Parabens: Cosmetic Preservatives, Estrogen Mimicry, and Exposure

Table of Contents

1. What Parabens Are
2. Types: Methyl, Ethyl, Propyl, Butyl
3. Sources and Exposure Routes
4. How Parabens Enter and Move Through the Body
5. Estrogen Mimicry and Hormonal Effects
6. Parabens Measured in Breast Tissue
7. Mechanisms of Endocrine Disruption
8. Body Burden and Biomonitoring
9. What Studies Report About Lowering Exposure
10. Regulatory Status and Policy
11. Key Research Papers
12. Connections
13. Featured Videos

What Parabens Are

Parabens are alkyl esters of p-hydroxybenzoic acid. The family typically includes methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben and benzylparaben (Tavares 2009). The parent acid and its salts (calcium, sodium and potassium paraben) are regulated alongside the esters in the EU, where no safety concerns were raised about them (Commission Regulation (EU) No 1004/2014; see Regulatory Status).

In volunteers given single labelled oral doses of methyl-, isobutyl- and n-butylparaben, the main urinary metabolite was p-hydroxyhippuric acid (57.2–63.8% of the dose), while p-hydroxybenzoic acid (PHBA) accounted for 3.0–7.2%. Parent methylparaben (free and conjugated) made up 17.4% of the dose excreted in urine, against 6.8% for isobutylparaben and 5.6% for n-butylparaben (Moos 2016).

Types: Methyl, Ethyl, Propyl, Butyl

• Methylparaben (MP). Detected in 99.1% of U.S. urine samples in NHANES 2005–2006, with the highest median concentration of the four parabens measured (Calafat 2010). In breast cancer cells it was the weakest of four parabens at displacing estradiol from its receptor (Byford 2002). EU limit: 0.4% (as acid) as a single ester.
• Ethylparaben (EP). Detected in 42.4% of NHANES 2005–2006 samples (Calafat 2010); intermediate in the same receptor-binding comparison (Byford 2002). EU limit: 0.4% (as acid) as a single ester.
• Propylparaben (PP). Detected in 92.7% of NHANES 2005–2006 samples (Calafat 2010). In young rats fed propylparaben, sperm reserves and serum testosterone fell (Oishi 2002; see below). In the EU, propyl- and butylparaben together are limited to 0.14% (as acid).
• Butylparaben (BP). Detected in 47% of NHANES 2005–2006 samples (Calafat 2010). The most potent of the four common parabens in a yeast estrogen assay, though 10,000-fold less potent than 17β-estradiol (Routledge 1998), and the strongest of the four at displacing estradiol in breast cancer cells (Byford 2002).
• Isobutylparaben and isopropylparaben. In a rat receptor-binding assay, isobutylparaben bound estrogen receptors most strongly of the parabens tested (Vo 2010). Both, together with phenyl-, benzyl- and pentylparaben, were prohibited in EU cosmetics in 2014 because limited or no information was submitted for their safety evaluation, so that the human risk could not be evaluated (Commission Regulation (EU) No 358/2014).

Sources and Exposure Routes

• Cosmetics and personal care products. The FDA describes parabens as commonly used preservatives in cosmetic products, often in combination with other preservatives; it lists makeup, moisturizers, hair care products and shaving products among cosmetics that may contain them, and states that many major deodorants do not currently contain parabens, although some may (FDA, Parabens in Cosmetics). A 2004 editorial described their use in underarm deodorants and antiperspirants and a wide range of other consumer products (Harvey 2004). The NHANES authors attribute the differences in urinary methyl- and propylparaben by sex and race/ethnicity to the likely use of personal care products containing them (Calafat 2010).
• Pharmaceuticals. Parabens are used as preservatives in pharmaceuticals (Calafat 2010; Oishi 2002).
• Food. In the United States, methylparaben and propylparaben are listed among direct food substances affirmed as generally recognized as safe (GRAS), used as antimicrobial agents at levels not exceeding good manufacturing practice, which the regulation states results in a maximum of 0.1% in food (21 CFR 184.1490; 21 CFR 184.1670).

How Parabens Enter and Move Through the Body

Skin absorption has been measured directly. In a two-week single-blinded study, 26 healthy young men applied a cream to the whole body daily, without added chemicals in week one and with 2% each of butylparaben and two phthalates in week two. Butylparaben was not detectable in serum before treatment; it peaked a few hours after application at a mean of 135 µg/L. The study found no short-term effect on the men’s reproductive or thyroid hormone levels (Janjua 2007).

A 2008 review summarized studies showing that parabens can penetrate human skin intact, without breakdown by skin esterases, and be absorbed systemically, and that intact paraben esters have been measured in human urine. The same review states that the estrogen-agonist properties of parabens and of their common metabolite, PHBA, have been extensively documented in laboratory assays (Darbre 2008).

Elimination is fast: after single oral doses, 80.5–85.3% of the dose captured in the measured metabolites was excreted in the first 24 hours (Moos 2016).

Estrogen Mimicry and Hormonal Effects

Parabens act as weak estrogens in laboratory tests:

• In a yeast-based estrogen assay, methyl-, ethyl-, propyl- and butylparaben were all weakly estrogenic, the most potent (butylparaben) being 10,000-fold less potent than 17β-estradiol. Butylparaben competed for binding to the rat estrogen receptor with an affinity about five orders of magnitude lower than that of diethylstilboestrol (Routledge 1998).
• In immature rats, parabens given by mouth were inactive in the uterotrophic assay; butylparaben given under the skin produced a positive response, at about 100,000 times less potency than 17β-estradiol (Routledge 1998).
• In MCF7 human breast cancer cells, a 1,000,000-fold molar excess displaced radiolabelled estradiol from the receptor by 86% (n-butylparaben), 77% (n-propylparaben), 54% (ethylparaben) and 21% (methylparaben). At 10⁻⁶ M and above, parabens increased expression of estrogen-regulated genes and cell proliferation, effects blocked by an antiestrogen (Byford 2002).
• In MCF-7 breast cancer cells exposed to 20 nM, methyl-, propyl- and butylparaben all increased expression of estrogen receptors α and β, with fewer effects in non-cancerous MCF-10A breast cells; some also raised progesterone-receptor expression (Wróbel 2014).
• A 2005 review compared the paraben doses needed to produce estrogenic effects in animals with effective doses of 17β-estradiol and diethylstilbestrol. It describes the active parabens as many orders of magnitude less active than estrogen and, using worst-case daily exposure estimates, concluded that it is biologically implausible that parabens could increase the risk of any estrogen-mediated endpoint, including male reproductive-tract effects or breast cancer (Golden 2005). Later cell studies, such as the growth-factor cross-talk work described under Mechanisms, propose that potency tested in isolation may understate activity (Pan 2016).

Animal studies used doses given in the diet or by mouth:

• In 3-week-old male rats fed propylparaben at 0.01%, 0.10% or 1.00% of the diet for 4 weeks, epididymal sperm reserves and concentrations fell in a dose-dependent manner (significant at 0.10% and above), daily sperm production fell in all treated groups, and serum testosterone fell significantly at the highest dose; organ weights were unaffected. The author notes that the effect level matched the upper-limit acceptable daily intake for parabens then used in the European Community and Japan (10 mg/kg body weight/day) (Oishi 2002).
• In young female rats dosed by mouth at 62.5–1,000 mg/kg/day from postnatal day 21 to 40, the highest doses of methyl- and isopropylparaben delayed vaginal opening; several parabens lowered serum estradiol and thyroxine and altered ovarian and uterine tissue (Vo 2010).

Human data are limited. In 27 healthy women, plasma methyl- and propylparaben were higher in those with a body-mass index of 25–34.9 than in those with 18.5–24.9, and methylparaben was associated with several hormones involved in energy balance (Kolatorova 2018); this was a small cross-sectional study.

Human studies of male reproduction and fertility are observational and their results are mixed:

• Among male partners attending a U.S. infertility clinic (semen quality measured in 190 men), urinary methyl- and propylparaben were not associated with hormone levels or semen quality; butylparaben was associated with sperm DNA damage but not with hormones or conventional semen measures. The authors note that paraben levels varied substantially over time in the same men and that the modest sample size could have limited the study (Meeker 2011).
• In young Danish men (65 carriers of filaggrin skin-barrier gene mutations and 130 non-carriers), no association was found between any paraben and reproductive hormones or semen quality; associations with other chemicals differed between the two groups (Joensen 2018).
• In a prospective cohort of 501 couples with urine collected before conception, the highest quartile of female urinary methylparaben, relative to the lowest, reflected a 34% reduction in fecundity, measured as time to pregnancy (adjusted fecundability odds ratio 0.66; 95% CI 0.45–0.97), with similar associations for ethylparaben; no associations were seen when the chemicals were modelled continuously (Smarr 2017).

Parabens Measured in Breast Tissue

The 2004 study by Darbre and colleagues (PubMed PMID: 14745841) measured individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography with tandem mass spectrometry. The mean total paraben concentration was 20.6 ng per gram of tissue; methylparaben was present at the highest level (mean 12.8 ng/g), 62% of the total recovered. What the study measured was presence in tumour samples only: no normal breast tissue was analysed for comparison, and the authors wrote that the findings should open the way to learning whether body burdens differ between cancerous and normal tissue (Darbre 2004). A 2022 review lists its limitations as a small sample size and the possibility that analytical blank values contained parabens introduced from other sources, and describes the epidemiological evidence directly linking paraben exposure with breast cancer as still limited (Hager 2022). An editorial published alongside it discussed what can and cannot be inferred from this type of data — including that it cannot show the cause of the tumours (Harvey 2004) — and three letters commenting on the study (Golden and Gandy; Jeffrey and Williams; Flower), with the authors’ replies, appeared in the same journal later in 2004.

A 2012 study involving the same senior author measured five parabens at four locations across the breast, from axilla to sternum, in tissue from 40 mastectomies for primary breast cancer (160 samples). One or more parabens were quantifiable in 158 of 160 samples (99%). Median concentrations were highest for n-propylparaben (16.8 ng/g) and methylparaben (16.6 ng/g), and the median total was 85.5 ng/g. n-Propylparaben was significantly higher in the axilla region than in the mid or medial regions. Parabens were also measured in the 7 of 40 patients who reported never having used underarm cosmetics, and the authors state that the source of the paraben cannot be identified. No correlations were found with age, length of breastfeeding, tumour location, or tumour estrogen receptor content (Barr 2012). A commentary concluded that intact esters in the breast are consistent with a local skin source, while noting the seven never-users and other possible sources (Harvey 2012).

Studies relating urinary parabens to breast cancer have not found a consistent direction. In the Long Island Breast Cancer Study Project (711 women with breast cancer, 598 without), the highest versus lowest quintiles of urinary methylparaben, propylparaben and total parabens were associated with breast cancer, with odds ratios of 1.31 to 1.50; among the women with breast cancer, whose urine was collected on average within three months of diagnosis, the same parabens were associated with lower all-cause mortality (hazard ratios 0.68 to 0.77) (Parada 2019). In the Multiethnic Cohort, which measured urine collected before diagnosis in 1,032 postmenopausal women with breast cancer and 1,030 matched controls, total parabens were weakly inversely associated with breast cancer risk (odds ratio 0.77 for the top versus bottom tertile; 95% CI 0.62–0.97); the authors call for studies with multiple pre-diagnosis urine samples (Wu 2021; a 2022 erratum was published).

Mechanisms of Endocrine Disruption

• Estrogen receptor binding. Parabens displace estradiol from the estrogen receptor and activate estrogen-regulated genes in breast cancer cells, at concentrations far higher than estradiol itself (Byford 2002; Routledge 1998).
• Growth-factor cross-talk. In ERα- and HER2-positive BT-474 breast cancer cells, butylparaben and the growth factor heregulin together produced a synergistic increase in the c-Myc oncogene, and heregulin lowered the butylparaben dose needed to stimulate cell proliferation. The authors suggest that parabens might be active at exposure levels not previously considered relevant from studies that tested them alone (Pan 2016).
• Anti-androgenic activity. In a cell-based androgen-receptor assay, methyl-, propyl- and butylparaben at 10 µM inhibited testosterone-induced transcriptional activity by 40%, 33% and 19%, respectively, while their metabolite 4-hydroxybenzoic acid had no effect (Chen 2007).
• Cell migration. Long-term (about 20-week) exposure of MCF-7 breast cancer cells to methyl-, n-propyl- or n-butylparaben increased migratory and invasive behaviour in laboratory assays (Khanna 2014).
• Mitochondria. A 2009 review proposes that interaction of parabens with mitochondrial function in the testis may be key to explaining a contribution of parabens to reduced reproductive potential; this is presented as a hypothesis for further study (Tavares 2009).

Body Burden and Biomonitoring

The CDC measured four parabens in 2,548 urine samples from people aged 6 and older in NHANES 2005–2006 (Calafat 2010):

• Methylparaben was detected in 99.1% of samples (median 63.5 µg/L) and propylparaben in 92.7% (median 8.7 µg/L).
• Ethylparaben (42.4%) and butylparaben (47%) were detected less often, at median concentrations at least ten times lower than methylparaben.
• Adolescent and adult females had significantly higher methyl- and propylparaben concentrations than adolescent and adult males.
• Methylparaben was significantly higher among non-Hispanic Black than non-Hispanic white participants, except at ages 60 and older.

The authors state that the differences by sex and race/ethnicity likely reflect use of personal care products containing these compounds. In breast tissue, one or more parabens were quantifiable in 99% of samples from 40 mastectomies (Barr 2012).

What Studies Report About Lowering Exposure

An intervention study has tested whether changing personal care products lowers urinary paraben levels. It compared urine samples taken before and after the change; its results are below:

• Personal care products (HERMOSA study). In a youth-led, community-based participatory study of 100 Latina adolescent girls, three days of using personal care products whose labels stated they did not contain phthalates, parabens, triclosan or benzophenone-3 (BP-3) were followed by average falls in urinary methylparaben of 43.9% (95% CI −61.3, −18.8) and propylparaben of 45.4% (95% CI −63.7, −17.9). Ethyl- and butylparaben unexpectedly rose, although their concentrations were low overall and not detected in almost half the samples. Over the same three days the phthalate metabolite MEP fell by 27.4%, triclosan by 35.7% and BP-3 by 36.0% (Harley 2016).
• Ingredient labels. The FDA states that cosmetics sold to consumers in stores or online must carry a list of ingredients, each listed by its common or usual name, and that parabens are usually easy to identify by names such as methylparaben, propylparaben, butylparaben or ethylparaben (FDA).
• Medicines. Parabens are also used as preservatives in pharmaceuticals (Calafat 2010). Questions about the ingredients of a specific medicine are for a pharmacist or clinician.

Regulatory Status and Policy

The FDA states: “At this time, we do not have information showing that parabens as they are used in cosmetics have an effect on human health,” and that its scientists continue to review published studies on paraben safety (FDA, Parabens in Cosmetics). The same page states that the FDA has no special rules that apply only to preservatives in cosmetics, that cosmetic products and ingredients other than color additives do not need FDA approval before going on the market, and that to act against a cosmetic for safety reasons the agency must have reliable scientific information showing that it is harmful when used as directed or in the customary way. In food, methylparaben and propylparaben are affirmed as GRAS (21 CFR 184.1490 and 184.1670; see Sources).

In the European Union, parabens are regulated as cosmetic preservatives in Annex V of the Cosmetics Regulation. Commission Regulation (EU) No 358/2014 prohibited isopropyl-, isobutyl-, phenyl-, benzyl- and pentylparaben, because limited or no information had been submitted for their safety evaluation, and kept the limits of 0.4% (as acid) for a single ester and 0.8% for mixtures of esters (Regulation (EU) No 358/2014, as adopted). The same regulation records that the SCCS conclusions on propyl- and butylparaben had been challenged by a study carried out by the French authorities, leading to a further SCCS risk assessment in May 2013. Commission Regulation (EU) No 1004/2014, applying from 16 April 2015, followed the Scientific Committee on Consumer Safety (SCCS) conclusion that butyl- and propylparaben are safe for consumers when the sum of their concentrations does not exceed 0.19% as esters, set as 0.14% expressed as acid, with the 0.8% total for all parabens kept. For general cosmetic products other than those for the nappy area, the SCCS found no safety concern for children of any age group. The regulation also prohibited butyl- and propylparaben in leave-on products designed for the nappy area of children under three years of age, because the SCCS could not exclude a risk for children below six months given their immature metabolism and possible damaged skin in that area. The SCCS confirmed that methylparaben and ethylparaben are safe at the maximum authorized concentrations (Regulation (EU) No 1004/2014, as adopted).

Both regulations record that the SCCS issued a clarification in October 2011 in response to a unilateral decision by Denmark to ban propylparaben and butylparaben, their isoforms and their salts in cosmetic products for children under three years of age, based on their potential endocrine activity.

Key Research Papers

1. Darbre PD, et al. Concentrations of parabens in human breast tumours. J Appl Toxicol. 2004;24(1):5–13. — PubMed PMID: 14745841
2. Darbre PD, et al. 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;28(5):561–578. — PubMed PMID: 18484575
3. Barr L, et al. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum. J Appl Toxicol. 2012;32(3):219–232. — PubMed PMID: 22237600
4. Oishi S. Effects of propyl paraben on the male reproductive system. Food Chem Toxicol. 2002;40(12):1807–1813. — PubMed PMID: 12419695
5. Wróbel AM, Gregoraszczuk EŁ. Actions of methyl-, propyl- and butylparaben on estrogen receptor-α and -β and the progesterone receptor in MCF-7 cancer cells and non-cancerous MCF-10A cells. Toxicol Lett. 2014;230(3):375–381. — PubMed PMID: 25128701
6. Vo TT, 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. — PubMed PMID: 20132880
7. Pan S, et al. Parabens and human epidermal growth factor receptor ligand cross-talk in breast cancer cells. Environ Health Perspect. 2016;124(5):563–569. — PubMed PMID: 26502914
8. Calafat AM, et al. Urinary concentrations of four parabens in the U.S. population: NHANES 2005–2006. Environ Health Perspect. 2010;118(5):679–685. — PubMed PMID: 20056562
9. Harvey PW, Everett DJ. Parabens detection in different zones of the human breast: consideration of source and implications of findings. J Appl Toxicol. 2012;32(5):305–309. — PubMed PMID: 22408000
10. Khanna S, Dash PR, Darbre PD. Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro. J Appl Toxicol. 2014;34(9):1051–1059. — PubMed PMID: 24652746
11. Kolatorova L, et al. Parabens and their relation to obesity. Physiol Res. 2018;67(Suppl 3):S465–S472. — PubMed PMID: 30484673
12. Routledge EJ, et al. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. Toxicol Appl Pharmacol. 1998;153(1):12–19. — PubMed PMID: 9875295
13. Byford JR, et al. Oestrogenic activity of parabens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2002;80(1):49–60. — PubMed PMID: 11867263
14. Chen J, et al. Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol Appl Pharmacol. 2007;221(3):278–284. — PubMed PMID: 17481686
15. Janjua NR, et al. Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans. Environ Sci Technol. 2007;41(15):5564–5570. — PubMed PMID: 17822133
16. Moos RK, et al. Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage. Arch Toxicol. 2016;90(11):2699–2709. — PubMed PMID: 26608183
17. Harvey PW, Everett DJ. Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours. J Appl Toxicol. 2004;24(1):1–4. — PubMed PMID: 14745840
18. Parada H Jr, et al. Urinary concentrations of environmental phenols and their associations with breast cancer incidence and mortality following breast cancer. Environ Int. 2019;130:104890. — PubMed PMID: 31228785
19. Wu AH, et al. Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study. Int J Cancer. 2021;149(7):1426–1434. — PubMed PMID: 34013527 (erratum: PubMed PMID: 35974458)
20. Tavares RS, et al. Parabens in male infertility — is there a mitochondrial connection? Reprod Toxicol. 2009;27(1):1–7. — PubMed PMID: 19007877
21. Harley KG, et al. Reducing Phthalate, Paraben, and Phenol Exposure from Personal Care Products in Adolescent Girls: Findings from the HERMOSA Intervention Study. Environ Health Perspect. 2016;124(10):1600–1607. — PubMed PMID: 26947464
22. 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;35(5):435–458. — PubMed PMID: 16097138
23. Hager E, Chen J, Zhao L. Minireview: Parabens Exposure and Breast Cancer. Int J Environ Res Public Health. 2022;19(3):1873. — PubMed PMID: 35162895
24. Meeker JD, et al. Urinary concentrations of parabens and serum hormone levels, semen quality parameters, and sperm DNA damage. Environ Health Perspect. 2011;119(2):252–257. — PubMed PMID: 20876036
25. Joensen UN, et al. Urinary excretion of phenols, parabens and benzophenones in young men: Associations to reproductive hormones and semen quality are modified by mutations in the Filaggrin gene. Environ Int. 2018;121(Pt 1):365–374. — PubMed PMID: 30245359
26. Smarr MM, et al. Urinary Concentrations of Parabens and Other Antimicrobial Chemicals and Their Association with Couples’ Fecundity. Environ Health Perspect. 2017;125(4):730–736. — PubMed PMID: 27286252

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Connections

• All Toxins
• BPA and Plastics
• Phthalates
• PFAS (Forever Chemicals)
• Microplastics & Nanoplastics
• Household Chemicals
• Heavy Metals in Cosmetics
• Pesticides
• Breast Cancer
• Hypothyroidism
• PCOS
• Detox Protocols

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