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Cosmetics use and age at menopause: is there a connection?

2016; Elsevier BV; Volume: 106; Issue: 4 Linguagem: Inglês

10.1016/j.fertnstert.2016.08.020

1556-5653

Erika Chow, Shruthi Mahalingaiah,

Agriculture Sustainability and Environmental Impact

Cosmetics contain a vast number of chemicals, most of which are not under the regulatory purview of the Food and Drug Administration. Only a few of these chemicals have been evaluated for potential deleterious health impact: parabens, phthalates, polycyclic aromatic hydrocarbons, and siloxanes. A review of the ingredients in the best-selling and top-rated products of the top beauty brands in the world, as well as a review of highlighted chemicals by nonprofit environmental organizations, reveals 11 chemicals and chemical families of concern: butylated hydroxyanisole/butylated hydroxytoluene, coal tar dyes, diethanolamine, formaldehyde-releasing preservatives, parabens, phthalates, 1,4-dioxane, polycyclic aromatic hydrocarbons, siloxanes, talc/asbestos, and triclosan. Age at menopause can be affected by a variety of mechanisms, including endocrine disruption, failure of DNA repair, oxidative stress, shortened telomere length, and ovarian toxicity. There is a lack of available studies to make a conclusion regarding cosmetics use and age at menopause. What little data there are suggest that future studies are warranted. Women with chronic and consistent use of cosmetics across their lifespan may be a population of concern. More research is required to better elucidate the relationship and time windows of vulnerability and the effects of mixtures and combinations of products on ovarian health. Cosmetics contain a vast number of chemicals, most of which are not under the regulatory purview of the Food and Drug Administration. Only a few of these chemicals have been evaluated for potential deleterious health impact: parabens, phthalates, polycyclic aromatic hydrocarbons, and siloxanes. A review of the ingredients in the best-selling and top-rated products of the top beauty brands in the world, as well as a review of highlighted chemicals by nonprofit environmental organizations, reveals 11 chemicals and chemical families of concern: butylated hydroxyanisole/butylated hydroxytoluene, coal tar dyes, diethanolamine, formaldehyde-releasing preservatives, parabens, phthalates, 1,4-dioxane, polycyclic aromatic hydrocarbons, siloxanes, talc/asbestos, and triclosan. Age at menopause can be affected by a variety of mechanisms, including endocrine disruption, failure of DNA repair, oxidative stress, shortened telomere length, and ovarian toxicity. There is a lack of available studies to make a conclusion regarding cosmetics use and age at menopause. What little data there are suggest that future studies are warranted. Women with chronic and consistent use of cosmetics across their lifespan may be a population of concern. More research is required to better elucidate the relationship and time windows of vulnerability and the effects of mixtures and combinations of products on ovarian health. Discuss: You can discuss this article with its authors and with other ASRM members at https://www.fertstertdialog.com/posts/11408-cosmetics-use-and-age-at-menopause-is-there-a-connection Discuss: You can discuss this article with its authors and with other ASRM members at https://www.fertstertdialog.com/posts/11408-cosmetics-use-and-age-at-menopause-is-there-a-connection Women are susceptible to the societal pressures of using cosmetics to beautify themselves (1Barker D.J. Barker M.J. The body as art.J Cosmet Dermatol. 2002; 1: 88-93Crossref PubMed Scopus (6) Google Scholar, 2Hill S.E. Rodeheffer C.D. Griskevicius V. Durante K. White A.E. Boosting beauty in an economic decline: mating, spending, and the lipstick effect.J Pers Soc Psychol. 2012; 103: 275-291Crossref PubMed Scopus (0) Google Scholar, 3Ehlinger-Martin A. Cohen-Letessier A. Taieb M. Azoulay E. du Crest D. Women's attitudes to beauty, aging, and the place of cosmetic procedures: insights from the QUEST Observatory.J Cosmet Dermatol. 2016; 15: 89-94Crossref PubMed Google Scholar). One theory behind the origins of the ♀ symbol used to denote "woman" is that it represents the hand mirror used by the Roman goddess Venus or the Greek goddess Aphrodite (4Stearn W.T. The origin of the male and female symbols of biology.Taxon. 1962; 11: 109-113Crossref Google Scholar). In their efforts to look beautiful, both men and women apply cosmetics to hide their flaws and accentuate their features. Cosmetics have been a part of human history as far back as the ancient Egyptians (5Oumeish O.Y. The cultural and philosophical concepts of cosmetics in beauty and art through the medical history of mankind.Clin Dermatol. 2001; 19: 375-386Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). The ancient Egyptians, Romans, and Greeks used various ingredients to soften, improve, exfoliate, and detoxify skin (5Oumeish O.Y. The cultural and philosophical concepts of cosmetics in beauty and art through the medical history of mankind.Clin Dermatol. 2001; 19: 375-386Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). The ancient Romans and Greeks used walnut extracts as hair dye, antimony (a known toxic heavy metal) as eye shadow, white lead carbonate as a skin lightener, charcoal crocodile excrement as a skin darkener, and cinnabar as rouge (5Oumeish O.Y. The cultural and philosophical concepts of cosmetics in beauty and art through the medical history of mankind.Clin Dermatol. 2001; 19: 375-386Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). The present article broadly addresses the question, "Cosmetics use and menopause—is there a connection?" The Oxford English Dictionary defines "cosmetics" as "A preparation intended to beautify the hair, skin, or complexion" (6Oxford English Dictionary. Cosmetic, adj. and n. Oxford: Oxford University Press. Available at: http://www.oxforddictionaries.com/us/definition/american_english/cosmetic. Last accessed August 30, 2016.Google Scholar). The word comes from the Greek word kosmetikos ("relating to adornment"), which is taken from the Greek word kosmein ("to arrange, adorn"), which itself is taken from the Greek word kosmos ("order, adornment") (6Oxford English Dictionary. Cosmetic, adj. and n. Oxford: Oxford University Press. Available at: http://www.oxforddictionaries.com/us/definition/american_english/cosmetic. Last accessed August 30, 2016.Google Scholar). For the purposes of this review, we define cosmetics as any product applied to the skin to enhance and beautify, i.e., products often labeled as "makeup." In 2014, the revenue of the cosmetics industry in the United States alone was 56.63 billion dollars (7Dawber T.R. Kannel W.B. Lyell L.P. An approach to longitudinal studies in a community: the Framingham Study.Ann N Y Acad Sci. 1963; 107: 539-556Crossref PubMed Google Scholar), compared with the global oral contraceptive pills market which was valued at 5.236 billion that same year (8Daan N.M. Fauser B.C. Menopause prediction and potential implications.Maturitas. 2015; 82: 257-265Abstract Full Text Full Text PDF PubMed Google Scholar). Companies sell a broad spectrum of cosmetic items, each item containing a huge variety of chemicals that all contribute to the color, texture, patina (sheen vs. matte), odor, preservation, suspension, lubrication, thermal stability, and finishing texture of the cosmetic. Given the widespread and frequent personal use of cosmetics containing classes of compounds that are endocrine disrupters, it is of great importance for women and health care providers to understand the potential harm that ingredients in cosmetics can have on women's reproductive health and reproductive aging. In a survey administered to pregnancy planners and pregnant women regarding risk perception of cosmetic use, out of 128 respondents (68 of whom were pregnant), 39.5% thought that cosmetics outside of pregnancy were "fairly safe" and 37.7% thought that cosmetics were "not really safe" (9Marie C. Cabut S. Vendittelli F. Sauvant-Rochat M.P. Changes in cosmetics use during pregnancy and risk perception by women.Int J Environ Res Public Health. 2016; 13: 383Crossref PubMed Google Scholar). Despite this fairly high level of concern, most women did not intend to/had not changed their cosmetics use during pregnancy (9Marie C. Cabut S. Vendittelli F. Sauvant-Rochat M.P. Changes in cosmetics use during pregnancy and risk perception by women.Int J Environ Res Public Health. 2016; 13: 383Crossref PubMed Google Scholar). While the United States Food and Drug Administration (FDA) closely monitors the chemicals that go into foods, drugs, and medical devices, cosmetics are not subjected to similar scrutiny. The FDA does not have to approve any cosmetics that go on the market unless the product claims to treat or prevent disease or alter the body in any way (in which case the product is classified as a drug) (10U.S. Food and Drug AdministrationIs it a cosmetic, a drug, or both? (or is it soap?).2002http://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm074201.htmGoogle Scholar). There are only 11 chemicals that are outright prohibited or restricted for use in cosmetics: bithionol, chlorofluorocarbon propellants, chloroform, halogenated salicylanilides, hexachlorophene, mercury compounds, methylene chloride, cattle materials, sunscreens, vinyl chloride, and zirconium-containing complexes (11Butler M.G. McGuire A. Manzardo A.M. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.J Assist Reprod Genet. 2015; 32: 495-508Crossref PubMed Scopus (1) Google Scholar). Of note, color additives must be approved by the FDA before use in any cosmetics (12U.S. Food and Drug AdministrationColor additives and cosmetics.2006http://www.fda.gov/ForIndustry/ColorAdditives/ColorAdditivesinSpecificProducts/InCosmetics/ucm110032.htmGoogle Scholar). The exception to this rule is color additives derived from mineral, plant, or animal sources, or additives derived from coal tar or petroleum (12U.S. Food and Drug AdministrationColor additives and cosmetics.2006http://www.fda.gov/ForIndustry/ColorAdditives/ColorAdditivesinSpecificProducts/InCosmetics/ucm110032.htmGoogle Scholar). However, coal tar dyes, especially para-phenylenediamine, have been linked to DNA damage (13IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, ed. Occupational exposures of hairdressers and barbers and personal use of hair colourants; some hair dyes, cosmetic colourants, industrial dyestuffs and aromatic amines. Lyon, France: International Agency for Research on Cancer, 1993.Google Scholar, 14Zanoni T.B. Hudari F. Munnia A. Peluso M. Godschalk R.W. Zanoni M.V. et al.The oxidation of p-phenylenediamine, an ingredient used for permanent hair dyeing purposes, leads to the formation of hydroxyl radicals: oxidative stress and DNA damage in human immortalized keratinocytes.Toxicol Lett. 2015; 239: 194-204Crossref PubMed Scopus (2) Google Scholar, 15Reena K. Ng K.Y. Koh R.Y. Gnanajothy P. Chye S.M. para-Phenylenediamine induces apoptosis through activation of reactive oxygen species-mediated mitochondrial pathway, and inhibition of the NF-kappaB, mTOR, and Wnt pathways in human urothelial cells.Environ Toxicol. 2016 Jan 19; ([Epub ahead of print.])https://doi.org/10.1002/tox.22233PubMed Google Scholar). This paper describes the chemicals that cosmetics contain and discusses the few studies that address how these chemicals can potentially affect human physiology, especially in relation to menopause. Owing to the vast number of chemical ingredients in cosmetics, we devised the following methodology to identify chemicals for which to conduct our literature review (Fig. 1). Once these chemicals were identified, we generated a word cloud to visualize the frequency of chemicals and undertook a literature review. To summarize our identification methodology, we began by using the Forbes list of top ten global beauty brands in 2012 (16Goudreau J. The top 10 global beauty brands. Forbes Magazine, 2012. Available at: http://www.forbes.com/sites/jennagoudreau/2012/04/20/the-top-10-global-beauty-brands/#4b034f99ec55. Last accessed August 23, 2016.Google Scholar). We did not use the top-grossing global beauty companies, because many companies own several brands. From the top ten beauty brand list, we went to the websites of the top five. These brands are denoted by symbolic letters X, A, B, C, and D (in order from largest to smallest global brand revenue) (16Goudreau J. The top 10 global beauty brands. Forbes Magazine, 2012. Available at: http://www.forbes.com/sites/jennagoudreau/2012/04/20/the-top-10-global-beauty-brands/#4b034f99ec55. Last accessed August 23, 2016.Google Scholar). On each site, we looked at lip makeup, face makeup, and eye makeup products of each company and extracted the ingredient list of the top three to five best-selling or top-rated products in each category, depending on the company (Table 1 provides a complete list of the products assessed in this paper). Brands X and D carry only skin care products and no makeup, so they were not included in the table.Table 1Complete list of products examined for the major ingredients in cosmetics as shown in the word cloud in Figure 2.Brand ABrand BBrand CFaceLipEyeFaceLipEyeFaceLipEyeSmooth Minerals BlushUltra Luxury Lip LinerGlimmersticks Brow DefinerVisible Lift Blur ConcealerColour Riche LipcolourStudio Secrets Professional Eye Shadow DuosShine Control Liquid MakeupMoistureShine GlossNourishing Long Wear Eye Shadow + Built-in PrimerSmooth Minerals Powder FoundationMark. Gloss Gorgeous Stay On Lip StainGlimmersticks Eye LinerInfallible Pro-Matte FoundationColour Riche La Lacque Lip PenBrow Stylist PlumperShine Control PrimerRevitalizing Lip Balm SPF 20Nourishing Eye LinerInvisible Coverage Liquid FoundationMark. Lipstick Full Color LipstickUltra Luxury Brow LinerTrue Match ConcealerInfallible Pro-Matte GlossInfallible 24 Hour Eye ShadowSkinClearing Mineral PowderMoistureSmooth Color StickHealthy Lengths MascaraIdeal Flawless Invisible Coverage Cream-to-Powder FoundationUltra Luxury Eye LinerInfallible Pro-Matte PowderColour Riche Collection Exclusive Red LipcolorHiP High Intensity Pigments Matte Shadow DuosMineral Sheers Loose Powder FoundationMoistureShine Lip Soother SPF 20Healthy Skin Brightening Eye Perfector Broad Spectrum SPF 25Ideal Luminous BlushSuperShock Mascara in BlackInfallible Pro Contour PaletteInfallible Matte-Matic LinerNourishing Long Wear Liquid Makeup Broad Spectrum SPF 20Healthy Volume Mascara Regular Open table in a new tab We defined face makeup as any product that is applied to the skin for enhancing purposes. Eye makeup encompassed any makeup that is applied near the eye, including eye liners, mascaras, eye shadows, and brow liners. Lip makeup is any lip color–or shape–enhancing makeup, therefore not including lip balms. Because several ingredients are in the same chemical family but have different names, we simplified the list of ingredients by replacing some with their chemical family name (e.g., paraben in place of methylparaben and ethylparaben) to better isolate which chemical families most commonly appear in the ingredients. Table 2 presents the ingredients and their associated chemical family names. Because different companies named some ingredients differently (e.g., "safflower seed oil" vs. "Carthamus tinctorius [safflower] seed oil"), we also standardized the names, but we did not include the standardizations in Table 2. The simplified ingredient list was then inserted into a word cloud generator to visualize which chemical families appeared the most (Fig. 2). There are two algorithms used in word cloud generation: One is a direct correlate of the count data and the other is a log function of the count. We used the direct correlation to best represent what cosmetic users may be most concerned about. From the word cloud, it was immediately apparent that coal tar dyes, siloxanes, and parabens were the most frequent chemical exposures from cosmetics application. Iron oxide and titanium dioxide color dyes appeared with high frequency, but because they are inorganic compounds that have little dermal penetration we did not include them in our literature search (17Environmental Working GroupSkin Deep Cosmetic Database.2004http://www.ewg.org/skindeep/Google Scholar). A total of 1,322 ingredients were compiled for the word cloud. Of the 1,322 ingredients, we consolidated chemicals into nine chemical families. Of the three largest chemical families, 145 ingredients were classified into the family of coal tar dyes, 95 into siloxanes, and 39 into parabens. Of the remaining 1,043 individual chemicals we identified that could not be consolidated into chemical families, we cross-referenced our list of chemicals with websites detailing chemicals of concern. From that, we identified an additional 12 chemicals to assess for ovarian toxicity and age at menopause.Table 2Chemicals assigned to a chemical family for the word cloud.Label usedReplaced namesAlpha-hydroxy acidCitric acidLactic acidBeta-hydroxyl acidSalicylic acidCoal tar dyeBlue 1/CI 42090Blue 1 Lake/CI 42090Brown 1/CI 20170Green 5/CI 61570Green 6/CI 61565Orange 4/CI 15510Orange 5/CI 45370Orange 5 Lake/CI 45370Red 4/CI 14700Red 7/CI 15850Red 7 Lake/CI 15850Red 6/CI 15850Red 6 Lake/CI 15850Red 17/CI 26100Red 21/CI 45380Red 21 Lake/CI 45380Red 22/CI 45380Red 22 Lake/CI 45380Red 30/CI 73360Red 33/CI 17200Red 33 Lake/CI 17200Red 34/CI 15880Red 34 Lake/CI 15880Red 36/CI 12085Red 36 Lake/CI 12085Red 40/CI 16035Red 40 Lake/CI 16035Violet 2/CI 60725Ext. Violet 2/CI 60730Yellow 5/CI 19140Yellow 5 Lake/CI 19140Yellow 7/CI 45350Ext. Yellow 7/CI 10316Yellow 8/CI 45350Yellow 10/CI 47005Yellow 10 Lake/CI 47005Ethylenediaminetetraacetic acid (EDTA)Disodium EDTATetrasodium EDTATrisodium EDTAParabenButylparabenEthylparabenIsobutylparabenIsopropylparabenMethylparabenPropylparabenPhthalatePolyethylene terephthalateTerephthalatePolyethylene glycol (PEG)PEG-6 beeswaxPEG-9PEG-40 stearatePyroglutamic acid (PCA)Calcium PCALauryl PCASodium PCAZinc PCASiloxaneBis-PEG/PPG-14/14 dimethiconeBis-PEG-12/dimethicone beeswaxC30–45 alkyl ceteayl dimethicone crosspolymerCaprylyl trimethiconeCetearyl dimethicone crosspolymerCetyl dimethiconeCetyl PEG/PPG-10/1 dimethiconeCyclohexasiloxaneCyclopentasiloxaneMethiconeDimethiconeDimethicone crosspolymerDimethicone/PEG-10/15 crosspolymerDimethicone/Vinyl dimethicone crosspolymerDiphenyl dimethiconeEthyl trisiloxaneHexamethyldisiloxane/disiloxaneLauryl PEG-9 polydimethylsiloxyethyl dimethiconeMethyl trimethiconeNylon-611/dimethicone copolymerPEG/PPG-18/18 dimethiconePEG/PPG-20/23 dimethiconePEG-9 polydimethylsiloxyethyl dimethiconePEG-10 dimethiconePhenyl trimethiconeSteardimonium hydroxypropyl panthenyl PEG-7 dimethicone phosphate chloride Stearoxymethicone/dimethicone copolymerStearyl dimethiconeTrimethylsiloxyphenyl dimethiconeVinyl dimethicone/methicone silsequioxane crosspolymerChemicals of concern that do not appear in the word cloudBeta-hydroxyl acidSodium laureth sulfateChemical families commonly found in cosmetics not found in the products in Table 1Butylated hydroxyanisoleTriclosanNote: All ingredients were taken from the ingredients list of the products mentioned in Table 1. Chemicals that were part of the same family were replaced with the family name (e.g., Blue 1/CI 42090 is a coal tar dye and was replaced with "coal tar dye" for the word cloud), making sure to preserve the frequency of appearance for each ingredient. Open table in a new tab Note: All ingredients were taken from the ingredients list of the products mentioned in Table 1. Chemicals that were part of the same family were replaced with the family name (e.g., Blue 1/CI 42090 is a coal tar dye and was replaced with "coal tar dye" for the word cloud), making sure to preserve the frequency of appearance for each ingredient. To determine if there were any remaining chemicals that were not identified through the methods above in our definition of makeup, we turned to the David Suzuki Foundation (a Canadian environmental nonprofit organization; www.davidsuzuki.org) and the cosmetics branch of the FDA (www.fda.gov/Cosmetics). In 2010, the David Suzuki Foundation investigated a list of "dirty dozen" cosmetics ingredients that contained butylated hydroxyanisole/butylated hydroxytoluene, coal tar dyes, diethanolamine compounds, dibutyl phthalate, formaldehyde-releasing preservatives, parabens, parfum, polyethylene glycol compounds, petrolatum, siloxanes, sodium laureth sulfate, and triclosan (18David Suzuki Foundation. The "dirty dozen" ingredients investigated in the David Suzuki Foundation survey of chemicals in cosmetics. 2010. Available at: http://www.davidsuzuki.org/issues/downloads/Dirty-dozen-backgrounder.pdf. Last accessed August 23, 2016.Google Scholar). The FDA website highlights certain additional cosmetic ingredients, which are alpha-hydroxy acids, beta-hydroxy acids, phthalates, and talc (19Blum A. Balan S.A. Scheringer M. Trier X. Goldenman G. Cousins I.T. et al.The Madrid Statement on poly- and perfluoroalkyl substances (PFASs).Environ Health Perspect. 2015; 123: A107-A111Crossref PubMed Scopus (11) Google Scholar). However, beta-hydroxy acids were an infrequent ingredient and did not appear in the word cloud. Based on our inclusion criteria for the word cloud, some other ingredients did not appear in the word cloud: diethanolamine (only triethanolamine appeared in the ingredients; ethanolamine compounds are used mostly in moisturizers or shampoos/soaps, which were not included in this review), butylated hydroxyanisole (used mostly in lipsticks and eye shadow but did not appear as an ingredient in any of the products we assessed), sodium laureth sulfate (infrequent in cosmetics—it is used mostly in shampoos/soaps, which were not included in this paper), and triclosan (used mostly in personal hygiene and deodorant products, which were not included in this paper). After identification of the final list, Pubmed was used to conduct a literature review with the chemical of interest and the following other search terms: "menopause," "reproductive senescence," and "ovarian failure." To assess the toxicity and endocrine disruption of each chemical, we used the United States National Library of Medicine's Toxicology Data Network (http://toxnet.nlm.nih.gov/), Cosmetic Ingredient Review's safety assessment reports (http://www.cir-safety.org/ingredients), the Endocrine Disruption Exchange's list of potential endocrine disruptors (http://endocrinedisruption.org/endocrine-disruption/tedx-list-of-potential-endocrine-disruptors/), and Pubmed searches for the chemical of interest and the following other search terms: "genotox*," "carcino*," "endocrine," "estrogen," and "androgen." Supplemental Table 1 (available online at www.fertstert.org) is a compilation of all of these chemicals, along with their primary use and their known toxicity to the human body (some ingredients have not been shown to be toxic to humans, but for the sake of completion we have listed all ingredients as well as all known information about relevant toxicity). We will focus on those chemicals that have relevant toxicities to humans. Some studies have examined the relationship between use of personal care products and serum or urinary concentrations of the ingredients. Because very few studies specifically examined the association between cosmetics use and ingredients absorption, we also included studies that examine topical personal care product use to provide a better picture of how these ingredients can be absorbed through the skin. This section discusses the studies that have been published on siloxanes, diethanolamine, phthalates, and parabens. One study looked at use of personal care products in a cohort of 94 postmenopausal women in Norway and serum levels of estrogenic (20Quinn A.L. Regan J.M. Tobin J.M. Marinik B.J. McMahon J.M. McNett D.A. et al.In vitro and in vivo evaluation of the estrogenic, androgenic, and progestagenic potential of two cyclic siloxanes.Toxicol Sci. 2007; 96: 145-153Crossref PubMed Scopus (33) Google Scholar) and antiandrogenic (21McKim Jr., J.M. Wilga P.C. Breslin W.J. Plotzke K.P. Gallavan R.H. Meeks R.G. Potential estrogenic and antiestrogenic activity of the cyclic siloxane octamethylcyclotetrasiloxane (D4) and the linear siloxane hexamethyldisiloxane (HMDS) in immature rats using the uterotrophic assay.Toxicol Sci. 2001; 63: 37-46Crossref PubMed Scopus (45) Google Scholar) cyclic volatile methylsiloxane (cVMS) (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). Sources of exposure to cVMS are generally through cVMS present in personal care products, inhalation due to the volatility of the compounds, or cVMS contained in breast implants (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). None of the women in the cohort had breast implants, and 90.5% of the women creamed more than 10% of their skin area each day (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). cVMS also has a low blood:air partition coefficient, and therefore inhalation exposure would have only had a minor contribution to serum levels of cVMS unless there was risk of workplace air exposure (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). Unfortunately, because different products carry varying levels of cVMS, no direct correlation was drawn between serum levels and specific personal care product use (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). Of the 94 women examined, 85% of the women exceeded the limit of quantification for octamethylcyclotetrasiloxane, 18% for decamethylcyclopentasiloxane, and 5% for dodecamethylcyclohexasiloxane (22Hanssen L. Warner N.A. Braathen T. Odland J.O. Lund E. Nieboer E. et al.Plasma concentrations of cyclic volatile methylsiloxanes (cVMS) in pregnant and postmenopausal Norwegian women and self-reported use of personal care products (PCPs).Environ Int. 2013; 51: 82-87Crossref PubMed Scopus (12) Google Scholar). A study provided three premenopausal women with lotion containing 1.8 mg diethanolamine/gram of lotion and instructed them to apply the lotion every day for a month (23Craciunescu C.N. Niculescu M.D. Guo Z. Johnson A.R. Fischer L. Zeisel S.H. Dose response effects of dermally applied diethanolamine on neurogenesis in fetal mouse hippocampus and potential exposure of humans.Toxicol Sci. 2009; 107: 220-226Crossref PubMed Scopus (5) Google Scholar). Diethanolamine is a compound that is antiestrogenic, antiandrogenic, and possibly carcinogenic (24Kassotis C.D. Klemp K.C. Vu D.C. Lin C.H. Meng C.X. Besch-Williford C.L. et al.Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice.Endocrinology. 2015; 156: 4458-4473Crossref PubMed Scopus (4) Google Scholar, 25Kassotis C.D. Tillitt D.E. Davis J.W. Hormann A.M. Nagel S.C. Estrogen and androgen receptor activities of hydraulic fracturing chemicals and surface and ground water in a drilling-dense region.Endocrinology. 2014; 155: 897-907Crossref PubMed Scopus (32) Google Scholar, 26Health and Human Services, National Institutes of HealthToxicology Data Network.2014http://toxnet.nlm.nih.gov/Google Scholar). Blood samples of the subjects revealed detectable plasma concentrations of diethanolamine after lotion application (23Craciunescu C.N. Niculescu M.D. Guo Z. Johnson A.R. Fischer L. Zeisel S.H. Dose response effects of dermally applied diethanolamine on neurogenesis in fetal mouse hippocampus and potential exposure of humans.Toxicol Sci. 2009; 107: 220-226Crossref PubMed Scopus (5) Google Scholar). An extensive study of personal care product use among pregnant women revealed significant associations between product use and urinary concentrations of phthalate metabolites and antiandrogenic (27Chen J. Ahn K.C. Gee N.A. Gee S.J. Hammock B.D. Lasley B.L. Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products.Toxicol Appl Pharmacol. 2007; 221: 278-284Crossref PubMed Scopus (83) Google Scholar) and estrogenic (28Routledge E.J. Parker J. Odum J. Ashby J. Sumpter J.P. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic.Toxicol Appl Pharmacol. 1998; 153: 12-19Crossref PubMed Scopus (375) Google Scholar) parabens. Phthalates are a class of chemicals that have different hormonal activities depending on the congener's compound structure (29Parveen M. Inoue A. Ise R. Tanji M. Kiyama R. Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (EstrArray).Environ Toxicol