Compendium of the most significant studies with reference to properties, intake, effects.

Kim MJ, Kim CH, An MJ, Lee JH, Shin GS, Song M, Kim JW. Ethylparaben induces apoptotic cell death in human placenta BeWo cells via the Caspase-3 pathway. Anim Cells Syst (Seoul). 2020 Jan 9;24(1):34-43. doi: 10.1080/19768354.2020.1711804.

Abstract. Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group Korean Society for Integrative Biology.

Golden R, Gandy J, Vollmer G. A review of the endocrine activity of parabens and implications for potential risks to human health. Crit Rev Toxicol. 2005 Jun;35(5):435-58. doi: 10.1080/10408440490920104. 

Abstract. Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible and appropriate, emphasis is placed on direct comparisons with human data with either 17beta-estradiol or DES, since this does not require extrapolation from animal data with the uncertainties inherent in such comparisons. Based on these comparisons using worst-case assumptions pertaining to total daily exposures to parabens and dose/potency comparisons with both human and animal no-observed-effect levels (NOELs) and lowest-observed-effect levels (LOELs) for estrogen or DES, it is biologically implausible that parabens could increase the risk of any estrogen-mediated endpoint, including effects on the male reproductive tract or breast cancer. Additional analysis based on the concept of a hygiene-based margin of safety (HBMOS), a comparative approach for assessing the estrogen activities of weakly active EACs, demonstrates that worst-case daily exposure to parabens would present substantially less risk relative to exposure to naturally occurring EACs in the diet such as the phytoestrogen daidzein.

Liu F, Kong X, Kong H. Ethylparaben induces subconjunctival fibrosis via the Wnt/β-catenin signaling pathway. Exp Ther Med. 2021 Apr;21(4):295. doi: 10.3892/etm.2021.9726.

Abstract. The aim of the present study was to explore the etiology of subconjunctival fibrosis (SCF) induced by ethylparaben, the most prevalent preservative in Chinese eye drops....Copyright © 2020, Spandidos Publications.

Wang D, Li W, Yang C, Chen X, Liu X, He J, Tong C, Peng C, Ding Y, Geng Y, Cao X, Li F, Gao R, Wang Y. Exposure to ethylparaben and propylparaben interfere with embryo implantation by compromising endometrial decidualization in early pregnant mice. J Appl Toxicol. 2021 Nov;41(11):1732-1746. doi: 10.1002/jat.4208.

Abstract. Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization.... © 2021 John Wiley & Sons, Ltd.

Sun L, Yu T, Guo J, Zhang Z, Hu Y, Xiao X, Sun Y, Xiao H, Li J, Zhu D, Sai L, Li J. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats. Sci Rep. 2016 Apr 28;6:25173. doi: 10.1038/srep25173.

Abstract. The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT-PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography-mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα).

Matwiejczuk N, Galicka A, Brzóska MM. Review of the safety of application of cosmetic products containing parabens. J Appl Toxicol. 2020 Jan;40(1):176-210. doi: 10.1002/jat.3917.

Abstract. Cosmetics are a source of lifetime exposure to various substances including parabens, being the most popular synthetic preservatives. Because the use of cosmetics shows an increasing trend and some adverse health outcomes of parabens present in these products have been reported, the present review focused on the safety of dermal application of these compounds. Special attention has been paid to the absorption of parabens and their retention in the human body in the intact form, as well as to their toxicological characteristics. Particular emphasis has been placed on the estrogenic potential of parabens....© 2020 John Wiley & Sons, Ltd.

Tavares RS, Martins FC, Oliveira PJ, Ramalho-Santos J, Peixoto FP. Parabens in male infertility-is there a mitochondrial connection? Reprod Toxicol. 2009 Jan;27(1):1-7. doi: 10.1016/j.reprotox.2008.10.002. 

Abstract. Parabens are widely used as preservatives in many foods, cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and to a long history of safe use. Parabens are alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben and benzylparaben. These compounds are known to have a null or very weak estrogenic activity in estrogen receptor assays in vitro. In recent years, an increasing concern has emerged regarding possible adverse effects of chemicals in food and in cosmetics on human reproduction outcomes. In developed countries about 15% of human couples are affected by infertility, almost half of these cases attributed to men, through low sperm motility or/and sperm count. It is known that a significant number of cases of male infertility results from exposure to xenobiotics, and also that testis mitochondria are particularly affected by drug-induced toxicity. The present review discusses evidence that parabens may not be as safe as initially thought, and suggests that the interaction between parabens and mitochondrial function in the testis may be key in explaining the contribution of parabens for a decrease in reproductive potential.

Dogan S, Tongur T, Erkaymaz T, Erdogan G, Unal B, Sik B, Simsek T. Traces of intact paraben molecules in endometrial carcinoma. Environ Sci Pollut Res Int. 2019 Oct;26(30):31158-31165. doi: 10.1007/s11356-019-06228-1. 

Abstract. Endometrial carcinoma is the most commonly encountered gynecological cancer in women worldwide and is also one of the popular models of the hormone-dependent carcinomas. This study was aimed to evaluate and compare the concentrations of five paraben molecules (methylparaben, ethylparaben, N-propylparaben, benzylparaben, isobutylparaben + N-butylparaben) in the endometrial and myometrial tissue samples of patients diagnosed with endometrial carcinoma and benign gynecologic diseases. A total of 88 patients were included in the study and chemical analysis was performed on 176 tissue samples. The study group comprised of 33 patients with endometrial carcinoma and 6 patients with endometrial intraepithelial neoplasia. The control group comprised of 49 patients. One endometrial and one myometrial tissue samples were collected from each patient. The analyses were performed using ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). At least one type of paraben molecule was detected in 23.07% (9/39) of the patients in the study group, and in 2.04% (1/49) of the patients in the control group; this difference between the groups was statistically significant (p = .002). N-Propylparaben and isobutyl + N-butylparaben were the most frequently detected (in 7/10 of the samples) paraben molecules in the study. Tumor characteristics (tumor diameter, myometrial invasion, architectural grade, nuclear grade, lymphovascular space invasion, and tumor stage) were comparable between the two groups of endometrial carcinoma (paraben-detected and paraben-undetected groups). In conclusion, paraben molecules were more frequently detected in the endometrial carcinoma tissue samples than in the normal endometrium.

Finot F, Kaddour A, Morat L, Mouche I, Zaguia N, Cuceu C, Souverville D, Négrault S, Cariou O, Essahli A, Prigent N, Saul J, Paillard F, Heidingsfelder L, Lafouge P, Al Jawhari M, Hempel WM, El May M, Colicchio B, Dieterlen A, Jeandidier E, Sabatier L, Clements J, M'Kacher R. Genotoxic risk of ethyl-paraben could be related to telomere shortening. J Appl Toxicol. 2017 Jun;37(6):758-771. doi: 10.1002/jat.3425.

Abstract. The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines....Copyright © 2016 John Wiley & Sons, Ltd.

Jensen TK, Andersson AM, Main KM, Johannsen TH, Andersen MS, Kyhl HB, Juul A, Frederiksen H. Prenatal paraben exposure and anogenital distance and reproductive hormones during mini-puberty: A study from the Odense Child Cohort. Sci Total Environ. 2021 May 15;769:145119. doi: 10.1016/j.scitotenv.2021.145119.

Abstract. Background: Parabens are added to personal care products as antimicrobial preservatives. They have been suggested to have endocrine disrupting abilities. Prenatal exposure to parabens has been associated with reproductive endpoints including reduced male anogenital distance (AGD, distance from anus to genitals), which is sensitive to prenatal anti-androgenic exposure. Objectives: To study the associations between maternal paraben concentrations in second trimester urine and AGD and reproductive hormone concentrations at 3 months of age in offspring....Copyright © 2021 The Authors.

Ethyl paraben: properties, uses, pros, cons, safety

Ethyl paraben is a preservative from the paraben family. It is known under different names depending on the sector: in food as E214, in cosmetics as ethylparaben (INCI: Ethylparaben), and in the pharmaceutical field as ethyl 4-hydroxybenzoate or ethyl para-hydroxybenzoate. Its main function is an antimicrobial preservative, with practical effectiveness depending on ph, matrix, solubilization, and the overall preservation strategy.

Definition

It is a single substance: the ethyl ester of p-hydroxybenzoic acid. In formulation, preservative activity is linked to the “available” fraction in the active phase and to system balance (free water, solvents, surfactants, chelators, packaging, and storage conditions). In highly aqueous systems, managing solubility can be necessary (directly or via co-solvent/solubilizer systems).

Main uses

Food.
As E214, it is a preservative additive. Use is tied to categories and maximum levels defined by applicable regulations and, in modern practice, may be less frequent than other preservation systems.

Cosmetics
As ethylparaben (INCI: Ethylparaben), it is used as a preservative to support microbiological stability of the finished product, especially in water-containing formulas. Selection and dosage depend on the regulatory framework, formulation compatibility, and challenge test outcomes.

INCI functions

Fragrance. It plays a very important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability. It is able to create a perceptible pleasant odour, masking a bad smell. The consumer always expects to find a pleasant or distinctive scent in a cosmetic product. 

Preservative. Any product containing organic, inorganic compounds, water, needs to be preserved from microbial contamination. Preservatives act against the development of harmful microorganisms and against oxidation of the product.

Medicine.
Not an active substance. Any uses are technical (preservation) and depend on the application context.

Pharmaceutical.
May be used as a preservative in specific preparations, with attention to compatibility, dose, route of use, and sensitive populations (e.g., mucosal or pediatric), according to the product’s standards and dossier.

Industrial use.
May be used as a preservative in certain technical matrices or as an analytical standard/reference, depending on sector requirements.

Identification data and specifications

Physico-chemical properties (indicative)

Functional role and mechanism of action (practical)

It acts as a preservative by limiting microbial growth. Real-world efficacy depends on: “available” concentration in the active phase, ph, partitioning between phases, interactions with ingredients that reduce availability, and storage conditions. Practical validation relies on verifying the robustness of the preservation system on the finished product.

Formulation compatibility

Must be assessed case by case, considering ph, electrolytes, surfactants, and co-solvents. In complex products, preservation is often a system strategy based on multiple levers (preservative blends, chelators, free-water control, suitable packaging).

Use guidelines

Define measurable targets through challenge testing and verify preservative stability over shelf life. Manage addition order, processing temperature, and final ph to reduce precipitation risk and efficacy loss. Ensure compliance with the rules of the target market and product category.

Quality, grades, and specifications

For food use, compliance with regulatory specifications and controls on impurities/critical parameters are essential. For cosmetics and pharmaceuticals, beyond purity, traceability, batch-to-batch consistency, and supplier technical documentation (TDS/SDS) are crucial, with verification of performance in the real system.

Safety, regulation, and environment

In food, use as E214 is subject to defined categories and limits. In cosmetics and pharmaceuticals, use is governed by specific constraints and by the finished product safety assessment. Practically, the main risk is linked to possible irritation or sensitization in predisposed individuals, especially in leave-on products or sensitive areas, and to correct management of use levels.

Allergen.
Not typically classified as an allergen. However, as with many preservatives, individual reactions are possible in sensitive subjects depending on dose, matrix, and use conditions.

Contraindications 
Use caution on very reactive skin and in products intended for sensitive populations; assessment should be based on the finished product, exposure profile, and compliance with applicable requirements.

For more information:  PARABENS

Safety

Parabens are preservative chemical compounds that have been the subject of attention in the scientific literature as possible endocrine disruptors (particularly propylparaben and butylparaben), i.e. with the possibility of damaging the hormone-producing glands in our bodies, particularly in the breasts. The 2004 study by Darbre et al. showed that parabens remain in our bodies as intact esters (2). Following this study, some of the scientific literature in 2005 and 2006 cast doubt on Darbre's conclusions and claimed they were limited. However, both the US FDA and the European SCCP authorised in 2006 the use of a single paraben in cosmetic products at a concentration of 0.4% and the use of total parabens at a concentration of 0.8%. However, there is no shortage of studies that consider the restrictions unnecessary: M. G. Kirchhof et al. in 2013 found that parabens are among the safest and most well-tolerated preservatives and that current data do not support drastic regulations or personal exposure restrictions. Darbre in 2014 published a further study in which he showed how parabens can cause DNA damage.

Parabens are components discussed and on whose safety many doubts have been raised, especially for the damage they would produce to the aquatic environment where they are discharged after use (1).

Parabens can contribute to obesity (2).

References_______________________________________________________________________

(1) Terasaki M, Abe R, Makino M, Tatarazako N. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.  Environ Toxicol. 2013 Dec 27. doi: 10.1002/tox.21944. [Epub ahead of print]

Popa DS, Bolfa P, Kiss B, Vlase L, Păltinean R, Pop A, Cătoi C, Crişan G, Loghin F.
 Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats. Biomed Environ Sci. 2014 Feb;27(2):85-96. doi: 10.3967/bes2014.021.

(2) Hu P, Chen X, Whitener RJ, Boder ET, Jones JO, Porollo A, Chen J, Zhao L. Effects of parabens on adipocyte differentiation. Toxicol Sci. 2013 Jan;131(1):56-70. doi: 10.1093/toxsci/kfs262. Epub 2012 Sep 5.

Darbre, P. D., & Harvey, P. W. (2014). 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. Journal of Applied Toxicology, 34(9), 925-938.

Abstract. A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm–1 μm range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue. Copyright © 2014 John Wiley & Sons, Ltd.

Hager E, Chen J, Zhao L. Minireview: Parabens Exposure and Breast Cancer. Int J Environ Res Public Health. 2022 Feb 8;19(3):1873. doi: 10.3390/ijerph19031873. 

Abstract. There is increasing recognition that environmental exposure to chemicals, such as endocrine-disruptive chemicals (EDCs), contributes to the development of breast cancer. Parabens are a group of EDCs commonly found in personal care products, foods, and pharmaceuticals. Systemic exposure to parabens has been confirmed by the ubiquitous detection of parabens in human blood and urine samples. Although evidence from in vivo and epidemiological studies linking parabens exposure to breast cancer is limited, the current evidence suggests that parabens may negatively interfere with some endocrine and intracrine targets relevant to breast carcinogenesis. So far, most studies have focused on a single paraben's effects and the direct modulating effects on estrogen receptors or the androgen receptor in vitro. Recent studies have revealed that parabens can modulate local estrogen-converting enzymes, 17β-hydroxysteroid dehydrogenase 1 and 2 and increase local estrogen levels. Also, parabens can crosstalk with the human epidermal growth factor receptor 2 (HER2) pathway and work with ER signaling to increase pro-oncogenic c-Myc expression in ER+/HER2+ breast cancer cells. Future studies investigating paraben mixtures and their crosstalk with other EDCs or signaling pathways both in vitro and in vivo in the context of breast cancer development are warranted.

Petric Z, Ružić J, Žuntar I. The controversies of parabens - an overview nowadays. Acta Pharm. 2021 Mar 1;71(1):17-32. doi: 10.2478/acph-2021-0001.

Abstract. Effects of paraben toxicity, i.e., endocrine-disruption properties, are in the focus of researchers for decades, but still - they are a hot subject of debate. Parabens are aliphatic esters of p-hydroxybenzoic acid, which are widely used as antimicrobial agents for the preservation of cosmetics, pharmaceuticals and foods. Mostly used parabens are methyl-, ethyl-, propyl- and butylparaben. Although the toxicity of parabens is reported in animals and in in vitro studies, it cannot be taken for granted when discussing hazards for human health due to an unrealistic exposure -safety profile. Many studies have demonstrated that parabens are non-teratogenic, non-mutagenic, non-carcinogenic and the real evidence for their toxicity in humans has not been established. For now, methyl-, ethyl- and propylparaben are considered safe for use in cosmetics and pharmaceuticals within the recommended range of doses. Regarding alternatives for parabens, a variety of approaches have been proposed, but every substitute would need to be tested rigorously for toxicity and safety.

Byford JR, Shaw LE, Drew MG, Pope GS, Sauer MJ, Darbre PD. Oestrogenic activity of parabens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2002 Jan;80(1):49-60. doi: 10.1016/s0960-

Abstract. Parabens (4-hydroxybenzoic acid esters) have been recently reported to have oestrogenic activity in yeast cells and animal models. Since the human population is exposed to parabens through their widespread use as preservatives in foods, pharmaceuticals and cosmetics, we have investigated here whether oestrogenic activity of these compounds can also be detected in oestrogen-sensitive human cells. We report on the oestrogenic effects of four parabens (methylparaben, ethylparaben, n-propylparaben, n-butylparaben) in oestrogen-dependent MCF7 human breast cancer cells. Competitive inhibition of [3H]oestradiol binding to MCF7 cell oestrogen receptors could be detected at 1,000,000-fold molar excess of n-butylparaben (86%), n-propylparaben (77%), ethyl-paraben (54%) and methylparaben (21%). At concentrations of 10(-6)M and above, parabens were are able to increase expression of both transfected (ERE-CAT reporter gene) and endogenous (pS2) oestrogen-regulated genes in these cells. They could also increase proliferation of the cells in monolayer culture, which could be inhibited by the antiestrogen ICI 182,780, indicating that the effects were mediated through the oestrogen receptor. However, no antagonist activity of parabens could be detected on regulation of cell proliferation by 17 beta-oestradiol at 10(-10)M. Molecular modelling has indicated the mode by which paraben molecules can bind into the ligand binding pocket of the crystal structure of the ligand binding domain (LBD) of the oestrogen receptor alpha (ERalpha) in place of 17beta-oestradiol; it has furthermore shown that two paraben molecules can bind simultaneously in a mode in which their phenolic hydroxyl groups bind similarly to those of the meso-hexoestrol molecule. Future work will need to address the extent to which parabens can accumulate in hormonally sensitive tissues and also the extent to which their weak oestrogenic activity can add to the more general environmental oestrogen problem.

Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS. Concentrations of parabens in human breast tumours. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13. doi: 10.1002/jat.958. PMID: 14745841.

Nowak K, Ratajczak-Wrona W, Górska M, Jabłońska E. Parabens and their effects on the endocrine system. Mol Cell Endocrinol. 2018 Oct 15;474:238-251. doi: 10.1016/j.mce.2018.03.014. Epub 2018 Mar 27. PMID: 29596967.

Wei F, Mortimer M, Cheng H, Sang N, Guo LH. Parabens as chemicals of emerging concern in the environment and humans: A review. Sci Total Environ. 2021 Jul 15;778:146150. doi: 10.1016/j.scitotenv.2021.146150. Epub 2021 Feb 27. PMID: 34030374.

Charles AK, Darbre PD. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells. J Appl Toxicol. 2013 May;33(5):390-8. doi: 10.1002/jat.2850. Epub 2013 Jan 31. PMID: 23364952

Darbre PD, Harvey PW. Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks. J Appl Toxicol. 2008 Jul;28(5):561-78. doi: 10.1002/jat.1358. PMID: 18484575.