Parabens Paradoxes in Cosmetic Formulations: A Review: August 2016

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PARABENS PARADOXES IN COSMETIC FORMULATIONS: A REVIEW

Article · August 2016


DOI: 10.5281/zenodo.61076

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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

PARABENS PARADOXES IN COSMETIC FORMULATIONS: A REVIEW


Francisco Ana*1 and Fonseca Ana Paula2
*1
Department of Pharmacy, Polytechnic Institute of Coimbra, ESTeSC-Coimbra Health School, Coimbra
Portugal
2
Department of Pharmacy, Polytechnic Institute of Coimbra, ESTeSC-Coimbra Health School, Coimbra
Portugal

Corresponding author: Fonseca Ana Paula

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.

In this paper, is reviewed parabens usage, characteristics and legislation associated, as


well as hazards to human health. This study also aims to determine the safety of
prolonged exposure to parabens used in cosmetics.

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].

Fig 1. Chemical structure of paraben and alkyl esters of para-hydroxybenzoic acid.

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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

This family of chemicals mainly includes methyl-paraben, ethylparaben, n-propylparaben, iso-propylparaben, n-


butylparaben, iso-butylparaben, benzylparaben, and heptylparaben and their respective sodium salts (Table 1) [2,3].

Table 1. Physical and chemical characteristics of parabens (PB).[2,3,4].


Characteristic MePB EtPB PrPB BuPB BePB
Chemical formula C8H8O3 C9H10O3 C10H12O3 C11H14O3 C14H12O3
Molecular weight (g/mol) 152.16 166.18 180.21 194.23 228.25
pKa 8.17 8.22 8.35 8.37 -
Log octanol–water partition coefficients (log
1.66 2.19 2.71 3.24 3.56
Kow)
Solubility in water at 25 °C (g/100 ml) 2.00 0.86 0.30 0.15 0.05

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.

MATERIAL AND METHODS


A review search of the literature was undertaken between January 1990 to May 2016 using the following
combinations of terms: Parabens, Parabens toxicity, Parabens safety, Parabens review and Parabens cosmetics.
Articles in English, Portuguese and Spanish were included. Electronic databases were searched in PubMed, Nature
Reviews, ScienceDirect, Elsevier, and b-on. Manual searches of bibliographies were also conducted to identify
additional pertinent studies. All of the studies were selected, analyzed and classified according to their quality
(Figure 2).

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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).

RECOMMENDATIONS AND INTERNATIONAL REGULATION


Current regulations on parabens usage differ by country [17]. According to European Union (EU) Council Directive,
the allowable content of parabens in cosmetic products is a maximum concentration of 0.4% for each ester and 0.8%
for total mixtures of esters [4,10,17].
However, in 2011, the Danish government decided to introduce additional restrictions, banning the use of some
parabens (propyl-, isopropyl-, butyl- and isobutyl-parabens) in personal care products intended for children younger
than 3 years. This led the EU Scientific Committee on Consumer Safety (SCCS) to reevaluate the subject and
suggest that allowed concentrations remain unchanged for methylparaben and ethylparaben but that the sum of
individual concentrations of propylparaben and butylparaben in finished products should be limited to 0.19% [4,18].
On the basis of this report, the EU Commission amended the Directive and, in 2014, banned isopropylparaben,
isobutylparaben, phenylparaben, benzylparaben, and pentylparaben. In 2015, April 16, the Commission limited
the maximum concentration of two preservatives, propylparaben and butylparaben, from currently allowed limit of
0.4% when used individually and 0.8% when mixed with other esters, to 0.14%, when used individually or together.
They are also banned from leave-on products designed for the nappy area of young children below the age of three
since existing skin irritation and occlusion may allow increased penetration than intact skin [18,19].
The governmental units of the United States, Food and Drug Administration (FDA) and Canada (Health Canada),
are not authorized to approve cosmetic ingredients under the Federal Food, Drug and Cosmetic Act, but an industry-
sponsored organization, the CIR (Cosmetic Ingredient Review) have recommended the same threshold for parabens
as that of EU [4,20].
On the other hand, the international certification agencies ECOCERT (France), BDIH (Germany), NaTrue
(Belgium), Soil Association (United Kingdom), ICEA (Italy), and BIOCOSC (Switzerland) agreed with the EU and
Danish EPA positions, and will no longer certify products containing parabens. The Professional Association for
Natural, Ecological and Organic cosmetics, CosmeBio (cosmebio.org), has also banned the use of parabens in
cosmetic products since 2002 as “a precautionary principle and out of concern for the health of consumers” [17].
Although no ban on paraben use currently exists in the United States, a number of prominent cosmetic
manufacturers are starting to migrate away from parabens and instead focus on alternative preservatives or decrease
the amount of parabens in their products due to increasing consumer concerns [17]. Some other commonly used
preservatives include formaldehyde, quaternium-15, imidazolidinyl urea, diazolidinyl urea and dimethyloldimethyl
hydantoin. Other natural preservatives include thymol, cinnamaldehyde, allyl isothiocyanate, citric acid, ascorbic
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Open Access Journal
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Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109

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].

BIOCHEMICAL AND TOXICOLOGICAL DATA


Pharmacokinetics
Animal studies have shown that parabens are rapidly absorbed, metabolized and excreted [10]. Metabolism of
parabens was studied by treating rats with 100mg of methyl- or propylparaben orally. After oral administration in
rats, parabens were rapidly absorbed from the gastrointestinal tract and blood [4,10].
Both oral and dermal administrations most likely lead to hydrolysis of parabens by non-specific esterase’s, widely
distributed in the body and abundant at sites of entry such as skin, subcutaneous fat tissue and digestive system. The
main product of the hydrolysis of parabens is p-hydroxybenzoic acid [4].
Because most paraben-containing products are topically applied to the skin, dermal absorption is particularly
important. The skin is not an impenetrable barrier, and depending on the specific paraben (i.e., Kow) and the type of
formulation (e.g., aqueous or lipid), some fraction of an applied dose may be absorbed and enter the systemic
circulation [4].
In an in vitro study using human epidermal membranes, the ability of different vehicles (acetone, ethanol or
ointment) to affect the permeability of four parabens (methyl, ethyl, propyl, and butyl) with or without occlusion
was determined. While the skin permeability of the parabens alone was not measured, the results demonstrated that
different vehicles, particularly in conjunction with occlusion, enhanced skin permeability. For example, the
percentages of butylparaben in ointment, acetone, or ethanol penetrating the skin over a period of 10 h were 39%,
44%, and 57%. These results suggest that parabens formulated into certain skin-care products can penetrate the skin.
The determinants of actual dermal permeability are likely to be a complex interaction of individual parabens,
partition coefficient (i.e., log Kow), and the presence of other ingredients in a particular product. It was also
demonstrated that permeability increased as a function of n-octanol/water partition coefficients (Kow) in the order
butyl > propyl > ethyl > methyl [4,25].
Efficiency and pattern of hydrolysis of parabens in the organism vary considerably depending on alkyl chain length
and tissue. Though human skin contains carboxylesterase isoforms, which are able to metabolize parabens to pHBA,
esterase’s levels and activities could be insufficient for a complete hydrolysis of dermally applied parabens.
Laboratory tests on rats revealed that over 50% of the paraben dose was unabsorbed following dermal application.
Interestingly, in vitro studies revealed that parabens undergo much slower hydrolysis in human skin than in human
liver, rat liver and rat skin [4].
Following dermal administration, part of MePB does not undergo hydrolysis and therefore a certain amount of
unmetabolized compound may remain systemically available. Additionally, skin damage can result in an increase of
MePB absorption rate. It is estimated that up to 923 μg/kg bw/day of unhydrolized MePB can become systemically
available, following application of leave-on emulsion containing PB to damaged skin [4].
In relation to excretion of parabens and their metabolites, orally or subcutaneously administered parabens were
predominantly excreted in the urine, mainly during the first 24 h. However, 2% of applied doses were retained in the
tissues and carcasses, while less than 4% were removed with the feces. Parabens and their hydrolysates are excreted
in urine as free form or glycine, glucuronide and sulfate conjugates [4].

TOXICITY AND ADVERSE EFFECTS OF PARABENS


Dermal absorption
An extensive number of cosmetic products are applied topically, often multiple times a day. These products are not
rinsed off but left on the skin, allowing for continuous dermal exposure, and therefore over a long period may result
in absorption and accumulation into underlying tissues [26,27].
Previous reviews have suggested that dermal rather than oral exposure is more likely to have resulted in the
parabens entering human tissue, and Janjua et al in 2007 demonstrated that parabens can be rapidly absorbed
through the skin into the human body even from a single dose of a body care product and long-term exposure results
in the accumulation of these chemicals [27–29].

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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].

Parabens and contact allergy


Parabens are practically non-irritating and non-sensitizing in the human population with normal skin. The first case
of paraben contact allergy was reported in 1940 by Bonnevie [30].
Allergic contact dermatitis from paraben is low, ranging from 0 to 4.2% [10]. Their capacity to act as sensitizers
when used in cosmetics (applied to healthy skin) is low, at around 1%, and in fact they have one of the lowest rates
of sensitization of all preservatives [22]. However, the percentage can be significantly increased in patients with
previously damaged or broken skin (for instance leg ulcers) [10,30]. A recent multicenter study in patients suffering
from chronic leg ulcers showed a percentage of sensitized patients to parabens of 3.1% [30].

Cancer and the use of paraben-containing cosmetics


In 2004, Darbre et al. published an article mentioning a possible link between the use of cosmetic products
containing parabens and the presence of such preservatives in breast cancer tissues [30]. They suggested that cream
or lotion-based cosmetics, containing preservatives such as parabens, used on the underarm, chest, or breast area
may be increasing breast cancer incidence in women [17].
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. For example, in a related study, butylparaben was applied via a topical
cream and was shortly thereafter detected in the blood of the human subjects. On the other hand, urine
concentrations of methyl- and propylparaben were higher in adolescent and young women compared to males,
which again correlated with increased use of personal care products and cosmetics by women [17].
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 [17]. For that reason, the measurement of intact esters in
human breast cancer tissue sparked an international debate in 2004 due to estrogenic properties of parabens.
Furthermore, the incidence of about 60% of breast cancers in the upper outer quadrant of the breast suggested that
there was a relationship between the chemicals applied underarm and the development of breast cancer [28].
Later, another study has actually shown that this MCF7 human breast cancer cell line is stimulated by ethylparabens
and butylparabens at concentrations respectively 1,000 and 10,000 times higher than the 17 ß-oestradiol
concentration but that the gene expression was different with parabens and oestrogens and that consequences to the
cell lines are therefore not identical [30].
The more recent and larger set of measurements of paraben esters in 160 samples of human breast tissue taken from
four serial locations across the breast from axilla to sternum from 40 patients undergoing mastectomy for breast
cancer has confirmed widespread distribution of parabens both across individual breasts and between women. One
or more paraben ester was detected in 158 of 160 of the tissue samples and 96 of 160 contained all five of the esters
measured (methylparaben, ethylparaben, n-propylparaben, n-butylparaben and isobutylparaben). In line with
measurements in other body tissues, methylparaben and propylparaben were the two parabens detected at highest
levels. Cell culture studies demonstrated that proliferation of human breast cancer cells could be increased by
exposure to these five parabens either alone or in combination at some of the measured breast tissue concentrations.
Forty-three of 160 human breast tissue samples contained at least one paraben at a concentration above that needed
for an observed effect on proliferation (lowest observed effect concentration) [27].
On the other hand, another study on the population of breast cancer patients reported that patients who used more
antiperspirant products were diagnosed with breast cancer at an earlier age. This study suggested a dose–response
relationship to chemical exposure and sensitivity at a younger age, consistent with the patterns of breast cancer
development, but it did not exclude other risk factors or consider the possibility that cosmetic use was simply higher
in younger women [28].
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©InternationalJournal of Medical Research and Pharmaceutical Sciences http://www.ijmprsjournal.com
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Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109

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].

Parabens and pregnancy


Exposure of pregnant women is of particular concern because of the potential health impact on the vulnerable fetus,
in which exposure may inflict lifelong adverse health effects [31].
It has been already demonstrated that parabens are able to cross the placental barrier and reach the developing
fetuses and the newborn through maternal milk [31,32]. Thus, a number of these preservatives measured in maternal
urine, serum and breast milk have also been found in amniotic fluid, cord blood and meconium [31,33]. Studies have
also suggested that use of personal care products are an important source of exposure to parabens in women and
children [34–36].
A recent study which involved a total of 50 pregnant patients, demonstrated that 47 were found to have
methylparaben in their blood, as well as in the cords bloods samples. For butylparaben, only 4 mothers showed
detectable levels, whereas 8 cord blood samples were positive [33].
This study confirms the presence of methylparaben and butylparaben in maternal blood and, indeed, cross the
placenta and enter fetal circulation. Further research is needed to determine what products are used by pregnant
women that contain these preservatives and any possible long-term effects in the growth and development of
exposed children [33].

Effects on Reproductive system


Although limited in scope and number, some studies demonstrated parabens effects on male reproductive organs,
testosterone levels, and sperm production [17]. The issue of paraben effects on human reproductive toxicity was
addressed by Glander et al. (1984), who studied primary microbiological contamination in human ejaculates, and
also secondary contamination after cryopreservation using methylparaben. These authors found that not only
methylparaben reduced microbiological contamination of the cryoprotective medium, but also decreased human
sperm motility [10].
Due to the important role of mitochondria in testis metabolism, it is logical to assume that parabens may also
interfere with mitochondrial energetics and thus disturb sperm function. Although no data exist on direct effects of
parabens on testis mitochondria, it seems possible that tissue accumulation of such compounds would lead to
toxicological relevant concentrations that would disturb mitochondrial bioenergetics. In fact, preliminary results
indicate that several parabens present direct toxicity on isolated testis mitochondria at low concentrations [10].
A study concerning the effects of maternal exposure to butylparaben during gestation and lactation periods
demonstrated that this exposure may adversely affect reproductive organ development of male F1 progeny. Also,
and more importantly, male reproductive organ weights (testes, seminal vesicles and prostate glands), sperm counts
and sperm motility were adversely affected. Vaginal opening also occurred earlier in female offspring, compared
with the control group [10].
Methyl and propylparaben treatment of neonatal female rats produced impaired postnatal ovarian follicle
development [17,37]. Prepubertal dosing of female SD rats with methyl- or isopropylparaben (1000 mg/kg bw/d but
not 250 mg/kg/d) from postnatal days 21–40 was also associated with endocrine changes, markedly delaying the day
of vaginal opening, decreasing serum estradiol levels, and shortening the estrous cycle length. These female rats also
displayed pathology in several endocrine organs that included ovaries, adrenal glands, thyroid glands, liver, and
kidneys [17].
Finally, a study which has assessed female reproductive health effects in relation to paraben exposure, provided
evidence suggesting that exposure to parabens may lead to diminished ovarian reserve and contribute to ovarian
aging among women [38].

SAFETY EVALUATION OF PARABENS


Parabens Sensitization
Parabens are practically nonirritating and nosensitizing in the population with normal skin. Paraben sensitization has
occurred and continues to be reported in the case literature, but principally when exposure involves damaged or
broken skin. Even when patients with chronic dermatitis are patch-tested to a parabens mix, parabens generally
induce sensitization in less than 4% of such individuals [13].
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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

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].

Paraben-containing cosmetics and cancer


Harvey and Darbre (2004) suggested that cream- or lotion-based cosmetics, containing preservatives such as
parabens, used on the underarm, chest, or breast area may be increasing breast cancer incidence in women [17].
However, in Darbre’s study, no clear link was established between parabens and breast cancer [30,39]. In order to
reach a true scientific conclusion, Darbre should have identified the route by which parabens enter the body (it
might for instance have been from food or medicines taken by the patients); there was no information provided
about the background of the patients, location and type of the tumor (ie, estrogen receptor positivity status), use of
cosmetics, and so forth; absence of control tissue; and most importantly; blanks (no tissue) were also positive for
parabens, suggesting contamination during the analytical process. Finally, this study was very small with only
twenty tumour samples [18,30].
Darbre and Harvey's review article (2008) repeats the arguments that have all been refuted, and it does not add new
data nor adds any conclusive evidence [39].
In 2012, Barr et al measured paraben levels in different regions of healthy breast tissue (without cancer). Except
propyloparaben (which was observed at higher levels in the upper outer quadrant compared with other breast
regions), the other parabens had similar concentrations in different breast regions [28]. Interestingly, 7 of these 40
patients had never used underarm cosmetics, suggesting they were exposed to parabens from other sources [17].

Parabens and reproductive system


Methyl, ethyl, propyl and butylparaben have been examined for effects on the reproductive organs [40]. Previous
studies have shown that methylparaben was nonteratogenic in rabbits, rats, mice, and hamsters, and ethylparaben
was nonteratogenic in rats. Parabens, even at levels that produce maternal toxicity, do not produce fetal anomalies in
animal studies [13].
In 2004, Cantox Health Sciences International prepared an assessment of the endocrine disrupting/estrogenic
potential of parabens. This assessment noted that parabens do not have genotoxic, carcinogenic, or teratogenic
potential and are rapidly hydrolyzed to p-hydroxybenzoic acid and excreted [13].
Decreased sperm numbers and activity were reported in female rats given butylparaben by subcutaneous injection at
100 or 200 mg/kg day(-1), but there were no abnormalities in the reproductive organs [13]. Male neonatal Wistar
rats were subjected to subcutaneous injection with butyl paraben at 2 mg/kg bw/day on postnatal days 2 to 18
showed no detectable effects on any reproductive parameter [40].
In another study it was revealed that pregnant and lactating dams presented no toxicity signs or body weight loss
during butylparaben treatment and the number of live delivered pups and pups weight were also similar among
experimental groups, indicating no toxic effects of parabens on the offspring and dams during gestation. In
agreement, on other study showed that butylparaben, even in higher doses (400 mg/kg), did not caused alterations on
maternal body weight, fetal weight, and number of fetuses [32].
Propylparaben and butylparaben were also administered subcutaneously at doses of up to 35 mg/d to pregnant mice
during days 1 to 4 of pregnancy and this study found no adverse reproductive or other effects in mice, whereas the
positive control substance, 17α-estradiol, produced the expected termination of pregnancy [18].

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.

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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

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Volume 3 (Issue 8) : August 2016 ISSN: 2394-9414
DOI: 10.5281/zenodo.61076 Impact Factor- 3.109

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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

AUTHOR BIBLIOGRAPHY

Ana Patrícia Domingues Francisco


Ana Francisco is a pharmacy student in Escola Superior de
Tecnologia da Saúde de Coimbra - Coimbra Health School at
Coimbra, Portugal.
Email: ana9francisco@gmail.com

Ana Paula Gomes Fonseca


Professor of Pharmacy Departament
GIAF/ Investigation Applied in Pharmacy Coordinator
Pharmacy Master Coordinator
Pedagogic Council President
Email: paula_fonseca@estescoimbra.pt

11
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