Written by Renata Filiaci, MSHW

Abstract

Over the last 100 years, parabens have been used in cosmetic products as a group of preservatives. The purpose of this study was to assess the negative effects parabens have on the endocrine system. The U.S. Food and Drug Administration presented this man-made chemical additive as prevention against mold and unwanted bacteria in common cosmetic and household products, such as makeup, moisturizers, cleaning agents, hair care products, deodorant, personal hygiene products, pharmaceuticals, food, and shaving products. Since detecting parabens in environmental settings, scientists have raised concern about the potential amount in the human body. In this review, the assessment of parabens as an endocrine-disrupting agent is evaluated through multiple human and animal studies. Each study presented how parabens affect specific endocrine organs in the subjects tested and the potential repercussions of absorbing the chemical for an extended period of time; urine samples, among other samples, have been found, in both men and women, to have an increased amount of parabens in it.

Introduction

Parabens are found in anything from food to cosmetic products to household products which leads to an estimated 76 milligrams of exposure per day showing up in urine, breast milk, serum, and seminal fluids (Kirchhof & de Gannes, 2012). Parabens have many names that can be located on the ingredient label of an abundance of household products. The most commonly used parabens are methyl, propyl, butyl, ethyl, and heptyl; however, can also be seen with the pseudonym of 4-hydroxyl benzoate or fragrance. Parabens are found in over 13,200 formulations because they formulate well as for they are small colorless crystals with no odor (Boyer & Becker, 2017). In 1984, a study was conducted by the Cosmetic Ingredient Review to show that parabens were safe. Many reports followed still concluding the safety of parabens (Boyer & Becker, 2017). Under the Food and Drug Administration (FDA), cosmetics are not regulated when it comes to additives or preservatives, except for color additives. The FDA and Center of Disease Control and Prevention believe that there is not enough evidence to prove that there are adverse effects on the endocrine system though studies have shown parabens in urine indicating exposure (U.S. Food and Drug Administration, 2017) (Center of Disease Control and Prevention, 2010).  In 2014, the European Commissioner banned the use of five parabens, isopropylparaben, isobutylparaben, phenylparaben, benzylparaben, and pentylparaben, as well as regulated the use of propyl and benzyl in cosmetic products (European Commissions, 2014).

The endocrine system is made up of organs and endocrine glands that are widespread throughout the body. This system influences metabolic activity using hormones which are chemical messengers secreted by cells into the extracellular fluids; these, in turn, travel through the blood regulating the metabolic function of other cells (Hoehn & Marieb, 2016). The endocrine glands include the pituitary, thyroid, parathyroid, adrenal, and pineal glands which produce hormones and lack ducts; these glands release their hormones into the surrounding tissues. The release of hormones is regulated by a type of negative feedback mechanism; internal and external stimuli trigger these glands to secrete hormones to bring the body back to a proper balance (Hoehn & Marieb, 2016). The pancreas, gonads, and placenta, are all organs of the endocrine system. The pancreas is filled with many cells that act as tiny fuel sensors which regulate the secretion of glucagon and insulin appropriately during fasting and fed states. The gonads of both the male and the female produce sex hormones such as, estrogen and progesterone in the female and testosterone in the male, which are responsible for the maturation of the reproductive organs. The placenta acts as a temporary endocrine organ needed to influence and regulate pregnancy by sustaining the fetus and secreting steroid and protein hormones. These are all required to work correctly for the maintaining of homeostasis throughout the body (Hoehn, Marieb, 2016). Specific parabens, butyl and propyl, mimic properties of estrogen as well as increase and interfere with particular hormone release activity, this could play a part in the development and growth of certain cancers and diseases (Faniband, Lindh, & Jonsson, 2013). The purpose of this study is to assess whether parabens have an adverse effect on the endocrine system.

Results

The Cosmetic Ingredient Review (CIR) performed studies throughout years on rats and rabbits to conclude if parabens hurt the body. The procedures and data acquired included, UV absorption spectrum in animals, data detailing the possible presence of impurities, subchronic feeding 90-day study in rats, mutagenicity studies and in vitro assays for genotoxicity, and eye irritation study at the concentration of use. The CIR found little to no negative correlation between parabens and the endocrine system (Boyer & Becker, 2017).

In a study performed by Sun, L et al. (2016), they administered methyl and ethyl parabens orally in Sprague-Dawley rats for three days. It is believed that the average daily dose is between 0 to 10 mg per body weight which was used as a reference when administering it to the rats. The table showed four experiments using a control with each method, substance given, and dose amount per administration. The amount of dosage ranged between .8, 4, and 20 ml. After gathering the results, they found that at high doses methyl and ethyl both increased uterine weight in the rats. Evidence also shows that estrogen response biomarkers are triggered and increased from interaction with parabens; parabens have been found to mimic estrogenic properties (Sun, L et al., 2016).

The authors, Boberg et al. (2016), assessed the effects butylparaben had on pregnant Wistar rats and their neonatal pups, a study carried out at the DTU National Food Institute. The scientists performing the research regulated the environment, as well as the rats, were fed a standard diet which kept the results distinguishable. The rats were given 0, 10, 100, or 500 mg of butylparaben orally from gestation to pup day 22. In male pups, sperm count and protein Cyp19a1 were very low after each dose of butylparaben was distributed. Also discovered was reduced prostate weight and decreased testosterone levels. In female pups, increased mammary growth and terminal end buds were noted (Boberg et al., 2016).

The research executed by Brown (2016), used zebrafish embryos to determine whether butylparaben affects pancreatic function. The pancreas of a zebrafish embryo is structurally similar to a human yet it is in vivo and see-through, making it easier to develop research. Researchers maintained a consistent environment by controlling the lightness, darkness, and temperatures for the embryos post-fertilization. They were separated into groups, exposed to specific amounts of butylparaben, and imaged within 3, 4, 5, and 7 days post fertilization. Differing levels of parabens received different calculations regarding developmental deformities and pancreatic malformation; however, the more parabens the embryos were exposed to, development was noticed to be irregular. There were five developmental deformities were observed which were fluid retention surrounding the heart and intestinal lining, brain and spinal malformations, and decreased yolk sac. Also noted was the increase of insulin-resistant hormones once exposed to butylparaben (Brown, 2016).

Urine concentrations containing methyl and propyl parabens were gathered from 2,548 participants of all age and races in a study performed by Calafat et al. (2010). A questionnaire was given to determine age group, weight, race, and household income. The urine of each participant was shipped, and the temperature was maintained before paraben levels were extracted. In general, adults had more significant levels of parabens in their urine than children. It was determined that women have higher levels than both men and children. Women of higher income had greater levels of parabens than other demographics; however, non-Hispanic black women had higher levels of methyl parabens than non-Hispanic white women and Mexicans (Calafat et al., 2010).

In a study performed by Meeker et al. (2011), it shows the correlation between urine paraben concentrations and reproductive health in men. Sub-fertile male participants were chosen between the ages of 18-55 years old. Throughout three different clinical visits, urine, semen, and blood samples were taken and measured to find the amount of methyl, propyl, and butylparaben levels. Urine concentrations were highest for methylparaben yet the most significant correlation was between butylparaben and sperm DNA damage, though more studies will need to be performed. Potential oxidative stress could have been caused by strong paraben levels, which can lead to further endocrine complications (Meeker et al., 2011) (Betteridge, 2000).

Discussion

The research findings support that parabens have a negative effect on the human body and the endocrine system at high amounts of exposure. However, the tests performed by the CIR showed no immediate negative response because the tests were executed in a 90 day period. If they were to continue an examination, they could potentially see the adverse effects on the endocrine system. The FDA and CIR are also government regulated and funded associations which present a possible limitation to the results.

In other studies, it was concluded that women have elevated amounts parabens in their system potentially due to type of hygienic, cosmetic, and cleaning products. Women typically use and buy more hygienic and cosmetic products, which tend to have some form of paraben. Non-Hispanic black women were found to have elevated levels of methylparaben which could be due to specific type of products marketed to that demographic. It has been shown that parabens have estrogenic and antiandrogenic properties which act on estrogen pathways in the reproductive and endocrine system of men and women (Faniband, Lindh, & Jonsson, 2013). Women are developing breast cancer at a rapid rate; breast cancer is now the most commonly reported cancer in women (Marchese, 2010). Poor newborn mammary development and terminal end bud growth is seen to be a problem in female rat pups due to paraben exposure, which is a clear indication of breast cancer development in adults.

Exposure to parabens while pregnant or in early development could lead to reproductive and fetal development issues later in life as seen in zebrafish embryos, pregnant rats, and newborn rat pups. In men, sperm DNA damage could potentially result in subfertility or infertility. Low development of the protein Cyp19a1 in the neonatal stage of life can lead to low sperm count in adult males. Also noted was elevated levels of estrogen in the newborn rat which can cause potential prostate cancer in adults. However, oxidative stress was observed as likely cause of sperm damage, though that is the body reacting to toxins entering the system; oxidative stress and exposure to parabens could be connected because parabens are chemical toxins.

The pancreas produces insulin; butylparaben initiates hormones such as leptin to become overactive which causes insulin resistance increases the risk of diabetes. Since parabens are in most household products and used as a preservative in food, could an over absorption of parabens as well as poor diet choices related to too many preservatives contribute to the rise of diabetes? Not only is oxidative stress linked to sperm damage, but it can also initiate pancreatic malfunction resulting in diabetes, which hypothetically relates to paraben absorption (Brown, 2016).

However, there are limitations in these studies because of lack of consistency within subjects, lack of evidence and research, type of subject, as well as factoring in other toxic entities and chemicals that reside in household products or our environment. Using animal subjects, such as rats, differ from human subjects because of metabolic rate.

Conclusion

The research findings support that parabens have a negative effect on the human body and the endocrine system at high amounts of exposure. Parabens are in most household and cosmetic products. Unless a person is consciously searching to find “paraben-free” products, they will most likely have a form of paraben in a product. While tests provided by the CIR have shown that low dosages cause no immediate harm to the human body, what about people who are exposed to parabens after using multiple products consistently for years, specifically women and their use of cosmetic and hygienic products? Though women have been seen to have higher amounts of parabens, there is a connection between butylparaben and reproductive issues in men. With correlations regarding high amounts of methyl, propyl, and butyl in both women and men’s urine, diet comes into question, as well, considering the number of paraben preservatives in food. However, lack of studies and proof of limitation is solidifying the notion that parabens don’t have to be regulated or prohibited in the United States even though Europe has already decided to restrict the use.

References

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