The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 2005, along with updated information regarding product types and concentrations of use, and confirmed that these 22 methacrylate ester monomers are safe as used in nail enhancement products in the practices of use and concentration as described in this report, when skin contact is avoided.
The Expert Panel for Cosmetic Ingredient Safety first published the Final Report on the Safety Assessment of methacrylate ester monomers in 2005.1 The Expert Panel concluded that the 22 methacrylate ester monomers listed below are safe as used in nail enhancement products when skin contact is avoided. The conclusion also states that products containing these ingredients should be accompanied with directions to avoid skin contact, because of the sensitizing potential of methacrylates.
It should be noted that two of the ingredients reviewed in the published final report, 2-Ethoxy Ethoxy Ethyl Methacrylate and Hexyl Methacrylate, are no longer listed in the International Cosmetic Ingredient Dictionary and Handbook.2 Because it has been at least 15 years since the final report was published, in accordance with Cosmetic Ingredient Review Procedures, the Expert Panel should determine whether the safety assessment should be reopened. At the December 2021 meeting, the Expert Panel considered updated information regarding product types and ingredient use frequencies as reported in the US Food and Drug Administration (FDA) Voluntary Cosmetic Registration Program (VCRP) database,3 and the maximum use concentrations provided by the Personal Care Products Council (Council).4 The cumulative frequency and concentration of use data are presented in Table 1 and described briefly below.
Current and Historical Frequency and Concentration of Use According to Duration and Exposure.
NR – not reported, NA – this ingredient is no longer in use; therefore 2021 data are not applicable.
aBecause each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses.
bAt the time of the 2003 safety assessment, concentration of use data were not reported by the FDA; however, industry provided a maximum concentration of use.
cIt is possible these products are sprays, but it is not specified whether the reported uses are sprays.
dIt is possible these products are powders, but it is not specified whether the reported uses are powders.
eNot specified whether a spray or a powder, but it is possible the use can be as a spray or a powder, therefore the information is captured in both categories.
Data submitted to the FDA in 2001 did not include any uses for 21 of the methacrylate ester monomers that were reviewed; only Tetrahydrofurfuryl Methacrylate had a reported use in one nail extender product. However, concentration of use data received from the cosmetics industry in 2001 indicated that all ingredients had reported uses, with maximum use concentrations of methacrylate ester monomers up to 85% (reported for Methoxydiglycol Methacrylate and Ethoxyethyl Methacrylate) in nail enhancement products. The results of a concentration of use survey conducted by the Council in 2020, and 2021 FDA VCRP data were provided. Collectively, these data indicate use of 14 methacrylate ester monomers in products that are applied to the nail. The most frequently used methacrylate ester monomer is HEMA, which has 149 uses and a reported maximum use concentration of 79% (in other manicuring products). Di-HEMA Trimethylhexyl Dicarbamate has a reported maximum use concentration of 91.8% (in nail extenders). Of the ingredients that are being reviewed, this is the highest reported maximum use concentration.
Importantly, the Expert Panel also reviewed safety data identified as published since 2001.3-193 The Expert Panel agreed that an updated search of the published literature did not reveal toxicity data that warrant re-evaluation of the safety of these ingredients in cosmetic products. After reviewing data on ingredient use frequencies and concentrations and safety data, the Expert Panel determined to not reopen this safety assessment on methacrylate ester monomers and reaffirmed the original conclusion.
Footnotes
Author Contributions
The articles in this supplement were sponsored by the Cosmetic Ingredient Review.
Author’s Note
Unpublished sources cited in this report are available from the Director, Cosmetic Ingredient Review, 1620 L Street, NW, Suite 1200, Washington, DC 20036, USA.
Declaration of Conflicting Interest
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The articles in this supplement were sponsored by the Cosmetic Ingredient Review. The Cosmetic Ingredient Review is financially supported by the Personal Care Products Council.
References
1.
EscobarAYamarikTA. Final report of the safety assessment of methacrylate ester monomers used in nail enhancement products. Int J Toxicol. 2005;24:53-100.
U.S. Food and Drug Administration Center for Food Safety & Applied Nutrition (CFSAN). Voluntary Cosmetic Registration Program - Frequency of Use of Cosmetic Ingredients. College Park, MD. 2021. (Obtained under the Freedom of Information Act from CFSAN; requested as “Frequency of Use Data” January 4, 2021; received January 21, 2021).
4.
Personal Care Products Council. Concentration of Use by FDA Product Category. Methacrylate Monomers; 2021.
5.
HenryBFotiCAlsanteK. Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule?J Photochem Photobiol B. 2009;96(1):57-62.
6.
ApiAMBelsitoDBotelhoD, et al.RIFM fragrance ingredient safety assessment, butyl methacrylate, CAS Registry Number 97-88-1. Food Chem Toxicol. 2020;144(Suppl 1):111613.
DurnerJWaltherUIZaspelJHickelRReichlFX. Metabolism of TEGDMA and HEMA in human cells. Biomaterials. 2010;31:818-823.
18.
DurnerJKreppelHZaspelJSchweiklHHickelRReichlFX. The toxicokinetics and distribution of 2-hydroxyethyl methacrylate in mice. Biomaterials. 2009;30:2066-2071.
19.
ReichlFXDurnerJHickelR, et al.Uptake, clearance and metabolism of TEGDMA in Guinea pigs. Dent Mater. 2002;18:581-589.
Van MillerJPGarmanRHHermanskySJMirsalisJCFrederickCB. Skin irritation, basal epithelial cell proliferation, and carcinogenicity evaluations of a representative specialty acrylate and methacrylate. Regul Toxicol Pharmacol. 2003;37:54-65.
Bielecka-KowalskaACzarnyPWignerP, et al.Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species. Toxicol Vitro. 2018;47:8-17.
AlbertiniRJ. The lower alkyl methacrylates: Genotoxic profile of non-carcinogenic compounds. Regul Toxicol Pharmacol. 2017;84:77-93.
81.
PawlowskaEPoplawskiTKsiazekDSzczepanskaJBlasiakJ. Genotoxicity and cytotoxicity of 2-hydroxyethyl methacrylate. Mutat Res. 2010;696(2):122-129.
82.
SzczepanskaJPoplawskiTSynowiecE, et al.2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation. Mol Biol Rep. 2012;39(2):1561-1574.
83.
HeilJReifferscheidGWaldmannPLeyhausenGGeurtsenW. Genotoxicity of dental materials. Mutat Res. 1996;368(3-4):181-194.
84.
KleinsasserNHWallnerBCHarreusUA, et al.Genotoxicity and cytotoxicity of dental materials in human lymphocytes as assessed by the single cell microgel electrophoresis (comet) assay. J Dent. 2004;32(3):229-234.
85.
KleinsasserNHSchmidKSassenAW, et al.Cytotoxic and genotoxic effects of resin monomers in human salivary gland tissue and lymphocytes as assessed by the single cell microgel electrophoresis (Comet) assay. Biomaterials. 2006;27(9):1762-1770.
86.
AnsteinssonVSolhaugASamuelsenJTHolmeJADahlJE. DNA damage, cell-cycle arrest and apoptosis induced in BEAS-2B cells by 2-hydroxyethyl methacrylate (HEMA). Mutat Res. 2011;723(2):158-164.
87.
SchweiklHSchmalzGSprussT. The induction of micronuclei in vitro by unpolymerized resin monomers. J Dent Res. 2001;80(7):1615-1620.
88.
LeeDHLimBSLeeYKAhnSJYangHC. Involvement of oxidative stress in mutagenicity and apoptosis caused by dental resin monomers in cell cultures. Dent Mater. 2006;22(12):1086-1092.
89.
ParanjpeABordadorLCFWangMYHumeWRJewettA. Resin monomer 2-hydroxyethyl methacrylate (HEMA) is a potent inducer of apoptotic cell death in human and mouse cells. J Dent Res. 2005;84(2):172-177.
DurnerJDebiakMBürkleAHickelRReichlF. Induction of DNA strand breaks by dental composite components compared to X-ray exposure in human gingival fibroblasts. Arch Toxicol. 2011;85:143-148.
93.
SchweiklHHartmannAHillerKA, et al.Inhibition of TEGDMA and HEMA-induced genotoxicity and cell cycle arrest by N-acetylcysteine. Dent Mater. 2007;23(6):688-695.
EckhardtAGerstmayrNHillerKA, et al.TEGDMA-induced oxidative DNA damage and activation of ATM and MAP kinases. Biomaterials. 2009;30:2006-2014.
101.
VolkJLeyhausenGGeurtsenW. Glutathione level and genotoxicity in human oral keratinocytes exposed to TEGDMA. J Biomed Mater Res, Part B. 2012;100:391-399.
102.
Wisniewska-JarosinskaMPoplawskiTChojnackiCJ, et al.Independent and combined cytotoxicity and genotoxicity of triethylene glycol dimethacrylate and urethane dimethacrylate. Mol Biol Rep. 2011;38:4603-4611.
MurakamiYKawataASuzukiSFujisawaS. Cytotoxicity and pro-inflammatory properties of aliphatic alpha, beta-unsaturated acid and ester monomers in RAW264.7 cells and their chemical reactivity. Vivo. 2019;33:313-323.
114.
VaraniJPeronePSpahlingerDM, et al.Human skin in organ culture and human skin cells (keratinocytes and fibroblasts) in monolayer culture for assessment of chemically Induced skin damage. Toxicol Pathol. 2007;35:693-701.
115.
MorisbakEUvsløkkSSamuelsenJT. In vitro effects of dental monomer exposure - Dependence on the cell culture model. Toxicol Vitro. 2020;67:104906.
116.
MorisbakEAnsteinssonVSamuelsenJT. Cell toxicity of 2-hydroxyethyl methacrylate (HEMA): The role of oxidative stress. Eur J Oral Sci. 2015;123:282-287.
KaufmanGKiburiNMSkrticD. The self-renewal dental pulp stem cell microtissues challenged by a toxic dental monomer. Biosci Rep. 2020;40(6):BSR20200210.
120.
NilsenBWSimon-SantamariaJOrtengrenU, et al.Dose- and time-dependent effects of triethylene glycol dimethacrylate on the proteome of human THP-1 monocytes. Eur J Oral Sci. 2018;126:345-358.
De RentiisAMAPinkMVermaNSchmitz-SpankeS. Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSensTM assay. Contact Dermatitis. 2021;84(5):317-325.
140.
FukumotoIMatsumuraMTamuraAMiuraHYuiN. Sensitization potential of dental resins: 2-hydroxyethyl methacrylate and its water-soluble oligomers have immunostimulatory effects. PLoS One. 2013;8(11):e82540.
AkiyamaTManabeATaniCTakahashiYItohKHisamitsuH. Guinea pig maximization test of tri-ethylene glycol mono-methacrylate. Dent Mater J. 2007;26(3):312-315.
Gatica-OrtegaMEPastor-NietoMAMercader-GarcíaPSilvestre-SalvadorJF. Allergic contact dermatitis caused by (meth)acrylates in long-lasting nail polish: Are we facing a new epidemic in the beauty industry?Contact Dermatitis. 2017;77:360-366.
166.
GoncaloMPinhoAAgnerT, et al.Allergic contact dermatitis caused by nail acrylates in Europe. An EECDRG study. Contact Dermatitis. 2018;78:254-260.
167.
GoonATBruzeMZimersonEGohCLSoo-Quee KohDIsakssonM. Screening for acrylate/methacrylate allergy in the baseline series: Our experience in Sweden and Singapore. Contact Dermatitis. 2008;59:307-313.
168.
IsakssonMLindbergMSundbergKHallanderABruzeM. The development and course of patch-test reactions to 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate. Contact Dermatitis. 2005;53:292-297.
169.
Aalto-KorteKAlankoKKuulialaOJolankiR. Methacrylate and acrylate allergy in dental personnel. Contact Dermatitis. 2007;57:324-330.
170.
RocheEde la CuadraJAlegreV. Sensibilización a acrilatos por uñas artificiales acrílicas. Revisión de 15 casos. Actas Dermosifiliog. 2008;99:788-794.
171.
GregoriouSTagkaAVelissariouE, et al.The rising incidence of allergic contact dermatitis to acrylates. Dermatitis. 2020;31(2):140-143.
172.
UterWGeierJ. Contact allergy to acrylates and methacrylates in consumers and nail artists – data of the Information Network of Departments of Dermatology, 2004–2013. Contact Dermatitis2015;72:224-228.
173.
LyapinaMDenchevaMKrastevaATzekovaMKisselova-YanevaA. Concomitant contact allergy to formaldehyde and methacrylic monomers in students of dental medicine and dental patients. Int J Occup Med Environ Health. 2014;27(5):797-807.
174.
LyapinaMGDenchevaMKrasteva-PanovaATzekova-YanevaMDeliverskaMKisselova-YanevaA. Concomitant sensitization to glutaraldehyde and methacrylic monomers among dentists and their patients. Med Pr. 2016;67(3):311-320.
175.
FischAHamneriusNIsakssonM. Dermatitis and occupational (meth)acrylate contact allergy in nail technicians-A 10-year study. Contact Dermatitis. 2019;81(1):58-60.
176.
RamosLCabralRGoncaloM. Allergic contact dermatitis caused by acrylates and methacrylates – a 7-year study. Contact Dermatitis. 2014;71:102-107.
177.
AsaiCInomataNSatoM, et al.Allergic contact dermatitis due to the liquid skin adhesive Dermabond predominantly occurs after the first exposure. Contact Dermatitis. 2021;84(2):103-108.
178.
DruckerAMPrattMD. Acrylate contact allergy: Patient characteristics and evaluation of screening allergens. Dermatitis. 2011;22(2):98-101.
179.
HavmoseMThyssenJPZachariaeCJohansenJD. Contact allergy to 2-hydroxyethyl methacrylate in Denmark. Contact Dermatitis. 2020;82(4):229-231.
180.
WarshawEMVollerLMSilverbergJI, et al.Contact dermatitis associated with nail care products: Retrospective analysis of North American Contact Dermatitis Group data, 2001–2016. Dermatitis2020;31(3):191-201.
181.
RollsSChowdhuryMMCooperS, et al.Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series. Br J Dermatol. 2019;181:811-817.
182.
LazarovA. Sensitization to acrylates is a common adverse reaction to artificial fingernails. JEADV. 2007;21:169-174.
Alcántara-NicolásFAPastor-NietoMASánchez-HerrerosC, et al.Allergic contact dermatitis from acrylic nails in a flamenco guitarist. Occup Med. 2016;66:751-753.
185.
LindstromMAlankoKKeskinenHKanervaL. Dentist’s occupational asthma, rhinoconjunctivitis, and allergic contact dermatitis from methacrylates. Allergy. 2002;57:543-545.
186.
VenablesZCNarayanaKJohnstonGA. Two unusual cases of allergic contact stomatitis caused by methacrylates. Contact Dermatitis. 2016;74:126-127.
187.
PanasoffJ. Leukoderma as a side-effect of patch testing with acrylates: A case report. Contact Dermatitis. 2020;82(6):403-404.
188.
HanselKTramontanaMBianchiLBrozziJStingeniL. Allergic contact stomatitis to dental prosthesis due to acrylic monomers with cross-reactivity to 2-hydroxyethyl methacrylate. Dermatitis. 2020;31(4):e28-e30.
189.
KjeldsenEWHavmoseMAhrensbøll-FriisUThyssenJPZachariaeC. Palmar eczema from secondary 2-hydroxyethyl methacrylate exposure - the artificial nail grip sign. Dermatitis. 2020;31(4):e26-e27.
190.
Gatica-OrtegaMEPastor-NietoMAGil-RedondoRMartínez-LorenzoERSchöendorff-OrtegaC. Non-occupational allergic contact dermatitis caused by long-lasting nail polish kits for home use: ‘The tip of the iceberg’. Contact Dermatitis. 2018;78:261-265.
191.
SuzukiKMatsunagaKSasakiKYagamiA. Allergic contact dermatitis caused by tetrahydrofurfuryl acrylate in the adhesive of clip-on earrings. Contact Dermatitis. 2020;82:131-133.
192.
ConstandtLHeckeEVNaeyaertJMGoossensA. Screening for contact allergy to artificial nails. Contact Dermatitis. 2005;52:73-77.
193.
DeKovenSDeKovenJHolnessDL. (Meth)acrylate occupational contact dermatitis in nail salon workers: A case series. J Cutan Med Surg. 2017;21(4):340-344.
