Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics

Transcription

1 Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: June 18, 2015 Panel Meeting Date: September 21-22, 2015 All interested persons are provided 60 days from the above date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Director, Dr. Lillian J. Gill. The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC ph fax cirinfo@cir-safety.org

2 INTRODUCTION This is a review of the available scientific literature and industry-provided unpublished data relevant to assessing the safety of 19 hexamethylene diisocyanate (HDI) polymers as used in cosmetics. These ingredients are composed of copolymers, the monomers of which are partially comprised of hexamethylene diisocyanate (1,6-diisocyanatohexane). The functions of HDI polymers include viscosity s aqueous, anticaking agents, and film formers (Table 1). 1 The ingredients in this safety assessment are: HDI/Trimethylol Hexyllactone bis-c16-20 Isoalkoxy TMHDI/PEG-90 bis-hydroxyethyl Acrylate Poly(1,4-Butanediol)-9/TMHDI bis-isostearyl 1,4-Butanediol/HDI/Hydrogenated Dimer Dilinoleyl Alcohol bis-lauryl Cocaminopropylamine/HDI/PEG-100 bis-methoxy PEG-10 Dimethyl MEA/HDI/bis-PEG-10 Dimethicone 1,4-Butanediol/Succinic Acid/Adipic Acid/HDI Cholesterol/HDI/Pullulan Decyl HDI/PEG-180 Diethylene Glycol/DMAP Acrylamide/ PEG-180/HDI HDI/Di-C12-14 Alkyl Tartrate/Hydrogenated Dilinoleyl Alcohol HDI/PEI-45/SMDI HDI/PPG/Polycaprolactone Methoxy PEG-17/Methoxy PEG-11/HDI Methoxy PEG-17/Methoxy PEG-11/HDI Isocyanurate Trimer PEG-240/HDI bis-decyltetradeceth- 20 Ether PPG-26/HDI Steareth-100/PEG-136/HDI Stearyl HDI/PEG-50 The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) has reviewed several of the constituent monomers of these ingredients (Table 2) Polyethylene glycols (PEG), PEG-10 dimethicone, adipic acid, succinic acid, cholesterol, pullulan, glycerin, and stearyl alcohol were determined to be safe as used. Methoxy PEG-10, decyltetradeceth-20, steareth-100, and PPG-26 were determined to be safe when formulated to be nonirritating. The ingredients in this report consist of copolymers, wherein each ingredient is synthesized, in part, from the monomer HDI. These ingredients are grouped together herein because they are all copolymers resulting, in part, from a common diisocyanate monomer. Exposure to diisocyanates, such as HDI, in the work place is one of the leading causes of occupational asthma. 13 Airway irritation and asthma-like symptoms, hypersensitivity pneumonitis, rhinitis, and accelerated lung deterioration have also been associated with exposure to diisocyanates. Diisocyanates can also cause both irritant and allergic contact dermatitis as well as skin and conjunctival irritation. Diisocyanates may act as haptens, associating with endogenous or extracellular protein carriers to induce an immune response. Covalent binding of a hapten to a protein is believed to be a relevant mechanism for immune recognition and further development of allergies. However, the ingredients in this report are not diisocyanates themselves, but are the end product of a polymerization process that includes hexamethylene diisocyanate as one of the starting materials (monomers). Accordingly, quantification of any residual hexamethylene diisocyanate in the final cosmetic ingredient may be paramount to determining safety. CHEMISTRY Definition, Structure, and Manufacture This group is comprised of copolymers, the monomers of which include HDI for each ingredient (also known as 1,6-diisocyanatohexane; Figure 1). Figure 1. Hexamethylene Diisocyanate These polymers are produced by reactions of HDI with alkoxy-group containing monomers, such as alcohols and polyethers. Some of these polymers are linear, but when tri-functional monomers (eg, glycerin) are used as reactants, branched or cross-linked structures are probable. The degree of polymerization of these chemicals can be controlled to obtain a desired functionality, such as a rheology modifier. Accordingly, the molecular weights and molecular volumes of these ingredients could vary widely, unless otherwise noted by actual use specifications. These polymers, by definition of their monomer compositions, contain various hydrophilic and hydrophobic groups. The ratio of these groups may vary within one ingredient name. Accordingly, in the absence of an ingredient-explicit specification in each case, estimation of some of the chemical and physical properties of these ingredients is extremely challenging. These ingredients could

3 potentially range from liquid to solid, soluble to insoluble, or even differ with regard to dermal penetration. However, aside from potential HDI residue, these ingredients are not all that different from polyurethane-type polymers (though many other polyurethanes are synthesized using various other diisocyanates). Physical and Chemical Properties Physical and chemical properties are presented in Table 3. HDI/trimethylol hexyllactone crosspolymer was reported to be available in 2 grades for cosmetics from a supplier. 14 The particle size distribution for grade 1 was reported to be: 100% <100 µm, 33.8% <10 µm, 5.5% <1 µm; the median diameter was µm. The particle size distribution for grade 2 was reported to be: 100% <100 µm, 87.5% <10 µm, 7.1% <1 µm; the median diameter was 6.16 µm. Analysis of HDI/trimethylol hexyllactone crosspolymer from another supplier showed that the overall distribution was: 100% <100 µm, 15.15% µm, and 0% <1 µm; the average diameter was µm (Table 4). Impurities The ingredients bis-lauryl cocaminopropylamine/hdi/peg-100 copolymer and bis-c16-20 isoalkoxy TMHDI/PEG- 90 copolymer were reported to contain <1 ppm mercury, <3 ppm arsenic, and <10 ppm lead. 15 No information was discovered or provided on residual monomers. It is not known if or how the HDI monomer is entrapped or scrubbed from the final product. USE Cosmetic The safety of the cosmetic ingredients included in this safety assessment is evaluated on the basis of the expected use in cosmetics. The Panel utilizes data received from the U.S. Food and Drug Administration (FDA) and the cosmetics industry in determining the expected cosmetic use. The data received from the FDA are those it collects from manufacturers on the use of individual ingredients in cosmetics by cosmetic product category in its Voluntary Cosmetic Registration Program (VCRP), and those from the cosmetic industry are submitted in response to a survey of the maximum reported use concentrations by category conducted by the Personal Care Products Council (Council). According to the 2015 VCRP survey data, HDI/trimethylol hexyllactone crosspolymer is reported to be used in 354 formulations, which includes 348 leave-on products and 6 rinse-off products (Table 5). 16 Fifty of these formulations are powders, 13 are lipsticks, and 329 have dermal contact. The 5 other ingredients with reported uses were reported to be used in 21 or fewer cosmetic formulations. The Council is conducting a survey of the maximum concentrations of use by product category. HDI/trimethylol hexyllactone crosspolymer and methoxy PEG-17/methoxy PEG-11/HDI crosspolymer were reported to be used in formulations that come in contact with mucus membranes. HDI/trimethylol hexyllactone crosspolymer and methoxy PEG-17/methoxy PEG-11/HDI crosspolymer were reported to be used in formulations that could be incidentally ingested. HDI/trimethylol hexyllactone crosspolymer, HDI/PPG/polycaprolactone crosspolymer, and PEG- 240/HDI copolymer bis-decyletradeceth-20 ether were reported to be used in formulations that are applied near the eye. Additionally, some of the HDI polymers are used in cosmetic sprays and powders and could possibly be inhaled; for example, HDI/trimethylol hexyllactone crosspolymer is reported to be used in fragrance and face powders as well as products that may be sprays. In practice, 95% to 99% of the droplets/particles released from cosmetic sprays have aerodynamic equivalent diameters >10 µm, with propellant sprays yielding a greater fraction of droplets/particles <10 µm compared with pump sprays. 17,18 Therefore, most droplets/particles incidentally inhaled from cosmetic sprays would be deposited in the nasopharyngeal and thoracic regions of the respiratory tract and would not be respirable (ie, they would not enter the lungs) to any appreciable amount. 19,20 The use of only 1 of the HDI polymers named in the report is restricted under the rules governing cosmetic products in the European Union. 21 Specifically, the European Union restricts the content of diethylene glycol to a total of 0.1% in any finished cosmetic product, including the amount of diethylene glycol contained in polymers, which includes diethylene glycol/dmap acrylamide/peg-180/hdi copolymer. TOXICOKINETICS Absorption, Distribution, Metabolism, and Excretion Data on toxicokinetics of HDI polymers were not found in the published literature nor were unpublished data TOXICOLOGICAL STUDIES Single Dose (Acute) Toxicity Dermal Data on acute dermal toxicity of HDI polymers were not found in the published literature nor were unpublished data

4 Oral Non-Human In an acute oral toxicity study using Wistar-strain rats (n=5/sex), a dose of 5000 mg/kg HDI/trimethylol hexyllactone crosspolymer administered by intragastric feeding caused no clinical signs or mortalities. 14 The rats were observed at 1, 3, 6, and 24 h then daily for 14 days. Inhalation Non-Human Data on acute inhalation toxicity of HDI polymers were not found in the published literature nor were unpublished data Repeated Dose Toxicity Data on dermal, oral, or inhalation repeated dose toxicity of HDI polymers were not found in the published literature nor were unpublished data REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Data on the reproductive and developmental toxicity of HDI polymers were not found in the published literature nor were unpublished data GENOTOXICITY Data on the genotoxicity of HDI polymers were not found in the published literature nor were unpublished data CARCINOGENICITY Data on the carcinogenicity of HDI polymers were not found in the published literature nor were unpublished data IRRITATION AND SENSITIZATION Irritation Dermal Non-Human When HDI/trimethylol hexyllactone crosspolymer (100%) was dermally administered to the intact or abraded skin of rabbits, slight irritation of the skin was observed in 5 of 6 rabbits in a primary dermal irritation study. 14 One rabbit showed well-defined erythema and slight edema 24 and 72 h after administration. The irritation scores were less than those needed to classify a test substance as an irritant according to the approved criteria of the National Occupational Health and Safety Commission (NOHSC) of Australia. 22 No further information was Dermal Human In a human patch test (n=21 male, 23 female) of HDI/trimethylol hexyllactone crosspolymer (100% as a dry powder), there were no effects observed when the patch was removed after 24 h. 14 It was noted that this study may not be predictive of effects that may occur upon exposure to this substance in moist formulations. No further information was Ocular In an eye irritation study of HDI/trimethylol hexyllactone crosspolymer (100%), mild to moderate conjunctival redness and mild chemosis were observed in 4 of 6 rabbits 24 and 48 h after administration into the eyes; 1 rabbit still showed redness after 4 days, which was resolved at 7 days. 14 One animal showed mild chemosis on day 1; this was resolved by day 2. The mean scores for observations 24, 48 and 72 h were 1.0 for redness and 0.1 for chemosis. It was concluded that the test substance was a slight ocular irritant but was not classified as an ocular irritant according to the criteria of NOHSC. 22 Considering the particle size range (at least 92.9% > 1 µm; Table 4) and the water insolubility of the tested polymer, the eye irritation observed was likely attributable to mechanical abrasion rather than chemical irritancy. Sensitization Data on sensitization by HDI polymers were not found in the published literature nor were unpublished data Phototoxicity Data on phototoxicity by HDI polymers were not found in the published literature nor were unpublished data

5 SUMMARY This is a review of the available scientific literature and industry-provided unpublished data relevant to assessing the safety of 19 HDI polymers as used in cosmetics. These ingredients are comprised of copolymers, the monomers of which are partially comprised of hexamethylene diisocyanate (1,6-diisocyanatohexane). The functions of HDI polymers include viscosity s-aqueous, anticaking agents, and film formers. Exposure to diisocyanates, such as HDI, have caused occupational asthma, hypersensitivity pneumonitis, rhinitis, and accelerated lung deterioration. It is not known whether, or to what extent, this monomer may be entrapped or scrubbed from the final product during the manufacture of the HDI polymers named in this report. According to the 2015 VCRP survey data, HDI/trimethylol hexyllactone crosspolymer is reported to be used in 354 formulations, 348 of which are leave-on products and 6 of which are rinse-off products. The Council is conducting a survey of the highest concentration of use. In an acute oral toxicity study using rats, a dose of 5000 mg/kg HDI/trimethylol hexyllactone crosspolymer administered by intra-gastric feeding caused no clinical signs or mortalities. HDI/trimethylol hexyllactone crosspolymer at 100% was not a dermal irritant to the intact and abraded skin of rabbits. Slight irritation of the skin was observed in 5 of 6 rabbits. In a human patch test of HDI/trimethylol hexyllactone crosspolymer at 100% (as a dry powder), there were no effects observed when the patch was removed. HDI/trimethylol hexyllactone crosspolymer at 100% was a slight ocular irritant but was not an ocular irritant according to the approved criteria of NOHSC. DATA NEEDS CIR is seeking all information pertaining to the safety of these ingredients in a wide range of areas, including: Chemical and physical properties; Impurities data; including data on hexamethylene diisocyanate, in particular, including how it is entrapped in or scrubbed from the final ingredient, and how much is biologically available in the final ingredient; Toxicokinetics data, specifically dermal absorption of these ingredients; if these ingredients were to have appreciable dermal absorption and other toxicokinetic data are not adequate, toxicity data, including reproductive/developmental toxicity and carcinogenicity data, are needed, as are genotoxicity data; these data may not be crucial if these ingredients have no appreciable dermal penetration, however, if these data were available, even though dermal penetration might be expected to be negligible, the data would strengthen the safety assessment; Oral and inhalation toxicity data; Dermal, ocular, and other mucous membrane toxicity data, including irritation and sensitization data; and Any other relevant safety information that may be available. Though there are data available on HDI/tromethylol hexyllactone crosspolymer, more data would be helpful.

6 TABLES AND FIGURES 1,CIR Staff Table 1. Definitions and functions of the HDI polymers in this safety assessment. Ingredient/CAS No. Definition Function HDI/Trimethylol Hexyllactone bis-c16-20 Isoalkoxy TMHDI/PEG-90 bis-hydroxyethyl Acrylate Poly(1,4-Butanediol)-9/TMHDI bis-isostearyl 1,4- Butanediol/HDI/Hydrogenated Dimer Dilinoleyl Alcohol bis-lauryl Cocaminopropylamine/HDI/ PEG-100 bis-methoxy PEG-10 Dimethyl MEA/HDI/bis-PEG-10 Dimethicone 1,4-Butanediol/Succinic Acid/Adipic Acid/HDI Cholesterol/HDI/Pullulan Decyl HDI/PEG-180 Diethylene Glycol/DMAP Acrylamide/PEG-180/HDI HDI/Di-C12-14 Alkyl Tartrate/Hydrogenated Dilinoleyl Alcohol HDI/PEI-45/SMDI HDI/PPG/Polycaprolactone Methoxy PEG-17/Methoxy PEG-11/HDI Methoxy PEG-17/Methoxy PEG-11/HDI Isocyanurate Trimer PEG-240/HDI bis- Decyltetradeceth-20 Ether PPG-26/HDI Steareth-100/PEG-136/HDI Stearyl HDI/PEG-50 HDI/Trimethylol Hexyllactone is a cross-linked condensation polymer formed from the reaction of hexamethylene diisocyanate (HDI) with the esterification product of trimethylolpropane with 6 to 7 moles of hexyllactone. Bis-C16-20 Isoalkoxy TMHDI/PEG-90 is a copolymer of trimethylhexanediisocyanate (TMHDI) and PEG-90 end-capped with a branched alcohol containing 16 to 20 carbons. bis-hydroxyethyl Acrylate Poly(1,4-Butanediol)-9/TMHDI is a copolymer of poly(1,4-butanediol)-9 and trimethylhexanediisocyanate (TMHDI) end-capped with hydroxyethylacrylate. bis-isostearyl 1,4-Butanediol/HDI/Hydrogenated Dimer Dilinoleyl Alcohol is a copolymer of hexamethylene diisocyanate (HDI), and hydrogenated dilinoleyl alcohol endcapped with isostearyl 1,4-butanediol. bis-lauryl Cocaminopropylamine/HDI/PEG-100 is a copolymer of cocoaminopropylamine, PEG-100, and hexamethylene diisocyanate (HDI) endcapped with lauryl alcohol. bis-methoxy PEG-10 Dimethyl MEA/HDI/bis-PEG-10 Dimethicone is a copolymer of hexamethylene diisocyanate (HDI), dimethylethanolamine and bis-peg-10 dimethicone endcapped with PEG-10 monomethyl ether. 1,4-Butanediol/Succinic Acid/Adipic Acid/HDI is a copolymer of 1,4-butanediol, succinic acid, adipic acid, and hexamethylene diisocyanate monomers. Cholesterol/HDI/Pullulan is a copolymer of cholesterol, hexamethylene diisocyanate, and pullulan monomers. Decyl HDI/PEG-180 is a copolymer of hexylmethylene diisocyanate (HDI), PEG-180, and decyl alcohol monomers crosslinked with glycerin. Diethylene Glycol/DMAP Acrylamide/PEG-180/HDI is a copolymer of diethylene glycol, dimethylaminopropyl (DMAP) acrylamide, PEG-180, and hexamethylene diisocyanate (HDI) monomers. HDI/Di-C12-14 Alkyl Tartrate/Hydrogenated Dilinoleyl Alcohol copolymer is a copolymer of 1,6-hexamethylene diisocyanate (HDI), di-c12-14 alkyl tartrate, and hydrogenated dilinoleyl alcohol, chain-terminated by ethyl alcohol. HDI/PEI-45/SMDI is the crosslinked polymer formed by the reaction of PEI-45 with saturated methylene diphenyldiisocyanate (SMDI) and hexamethylene diisocyanate (HDI). [PEI is an acronym for pethylenimine.] HDI/PPG/Polycaprolactone is a cross-linked condensation polymer of polycaprolactone, a sorbitol initiated polypropylene glycol with hexamethylene diisocyanate and trimethylolpropane. Methoxy PEG-17/Methoxy PEG-11/HDI is a copolymer of methoxy PEG-17, methoxy PEG-11, and hexamethylene diisocyanate (HDI) crosslinked by water and the addition of sodium hydroxide. Methoxy PEG-17/Methoxy PEG-11/HDI Isocyanurate Trimer is a copolymer of methoxy PEG-17, methoxy PEG-11, and hexamethylene diisocyanate (HDI) trimer in which the free isocyanate groups are crosslinked by water to form urea linkages. PEG-240/HDI bis-decyltetradeceth-20 Ether is a copolymer of PEG- 240, decyltetradeceth-20, and hexamethylene diisocyanate monomers. PPG-26/HDI is a copolymer of hexamethylene diisocyanate and PPG- 26 monomers. Steareth-100/PEG-136/HDI is a copolymer of steareth-100, PEG-136, and hexamethylene diisocyanate monomers. Stearyl HDI/PEG-50 is a copolymer of hexylmethylene diisocyanate, PEG-50, and stearyl alcohol monomers. Anticaking agent Viscosity - aqueous Film former Viscosity - nonaqueous Viscosity - nonaqueous Hair conditioning agent Abrasive, binder, film former Emulsion stabilizer, humectant, viscosity - aqueous Viscosity - aqueous Hair conditioning agents/ skin protectants, skinconditioning agent - miscellaneous Film former Absorbent, dispersing agent - nonsurfactant Anticaking agents, bulking agent Anticaking agent Anticaking agent Viscosity aqueous Film former, plasticizer Viscosity aqueous Film former

7 Table 2. Previous safety assessments of components/monomers of HDI polymers in this safety assessment. concentration of use reported for ingredients in the latest safety Constituent and ingredient group Conclusion assessment or re-review Reference Polyethylene glycols (PEGs) in triethylene glycol Safe for use in cosmetics in the present 85% 2,4,7 and any PEGs 4 practices of use and concentration. PEG-10 dimethicone in polyoxyalkylene Safe for use in cosmetics in the present 22% hair; 15% dermal 3,5 siloxane copolymers, alkyl-polyoxyalkylene siloxane copolymers, and related ingredients practices of use and concentration. Methoxy PEG-10, decyltetradeceth-20, steareth- Safe as used when formulated to be 32% in a product to be in alkyl PEG ethers nonirritating diluted; 25% Adipic acid, succinic acid in dicarboxylic acids, Safe for use in cosmetics in the present 26% in a product to be 10 salts, and esters practices of use and concentration. diluted; 0.4% Cholesterol Safe as used. 3% 8,23 Pullulan in microbial polysaccharide gums Safe for use in cosmetics in the present 12% hair; 17% in oral 11 practices of use and concentration. hygiene; 6% in dermal Glycerin Safe for use in cosmetics in the present 79.2% 6 practices of use and concentration. PPG-26 in propylene glycol, tripropylene glycol, Safe as used when formulated to be 99% in product to be diluted; 12 and PPGs Stearyl alcohol with oleyl alcohol and octyl dodecanol nonirritating. 73% in dermal Safe as used. 56% 6,23 Table 3. Chemical and physical properties of hexamethylene diisocyanate polymers. Property Value Reference HDI/Trimethylol Hexyllactone Physical Form Fine powder Color White to pale yellow Molecular Weight g/mol > Density/Specific 20 o C Melting Point o C > Color Color bis-c16-20 Isoalkoxy TMHDI/PEG-90 Translucent bis-lauryl Cocaminopropylamine/HDI/PEG-100 Translucent 15,24 15 Steareth-100/PEG-136/HDI Physical Form Powder Color White Melting Point o C Water Solubility Dispersible

8 Table 4. Reported particle size distribution for 2 grades of HDI/trimethylol hexyllactone crosspolymer from 1 supplier and another sample from a second supplier. 14 Median <100 µm (%) <10 µm (%) <1 µm (%) diameter (µm) Grade Grade Second supplier * ** * µm ** Average diameter Use type Table 5. Frequency of use according to duration and exposure of HDI polymers. 16 Uses (%) Uses (%) Uses (%) Uses HDI/Trimethylol Hexyllactone bis-c16-20 Isoalkoxy TMHDI/PEG-90 bis-hydroxyethyl Acrylate Poly(1,4-Butanediol)-9/ TMHDI (%) bis-isostearyl 1,4-Butanediol/HDI/ Hydrogenated Dimer Dilinoleyl Alcohol Total/range 354 NS NR NS NR NS NR NS Duration of use a Leave-on 348 NS NR NS NR NS NR NS Rinse-off 6 NS NR NS NR NS NR NS Diluted for (bath) use Exposure type Eye area 118 NS NR NS NR NS NR NS ingestion 13 NS NR NS NR NS NR NS Inhalation-sprays 34 b ; 33 c NS NR NS NR NS NR NS inhalation-powders 50; 33 c NS NR NS NR NS NR NS Dermal contact 329 NS NR NS NR NS NR NS Deodorant (underarm) Hair-noncoloring Hair-coloring Nail 1 NS NR NS NR NS NR NS Mucous Membrane 13 NS NR NS NR NS NR NS Baby

9 Use type Table 5. Frequency of use according to duration and exposure of HDI polymers. 16 Uses (%) Uses (%) Uses (%) Uses bis-lauryl Cocaminopropylamine/ HDI/ PEG-100 bis-methoxy PEG-10 Dimethyl MEA/HDI/bis- PEG-10 Dimethicone 1,4-Butanediol/Succinic Acid/Adipic Acid/HDI (%) Cholesterol/HDI/Pullulan Total/range Duration of use Leave-on Rinse-off Diluted for (bath) use Exposure type Eye area ingestion Inhalation-sprays inhalation-powders Dermal contact Deodorant (underarm) Hair-noncoloring Hair-coloring Nail Mucous Membrane Baby Diethylene Glycol/DMAP Acrylamide/PEG-180/ HDI HDI/Di-C12-14 Alkyl Tartrate/Hydrogenated Dilinoleyl Alcohol Decyl HDI/PEG-180 HDI/PEI-45/SMDI Total/range NR NS 6 NS NR NS NR NS Duration of use Leave-on NR NS 1 NS NR NS NR NS Rinse-off NR NS 5 NS NR NS NR NS Diluted for (bath) use Exposure type Eye area ingestion Inhalation-sprays NR NS 1 b NS NR NS NR NS inhalation-powders Dermal contact Deodorant (underarm) Hair-noncoloring NR NS 6 NS NR NS NR NS Hair-coloring Nail Mucous Membrane Baby

10 Use type Table 5. Frequency of use according to duration and exposure of HDI polymers. 16 Uses (%) Uses (%) Uses (%) Uses HDI/PPG/ Polycaprolactone Methoxy PEG-17/ Methoxy PEG-11/HDI Methoxy PEG-17/ Methoxy PEG-11/HDI Isocyanurate Trimer (%) PEG-240/HDI bis-decyltetradeceth-20 Ether Total/range 21 NS 1 NS NR NS 2 NS Duration of use Leave-on 21 NS 1 NS NR NS 2 NS Rinse-off Diluted for (bath) use Exposure type Eye area 4 NS NR NS NR NS 1 NS ingestion NR NS 1 NS NR NS NR NS Inhalation-sprays 5 b ; 2 c NS NR NS NR NS 1 b NS inhalation-powders 3; 2 c NS NR NS NR NS NR NS Dermal contact 19 NS NR NS NR NS 2 NS Deodorant (underarm) Hair-noncoloring Hair-coloring Nail Mucous Membrane NR NS 1 NS NR NS NR NS Baby PPG-26/HDI Steareth-100/PEG- 136/HDI Stearyl HDI/PEG-50 Total/range NR NS 1 NS NR NS Duration of use Leave-on NR NS 1 NS NR NS Rinse-off NR NS NR NS NR NS Diluted for (bath) use NR NS NR NS NR NS Exposure type Eye area NR NS NR NS NR NS ingestion NR NS NR NS NR NS Inhalation-sprays NR NS NR NS NR NS inhalation-powders NR NS NR NS NR NS Dermal contact NR NS NR NS NR NS Deodorant (underarm) NR NS NR NS NR NS Hair-noncoloring NR NS 1 NS NR NS Hair-coloring NR NS NR NS NR NS Nail NR NS NR NS NR NS Mucous Membrane NR NS NR NS NR NS Baby NR NS NR NS NR NS NR = Not Reported; NS = The Council is conducting a survey of the maximum concentrations of use for the ingredients in this safety assessment; Totals = Rinse-off + Leave-on Product Uses. Note: Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure type uses may not equal the sum total uses. a Because 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. b It is possible these products may be sprays, but it is not specified whether the reported uses are sprays. c Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation.

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