Parabens - Dr. Michelle Lam Power Point & Script

Parabens

Preservatives are required in many skincare products, cosmetics, and pharmaceutical products to prevent the growth of microbes that can contaminate products. Common preservatives used are parabens which are aliphatic esters. Other preservatives include sodium benzoate, phenoxyethanol, and formaldehyde. Parabens include methyl-, ethyl-, propyl-, and butylparaben. They are mainly used topically in cosmetics and skincare, and can be used in different formulations of pharmaceuticals. There are concerns that they are capable of disrupting the endocrine system and may have obesogenic properties. They are estrogenic and antiandrogenic. Parabens have wide antimicrobial activity, including activity against gram positive bacteria, fungi, and molds. The length of the aliphatic chain affects the antimicrobial activity and the solubility of the paraben. Parabens have been discovered in cancerous breast tissue which led to further investigation in the body. They have been found in urine, blood, semen, adipose tissue, placenta, amniotic fluid, and breast milk (Petric, Z., Ružić, J., & Žuntar, I.). Studies have shown that over 90% of parabens go through biotransformation and are excreted in the urine as glucuronide and sulfate conjugates.

It is being investigated whether parabens are a potential endocrine disrupting chemical and its implications in puberty. The age for puberty and menarche have decreased in the last century. There have been possible links to reproductive cancers, metabolic dysregulation, and changes in mental health with the younger age of menarche. Puberty is a period of time that involves many hormones and endocrine disrupting chemicals can have effects on health. Important hormones at this time include gonadotropin releasing hormone, follicle stimulating hormone, luteinizing hormone, dehydroepiandrosterone, and estrogens (Petric, Z., Ružić, J., & Žuntar, I.). There have not been many studies on parabens and their effect on puberty. The information that exists on parabens shows that there is potential for earlier onset of thelarche, pubarche, and menarche (Rivera-Núñez, Z. et al.). The evidence for these results are mixed and there is a need for further investigation. Although the connection between parabens and age of puberty was weak, it is still an important area of focus since there are many compounding factors that contribute as well during that time.

Parabens have a potential effect on obesity during windows of development. Parabens are capable of activating the peroxisome proliferator-activated receptors (PPARs) and glucocorticoid receptor (GR) exhibiting their adipogenic effects. It is believed that parabens could affect adiposity in children when exposed prenatally (Xu. X. et al). It is recommended for pregnant women to try to limit their use of products with paraben content. Many of these studies were not initially conducted to study parabens, thus the results of these studies may not be accurate and further studies are required.

During time periods like pregnancy and adolescence, there are many hormone fluctuations. These are times where parabens and other endocrine disrupting chemicals can also have an effect on changing hormones. The presence of parabens in different tissues gives reason to believe that they can negatively impact these areas. It is important that more studies are performed with parabens as the focus to determine whether they have an impact that is worth limiting their use.

Resources:

Petric, Z., Ružić, J., & Žuntar, I. (2021). The controversies of parabens - an overview nowadays. Acta pharmaceutica (Zagreb, Croatia), 71(1), 17–32. https://doi.org/10.2478/acph-2021-0001

Rivera-Núñez, Z., Kinkade, C. W., Zhang, Y., Rockson, A., Bandera, E. V., Llanos, A. A. M., & Barrett, E. S. (2022). Phenols, Parabens, Phthalates and Puberty: a Systematic Review of Synthetic Chemicals Commonly Found in Personal Care Products and Girls' Pubertal Development. Current environmental health reports, 9(4), 517–534. https://doi.org/10.1007/s40572-022-00366-4

Xu, X., Wu, H., Terry, P. D., Zhao, L., & Chen, J. (2022). Impact of Paraben Exposure on Adiposity-Related Measures: An Updated Literature Review of Population-Based Studies. International journal of environmental research and public health, 19(23), 16268. https://doi.org/10.3390/ijerph192316268

Natalie Eshaghian & Donna Salib

Parabens

Parabens are one of the most used antimicrobial agents for preservation of products, such as cosmetics, foods, toothpastes, shampoos and conditioners, and even our medications. Parabens are used as preservatives so often because they have been around since the 1920s and have low incidence of allergies or irritation associated with them. They are initially derived from parahydroxybenzoic acid, a chemical present in many different fruits and vegetables. What is not so widespread is the fact that these parabens are causing endocrine disruption and in turn leading to obesity.(1)The different types of parabens used to preserve these products are methylparaben, propylparaben, butylparaben, and ethylparaben.(2) These parabens are most commonly found in cosmetics and are used at low ranges limited at 0.01 to a maximum of 0.3. As of July 2020, the CIR panel found that 20 of the 21 parabens included in their report are safe in cosmetics when the sum of the total parabens in any given formulation does not exceed 0.8%.(3)

To really understand how the safety of parabens became a popular topic, we can evaluate the trials that have been testing this topic. In 1998, a study(4) showed that parabens mimic certain types of hormones such as estradiol and could potentially disrupt a person’s hormone balance. This study has started a cascade of multiple trials assessing the effects of parabens but also remains controversial in that this study cannot be used to describe the use of parabens in cosmetics as its methods included subcutaneous injection of parabens and evaluated parabens at high toxic concentrations rather than the maximum limit of 0.3. In 2004, a second study(5) found five parabens present in breast tissue in 19 out of 20 women who had breast cancer. This study’s biggest fault was lacking in a control group, only studying those with breast cancer and not those without. Scientific studies have directly linked parabens to the cause of breast cancer. It is seen that the estrogenic potency increases with the length of the paraben.(6) Parabens are endocrine disruptors because they mimic estrogen and bind to the estrogen receptor, which in turn causes a surplus of the hormone. This in turn causes toxic levels of parabens and estrogen in the system, leading to issues such as breast cancer and reproductive toxicity. In addition, it is found to decrease the effects of chemo agents used for breast cancer, causing the degree of the cancer to be more severe.(7)

Furthermore, high concentrations of parabens are seen to not only harm women, but men as well. Studies have found that there are parabens found in many male products, such as deodorants and colognes, which causes the paraben concentration to be high in the urine after its use. Furthermore, it was seen in various lotions as well, such as sunblock and body lotion as well as gels.(8) Men have endocrine systems as well, causing them to have these harmful effects. These parabens can cause a disruption in fertility, decrease in sperm, as well as decreased testosterone levels. The issue is that many of these products are not regulated by the FDA and can cause harm to our bodies. As of now, the FDA does not have enough information regarding parabens' effect on health and is evaluating safer alternatives for preservatives. Although both men and women are both at risk of the effects of parabens, it is seen to be more harmful to women because of the many products women use that contain these parabens. Men use half the amount of products than women use, allowing them to be at half the risk of the effects of parabens. Although the products that we use may contain parabens at low toxic levels, when a person uses multiple different products that contain parabens in them it adds up to a toxic level in a person’s body. Thus, products containing parabens are a concern for toxicity and adverse effects.

Major retailers have placed bans on the use of parabens such as WholeFoods which bans all four parabens as part of its premium body care standard. It is important to read product labels and to identify these harmful chemicals in our products, such as parabens. Educate yourself on the topic and the different types of parabens there are to be able to identify them on a label. Furthermore, it is important to use products that state they are paraben free. However, if that is not possible, limit the amount of products a person uses that contain parabens to decrease the toxicity level that can be reached in your body. The more healthier products are the ones with less ingredients listed in them, so a consumer and/or pharmacist should be able to read the label and identify if all the ingredients are necessary in these products. As a pharmacist, it’s important to look at other preservatives that would be compatible with a product which have less harmful effects. In addition, as a consumer, it is important to learn to read the labels and identify if there are parabens present in the product, and if so at what levels and to limit the use of these products.

References:

1 Darbre PD. Endocrine Disruptors and Obesity. Curr Obes Rep. 2017;6(1):18-27. doi:10.1007/s13679-017-0240-4

2 Center for Food Safety and Applied Nutrition. Parabens in Cosmetics. U.S. Food and Drug Administration. Accessed: July 19th,2021 https://www.fda.gov/cosmetics/cosmetic-ingredients/parabens-cosmetics#what_are_parabens.

3 Cherian P, Zhu J, Bergfeld WF, et al. Amended Safety Assessment of Parabens as Used in Cosmetics. Int J Toxicol. 2020;39(1_suppl):5S-97S. doi:10.1177/1091581820925001

4 Routledge EJ, Parker J, Odum J, et.al. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. Toxicol Appl Pharmacol. 1998;153(1):12-19. doi:10.1006/taap.1998.8544

5 Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS. Concentrations of parabens in human breast tumours. J Appl Toxicol. 2004;24(1):5-13. doi:10.1002/jat.958

6 Vo TT, Yoo YM, Choi KC, et al. Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod Toxicol. 2010;29(3):306-316. doi:10.1016/j.reprotox.2010.01.013

7 Kirchhof MG, de Gannes GC. The health controversies of parabens. Skin Therapy Lett. 2013;18(2):5-7. https://www.skintherapyletter.com/dermatology/parabens-controversies/

8 Nassan FL, Coull BA, Gaskins AJ, et al. Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study. Environ Health Perspect. 2017;125(8):087012. Published 2017 Aug 18. doi:10.1289/EHP1374

Parabens in the beauty industry. What are parabens and how do they have an effect on our bodies? Parabens are known as preservatives and they are added as to help protect the products from growing harmful bacteria overtime. Parabens are used in the cosmetic industry as well as body care products in order to increase the shelf life of the product. They are great preservatives but there is a concern that they can have a negative effect on the body.

There are six different types of parabens that are popularly used in the market. They are methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, and isobutylparaben. There are some parabens that are used in combination so it is common to see two different parabens on the ingredients list. There are other parabens that can be used alone and at times those are more potent and are linked to have an effect on hormone levels. The parabens have a skin deep score of 7 or 8. A skin deep score indicates how hazardous the product applied on the skin might be. A score of 7-10 indicates high hazard. Parabens with high skin deep score include propylparaben, isopropylparaben, butylparaben, and isobutylparaben. These are all popular ingredients included in some products and can have various health effects. The ingredient list on any product can be overwhelming with a list of names that look like random letters put together. Do not be afraid to look at the ingredient list. You will be able to identify many parabens on the ingredients list because many include the word paraben in their name.

What products have parabens? Parabens are included in cosmetic products as well as personal care products. Such products include shampoos, conditioners, face wash, sunscreens, moisturizers, deodorants, makeup and many more. Parabens have various health effects on the body. It can cause reproductive harm, skin irritation, and might contribute to some forms of cancer. Parabens can have an effect on the hormones in the body such as estrogen which can affect both the male and female reproductive system, development, fertility and even birth outcomes. Long exposure to paraben can also decrease sperm production and lower testosterone levels. Other than the reproductive system, parabens can also cause skin irritation and increase skin aging which can also increase skin sensitivity and cause damage from the sun. Parabens are also associated with the risk of cancer development specifically breast cancer in women. The more potent parabens can alter the gen expression which can cause mutation in the genes leading to cells that grow into breast cancer cells.

If parabens are a concern to the human health and have harmful effects then why is it not banned by the Food and Drug Administration (FDA)? Under the Federal Food, Drug and Cosmetic Act (FD&C Act), cosmetic ingredients do not need FDA approval before they are available to the market. Although this does not sound safe, the FDA can take action at any point against a cosmetic product on the market that has ingredients which are shown to not be safe for customers when used according to the directions on the label of the product.

How can I protect myself from the use of parabens? There are many alternatives that are “paraben-free” and are safer to be used on the skin. The Breast Cancer Action has a comprehensive list of cosmetic companies with products that are completely paraben-free. Overall, it is better to avoid the use of paraben ingredients especially the more potent ones on day-to-day life.

“What Are Parabens, and Why Don't They Belong in Cosmetics?” Environmental Working Group, www.ewg.org/what-are-parabens.

Center for Food Safety and Applied Nutrition. “Parabens in Cosmetics.” U.S. Food and Drug Administration, FDA, www.fda.gov/cosmetics/cosmetic-ingredients/parabens-cosmetics.

“Paraben-Free Cosmetics.” Breast Cancer Action, www.bcaction.org/our-take-on-breast-cancer/environment/safe-cosmetics/paraben-free-cosmetics/.

Parabens can be classified as non-persistent endocrine disrupting chemicals (EDCs). EDCs are defined as substances that may interfere with hormonal pathways possibly leading to negative health consequences. One concern is EDC influence on a woman’s ability to become pregnant, since EDCs may be linked to rising rates of infertility worldwide.

Parabens are used as antimicrobial preservatives against molds/yeasts usually present in body care products, cosmetics, foods and pharmaceuticals. Parabens can be measured in human tissues such as breast tissue, milk, blood and urine. EDCs include environmental pollutant chemicals known to cause endocrine dysfunction and parabens are detected in the environment including water, soil and air due to indoor air becoming polluted from use of consumer products. Parabens are formed from alkyl esters of p-hydroxybenzoic acid and the most commonly used parabens are propyl paraben (PP), methyl paraben (MP), ethyl paraben (EP), and butyl paraben (BP).

Parabens are a common choice due to their reported low cost, minimal toxicity, and chemical inertness. Chemists who formulate cosmetics will opt for parabens because they have no identifiable taste/odor, are pH neutral and less chance of discoloration or hardening. Parabens are seen as a necessity to protect against problematic microbes such as gram negative Escherichia coli and gram positive Staphylococcus aureus.

Regarding in vitro and in vivo studies, parabens have exhibited estrogenic and androgenic activity and played a role in breast cancer development. In particular, in vitro studies showed that parabens binded to estrogen receptors and showed adverse reactions on female reproductive system in animal toxicity studies. Butyl paraben has lead to reduced testosterone production and sperm production in rats. In an in utero study, pregnant rats were exposed to butyl and ethyl paraben to properly evaluate the extent of parabens on steroidogenesis. Results showed that neither butyl nor ethyl paraben affected testosterone production/testicular histopathology but exhibited several effects on the female reproductive system. Butyl paraben had shown a significant decrease in mRNA expression of estradiol beta receptor in fetal ovaries, decreased mRNA expression of steroidogenic regulatory protein and benzodiazepine receptors in adrenal glands. In an vitro study also done in rats, butyl paraben showed weak thyroid hormone antagonism by increasing proliferation of GH3 cells in T-screen assay and both ethyl & butyl paraben showed progesterone formation.

Since parabens are found in the air, exposure to parabens occurs through inhalation, ingestion and dermal contact. Parabens are defined as non-persistent EDCs because they are usually excreted from the body within hours upon exposure. Parabens will either be hydrolyzed to p-hydroxybenzoic acid which is then conjugated via urinary excretion or excreted as intact esters. Parabens do not typically accumulate in body tissues and organs, and have not proven to be cytotoxic or carcinogenic. Studies have shown that depending on sex/race/ethnicity, there are established differences in paraben concentration amongst demographic populations. Data suggests that female non-Hispanic blacks and Mexican Americans are in the category for highest exposure to MP and PP.

1. Mínguez-Alarcón L, Gaskins AJ. Female exposure to endocrine disrupting chemicals and fecundity: a review. Curr Opin Obstet Gynecol. 2017;29(4):202-211. doi:10.1097/GCO.0000000000000373

2. Darbre PD. Overview of air pollution and endocrine disorders. Int J Gen Med. 2018;11:191-207. Published 2018 May 23. doi:10.2147/IJGM.S102230

3. Camilla Taxvig, Anne Marie Vinggaard, Ulla Hass, Marta Axelstad, Julie Boberg, Pernille Reimer Hansen, Hanne Frederiksen, Christine Nellemann, Do Parabens Have the Ability to Interfere with Steroidogenesis?, Toxicological Sciences, Volume 106, Issue 1, November 2008, Pages 206–213, https://doi.org/10.1093/toxsci/kfn148

4. Calafat AM, Ye X, Wong LY, Bishop AM, Needham LL. Urinary concentrations of four parabens in the U.S. population: NHANES 2005-2006. Environ Health Perspect. 2010;118(5):679-685. doi:10.1289/ehp.0901560

5. Fransway, Anthony F. MD*; et al. Parabens, Dermatitis: 1/2 2019 - Volume 30 - Issue 1 - p 3-31 doi: 10.1097/DER.0000000000000429

Parabens are used as preservatives in many food, pharmaceutical, and cosmetic products for their antimicrobial effects. Many people use paraben-containing products daily through ingestion, absorption through pores on the skin, and through inhalation. Therefore, many cosmetic manufacturers market some of their products as ‘paraben-free’ for the consumer. Consumers know parabens for their ability to accumulate in the tissues, especially breast tissue. Parabens have estrogenic and anti-androgenic effects and are often considered as endocrine disruptors. Endocrine disruptors can affect the hormones in the endocrine system which may be linked to diabetes and obesity because they can bind to nuclear receptors and induce harsh responses and activity. The most common parabens used in every day products include methylparaben, propylparaben, ethylparaben, butylparaben, and benzylparaben. It has been hypothesized that the increased estrogenic and adipogenic effects of parabens may be associated with the chemical structure of the alkyl chain in these compounds. The longer the alkyl substituent is the more that these effects will predominate. This is due to the longer alkyl chain possessing a stimulating effect on peroxisome proliferator-activated receptor γ (PPARγ) which is known for adipogenesis and obesity.

Parabens may be linked to obesity because they have obesogen mechanisms. An obesogen is a chemical in the body that can stimulate obesity by increasing the number of adipose cells which can lead to changes decreased calories burnt in a day, increased weight gain, and alteration in the mechanisms for appetite and satiety. Some of the mechanisms of parabens may also affect insulin production and the metabolism of lipids which can be linked to diabetes. In a study, it was observed that women who had a higher BMI had elevated levels of parabens (i.e. methylparaben and propylparaben) which may be associated with the obesogenic effects and the accumulation of adipose in the cells. Higher concentrations of parabens could be seen in the higher BMI group. The hypothesis is that lower concentrations of parabens enter the body through the pores of the skin found in cosmetic products, while higher concentrations of parabens are ingested through food and supplements. Certain cytokines such as adipsin showed positive correlation with the severity of obesity. The accumulated levels of parabens (mainly methylparaben) correlated with the elevated levels of adipsin and may therefore be linked to obesity. However, parabens (mainly propylparaben) were showing positive correlation with hip circumference, showing a more even distribution of fat. Some may classify paraben consumption as a ‘healthier’ way to redistribute fat, however, that statement is still controversial.

As most people know, there are a couple of factors that can influence obesity such as lack of exercise and increased calorie intake. More evidence is being brought to light about other factors that can affect obesity such as parabens which are considered obesogenic endocrine disruptors. Methylparaben and propylparaben are two compounds that are commonly found in many different food, pharmaceutical, and cosmetic products. One thing a patient can do is avoid products that use parabens to decrease exposure to these chemicals or take precautionary measures by reading labels to limit their intake. All of this information is still being studied and conclusions to this matter remains to be seen.

References

Darbre P. D. (2017). Endocrine Disruptors and Obesity. Current obesity reports, 6(1), 18–27. https://doi.org/10.1007/s13679-017-0240-4

Kolatorova, L., Sramkova, M., Vitku, J., et al. (2018). Parabens and Their Relation to Obesity. Physiol. Res, 67(3), S465-72. https://doi.org/10.33549/physiolres.934004

Parabens are used for their extremely effective antimicrobial properties when preserving food, cosmetics, and pharmaceutical products. They accomplish this task by stopping pathogens from creating an effective phospholipid bilayer which results in them not being able to maintain their shape and function. In addition, parabens are relatively safe for human consumption showing no signs of toxicity to humans while maintaining good stability and non volatility. Recent studies, however, have been suggesting that parabens maybe are not as harmless as we think they are. In this study they tried to see if methylparaben and ethylparaben, two of the most commonly used paraben preservatives, had any effect on the lifespan of flies. The study found that methylparaben and ethylparaben could reduce the mean lifespan, maximum lifespan, and survival time of flies when compared with that of the control group. More importantly, the mean lifespan in the methylparaben and ethylparaben group was about a half of that in the control group, while the mean lifespan in the ethylparaben group was nearly three quarters of that in the control group. This indicates that methylparaben and ethylparaben may present a greater toxic effect on the lifespan of flies than individual paraben at the same concentration. This shows that not only do parabens have a negative impact on the longevity of flies, but that this negative effect increases with the combined use of two parabens together. However, the study only focused on the additive toxicity when combining two kinds of parabens and didn’t really focus too much on the toxicity on fertility and the mechanism of parabens-induced endocrine disruption in flies. As a result, additional studies are needed in order to investigate the reason behind parabens’ toxicity on flies and, more importantly, if this decreased lifespan transfers over to humans as well.

References

Chen Q, Pan C, Li Y, Zhang M, Gu W. The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae). J Insect Sci. 2016;16(1)

Turakka L, Ojanen T, Henell U, Karjalainen A. Parabens as antimicrobial preservatives in creams. Pharmazie. 1988;43(10):701-3.

Parabens are used as a preservative used in numerous cosmetics, food and pharmaceuticals products due to its antimicrobial property. Its mechanism of action includes disruption of the lipid bilayer and membrane transport processes. The parabens mostly used are methylparaben, ethylparaben, propylparaben and butylparaben. They prevent products from becoming contaminated from mold, fungi, and bacteria. It has excellent coverage against fungi and gram-positive bacteria such as the staphylococcus species. The FDA has classified parabens as safe. They are stable, nonvolatile, and have not been proven to be carcinogenic or cytotoxic. There was some evidence that suggested parabens can exert estrogenic effects by interfering with the estrogen-activating enzyme 17b-hydroxysteroid dehydrogenase. They detected unconjugated parabens in breast cancer tissue which caused some to investigate the possible estrogenic effect of parabens. Butylparaben was found to be the most active estrogenic paraben but it was still 10,000 less potent than estradiol. The tested parabens did interfere with 17β-HSD2 which prevents local inactivation of the active estrogen. However, the parabens used in cosmetics are short parabens not the larger ones so this wouldn’t be harmful to people using them. When lower concentrations of multiple parabens are used, there is improved antimicrobial efficacy. The American Contact Dermatitis Society keeps a database of cosmetic and household products so a patient can search this to find paraben free products. It was estimated that people in the US are exposed to an average of 76 mg of paraben per day. Most food contains paraben too with processed food having a higher paraben content. Parabens can cause contact dermatitis in some cases but it is not a common cause. 

References

Engeli RT, Rohrer SR, Vuorinen A, et al. Interference of Paraben Compounds with Estrogen Metabolism by Inhibition of 17β-Hydroxysteroid Dehydrogenases. Int J Mol Sci. 2017;18(9):2007. Published 2017 Sep 19. doi:10.3390/ijms18092007

Fransway AF, Fransway PJ, Belsito DV, et al. Parabens. Dermatitis. 2019;30(1):3-31. doi:10.1097/DER.0000000000000429