmaceuticals and personal care products (PCP) such as lotions, sunscreens, cleansers, shampoos, deodorants, hair care products, and toothpaste, which are in frequent contact with skin, lips, eyes, oral mucosa, nails, and hair. Tables 1 and 2 depict the frequency of use and percent of use of parabens in a select number of PCP and cosmetic products, respectively (CTFA 2008). Parabens are also common ingredients in food products used to inhibit microbial growth and extend product shelf life (Liao et al. 2013). The synthetic parabens include methyl-, ethyl-, propyl-, isobutyl-, butyl-, isopropyl-, and benzyl-, show increasing antimicrobial activity

with increasing alkyl chain length (Figure 1) (Darbre et al. 2002; 2003; Golden et al. 2005). The estrogen receptor binding affinities of parabens are 10,000- to 100,000-fold lower than for estrogen (17β-estradiol; shown in Figure 1 for comparison), and decrease in order as: isobutylparaben > butylparaben > isopropylparaben = propylparaben > ethylparaben (Vo et al. 2010). Such parabens have been in use for more than 80 years due to (1) antibacterial and fungicidal properties, (2) high stability at different pH and temperatures, (3) inertness, and (4) low cost, which has resulted in widespread, chronic human exposures (Daughton and Ternes 1999). This review focuses on current knowledge regarding potential effects of parabens on endocrineresponsive systems, including the reproductive, immune, and nervous systems.

Address correspondence to Robert M. Gogal, Jr., Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382, USA. E-mail: [email protected] 321


0.16–0.4% 0.07–0.4% 0.2–0.44% 0.15–0.4% 0.1–0.5% 0.0008–0.3% 0.15–0.4% 0.1–0.4% 0.1–0.4%

533 787 317 631 167 35 63 381 331

227 183

135 29 61

591 215 478


0.04–0.4% 0.03–0.2%

0.001–0.3% 0.002–0.2% 0.1–0.3%

0.05–0.35% 0.03–0.35% 0.1–0.4%


0.16–0.7% 0.1–0.3% 0.1–0.5% 0.17–0.6% 0.15–1%

296 189 282 338 286

4 33

Baby products (number of products) Shampoos (38) Creams, lotions, oils, or powders (67) — 0.2–0.4%

0.15–0.5% 0.25–0.54% 0.13–0.6% 0.1–0.35% 0.07–0.4%

613 213 485 77 67

4 31


325 193 250 308

541 190 477 83 45

0.1% 0.2%


0.05–0.4% 0.02–0.5% 0.1–0.5% 0.1–0.6%

0.1–0.5% 0.1–0.32% 0.05–0.4% 0.13–0.2% 0.05–0.15%

Percent in product

Frequency of use

Percent in product

Frequency of use

Eyes (number of products) Eye shadow (1061) Mascara (308) Eyeliner (liquid or pencil) (639) Eyebrow pencil (124) Eye makeup remover (114) Face (number of products) Foundations (530) Makeup Base (i.e., primers) (273) Powders (447) Blushes (cream or powder) (459) Lips Lipstick (1681)

Cosmetic products



TABLE 2. Frequency of use and percent concentration of parabens in cosmetic products

Cleansing creams, lotions, or gels (1009) Moisturizers (1200) Face and neck skin care (546) Body skin care (creams, lotions etc.) (992) Night skin care (229) Deodorants (281) Sunscreen skin care (Creams, gels, sprays, lotions) (138) Shampoos (1022) Hair conditioners (715)

PCP (number of products)

Percent in product

Propylparaben Frequency of use

Frequency of use

Percent in product


0.03–0.2% 0.001–0.3%

0.0001–0.25% 0.002–0.1% 0.04–0.2%

0.001–0.3% 0.03–0.3% 0.001–0.4%


Percent in product

1 12


150 35 119 84

295 127 23 5 17

Frequency of use

— —


0.001–0.5% 0.00006–0.35% 0.04–0.5% 0.04–0.3%

0.06–0.49% 0.00002–0.4% 0.03–0.4% 0.4% 0.03–0.3%

Percent in product


108 33

64 10 22

268 169 153


Frequency of use


TABLE 1. Frequency of use and percent concentration of parabens in Personal Care Products (PCP)

0.01–0.25% 0.02–0.25%

0.04–0.15% 0.002% 0.03–0.4%

0.06–0.2% 0.09–0.4% 0.09–0.4%


Percent in product

2 21


96 51 67 35

199 80 398 60 27

Frequency of use

— 0.05%


0.06–0.2% 0.00006–0.1% 0.07–0.14% 0.07–0.2%

0.05–0.3% 0.00002–0.21% 0.05–0.2% 0.05–0.1% 0.07–0.15%

Percent in product


108 49

65 10 28

278 157 157


Frequency of use


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0.02–0.1% 0.01–0.02%

— 0.002% 0.02%

0.0002–0.02% 0.02–0.09% 0.02–0.4%


1 5


15 1 6 2

3 17 9 4 6

Frequency of use

— —


0.00001–0.06% 0.00003–0.02% 0.00001–0.04% 0.00001–0.04%

0.05–0.4% 0.000007–0.1% 0.02–0.1% 0.06% 0.02%

Percent in product


38 12

14 3 9

67 75 52


Percent in product

Isobutylparaben Frequency of use





HO CH 3 methylparaben


CH CH33 propylparaben

CH3 butylparaben

Downloaded by [Moskow State Univ Bibliote] at 10:40 04 December 2013

CH3 CH3 isopropylparaben

recent study, blood samples from 268 pregnant women all showed traces of at least several of the 163 different chemicals evaluated, including parabens used in PCP (Woodruff et al. 2011). In addition to adult exposure, children up to 9 yr of age are exposed to approximately 61 PCP ingredients daily, suggesting potential endocrine-modulating effects (EWG 2007). Collectively, these reports suggest that parabens exposure frequency and concentration vary significantly by individual, and exposure is widespread in adults and children of both genders, with women on average receiving the highest exposure.


FIGURE 1. The structure of parabens and estrogen (17βestradiol).

PARABEN PRODUCTION AND SOURCES In a 1984 study, greater than 13,000 cosmetic products were found to contain parabens (Elder 1984), and by 1987 approximately 7000 kg of parabens was used annually in cosmetics and PCP (Soni et al. 2005). Given that the number and type of PCP and cosmetics have increased since the 1980s, it is reasonable to predict that the percentage of products containing parabens and thus frequency of human exposure to these chemicals have also risen in societies where cosmetics and PCP are in constant use. One question that remains unresolved is whether frequent exposure to varying concentrations of these weakly estrogenic compounds poses a threat to humans, in particular, estrogen-sensitive human cohorts. In a 2004 survey, the Environmental Working Group (EWG) reported that women on average used 12 PCP containing a total of 168 ingredients per day, whereas men used approximately 10 products with a total of 85 ingredients daily (EWG 2004). The skin, with one of the largest body surface areas, absorbs approximately 50 to 70% of a topically applied PCP (Bronaugh et al. 1994). However, there are no available data for potential harmful effects of topical parabens exposure on immune-mediated skin irritations such as eczema or allergies (Savage et al. 2012). In a

THE SKIN: PRIMARY GATEWAY OF PARABEN ENTRY INTO THE BODY A number of in vitro and in vivo studies demonstrated that skin might absorb parabens, which are then readily detected in tissue, blood, and urine samples. In a comparative animal study, human skin was observed to retain parabens longer than skin of rats, suggesting a potential for prolonged estrogenic influence on human skin (Harville et al. 2007). In a related study, butylparaben was applied via a topical cream and was shortly thereafter detected in the blood of the human subjects (Janjua et al. 2007). Further, the absorption of methyl-, ethyl-, and propylparaben via the skin was found to be 60, 40, and 20%, respectively, 8 h after application, independent of different formulations of the creams (Pedersen et al. 2007). Analysis of plasma samples from 332 women showed median levels of 9.4 ng/ml methylparaben,

Parabens: potential impact of low-affinity estrogen receptor binding chemicals on human health.

Parabens, alkyl esters of p-hydroxybenzoic acid, are widely used in cosmetics, pharmaceuticals, personal care products and as food additives to inhibi...
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