Table 3. Summary of chemicals in chemical families and potential harmful mechanisms.
Many of these chemical ingredients have varying routes of exposure and toxicities (e.g. oral, inhalation, dermal) reported by various databases and studies. Representative chemicals from each family will be reviewed, and only information relevant to our topic will be reported in this chart.
| Name Primary Use of Ingredient |
Endocrine Receptor Mechanisms | Other Nuclear Mechanisms |
|---|---|---|
|
Alpha hydroxy acids (used glycolic acid as a representative) Skin plasticizer (1) |
None found (1–3) | None found (1, 2) |
|
Beta hydroxy acids (used salicylic acid as a representative) Exfoliant (4) |
None found (2, 3, 5) | None found (2, 5) |
|
Butylated hydroxyanisole/butylated hydroxytoluene Cosmetic preservative (6) |
Butylated hydroxyanisole | |
| Reduces binding of estradiol to its receptor (7, 8), increases estrogen receptor transcription and binds estrogen receptor (8–11), and antagonizes dihydrotestosterone activation of androgen receptor (12) | Possibly carcinogenic in humans due to extensive evidence of carcinogenicity in animals (2) Evidence of gene toxicity in in vivo studies (2) |
|
| Butylated hydroxytoluene | ||
| Even more weakly anti-estrogenic and estrogenic effects than butylated hydroxyanisole (8) | None found (2, 13) | |
|
Coal tar dyes (used para- phenylenediamine as a representative)* Color dye (6) |
None found (2, 3, 14) | Not carcinogenic (14) Evidence of genotoxicity via oxidative stress and suppression of antioxidant activity (15–18) |
|
Diethanolamine compounds (used diethanolamine as a representative)** Emulsifier, foaming agent, pH adjuster (4) |
Anti-estrogenic and anti-androgenic (mechanism unknown) (19, 20) | Possibly carcinogenic in humans due to extensive evidence of carcinogenicity in animals (2) Not genotoxic (21) |
|
Formaldehyde releasing preservatives (toxicity search used “formaldehyde”) Slowly release formaldehyde over time (6). Formaldehyde is a cosmetic biocide and preservative (22). |
None found (2, 3, 22) | Known human carcinogen (23, 24) Evidence of genotoxicity via direct evidence of DNA damage in humans and oxidative stress particularly in ovaries (25–27) |
|
Parabens (used methylparaben as a representative) Cosmetic preservative (4) |
Inhibits testosterone-induced transcriptional activity (28) and interacts with estrogen receptor and increases expression of estrogen regulated genes (29, 30). | None found (31) |
|
Parfum/fragrance
*** Cosmetic fragrance |
See note | |
|
Phthalates (used diethylphthalate as a representative)
**** Fixative in fragrances and solvent (4) |
Different based on compound structure (32). Proposed mechanism of estrogenicity of DEP - binds and transactivates ERα receptors (33, 34). Evidence of anti-androgenicity as well but mechanism unknown (35). |
None found (36) |
|
Polyethylene glycol compounds
† Used as a cream base, increases permeability of skin to cosmetics (6) |
See note | |
|
Petrolatum
‡ Locks moisture into skin (6) |
Antagonistic activity at androgen receptors (37, 38) and interacts with estrogen receptor and upregulates transcription of ERβ (39, 40) | Known human carcinogen (41, 42) Evidence of genotoxicity via differing mechanisms depending on the specific polycyclic aromatic hydrocarbon and specific target tissue (43–45) |
|
Siloxanes (used cyclotetrasiloxane as a representative) Softens, smooths, and moistens cosmetics (6) |
Weakly estrogenic (binds ERα receptors) (46–49) and evidence of anti-androgenicity but mechanism unknown (46) | Limited evidence for carcinogenicity in rats (50) Not genotoxic (51) |
|
Sodium laureth sulfate
† Cleansing and foaming agent (6) |
None found (2, 3, 52) | Not carcinogenic (2, 52) |
|
Talc
§ Many uses, e.g. absorbs moisture, prevents caking, and increases opacity (4) |
See note | |
|
Triclosan Preservative and anti-bacterial agent (6) |
Inhibits testosterone-induced transcriptional activity (28), enhances androgen-induced transcriptional activity (35), and decreases E2-dependent reporter gene expression, inhibits estradiol and estrogen sulfotransferase activity (53, 54) | Evidence of carcinogenicity in mice but likely not in humans (2, 55) Not genotoxic (2, 55) |
Coal tar dyes are so named because the dyes were traditionally made with processed coal tar. Most companies have made the switch over to synthesizing these colors from petroleum, but consumers have no way of knowing how the dye used in the cosmetics was synthesized, and using petroleum has its own hazards (See Petrolatum).
Another major concern of ethanolamine compounds is their ability to react with nitrites and form carcinogenic nitrosamines (21, 56). Nitrites can come from degradation of some cosmetic preservatives when they are exposed to air (57) and nitrites are sometimes used in cosmetics as anti-corrosive ingredients (58).
Parfum/fragrance is created by cosmetic companies out of many different ingredients. Beauty companies are not required to list the exact ingredients in each product and can just list fragrance or flavor ingredients as “fragrance” or “flavor” (4). Out of the top five companies we examined, only Olay makes available a complete list of all components they use for fragrance across all of their products (59), and there are around 3,000 chemicals that can be used as fragrances (6). A glance at the list reveals that parfum can be composed of a huge variety of chemicals which are unregulated, as well as diethyl phthalate, which is a phthalate commonly used in fragrances (4). Due to the sheer number of chemicals that can act as fragrance components, it is impossible to examine their individual toxicities.
While there is a lot of evidence that exposure to phthalates causes a variety of health issues, those toxic effects are seen in longer-chain phthalates. The three most common phthalates use in cosmetics are dibutyl phthalate (DBP; as a plasticizer for nail polish to prevent cracking), dimethyl phthalate (DMP; as a plasticizer for hair spray to avoid stiffness), and diethyl phthalate (DEP; as a solvent and fixative in fragrances) (4). In 2010, the FDA conducted a study measuring phthalate levels in various cosmetics and found that DBP and DMP are not used as often anymore, and DEP is the only remaining phthalate that can be found in significant concentrations in cosmetics (4). Regardless, these three phthalates are not considered longer chain phthalates and therefore have fewer associated health risks.
The major concern of these chemicals is that depending on how the compound is manufactured, it can be contaminated with 1,4-dioxane (55, 60). Consumers have no way of knowing if the ingredients in their cosmetics are 1,4-dioxane free, and the Organic Consumers Association commissioned a study in 2008 that found 1,4-dioxane in a significant percentage of the organic products analyzed (61). 1,4-dioxane has been shown to be carcinogenic in animals (62).
The major concern of petrolatum is that incompletely refined petrolatum can be contaminated by polycyclic aromatic hydrocarbons (PAHs) (2). The toxicity data presented here for petrolatum will therefore be for PAHs.
The major concern of talc in cosmetics is that talc is a naturally occurring mineral that is mined from the earth, and some talc mining sites are contaminated by asbestos, which is a closely related naturally occurring mineral with a different crystal structure (4). Cosmetics companies are now careful about selecting talc mining sites, and the FDA did a study in 2009–2010 to detect asbestos from different suppliers of several cosmetic-grade raw talc as well as cosmetic products containing talc and found no detectable levels of asbestos in any of the samples (4).
Fiume MZ. Final report on the safety assessment of glycolic acid, ammonium, calcium, potassium, and sodium glycolates, methyl, ethyl, propyl, and butyl glycolates, and lactic acid, ammonium, calcium, potassium, sodium, and tea-lactates, methyl, ethyl, isopropyl, and butyl lactates, and lauryl, myristyl, and cetyl lactates. International Journal of Toxicology. 1998;17(Supplement 1):234.
Toxicology Data Network [database on the Internet]. National Institutes of Health, Health & Human Services. 2014 [cited 4/15/2016]. Available from: http://toxnet.nlm.nih.gov/.
TEDX List of Potential Endocrine Disruptors [database on the Internet]. The Endocrine Disruption Exchange, Inc. 2015 [cited 4/15/2016]. Available from: http://endocrinedisruption.org/endocrine-disruption/tedx-list-of-potential-endocrine-disruptors/overview.
Blum A, Balan SA, Scheringer M, Trier X, Goldenman G, Cousins IT, et al. The Madrid Statement on Poly- and Perfluoroalkyl Substances (PFASs). Environ Health Perspect. 2015 May;123(5):A107–11.
Fiume MZ. Safety assessment of salicylic acid, butyloctyl salicylate, calcium salicylate, C12–15 alkyl salicylate, capryloyl salicylic acid, hexyldodecyl salicylate, isocetyl salicylate, isodecyl salicylate, magnesium salicylate, MEA-salicylate, ethylhexyl salicylate, potassium salicylate, methyl salicylate, myristyl salicylate, sodium salicylate, TEA-salicylate, and tridecyl salicylate. International Journal of Toxicology. 2003;22(Supplement 3):108.
The “Dirty Dozen” Ingredients Investigated in the David Suzuki Foundation Survey of Chemicals in Cosmetics. David Suzuki Foundation, 2010.
Kang HG, Jeong SH, Cho JH, Kim DG, Park JM, Cho MH. Evaluation of estrogenic and androgenic activity of butylated hydroxyanisole in immature female and castrated rats. Toxicology. 2005 Sep 15;213(1–2):147–56.
Jobling S, Reynolds T, White R, Parker MG, Sumpter JP. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect. 1995 Jun;103(6):582–7.
Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995 Oct;103 Suppl 7:113–22.
ter Veld MG, Schouten B, Louisse J, van Es DS, van der Saag PT, Rietjens IM, et al. Estrogenic potency of food-packaging-associated plasticizers and antioxidants as detected in ERalpha and ERbeta reporter gene cell lines. Journal of agricultural and food chemistry. 2006 Jun 14;54(12):4407–16.
Amadasi A, Mozzarelli A, Meda C, Maggi A, Cozzini P. Identification of xenoestrogens in food additives by an integrated in silico and in vitro approach. Chem Res Toxicol. 2009 Jan;22(1):52–63.
Schrader TJ, Cooke GM. Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro. Toxicol Sci. 2000 Feb;53(2):278–88.
Lanigan RS, Yamarik TA. Final report on the safety assessment of BHT(1). Int J Toxicol. 2002;21 Suppl 2:19–94.
Johnson W, Jr. Amended Final Report of the Safety Assessment of p-Phenylenediamine, p-Phenylenediamine HCl, and p-Phenylenediamine Sulfate. Washington, DC: Cosmetic Ingredient Review, 2007.
Reena K, Ng KY, Koh RY, Gnanajothy P, Chye SM. 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. Environmental toxicology. 2016 Jan 19.
Zanoni TB, Hudari F, Munnia A, Peluso M, Godschalk RW, Zanoni MV, 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 Dec 15;239(3):194–204.
Anundi I, Hogberg J, Stead AH. Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage. Acta Pharmacol Toxicol (Copenh). 1979 Jul;45(1):45–51.
Picardo M, Zompetta C, Grandinetti M, Ameglio F, Santucci B, Faggioni A, et al. Paraphenylene diamine, a contact allergen, induces oxidative stress in normal human keratinocytes in culture. Br J Dermatol. 1996 Apr;134(4):681–5.
Kassotis CD, Klemp KC, Vu DC, Lin CH, Meng CX, Besch-Williford CL, et al. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice. Endocrinology. 2015 Dec;156(12):4458–73.
Kassotis CD, Tillitt DE, Davis JW, Hormann AM, Nagel SC. Estrogen and androgen receptor activities of hydraulic fracturing chemicals and surface and ground water in a drilling-dense region. Endocrinology. 2014 Mar;155(3):897–907.
Fiume MM, Heldreth B. Amended Final Safety Assessment of Diethanolamine and its Salts as Used in Cosmetics. Washington, DC: Cosmetic Ingredient Review, 2011.
Boyer IJ, Heldreth B, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, et al. Amended safety assessment of formaldehyde and methylene glycol as used in cosmetics. Int J Toxicol. 2013 Nov–Dec;32(6 Suppl):5S–32S.
Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, et al. A review of human carcinogens--Part F: chemical agents and related occupations. Lancet Oncol. 2009 Dec;10(12):1143–4.
Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol. Lyon, France: World Health Organization, 2006.
Ozen OA, Akpolat N, Songur A, Kus I, Zararsiz I, Ozacmak VH, et al. Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes: an immunohistochemical study. Toxicol Ind Health. 2005 Nov;21(10):249–54.
Peteffi GP, Antunes MV, Carrer C, Valandro ET, Santos S, Glaeser J, et al. Environmental and biological monitoring of occupational formaldehyde exposure resulting from the use of products for hair straightening. Environ Sci Pollut Res Int. 2016 Jan;23(1):908–17.
Wang HX, Wang XY, Zhou DX, Zheng LR, Zhang J, Huo YW, et al. Effects of low-dose, long-term formaldehyde exposure on the structure and functions of the ovary in rats. Toxicol Ind Health. 2013 Aug;29(7):609–15.
Chen J, Ahn KC, Gee NA, Gee SJ, Hammock BD, Lasley BL. Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol Appl Pharmacol. 2007 Jun 15;221(3):278–84.
Routledge EJ, Parker J, Odum J, Ashby J, Sumpter JP. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. Toxicol Appl Pharmacol. 1998 Nov;153(1):12–9.
Byford JR, Shaw LE, Drew MG, Pope GS, Sauer MJ, Darbre PD. Oestrogenic activity of parabens in MCF7 human breast cancer cells. The Journal of steroid biochemistry and molecular biology. 2002 Jan;80(1):49–60.
Panel CIRE. Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products. International Journal of Toxicology. 2008;27(Supplement 4):1–82.
Parveen 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 Chem. 2008 Jun;27(6):1416–25.
Harris CA, Henttu P, Parker MG, Sumpter JP. The estrogenic activity of phthalate esters in vitro. Environ Health Perspect. 1997 Aug;105(8):802–11.
Kumar N, Sharan S, Srivastava S, Roy P. Assessment of estrogenic potential of diethyl phthalate in female reproductive system involving both genomic and non-genomic actions. Reproductive toxicology. 2014 Nov;49:12–26.
Christen V, Crettaz P, Oberli-Schrammli A, Fent K. Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere. 2010 Nov;81(10):1245–52.
Panel CIRE. Annual Review of Cosmetic Ingredient Safety Assessments - 2002/2003. International Journal of Toxicology. 2005;24(Supplement1):1–102.
Vinggaard AM, Hnida C, Larsen JC. Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro. Toxicology. 2000 Apr 14;145(2–3):173–83.
Hawliczek A, Nota B, Cenijn P, Kamstra J, Pieterse B, Winter R, et al. Developmental toxicity and endocrine disrupting potency of 4-azapyrene, benzo[b]fluorene and retene in the zebrafish Danio rerio. Reproductive toxicology. 2012 Apr;33(2):213–23.
Li F, Wu H, Li L, Li X, Zhao J, Peijnenburg WJ. Docking and QSAR study on the binding interactions between polycyclic aromatic hydrocarbons and estrogen receptor. Ecotoxicol Environ Saf. 2012 Jun;80:273–9.
Sievers CK, Shanle EK, Bradfield CA, Xu W. Differential action of monohydroxylated polycyclic aromatic hydrocarbons with estrogen receptors alpha and beta. Toxicol Sci. 2013 Apr;132(2):359–67.
Flesher JW, Lehner AF. Structure, function and carcinogenicity of metabolites of methylated and non-methylated polycyclic aromatic hydrocarbons: a comprehensive review. Toxicology mechanisms and methods. 2016 Mar;26(3):151–79.
White AJ, Bradshaw PT, Herring AH, Teitelbaum SL, Beyea J, Stellman SD, et al. Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence. Environ Int. 2016 Apr–May;89–90:185–92.
Labib S, Williams A, Guo CH, Leingartner K, Arlt VM, Schmeiser HH, et al. Comparative transcriptomic analyses to scrutinize the assumption that genotoxic PAHs exert effects via a common mode of action. Arch Toxicol. 2015 Sep 16.
Long AS, Lemieux CL, Arlt VM, White PA. Tissue-specific in vivo genetic toxicity of nine polycyclic aromatic hydrocarbons assessed using the MutaMouse transgenic rodent assay. Toxicol Appl Pharmacol. 2016 Jan 1;290:31–42.
Einaudi L, Courbiere B, Tassistro V, Prevot C, Sari-Minodier I, Orsiere T, et al. In vivo exposure to benzo(a)pyrene induces significant DNA damage in mouse oocytes and cumulus cells. Hum Reprod. 2014 Mar;29(3):548–54.
McKim JM, Jr., Wilga PC, Breslin WJ, Plotzke KP, Gallavan RH, Meeks RG. 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 Sep;63(1):37–46.
Quinn AL, Dalu A, Meeker LS, Jean PA, Meeks RG, Crissman JW, et al. Effects of octamethylcyclotetrasiloxane (D4) on the luteinizing hormone (LH) surge and levels of various reproductive hormones in female Sprague-Dawley rats. Reproductive toxicology. 2007 Jun;23(4):532–40.
He B, Rhodes-Brower S, Miller MR, Munson AE, Germolec DR, Walker VR, et al. Octamethylcyclotetrasiloxane exhibits estrogenic activity in mice via ERalpha. Toxicol Appl Pharmacol. 2003 Nov 1;192(3):254–61.
Quinn AL, Regan JM, Tobin JM, Marinik BJ, McMahon JM, McNett DA, et al. In vitro and in vivo evaluation of the estrogenic, androgenic, and progestagenic potential of two cyclic siloxanes. Toxicol Sci. 2007 Mar;96(1):145–53.
Lee M. 24-month combined chronic toxicity and oncogenicity whole body vapor inhalation study of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats. Unpublished data submitted by Silicones Environmental, Health and Safety Council of North America. 2004:4801.
Johnson W, Jr., Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, et al. Safety assessment of cyclomethicone, cyclotetrasiloxane, cyclopentasiloxane, cyclohexasiloxane, and cycloheptasiloxane. Int J Toxicol. 2011 Dec;30(6 Suppl):149S–227S.
Robinson VC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Marks JG, Jr., et al. Final report of the amended safety assessment of sodium laureth sulfate and related salts of sulfated ethoxylated alcohols. Int J Toxicol. 2010 Jul;29(4 Suppl):151S–61S.
Ahn KC, Zhao B, Chen J, Cherednichenko G, Sanmarti E, Denison MS, et al. In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environ Health Perspect. 2008 Sep;116(9):1203–10.
James MO, Li W, Summerlot DP, Rowland-Faux L, Wood CE. Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta. Environ Int. 2010 Nov;36(8):942–9.
Panel CIRE. Final Report: Triclosan. Washington, DC: Cosmetic Ingredient Review, 2010.
Some N-Nitroso Compounds. World Health Organization, 1978.
Epstein SS. Toxic Beauty. Dallas: BenBella Books; 2009.
Skin Deep Cosmetic Database [database on the Internet]. Environmental Working Group. 2004 [cited 4/15/2016]. Available from: http://www.ewg.org/skindeep/.
Perfume & Scents. Cincinnati, OH: Proctor & Gamble.
Black PN, Sharpe S. Dietary fat and asthma: is there a connection? Eur Respir J. 1997 Jan;10(1):6–12.
Association OC. Carcinogenic 1,4-Dioxane Found in Leading “Organic” Brand Personal Care Products. Anaheim, CA: Organic Consumers Association; 2008.
National Toxicology P. Bioassay of 1,4-dioxane for possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser. 1978;80:1–123.