Parabens Paradoxes in Cosmetic Formulations: A Review: August 2016
Parabens Paradoxes in Cosmetic Formulations: A Review: August 2016
Parabens Paradoxes in Cosmetic Formulations: A Review: August 2016
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Abstract
Cosmetics are defined as "articles intended to be rubbed, poured, sprinkled, or
Keywords: sprayed on, introduced into, or otherwise applied to the human body, for cleansing,
Parabens, Cosmetics, beautifying, promoting attractiveness, or altering the appearance." Consequently, they
Parabens toxicity, include products such as skin moisturizers, perfumes, lipsticks, shampoos,
Parabens safety. deodorants, as well as any material intended for use as a component of a cosmetic
product. In order to enhance cosmetic properties, promote cosmetic efficacy and
produce more viable products, many cosmetics contain chemical additives, such as
parabens. However, recent studies have cautioned that exposure to parabens may
have harmful consequences on human health. Therefore, the safety of parabens for
use as preservatives in cosmetics has come into controversy, and as a result,
consumer demand for paraben-free products, is widely increasing.
For this literature review without meta-analysis were used as databases PubMed and
b-on in order to find reliable information on the subject under study.
Therefore, it was possible to confirm that parabens are safe, when used at the
maximum authorized concentrations.
INTRODUCTION
‘‘Paraben’’ is an abbreviation of para-hydroxybenzoic acid, which refers to a group of alkyl esters with substitutions
at the para site of the hydroxybenzoic acid benzene ring (Figure 1) [1].
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©InternationalJournal of Medical Research and Pharmaceutical Sciences http://www.ijmprsjournal.com
Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
Parabens were first introduced as preservatives in drug products in mid 1920s. Currently, they are widely used
preservatives, mainly in cosmetics and pharmaceuticals, but also in food commodities and industrial products [4,5].
Human exposure to parabens occurs mostly through the consumption of personal care products containing parabens
[6,7], as cosmetic preparations are frequently used by a great number of people without distinction of age, gender or
race and, generally, during a long period of time [8].
Parabens can have multiple biological actions, but it is generally believed that their inhibitory effects on membrane
transport and mitochondrial function processes are key for their actions [9]. Their popularity is based on several
advantages when compared to other alternatives:
• broad spectrum of activity against yeasts, molds and bacteria;
• chemical stability (for a wide temperature interval and pHs ranging from 4.5 to 7.5);
• inertness;
• low degree of systemic toxicity;
• low frequency of sensitization;
• sufficient water solubility (enabling to obtain effective concentration);
• relatively safe use;
• low costs of production;
• no perceptible odor or taste:
• not causing changes in consistency or coloration of products [2,4,9,10].
Even though parabens have been used for more than 50 years and are generally considered as safe, several studies
concerning on the safety of parabens have been published [4,9–13]. Some research results on parabens claimed that
they can cause breast cancer or problems in male reproductive system, among other effects [2,14–16].
This review study aims to emphasize the safety of prolonged exposure to parabens used in cosmetics formulations,
as an issue of public health.
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©InternationalJournal of Medical Research and Pharmaceutical Sciences http://www.ijmprsjournal.com
Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
Fig 2. Selection process of the articles (identification, screening, eligibility and inclusion).
acid and rosemary extract. The use of "natural" preservatives has been advocated, including grapefruit seed extract
(GSE).Unfortunately, these preservatives are linked to allergic reactions, among other health problems, and there is
a lack of studies to determine their efficacy, safety and toxicology before widespread use [1,20–24]. As a result,
fully satisfactory substitutes have yet to be discovered [17].
4
©InternationalJournal of Medical Research and Pharmaceutical Sciences http://www.ijmprsjournal.com
Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
Compared with oral ingestion, uptake of parabens through the skin may thus result in higher serum and urine
concentrations of the parent compounds because they bypass hepatic degradation [18].
Others studies have shown parabens to be readily absorbed through animal skin but absorption kinetics combined
with lower rates of metabolism in human skin suggests that absorption through human skin is higher than through
animal skin. Several studies have now reported a positive correlation between the amount of one or more personal
care products used and levels of parabens measured in human blood or urine [8,9,14,18,27,29,34,35,38].
Higher levels of parabens in urine from women over men has been interpreted as related to a higher use of cosmetic
products in women. Likewise, higher levels of parabens in African Americans over Caucasians may also relate to
patterns of personal care product usage [27].
The estrogenic activity of some cosmetic products with parabens has recently been confirmed again by the
development of gynecomastia in 3 prepubertal boys as a consequence of the topical application of body oils [28].
Many patients sensitized to paraben-containing medications can wear cosmetics containing these ingredients with no
adverse effects. Clinical patch testing data available over the past 20 years demonstrate no significant change in the
overall portion of dermatitis patients that test positive for parabens. As reviewed by the Cosmetic Ingredient Review
(CIR) Expert Panel, the available acute, subchronic, and chronic toxicity tests, using a range of exposure routes,
demonstrate a low order of parabens' toxicity at concentrations that would be used in cosmetics [13].
Parabens are rarely irritating or sensitizing to normal human skin at concentrations used in cosmetics. Although
parabens do penetrate the stratum corneum, metabolism of parabens takes place within viable skin, which is likely to
result in only 1% unmetabolized parabens available for absorption into the body [13].
CONCLUSION
Preservatives are essential in cosmetics as they protect consumers from harmful pathogens that would otherwise
invade the creams and products people use on a daily basis. Without preservatives all cosmetics would have a very
short shelf life and would, in the most part, have to be stored in a fridge.
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©InternationalJournal of Medical Research and Pharmaceutical Sciences http://www.ijmprsjournal.com
Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
The group of chemicals known as parabens make up an important part of the preservatives which could be used in
cosmetics. However, it is crucial to ensure that preservatives guarantee the maximum degree of protection to people.
In the past years, the safety of parabens has been challenged. Concerns have been raised about the possible adverse
effects of the properties of parabens, as they are suspected to be potential endocrine disrupters that may contribute to
the development of breast cancer and the occurrence of male infertility.
The SCCS confirmed that methylparaben and ethylparaben are safe at the maximum authorized concentrations as
well as propylparaben and butylparaben. No concerns were raised on the safety of 4-Hydroxybenzoic acid and its
salts (calcium paraben, sodium paraben, potassium paraben).
In addition, the Commission banned the use of five other parabens in cosmetic products due to the lack of data
necessary for reassessment. As a result, for these compounds, the human risk cannot be evaluated. Therefore, more
studies should be performed in humans, with larger sample sizes and with special focus on the male reproductive
system and effects on the fetus that could occur during pregnancy or in later life.
Moreover, most of the toxicological studies for parabens were performed through the oral route, yet data on the
effect of parabens or their intact esters via dermal administration, which is also a major route of exposure, are
lacking and warrant thorough investigation. On the other hand, these studies should also address acute and long-term
multiple parabens exposure (i.e., combinations of parabens).
In summary, some available studies showed endocrine-disrupting effects of parabens at environmentally relevant
doses, which led several countries to already ban parabens, while others are working toward eliminating parabens in
cosmetics as a precautionary measure. Although numerous studies involving parabens have been conducted, there
are still significant gaps in knowledge regarding parabens exposure. For example, studies are designed under
specific in vitro and in vivo experimental protocols when they are not reflective of human effects mainly because
they fail to prove hormonal activity in humans and fail to consider the metabolism, degradation, and elimination of
parabens in human subjects. Limited yet suggestive data highlight the need for further research on these chemicals.
REFERENCES
[1] L.E. Maier, H.P. Lampel, T. Bhutani, S.E. Jacob, Hand Dermatitis: A Focus on Allergic Contact Dermatitis
to Biocides, Dermatol. Clin. 27 (2009) 251–264. doi:10.1016/j.det.2009.05.007.
[2] J.A. Ocaña-González, M. Villar-Navarro, M. Ramos-Payán, R. Fernández-Torres, M.A. Bello-López, New
developments in the extraction and determination of parabens in cosmetics and environmental samples. A
review, Anal. Chim. Acta. (2014). doi:10.1016/j.aca.2014.07.002.
[3] C. Piao, L. Chen, Y. Wang, A review of the extraction and chromatographic determination methods for the
analysis of parabens, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 969 (2014) 139–148.
doi:10.1016/j.jchromb.2014.08.015.
[4] D. Błędzka, J. Gromadzińska, W. Wąsowicz, Parabens. From environmental studies to human health.,
Environ. Int. 67 (2014) 27–42. doi:10.1016/j.envint.2014.02.007.
[5] M. Flasiński, M. Gawryś, M. Broniatowski, P. Wydro, Studies on the interactions between parabens and
lipid membrane components in monolayers at the air/aqueous solution interface, Biochim. Biophys. Acta -
Biomembr. (2016). doi:10.1016/j.bbamem.2016.01.002.
[6] C. Moreta, M.T. Tena, K. Kannan, Analytical method for the determination and a survey of parabens and
their derivatives in pharmaceuticals, Environ. Res. 142 (2015) 452–460. doi:10.1016/j.envres.2015.07.014.
[7] H.-S. Kang, M.-S. Kyung, A. Ko, J.-H. Park, M.-S. Hwang, J.-E. Kwon, J.-H. Suh, H.-S. Lee, G.I. Moon, J.-
H. Hong, I.G. Hwang, Urinary concentrations of parabens and their association with demographic factors:
A population-based cross-sectional study, Environ. Res. 146 (2016) 245–251.
doi:10.1016/j.envres.2015.12.032.
[8] S. El Hussein, P. Muret, M. Berard, S. Makki, P. Humbert, Assessment of principal parabens used in
cosmetics after their passage through human epidermis-dermis layers (ex-vivo study)., Exp. Dermatol. 16
(2007) 830–6. doi:10.1111/j.1600-0625.2007.00625.x.
[9] M.G. Soni, I.G. Carabin, G. a Burdock, Safety assessment of esters of p-hydroxybenzoic acid (parabens).,
Food Chem. Toxicol. 43 (2005) 985–1015. doi:10.1016/j.fct.2005.01.020.
[10] R.S. Tavares, F.C. Martins, P.J. Oliveira, J. Ramalho-Santos, F.P. Peixoto, Parabens in male infertility-Is
there a mitochondrial connection?, Reprod. Toxicol. 27 (2009) 1–7. doi:10.1016/j.reprotox.2008.10.002.
8
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Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
[11] S. Ishiwatari, T. Suzuki, T. Hitomi, T. Yoshino, S. Matsukuma, T. Tsuji, Effects of methyl paraben on skin
keratinocytes., J. Appl. Toxicol. 27 (2006) 1–9. doi:10.1002/jat.1176.
[12] J.J. Prusakiewicz, H.M. Harville, Y. Zhang, C. Ackermann, R.L. Voorman, Parabens inhibit human skin
estrogen sulfotransferase activity: possible link to paraben estrogenic effects., Toxicology. 232 (2007) 248–
56. doi:10.1016/j.tox.2007.01.010.
[13] Cosmetic Ingredient Review, Final amended report on the safety assessment of Methylparaben,
Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as
used in cosmetic products., Int. J. Toxicol. 27 Suppl 4 (2008) 1–82. doi:10.1080/10915810802548359.
[14] M.J. Kim, S.J. Kwack, S.K. Lim, Y.J. Kim, T.H. Roh, S.M. Choi, H.S. Kim, B.M. Lee, Toxicological
evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of
dermal exposure., Regul. Toxicol. Pharmacol. 73 (2015) 544–51. doi:10.1016/j.yrtph.2015.08.005.
[15] K. Yoon, S.J. Kwack, H.S. Kim, B.-M. Lee, Estrogenic endocrine-disrupting chemicals: molecular
mechanisms of actions on putative human diseases., J. Toxicol. Environ. Health. B. Crit. Rev. 17 (2014)
127–74. doi:10.1080/10937404.2014.882194.
[16] P.D. Darbre, A. Aljarrah, W.R. Miller, N.G. Coldham, M.J. Sauer, G.S. Pope, Concentrations of Parabens
in human breast tumours, J. Appl. Toxicol. 24 (2004) 5–13. doi:10.1002/jat.958.
[17] E. Karpuzoglu, S.D. Holladay, R.M. Gogal, Parabens: potential impact of low-affinity estrogen receptor
binding chemicals on human health., J. Toxicol. Environ. Health. B. Crit. Rev. 16 (2013) 321–35.
doi:10.1080/10937404.2013.809252.
[18] D. Sasseville, M. Alfalah, J.-P. Lacroix, “Parabenoia” Debunked, or “Who’s Afraid of Parabens?,”
Dermatitis. 26 (2015) 254–259. doi:10.1097/DER.0000000000000147.
[19] European Commission, Consumers: Commission improves safety of cosmetics, (2014).
http://europa.eu/rapid/press-release_IP-14-1051_en.htm (accessed April 26, 2016).
[20] E. Yim, K.L. Baquerizo Nole, A. Tosti, Contact dermatitis caused by preservatives., Dermat. Contact,
Atopic, Occup. Drug. 25 (2014) 215–31. doi:10.1097/DER.0000000000000061.
[21] D. Sasseville, Hypersensitivity to preservatives, Dermatol. Ther. 17 (2004) 251–263. doi:10.1111/j.1396-
0296.2004.04028.x.
[22] P. González-Muñoz, L. Conde-Salazar, S. Vañó-Galván, Allergic Contact Dermatitis Caused by Cosmetic
Products, Actas Dermo-Sifiliográficas (English Ed. 105 (2014) 822–832. doi:10.1016/j.adengl.2014.09.007.
[23] H. Brandin, O. Myrberg, T. Rundlöf, A.K. Arvidsson, G. Brenning, Adverse effects by artificial grapefruit
seed extract products in patients on warfarin therapy, Eur. J. Clin. Pharmacol. 63 (2007) 565–570.
doi:10.1007/s00228-007-0289-1.
[24] M.G. Kirchhof, G.C. De Gannes, The Health Controversies of Parabens, Ski. Ther. Lett. 18 (2013) 11–15.
[25] R. Golden, J. Gandy, G. Vollmer, A review of the endocrine activity of parabens and implications for
potential risks to human health., Crit. Rev. Toxicol. 35 (2005) 435–458. doi:10.1080/10408440490920104.
[26] P.D. Darbre, Underarm antiperspirants/deodorants and breast cancer, Breast Cancer Res. BCR. 11 Suppl 3
(2009) S5. doi:10.1186/bcr2424.
[27] P.D. Darbre, P.W. Harvey, Parabens can enable hallmarks and characteristics of cancer in human breast
epithelial cells: A review of the literature with reference to new exposure data and regulatory status, J. Appl.
Toxicol. 34 (2014) 925–938. doi:10.1002/jat.3027.
[28] E. Konduracka, K. Krzemieniecki, G. Gajos, Relationship between everyday use cosmetics and female
breast cancer, Pol. Arch. Med. Wewn. 124 (2014) 264–269.
[29] N.R. Janjua, G.K. Mortensen, A.M. Andersson, B. Kongshoj, N.E. Skakkebæk, H.C. Wulf, Systemic uptake of
diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and
reproductive and thyroid hormone levels in humans, Environ. Sci. Technol. 41 (2007) 5564–5570.
doi:10.1021/es0628755.
[30] F. Castelain, M. Castelain, Parabens: a real hazard or a scare story?, Eur. J. Dermatol. 22 (2012) 723–7.
doi:10.1684/ejd.2012.1835.
[31] K.T. De Renzy-Martin, H. Frederiksen, J.S. Christensen, H.B. Kyhl, A.M. Andersson, S. Husby, T. Barington,
K.M. Main, T.K. Jensen, Current exposure of 200 pregnant Danish women to phthalates, parabens and
phenols, Reproduction. 147 (2014) 443–453. doi:10.1530/REP-13-0461.
[32] M.T. Guerra, M. Sanabria, S.V. Cagliarani, G.A.A. Leite, C. dos S. Borges, W. De Grava Kempinas, Long-
term effects of in utero and lactational exposure to butyl paraben in female rats, Environ. Toxicol. (2016).
9
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Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
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doi:10.1002/tox.22277.
[33] C. V Towers, P.D. Terry, D. Lewis, B. Howard, W. Chambers, C. Armistead, B. Weitz, S. Porter, C.J.
Borman, R.C.M. Kennedy, J. Chen, Transplacental passage of antimicrobial paraben preservatives., J. Expo.
Sci. Environ. Epidemiol. 25 (2015) 604–607. doi:10.1038/jes.2015.27.
[34] T.M. Sandanger, S. Huber, M.K. Moe, T. Braathen, H. Leknes, E. Lund, Plasma concentrations of parabens
in postmenopausal women and self-reported use of personal care products: the NOWAC postgenome study,
J. Expo. Sci. Environ. Epidemiol. 21 (2011) 595–600. doi:10.1038/jes.2011.22.
[35] J.M. Braun, A.C. Just, P.L. Williams, K.W. Smith, A.M. Calafat, R. Hauser, Personal care product use and
urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility
clinic., J. Expo. Sci. Environ. Epidemiol. 24 (2014) 459–66. doi:10.1038/jes.2013.69.
[36] C. Philippat, D. Bennett, A.M. Calafat, I.H. Picciotto, Exposure to select phthalates and phenols through
use of personal care products among Californian adults and their children, Environ. Res. 140 (2015) 369–
376. doi:10.1016/j.envres.2015.04.009.
[37] H.J. Ahn, K.C. Choi, E.B. Jeung, Effect of parabens on the disruption of ovarian follicle maturation in a
neonatal female rat model., Reprod. Fertil. Dev. 24 (2011) 178. doi:10.1071/RDv24n1Ab131.
[38] K.W. Smith, I. Souter, I. Dimitriadis, S. Ehrlich, P.L. Williams, A.M. Calafat, R. Hauser, Urinary Paraben
Concentrations and Ovarian Aging among Women from a Fertility Center, Environ. Health Perspect. 121
(2013) 11–12.
[39] European Commission - SCCP, Opinion on Parabens, (2011) 1–50. doi:10.2772/30176.
[40] European Commission, Extended Opinion on the Safety Evaluation of Parabens, (2005) 1–39.
http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_019.pdf.
[41] L. Mathiesen, G. Zuri, M.H. Andersen, L.E. Knudsen, A Proposed Study on the Transplacental Transport of
Parabens in the Human Placental Perfusion Model, (2013) 473–482.
[42] European Commission, Amending Annexes II and V to Regulation (EC) No 1223/2009 of the European
Parliament and of the Council on cosmetic products, Off. J. Eur. Union. (2014). http://eur-
lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32014R0358&from=EN (accessed June 16, 2016).
[43] European Commission - SCCP, Opinion on Parabens, (2008).
http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_138.pdf.
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Open Access Journal
International Journal of Medical Research and Pharmaceutical Sciences
Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109
AUTHOR BIBLIOGRAPHY
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