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Memorandum
To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF
Senior Scientific Analyst/Writer Date: September 1, 2011 Subject: Draft Final Safety Assessment on Crosslinked Alkyl Acrylates as Used in Cosmetics Included is the draft Final Safety Assessment on the Crosslinked Alkyl Acrylates as Used in Cosmetics. At the March meeting, the Panel indicated it was concerned that residual benzene may be present in the crosspolymers, and issued an Insufficient Data Announcement requesting impurity data, particularly with respect to the amount of residual benzene that may be present. At the June meeting, data were submitted that confirmed that one crosspolymer was sometimes polymerized in benzene under one trade name, and that up to 0.5% residual benzene could be present in the raw material. The Panel was concerned with the presence of residual benzene in a cosmetic ingredient. The Panel therefore issued a tentative report with the conclusion that the crosslinked alkyl acrylates named in this report are safe for use in the present practices of use and concentration described in this safety assessment, except when they are polymerized in benzene, and that the available data are insufficient to make a determination of safety for these ingredients when polymerized in benzene. The Panel expressed their concern regarding residual benzene in the Discussion of the report, and included a calculation as to the amount of benzene that could be present. That calculation was done using 0.5% as the maximum impurity level for benzene, and 6% as the maximum use concentration for crosspolymers. The Council has commented that it was inappropriate to use the 6% use concentration to calculate benzene levels, in that 6% is the concentration of use reported for Acrylates/Ethylhexyl Acrylate, which is not reported to be polymerized in benzene. The ingredient that can be polymerized in benzene is Acrylates/C10-30 Alkyl Acrylate Crosspolymer. This ingredient has a maximum use concentration of 5%, and it is this value the Council is proposing be used in the calculation of residual benzene. That change has been made in the Discussion of the report.
CROSSLINKED ALKYL ACRYLATES
December 23, 2010: SLR Issued March 3-4, 2011: Draft Report The following unpublished data were submitted by the Council, following the announcement of the SLR, and are included in the draft report:
1. Information on Sodium Acrylates Crosspolymer-2. Memo dated Nov. 30, 2010. a. Sumitomo Seika. 2010 Cosmetic Grade: AQUAKEEP 10SH-NFC (Sodium Acrylates Crosspolymer-2) b. Sumitomo Seika. 2010. Material safety data sheet: AQUAKEEP 10SH-NFC (Sodium Acrylates
Crosspolymer-2) 2. Information on Acrylates/Vinyl Isodecanoate Crosspolymer. Memo dated Dec. 14, 2010
a. 3V Sigma. 2010. Stabylen 30 (Acrylates/Vinyl Isodecanoate Copolymer): Toxicological Summary Review.
3. Specification information on Acrylates/C10-30 Alkyl Acrylates Crosspolymer. Memo dated Dec. 15, 2010. 4. HRIPTs on Products Containing Acrylates/C10-30 Alkyl Acrylate Crosspolymer. Memo dated Jan. 11, 2011.
a. Consumer Product Testing Co. 2009. Repeated insult patch test of a body lotion containing 0.15% Acrylates/C10-30 Alkyl Acrylate Crosspolymer. Experiment Reference Number: C09-1 109.01.
b. Consumer Product Testing Co. 2010. Repeated insult patch test of a foot cream containing 0.6% Acrylates/C10-30 Alkyl Acrylate Crosspolymer. Experiment Reference Number: C10-0602.01.
5. Specifications for Allyl Methacrylates Crosspolymer. Memo dated Jan, 13, 2011. 6. Updated concentration of use by FDA product category: Acrylate Crosspolymer Ingredients. Memo dated Jan. 28,
2011. At the meeting, the Panel issued an insufficient data announcement requesting impurity data for the crosspolymers, particularly with respect to the amount of residual benzene that may be present. June 27-28, 2011: Tentative Report The following unpublished data were submitted by the Council and added to the report:
1. Dow Chemical Company. 2011. ACULYN 88 Polymer (Acrylates/Steareth-20 Methacrylate Crosspolymer)Global Cosmetic Dossier. Submitted by the Council on May 3, 2011.)
2. Dow Chemical Company. 2011. ACULYN 38 Polymer (Acrylates/Vinyl Neodecanoate Crosspolymer) Global Cosmetic Dossier. Submitted by the Council on May 3, 2011.)
3. Personal Care Products Council. 2011. Benzene impurity in acrylates/C10-30 alkyl acrylate crosspolymer.
The Panel issued a tentative report with a conclusion of safe as used for the crosslinked alkyl acrylates provided that they are not polymerized in benzene; the available data are insufficient to make a determination of safety for those polymerized in benzene. Were the ingredients not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. September 26-27, 2011: Draft Final Report
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 2
April 7, 2011 – Searched using SciFinder History April 7, 2011 2:18 PM Explore references by research topic: crosslinked polymers initiated, resulting in 2 candidates April 7, 2011 2:19 PM Explore references by research topic: acrylate crosspolymer initiated, resulting in 2 candidates Explore complete Candidates Selected 110 references were found containing the concept "acrylate crosspolymer". Explore results Answer set 45 created with 108 answers from CAPLUS 2 answers from MEDLINE April 7, 2011 2:20 PM Explore references by research topic: acrylate crosspolymer initiated, resulting in 2 candidates Limiters Book, Preprint, Report, Journal, Review Explore complete Candidates Selected 8 references were found containing the concept "acrylate crosspolymer". Explore results Answer set 46 created with 6 answers from CAPLUS 2 answers from MEDLINE Detailed display from Answer set 46 of Development of a new cosmetic active for safe skin brightening Detailed display from Answer set 46 of The properties of lecithin and lecithin-liposome containing emulsions, emulsified with crosslinked acrylic acid-alkyl acrylate crosspolymer. Keep Me Posted profile 'acrylates crosspolymers' created from Answer set 46 Exported 1 reference answer from Answer set 46 in 'RIS' format as "acrylates crosspolymer.ris" April 7, 2011 2:24 PM Explore references by research topic: methacrylic crosspolymer initiated, resulting in 2 candidates Limiters Book, Preprint, Clinical Trial, Report, Journal, Review Explore complete Candidates Selected 4 references were found containing the concept "methacrylic crosspolymer". Explore results Answer set 47 created with 4 answers from CAPLUS Detailed display from Answer set 47 of Aculyn 88 rheology modifier Detailed display from Answer set 47 of AculynT 88 rheology modifier and laponite clay Detailed display from Answer set 47 of Rheological effects with a hydrophobically modified polymer Exported 1 reference answer from Answer set 47 in 'RIS' format as "methacrylate crosspolymer.ris" April 7, 2011 2:27 PM Explore references by research topic: methacrylic crosspolymer initiated, resulting in 2 candidates Limiters Book, Preprint, Clinical Trial, Report, Journal, Review Explore complete Candidates Selected 4 references were found containing the concept "methacrylic crosspolymer". Explore results Answer set 48 created with 4 answers from CAPLUS Keep Me Posted profile 'Methacrylate Crosspolymer' created from Answer set 48 April 7, 2011 2:39 PM Explore substances by ID: acrylates/C10-30 Alkyl Acrylate Crosspolymer, 26794-61-6, 74464-10-1, Acrylates/ethylhexyl acrylate crosspolymer, acrylates/ethylhexyl acrylate/glycidyl methacrylate crosspolymer, 50657-38-0, acrylates/steareth-20 methacrylate crosspolymer, acrylates/vinyl isodecanoate crosspolymer, acrylates/vinyl neodecanoate crosspolymer, 779327-42-3, 182212-41-5, butyl acrylate/glycol diemethacrylate crosspolymer, C8-22 acrylates/methacrylic acid crosspolymer, glycol diemethacrylate/vinyl alcohol crosspolymer, lauryl methacrylate/glycol dimethacrylate crosspolymer, lauryl methacrylate/sodium methacrylate crosspolymer, acrylates/C12-13 alkyl methacrylates/methoxyethyl acrylate crosspolymer, methacrylic acid/PEG-6 methacrylate
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 3
crosspolymer, PEG/PPG-5/2 methacrylate/methacrylic acid crosspolymer, potassium acrylates/C10-30 alkyl acrylate crosspolymer, sodium acrylates/C10-30 alkyl acrylate crosspolymer, sodium acrylates crosspolymer-2, sodium acrylates/vinyl isodecanoate crosspolymer, stearyl/lauryl methacrylate crosspolymer initiated Explore complete Explore results Answer set 49 created with 5 answers from REGISTRY Saved 5 substance answers from Answer set 49 as 'Some Acrylates Crosspolymers' Retrieve reference information in 5 substances of Answer set 49 Answer set 50 created with 257 answers from CAPLUS Saved 257 reference answers from Answer set 50 as 'All Acrylates Crosspolymer Listings' Keep Me Posted profile 'Acrylates Crosspolymer Substances' created from Answer set 50 Refine Answer set 50 by document type Book, Clinical Trial, Conference, Journal, Preprint, Report, Review Answer set 51 created with 137 answers from CAPLUS Saved 137 reference answers from Answer set 51 as 'Acrylates Crosspoly Substances by Doc Type' Copyright © 2011 American Chemical Society. All Rights Reserved. Copyright © 1994-2011 Sun Microsystems, Inc. All Rights Reserved. (Java runtime environment) Copyright © 2011, Yahoo! Inc. All Rights Reserved. (YUI Base, Fonts, Reset CSS) Copyright © 2005-2011, The Dojo Foundation. All Rights Reserved Copyright © 2011, Exadel, Inc. All Rights Reserved. (JBoss RichFaces) Copyright © 2002 InfoChem GmbH. All Rights Reserved. (InfoChem’s reaction classification program CLASSIFY) CAplus SM: Copyright © 2011 American Chemical Society. All Rights Reserved. (The U.K. patent material in this product/service is U.K. Crown copyright and is made available with permission. Copyright © Crown Copyright. The French (FR) patent material in this product/service is made available from Institut National de la Propriete Industrielle (INPI).) CAS REGISTRY SM: Copyright © 2011 American Chemical Society. All Rights Reserved. (Some records contain information from GenBank ® . See also: Benson D.A., Karsch-Mizarachi I., Lipman D.J., Ostel J., Rapp B.A., Wheeler D.L. Genbank. Nucl. Acids Res. 28(1):15-18 (2000). Property values tagged with IC are from the ZIC/VINITI data file provided by InfoChem.) CAS Registry is a service mark of the American Chemical Society. GenBank is a registered trademark of the U.S. Library of Medicine. CASREACT ® : Copyright © 2011 American Chemical Society. All Rights Reserved. CASREACT contains reactions from CAS and from: ZIC/VINITI database (1974-1999) provided by InfoChem; INPI data prior to 1986; Biotransformations database compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006 John Wiley & Sons, Ltd., John Wiley and Sons, Inc., Organic Reactions Inc., and Organic Synthesis Inc. Reproduced under license. All Rights Reserved. CHEMCATS ® : Copyright © 2011 American Chemical Society. All Rights Reserved. Chemical supplier information is supplied on an "as is" basis. Full information regarding substance availability, price, etc., is provided when you request supplier information. CHEMLIST ® : Copyright © 2011 American Chemical Society. All Rights Reserved. MEDLINE ® : is produced by the U.S. National Library of Medicine. MEDLINE is a registered trademark of the U.S. National Library of Medicine. KEEP ME POSTED RESULTS reviewed weekly
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 4
Cro
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Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 5
Cro
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Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 6
Search Terms (ACRYLATES AND ALKYL AND ACRYLATE AND CROSSPOLYMER) OR 503867-23-0 OR (ACRYLIC AND ACID AND ALKYL AND METHACRYLATE AND COPOLYMER) OR (ACRITAMER AND (501ED OR 505ED)) OR (AQUPEC AND HV) OR (CARBOPOL AND (2020 OR 1342 OR 1382) AND POLYMER) OR (CARBOPOL AND ULTREZ AND (20 OR 21) AND POLYMER) OR (PEMULEN AND (TR-1 OR TR-2) AND POLYMER) OR (TEGO AND CARBOMER) (ACRYLATES AND CROSSPOLYMER) OR 26794-61-6 OR 74464-10-1 OR (PROPENOIC AND ACID AND (METHYL OR BUTYL) AND ESTER AND (COPOLYMER OR POLYMER)) OR (ETHYLENE AND DIMETHACRYLATE AND (ISOBUTYL OR METHYL) AND (POLYMER OR COPOLYMER)) OR (BUTYL AND METHACRYLATE AND *ETHYLENE AND DIMETHACRYLATE AND (COPOLYMER OR POLYMER)) OR (ETHANEDIOL AND METHYL AND METHACRYLATE AND (POLYMER OR COPOLYMER)) OR 937245-97-1 OR 1034390-08-3 OR 1042425-25-1 OR 66988-53-2 OR 108772-06-1 OR 66231-58-1 OR 66231-62-7 OR 37211-40-8 OR 141255-82-5 OR 138454-61-2 OR 73928-89-9 OR 144610-95-7 OR 86438-61-1 OR 219531-90-5 AND (GANZPEARL (GBX OR GME OR GMH OR GMP)) (ACRYLATES AND (ETHYLHEXYL OR (ETHYL AND HEXYL)) AND ACRYLATE AND CROSSPOLYMER) OR (TECHNOPOLYMER AND (ACP OR ACX)) (ACRYLATES AND (ETHYLHEXYL OR (ETHYL AND HEXYL)) AND ACRYLATE AND GLYCIDYL AND METHACRYLATE AND CROSSPOLYMER) OR (ACRIT AND SE) (ACRYLATES AND (PEG OR (POLYETHYLENE AND GLYCOL)) AND DIMETHACRYLATE AND CROSSPOLYMER) OR 50657-38-0 OR (COSMO AND PEARL) (ACRYLATES AND STEARETH AND METHACRYLATE AND CROSSPOLYMER) OR (ACULYN AND POLYMER) (ACRYLATES AND VINYL AND ISODECANOATE AND CROSSPOLYMER) OR 191808-02-3 OR 362523-28-2 (ACRYLATES AND VINYL AND NEODECANOATE AND CROSSPOLYMER) OR CUSTOPOLY OR STABYLEN (ALLYL AND METHACRYLATE AND GLYCOL AND DIMETHACRYLATE AND CROSSPOLYMER) OR 779327-42-3 (ALLYL AND METHACRYLATES AND CROSSPOLYMER) OR 182212-41-5 OR 286962-86-5 OR (ALLYL AND METHACYLATE AND DIMETHACRYLATE AND (POLYMER OR COPOLYMER)) OR (POLYPORE OR (POLY AND PORE)) (BUTYL AND ACRYLATE AND GLYCOL AND DIMETHACRYLATE AND CROSSPOLYMER) OR (MATSUMOTO AND MICROSPHERE) ALKYL AND ACRYLATES AND METHACRYLIC AND ACID AND CROSSPOLYMER (GLYCOL AND DIMETHACRYLATE AND VINYL AND ALCOHOL AND CROSSPOLYMER) OR POROSORP (LAURYL AND METHACRYLATE AND GLYCOL AND DIMETHACRYLATE AND CROSSPOLYMER) OR (POLYTRAP AND ADSORBER) (LAURYL AND METHACRYLATE AND SODIUM AND METHACRYLATE AND CROSSPOLYMER) OR SOFCARE (ACRYLATES AND ALKYL AND METHACRYLATES AND METHOXYETHYL AND ACRYLATE AND CROSSPOLYMER) OR DIAHOLD METHACRYLIC AND ACID AND (PEG OR (POLYETHYLENE AND GLYCOL)) AND METHACRYLATE AND CROSSPOLYMER ((PEG OR (POLYETHYLENE AND GLYCOL)) AND (PPG OR (POLYPROPYLENE AND GLYCOL)) AND
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 7
METHACRYLATE AND METHACRYLIC AND ACID AND CROSSPOLYMER) OR (TECHPOLMER AND SERIES) POTASSIUM AND ACRYLATES AND ALKYL AND ACRYLATE AND CROSSPOLYMER SODIUM AND ACRYLATES AND ALKYL AND ACRYLATE AND CROSSPOLYMER (SODIUM AND ACRYLATES AND CROSSPOLYMER) OR (AQUA AND KEEP) SODIUM AND ACRYLATES AND VINYL AND ISODECANOATE AND CROSSPOLYMER (STEARYL AND LAURYL AND METHACRYLATE AND CROSSPOLYMER) OR SOFCARE (ACRYLATE OR ACRYLATES) AND CROSSPOLYMER
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 8
1
CrosslinkedAlkylAcrylatesDataProfile*–Sept2011–Writer,MoniceFium
e
Reported Use
Method of Manufacture
Monomer Content
Animal Tox – Acute, Derrmal
Animal Tox – Acute, Oral
Animal Tox, Acute, Inhalation
Animal Tox – Rptd Dose, Dermal
Animal Tox, Rptd Dose, Oral
Animal Tox – Rptd Dose, Inhalaiton
Repro/Dev Tox
Genotoxicity
Carcinogeni-city
Dermal Irr/Sens
Ocular Irritaton
Acrylates/C10‐30AlkylAcrylateCrosspolym
er
x x
x x
x
x
x
x x
Acrylates/C12‐13AlkylMethacrylates/M
ethoxyethylAcrylateCrosspolym
er
AcrylatesCrosspolymer
x
x
x x
Acrylates/EthylhexylAcrylateCrosspolym
er
x
x
Acrylates/EthylhexylAcrylate/GlycidylMethacrylateCrosspolym
er
Acrylates/PEG‐4DimethacrylateCrosspolym
er
Acrylates/Steareth‐20MethacrylateCrosspolym
er
x x
x
x
Acrylates/VinylIsodecanoateCrosspolym
er
x x
x
x
x x
Acrylates/VinylNeodecanoateCrosspolym
er
x x
x x
x x
x
x
AllylM
ethacrylate/GlycolDimethacrylateCrosspolym
er
AllylM
ethacrylatesCrosspolymer
x
ButylAcrylate/GlycolDimethacrylateCrosspolym
er
C8‐22AlkylAcrylates/M
ethacrylicAcidCrosspolym
er
GlycolDimethacrylate/VinylAlcoholCrosspolymer
LaurylMethacrylate/GlycolDimethacrylateCrosspolym
er
x
x
x x
LaurylMethacrylate/Sodium
MethacrylateCrosspolym
er
x
MethacrylicAcid/PEG‐6Methacrylate/PEG‐6DimethacrylateCrosspolym
er
PEG/PPG‐5/2Methacrylate/MethacrylicAcidCrosspolym
er
PotassiumAcrylates/C10‐30AlkylAcrylateCrosspolym
er
Sodium
AcrylatesCrosspolymer‐2
x
x
x
x
x x
Sodium
Acrylates/C10‐30AlkylAcrylateCrosspolym
er
x
Sodium
Acrylates/VinylIsodecanoateCrosspolymer
Stearyl/LaurylMethacrylateCrosspolym
er
Monom
ers
AcrylicAcid
x
x x
x x
x x
x x
x x
MethylAcrylate
x
x
x
x x
EthylAcrylate
x
x
x
x x
ButylAcrylate
x
x
x
x x
2‐EthylhexylAcrylate
x
x x
x
PolyacrylicAcid
x
Sodium
Polyacrylate
x
x
x
x x
MethacrylicAcid
x
x x
x
x x
x x
x x
MethylM
ethacrylate
x
x
x x
x
EthylM
ethacrylate
x
x
ButylM
ethacrylate
x
x x
x
x x
x
x x
IsobutylMethacrylate
x
x x
x
x x
LaurylMethacrylate
x x
x
x
PEG‐4Dimethacrylate
x
x
x x
x
*“X
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Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 9
June 2011 Meeting – Belsito Team
DR. BELSITO: Okay. So, we're going back now to acrylates crosspolymers, is that correct? Okay. So, the title has now
been generalized to crosslinked alkyl acrylates. In March, insufficient data asking for impurities with a focus on residual
benzene. Those have been provided and incorporated into the report. The panel -- so, basically that's what we're looking at.
We have, just to remind you, the highest concentration -- at least, this is my scribble -- 6 percent leave-on n-hexane at.2 and
benzene at.5 percent were the maxes that I scribbled down. So, assuming that Curt and Paul and Dan are okay with those
levels, safe as used for this acrylate copolymer group.
DR. BERGFELD: Before you go there, could I have you remind me about how you felt about the human sensitization,
irritation? Are you using -- trying to look at this particular document, how it's arranged? But anything but particle size or size
of molecule? There's not a lot here.
DR. BELSITO: You mean because of the acrylic component to them or what?
DR. BERGFELD: Yeah. Well, and just the fact that there's little information on it.
DR. BELSITO: It's Table 5. There's quite a bit of information in Table 5.
DR. BERGFELD: Non-human.
DR. BELSITO: No irritation, no sensitization. I mean, it's only summarized in two short lines in the text, but the table
has quite a bit of data.
DR. BERGFELD: Yeah, you're right. It is.
MS. FIUME: I did just want to point out
so it's not missed, on Panel Book page 49, the calculation for the amount of benzene that could be in cosmetic formulations
has an extra zero after the decimal point. It's actually.03 percent, not.003.
DR. BELSITO: What line is this, Monice?
MS. FIUME: Fourth line from the bottom, very left.
DR. BELSITO: Okay, 0.03, not --
MS. FIUME: Yes.
DR. SNYDER: I had a question. Are we okay with that language, that last sentence there? That care should be taken to
minimize the amount of residual benzene?
DR. BELSITO: Why? What is your concern with that?
DR. SNYDER: I mean, I think we could -- I think because it is such a significant toxicant that we probably should be a
little bit more --
DR. BERGFELD: Specific --
DR. SNYDER: -- specific as to what we mean by minimize. I mean, it --
DR. LIEBLER: Well, I think you just said in the sentence prior to that, such a trace amount presents no safety issues.
DR. BERGFELD: Why don't you just end there?
DR. LIEBLER: I would recommend deleting the last sentence.
DR. KLAASSEN: I would, too. It kind of sounds the opposite.
DR. BELSITO: Yeah, so --
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 10
DR. EISENMANN: But did you catch it's 03 not 003. That's --
DR. BELSITO: .03 percent.
DR. EISENMANN: Right.
DR. BELSITO: You're okay with that?
DR. SNYDER: I'm asking that also, I guess. As to what level -- if we're comfortable with that level.
DR. KLAASSEN: Well, one thing with benzene is that we know it's a human carcinogen. And thus, people get very
excited about it. But the amount of benzene that it takes to be a human carcinogen actually is very high. So, I have no concern
with this concentration in this compound or class of compounds.
DR. BELSITO: Okay.
DR. LIEBLER: I agree.
DR. BELSITO: Okie-doke. So, safe as used.
DR. SNYDER: Monice, had a comment on Table 6. When you compile the tables like this, which are highly informative, like
on Page 71? If you look under acrylic acid, under toxicological studies, there's an inhalation study there that says lesions were
observed in rats and mice in 4-day, 2-week, 20-day, and 13-week studies. But there's no dose information. And particularly if
we could just at least have the doses that were tested, and if there was any way to calculate an NOAEL. And the same thing
down on methyl methacrylate, toxicological studies: Single dose, oral, produced gastric lesions, but there's no indication of
what doses to give us some idea. And likewise, even in the negative studies, like the repro studies, did not produce teratogenic
or reproductive effects in rats. But I'd like to really know the doses that they tested.
MS. FIUME: Can I ask, if there's multiple studies, do you want me to just pick the one that had the lowest or -- you know,
that was most representative for that amount? How do you want that handled?
DR. SNYDER: Certainly a study that could derive an NOAEL is the most -- going to be the most informative.
DR. BRESLAWEC: Keeping in mind that these are components, not the actual ingredients that we're talking about.
DR. EISENMANN: I have one thing in the discussion. This sentence, "The panel indicated that competence in these
assumptions would be bolstered by data from well-conducted absorption penetration studies on, for example," and it continues.
I don't remember you guys saying that, and these things are -- I am -- it's in the second paragraph, last -- or the third paragraph,
actually, the last sentence.
DR. LIEBLER: "The panel indicated that confidence in these assumptions would be bolstered," that sentence?
DR. EISENMANN: Yes.
DR. LIEBLER: Yeah, I flagged that, also. And I asked whether it suggests that we want or expect to see these data.
DR. EISENMANN: I mean --
DR. LIEBLER: That was my question.
DR. EISENMANN: These are -- they're just so large. At least the ones that you have in the molecular weight
information are just so large that I don't know why you would need any information at all.
DR. LIEBLER: I agree with that view.
MS. FIUME: So just delete that sentence?
DR. LIEBLER: Yes, right?
MR. DEMARIA: Anything else?
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DR. SNYDER: I have just a kind of global editorial thing. That in all of these reports, when we talk about the ingredients and
their use in cosmetics, we use various terms like are used, "may function as," "can function as." And I think what we're really
talking about, "as they're reportedly used," because that's what it's based on, correct?
DR. BRESLAWEC: Right. We've tried to standardize that language. And instead of saying "used as," we're trying to
say, "reported to function as." So that's the language we're trying to move toward.
DR. SNYDER: Yeah, because it is a reported use to us and that's what we base all of our conclusions on. So I think it's
really important that we are accurate on what it is. Not that they can or may or --
DR. BELSITO: I'd like the "reported to function as." Comments? Monice, you have everything you need from us for
this one?
MS. FIUME: Yes, thank you.
DR. BELSITO: Okay.
DR. BERGFELD: The only passing comment is on page 7, where you -- alternative studies. Under mucosal irritation,
there you have a bunch of eye studies. They're a little bit tough to pull out, if you're just looking for eye. And in other
documents, it was non-human eye or eye toxicity. I'm not sure what you're going to do about that, but this is inconsistent now
with several documents.
MS. FIUME: So you're looking for eye.
DR. BERGFELD: And frequently look for eye, because of irritation.
MS. FIUME: So you would prefer the term "ocular" versus "mucosal?"
DR. BERGFELD: No. I prefer "eye" appear somewhere in the title so I can find it. That's basically what I'm saying.
DR. BRESLAWEC: Got it. What we occasionally come up with is that we have more headings than text, and then we
go through this heading removal exercise. And I think this is a victim -- fell victim to that.
Marks Team
Next is the Pink Book, acrylic crosspolymers or crosslinked alkyl acrylates. In March of this year, the panel issued an
insufficient data announcement asking for impurities particularly focusing on residual benzene. Data has been provided and it's
found in the report. Ron or Tom? How do you feel?
DR. SHANK: On page 49 of the book, page 9 of the report near the very bottom, it says that in worst case for benzene
concentrations 0.003 percent, that's not correct. There is one too many zeros. So multiply that by 10 and it's 0.03 percent.
And I calculated that if the maximum concentration of the polymer in a cosmetic formulation is 6 percent, for every gram of
formulation would produce three- tenths of a milligram of benzene. And the EPA water standard for benzene is a maximum of
5 micrograms per liter, so this works out that an adult would be exposed to 10 micrograms per liter in drinking water as a
maximum. The cosmetic concentration would be 30 times above that. So I think we need to say something about limiting the
benzene concentration in the polymer.
DR. BRESLAWEC: Dr. Loretz, do you want to comment on that? There is some discussion about how it's lodged in and that
the 6-percent concentration actually could be more like 1 percent.
DR. LORETZ: I think this is the supplier that provided information suggesting that the maximum concentration that
they were aware of in use was less than that, so this is the worst case in the course of the study minus the zero. So I think this is
the highest concentration and higher than you would see, and then they've raised the issue of benzene when you mix it, et
cetera, as it's volatile and expect to get some amount although we don't have anything.
DR. SHANK: I did a calculation based on 1 gram of cosmetic applied to the skin, that a concentration limit for benzene
of 0.016 percent would be the same exposure as the EPA drinking water standard just as a reference. What we want to say is
up to everybody. That would be 167 PPM in the cosmetic formulation. In the polymer, pardon me.
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DR. MARKS: And the benzene is the only issue at this point with the safety of these ingredients. Ron, how would you work
that in the conclusion then? I am presenting it so I'm going to ask you have you figured out how you'd like to work this?
DR. SHANK: No, I have not.
DR. MARKS: It obviously would be safe as used as long as the crosslinked alkyl acrylates have less than X- amount of
benzene impurity or something to that effect. Is that what you were thinking, Ron, the way we'd do this, that we would in the
conclusion state that we want a maximum amount of benzene impurity in it?
DR. SHANK: I was trying to find out in other ingredients we have reviewed. Have we asked this question before, a
limitation on the amount of free benzene in an ingredient? Unfortunately, my access to the website doesn't work again, so I
tried to do it through the compendium and I couldn't find anything, fortunately, the compendium we have online. So perhaps
we have already asked this question about free benzene in other ingredients and refer to that. Otherwise we'll have to discuss
what basis we want to -- I just took the EPA drinking water standard because it was an easy number to find, but maybe there's a
better way to do this.
MS. FIUME: I have a question per the discussions. Last night I pulled up the NIOSH and the OSHA limitations, but if
we were to use EPA drinking water, in the discussion we currently say that we don't really expect it to absorb so the rationale
for using the discussion of using an oral limitation versus something else, what type of wording would you want for something
like that?
DR. SHANK: If the benzene in the ingredient polymer is free, then it will be absorbed through the skin. So that's why
using an oral -- the polymer stays behind, but the benzene would be absorbed into the blood.
DR. SLAGA: In the past we always discussed the level of impurity is the word to make sure that benzene between 5 or
less. Wouldn't just be as easy based on your calculation?
DR. SHANK: Putting 5 percent I think is too high.
DR. MARKS: Right.
DR. SHANK: Because.6 percent of 6 percent is 300 micrograms of benzene per gram of formulation. You can check
my calculations. So 1 gram of formulation would give 300 micrograms of benzene. Two liters of drinking water at the
maximum EPA limit would give you 10 micrograms of benzene. So 1 gram of cosmetic formulation at 6 percent polymer
content would be 30 times above the EPA water standard.
DR. MARKS: That's assuming you only apply 1 gram.
DR. SHANK: Yes.
DR. MARKS: In a normal application if you're doing total body it would be 30 grams.
DR. LORETZ: It would depend on the product type, too.
DR. MARKS: Exactly. It could be significantly more than just 1 gram applied. Again, on page 49, you took one of the zeros
for a final level of 0.03 percent of benzene? Is that what you said, Ron?
DR. SHANK: Yes.
DR. MARKS: Such trace amounts presents no safety issues. You want that sentence struck obviously.
DR. SHANK: Yes, please.
DR. MARKS: And now the question is such trace amounts may present a safety issue might be the better way of doing
it since you have the EPA level. The panel did caution that care should be taken to minimize the amount of residual benzene.
We're sort of addressing it with that but we haven't set a level.
DR. SLAGA: What level would you suggest?
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DR. SHANK: As a starter for discussion tomorrow I guess, that application of the formulation would provide no more than 10
micrograms of benzene. That would be equivalent to 2 liters of drinking water. That's the rationale. I'm sure the others will
find that worthy of comment.
DR. BRESLAWEC: And that is based on the EPA drinking water standard?
DR. SHANK: This is the EPA drinking water standard and that standard is a maximum concentration of 5 micrograms
of benzene per liter of water assuming an adult drinks 2 liters of water a day.
DR. BRESLAWEC: I'm sorry. Could you repeat that definition?
DR. SHANK: The EPA standard is a maximum concentration of benzene in drinking water of 5 micrograms of benzene
per liter, and the assumption is that an adult would drink 2 liters of water a day. So the total exposure would be 10 - 15
micrograms per day of benzene.
MS. FIUME: Dr. Shank, out of my own curiosity, I've gotten lost in the numbers. That's my own fault. The California Prop
65 limits, are they higher or lower than the EPA that was listed in the text?
DR. SHANK: They would not be higher. If anything, they would be lower.
MS. FIUME: They would be lower. There is 6.4 micrograms per day.
DR. SHANK: So that would be lower.
DR. MARKS: So one part would be in the discussion we're explaining the rationale based on the EPA 2 liters of water
adjusted daily in that total of 10 micrograms of benzene. The other is going to be how we word the conclusion that these
crosslinked alkyl acrylates are safe as used as long as the limit of benzene is no greater than 10 micrograms total daily exposure
or something like that. How do you like that, Ron or Tom?
DR. SLAGA: That sounds good.
DR. SHANK: The rationale is the EPA drinking water standard. I should know this. The Prop 65 limit is 6 micrograms.
MS. FIUME: 6.4 micrograms per day orally.
DR. SHANK: Oral?
MS. FIUME: Yes. That's actually in there.
DR. SHANK: Does that mean if a cosmetic formulation has 10 that it can't be sold in California which is 10 percent of
the U.S. population?
DR. SLAGA: They probably use more cosmetics out there.
DR. MARKS: What was California?
MS. FIUME: 6.4 micrograms per day for oral exposure and 13 for inhalation.
DR. SHANK: I don't know that I would recommend using the California Prop 65. I won't comment further. I wouldn't use
that as the standard.
MS. FIUME: I would imagine that suppliers have had to do something because the European limits are very different.
There are different limits for the amount of residual benzene based on where they're supplying to. Europe has a level of.1 so
certainly they can't use that in their jurisdiction.
DR. SHANK: .1 microgram?
MS. FIUME: .1 percent.
DR. LORETZ: .1 percent.
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DR. SHANK: .1 percent.
DR. SLAGA: That adds up to impurities?
DR. LORETZ: They showed that the loss they looked at, it range and I think the highest was.41 and that some fall well
below that.
MS. FIUME: I tried to find what Europe's rationale was for the limit and I wasn't able to find it to really pinpoint what
they were basing their number on.
DR. LORETZ: We would assume that somebody selling it in California is aware of that and in compliance with Prop
65 but we don't have any more information.
DR. MARKS: So you don't have a problem, Ron, with saying we're going to limit it to 10 even though California has 6.4?
MS. FIUME: Actually in the memo it does say that formulators that sell products in California must comply with
California's Prop 65 which limits benzene exposure from a product to 6.4 micrograms per day for oral exposure. So the
information that did come from industry does state that they are aware of what California's limit is and that they have to
comply.
DR. MARKS: I would say we go to 6.4.
DR. SLAGA: It's easier for the formula based on the lowest.
DR. MARKS: Yes.
DR. SLAGA: You don't have to mention California.
DR. SHANK: You'd have to mention why is it 6. --
DR. SLAGA: That's true.
MS. FIUME: Provide it just in case you --
DR. MARKS: Then we get into we think that EPA is better than the California Prop 65. I don't know. I just see that if I were
a formulator a conflict when I look at the CIR recommendation of 10, although maybe that happens all the time. I'm not sure.
We can certainly leave it at 10. You're our California representative here, Dr. Shank. So it's going to be safe?
DR. SLAGA: Industry will probably try to keep it below Proposition 65, I'd guess.
MS. FIUME: Because there's multiple solvents.
DR. BRESLAWEC: And that.1 percent, how does that compare to the 10 micrograms per day?
DR. MARKS: Let me see. I think I'm the one proposing, so tomorrow I'm going to move that we issue a tentative
report on the crosslinked.
MS. FIUME: Insufficient?
DR. MARKS: Yes. It was insufficient. So a tentative report on -- yes, I know the subject says tentative report, but actually it's
what we're moving. A tentative report on crosslinked alkyl acrylates as safe as used as long as the benzene impurity limit is no
greater than 10 micrograms of benzene total exposure daily or daily total exposure. Does that sound like the way to handle it?
DR. SLAGA: Total from all sources or cosmetics?
DR. MARKS: We say there that in cosmetics safe for cosmetics. So you think somebody would interpret the
conclusion total or should we be more specific and say 10 micrograms of total exposure? Now you get into all the other issues
we have like the phthalates in nail. We limited in the nail cosmetic but we're not limiting it to all phthalate exposure from --
DR. SLAGA: Any source.
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DR. MARKS: Yes.
DR. SHANK: I haven't reviewed the EPA document for some time, but I would be -- I'm fairly sure that they
considered other sources of exposure because it's an additive to gasoline. People who pump gasoline are exposed by inhalation
to benzene. There are several sources of benzene in the environment and I'm pretty sure the EPA water standard took that into
account. So I would put the benzene limitation as 10 micrograms per cosmetic exposure or however you word that.
DR. MARKS: Personal care product.
DR. SHANK: Personal care product.
DR. MARKS: Personal care product exposure.
DR. LORETZ: That's a little complicated as to you don't know if -- still in theory so if you're putting in your five and
he's putting his five, it gets challenging that way.
DR. MARKS: Another nuance.
MS. FIUME: And that will be in the conclusion and not just the discussion?
DR. SHANK: It would have to be in the discussion to say how we arrived at that number.
DR. MARKS: But the conclusion would limit.
DR. SHANK: The limit would be in the conclusion, yes.
DR. MARKS: Right.
DR. SHANK: Is there some way to scan previous documents to see if we've asked this question about limited benzene before?
DR. LORETZ: There's one coming up on today's agenda that refers to benzene free.
DR. SHANK: For benzyl alcohol?
DR. LORETZ: It must be in that.
DR. BRESLAWEC: I'm not particularly aware that we've limited it per product exposure before. I think, and I honestly
can't say this with 100 percent certainty, but I think it's always been concentration in the ingredient because we're looking at an
ingredient and not the product.
DR. MARKS: Right.
DR. BRESLAWEC: So I would urge you to characterize it in a way that focuses on the level of impurity in the ingredient
rather than in the product.
DR. SLAGA: In this specific ingredient.
DR. MARKS: This is for the specific ingredient.
DR. SLAGA: Not in personal care products.
MS. FIUME: But I think it was just PEG alkyl ethers that there was concern over some of the residual solvents or residual
components. In the discussion it was worded a certain way without specifics, but I would have to go back and look at it
because I want to think it was the alkyl PEG ethers that addressed that. Same type of concept.
DR. MARKS: What do we do with heavy metals, aflatoxins and that sort of thing? We don't do limits do we?
DR. BRESLAWEC: We have in the past.
DR. SLAGA: We have a boilerplate.
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DR. MARKS: Right. A boilerplate.
DR. BRESLAWEC: But it's based on the ingredient.
DR. MARKS: Right.
MS. BECKER: Dr. Marks? It's in the silylate report in the report on toluene. The CIR Expert Panel has stated that all
cosmetic ingredients should be benzene free.
DR. BRESLAWEC: But there was a comment from industry where they questioned where CIR had stated that, so that's an
issue we need to address.
MS. BECKER: I can go get my computer and pull it up.
DR. BRESLAWEC: Let's do that.
DR. SHANK: It's hard to say because I based my calculations on 1 gram, but that was arbitrary, so I guess it depends on
what the product is and how much is applied to the skin. So how do you set a limit on the concentration in the ingredient based
on the maximum amount you apply to the skin and what would that be? I have no idea.
DR. BRESLAWEC: I think you can help us on that.
DR. MARKS: Because here we have -- I mean there's a lot of leave-on use. For the C-10 to 30 acrylates there are over 1,300
leave-on products.
MS. FIUME: Another complicating factor and I think Linda was alluding to this earlier is that from that manufacturer
under that trade name they state that they're aware of it being used at a maximum of 1 percent, but the problem is we don't have
the concentration of use breakdown by trade name, it's by INCI name. So they may only be using it at 1 percent and we're
using it at 6 percent as the worst-case scenario, so it also complicates what is actually being put in. In one of my reports there's
actually a calculation of how much is exposed based on product type. I don't know if this is helpful, but in the TEA report a
company actually came up with an exposure of consumers. It's on page 6 of the report.
DR. SHANK: Of the report. Yes?
MS. FIUME: And then on page 6, the third full paragraph down, it --
DR. SLAGA: What page, ma'am?
MS. FIUME: Page 6 of the report, which is Panel Book page 25, and that's TEA.
DR. MARKS: It's a different book.
MS. FIUME: Yes.
DR. MARKS: TEA.
DR. SLAGA: Yes, I have that.
MS. FIUME: I don't know if that's helpful at all.
DR. SHANK: So there is some kind of algorithm to use?
MS. FIUME: That was submitted to us. And I know calculations have been done for things like the diluted products,
how much is actually exposed per day, but I don't know of any other products if there's been calculations as to what type of
product, how much exposure actually occurs per day.
DR. MARKS: I think we saw that with the RFL presentations on fragrance exposure and they did it with various
product categories.
DR. LORETZ: And we've published. There are a lot of publications.
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MS. FIUME: It sounds familiar because I know the diluted ones, if that would be referred to more often in the report.
Yes, that calculation actually came from an OECD SIDS document that was their calculation that was included in their report.
DR. SHANK: Okay.
DR. LORETZ: I know the Expert Panel has used the Prop 65 levels before. I guess this one's just more complicated because
if you take the worst case then you start getting into a different --
DR. MARKS: Here we go. On toluene it says that was the question actually I was going to ask, and I don't know
whether it can be answered, can these acrylics be manufactured free of benzene?
DR. LORETZ: I think benzene is just way of making it. It's not necessarily a common way. It's just one way.
DR. MARKS: So if it isn't a common way then to me the way to solve it would be that we recommend there be no
benzene.
DR. LORETZ: I think it's a certain product type that some people find have some benefits.
DR. SHANK: I'm perfectly happy with this. What year was this written? Back in the day.
DR. MARKS: Do you want to read it? I like the second sentence under the discussion I guess it is or the summary.
DR. SHANK: This is on the toluene document in the 1980s I guess, "One possible impurity, benzene, is a carcinogen.
Therefore, cosmetic products formulated with toluene should be benzene free." That's the best way for us to go if that doesn't
cripple the manufacturer if there are other solvents that can be used.
DR. MARKS: Is there anybody from -- of course that's not going to influence our decision on safety other than to say is
that an issue with the manufacturer.
DR. LORETZ: I think what the manufacturer said is that is an issue, that they do sell that product and that product has value,
so I guess that's why they -- you know, we think it would be a safety assessment on the benzene levels rather than just a flat-out
ban.
MR. LABA: Dennis Laba from Presperse. Presperse represents one manufacturer that makes products. These products
were originally precipitated in benzene and they have been moving more and more environmentally friendly solvents and
toxicity safe solvents. But the whole industry has not moved as fast as the manufacturers though these other products have
been available. People who have been using these for years have not changed all of their products over to the other ones.
There is one particular manufacturer that has most of the market and they would probably be the ones most upset about that,
saying that there can't be any benzene, but the alternatives are out there certainly.
DR. SHANK: Thank you.
DR. SLAGA: Let's proceed then.
DR. SHANK: So the precedent if the benzene document is that we say benzene free.
DR. BRESLAWEC: The toluene, yes.
DR. SHANK: Toluene document. Thank you.
DR. MARKS: I like safe. And then in the discussion because that's the way it is in the toluene document, in the
discussion we say that it's benzene free, that we're concerned about benzene and unless there's an alternative way of arriving at
a safe limit which we've discussed, it doesn't sound like that's going to be easy.
DR. LORETZ: I guess I have some real concerns about benzene free because that implies a zero tolerance which, I
mean, when you look at like traces in things that are like in Annex 2 in Europe, I mean, they, you know, qualify that as a good
manufacturing practice, et cetera. It's not a true zero. So, but to me benzene free taken literally is a true zero which is --
DR. SHANK: The original toluene document is dated 1987, so that must have gone through re-review. So if we could
find the re-review to see -- because I'm sure we've handled this before.
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DR. MARKS: So we're back to safe, and then in the conclusion do we mention there it should be benzene free or should
we put that in the discussion? Because in the toluene document it's in the discussion, is it not?
DR. SLAGA: Not in the conclusion.
DR. MARKS: Right.
DR. SLAGA: We ought to be consistent depending on what the re-review was.
DR. MARKS: Then the question also there is do we want to as you suggested what may create heartburn, but from a
safety point of view do we want to be benzene free? Because obviously what we've struggled is if we don't say it's benzene
free, what is the limit we're going to set?
DR. SLAGA: In the original discussion we were talking about benzene that's trapped.
DR. BRESLAWEC: I think that was a misunderstanding on my part.
DR. SLAGA: I'm sorry. We'd have to have had some kind of linkage wouldn't we to keep it --
DR. SHANK: It's a polymer so it could be physically trapped, not chemically trapped.
DR. LORETZ: I think benzene is referred to a monomer at some point in here and that's not correct.
DR. SLAGA: I think in reality we're worried about the total exposure of benzene so maybe we're going into cosmetic and
looking for environmentally safe alternative solvents here, then it seems to me that's as good a case.
DR. LORETZ: While that may be the ideal, does it make sense if your product is in compliance with Prop 65 and you
specify that that's what you recognize is your safe level?
DR. SLAGA: That means that we would be going beyond Proposition 65.
DR. LORETZ: Right.
DR. SLAGA: We can't say we're excepting Prop 65.
DR. SHANK: Another way is to take the EPA water standard for a total exposure of 10 and that cosmetic personal
product care use should contribute no more than half of that, so that would be 5 micrograms?
DR. BRESLAWEC: At what level?
DR. SLAGA: That's getting a little wishy.
DR. SHANK: Somebody else try it.
DR. SLAGA: This is toluene sulfonamide formaldehyde residue and that was straight toluene in that one.
DR. SHANK: Yes.
DR. LORETZ: I think for consistency I'm concerned about again setting a zero standard because we're going risk based
throughout and not just benzene.
MS. FIUME: I'm trying to think about in the past with the wording where is a maximum is allowed per day, but you
could have multiple exposures how we've worded it in the conclusion. Peppermint oil might be one because I think peppermint
oil didn't have a maximum that should be allowed per day and I don't know if the discussion handled that at all or not.
DR. SHANK: What was it called?
DR. MARKS: That was a sensitivity issue.
MS. FIUME: Peppermint oil.
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DR. MARKS: Let me see. I'm trying to think. Again, I come back to the phthalates because there was the concern that nail
polish would add to the total burden of phthalates, but I think we just did a safe because our margin of safety calculation with
that showed that it would be --
DR. SLAGA: Wouldn't have been very large.
DR. MARKS: -- a very small contribution by nail. Whereas this potentially --
DR. SLAGA: We've added significant with our approval.
DR. MARKS: Yes. This with your calculation, Ron, would give a significant amount of exposure.
DR. LORETZ: Would you maybe then be going to ask industry for more information on use levels and risk to defend
the risk assessment?
DR. SHANK: It's a genotoxic carcinogen.
DR. MARKS: The way we could proceed is to with the benzene free and that goes out as a tentative report which
means industry can react to it. And if they can show us some margin-of-safety calculation that is reassuring -- we're obviously
struggling with coming up with establishing a limit. Maybe industry could suggest a limit.
DR. SLAGA: We'll have the discussion tomorrow.
DR. SHANK: The limit on aflatoxin is a lot more potent carcinogen than benzene by far. That limitation is based on the
fact that in certain things you can't get it any lower so you just have to live with it. Even FDA allows it in food at a certain
level because it's associated with the use of peanuts. You can't get it to zero. But here if it's used a solvent, you can get it to
zero by not using it as a solvent.
DR. SLAGA: Let's go with benzene free because at least we have the toluene document to base it on.
DR. LORETZ: I guess I'm still struggling with the free and that meaning zero and that being kind of a scary precedent.
Would it maybe make more sense or would it be just as well to say benzene should not be used as a solvent and then leave
open the door for industry to come back with some kind of a risk assessment to defend it?
DR. MARKS: If they don't use it as a solvent, there won't be any benzene. Correct?
DR. SLAGA: Yes.
DR. LORETZ: I guess I'm struggling again with the zero because benzene free to me is too absolute.
DR. BRESLAWEC: Perhaps we can say something alone the lines of benzene no higher than a safe level as determined
by a risk assessment and then expect the risk assessment to come in from industry to provide a level that the panel would
consider safe at its next deliberation. Bart Heldreth is here.
DR. SHANK: Benzene in crosslinked polymer.
DR. MARKS: Alkyl acrylates.
DR. SHANK: Alkyl acrylates. Is the benzene that's a solvent physically trapped in the polymer so that it can't be
absorbed?
DR. HELDRETH: That potentially could be the case. We don't have any data from industry saying that they used it as a
solvent and during the crosslinking it got trapped in there. Potentially, sure. Anytime you do crosslinking you could trap the
solvent or anything else that's in the solution inside small spaces inside the polymer. Whether that's the case here we don't
know. The other thing, once you have a polymer, especially a crosslinked polymer, there's also the possibility of the
solvent absorbing into the polymer even though it didn't get tracked on crosslinking and residing in there and even upon
heating and doing lyophilization to try to get things out of there, it could stay in there a little longer than you would expect.
Whether that's the case here, though, we don't have any data on that, but there is that potential.
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DR. SHANK: Thank you. I guess we can say in the discussion that benzene should not be used as a solvent. Then the
question is what do you put in the conclusion.
DR. MARKS: If we do what you suggest, it was a draft tentative report, we could issue a tentative report with
insufficient and out concern about benzene and let industry come back and provide sufficient information to declare it safe.
That would be another tact, move forward with a formal insufficient report.
DR. SHANK: Could you go sufficient for a crosspolymer that is made without benzene and insufficient for a
crosspolymer that is made with benzene?
DR. MARKS: That's another option.
DR. SHANK: Because if a lot of this product is made without benzene, it seems unfair to put it all into insufficient.
DR. BRESLAWEC: I think there's only one
39 polymer that we have data on.
DR. SHANK: We've never done that before, split it.
DR. BRESLAWEC: You're making a distinction on the method of manufacture rather than levels of something in the
ingredients.
DR. MARKS: Ron, we've been struggling here. We've only gotten to the third ingredient. The first two we did not
reopen, HC Red No. 1 and the glutaral. Where we're struggling with the crosslinked alkyl acrylates is the benzene impurity,
benzene using a solvent. If we go on page 49, Ron pointed out that the actual calculation there in the next to the last paragraph
should be 0.03 percent of benzene in cosmetic formulations. Is that correct, Ron?
DR. SHANK: Yes.
DR. HILL: Is that by the California numbers?
DR. MARKS: No.
DR. SHANK: It's based on industry data and it was calculated --
DR. HILL: Five times formula 6.
DR. SHANK: Right.
DR. HILL: There it is.
DR. MARKS: Ron further calculated that if we had the maximum concentration and we applied 1 gram of a cosmetic
ingredient, all the benzene in this polymer was released and that would be equivalent of 300 micrograms. Did I recall that
correctly?
DR. SHANK: Correct.
DR. MARKS: Which is 30 times -- in the EPA and drinking 2 liters of water a day. So assuming all this benzene is
absorbed or even a large portion of it, we've exceeded the EPA limits for exposure to benzene systemically. So we're
struggling on in the one case trying to set a limit based on the EPA drinking water or the California Prop or going back to a
1987 report on toluene which in the discussion it was stated that toluene should be benzene free. So we're exploring the idea of
having this document saying safe but in the discussion put benzene free. That gets into the issues that some of these products
apparently are now made without benzene as a solvent. Should we go that strict and say benzene free or should we try and
establish some sort of a limit and what is that limit going to be? Do we move forward by issuing a tentative report splitting out
these product whether they have benzene or not benzene and safe for benzene free, obviously insufficient for benzene
containing or just go to an insufficient tentative report? So that's sort of where we were and we're struggling with how to
present this tomorrow. Does that pretty much summarize where we are?
DR. SHANK: Yes.
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MS. FIUME: As a suggestion, if somehow the discussion or the risk assessment can be written in giving industry the
option to either bring in information or send information with a safe as used conclusion and then the comments came in, as
long as it didn't become more restrictive, that wording in the discussion can change based on the industry comments and it
could still go as a final report next time as long as it didn't change the conclusion and the main point of the discussion. Not that
that's a reason to do it one way or the other, but that is a consideration as you write the conclusion as to the next step of the
report.
DR. MARKS: Tom and Ron, do you think there is a safe limit that benzene could be used or exposure? It seems like
there is since the EPA has set a safe limit. So I guess, yes, you could put safe and then the challenge will be somehow crafting
a way of setting that limit. What you're doing is helping facilitate so the next time if there are any changes you can move right
on to a final. I'm not quite so sure that procedurally that's -- even though that's expeditious, I'm not sure it sends the right
message that it's safe, but we really have concerns.
MS. FIUME: I was thinking is that we have items that are sensitizers. We don't set a limit. It's formulated so that
they're not sensitizing, so if it was formulated so that the amount of benzene isn't above safe limits, because when I searched
benzene using our SciFinder and you hit regulations, there are so many different numbers. There was page after page after
page. So I think trying to find a specific number is going to be difficult.
DR. BRESLAWEC: You could specify in the discussion which standard and you could say to the EPA standard.
DR. SHANK: You can't formulated to be non- carcinogenic.
DR. MARKS: Here are some more complications. We don't get hell from the re-review. It doesn't mention benzene in
the re-review Lillian tells us.
DR. SLAGA: We didn't re-review it did we?
DR. SHANK: Toluene.
DR. MARKS: Toluene.
DR. BRESLAWEC: There should have been probably two by now.
DR. MARKS: Which year is this?
MS. BECKER: This is 2005.
DR. MARKS: So it's the most recent one.
DR. SLAGA: We didn't re-review it. We didn't reopen it did we?
MS. BECKER: No.
DR. SLAGA: So that's the reason.
DR. SHANK: We agreed with the benzene
free.
DR. MARKS: Right.
DR. SLAGA: I think we ought to use that. Don't you?
DR. MARKS: Obviously industry didn't have a problem with benzene free.
DR. HILL: Yes, but the catch to that there's no such thing as benzene-free toluene. What you're really dealing with is a
detection limit issue and now with the mass specs available I think that would be way down there compared to whatever year
that was sent. There's no such thing as benzene-free toluene.
DR. SLAGA: Approaching benzene free.
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DR. BRESLAWEC: I actually think that it might be worth asking FDA whether FDA has a benzene limit.
MS. DEWAN: Not that I'm aware of as far as know.
DR. HILL: And these California standards are for ingestion. Right?
MS. FIUME: One is oral and one is inhaled.
DR. HILL: Inhalation and oral, but we don't have any dermal.
DR. MARKS: No, and one of the problems we have with that, Ron, is that when Ron Shank was calculating, he was
using an EPA standard with a 10. With California Prop 65 the limit is 6.5 for oral exposure. So it's actually lower.
DR. HILL: 6.5.
DR. MARKS: Yes, 6.5.
DR. HILL: That's practically nothing. It's about the same.
DR. SLAGA: And we're assuming that it all gets absorbed.
DR. MARKS: I shouldn't have written this many notes over here because I still have to make a motion tomorrow and
I'm not sure what motion I'm going to make.
DR. HILL: In the EU the raw material has to be.1 percent or less. Do I remember that correctly?
DR. MARKS: Yes.
DR. BRESLAWEC: To me it seems as if you are lacking data to make a decision.
DR. MARKS: I wait.
MS. FIUME: Actually that's not raw material. It's mixtures I think so that it should be final product.
DR. MARKS: Right.
DR. HILL: In the final product makes your point. Is that right? I don't trust my memory.
MS. FIUME: A constituent of other substances or in mixtures. So that would be final product. Correct?
DR. HILL: My impression was it was in
47 the raw material.
DR. LORETZ: That was my understanding as well.
DR. HILL: Again, lots of water has flowed under the bridge.
DR. MARKS: I don't know how that is calculating now.
DR. LORETZ: That sounds fine in the final product.
DR. HILL: The final product?
DR. LORETZ: No, I said that sounds fine in the final product.
DR. HILL: Yes.
MS. FIUME: Other directive. As a constituent of other substances or in mixtures in concentrations equal to or greater
than 0.1 percent by weight.
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DR. MARKS: That seems like a higher limit than micrograms of drinking water. Options? We can't take this. We've
got to move it forward.
DR. SLAGA: No, we have to move it forward.
DR. MARKS: So the next is, and we've already had a draft, we had the insufficient data announcement, so we're into a
tentative report and the options there are safe, insufficient, unsafe. We aren't at unsafe. That's for sure. So do we do safe and
address the benzene impurity in the discussion? Or do we put insufficient and ask industry to help us reach a margin of safety?
DR. HILL: My impression is that if the EU sets the standard which again I interpret to be a raw material number, that
it's possible to achieve that and that maybe people are formulating with a less-expensive grade, we've talked about and that
maybe better grades either because it's not pulverized in benzene in the first place or because it's processed more to get rid of
the benzene more thoroughly, then it's available to them. But I also realize whenever you say somebody has to reformulate a
product that's a big deal.
DR. SLAGA: There are a number of products that don't use benzene as a solvent.
DR. HILL: That's what I'm saying. They use either hexane/ethyl acetate or something unspecified.
DR. MARKS: We could do the safe and in the discussion mention that a number of products do not use benzene. The ones
who use the benzene, the panel is concerned about its toxicity and then elaborate on that. Then if we can get a margin of safety
in and have a suggested limit it would be good, but we could certainly reference the California Prop and the EPA. So that
might be another way of handling it. I know that gets to what you said in terms of let's do safe and move forward, but that
would be another way of handling it.
DR. SLAGA: We're discussing all the possibilities.
MS. FIUME: That's right, and there are at least four solvents that are available for that one ingredient which is the one
trade name.
DR. MARKS: Tom, how do you want to proceed?
DR. SLAGA: I would go with that. I definitely don't want to table it.
DR. MARKS: No.
DR. SLAGA: And I'm just thinking what the other group would do. None of them would say it's safe too.
DR. MARKS: I think we'll find out tomorrow when I make our team's move and our team needs to feel comfortable
with that. It is a little bit different knowing that we really feel it's safe when it's benzene free. That's the easiest way of looking
at it.
DR. SLAGA: When benzene is not used as
a solvent.
DR. MARKS: Right.
DR. SHANK: I'm not at ease calling it safe if our calculations are that it can contain levels of benzene that have been
found in excess of several regulatory bodies' standards. So I don't like saying it's safe alone unless it's qualified. Polymers
made with solvents other than benzene are safe, and then in the discussion say
why we say that. If you're going go safe I'd put in there for those polymers that are not made with benzene. That's not saying
benzene free or anything.
DR. HILL: To me that seems overly restrictive given the fact, although I'm not thoroughly familiar with what happens to
small, small amounts of benzene when it gets into the skin or an even smaller amount if it entered the nasopharyngeal region
than was suggested, I would think those kinds of levels if we were within the European limits of.1 percent and then formulate it
a maximum of 6 percent if we're going to put it way down in the levels of benzene, I wouldn't think anything systemic would
be any problem. Are there any dermal carcinogenesis sorts of things that one needs to worry about with that small an amount
of benzene?
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DR. SLAGA: It's extremely weak activity.
DR. HILL: I used to wash my hands in it.
DR. SHANK: I don't think that's the problem. I think the problem is setting the concentration limit in personal care
products.
DR. HILL: Right. I know. I get that.
DR. SHANK: Finding the number.
DR. HILL: We don't have the information that lets us do that.
DR. SHANK: That's correct.
DR. MARKS: So we could go forward with insufficient.
DR. HILL: Insufficient with anything with benzene in it?
DR. MARKS: Just insufficient. We keep coming back to saying either there is no benzene or there is a benzene limit
and we have a problem with finding what the benzene limit is and determining that.
DR. LORETZ: You're not comfortable with splitting them into insufficient for the benzene and asking for further
information and safe for the others?
DR. MARKS: We could say, yes, the conclusion could be safe and as we've done -- this would be the first we've had the same
ingredient and said they're safe when they're done one way and insufficient in another way. We've done that for ingredients
within groups where there are different ingredients, some are safe and some are insufficient.
DR. HILL: But I'm thinking why not?
DR. MARKS: Yes, that's an interesting -- precedent setting, but maybe that's the way it should be.
DR. SHANK: I favor that. Safe for rinse-off, safe for leave-ons when the polymer is made with solvents other than
benzene, insufficient for leave-on when the polymer is made with benzene.
DR. SLAGA: That could start a discussion tomorrow.
DR. SHANK: That will start a discussion.
DR. HILL: It sure will. Were there any concerns about the residual ester monomers at.5 percent when we're talking
alkyl acrylates? I'm looking at page 3 at the bottom. Did anybody have any concerns related to those? I'm looking at Panel
Book page 43, which is draft report page 3, talking about.5 percent residual ester in the C-10 and C-30 alkyl acrylates. So in
formulation that would be again down in the.03 percent range or something like that, but we are talking alkyl acrylates.
DR. SHANK: I think our only concern was acrylic acid itself and the concentration is below our concern.
DR. HILL: Okay.
DR. SHANK: The larger ones were not our concern.
DR. HILL: I was thinking that the esters might be more problematic than the acids. I don't know that for a fact, but that
was my sense is the esters could be thermally absorbed. I'm not sure how much the acid would penetrate past upper stratum
corneum, but the esters might. I think defenses such as glutathione would take this out pretty effectively, but I wondered if
anybody else even thought about that. And I'm guessing it was thought about -- it wasn't this that was the original review, but
the other alkyl acrylate polymers there was discussion of monomers. We don't have that report, but I at least glanced at it.
DR. MARKS: I'm going to summarize where I think we are, and Tom, Ron and Ron just be sure I'm on the same page
with you. Tomorrow I'll move that we issue a tentative report on the crosslinked alkyl acrylates, that they're safe, but they're
insufficient for leave-on products having benzene impurities.
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DR. LORETZ: You don't want to say polymerized with benzene just for clarity?
DR. MARKS: No, I think benzene impurity.
DR. HILL: Yes, because in principle that's the only place it could come from, but it would be good either way.
DR. MARKS: Safe, however insufficient.
DR. HILL: I suppose it's polymerized in the other solvent, but then recrystallized with benzene and you'd have the
possibility of getting the benzene active. I don't know anybody would do that, but then I've done a lot of crystallization in my
life and sometimes --
DR. MARKS: Leave-ons having benzene impurities. That can be refined, but does that catch it?
DR. SHANK: Yes. That's okay. I can be wordsmithed.
DR. MARKS: Then the insufficient data is we need a margin-of-safe calculation with a limit and establish a limit so if
industry came back and showed us a margin of safety with establishing a limit for benzene impurity on a leave-on then we'd
feel comfortable. Does that capture it? Do you think this is going to make an interesting discussion on the conclusion in this
tentative report and then of course the discussion is going to go all around what we just talked about, the EPA limits, the
California Prop 65, the European and all that and their concern that benzene is a carcinogen. Does that sound good?
DR. SHANK: I'm going to change my flight tomorrow.
DR. MARKS: We haven't even gotten to the formaldehydes.
DR. BRESLAWEC: Apparently the other group is still on formaldehydes.
DR. MARKS: Who knows? Maybe ours will go quicker. At any rate, are there any other discussions? Safe, however
insufficient data for leave-ons having benzene impurities and that's how we're going to deal with the benzene impurity and deal
with that the industry can help us with this. Ron Shank? Be prepared tomorrow. I'm going to say, Ron, would you make
comments on this?
Full Panel
Thank you. Unanimous. Then we're skipping the next ingredient and going on to the crosslinked alkyl acrylates and that is Dr.
Marks again.
DR. MARKS: So, in March of this year's meeting, the panel issued an insufficient data announcement asking for
impurity data and what we were concerned about was benzene as the impurity in these crosslink alkyl acrylates, which are 23
compounds, and we had extensive discussion on how to deal with this benzene impurity, whether or not we should try and set
limits to what should be in a cosmetic product and where would those limits be derived from. Would it be from the California
Prop 65 limits? Would it be EPA drinking water limits of benzene? And how we finally ended up is feeling, since a number of
these crosslink alkyl acrylates are -- benzene is not used in the manufacturing process, we felt that a reasonable conclusion
would be safe, however insufficient data for leave-ons having benzene impurity within it.
DR. BERGFELD: And that's a motion?
DR. MARKS: That's a motion. I'm sure there will be discussion.
DR. BERGFELD: Discussion? Belsito response?
DR. BELSITO: Yeah, we, in the draft discussion, in the third -- fourth paragraph, the next to the last sentence, it says,
"For example, a worse case for benzene as an impurity would be 0.5 max times 6 percent maximum use concentration in the
ingredient for a final level of 0.03 percent in a cosmetic formulation. Such a trace amount presents no safety issue," and then
just deleted that last sentence. So, the feeling of my panel members was that 0.03 percent did not represent a safety issue.
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CIR Panel Book Page 26
DR. MARKS: So, Ron Shank actually did the calculations on this comparing it to the EPA water level of 10 microns --
I'll tell you what, Ron, why don't you go through your calculations with the 10 micrograms if you drank 2 liters of water -- and
then he calculated in a cosmetic ingredient that you could apply 1 gram and get a third of that potentially.
DR. SHANK: Right. I took the maximum concentration of a polymer in cosmetics is 6 percent and 1 gram of that cosmetic
applied, which would give 60 micrograms of the polymer. If that's a half percent benzene, that would produce 300 micrograms
of benzene per gram of formula -- formulation. That 300 micrograms is 30 times higher than the EPA maximum benzene
drinking water standard of 5 micrograms per liter. Assuming an adult drinks 2 liters, that would be 10 micrograms of benzene
per day. The cosmetic formulation would provide 300 micrograms per day. So, the benzene concentration is too high. And
that's for one gram of cosmetic applied to the skin.
DR. BELSITO: I mean, we obviously had concerns with benzene as did you. I mean, I don't really have a problem with
your conclusion. I mean, that's what we're all trying to get at is the restriction of benzene. So, I mean --
DR. LIEBLER: So, I think the calculation's valid. The question I have is, drinking water, obviously you're ingesting it
and that means you're ingesting all the benzene in the calculation in the drinking water side. With a cosmetic ingredient you're
applying an ingredient, and the question remains, how much of that ingredient -- of the benzene in that ingredient would
actually be absorbed. And, you know, you would certainly be losing it -- if it's there, you'd be losing it to evaporation as well
as absorbing whatever you could absorb. So, I mean, the difference you point out is high, except that the amount that you'd
actually get into the body would be much lower -- lower fraction of what's presented to the body.
DR. SHANK: But you have to know how much.
DR. MARKS: And that's what we struggle with, and that's only one gram, Dan. If we applied this total body to an adult
it would be 30 grams, and there are some baby products here, so if you did total body application, it could be not 300 in an
adult, but exposure to 30 times that and then we don't know what percentage of that -- I agree, that's why we struggle trying to
figure out how we could set a limit. And then we ended up with insufficient for leave-on just because we couldn't determine
the limit and we didn't know how much absorption would occur. And we even asked the manufacturers how much benzene
would be free within these acrylate ingredients and we couldn't come up with an answer to that.
DR. LIEBLER: It's insufficient for leave-on at a given concentration of benzene? Is that what you said?
DR. MARKS: Yes, insufficient data for leave-ons having benzene impurity within it. We're told that a number of these
acryl acrylates are actually manufactured without benzene, so.
DR. SLAGA: As a solvent.
DR. MARKS: Yeah, as a solvent, so it would -- if it's not manufactured with benzene as a solvent, then it's a nonissue.
It's only those ones in which benzene is a solvent.
DR. BELSITO: So, you need to be careful how you craft that because what you're saying is that it's -- the data are sufficient to
support the safety for leave-on and rinse-off products, however, the assumption is that the leave-on products will not be
manufactured with the use -- or however you want to say it -- of benzene.
DR. MARKS: Yeah, that's correct, Don. That's essentially it. However, insufficient data for leave-ons having benzene
impurity.
DR. BRONAUGH: Could I just add that 1 gram of product probably, you know, that would cover 1,000 square centimeters of
a baby. You couldn't get much more than one gram on --
DR. SHANK: It's still, at this concentration of a half a percent, it's still more benzene for a baby than would be allowed
if the baby had that benzene in drinking water.
DR. BERGFELD: You're going out as insufficient in the leave-ons, did you want to modify?
DR. BELSITO: Only if the product is manufactured with benzene.
DR. MARKS: Correct.
DR. BERGFELD: Is there another way of stating that where it would be fine or safe if benzene-free leave- ons, but unsafe or
insufficient for those who contain benzene?
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DR. MARKS: That's exactly what we said.
DR. BELSITO: Have we ever set a limit for benzene?
DR. MARKS: Well, we tried doing that, Don, and if we can -- you know, as this goes out, issuing a tentative report, one of
the data needs we would want for the insufficient data is establish a limit. We struggled with that so we would ask industry to
help us with establishing a limit and a margin of safety calculation.
DR. BERGFELD: Would you restate your motion then again and --
DR. MARKS: We would move to issue a tentative report on these ingredients, and I have noted that there are 23 of
them, that they're safe; however, insufficient data for leave-ons having benzene impurity.
DR. BERGFELD: Is there a second?
DR. BELSITO: Second.
DR. BERGFELD: Second. Any further discussion?
DR. BELSITO: Yeah, what we would need would be, as Jim said, for -- they may be safe if they have a benzene impurity, but
what is the level and what's the margin of safety?
DR. BERGFELD: All right. Calling the question then, all those in favor of this motion? Approved, thank you.
DR. MARKS: And let me just reference one thing we did consider and look at was the 1987 report on toluene and
actually in that conclusion it was that that ingredient would be benzene free, but we decided not to go to that extent that it had
to be benzene free.
DR. BERGFELD: Any other points that need to be made at this time?
DR. KLAASSEN: Yes, I think it's very important that we don't say something like that, that it -- and if we said that for
toluene before we should all be spanked.
DR. MARKS: Well, you can review the report. We pulled it up yesterday.
DR. KLAASSEN: I believe you, but we made a mistake.
DR. BELSITO: Last comment was we were asked whether if other chain length molecular weight acrylate
crosspolymers came on could we do like what we did with PEGs and just say safe if they're used in the same way? And our
group felt we could not, we would like to see each individually.
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Draft Final Safety Assessment
Crosslinked Alkyl Acrylates as Used in Cosmetics
September 27, 2011
The 2011 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 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 F. Alan Andersen, Ph.D. This report was prepared by Monice M. Fiume, Senior Scientific Analyst/Writer, and Bart Heldreth, Chemist, CIR.
© Cosmetic Ingredient Review
1101 17th Street, NW, Suite 412 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢
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CIR Panel Book Page 29
ii
TABLE OF CONTENTS
Abstract ............................................................................................................................................................................................................ 1 Introduction ...................................................................................................................................................................................................... 1 Chemistry ......................................................................................................................................................................................................... 2
Definition and Structure ............................................................................................................................................................................... 2 Physical and Chemical Properties ................................................................................................................................................................ 2 Method of Manufacture ............................................................................................................................................................................... 3 Impurities and Residual Monomer or Solvent ............................................................................................................................................. 3
Use .................................................................................................................................................................................................................... 4 Cosmetic ...................................................................................................................................................................................................... 4 Non-Cosmetic .............................................................................................................................................................................................. 5
Toxicokinetics .................................................................................................................................................................................................. 5 Effect on Skin Permeation ........................................................................................................................................................................... 5
Toxicological studies ........................................................................................................................................................................................ 5 Single Dose (Acute) Toxicity ...................................................................................................................................................................... 5
Dermal .................................................................................................................................................................................................... 5 Oral ......................................................................................................................................................................................................... 5 Inhalation ................................................................................................................................................................................................ 6
Repeated Dose Toxicity ............................................................................................................................................................................... 6 Inhalation ................................................................................................................................................................................................ 6
Reproductive and Developmental Toxicity ...................................................................................................................................................... 6 Genotoxicity ..................................................................................................................................................................................................... 6 Carcinogenicity ................................................................................................................................................................................................. 6 Irritation and Sensitization ................................................................................................................................................................................ 6
Skin Irritation and Sensitization ................................................................................................................................................................... 7 Ocular Irritation ........................................................................................................................................................................................... 7
Alternative Studies .................................................................................................................................................................................. 7 Non-Human ............................................................................................................................................................................................ 7
Industrial Exposure Limits................................................................................................................................................................................ 8 Summary .......................................................................................................................................................................................................... 8 Discussion......................................................................................................................................................................................................... 9 Conclusion ........................................................................................................................................................................................................ 9 Tables ............................................................................................................................................................................................................. 11
Table 1. Definitions, functions, and structures .......................................................................................................................................... 11 Table 2. Chemical and physical properties ............................................................................................................................................... 24 Table 3a. Monomers used to create crosslinked alkyl acrylates ................................................................................................................ 25 Table 3b. Crosslinkers and initiators used in manufacture of acrylate crosspolymers .............................................................................. 25 Table 4a. Frequency and concentration of use according to duration and type of exposure ..................................................................... 26 Table 4b. Ingredients Not Reported to be Used ........................................................................................................................................ 27 Table 5. Dermal irritation and sensitization – alternative, non-human, and human .................................................................................. 28 Table 6. Relevant summary information on component monomers .......................................................................................................... 32
References ...................................................................................................................................................................................................... 39
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CIR Panel Book Page 30
1
ABSTRACT
The CIR Expert Panel assessed the safety of crosslinked alkyl acrylates as used in cosmetics. The 23 crosslinked alkyl acrylates included in this safety assessment are reported to function as absorbents, film formers, emulsion stabilizers, viscosity increasing agents, suspending agents, binders, and/or skin conditioning agents. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports on monomer components. Because data were not available for the individual ingredients, and because residual monomer may be present, the Panel extrapolated from previous reports to support safety. The Panel concluded that crosslinked alkyl acrylates are safe in the present practices of use and concentration, provided that they are not polymerized in benzene. For those ingredients polymerized in benzene, the data available were insufficient to make a determination of safety. A risk assessment for the amount of benzene present would be needed.
INTRODUCTION
This draft final report includes information relevant to the safety of 23 crosslinked alkyl acrylates as used in
cosmetic formulations. These crosslinked polymers consist of co-monomers of at least one of: acrylic acid, sodium acrylate,
methacrylic acid, or alkyl acrylate that share chemical properties, including a general lack of chemical reactivity. The ingre-
dients included in this group are:
Acrylates/C10-30Alkyl Acrylate Crosspolymer Acrylates/C12-13 Alkyl Methacrylates/Methoxyethyl Acrylate Crosspolymer Acrylates Crosspolymer Acrylates/Ethylhexyl Acrylate Crosspolymer Acrylates/Ethylhexyl Acrylate/Glycidyl Methacrylate Crosspolymer Acrylates/PEG-4 Dimethacrylate Crosspolymer Acrylates/Steareth-20 Methacrylate Crosspolymer Acrylates/Vinyl Isodecanoate Crosspolymer Acrylates/Vinyl Neodecanoate Crosspolymer Allyl Methacrylate/Glycol Dimethacrylate Crosspolymer Allyl Methacrylates Crosspolymer Butyl Acrylate/Glycol Dimethacrylate Crosspolymer C8-22 Alkyl Acrylates/Methacrylic Acid Crosspolymer Glycol Dimethacrylate/Vinyl Alcohol Crosspolymer Lauryl Methacrylate/Glycol Dimethacrylate Crosspolymer Lauryl Methacrylate/Sodium Methacrylate Crosspolymer Methacrylic Acid/PEG-6 Methacrylate/PEG-6 Dimethacrylate Crosspolymer PEG/PPG-5/2 Methacrylate/Methacrylic Acid Crosspolymer Potassium Acrylates/C10-30 Alkyl Acrylate Crosspolymer Sodium Acrylates Crosspolymer-2 Sodium Acrylates/C10-30 Alkyl Acrylate Crosspolymer Sodium Acrylates/Vinyl Isodecanoate Crosspolymer Stearyl/Lauryl Methacrylate Crosspolymer
These ingredients are reported to function in cosmetics as absorbents, film formers, emulsion stabilizers, viscosity
increasing agents, suspending agents, binders, or skin conditioning agents.
In 2002, the Cosmetic Ingredient Review (CIR) published the Final Report on the Safety Assessment of Acrylates
Copolymer and 33 Related Cosmetic Ingredients.1 The Panel concluded that those ingredients were safe for use in cosmetics
when formulated to avoid skin irritation. While copolymers are polymers synthesized from two or more different monomers,
crosspolymers are polymers that are crosslinked (i.e. individual polymer chains are connected by bridging molecules [cross-
linking agents]). Crosslinked polymers are generally less chemically reactive and less soluble (if not totally insoluble) than
their respective non-crosslinked counterparts.
A CIR report on another family of polymers is also available. In 1982, the CIR published the Final Report on the
Safety Assessment of Carbomers-934, -910, -934P, 940, -941, and -962, in which it was concluded that carbomers are safe as
used.2 A carbomer is a homopolymer of acrylic acid crosslinked with an allyl ether of pentaerythritol, an allyl ether of
sucrose, or an allyl ether of propylene.3
Due to the paucity of published safety and toxicity data on these ingredients, this draft report includes summary
information included in technical data sheets, ingredient specification sheets, and material safety data sheets (MSDSs); this
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2
information is identified as such. Also included at the end of this report is a table that provides a brief summary of relevant
data that exist for a number of the monomer components (Table 6).
CHEMISTRY
Definition and Structure
Crosslinked alkyl acrylates are crosslinked polymers in which the co-monomers consist of at least one of the follow-
ing: acrylic acid, sodium acrylate, methacrylic acid, or alkyl acrylate. Whereas polymers consisting purely of acrylic acid are
often referred to as “carbomers,” copolymers comprised of mixtures of acrylic acid and alkyl acrylate monomers may some-
times be referred to as “alkyl carbomers.” In that vein, most of the ingredients in this report could be classified as cross-
linked alkyl carbomers. For example, dodecyl (C12 alkyl) acrylate, acrylic acid, and methacrylic acid could be copolymer-
ized and crosslinked with diallyl sucrose to form an acrylates/C10-30 alkyl acrylate crosspolymer with the internal structure:
O
OH
OH
O
OH
O
OHHO
HO
OO
OO
O
HO
O
OO
O
OH
Theoretical magnifiedviewof thecrosslinkednetworkinapolymerbeadofAcrylates/ C10-30AlkylAcrylateCrosspolymer.
H3C
Accordingly, although all of the monomers and crosslinking agents may be the same, two polymers with very
different physical properties may share the same name under INCI conventions. The definitions and structures of the
ingredients included in this review are provided in Table 1.
Physical and Chemical Properties
The available physical and chemical property information is provided in Table 2. The properties of a single ingre-
dient, such as the above crosspolymer, can vary from a highly swellable, soft material to an unswellable, very hard material
because of the multitude of possible reaction conditions and methods involved in the manufacture of these polymers. The
nature of these ingredients is highly dependent on the identity of the alcohol radicals of these acrylate esters (e.g., the stearyl
and lauryl groups of stearyl/lauryl methacrylate crosspolymer).4 Acrylate crosspolymers that correspond to one INCI name
often have many trade names, and production processes may vary for different trade name products bearing the same INCI
name. Since the products may have different properties, the trade name is included in parenthesis when available.
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The polymers in this group share a general lack of chemical reactivity that renders them nearly impervious to
degradation. These ingredients are essentially insensitive to solar ultraviolet light (UV) degradation, as the primary UV
absorption of acrylics is at a lower wavelength.
Method of Manufacture
Crosslinked alkyl acrylates are typically produced via free-radical, head-to-tail chain-propagation polymerization.4
The most common method is the emulsion method, but bulk and solution methods are also used. The marked variability in
the identity of monomers and crosslinking agents, the ratio of co-monomers, the order of addition of co-monomers, the level
of crosslinking, and other reaction conditions in the polymerization process can significantly alter the polymeric structure and
properties of the product.5 Additionally, post-synthesis, mechanical processing of these products can also significantly affect
the consistency of these ingredients. These variables will likely differ from vendor to vendor, and possibly even from batch
to batch.
Table 3a lists the monomers used to create these crosspolymers (based on INCI definition), and Table 3b names the
crosslinking compounds and initiators used.3
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
According to a trade product technical data sheet, acrylates/C10-30 alkyl acrylate crosspolymer (as Pemulen) is
polymerized in an ethyl acetate-cyclohexane mixture.6 Another source reports that acrylates/C10-30 alkyl acrylate cross-
polymer may be polymerized in benzene.7 A third supplier reports that acrylates/C10-30 alkyl acrylate crosspolymer is
polymerized in n-hexane.8
Acrylates/Steareth-20 Methacrylate Crosspolymer
Acrylates/steareth-20 methacrylate crosspolymer (as Aculyn 88 polymer) is manufactured by an emulsion polymeri-
zation process.9
Acrylates/Vinyl Isodecanoate Crosspolymer
Acrylates/vinyl isodecanoate crosspolymer (as Stabylen 30) is produced synthetically by a free radical polymeriza-
tion.10
Acrylates/Vinyl Neodecanoate Crosspolymer
Acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) is manufactured by an emulsion polymerization
process.11
Impurities and Residual Monomer or Solvent
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
According to product specification sheets from one company, acrylates/C10-30 alkyl acrylate crosspolymer can con-
tain (total) residual solvent (ethyl acetate + cyclohexane) at a maximum of 0.45% (Carbopol 1382; Carbopol Ultrez 20; Car-
bopol Ultrez 21)12-14 or 0.5% (Pemulen TR1; Pemulen TR2; Carbopol ETD 2020).15-17 Another supplier, who uses n-hexane
as a solvent, reported that the maximum residual solvent in the polymer is 0.2% n-hexane.8
As Carbopol 1342, the product specifications state that acrylates/C10-30 alkyl acrylate crosspolymer can contain
0.5% (max.) residual benzene.18 A supplier reported that analysis of 40 lots of Carbopol 1342 indicated that the average level
of benzene was 0.25%, and the level ranged from 0.04-0.41% benzene.19 (According to the European Commission Cosme-
tics Directive, benzene cannot be present as a constituent of other substances, or in mixtures, in concentrations equal to, or
greater than 0.1% by weight.20 As another point of reference, United States Pharmacopeia (USP) limits for benzene for
several carbomers manufactured with benzene range from 0.01-0.5%.21)
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One source stated that residual monomer content of acrylates/C10-30 alkyl acrylate crosspolymer (trade name not
provided) is typically less than 0.25% acrylic acid and less than 0.5% residual ester (C10-30 alkyl acrylate),7 while another
stated that acrylic acid monomer content is <0.1%.22
Acrylates Crosspolymer
One source reported that acrylates crosspolymer contained <0.005% methyl methacrylate and <0.005% butyl
acrylate,23 and another reported 0.005% (max) of methyl methacrylate, ethylene methacrylate, and isobutyl methacrylate, and
that acrylates crosspolymer did not contain residual solvents or preservatives.24
Acrylates /Steareth-20 Methacrylate Crosspolymer
The composition of acrylates/steareth-20 methacrylate crosspolymer (as Aculyn 88 polymer) is stated as 28.0-30.0%
acrylates/steareth-20 methacrylate crosspolymer, <0.01% residual monomer, 70.0-72.0% solvent (water), and 0.195% (max)
sodium benzoate.9 According to actual analytical specifications, the amount of residual ethyl acrylate present is ≤0.0001%.
Acrylates/Vinyl Isodecanoate Crosspolymer
The residual acrylic acid monomer content of acrylates/vinyl isodecanoate crosspolymer (Stabylen 30) is reported to
be <0.05% by weight.10
Acrylates/Vinyl Neodecanoate Crosspolymer
The composition of acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) is stated as 28.0-30.0%
acrylates/vinyl neodecanoate crosspolymer, <0.1% residual monomer, and 70.0-72.0% solvent (water).11 According to actual
analytical specifications, the amount of residual ethyl acrylate present was ≤0.0001%.
Another source reported the residual monomer level of acrylates/vinyl neodecanoate crosspolymer is <0.01%.25
Lauryl Methacrylate/Glycol Dimethacrylate Crosspolymer
The residual monomer levels of lauryl methacrylate/glycol dimethacrylate crosspolymer are <0.01% lauryl meth-
acrylate and <0.01 ppm ethylene glycol dimethacrylate.26 Lauryl methacrylate/glycol dimethacrylate crosspolymer has a re-
sidual solvent level of ≤0.1% isopropanol. The ingredient can contain up to 2% adsorbed water.
Sodium Acrylates Crosspolymer-2
The maximum amount of residual monomer content of in sodium acrylates crosspolymer-2 (Aqua Keep 10SH-NFC)
is 0.02%.27
USE
Cosmetic
Crosslinked alkyl acrylates are reported to function as absorbents, film formers, emulsion stabilizers, viscosity
increasing agents, suspending agents, binders, and/or skin conditioning agents in cosmetic formulations.3 Acrylates/C10-30
alkyl acrylate crosspolymer functions as a primary emulsifier in oil-in-water emulsions.6 Voluntary Cosmetic Registration
Program (VCRP) data obtained in 2011,28 and concentration of use information received in response to a survey conducted
by the Personal Care Products Council,29 indicate that 11 of the 23 crosslinked alkyl acrylates named in this report currently
are used in cosmetic formulations. Acrylates/C10-30 alkyl acrylate crosspolymer has the greatest number of uses, with 1696
reported; 1365 of those uses are in leave-on products. Acrylates crosspolymer, acrylates/vinyl isodecanoate crosspolymer,
acrylates/vinyl neodecanoate crosspolymer, allyl methacrylates crosspolymer, lauryl methacrylate/glycol dimethacrylate
crosspolymer, lauryl methacrylate/sodium methacrylate crosspolymer, and sodium acrylates/C10-30 alkyl acrylate cross-
polymer are all used in less than 75 formulations.
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The highest concentration of use reported in leave-on products is 6% acrylates/ethylhexyl acrylate crosspolymer,
and the highest concentration of use reported in rinse-off products is 5% acrylates/C10-30 alkyl acrylate crosspolymer. Fre-
quency and concentration of use data are provided in Table 4a. The ingredients not reported to be used are listed in Table 4b.
Products containing some crosslinked alkyl acrylates may be applied to baby skin, used near the eye area or mucous
membranes, or could possibly be ingested or inhaled. Since some of the crosslinked alkyl acrylates are reported to be in
products that could be inhaled, and effects on the lungs that may be induced by aerosolized products containing these ingre-
dients are of concern. The particle size of aerosol hair sprays and in pump hair sprays is around 38 μm and >80 μm,
respectively, and is large compared to respirable particle sizes (≤10 μm). Therefore, because of their size, most aerosol
particles are deposited in the nasopharyngeal region and are not respirable.
All of the ingredients included in this review, with the exception of acrylates/C12-13 alkyl methacrylates methoxy-
ethyl acrylate crosspolymer and methacrylic acid/PEG-6 methacrylate/PEG-6 dimethacrylate crosspolymer, are listed in the
European Union inventory of cosmetic ingredients.30 The two ingredients that are not included in the EU inventory are in the
process of being named and will be added once that process is complete.31
Non-Cosmetic
Acrylic ester polymers are used in coatings, textiles, adhesives, and paper manufacture.4
TOXICOKINETICS
Published toxicokinetics, absorption, distribution, metabolism, and excretion data were not found for the cross-
polymers. Large polymeric structures, however, such as cross-linked alkyl acrylates generally are not absorbed through the
skin. Toxicokinetics data on some of the monomers are provided in Table 6.
Effect on Skin Permeation
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
A topical formulation vehicle that included acrylates/C10-30 alkyl acrylate crosspolymer (Pemulen TR-2), in
combination with PEG 400 and carbomer, reduced the permeation of N,N-diethyl-m-toluamide (DEET) through skin.32
Evaluations were made in vitro using excised rat skin and in vivo using Beagle dogs.
TOXICOLOGICAL STUDIES
To aid in the evaluation of the safety of these crosspolymers, Table 6 provides a brief summary of relevant data on a
number of monomer components. (This summary is not intended to be an all-encompassing review of these monomers.)
Single Dose (Acute) Toxicity
Dermal
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
According to an industry MSDS, the dermal LD50 of acrylates/C10-30 alkyl acrylate crosspolymer (as Pemulen
TR1) in rabbits is >2.0 g/kg.33
Acrylates/Vinyl Neodecanoate Crosspolymer
The dermal LD50 of acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) in rabbits is >5.0 g/kg.11
Oral
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
According to an industry MSDS, the oral LD50 of acrylates/C10-30 alkyl acrylate crosspolymer (as Pemulen TR1) in
rats is >10 g/kg.33 Another source provided information from an MSDS, stating that the oral LD50 in rats is >2 g/kg.22
Acrylates/Vinyl Isodecanoate Crosspolymer
The oral LD50 acrylates/vinyl isodecanoate crosspolymer (as Stabylen 30) in rats is >2 g/kg body wt.34
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Acrylates/Vinyl Neodecanoate Crosspolymer
The oral LD50 of acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) in rats is >5.0 g/kg.11
Sodium Acrylates Crosspolymer-2
According to an industry MSDS, the oral LD50 of sodium acrylates crosspolymer-2 (as Aqua Keep 10SH-NFC) in
rats is >2 g/kg.35
Inhalation
Acrylates/Vinyl Neodecanoate Crosspolymers
The inhalation LC50 of acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) in rats is >16,340 mg/m3
air (1 h).11
Repeated Dose Toxicity
Inhalation
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
In an industry MSDS for acrylates/C10-30 alkyl acrylate crosspolymers (as Pemulen TR-1), a 2-yr inhalation study
in which rats were exposed to a respirable, water-absorbent sodium polyacrylate dust is described under toxicological
information. Lung effects such as inflammation, hyperplasia, and tumors, were observed.33 There were no observed adverse
effects at exposures of 0.05 mg/m3.
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
Published reproductive and developmental toxicity data were not found. Reproductive and developmental toxicity
data on some of the monomers are provided in Table 6.
GENOTOXICITY
Genotoxicity data on some of the monomers are provided in Table 6.
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
Acrylates/C10-30 alkyl acrylate crosspolymer, tested at 156-500 µg/plate in dimethyl sulfoxide, was not mutagenic
in an Ames assay with Salmonella typhimurium TA98 and TA100.22 It is not stated directly, but it appears that the studies
were performed with and without metabolic activation.
Acrylates/Steareth-20 Methacrylate Crosspolymer
The acrylic copolymer of acrylates/steareth-20 methacrylate crosspolymer (as Aculyn 88 polymer) was not muta-
genic in an Ames test, with or without metabolic activation.9 (Study performed using good laboratory practices (GLP);
details not provided.)
Acrylates/Vinyl Neodecanoate Crosspolymer
The acrylic copolymer of acrylates/vinyl neodecanoate crosspolymer (as Aculyn 38 polymer) was not mutagenic in
an Ames test, with or without metabolic activation.11 (GLP study; details not provided.)
Sodium Acrylates Crosspolymer-2
According to an industry MSDS, sodium acrylates crosspolymer-2 (as Aqua Keep 10SH-NFC) was negative in an
Ames test using S. typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2uvrA.35
CARCINOGENICITY
Published carcinogenicity studies were not found. Carcinogenicity data on some of the monomers are provided in
Table 6.
IRRITATION AND SENSITIZATION
Irritation and sensitization data on some of the monomers are provided in Table 6.
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Skin Irritation and Sensitization
Dermal irritation and sensitization studies, using alternative methods and non-human and human test populations,
are presented in Table 5.
In an alternative method study, acrylates/vinyl neodecanoate crosspolymer was predicted to be a non-irritant. The
non-human studies reported no to slight irritation with undiluted and weak sensitization with 2% aq., acrylates/C10-30 alkyl
acrylate crosspolymer, no irritation with acrylates crosspolymer at 30% in olive oil, and no irritation or sensitization with
sodium acrylates crosspolymer-2 (concentration not specified). Mostly, human testing with undiluted acrylates/C10-30 alkyl
acrylate crosspolymer, acrylates crosspolymer, and acrylates/ethylhexyl acrylate crosspolymer, up to 2.5% aq. acrylates/vinyl
isodecanoate crosspolymer, 1% aq. dilutions of formulations containing 2% acrylates/vinyl neodecanoate crosspolymer, and
formulations containing up to 2.6% lauryl methacrylate/glycol dimethacrylate crosspolymers are not indicate any dermal
irritation or sensitization. The only exception was a weak irritant response noted during an intensified Shelanski human re-
peated insult patch test (HRIPT) with undiluted acrylates/C10-30 alkyl acrylate crosspolymer.
Ocular Irritation
Alternative Studies
Acrylates/Vinyl Isodecanoate Crosspolymer
The EYE-TEX alternative method was used to predict the in vivo ocular irritation classification of acrylates/vinyl
isodecanoate crosspolymer (as Stabylen 30).34 The results obtained in a standard volume-response study using samples of
≤100 µl test material corresponded to a Draize ocular irritation classification of non-irritant.
Lauryl Methacrylate/Glycol Dimethacrylate Crosspolymer
The EpiOcular Human Cell Construct (MTT assay), was used to assess the potential ocular irritation of a face
powder containing 1% lauryl methacrylate/glycol dimethacrylate crosspolymer.36 The ET50 (duration of exposure resulting in
a 50% decrease in MTT conversion) of the test material was >1440 min, which was the maximum exposure time. (As a
reference point, the ET50 of the positive control, 0.3% Triton X-100, was 16.3 min.)
Non-Human
Acrylates/C10-30 Alkyl Acrylate Crosspolymer
The ocular irritation potential of acrylates/C10-30 alkyl acrylate crosspolymer (as Carbopol ETD) was evaluated
using groups of 3 albino rabbits.37 The test material, undiluted and as a 1% neutralized solution (pH 6.9-7.0), was instilled
into the conjunctival sac of one eye of each rabbit per group; the contralateral eyes served as a control. The eyes were not
rinsed. The undiluted test material produced slight to moderate corneal and conjunctival irritation which cleared by day 7.
Slight iridal and conjunctival irritation was observed with the 1% solution. All signs of irritation cleared with 72 h.
In other studies using the same procedure, the ocular irritation potential of acrylates/C10-30 alkyl acrylate cross-
polymer (as Carbopol Ultrez 20 and as Carbopol Ultrez 21) was evaluated using groups of 3 rabbits.38,39 The test material
was evaluated undiluted and as a 5% dilution in distilled water. The undiluted test material produced moderate corneal irrita-
tion and conjunctival irritation which cleared by day 21. (The maximum mean score (MMS) was 37.7/110.) Moderate con-
junctival irritation (MMS 9.3/110) was observed with the 5% solution, which was classified as a minimal irritant.
The ocular irritation potential of acrylates/C10-30 alkyl acrylate crosspolymer (as Pemulen) was evaluated by instill-
ing 0.021 g of the test article into the conjunctival sac of one eye of 9 New Zealand White (NZW) rabbits.40 The contralateral
eyes were untreated and served as the control. At 30 sec post-instillation, both eyes of 3 rabbits were rinsed; the eyes of the
other 6 rabbits were not rinsed. The eyes were examined for irritation for up to 72 h following dosing. “Significant” ocular
irritation was observed in 3 of the 6 unrinsed eyes. At 24 h after instillation, corneal opacity was observed in 3 and iritis in
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one unrinsed eye; minimal conjunctivitis was seen in all 6 unrinsed eyes. These observations were resolved by 72 h. “Less
severe responses” were observed in the rinsed eyes. Iritis was observed in one and conjunctivitis in 3 of the rinsed eyes at 24
h after dosing. At 48 h after dosing, conjunctivitis was observed in one rinsed eye. Based on the observations made for the
unrinsed eyes, this product was considered a “borderline irritant.”
Acrylates Crosspolymer
The ocular irritation potential of acrylates crosspolymer was evaluated by instilling 0.1 ml of the test material, at a
concentration of 50% in olive oil, into the conjunctival sac of one eye of 3 Japanese white rabbits.23 The Draize score was
1.3. (Additional details were not provided.)
Sodium Acrylates Crosspolymer-2
According to an industry MSDS, sodium acrylates crosspolymer-2 (as Aqua Keep 10SH-NFC) is not an ocular
irritant in rabbits.35
INDUSTRIAL EXPOSURE LIMITS
According to an industry MSDS, no exposure limits have been established for acrylates/C10-30 alkyl acrylate cross-
polymer.33 The industry-recommended permissible exposure limits for respirable polyacrylate dusts is 0.05 mg/m3.
Breathing of dust may cause coughing, mucous production, and shortness of breath. According to an industry MSDS, the
exposure limit for respirable sodium acrylates crosspolymer-2 dust (particle size <10 µm) is 0.05 mg/m3.35
SUMMARY
The crosslinked alkyl acrylates are crosslinked polymers and are very large molecules that consist of co-monomers
of acrylic acid, sodium acrylate, methacrylic acid, and/or alkyl acrylate, and they share chemical properties, including a
general lack of chemical reactivity. Crosslinked alkyl acrylates are typically produced via free-radical, head-to tail chain-
propagation polymerization. Ethyl acetate + cyclohexane, water, n-hexane, and benzene are all named as solvents. Because
of the manner in which these polymers are created and the mixture of monomers and cross-linking agents that can be used,
two polymers that have the same INCI name can have very different physical consistencies. Small amounts of residual
monomer and/or solvent may be present in the raw ingredients.
Crosslinked alkyl acrylates are reported to function in cosmetic formulations as absorbents, film formers, emulsion
stabilizers, viscosity increasing agents, suspending agents, binders, and/or skin conditioning agents. In 2011, it was reported
that acrylates/C10-30 alkyl acrylate crosspolymer was used in 1696 cosmetic formulations; 1365 of those uses are in leave-on
products, and the reported concentration of use in these leave-on products is up to 5%. According to industry data,
acrylates/ethylhexyl acrylate crosspolymer had the highest concentration of use in a leave-on product at 6%; the highest
concentration of use reported in rinse-off products was 5% acrylates/C10-30 alkyl acrylate crosspolymer.
Toxicokinetic data were not found in the published literature. Little toxicity data were available; the acute dermal
and oral toxicity data that were found indicated that these ingredients are not very toxic. The little genotoxicity data that
were available reported negative results in Ames tests. Carcinogenicity data were not found in the published literature.
In an alternative method study, acrylates/vinyl neodecanoate crosspolymer was predicted to be a non-irritant. The
non-human studies reported no to slight irritation with undiluted and weak sensitization with 2% aq., acrylates/C10-30 alkyl
acrylate crosspolymer, no irritation with acrylates crosspolymer at 30% in olive oil, and no irritation or sensitization with
sodium acrylates crosspolymer-2 (concentration not specified). Mostly, human testing with undiluted acrylates/C10-30 alkyl
acrylate crosspolymer, acrylates crosspolymer, and acrylates/ethylhexyl acrylate crosspolymer, up to 2.5% aq. acrylates/vinyl
isodecanoate crosspolymer, 1% aq. dilutions of formulations containing 2% acrylates/vinyl neodecanoate crosspolymer, and
formulations containing up to 2.6% lauryl methacrylate/glycol dimethacrylate crosspolymers are not indicate any dermal
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irritation or sensitization. The only exception was a weak irritant response noted during an intensified Shelanski human re-
peated insult patch test (HRIPT) with undiluted acrylates/C10-30 alkyl acrylate crosspolymer.
Alternative test methods for ocular irritation indicated that acrylates/vinyl isodecanoate crosspolymer and a formula-
tion containing 1% lauryl methacrylate/glycol dimethacrylate crosspolymer are not likely ocular irritants. In studies using
rabbits, undiluted acrylates/C10-30 alkyl acrylate crosspolymer produced minimal to moderate irritation, and it was con-
sidered a borderline irritant in unrinsed rabbit eyes. Acrylates crosspolymer, at 50% in olive oil, and sodium acrylates cross-
polymer-2 did not appear to be ocular irritants in rabbit eyes.
DISCUSSION
Very little published data were available on the crosslinked alkyl acrylates. The Panel was provided with some
summary information on the monomers for their use in evaluating these crosspolymers.
The Panel noted that these crosslinked alkyl acrylates are macromolecules that are not expected to pass through the
stratum corneum of the skin. Since significant dermal absorption is not expected, data regarding systemic toxicity,
reproductive and developmental toxicity, genotoxicity, carcinogenicity, etc. are not relevant because there would be no
exposure that could produce these endpoints were these ingredients to be used in topically applied cosmetics.
The Panel noted that cosmetic products containing these ingredients are reportedly used around the eyes, on the lips,
and on other mucous membranes. Thus, crosslinked alkyl acrylates could be absorbed systemically through the relatively
moist, very thin stratum cornea of the conjunctiva, lips, and other mucous membranes, and through ingestion when applied to
the lips. However, the Panel noted that any absorption through healthy intact mucous membranes is likely to be not signifi-
cant, primarily because of the relatively large molecular sizes. Furthermore, the chemically inert nature of the polymers pre-
cludes degradation to smaller absorbable species. Absorption of the polymers and their residual monomers in cosmetic
products also would be limited after application to the lips or eye area based on the relatively small fractions of the applied
products that might be inadvertently ingested or make direct contact with the conjunctiva.
The CIR Expert Panel addressed the concern of residual monomer or solvent that might be present in the cross-
polymers. In most cases, taking into consideration the low amount of residual monomer in the crosspolymers and the low use
concentration of the polymers themselves, the Panel was not concerned that the residual monomer would result in adverse
effects. However, the use of benzene as a solvent is an exception and did cause concern. If residual benzene was present at
0.5% (maximum residual benzene reported to be allowed), and a formulation contained 5% of a crosspolymer polymerized in
benzene (maximum use concentration for acrylates/C10-30 alkyl acrylate crosspolymer), 0.025% benzene would be present
in the cosmetic formulation. The data were insufficient for the Panel to conclude that 0.025% benzene would be a safe level;
risk assessment data are needed before a safe level could be determined.
Certain of these crosslinked alkyl acrylates are used in cosmetic products that may be inhaled during their use. In
practice, however, the particle sizes produced by cosmetic sprays are typically not respirable.
CONCLUSION
The CIR Expert Panel concluded that the ingredients listed below are safe in the present practices of use and
concentration described in this safety assessment, except when they are polymerized in benzene, and that the available data
are insufficient to make a determination of safety for these ingredients when polymerized in benzene. Were the ingredients
not in current use (as indicated by *) to be used in the future, the expectation is that they would be used in product categories
and at concentrations comparable to others in this group.
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10
Acrylates/C10-30Alkyl Acrylate Crosspolymer Acrylates/C12-13 Alkyl Methacrylates/Methoxyethyl Acrylate Crosspolymer* Acrylates Crosspolymer Acrylates/Ethylhexyl Acrylate Crosspolymer Acrylates/Ethylhexyl Acrylate/Glycidyl Methacrylate Crosspolymer* Acrylates/PEG-4 Dimethacrylate Crosspolymer* Acrylates/Steareth-20 Methacrylate Crosspolymer Acrylates/Vinyl Isodecanoate Crosspolymer Acrylates/Vinyl Neodecanoate Crosspolymer Allyl Methacrylate/Glycol Dimethacrylate Crosspolymer* Allyl Methacrylates Crosspolymer Butyl Acrylate/Glycol Dimethacrylate Crosspolymer* C8-22 Alkyl Acrylates/Methacrylic Acid Crosspolymer* Glycol Dimethacrylate/Vinyl Alcohol Crosspolymer* Lauryl Methacrylate/Glycol Dimethacrylate Crosspolymer Lauryl Methacrylate/Sodium Methacrylate Crosspolymer Methacrylic Acid/PEG-6 Methacrylate/PEG-6 Dimethacrylate Crosspolymer* PEG/PPG-5/2 Methacrylate/Methacrylic Acid Crosspolymer* Potassium Acrylates/C10-30 Alkyl Acrylate Crosspolymer* Sodium Acrylates Crosspolymer-2 Sodium Acrylates/C10-30 Alkyl Acrylate Crosspolymer Sodium Acrylates/Vinyl Isodecanoate Crosspolymer* Stearyl/Lauryl Methacrylate Crosspolymer*
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 40
11
TABLES
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ C10-30 Alkyl Acrylate Crosspolymer
a copolymer of C10-30 alkyl acrylate and one or more monomers of acrylic acid, methacrylic acid or one of their simple* esters crosslinked with an allyl (2-propenyl) ether of sucrose or an allyl ether of pentaerythritol
Emulsion Stabilizer; Viscosity Increasing Agent – Aq.; Viscosity Increasing Agent - NonAq.
O
O
RH2C
O
O
R'H2C
O
O
R'H2C
CH3R = 10 to 30 carbon alkyl chainR' = hydrogen or a "simple" alkyl chain
Copolymer of:
Crosslinked with:
OR"
OR"
R"O
O
R"O
O
OR"
OR"
R"O
R"O
O or
R"O
R"O
OR"
OR"
R" = hydrogen or 2-propenyl, wherein at least two R" groups are 2-propenyl
* According to the International Cosmetic Ingredient Dictionary and Handbook nomenclature conventions, “simple,” as used herein, is “described as simple alkyls ranging from C1 to C4 (linear or branched).”
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CIR Panel Book Page 41
12
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ C12-13 Alkyl Meth-acrylates/ Methoxyethyl Acrylate Crosspolymer
a copolymer of C12-13 alkyl methacrylates, methoxyethyl acrylate, and one or more monomers of acrylic acid, methacrylic acid or one of their simple esters, crosslinked with vinyloxazoline
hair fixative
O
O
H2C
O
O
RH2C
O
O
R'H2C
CH3
R = hydrogen or a "simple" alkyl chainR' = a 12 or 13 carbon alkyl chain
Crosslinked with:
O
CH3
vinyloxazolineO
N
Copolymer of:
Acrylates Crosspolymer 26794-61-6 (when R is butyl) 74464-10-1 (when R is isobutyl)
a copolymer of acrylic acid, methacrylic acid or one of its simple esters, cross-linked with glycol dimethacrylate
Absorbent
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CIR Panel Book Page 42
13
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ Ethylhexyl Acrylate Crosspolymer
a copolymer of 2-ethylhexylacrylate and one or more monomers of acrylic acid, methacrylic acid or one of their simple esters, crosslinked with ethylene glycol dimethacrylate
Binder
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 43
14
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ Ethylhexyl Acrylate/ Glycidyl Methacrylate Cross-polymer
a copolymer of 2-ethylhexyl acrylate, glycidyl methacrylate and one or more monomers consisting of acrylic acid, methacrylic acid or one of their simple esters, crosslinked with triethylene glycol dimethacrylate
Film Former
O
O
H2C
O
O
RH2C
O
O
RH2C
CH3
R = hydrogen or a "simple" alkyl chain
Copolymer of:
Crosslinked with:
CH3
CH3
CH3
H2C
O
O
O
O
O
CH3
CH2
O
O
CH3
H2C
O
O
Acrylates/ PEG-4 Dimethacrylate Crosspolymer 50657-38-0
a copolymer of one or more monomers of acrylic acid, methacrylic acid or one of their simple esters crosslinked by PEG-4 dimethacrylate
Film Former
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CIR Panel Book Page 44
15
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ Steareth-20 Methacrylate Crosspolymer
a copolymer of steareth-20 methacrylate and one or more monomers consisting of acrylic acid, methacrylic acid or one of their simple esters, crosslinked with an allyl ether of pentaerythritol or an allyl ether of trimethylolpropane
Film Former; Suspending Agent – Non-Surfactant
(OCH2CH2)20(CH2)17CH3
O
H2C
O
O
RH2C
O
O
RH2C
CH3
R=hydrogenora"simple"alkylchain
Copolymerof:
Crosslinkedwith:
orR'O
R'O
OR'
OR'
R'=hydrogenor2-propenyl,whereinatleasttwoR'groupsare2-propenyl
CH3
CH3
R'O
R'O
OR'
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 45
16
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ Vinyl Isodecanoate Crosspolymer
a copolymer of the ester of vinyl isodeca-noate and one or more monomers of acrylic acid, methacrylic acid or one of their simple esters crosslinked with poly-alkenyl polyether
Emulsion Stabilizer; Sus-pending Agent – Non-Surfac-tant; Viscosity Increasing Agent - Aq.
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CIR Panel Book Page 46
17
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Acrylates/ Vinyl Neodecanoate Crosspolymer
a copolymer of vinyl neodecanoate and one or more monomers of acrylic acid, methacrylic acid or one of their simple esters crosslinked with an allyl ether of trimethylolpropane or pentaerythritol
Emulsion Stabilizer; Film Former; Viscosity Increasing Agent - Aq.
Allyl Methacrylate/Glycol Dimeth-acrylate Crosspolymer 779327-42-3
a highly crosslinked polymer of allyl methacrylate and ethylene glycol dimeth-acrylate (diisopropyl peroxydicarbonate initiated)
Oral Care Agent; Skin Protectant; Skin-Conditioning Agent - Emollient; Skin-Conditioning Agent – Misc.
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CIR Panel Book Page 47
18
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Allyl Methacrylates Crosspolymer 182212-41-5
a copolymer of allyl methacrylate crosslinked with ethylene glycol dimethacrylate
Emulsion Stabilizer; Opacifying Agents; Viscosity Increasing Agent – NonAq.
Butyl Acrylate/ Glycol Dimeth-acrylate Crosspolymer
a homopolymer of butyl acrylate cross-linked with ethylene glycol dimethacrylate
Absorbent; Film Former
C8-22 Alkyl Acrylates/ Methacrylic Acid Crosspolymer
a copolymer of C8-22 alkyl acrylate and methacrylic acid crosslinked with hexanediol diacrylate
Film Former; Hair Fixative; Hair-Waving/ Straightening Agent
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CIR Panel Book Page 48
19
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Glycol Dimethacrylate/ Vinyl Alcohol Crosspolymer
vinyl alcohol and ethylene glycol dimethacrylate
Film Former
Lauryl Methacrylate/Glycol Di-methacrylate Crosspolymer
a crosslinked copolymer of lauryl meth-acrylate and ethylene glycol dimethacryl-ate monomers
Film Former; Hair Fixative
Lauryl Methacrylate/Sodium Meth-acrylate Crosspolymer
a copolymer of lauryl methacrylate and sodium methacrylate crosslinked with ethylene glycol dimethacrylate.
Slip Modifier; Surface Modifier
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CIR Panel Book Page 49
20
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Methacrylic Acid/PEG-6 Methacrylate/PEG-6 Dimethacrylate Crosspolymer
a copolymer of methacrylic acid and PEG-6 methacrylate crosslinked with polyethyl-ene glycol dimethacrylate
film former.
wherein “n” is variable
PEG/PPG-5/2 Methacrylate/Meth-acrylic Acid Crosspolymer
a copolymer of methacrylic acid and polyethylene glycol, polypropylene glycol methacrylate containing an average of 5 moles of ethylene oxide and 2 moles of propylene oxide, crosslinked with ethylene glycol dimethacrylate
Film Former
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CIR Panel Book Page 50
21
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Potassium Acrylates/ C10-30 Alkyl Acrylate Crosspolymer
the potassium salt of Acrylates/C10-30 Alkyl Acrylate Crosspolymer.
Film Former
Sodium Acrylates Crosspolymer-2
the sodium salt of a copolymer of acrylic acid, methacrylic acid or one or more of its simple esters crosslinked with ethylene diglycidyl ether
Absorbent
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CIR Panel Book Page 51
22
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Sodium Acrylates/ C10-30 Alkyl Acrylate Crosspolymer
the sodium salt of Acrylates/C10-30 Alkyl Acrylate Crosspolymer
Film Former
O
O
RH2C
OR'
O
H2C
OR'
O
H2C
CH3R = 10 to 30 carbon alkyl chainR' = H or a "simple" alkyl group (the sodium salt is formed post-polymerization)
Copolymer of:
Crosslinked with:
OR"
OR"
R"O
O
R"O
O
OR"
OR"
R"O
R"O
O or
R"O
R
OR"
OR"
R" = hydrogen or 2-propenyl, wherein at least two R" groups are 2-propenyl
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23
Table 1. Definitions, functions, and structures
Ingredient/CAS No. Definition Reported Function(s) Formula/Structure Sodium Acrylates/ Vinyl Iso-decanoate Crosspolymer
the sodium salt of Acrylates/Vinyl Iso-decanoate Crosspolymer.
Emulsion Stabilizer; Sus-pending Agent - Non-Surfactant; Viscosity Increasing Agent – Aq.
O
O
R'H2C
O
O
R'H2C
CH3
R = isododecyl (branched, 12 carbon chain)R' = H or a "simple" alkyl group (the sodium salt is formed post-polymerization)
Copolymer of:
Crosslinked with a "polyalkenyl polyether." One example of such could be:
R"O
R"O
OR"
OR"
R" = hydrogen or 2-propenyl, wherein at least two R" groups are 2-propenyl
CH3
H3C
O
O CH2
one example of an "iso"
Stearyl/ Lauryl Methacrylate Crosspolymer
a copolymer of lauryl methacrylate and stearyl methacrylate crosslinked with ethylene glycol dimethacrylate
Skin-Conditioning Agent - Misc.
References3,7,41
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CIR Panel Book Page 53
24
Table 2. Chemical and physical properties
Property Description Reference Acrylates/C10-30 Alkyl Acrylate Crosspolymer
appearance white powder; 12-18 odor slightly acetic 12-18
activity, as supplied approximately 100% active 7 molecular weight >500,000 Daltons 7 solubility swells in water 33 pH ~2.5 – 3 at 1% in water33 heavy metals content 10 ppm (max), under all trade names 12-18 specific gravity 1.4 (at 20°C) 33 particle size (as tested by one source) 2-7 µm 22 bulk density <0.24 kg/l; <2 lb/gal 33
Acrylates Crosspolymer particle size (as tested by one source) 18-22 µm 23 heavy metal content lead, 10 ppm (max)
arsenic, 2 ppm (max)
24
Acrylates/Steareth-20 Methacrylate Crosspolymerappearance (Aculyn 88 polymer) milk-white fluid 9 solids content (Aculyn 88 polymer) 28.0-30.0% by wt 9 heavy metal content (Aculyn 88 polymer) iron, 1.028 ppm
zinc, 0.082 ppm
pH (Aculyn 88 polymer) 3.30-4.30 9
Acrylates/Vinyl Isodecanoate Crosspolymer molecular weight 24,400 Daltons (avg; <1% by weight is <1000 Daltons) 10
Acrylates/Vinyl Neodecanoate Crosspolymer appearance (Aculyn 38 polymer) milk-white fluid 11 solids content (Aculyn 38 polymer) 28.0-30.0% by weight 11 activity, as supplied 29% solids in 71% water 25 heavy metal content (Aculyn 38 polymer) copper, 0.2 ppm
iron, 0.5 ppm zinc, 1.2 ppm
11
pH (as Aculyn 38 polymer) 2.10-3.20 11 Allyl Methacrylates Crosspolymer
appearance fine white powder 42,43 solubility insoluble 42,43
refractive index 1.517-1.519 1.511-1.513
42 43
particle size (by laser diffraction) 5-15 µm 15-25 µm
42 43
bulk density 0.03 g/cc 42,43 water adsorption oleophilic (hydrophobic)
dual: hydrophilic and oleophilic
43
Sodium Acrylates Crosspolymer-2 appearance white powder 27 odor odorless 35 solubility swells in water 35 pH 6-8 35 particle size approx. 20 µm 27 bulk density 0.75-0.95 g/ml 35 stability stable at room temperature 35
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CIR Panel Book Page 54
25
Table 3a. Monomers used to create crosslinked alkyl acrylates acrylic acid acrylic acid, simple esters (simple alkyls ranging from C1 to C4, linear or branched , i.e., methyl, ethyl, propyl, and butyl esters, including branched versions: isopropyl, isobutyl, sec-butyl, and tert-butyl esters) butyl acrylate C8-22 alkyl acrylate 2-ethylhexyl acrylate glycidyl methacrylate lauryl methacrylate methacrylic acid methacrylic acid, simple esters (simple alkyls ranging from C1 to C4, linear or branched , i.e., methyl, ethyl, propyl, and butyl esters, including branched versions: isopropyl, isobutyl, sec-butyl, and tert-butyl esters) PEG-6 methacrylate PEG/PPG-5/2 sodium methacrylate steareth-20 methacrylate stearyl methacrylate vinyl alcohol vinyl isodecanoate, ester of vinyl neodecanoate Table 3b. Crosslinkers and initiators used in manufacture of acrylate crosspolymers allyl methacrylate ethylene diglycidyl ether glycol dimethacrylate hexanediol diacrylate PEG-4 dimethacrylate pentaerythritol, allyl ether polyalkenyl polyether polyethylene glycol dimethacrylate sucrose, allyl ether triethylene glycol dimethacrylate trimethylolpropane, allyl ether diisopropyl peroxydicarbonate (initiator)
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 55
26
Table 4a. Frequency and concentration of use according to duration and type of exposure
# of Uses28 Conc of Use (%)29 # of Uses28 Conc of Use (%)29 # of Uses28 Conc of Use (%)29
Acrylates/C10-30 Alkyl Acrylate
Crosspolymer Acrylates Crosspolymer
Acrylates/Ethylhexyl Acrylate Crosspolymer
Totals* 1696 0.0002-5 2 0.1-4 NR 4-6
Duration of Use
Leave-On 1365 0.0002-5 2 0.1-4 NR 4-6
Rinse Off 313 0.002-5 NR 0.3-0.8 NR NR
Diluted for (Bath) Use 18 1 NR NR NR NR
Exposure Type
Eye Area 132 0.003-2 NR 0.8 NR 6
Incidental Ingestion 3 0.5 NR 4 NR NR
Incidental Inhalation-Sprays 70a,b 0.001-2 NR NR NR NR
Incidental Inhalation-Powders 6 0.0002-.02 NR 2 NR NR
Dermal Contact 1591 0.0002-3 2 0.1-4 NR 4-6
Deodorant (underarm) 1 0.001 NR NR NR NR
Hair - Non-Coloring 77 0.1-2 NR NR NR NR
Hair-Coloring 11 0.4-5 NR NR NR NR
Nail 9 0.1-5 NR NR NR NR
Mucous Membrane 111 0.002-3 NR 4 NR NR
Baby Products 10 0.2 NR NR NR NR
Acrylates/Steareth-20 Methacrylate
Crosspolymer Acrylates/Vinyl Isodecanoate
Crosspolymer Acrylates/Vinyl Neodecanoate
Crosspolymer Totals* NR 0.1-2 33 0.2-0.5 10 2 Duration of Use Leave-On NR 0.1-2 25 0.3-0.5 4 NR
Rinse Off NR 1 8 0.2-0.5 4 2
Diluted for (Bath) Use NR NR NR NR 2 2
Exposure Type
Eye Area NR NR NR NR NR NR
Incidental Ingestion NR NR NR NR NR NR
Incidental Inhalation-Sprays NR NR NR 0.4 NR NR
Incidental Inhalation-Powders NR NR NR NR NR NR
Dermal Contact NR 0.1-1 33 0.2-0.5 10 2
Deodorant (underarm) NR NR NR NR NR NR
Hair - Non-Coloring NR 2 NR NR NR NR
Hair-Coloring NR NR NR NR NR NR
Nail NR NR NR NR NR NR
Mucous Membrane NR 1 NR NR 6 2
Baby Products NR NR NR NR NR NR
Allyl Methacrylates Crosspolymer
Lauryl Methacrylate/Glycol Dimethacrylate Crosspolymer
Lauryl Methacrylate/Sodium Methacrylate Crosspolymer
Totals* 48 0.003-2 63 0.06-3 1 0.004-4
Duration of Use
Leave-On 44 0.003-2 56 0.06-3 1 0.1-4 Rinse Off 4 0.1 7 0.2-3 NR 0.004-0.1 Diluted for (Bath) Use NR NR NR NR NR NR
Exposure Type
Eye Area 4 0.003-0.8 9 0.1-3 NR NR
Incidental Ingestion 16 0.04-0.2 8 0.06-2 NR NR
Incidental Inhalation-Sprays 2b NR 1a 0.3 NR NR
Incidental Inhalation-Powders 2 0.3-0.8 8 0.1-1 NR NR
Dermal Contact 31 0.003-2 53 0.06-3 1 0.004-4
Deodorant (underarm) NR NR 1 0.3 NR NR
Hair - Non-Coloring NR NR NR NR NR NR
Hair-Coloring NR NR NR NR NR NR
Nail NR NR 1 NR NR NR
Mucous Membrane 16 0.04-0.2 8 0.06-2 NR NR
Baby Products NR NR NR NR NR NR
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 56
27
Table 4a. Frequency and concentration of use according to duration and type of exposure (continued)
# of Uses28 Conc of Use (%)29 # of Uses28 Conc of Use (%)29 # of Uses28 Conc of Use (%)29
Sodium Acrylates/C10-30 Alkyl Acrylate
Crosspolymer Sodium Acrylates Crosspolymer-2
# of Uses28 Conc of Use (%)29 # of Uses28 Conc of Use (%)29
Totals* 6 NR NR 0.8
Duration of Use
Leave-On 6 NR NR 0.8 Rinse Off NR NR NR NR
Diluted for (Bath) Use NR NR NR NR
Exposure Type
Eye Area NR NR NR NR
Incidental Ingestion NR NR NR NR
Incidental Inhalation-Sprays 1 NR NR NR
Incidental Inhalation - Powders NR NR NR NR
Dermal Contact 6 NR NR 0.8
Deodorant (underarm) NR NR NR NR
Hair - Non-Coloring NR NR NR NR
Hair-Coloring NR NR NR NR
Nail NR NR NR NR
Mucous Membrane NR NR NR NR
Baby Products NR NR NR NR
* Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types my not equal the sum of total uses. a Includes deodorants, in that it is not known whether or not the product is a spray. b Includes suntan products, in that it is not known whether or not the reported product is a spray. NR – no reported uses
Table 4b. Ingredients Not Reported to be Used
Acrylates/C12-13 Alkyl Methacrylates/Methoxyethyl Acrylate Crosspolymer Acrylates/Ethylhexyl Acrylate/Glycidyl Methacrylate Crosspolymer Acrylates/PEG-4 Dimethacrylate Crosspolymer Allyl Methacrylate/Glycol Dimethacrylate Crosspolymer Butyl Acrylate/Glycol Dimethacrylate Crosspolymer C8-22 Alkyl Acrylates/Methacrylic Acid Crosspolymer Glycol Dimethacrylate/Vinyl Alcohol Crosspolymer Methacrylic Acid/PEG-6 Methacrylate/PEG-6 Dimethacrylate Crosspolymer PEG/PPG-5/2 Methacrylate/Methacrylic Acid Crosspolymer Potassium Acrylates/C10-30 Alkyl Acrylate Crosspolymer Sodium Acrylates/Vinyl Isodecanoate Crosspolymer Stearyl/Lauryl Methacrylate Crosspolymer
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 57
T
able
5.
Der
mal
irri
tati
on a
nd
sen
siti
zati
on –
alt
erna
tive
, non
-hu
man
, an
d h
um
an
Tes
t A
rtic
le
Con
cent
rati
on/D
ose
Tes
t P
opul
atio
n P
roce
dure
R
esul
ts
Ref
eren
ce
AL
TE
RN
AT
IVE
ST
UD
IES
Acr
ylat
es/V
inyl
Iso
deca
noat
e C
ross
poly
mer
as S
taby
len
30 (
trad
enam
e)
SK
IN-T
EX
met
hod;
sta
ndar
d vo
lum
e-re
spon
se s
tudy
us
ing ≤1
00 m
l sam
ples
no
n-ir
rita
nt (
pred
icte
d cl
assi
fica
tion
) 34
NO
N-H
UM
AN
Acr
ylat
es/C
10-3
0 A
lkyl
Acr
ylat
e C
ross
poly
mer
as P
emul
en (
trad
enam
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0.5
g un
dilu
ted
6
NZ
W r
abbi
ts
sem
i-oc
clus
ive;
abr
aded
and
non
-abr
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sit
es; 2
4 h
appl
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ion
PII
0.4
2/8
– ne
glig
ible
irri
tati
on p
oten
tial
very
sli
ght e
ryth
ema
was
obs
erve
d at
1 h
; no
irri
tati
on o
bser
ved
at 7
2 h
40
as C
arbo
pol E
TD
(t
rade
nam
e)
0.5
g un
dilu
ted
3 ra
bbit
s se
mi-
occl
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e pa
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non
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aded
ski
n; 4
h a
ppli
cati
on
PII
0.0
-1.5
; non
- to
sli
ght i
rrit
ant
very
sli
ght e
ryth
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and
edem
a
37
0.5
ml o
f a
1%
neut
rali
zed
solu
tion
P
II 0
.0-0
.1; n
on-
to v
ery
slig
ht ir
rita
nt
as C
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pol U
ltre
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(t
rade
nam
e)
0.5
g, m
oist
ened
w
ith
0.5
ml w
ater
3
rabb
its
sem
i-oc
clus
ive
patc
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on-a
brad
ed s
kin;
4 h
app
lica
tion
P
II 0
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pro
duce
d sl
ight
irri
tati
on
38
as C
arbo
pol U
ltre
z-20
(t
rade
nam
e)
0.5
g, m
oist
ened
w
ith
0.5
ml w
ater
3
rabb
its
sem
i-oc
clus
ive
patc
h; n
on-a
brad
ed s
kin;
4 h
app
lica
tion
P
II 0
.3 –
pro
duce
d sl
ight
irri
tati
on
39
Acr
ylat
es/C
10-3
0 A
lkyl
A
cryl
ate
Cro
sspo
lym
er
2% a
q.
5 gu
inea
pig
s m
axim
izat
ion
(spl
it a
djuv
ant)
test
(de
tails
not
pro
vide
d)
wea
k se
nsiti
zer
22
Acr
ylat
es C
ross
poly
mer
Acr
ylat
es C
ross
poly
mer
30
% in
oli
ve o
il
3 ra
bbit
s op
en a
ppli
catio
n of
0.1
ml t
o a
2.5
cm x
2.5
cm
sit
e;
1x/d
ay f
or 4
day
s no
irri
tati
on
23
Sod
ium
Acr
ylat
es C
ross
poly
mer
-2
as A
qua
Kee
p 10
SH-N
FC
(tra
dena
me)
no
t sta
ted
rabb
its
info
rmat
ion
prov
ided
in a
n in
dust
ry M
SD
S
not a
n ir
rita
nt
35
guin
ea p
igs
not a
sen
siti
zer
HU
MA
NA
cryl
ates
/C10
-30
Alk
yl A
cryl
ate
Cro
sspo
lym
er
Acr
ylat
es/C
10-3
0 A
lkyl
A
cryl
ate
Cro
sspo
lym
er
15 µ
l of
2% a
q.
dilu
tion
20
sub
ject
s si
ngle
24-
h oc
clus
ive
patc
h 24
h:
± r
espo
nse
in 3
/20
subj
ects
84
h:
± r
espo
nse
in 1
/20
subj
ects
(r
esul
ts w
ere
base
d on
Jap
anes
e cr
iter
ia)
22
as C
arbo
pol E
TD
(t
rade
nam
e)
undi
lute
d (>
97.5
%)44
10
0 su
bjec
ts
mat
eria
l was
app
lied
to a
2 c
m x
2 c
m p
ad; p
atch
was
ap
plie
d fo
r 4
cons
ecut
ive
days
dur
ing
wks
1-3
; ch
alle
nge
was
per
form
ed a
fter
1 w
k an
d in
clud
ed 4
ap
plic
atio
ns
not a
n ir
rita
nt o
r se
nsit
izer
37
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 58
Tab
le 5
. D
erm
al ir
rita
tion
and
sen
siti
zati
on –
alte
rnat
ive
stud
ies,
non
-hum
an, a
nd h
uman
(co
ntin
ued)
29
Tes
t A
rtic
le
Con
cent
rati
on/D
ose
Tes
t P
opul
atio
n P
roce
dure
R
esul
ts
Ref
eren
ce
as C
arbo
pol U
ltre
z 21
(t
rade
nam
e)
150
mg
of a
10%
di
luti
on
111
subj
ects
te
st m
ater
ial w
as a
pplie
d to
a 2
cm
x 2
cm
pad
; pat
ch
was
app
lied
for
4 c
onse
cuti
ve d
ays
duri
ng w
ks 1
-3;
chal
leng
e w
as p
erfo
rmed
aft
er 1
wk
and
incl
uded
4
appl
icat
ions
not a
n ir
rita
nt o
r se
nsit
izer
38
as C
arbo
pol U
ltre
z 20
(t
rade
nam
e)
150
mg
of a
10%
di
luti
on
111
subj
ects
te
st m
ater
ial w
as a
pplie
d to
a 2
cm
x 2
cm
pad
; pat
ch
was
app
lied
for
4 c
onse
cuti
ve d
ays
duri
ng w
ks 1
-3;
chal
leng
e w
as p
erfo
rmed
aft
er 1
wk
and
incl
uded
4
appl
icat
ions
not a
n ir
rita
nt o
r se
nsit
izer
39
as P
emul
en (
trad
enam
e)
undi
lute
d (9
7.5%
)44
54 s
ubje
cts
“int
ensi
fied
” Sh
elan
ski H
RIP
T; t
est m
ater
ial w
as
appl
ied
to a
1”
x 1”
pat
ch
wea
k ir
rita
nt r
espo
nse;
not
a s
ensi
tize
r du
ring
indu
ctio
n, f
aint
or
mod
erat
e er
ythe
ma
was
obs
erve
d on
ce f
or 9
sub
ject
s an
d tw
ice
for
2 su
bjec
ts; a
t cha
lleng
e, f
aint
er
ythe
ma
was
obs
erve
d on
ce f
or 3
sub
ject
s
40
body
loti
on w
ith
0.15
%
Acr
ylat
es/C
10-3
0 A
lkyl
A
cryl
ate
Cro
sspo
lym
er
0.2
g 10
7 su
bjec
ts
test
mat
eria
l was
app
lied
to a
1”
x 1”
abs
orbe
nt p
ad a
nd
allo
wed
to v
olat
ize
for
seve
ral m
in; s
emi-
occl
usiv
e pa
tch;
24
h ap
plic
atio
ns m
ade
3 x/
wk
for
3 w
k;
chal
leng
e w
as a
ppli
ed a
fter
2 w
ks
not a
der
mal
irri
tant
or
sens
itiz
er
45
crèm
e w
ith
0.60
%
Acr
ylat
es/C
10-3
0 A
lkyl
A
cryl
ate
Cro
sspo
lym
er
0.2
g 51
sub
ject
s te
st m
ater
ial w
as a
ppli
ed to
a 1
” x
1” a
bsor
bent
pad
and
al
low
ed to
vol
atiz
e fo
r se
vera
l min
; sem
i-oc
clus
ive
patc
h; 2
4 h
sem
i-oc
clus
ive
patc
hes
appl
ied
3 x/
wk
for
3 w
k; c
hall
enge
was
app
lied
afte
r 2
wks
not a
der
mal
irri
tant
or
sens
itiz
er
46
Acr
ylat
es C
ross
poly
mer
Acr
ylat
es C
ross
poly
mer
15
µl;
30%
in o
live
oi
l 20
sub
ject
s si
ngle
24-
h oc
clus
ive
patc
h no
t an
irri
tant
acc
ordi
ng to
Jap
anes
e cr
iteri
a 23
eye
loti
on w
ith
0.75
%
Acr
ylat
es C
ross
poly
mer
un
dilu
ted
46 s
ubje
cts
HR
IPT
wit
h oc
clus
ive
patc
h no
t an
irri
tant
or
sens
itiz
er
47
skin
cle
anse
r w
ith 0
.8%
A
cryl
ates
Cro
sspo
lym
er
1% a
q. d
iluti
on
60 s
ubje
cts
HR
IPT
wit
h oc
clus
ive
patc
h no
t an
irri
tant
or
sens
itiz
er
47
lips
tick
wit
h 4%
Acr
ylat
es
Cro
sspo
lym
er
0.2
g 85
sub
ject
s H
RIP
T w
ith
occl
usiv
e pa
tch
not a
n ir
rita
nt o
r se
nsit
izer
48
Acr
ylat
es/E
thyl
hex
yl A
cryl
ate
Cro
sspo
lym
er
faci
al s
unsc
reen
wit
h 6.
8565
% A
cryl
ates
/Eth
yl-
hexy
l Acr
ylat
e C
ross
poly
mer
undi
lute
d 60
0 su
bjec
ts
mod
ifie
d D
raiz
e R
IPT
wit
h te
n 48
-h in
duct
ion
patc
hes
usin
g 0.
5 in
squ
are
occl
usiv
e pa
tche
s; th
e fi
rst c
hall
enge
w
as a
ppli
ed a
fter
a 2
-wk
non-
trea
tmen
t per
iod;
an
addi
-ti
onal
cha
llen
ge a
ppli
cati
on w
as m
ade
1 w
k af
ter
the
firs
t cha
lleng
e ap
plic
atio
n
no e
vide
nce
of p
rim
ary
irri
tati
on, s
kin
fati
gue,
or
sens
itiza
tion
49
Acr
ylat
es/S
tear
eth
-20
Met
hac
ryla
te C
ross
poly
mer
the
acry
lic c
opol
ymer
of
Acu
lyn
88 P
olym
er
(tra
dena
me)
not s
tate
d no
t sta
ted
21-d
ay c
umul
ativ
e ir
rita
tion
stu
dy (
GC
P)
no ir
rita
tion
or
sens
itiz
atio
n 9
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 59
Tab
le 5
. D
erm
al ir
rita
tion
and
sen
siti
zati
on –
alte
rnat
ive
stud
ies,
non
-hum
an, a
nd h
uman
(co
ntin
ued)
30
Tes
t A
rtic
le
Con
cent
rati
on/D
ose
Tes
t P
opul
atio
n P
roce
dure
R
esul
ts
Ref
eren
ce
the
acry
lic c
opol
ymer
of
Acu
lyn
88 P
olym
er
(tra
dena
me)
not s
tate
d no
t sta
ted
HR
IPT
(G
CP
)
no ir
rita
tion
or
sens
itiz
atio
n 9
Acr
ylat
es/V
inyl
Iso
deca
noa
te C
ross
poly
mer
as S
taby
len
30 (
trad
enam
e)
0.5-
2.5%
aq.
25
sub
ject
s K
ligm
an te
st (
addi
tion
al d
etai
ls w
ere
not p
rovi
ded)
no
t an
irri
tant
or
sens
itiz
er
34
Acr
ylat
es/V
inyl
Neo
deca
noa
te C
ross
poly
mer
the
acry
lic c
opol
ymer
of
Acu
lyn
38 P
olym
er
(tra
dena
me)
not s
tate
d no
t sta
ted
21-d
ay c
umul
ativ
e ir
rita
tion
stu
dy (
GC
P)
at
mos
t, a
mil
d ir
rita
nt w
ith
unfo
rmul
ated
po
lym
er a
nd u
nder
wor
se-c
ase
cond
itio
ns
11
the
acry
lic c
opol
ymer
of
Acu
lyn
38 P
olym
er
(tra
dena
me)
not s
tate
d no
t sta
ted
HR
IPT
(G
CP
)
not a
n ir
rita
nt o
r se
nsit
izer
11
bath
crè
me
with
2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
108
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
50
bath
crè
me
with
2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
109
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
51
bubb
le b
ath
wit
h 2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
108
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
52
bath
gel
wit
h 2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
108
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
53
bath
pro
duct
wit
h 2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
106
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
54
bath
foa
m w
ith
2% A
cry-
late
s/V
inyl
Neo
deca
noat
e C
ross
poly
mer
1% a
q. d
ilut
ion
106
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
55
bath
foa
m w
ith
2% A
cry-
late
s/V
inyl
Neo
deca
noat
e C
ross
poly
mer
1% a
q. d
ilut
ion
106
subj
ects
(s
ame
subj
ects
as
abov
e)
HR
IPT
; 24-
h oc
clus
ive
patc
hes
appl
ied
3x/w
k fo
r 3
wks
; 24-
h ch
alle
nge
afte
r a
2-w
k no
n-tr
eatm
ent p
erio
d;
(siz
e of
pat
ch w
as n
ot p
rovi
ded)
not a
n ir
rita
nt o
r se
nsit
izer
56
bath
foa
m w
ith
2% A
cry-
late
s/V
inyl
Neo
deca
noat
e C
ross
poly
mer
1% a
q. d
ilut
ion
106
subj
ects
(s
ame
subj
ects
as
abov
e)
HR
IPT
; 24-
h oc
clus
ive
patc
hes
appl
ied
3x/w
k fo
r 3
wks
; 24-
h ch
alle
nge
afte
r a
2-w
k no
n-tr
eatm
ent p
erio
d;
(siz
e of
pat
ch w
as n
ot p
rovi
ded)
not a
n ir
rita
nt o
r se
nsit
izer
57
bubb
le b
ath
wit
h 2%
Acr
y-la
tes/
Vin
yl N
eode
cano
ate
Cro
sspo
lym
er
1% a
q. d
ilut
ion
107
subj
ects
H
RIP
T; 2
4-h
occl
usiv
e pa
tche
s ap
plie
d 3x
/wk
for
3 w
ks; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t per
iod;
(s
ize
of p
atch
was
not
pro
vide
d)
not a
n ir
rita
nt o
r se
nsit
izer
58
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 60
Tab
le 5
. D
erm
al ir
rita
tion
and
sen
siti
zati
on –
alte
rnat
ive
stud
ies,
non
-hum
an, a
nd h
uman
(co
ntin
ued)
31
Tes
t A
rtic
le
Con
cent
rati
on/D
ose
Tes
t P
opul
atio
n P
roce
dure
R
esul
ts
Ref
eren
ce
Lau
ryl M
eth
acry
late
/Gly
col D
imet
hac
ryla
te C
ross
poly
mer
face
pow
der
wit
h 1%
Lau
r-yl
Met
hacr
ylat
e/G
lyco
l Di-
met
hacr
ylat
e C
ross
poly
mer
0.2
g 10
4 su
bjec
ts
HR
IPT
; 24-
h oc
clus
ive
patc
hes
appl
ied
3x/w
k fo
r 3
wks
; 24-
h ch
alle
nge
afte
r a
10-1
5 da
y no
n-tr
eatm
ent
peri
od; (
size
of
patc
h w
as n
ot p
rovi
ded)
not a
n ir
rita
nt o
r se
nsit
izer
59
exfo
liat
or c
ream
wit
h 2.
6%
Lau
ryl M
etha
cryl
ate/
Gly
col
Dim
etha
cryl
ate
Cro
ss-
poly
mer
0.2
g 61
9 su
bjec
ts
HR
IPT
wit
h te
n 24
h o
cclu
sive
app
lica
tion
s of
a ¾
” x
¾”
patc
h; 2
4-h
chal
leng
e af
ter
a 2-
wk
non-
trea
tmen
t pe
riod
; rec
hall
enge
was
per
form
ed o
n 2
subj
ects
usi
ng
sem
i-oc
clus
ive
and
open
rep
etit
ive
appl
icat
ion
not a
n ir
rita
nt o
r se
nsit
izer
af
ter
chal
leng
e, o
ne s
ubje
ct h
ad m
oder
ate
(at
24 h
) an
d m
ild
(at 7
2 h)
ery
them
a an
d ed
e-m
a, a
nd o
ne s
ubje
ct h
ad b
arel
y pe
rcep
tibl
e er
ythe
ma
at 7
2 h;
thes
e re
sult
s w
ere
not
repr
oduc
ible
at r
echa
llen
ge
60
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 61
T
able
6.
Rel
evan
t su
mm
ary
info
rmat
ion
on
com
pon
ent
mon
omer
s
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
Acr
ylic
Aci
d T
oxic
okin
etic
s D
erm
al:
radi
oact
ivity
was
rec
over
ed m
ostly
in th
e sk
in tr
ap, a
nd th
en in
exp
ired
CO
2 O
ral:
In
num
erou
s st
udie
s us
ing
rats
,, th
e do
se w
as p
rim
arily
exc
rete
d in
exp
ired
air
in m
ost c
ases
; eli
min
atio
n w
as
gene
rall
y ra
pid;
upt
ake
and
elim
inat
ion
appe
ared
to b
e bi
phas
ic; a
bsor
ptio
n an
d ex
cret
ion
wer
e al
so r
apid
in m
ice
Inha
lati
on:
Rat
s w
ere
expo
sed
to a
cryl
ic a
cid
via
inha
lati
on; m
ost o
f th
e ra
dioa
ctiv
ity
was
fou
nd in
the
head
and
sno
ut,
wit
h re
lati
vely
larg
e am
ount
s al
so r
ecov
ered
in th
e up
per
resp
irat
ory
trac
t
1
T
oxic
olog
ical
Stu
dies
S
ingl
e D
ose
- D
erm
al:
LD
50 –
295
to 9
50 m
g/kg
in r
abbi
ts
Ora
l: L
D50
– 2
100
to 3
200
mg/
kg in
rab
bits
and
rat
s; p
rodu
ced
gast
ric
lesi
ons
Inh
alat
ion:
LC
50 –
360
0 m
g/m
3 in r
ats
1
Rep
eate
d D
ose
– D
erm
al:
4% p
rodu
ced
toxi
c ef
fect
s in
mic
e in
a 1
3-w
k st
udy
Ora
l: to
xic
effe
cts
wer
e ob
serv
ed in
rat
s in
a 9
0-da
y dr
inki
ng w
ater
stu
dy w
ith
dose
s of
≤75
0 m
g/kg
and
in a
90-
day
gava
ge s
tudy
in r
ats
dose
s w
ith
150
or 3
75 m
g/kg
; sto
mac
h le
sion
s w
ere
not o
bser
ved
wit
h up
to 5
00 p
pm in
a 1
2-m
os
drin
king
stu
dy w
ith
rats
I
nhal
atio
n: n
asal
irri
tati
on a
nd/o
r le
sion
s w
ere
obse
rved
in r
ats
and/
or m
ice
expo
sed
to 1
500
ppm
for
4-d
ay u
p to
225
pp
m f
or 2
-wk
, 300
ppm
for
20-
days
, and
75
ppm
for
13-
wks
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Ora
l: d
id n
ot p
rodu
ce te
rato
geni
c ef
fect
s in
rat
s, N
OA
EL
of
250
mg/
kg; d
id a
ffec
t bod
y w
eigh
ts a
nd s
ome
orga
n w
eigh
ts
in th
e pa
rent
al a
nim
als
Inha
lati
on:
not t
erat
ogen
ic o
r em
bryo
toxi
c in
rat
s at
con
cent
rati
ons
up to
120
ppm
; did
pro
duce
mat
erna
l tox
icit
y at
co
ncen
trat
ions
of
120
ppm
and
gre
ater
1
G
enot
oxic
ity
geno
toxi
c in
mou
se ly
mph
oma
assa
ys, a
nd in
an
in v
itro
cyt
ogen
etic
ass
ay; n
ot g
enot
oxic
or
mut
agen
ic in
Am
es te
sts,
un
sche
dule
d D
NA
syn
thes
is (
UD
S)
assa
y, m
icro
nucl
eus
assa
y, in
viv
o tr
ansf
orm
atio
n as
say,
Chi
nese
ham
ster
ova
ry
(CH
O)/
HG
PR
T, i
n vi
vo c
ytog
enet
ic a
ssay
, Dro
soph
ila
test
, or
mou
se d
omin
ant l
etha
l ass
ay
1
C
arci
noge
nici
ty
Der
mal
: in
one
stu
dy, 4
% in
ace
tone
was
a c
ompl
ete
but w
eak
carc
inog
en in
mic
e; in
ano
ther
, 1%
was
not
car
cino
geni
c in
mic
e O
ral:
not
car
cino
geni
c in
rat
s w
hen
give
n in
dri
nkin
g w
ater
at u
p to
120
0 pp
m
Par
ente
ral:
not
car
cino
geni
c w
hen
1.4
mg
was
inje
cted
sub
cuta
neou
sly
(s.c
.) to
mic
e IA
RC
Eva
luat
ion:
no
epid
emio
logi
cal d
ata
rele
vant
to c
arci
noge
nici
ty w
ere
avai
labl
e; n
o ex
peri
men
tal d
ata
rele
vant
to
carc
inog
enic
ity
wer
e av
aila
ble;
not
cla
ssif
iabl
e as
to it
s ca
rcin
ogen
icit
y to
hum
ans
(Gro
up 3
)
1
61
Ir
rita
tion
and
Sen
siti
zati
on
Ski
n: 4
% w
as ir
rita
ting
to th
e sk
in o
f m
ice
Muc
osal
: a
1% s
olut
ion
caus
ed s
igni
fica
nt in
jury
to th
e ra
bbit
eye
1
Met
hyl
Acr
ylat
e T
oxic
okin
etic
s D
erm
al:
In g
uine
a pi
gs e
xpos
ed d
erm
ally
to m
ethy
l [2,
3-14
C]a
cryl
ate,
rad
ioac
tivi
ty w
as s
een
in th
e s.
c. ti
ssue
s an
d th
roug
hout
the
body
O
ral:
the
dose
was
pri
mar
ily e
xcre
ted
in e
xpir
ed a
ir; e
lim
inat
ion
was
rap
id (
rats
)
62
T
oxic
olog
ical
Stu
dies
S
ingl
e D
ose
- O
ral;
pro
duce
d ga
stri
c le
sion
s w
hen
give
n in
hibi
ted
wit
h 20
0 pp
m h
ydro
quin
one
mon
omet
hyl e
ther
(H
QM
ME
)
1
Rep
eate
d D
ose
– O
ral:
not
toxi
c w
hen
give
n or
ally
to r
ats
(det
ails
not
pro
vide
d)
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Inha
lati
on:
up to
200
ppm
did
not
pro
duce
tera
toge
nic
or r
epro
duct
ive
effe
cts
in r
ats
1
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 62
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
33
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
G
enot
oxic
ity
geno
toxi
c in
mou
se ly
mph
oma
and
chro
mos
omal
abe
rrat
ion
assa
ys; p
osit
ive
in o
ne a
nd n
egat
ive
in tw
o m
icro
nucl
eus
test
s; n
ot m
utag
enic
or
geno
toxi
c in
an
Am
es, S
alm
onel
la/m
icro
som
e, li
quid
incu
bati
on, m
onol
ayer
, sus
pens
ion,
or
AS
52/X
RP
T a
ssay
1
C
arci
noge
nici
ty
Inha
lati
on:
up to
135
ppm
was
not
car
cino
geni
c to
rat
s IA
RC
Eva
luat
ion:
no
epid
emio
logi
cal d
ata
rele
vant
to th
e ca
rcin
ogen
icit
y; in
adeq
uate
evi
denc
e in
exp
erim
enta
l ani
mal
s;
not c
lass
ifia
ble
as to
its
carc
inog
enic
ity
to h
uman
s (G
roup
3)
1
62
Eth
yl A
cryl
ate
Tox
icok
inet
ics
Ora
l: th
e do
se w
as p
rim
arily
exc
rete
d in
exp
ired
air
; eli
min
atio
n w
as r
apid
(ra
ts)
1
T
oxic
olog
ical
Stu
dies
S
ingl
e D
ose
- O
ral;
pro
duce
d ga
stri
c le
sion
s w
hen
give
n in
hibi
ted
wit
h 15
-20
ppm
HQ
MM
E
1
Rep
eate
d D
ose
– O
ral:
2-w
k st
udy
in r
ats
wit
h do
sing
via
gav
age
or d
rink
ing
wat
er -
gas
tric
lesi
ons
wer
e ob
serv
ed,
prim
aril
y in
the
fore
stom
ach.
, at d
oses
of
20-1
00 m
g/kg
giv
en b
uy g
avag
e an
d at
con
cent
rati
ons1
000-
4000
ppm
in
drin
king
wat
er; i
n a
13-w
k ga
vage
stu
dy, d
oses
of ≤2
00 m
g/kg
pro
duce
d le
sion
s in
the
fore
stom
ach
of r
ats;
sto
mac
h le
sion
s w
ere
not o
bser
ved
at c
once
ntra
tion
s up
to 2
000
ppm
in a
2-y
r dr
inki
ng s
tudy
wit
h ra
ts o
r up
to 1
000
ppm
in a
2-y
r ca
psul
e st
udy
wit
h do
gs
Inh
alat
ion:
no
nasa
l les
ions
wer
e ob
serv
ed w
ith
up to
300
ppm
in a
1-m
onth
stu
dy u
sing
rat
s an
d m
ice;
nas
al le
sion
s w
ere
obse
rved
at c
once
ntra
tion
s of
≥24
2 pp
m in
rat
s in
a 1
2-w
k st
udy
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Inha
lati
on:
up to
200
ppm
was
not
em
bryo
toxi
c or
fet
otox
ic in
rat
s; m
ater
nal t
oxic
ity
obse
rved
wit
h 15
0 pp
m
1
G
enot
oxic
ity
geno
toxi
c in
a m
ouse
lym
phom
a an
d ch
rom
osom
al a
berr
atio
n as
say;
indu
ced
chro
mos
omal
mal
segr
egat
ion
and
mit
otic
re
com
bina
tion
usi
ng S
. cer
evis
iae;
pos
itiv
e in
one
and
neg
ativ
e in
one
mic
ronu
cleu
s as
say;
not
mut
agen
ic o
r ge
noto
xic
in
an A
mes
, Sal
mon
ella
/mic
roso
me,
liqu
id in
cuba
tion
, mon
olay
er, c
hrom
osom
al ,
sist
er c
hrom
atid
exc
hang
e (S
CE
), o
r D
roso
phil
a as
say
1
C
arci
noge
nici
ty
Der
mal
: te
sted
und
ilut
ed, n
ot c
arci
noge
nic
to m
ice
Ora
l: i
n co
rn o
il, c
arci
noge
nic
in m
ale
and
fem
ale
rats
and
mic
e at
100
and
200
mg/
kg
Inha
lati
on:
up to
225
ppm
was
not
car
cino
geni
c in
mic
e or
rat
s IA
RC
Eva
luat
ion:
no
epid
emio
logi
cal d
ata
rele
vant
to th
e ca
rcin
ogen
icity
; suf
fici
ent e
vide
nce
in e
xper
imen
tal a
nim
als;
po
ssib
ly c
arci
noge
nic
to h
uman
s (G
roup
2B
)
1
63
Bu
tyl A
cryl
ate
Tox
icok
inet
ics
Ora
l: th
e do
se w
as p
rim
arily
exc
rete
d in
exp
ired
air
(ra
ts)
1
T
oxic
olog
ical
Stu
dies
S
ingl
e D
ose
Ora
l; p
rodu
ced
gast
ric
lesi
ons
whe
n gi
ven
inhi
bite
d w
ith
10-5
5 H
QM
ME
1
Rep
eate
d D
ose
– O
ral:
not
toxi
c w
hen
give
n or
ally
to r
ats
(det
ails
not
pro
vide
d)
Inh
alat
ion:
tox
icit
y w
as o
bser
ved
in r
ats
and
ham
ster
s up
on 3
6-h
exp
osur
es to
820
and
817
ppm
, res
pect
ivel
y; n
asal
le
sion
s w
ere
obse
rved
in r
ats
expo
sed
to c
once
ntra
tion
s ≥1
08 p
pm in
a 1
3-w
k st
udy
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Inha
lati
on:
no to
xic
effe
cts
wer
e se
en w
ith
25 p
pm; h
igh
conc
entr
atio
ns h
ad to
xic
effe
cts
on th
e fe
tuse
s an
d da
ms
1
G
enot
oxic
ity
posi
tive
in o
ne a
nd n
egat
ive
in o
ne c
hrom
osom
al a
berr
atio
n as
say;
not
mut
agen
ic o
r ge
noto
xic
in a
n A
mes
, Sa
lmon
ella
/mic
roso
me,
liqu
id in
cuba
tion
, UD
S, m
icro
nucl
eus,
or
in v
itro
tran
sfor
mat
ion
assa
y
1
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 63
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
34
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
C
arci
noge
nici
ty
Der
mal
: 1%
was
not
car
cino
geni
c in
mic
e In
hala
tion
: up
to 1
35 p
pm w
as n
ot c
arci
noge
nic
to r
ats
IAR
C E
valu
atio
n: n
o ep
idem
iolo
gica
l dat
a re
leva
nt to
the
carc
inog
enic
ity;
inad
equa
te e
vide
nce
in e
xper
imen
tal a
nim
als;
no
t cla
ssif
iabl
e as
to it
s ca
rcin
ogen
icit
y to
hum
ans
(Gro
up 3
)
1
64
2-E
thyl
hex
yl A
cryl
ate
Tox
icok
inet
ics
Ora
l: th
e do
se w
as p
rim
arily
exc
rete
d in
exp
ired
air
; eli
min
atio
n w
as r
apid
(ra
ts)
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Inha
lati
on:
up to
100
ppm
did
not
pro
duce
tera
toge
nic
or r
epro
duct
ive
effe
cts
in r
ats
1
G
enot
oxic
ity
geno
toxi
c in
a m
ouse
lym
phom
a fo
rwar
d m
utat
ion
assa
y w
ith
met
abol
ic a
ctiv
atio
n; e
quiv
ocal
ly g
enot
oxic
in m
utat
ion
and
aber
rati
ons
assa
ys; w
eakl
y m
utag
enic
in S
CE
and
UD
S as
says
; not
mut
agen
ic o
r ge
noto
xic
in a
mic
robi
al m
utag
en
test
, Am
es te
st, m
amm
alia
n ce
ll tr
ansf
orm
atio
n as
say,
mic
ronu
cleu
s te
st, m
onol
ayer
or
susp
ensi
on a
ssay
, CH
O a
ssay
, or
in v
ivo
cyto
geni
c as
say
1
C
arci
noge
nici
ty
Der
mal
: ca
rcin
ogen
ic a
t a d
ose
of ≥
21%
whe
n ap
plie
d to
mic
e –
the
carc
inog
enic
res
pons
e m
ay h
ave
been
ass
ocia
ted
wit
h th
e se
vere
ski
n ir
rita
tion
indu
ced
by th
e ch
emic
al
Tes
ted
by s
kin
appl
icat
ion
in th
ree
expe
rim
ents
in m
ice;
it in
crea
sed
the
inci
denc
e of
squ
amou
s-ce
ll ca
rcin
omas
of
the
skin
in 2
exp
erim
ents
and
of
mal
igna
nt m
elan
omas
in o
ne e
xper
imen
t; in
the
thir
d ex
peri
men
t, in
a d
iffe
rent
str
ain
of
mic
e, n
o in
crea
se s
kin
tum
or in
cide
nce
was
see
n w
ith
or w
itho
ut s
ubse
quen
t app
lica
tion
of
12-0
-tet
rade
cano
ylph
orbo
l 13
-ace
tate
IA
RC
Eva
luat
ion:
ina
dequ
ate
evid
ence
in h
uman
s fo
r ca
rcin
ogen
icity
; lim
ited
evid
ence
in e
xper
imen
tal a
nim
als;
not
cl
assi
fiab
le a
s to
its
carc
inog
enic
ity
to h
uman
s (G
roup
3)
1
65
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
- N
on-H
uman
: se
nsiti
zatio
n w
as o
bser
ved
whe
n gu
inea
-pig
s w
ere
trea
ted
wit
h 2-
ethy
lhex
yl a
cryl
ate
in F
reun
d’s
com
plet
e ad
juva
nt
Hum
an:
in a
pro
voca
tive
test
wit
h 24
3 pa
tien
ts w
ith
a h
isto
ry o
f ex
posu
re to
(m
eth)
acry
late
s, n
one
of th
e pa
tien
ts w
ere
sens
itiz
ed w
ith
patc
hes
cont
aini
ng 0
.1-0
.5%
2-e
thyl
hexy
l acr
ylat
e
65
1
Pol
yacr
ylic
Aci
d
Ani
mal
Tox
icol
ogy
Sing
le D
ose
- O
ral:
LD
50 –
250
0 m
g/kg
in r
ats
1
C
IR C
oncl
usio
n (2
002)
sa
fe a
s us
ed w
hen
form
ulat
ed to
avo
id s
kin
irri
tati
on
1
Sod
ium
Pol
yacr
ylat
e A
nim
al T
oxic
olog
y Si
ngle
Dos
e –
Ora
l: L
D50
- >
40 g
/kg
in r
ats
for
a 15
% s
olut
ion
1
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Ora
l: u
p to
300
0 m
g/kg
/day
low
-mol
-wt a
nd u
p to
112
5 m
g/kg
/day
hig
h-m
ol-w
t did
not
cau
se r
epro
duct
ive
effe
cts
in
rats
1
G
enot
oxic
ity
not g
enot
oxic
in a
n A
mes
ass
ay, a
pla
te te
st, a
mou
se ly
mph
oma
assa
y, c
hrom
osom
al a
berr
atio
n as
says
, a U
DS
ass
ay, o
r an
in v
ivo
mou
se m
icro
nucl
eus
assa
y
1
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
– N
on-H
uman
: no
t an
irri
tant
to r
abbi
t ski
n w
hen
appl
ied
undi
lute
d H
uman
: no
t an
irri
tant
or
sens
itiz
er (
conc
entr
atio
n no
t giv
en)
Ocu
lar:
the
gre
ates
t tol
erat
ed c
once
ntra
tion
s w
ere
13-2
0% f
or u
nrin
sed
and
20-3
0% f
or r
inse
d ra
bbit
eye
s; in
an
irri
tant
-th
resh
old
test
, 2%
was
the
grea
test
con
cent
rati
on th
at d
id n
ot p
rodu
ce ir
rita
tion
in r
abbi
t eye
s
1
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 64
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
35
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
C
IR C
oncl
usio
n (2
002)
sa
fe a
s us
ed w
hen
form
ulat
ed to
avo
id s
kin
irri
tati
on
1
Met
hacr
ylic
Aci
d T
oxic
okin
etic
s re
adil
y ab
sorb
ed th
roug
h th
e m
ucou
s m
embr
anes
of
the
lung
s an
d ga
stro
inte
stin
al tr
act o
f a
nd th
e sk
in, a
nd is
rea
dily
di
stri
bute
d to
all
maj
or ti
ssue
s
66
A
nim
al T
oxic
olog
y S
ingl
e D
ose
– D
erm
al:
repo
rted
LD
50 v
alue
s ra
nged
fro
m 5
00-1
243
mg/
kg f
or r
abbi
ts
Ora
l: r
epor
ted
LD
50 v
alue
s ra
nged
fro
m 8
27-1
600
mg/
kg f
or m
ice,
277
-226
0 m
g/kg
for
rat
s, a
nd 2
80-1
200
mg/
kg f
or
rabb
its
Inh
alat
ion:
rep
orte
d L
C50
val
ues
wer
e 36
57 p
pm in
mic
e, 1
350
ppm
/4 h
in r
ats,
and
252
2 pp
m/1
h in
rab
bits
66
Rep
eate
d D
ose
– O
ral:
no
sign
s of
toxi
city
in a
sho
rt-t
erm
stu
dy
Inh
alat
ion:
nos
e an
d ey
e ir
rita
tion
and
wei
ght l
oss
in r
ats
wit
h 5
expo
sure
s to
130
0 pp
m; o
nly
rena
l con
gest
ion
in r
ats
wit
h 20
exp
osur
es to
300
ppm
; in
a 2-
wk
stud
y, r
epea
ted
dose
s of
≥10
0 pp
m c
ause
d re
acti
ons
in r
ats,
of ≥5
00 p
pm
caus
ed r
eact
ions
in m
ice,
and
100
0 pp
m k
ille
d al
l rat
s an
d m
ice;
in a
90-
day
stud
y, r
espi
rato
ry e
ffec
ts w
ere
seen
in r
ats
and
mic
e ex
pose
d to
300
ppm
– c
ytom
egal
y of
ren
al tu
bula
r ep
ithe
lium
was
obs
erve
d in
>50
% o
f te
st m
ale
mic
e
66
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Inha
lati
on:
no r
epro
duct
ive
or d
evel
opm
enta
l eff
ects
at c
once
ntra
tion
s up
to 3
00 p
pm
In V
itro
: ad
vers
e ef
fect
s w
ere
seen
wit
h ex
posu
re o
f ra
t em
bryo
s to
≥12
9 µ
g/m
l
66
G
enot
oxic
ity
posi
tive
in a
DN
A c
ell-
bind
ing
assa
y; n
egat
ive
in a
n A
mes
test
66
C
arci
noge
nici
ty
it w
as r
epor
ted
that
IA
RC
rev
iew
ed m
etha
cryl
ic a
cid,
but
did
not
pre
pare
a m
onog
raph
bec
ause
inad
equa
te d
ata
wer
e av
aila
ble
66
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
– N
on-H
uman
: co
rros
ive
to r
abbi
t and
gui
nea
pig
skin
; in
a gu
inea
pig
max
imiz
atio
n st
udy,
it w
as d
iffi
cult
to
dete
rmin
e if
obs
erve
d re
acti
ons
wer
e hy
pers
ensi
tivi
ty o
r ir
rita
tion
; gui
nea
pigs
wer
e no
t sen
siti
zed
in 3
oth
er s
tudi
es
Muc
osal
: ca
used
sev
ere
corn
eal,
irid
al, a
nd c
onju
ncti
val e
ffec
ts in
rab
bits
in o
ne s
tudy
; in
an in
hala
tion
stu
dy, 5
6,91
6 pp
m w
as c
orro
sive
to r
abbi
t eye
s
66
C
lini
cal U
se
nega
tive
resu
lts
wer
e re
port
ed in
a n
umbe
r of
pat
ch te
sts
of p
atie
nts
alle
rgic
to m
ethy
l met
hacr
ylat
e an
d to
wor
kers
ex
pose
d to
acr
ylat
es
66
D
iscu
ssio
n It
ems
the
Pane
l was
con
cern
ed w
ith
the
extr
eme
corr
osiv
ity;
a p
rese
ntat
ion
dem
onst
rate
d th
at a
trai
ned
prof
essi
onal
cou
ld
appl
y th
e ac
id to
the
nail
wit
hout
exp
osur
e to
the
skin
, but
this
cou
ld n
ot b
e de
mon
stra
ted
for
reta
il c
onsu
mer
s; d
ue to
co
ncer
ns th
at in
hala
tion
cou
ld a
ffec
t the
res
pira
tory
trac
t, an
d th
e na
il te
chni
cian
cou
ld b
e su
bjec
ted
to in
crea
sed
expo
sure
in a
com
mer
cial
set
ting
, the
NIO
SH
-rec
omm
ende
d ex
posu
re li
mit
of 2
0 pp
m a
s a
tim
e-w
eigh
ted
aver
age
conc
entr
atio
n sh
ould
not
be
exce
eded
; the
Con
sum
er P
rodu
ct S
afet
y C
omm
issi
on r
ule
req
uire
s ch
ild-
resi
stan
t pac
kagi
ng
for
liqu
id h
ouse
hold
pro
duct
s co
ntai
ning
>5%
met
hacr
ylic
aci
d (w
t to
vol)
66
C
IR C
oncl
usio
n (2
005)
sa
fe a
s u
sed
as a
nai
l pri
mer
by
trai
ned
pro
fess
ion
als;
insu
ffic
ien
t dat
a fo
r re
tail
use
by
con
sum
ers
66
Met
hyl
Met
hac
ryla
te
Tox
icok
inet
ics
can
be a
bsor
bed
thro
ugh
the
skin
of
hum
ans
67
A
nim
al T
oxic
olog
y R
epea
ted
Dos
e -
Ora
l: c
hron
ic e
xpos
ure
to ≤
400
ppm
did
not
cau
se tu
mor
s in
ham
ster
s or
rat
s 68
G
enot
oxic
ity
geno
toxi
c in
a c
hrom
osom
al a
berr
atio
n, S
CE
, and
mou
se ly
mph
oma
assa
y; n
ot m
utag
enic
in a
Sal
mon
ella
/mic
roso
me
or
liqu
id in
cuba
tion
ass
ay
1
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 65
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
36
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
C
arci
noge
nici
ty
Ora
l: n
ot c
arci
noge
nic
in a
dri
nkin
g st
udy
usin
g ra
ts
Inha
lati
on:
up to
400
ppm
was
not
car
cino
geni
c in
mic
e or
rat
s IA
RC
: in
adeq
uate
evi
denc
e in
hum
ans
for
carc
inog
enic
ity;
evi
denc
e su
gges
ting
lack
of c
arci
noge
nici
ty in
exp
erim
enta
l an
imal
s; n
ot c
lass
ifia
ble
as to
its
carc
inog
enic
ity
in h
uman
s (G
roup
3)
67,6
8
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
– N
on-H
uman
: se
nsiti
zing
at 2
5% in
gui
nea
pigs
; min
imum
indu
ctio
n co
ncen
trat
ion
was
1 M
; was
a w
eak
cont
act a
ller
gen
in a
loca
l lym
ph n
ode
assa
y H
uman
: th
e fr
eque
ncy
of p
osit
ive
reac
tion
s am
ong
all p
atie
nts
to m
ethy
l met
hacr
ylat
e w
as 7
/22;
the
freq
uenc
y o
f po
siti
ve r
eact
ions
am
ong
patie
nts
wit
h ar
tific
ial n
ails
was
1/1
0
69
Eth
yl M
eth
acry
late
G
enot
oxic
ity
not m
utag
enic
in a
Sal
mon
ella
/mic
roso
me
assa
y; g
enot
oxic
ity
in a
mou
se ly
mph
oma
cell
ass
ay w
as c
onsi
dere
d li
kely
due
to
a c
last
ogen
ic m
echa
nism
1
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
– H
uman
: th
e fr
eque
ncy
of p
ositi
ve r
eact
ions
am
ong
all p
atie
nts
test
ed w
as 1
4/22
; The
fre
quen
cy o
f po
siti
ve
reac
tion
s am
ong
pati
ents
wit
h ar
tifi
cial
nai
ls w
as 7
/11
(64%
),
69
D
iscu
ssio
n It
ems
(Thi
s in
gred
ient
was
rev
iew
ed f
or it
s us
e na
il e
nhan
cem
ent p
rodu
cts.
) th
e Pa
nel w
as c
once
rned
wit
h th
e st
rong
sen
sitiz
a-ti
on a
nd c
ross
- or
co-
reac
tivi
ty p
oten
tial o
f m
etha
cryl
ates
; how
ever
dat
a w
ere
subm
itte
d th
at in
dica
ted
ther
e w
ould
be
littl
e m
onom
er a
vaila
ble
for
expo
sure
to th
e sk
in; g
enot
oxic
ity d
ata
indi
cate
d th
e so
me
met
hacr
ylat
es c
ould
pro
duce
ch
rom
osom
e da
mag
e; th
e P
anel
res
tric
ted
met
hacr
ylat
es to
the
nail
, and
they
mus
t not
com
e in
con
tact
wit
h sk
in; i
niti
al
conc
ern
that
exo
ther
ms
crea
ted
from
the
rapi
d po
lym
eriz
atio
n of
the
mon
omer
s co
uld
dam
age
the
nail
wer
e al
levi
ated
68
C
IR C
oncl
usio
n (2
005)
sa
fe a
s us
ed in
nai
l enh
ance
men
t pro
duct
s w
hen
skin
con
tact
is a
void
ed;
prod
uct
s co
nta
inin
g th
is in
gred
ien
t sho
uld
be
acc
ompa
nie
d w
ith
dir
ectio
ns
to a
void
ski
n c
onta
ct, b
ecau
se o
f th
e se
nsi
tizin
g po
ten
tial
of
met
hac
ryla
tes
68
Bu
tyl M
eth
acry
late
A
nim
al T
oxic
olog
y Si
ngle
Dos
e –
Der
mal
: 10
cc/
kg d
id n
ot c
ause
mor
tali
ty in
rab
bits
, but
acu
te d
erm
al ir
rita
tion
was
rep
orte
d; o
ne L
D50
va
lue
of >
2000
mg/
kg in
rab
bits
was
rep
orte
d; th
e L
D50
in g
uine
a pi
gs w
as >
20 m
l/kg
O
ral;
rep
orte
d o
ral L
D50
val
ues
in r
ats
rang
ed f
rom
>20
00 to
>20
,000
mg/
kg
Inh
alat
ion:
rep
orte
d L
C50
val
ue w
as 2
8,46
9 m
g/m
3 rat
s;
68
Rep
eate
d D
ose
– O
ral:
in
rats
, the
NO
EL
S w
ere
20 m
g/kg
/day
in a
28-
day
stud
y, 3
0 (
mal
es)
and
300
(fem
ales
) m
g/kg
/day
in a
45-
day
stud
y, a
nd <
30 (
mal
es)
and
30 (
fem
ales
) m
g/kg
/day
in a
50-
day
stud
y I
nhal
atio
n: c
ause
d up
per
airw
ay ir
rita
tion
in a
28-
day
stud
y in
rat
s –
the
NO
EL
was
180
1 m
g/m
3
68
R
epro
duct
ive
and
Dev
elop
men
tal T
oxic
ity
Ora
l: a
dec
reas
e in
cor
pora
lute
a an
d im
plan
tati
ons
was
rep
orte
d in
rat
s; th
e pa
rent
al N
OA
EL
s w
ere
1000
and
300
m
g/kg
/day
for
mal
es a
nd f
emal
es, r
espe
ctiv
ely
Inha
lati
on:
thre
shol
d co
ncen
trat
ion
for
embr
yoto
xic
and
tera
toge
nic
effe
cts
in r
ats
was
0.1
mg/
m3 ; s
ligh
t fet
otox
icit
y w
as
repo
rted
in r
ats
expo
sed
to ≤
1200
ppm
on
days
6-2
0 of
ges
tati
on
68
G
enot
oxic
ity
not m
utag
enic
in m
ulti
ple
Am
es te
sts
wit
h or
wit
hout
met
abol
ic a
ctiv
atio
n; w
as m
utag
enic
to S
alm
onel
la ty
phim
uriu
m
TA
1538
wit
h m
etab
olic
act
ivat
ion
in o
ne s
tudy
68
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
- N
on-H
uman
: a
very
str
ong
sens
itiz
er in
one
stu
dy u
sing
gui
nea
pigs
; con
side
red
a m
oder
ate
sens
itiz
er in
an
othe
r st
udy
usin
g gu
inea
pig
s; in
a f
ew s
tudi
es, a
sen
sitiz
atio
n re
actio
n w
as n
ot p
rodu
ced
Hum
an:
1% c
ause
d 1
posi
tive
rea
ctio
n in
12
subj
ects
in a
Dra
ize
cont
act s
ensi
tiza
tion
stu
dy; i
n pr
ovoc
ativ
e te
stin
g, 1
%
elic
ited
posi
tive
reac
tion
s to
pat
ch te
sts
Ocu
lar:
mil
dly
irri
tati
ng to
rab
bit e
yes
68
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 66
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
37
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
D
iscu
ssio
n It
ems
(Thi
s in
gred
ient
was
rev
iew
ed f
or it
s us
e na
il e
nhan
cem
ent p
rodu
cts.
) T
he P
anel
was
con
cern
ed w
ith
the
stro
ng s
ensi
ti-
zati
on a
nd c
ross
- or
co-
reac
tivity
pot
entia
l of
met
hacr
ylat
es; h
owev
er d
ata
wer
e su
bmit
ted
that
indi
cate
d th
ere
wou
ld b
e li
ttle
mon
omer
ava
ilabl
e fo
r ex
posu
re to
the
skin
; gen
otox
icity
dat
a in
dica
ted
the
som
e m
etha
cryl
ates
cou
ld p
rodu
ce
chro
mos
ome
dam
age;
the
Pan
el r
estr
icte
d m
etha
cryl
ates
to th
e na
il, a
nd th
ey m
ust n
ot c
ome
in c
onta
ct w
ith
skin
; ini
tial
co
ncer
n th
at e
xoth
erm
s cr
eate
d fr
om th
e ra
pid
poly
mer
izat
ion
of th
e m
onom
ers
coul
d da
mag
e th
e na
il w
ere
alle
viat
ed.
68
C
IR C
oncl
usio
n (2
005)
sa
fe a
s us
ed in
nai
l enh
ance
men
t pro
duct
s w
hen
skin
con
tact
is a
void
ed;
prod
uct
s co
nta
inin
g th
is in
gred
ien
t sho
uld
be
acc
ompa
nie
d w
ith
dir
ectio
ns
to a
void
ski
n c
onta
ct, b
ecau
se o
f th
e se
nsi
tizin
g po
ten
tial
of
met
hac
ryla
tes
68
Isob
uty
l Met
hac
ryla
te
Ani
mal
Tox
icol
ogy
Sin
gle
Dos
e –
Der
mal
: th
e re
port
ed d
erm
al L
D50
was
>20
ml/
kg in
gui
nea
pigs
O
ral:
rep
orte
d L
D50
valu
es in
rat
s ra
nged
fro
m >
5000
to 1
2,80
0 m
g/kg
I
nhal
atio
n: 5
0% o
f m
ice
died
aft
er e
xpos
ure
to 2
9.74
mg/
l for
289
min
utes
; was
con
side
red
a to
xic
(but
not
hig
hly
toxi
c) s
ubst
ance
by
inha
lati
on e
xpos
ure
68
G
enot
oxic
ity
not m
utag
enic
in m
ulti
ple
Am
es te
sts
wit
h or
wit
hout
met
abol
ic a
ctiv
atio
n 68
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
- H
uman
: 1%
cau
sed
no p
osit
ive
reac
tion
in 1
1 su
bjec
ts in
a c
onta
ct s
ensi
tiza
tion
stu
dy; i
n pr
ovoc
ativ
e te
stin
g,
1% e
licit
ed p
ositi
ve r
eact
ions
to p
atch
test
s O
cula
r: m
ildl
y ir
rita
ting
to r
abbi
t eye
s
68
D
iscu
ssio
n It
ems
(Thi
s in
gred
ient
was
rev
iew
ed f
or it
s us
e na
il e
nhan
cem
ent p
rodu
cts.
) T
he P
anel
was
con
cern
ed w
ith
the
stro
ng s
ensi
ti-
zati
on a
nd c
ross
- or
co-
reac
tivity
pot
entia
l of
met
hacr
ylat
es; h
owev
er d
ata
wer
e su
bmit
ted
that
indi
cate
d th
ere
wou
ld b
e li
ttle
mon
omer
ava
ilabl
e fo
r ex
posu
re to
the
skin
; gen
otox
icity
dat
a in
dica
ted
the
som
e m
etha
cryl
ates
cou
ld p
rodu
ce
chro
mos
ome
dam
age;
the
Pan
el r
estr
icte
d m
etha
cryl
ates
to th
e na
il, a
nd th
ey m
ust n
ot c
ome
in c
onta
ct w
ith
skin
; ini
tial
co
ncer
n th
at e
xoth
erm
s cr
eate
d fr
om th
e ra
pid
poly
mer
izat
ion
of th
e m
onom
ers
coul
d da
mag
e th
e na
il w
ere
alle
viat
ed.
68
C
IR C
oncl
usio
n (2
005)
sa
fe a
s us
ed in
nai
l enh
ance
men
t pro
duct
s w
hen
skin
con
tact
is a
void
ed;
prod
uct
s co
nta
inin
g th
is in
gred
ien
t sho
uld
be
acc
ompa
nie
d w
ith
dir
ectio
ns
to a
void
ski
n c
onta
ct, b
ecau
se o
f th
e se
nsi
tizin
g po
ten
tial
of
met
hac
ryla
tes
68
Lau
ryl M
eth
acry
late
A
nim
al T
oxic
olog
y S
ingl
e D
ose
– O
ral:
no
rats
dos
ed w
ith ≤2
1.5
ml/
kg C
12-C
18 m
etha
cryl
ate
mon
omer
s di
ed
Inh
alat
ion:
the
RD
50 w
as 3
900
mg/
m3 in
mic
e
68
Rep
eate
d D
ose
– In
hala
tion
: not
toxi
c to
rat
s in
a 2
0-da
y st
udy
68
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
– N
on-H
uman
: st
rong
sen
siti
zer
in g
uine
a pi
gs
68
D
iscu
ssio
n It
ems
(Thi
s in
gred
ient
was
rev
iew
ed f
or it
s us
e na
il e
nhan
cem
ent p
rodu
cts.
) T
he P
anel
was
con
cern
ed w
ith
the
stro
ng s
ensi
ti-
zati
on a
nd c
ross
- or
co-
reac
tivity
pot
entia
l of
met
hacr
ylat
es; h
owev
er d
ata
wer
e su
bmit
ted
that
indi
cate
d th
ere
wou
ld b
e li
ttle
mon
omer
ava
ilabl
e fo
r ex
posu
re to
the
skin
; gen
otox
icity
dat
a in
dica
ted
the
som
e m
etha
cryl
ates
cou
ld p
rodu
ce
chro
mos
ome
dam
age;
the
Pan
el r
estr
icte
d m
etha
cryl
ates
to th
e na
il, a
nd th
ey m
ust n
ot c
ome
in c
onta
ct w
ith
skin
; ini
tial
co
ncer
n th
at e
xoth
erm
s cr
eate
d fr
om th
e ra
pid
poly
mer
izat
ion
of th
e m
onom
ers
coul
d da
mag
e th
e na
il w
ere
alle
viat
ed.
68
C
IR C
oncl
usio
n (2
005)
sa
fe a
s us
ed in
nai
l enh
ance
men
t pro
duct
s w
hen
skin
con
tact
is a
void
ed;
prod
uct
s co
nta
inin
g th
is in
gred
ien
t sho
uld
be
acc
ompa
nie
d w
ith
dir
ectio
ns
to a
void
ski
n c
onta
ct, b
ecau
se o
f th
e se
nsi
tizin
g po
ten
tial
of
met
hac
ryla
tes
68
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 67
Tab
le 6
. R
elev
ant s
umm
ary
info
rmat
ion
on c
ompo
nent
s (c
onti
nued
)
38
Mon
omer
Com
pone
nt
Par
amet
er E
valu
ated
O
utc
ome
Ref
eren
ce
PE
G-4
Dim
eth
acry
late
A
nim
al T
oxic
olog
y S
ingl
e D
ose
– D
erm
al:
the
LD
50 w
as >
3 g/
kg in
rat
s O
ral:
LD
50 w
as >
5000
mg/
kg in
rat
s
68
G
enot
oxic
ity
not m
utag
enic
in m
ulti
ple
Am
es te
sts
wit
h or
wit
hout
met
abol
ic a
ctiv
atio
n; w
eakl
y po
siti
ve in
a m
ouse
lym
phom
a ce
ll as
say
wit
h m
etab
olic
act
ivat
ion
68
C
arci
noge
nici
ty
Der
mal
: no
incr
ease
in s
kin
or v
isce
ral t
umor
s in
an
80-w
k st
udy
wit
h 25
mg
give
n tw
ice
wee
kly
68
Ir
rita
tion
and
Sen
siti
zati
on
Der
mal
- N
on-H
uman
: m
oder
ate
sens
itize
r in
gui
nea
pigs
; not
a s
ensi
tizer
in o
ne s
tudy
O
cula
r: m
inim
ally
irri
tati
ng to
rab
bit e
yes
68
D
iscu
ssio
n It
ems
(Thi
s in
gred
ient
was
rev
iew
ed f
or it
s us
e na
il e
nhan
cem
ent p
rodu
cts.
) T
he P
anel
was
con
cern
ed w
ith
the
stro
ng s
ensi
ti-
zati
on a
nd c
ross
- or
co-
reac
tivity
pot
entia
l of
met
hacr
ylat
es; h
owev
er d
ata
wer
e su
bmit
ted
that
indi
cate
d th
ere
wou
ld b
e li
ttle
mon
omer
ava
ilabl
e fo
r ex
posu
re to
the
skin
; gen
otox
icity
dat
a in
dica
ted
the
som
e m
etha
cryl
ates
cou
ld p
rodu
ce
chro
mos
ome
dam
age;
the
Pan
el r
estr
icte
d m
etha
cryl
ates
to th
e na
il, a
nd th
ey m
ust n
ot c
ome
in c
onta
ct w
ith
skin
; ini
tial
co
ncer
n th
at e
xoth
erm
s cr
eate
d fr
om th
e ra
pid
poly
mer
izat
ion
of th
e m
onom
ers
coul
d da
mag
e th
e na
il w
ere
alle
viat
ed.
68
C
IR C
oncl
usio
n (2
005)
sa
fe a
s us
ed in
nai
l enh
ance
men
t pro
duct
s w
hen
skin
con
tact
is a
void
ed;
prod
uct
s co
nta
inin
g th
is in
gred
ien
t sho
uld
be
acc
ompa
nie
d w
ith
dir
ectio
ns
to a
void
ski
n c
onta
ct, b
ecau
se o
f th
e se
nsi
tizin
g po
ten
tial
of
met
hac
ryla
tes
68
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 68
39
REFERENCES
1. Andersen FA (ed). Final report on the safety assessment of acrylates copolymer and 33 related cosmetic ingredients. Int J
Toxicol. 2002;21:(Suppl 3):1-50.
2. Elder RL (ed). Final report on the safety assessment of carbomers-934, -910, -934P, -940, -941, and -962. J Am Coll Toxicol. 1982;1:(2):109-141.
3. Gottschalck T.E. and Bailey, J. E. International Cosmetic Ingredient Dictionary and Handbook. Washington, DC: Personal Care Products Council, 2010.
4. Kirk-Othmer Concise Encyclopedia of Chemical Technology. 4th ed. NY: Wiley, 1999.
5. Sojka, M. and Matushek, M. New polymer technology for skin oil adsorbers and controlled release. Cosmet.Toiletries. 1999;114:(Mar):83-86, 88.
6. Lubrizol. Introducing PemulenTM polymeric emulsifiers. TDS 114. http://www.lubrizol.com/PersonalCare/Products/Pemulen/TDS.html. 2002. Date Accessed 12-7-2010.
7. Personal Care Products Council. Specification information on acrylates/C10-30 alkyl acrylate crosspolymer. 2-28-2011. Unpublished data; originally submitted by the Council on December 15, 2010, corrected version submittedon Feb. 28, 2011. (1 p) Available from CIR.
8. Personal Care Products Council. Acrylates/C10-30 Alkyl Acrylate Crosspolymer: Potential contamination with benzene. 5-9-2011. Unpublished data submitted by the Council on May 9, 2011. (1 p).
9. Dow Chemical Company. ACULYNTM 88 Polymer (Acrylates/Steareth-20 Methacrylate Crosspolymer) Global Cosmetic Dossier. Version 10. 5-2-2011. Unpublished data submitted by the Council on May 3. (12 pp).
10. Personal Care Products Council. Molecular weight, residual monomer data, and method of manufacture on acrylates/vinyl isododecanoate crosspolymer. 12-14-2010. Unpublished data submitted by the Council on Dec 14, 2010. (1 p) Available from CIR.
11. Dow Chemical Company. ACULYNTM 38 Polymer (Acrylates/Vinyl Neodecanoate Crosspolymer) Global Cosmetic Dossier. Version 5. 5-2-2011. Unpublished data submitted by the Council on May 3, 2011. (12 pp).
12. Lubrizol. Carbopol® 1382 Polymer (alkyl/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Carbopol/Carbopol1382.html. 7-17-1997. Date Accessed 12-7-2010.
13. Lubrizol. Carbopol Ultrez 21 Polymer (acrylates/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolUltrez21.html. 9-16-2003. Date Accessed 12-7-2010.
14. Lubrizol. Carbopol® Ultrez 20 polymer (acrylates/C10-30 alkyl acrylate copolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolUltrez20.html. 10-26-2006. Date Accessed 12-7-2010.
15. Lubrizol. PemulenTM TR-1 Polymeric Emulsifier (acrylates/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.essentialingredients.com/spec/Pemulen%20TR-1.pdf. 1997. Date Accessed 12-7-0010.
16. Lubrizol. PemulenTM TR-2 Polymeric Emulsifier (acrylates/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Pemulen/PemulenTR-2.html. 1997. Date Accessed 12-7-2010.
17. Lubrizol. Carbopol® ETD 2020 polymer (acrylates/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolETD2020.html. 2001. Date Accessed 12-7-2010.
18. Lubrizol. Carbopol® 1342 Polymer (acrylates/C10-30 alkyl acrylate crosspolymer) product specifications. http://www.lubrizol.com/PersonalCare/Products/Carbopol/Carbopol1342.html. 7-17-1997. Date Accessed 12-7-2010.
19. Personal Care Products Council. Benzene impurity in acrylates/C10-30 alkyl acrylate crosspolymer. 5-4-2011. Unpublishe data submitted by the Council on May 4, 2011. (1 p).
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 69
40
20. European Commission. European Commission CosIng Cosmetics Directive (v.1); Annex II/47 - benzene. http://ec.europa.eu/consumers/cosmetics/cosing/index.cfm?fuseaction=search.details&id=28884. 2009. Date Accessed 5-3-0011.
21. United States Pharmacopeial Convention. USP 32/NF 27. The Official Compendia of Standards. 2009.
22. Personal Care Products Council. Memo introducing summaries of an MSDS acute oral toxicity study, guinea pig sensitization data, an Ames assay, and a human single insult patch test, performed in 2010, on acrylate/C10-30 alkyl acrylate crosspolymer. 2-11-2011. Unpublished data submitted by the Council on Feb. 11, 2011. (2 pp) Available from CIR.
23. Personal Care Products Council. Memo introducing summaries of a dermal irritation study, ocular irritation study, and a human single insult patch test, performed in 2004, on acrylates crosspolymer. 2-11-2011. Unpublished data submitted by the Council on Feb. 11, 2011. (2 pp) Available from CIR.
24. Personal Care Products Council. Memo introducting an HRIPT of a lipstick containing 4% acrylates crosspolymer. 2-22-2011. Unpublished data submitted by the Council on Feb 22, 2011. (1 p) Available from CIR.
25. Personal Care Products Council. Memo introducting HRIPTs on bubble bath and bath and shower foam containing 2% acrylates/vinyl neodecanoate crosspolymer. 2-4-2011. Unpublished data submitted by the Council on Feb. 4, 2011. (1 p) Available from CIR.
26. Personal Care Products Council. Memo introducing studies ona face powder containing 1% lauryl methacrylate/glycol dimethacrylate crosspolymer (product tested as used). 2-7-2011. Unpublished data submitted by the Council on Feb. 7, 2011. (1 p) Available from CIR.
27. Sumitomo Seika. Cosmetic grade AquaKeep 10SH-NFC (Sodium Acrylates Crosspolymer-2). 11-24-2010. Unpublished data submitted by the Personal Care Products Council on Nov. 30, 2010. (1 p). Available from CIR.
28. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA Database. 2011. Washington, DC: FDA.Updated Feb 25.
29. Personal Care Products Council. Updated concentration of use by FDA product category: Acrylates Crosspolymer Ingredients. 1-28-2011. Unpublished data submitted by the Council on Jan. 28, 2011. (5 pp) Available from CIR.
30. European Commission. European Commission Health and Consumers Cosmetics - Cosing - Database. http://ec.europa.eu/consumers/cosmetics/cosing/. 2010. Date Accessed 11-30-2010.
31. Personal Care Products Council. Comments on the Scientific Literature Review on Crosslinked Alkyl Acrylates. 2011. Memorandum received from the Personal Care Products Council on Jan 20, 2011. (2 pp) Available from CIR.
32. Qiu, H., Mccall, J. W., and Jun, H. W. Formulation of topical insect repellent N,N-diethyl-m-toluamide (DEET): Vehicle effects on DEET in vitro skin permeation. International Journal of Pharmaceutics (Amsterdam). 1998;163:(1-2):167-176.
33. Lubrizol. Material safety data sheet for Pemulen (TM) TR-1 NF Polymer (acrylates/C10-30 alkyl acrylate crosspolymer). http://online.lubrizol.com/msds/MSDSDisplay.aspx?L=941&c=1942&p=PEM1005. 11-20-2010. Date Accessed 12-9-2010.
34. 3V Sigma. Toxicological summary review on acrylates/vinyl isododecanoate crosspolymer. 2010. Unpublished data submitted by the Council on Dec 14, 2010. (3 pp) Available from CIR.
35. Sumitomo Seika Chemicals Co. Material safety data sheet on Aqua Keep 10SH-NFC (Sodium Acrylates Crosspolymer-2). 1-11-2010. Unpublished data submitted by the Personal Care Products Council on Nov. 30, 2010. (5 pp). Available from CIR.
36. Institute for In Vitro Sciences, Inc. Topical application ocular irritation screening assay using the epiocular human cell construct on a facepowder containing 1% lauryl methacrylate/glycol dimethacrylate crosspolymer. Study no. 09AC65, 03AA05.015001. Laboratory project no. 5463. 4-20-2009. Unpublished data submittd by the Council on Feb. 7, 2011. (10 pp) Available from CIR.
37. Lubrizol. Carbopol® ETD polymer (acrylates/C10-30 alkyl acrylate crosspolymer) toxicology studies. TOX-003. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolETD2020.html. 1996. Date Accessed 12-7-2010.
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 70
41
38. Lubrizol. Carbopol® Ultrez 21 polymer (acrylates/C10-30 alkyl acrylate crosspolymer) toxicology studies. TOX-023. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolUltrez21.html. 7-10-2002. Date Accessed 12-7-2010.
39. Lubrizol. Carbopol® Ultrez 20 polymer (acrylates/C10-30 alkyl acrylate crosspolymer) toxicology studies. TOX-080. http://www.lubrizol.com/PersonalCare/Products/Carbopol/CarbopolUltrez20.html. 2-5-2004. Date Accessed 12-7-2010.
40. Lubrizol. Toxicology/regulatory/health, safety & environmenal studies of Pemulen polymer emulsifiers. TOX-007. http://www.lubrizol.com/PersonalCare/Products/Pemulen/PemulenTR-2.html. 7-15-2003. Date Accessed 12-7-2010.
41. CAS Registry Online Database. 2010.
42. CosPharm Inc. Product characeteristics of Poly-Pore L200 (Allyl Methacrylates Crosspolymer). http://www.cospharm.com/chemdal/p1200.htm. 2011. Date Accessed 1-19-2011.
43. CosPharm Inc. Product characteristics of Poly-Pore E200 (Allyl Methacrylates Crosspolymer). http://www.cospharm.com/chemdal/pe200.htm. 2011. Date Accessed 1-19-2011.
44. Personal Care Products Council. Comments on the draft report on crosslinked alkyl acrylates prepared for the March 3-4, 2011 CIR Expert Panel meeting. 2-28-2011. Submitted by the Council on FEb. 28, 2011. (1 p) Available from CIR.
45. Consumer Product Testing Co. Final report on a repeated insult patch test of a body lotion containing 0.15% acrylates/C10-30 alkyl acrylate crosspolymer. Exp. Ref. No. C09-1109.01. 5-1-2009. Unpublished data submitted by the Council on Jan 11, 2011. (9 pp) Available from CIR.
46. Consumer Product Testing Co. Final report on a repeated insult patch test on a crème to powder foot crème containing 0.60% acrylates C10-30 alkyl acrylate crosspolymer. Exp. Ref. No. C10-0602.01. 2010. Unpublished data submitted by the Council on Jan 11, 2011. (7 pp) Available from CIR.
47. Personal Care Products Council. Summaries of HRIPTs on products containing acrylates crosspolymer. 2-7-2011. Unpublished data submitted by the Council on Feb. 7, 2011. (1 p) Available from CIR.
48. Consumer Product Testing Co. Repeated insult patch test of a lipstick containing 4% acrylates crosspolymer. Experiment Ref. nO. c07-3553.01. 2007. Unpublished data submitted by the Council on Feb. 22, 2011. (13 pp) Available from CIR.
49. Orentreich Research Corporation. Predictive patch test study on a face powder + SPF containing 6.8565% acryaltes/ethylhexyl acrylate crosspolymer. 2005. Unpublished data received from the Council on Feb. 8, 2011. (27 pp) Available from CIR.
50. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath creme containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL81207-15. 8-3-2007. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
51. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath creme containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL148107-4. 12-21-2007. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
52. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bubble bath formulation containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL62208-14. 7-11-2008. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
53. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath gel containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL69608-15. 8-1-2008. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
54. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath product containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL75208-6. 8-8-2008. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
55. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath and shower foam containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL43409-8. 7-10-2009. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 71
42
56. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath and shower foam containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL43409-9. 7-10-2009. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
57. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bath and shower foam containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL43409-10. 7-10-2009. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
58. Clinical Research Laboratories, Inc. Final report of a repeated insult patch test on a bubble bath formulation containing 2% acrylates/vinyl neodecanoate crosspolymer. CRL study no. CRL31010-15. 6-11-2010. Unpublished data received from the Council on Feb. 4, 2011. (13 pp) Available from CIR.
59. TKL Research. Summary report on a repeated insult patch rest of a face powder containing 1% lauryl methacrylate/glycol dimethacrylate crosspolymer. TKL study no. DS102909-9. 5-20-2009. Unpublished data submittd by the Council on Feb. 7, 2011. (19 pp) Available from CIR.
60. Orentreich Research Corporation. Repeated insult patch test of an exfoliating facial mask containing 2.6% lauryl methacrylate/glycol dimethacrylate crosspolymer. 9-17-2008. Unpublished data submittd by the Council on Feb. 8, 2011. (33 pp) Available from CIR.
61. International Agency for Research on Cancer. Acrylic acid. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-60.pdf. 1987. Date Accessed 1-21-2011.
62. International Agency for Research on Cancer. Methyl acrylate. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-104.pdf. 1987. Date Accessed 1-21-2011.
63. International Agency for Research on Cancer. Ethyl acrylate. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-99.pdf. 1987. Date Accessed 1-21-2011.
64. International Agency for Research on Cancer. n-Butyl acrylate. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-14.pdf. 1987. Date Accessed 1-21-2011.
65. International Agency for Research on Cancer. 2-Ethylhexyl acrylate. http://monographs.iarc.fr/ENG/Monographs/vol60/mono60-19.pdf. 1994. Date Accessed 1-21-2011.
66. Andersen FA (ed). Final report on the safety assessment of methacrylic acid. Int J Toxicol. 2005;24:(Suppl 5):33-51.
67. International Agency for Research on Cancer. Methyl methacrylate. http://monographs.iarc.fr/ENG/Monographs/vol60/mono60-18.pdf. 1994. Date Accessed 1-21-2011.
68. Andersen FA (ed). Final report of the safety assessment of methacylate ester monomers used in nail enhancement products. Int J Toxicol. 2005;24:(Suppl 5):53-100.
69. Becker LC, Berfgeld WF, Belsito DV, Klaassen CD, Liebler DC, Hill RA, Marks JG, Shank RC, Slaga TJ, Snyder PW, and Andersen FA. Final report of the CIR Expert Panel on the safety assessment of polymethyl methacrylate (PMMA), methyl methacrylate crosspolymer, and methyl methacrylate/glycol dimethacrylate crosspolymer. 11-15-2010. Available from CIR, 1101 17th St, NW, Ste 412, Washington, DC 20036 www.cir-safety.org.
Distributed for Comment Only - Do Not Cite or Quote
CIR Panel Book Page 72
TO:
iProducts Council
F. Alan Andersen, Ph.D.Director - COSMETIC INGREDIENT REVIEW (CW)
Committed to Safety,Quality & Innovation
FROM:
DATE:
John Bailey, Ph.D.Industry Liaison to the CIR Expert Panel
July 5,2011
SUBJECT: Concentration of Use: Methacrylic AcidIPEG-6 Methacrylate/PEG-6 DimethacrylateCrosspolymer
Methacrylic AcidIPEG-6 Methacrylate/PEG-6 Dimethacrylate Crosspolymer was included in aconcentration of use survey. No uses of this ingredient were reported.
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Personal Care
Memorandum
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CIR Panel Book Page 73
Persona Care Products CouncilCommitted to Safety,Quality & Innovation
Memorandum
TO: F. Alan Andersen, Ph.D.Director - COSMETIC E’4GREDIENT REWEW (CJR)
FROM: John Bailey, Ph.D.Industry Liaison to the CIR Expert Panel
DATE: July 21, 2011
SUBJECT: Comments on the Tentative Safety Assessment on Crosslinked Alkyl Acrylates as usedin Cosmetics
Although the disclaimer on the CW website (“Tentative reports are distributed for comment only -- donot cite.”) is helpful, it should be on every page of draft CIR reports.
p.1, Abstract - As benzene is a carcinogen, it is not appropriate to complete a margin of safetycalculation. It would be better to state that a risk assessment should be completed.
p.2-3 - Please include USP limits (found in John Krowka’ s office) for benzenc, Carbomer 1342 (0.2%)and other Carbomer ingredients manufactured with the use of benzene (Cabomer 934, 934P,940, 941) (0.5%).
p.5 - The observation that Sodium Acrylates Crosspolymer-2 is not a vaginal mucosa irritant in dogsshould not be in the ocular irritation section.
p.S - Is it necessary to have two subsections under Industrial Exposure limits? Perhaps it should statethat there are no exposure limits established for any of the ingredients in this report and thatMSDs for Acrylates/C10-30 Alkyl Acrylate Crosspolymer and Sodium AcrylatesCrosspolymer-2 suggest that a limit of 0.05 mg/m3 for respirable polyacrylate dusts isapplicable to these compounds.
p.5 - The following, which starts the Summary section, does not make sense: “The crosslinked alkylacrylates are crosslinked polymers are very large molecules....”
p.5 - As Acrylates/C10-30 Alkyl Acrylate Crosspolymer has the highest number of reported uses, itwould be helpful to include the highest concentration of use of this ingredient in the Summary
p.S - In the Summary, please include some indication of the concentrations of the crosspolymeringredients that were not irritating or sensitizing.
p.6 - The maximum use concentration of 6% was for Acrylates/Ethylhexyl Acrylate Crosspolymer inan eye shadow. There is no information to indicate that benzene is used as a solvent in themanufacture of this ingredient. Therefore, it is inappropriate to use 6% to calculate a benzenelevels in a product. As one trade name material with the INCI name Acrylates/C 10-30 AlkylAcrylates Crosspolymer is reported to be made with benzene, the maximum concentration ofAcrylates/C10-30 Alkyl Acrylates Crosspolymer should be used. The Council is working to
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clarify which concentration of use values are actually for the ingredient made with benzene as asolvent.
p.6 - As benzene is a carcinogen, a risk assessment should be completed rather than a margin of safetycalculation. It is not appropriate to imply that there is a NOAEL for the carcinogenic effects ofbenzene.
2
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Personal Care Products CouncilCommitted to Safety,Quality & Innovation
Memorandum
TO: F. Alan Andersen, Ph.D.Director - COSMETIC INGREDIENT REVIEW (CIR)
FROM: John Bailey, Ph.D.JZ_ (,_ zq — I
Industry Liaison to the CW Expert Panel
DATE: June 24, 2011
SUBJECT: Comments on the Draft Report on Crosslinked Alkyl Acrylates as used in CosmeticsPrepared for the June 27-28, 2011 CIR Expert Panel Meeting
Cover - This draft of the Crosslinked Alkyl Acrylates report should not be considered the TentativeReport. Depending on the outcome of the June meeting, the tentative report should be the draftprepared after the June meeting. The comment period should begin when the post meetingdraft is available. The date needs to be changed from 2010 to 2011.
p.1 (and throughout the report) - Methacrylic AcidJPEG-6 Methacrylate/PEG-6 DimethacrylateCrosspolymer is the colTect name for Methacrylic AcidJPEG-6 Methacrylate Crosspolymer.Please see the attached mongraph proof of the completed monograph for this ingredient.
p.1 - In the Introduction, it would be helpful to also mention the CW report on Carbomer that has a safeas used conclusion.
p.1 - If true, please note that the information on monomers is from previous CIR reports on monomers.p.2 - In the Physical and Chemical Properties section, it would be helpful to note that these are large
molecular weight compounds and give an example of molecular weights and particle sizes.p.7 - Please include the concentration/dose of Acrylates/C10-30 Alkyl Acrylates Crosspolymer that was
a weak irritant in the intensified Shelanski HRIPT.p.8 - The Summary should also include n-hexane as a solvent.p.8 - In the Summary, it would be helpful to state that based on the large size of these compounds,
dermal penetration is unlikely.p.9 - The following sentence should be deleted. “The Panel indicated that confidence in these
assumptions would be bolstered by data from well-conducted absorption/penetration studies on,for example, mucous membranes, tape-stripped skin or the gastrointestinal tract.” There is norecord in the transcript that the CW Expert Panel asked for this additional information. Basedon the information in the report, these molecules are so large (based on molecular weight andlorparticle size) there is no potential for dermal absorption. In the Discussion, it would beappropriate for the Cifi Expert Panel to acknowledge that molecular weight information wasnot available for all compounds, and that it is expected that molecular weights of all thecompounds in the report are much greater than 1000 daltons. If a compound has a molecularweight of 1000 or less, dermal penetration data would be helpful.
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p.9 - Benzene is not monomer, it is a solvent. If a product contained 6% Acrylates/ClO-30 AlkylAcrylates Crosspolymer that contained a maximum of 0.5% benzene, it would contain (0.005 x6% = 0.03%) 0.03% benzene (not 0.003% as stated in the report).
p.25, Table 4a - “Lauryl Methacrylate/Sodium Methacrylate Copolymer” needs to be changed to“Lauryl Methacrylate/Sodium Methacrylate Crosspolymer”
p.28-29, Table 5 - Please define GCP.
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CIR Panel Book Page 77
06/06/2011
Monograph Proof
25230: METHACRYLIC ACID/PEG-6METHACRYLATE/PEG-6DIMETHACRYLATE CROSSPOLYMER.
INCI Monograph ID: 25230
Flags: ReadyToPublish,UnderDevelopment
Definition: Methacrylic Acid/PEG-6Methacrylate/PEG-6 DimethacrylateCrosspolymer. is a copolymer of methacrylicacid and PEG-6 methacrytate crosslinkedwith PEG-6 dimethacrylate.
Chemical Class: C942- Synthetic Polymers
Reported Function: F340- Film Former
Ingredient Source: Synthetic
Trade Name Mixtures:N97208- Nabion Anti-Wrinkle Complex
LabO2 (S9202- Nabion Co.)N97209- Nabion Whitening Complex LabOl
(S9202- Nabion Co.)
International Cosmetic Ingredient Dictionary and Handbook Monograph Proof • 1
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CIR Panel Book Page 78
ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 01A - Baby ShampoosACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 6 01B - Baby Lotions, Oils, Powders, and CreamsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 3 01C - Other Baby ProductsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 02A - Bath Oils, Tablets, and Salts 111ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 7 02B - Bubble BathsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 10 02D - Other Bath PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 13 03B - EyelinerACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 03C - Eye ShadowACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 60 03D - Eye LotionACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 12 03E - Eye Makeup RemoverACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 5 03F - MascaraACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 41 03G - Other Eye Makeup PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 2 04B - Perfumes 70ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 36 04E - Other Fragrance PreparationACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 4 05A - Hair Conditioner 77ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 05B - Hair Spray (aerosol fixatives)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 19 05F - Shampoos (non-coloring)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 34 05G - Tonics, Dressings, and Other Hair Grooming AidsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 05H - Wave SetsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 17 05I - Other Hair PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 06F - Hair Lighteners with ColorACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 9 06G - Hair BleachesACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 06H - Other Hair Coloring PreparationACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 8 07C - FoundationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 3 07E - LipstickACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 5 07F - Makeup BasesACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 9 07I - Other Makeup PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 3 08B - Cuticle SoftenersACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 2 08C - Nail Creams and LotionsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 4 08G - Other Manicuring PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 56 10A - Bath Soaps and DetergentsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 10B - Deodorants (underarm)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 1 10C - DouchesACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 33 10E - Other Personal Cleanliness ProductsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 65 11A - Aftershave LotionACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 2 11D - Preshave Lotions (all types)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 2 11E - Shaving CreamACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 18 11G - Other Shaving Preparation ProductsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 131 12A - CleansingACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 234 12C - Face and Neck (exc shave)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 244 12D - Body and Hand (exc shave)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 366 12F - MoisturizingACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 61 12G - NightACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 22 12H - Paste Masks (mud packs)ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 7 12I - Skin FreshenersACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 104 12J - Other Skin Care PrepsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 9 13A - Suntan Gels, Creams, and LiquidsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 13 13B - Indoor Tanning PreparationsACRYLATES/C10-30 ALKYL ACRYLATE CROSSPO 8 13C - Other Suntan Preparations 1,696
ACRYLATES CROSSPOLYMER 2 12C - Face and Neck (exc shave)
ACRYLATES/VINYL ISODECANOATE CROSSPOLY 1 11D - Preshave Lotions (all types)ACRYLATES/VINYL ISODECANOATE CROSSPOLY 7 12A - CleansingACRYLATES/VINYL ISODECANOATE CROSSPOLY 3 12C - Face and Neck (exc shave)ACRYLATES/VINYL ISODECANOATE CROSSPOLY 5 12D - Body and Hand (exc shave)ACRYLATES/VINYL ISODECANOATE CROSSPOLY 12 12F - MoisturizingACRYLATES/VINYL ISODECANOATE CROSSPOLY 2 12G - NightACRYLATES/VINYL ISODECANOATE CROSSPOLY 3 12J - Other Skin Care Preps
ACRYLATES/VINYL NEODECANOATE CROSSPOLY 1 02B - Bubble Baths 6ACRYLATES/VINYL NEODECANOATE CROSSPOLY 1 02D - Other Bath Preparations
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ACRYLATES/VINYL NEODECANOATE CROSSPOLY 1 10A - Bath Soaps and DetergentsACRYLATES/VINYL NEODECANOATE CROSSPOLY 3 10E - Other Personal Cleanliness ProductsACRYLATES/VINYL NEODECANOATE CROSSPOLY 3 12F - MoisturizingACRYLATES/VINYL NEODECANOATE CROSSPOLY 1 12J - Other Skin Care Preps
ALLYL METHACRYLATES CROSSPOLYMER 3 03C - Eye Shadow 31ALLYL METHACRYLATES CROSSPOLYMER 1 03F - MascaraALLYL METHACRYLATES CROSSPOLYMER 1 04E - Other Fragrance PreparationALLYL METHACRYLATES CROSSPOLYMER 1 07A - Blushers (all types)ALLYL METHACRYLATES CROSSPOLYMER 2 07B - Face PowdersALLYL METHACRYLATES CROSSPOLYMER 16 07E - LipstickALLYL METHACRYLATES CROSSPOLYMER 1 07F - Makeup BasesALLYL METHACRYLATES CROSSPOLYMER 1 07I - Other Makeup PreparationsALLYL METHACRYLATES CROSSPOLYMER 2 12A - CleansingALLYL METHACRYLATES CROSSPOLYMER 5 12C - Face and Neck (exc shave)ALLYL METHACRYLATES CROSSPOLYMER 4 12F - MoisturizingALLYL METHACRYLATES CROSSPOLYMER 1 12G - NightALLYL METHACRYLATES CROSSPOLYMER 2 12H - Paste Masks (mud packs)ALLYL METHACRYLATES CROSSPOLYMER 7 12J - Other Skin Care PrepsALLYL METHACRYLATES CROSSPOLYMER 1 13B - Indoor Tanning Preparations
LAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 03B - Eyeliner 53LAURYL METHACRYLATE/GLYCOL DIMETHACRYL 6 03C - Eye ShadowLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 03F - MascaraLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 03G - Other Eye Makeup PreparationsLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 2 07A - Blushers (all types)LAURYL METHACRYLATE/GLYCOL DIMETHACRYL 8 07B - Face PowdersLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 20 07C - FoundationsLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 8 07E - LipstickLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 3 07I - Other Makeup PreparationsLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 08G - Other Manicuring PreparationsLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 10B - Deodorants (underarm)LAURYL METHACRYLATE/GLYCOL DIMETHACRYL 4 12A - CleansingLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 12C - Face and Neck (exc shave)LAURYL METHACRYLATE/GLYCOL DIMETHACRYL 2 12F - MoisturizingLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 1 12G - NightLAURYL METHACRYLATE/GLYCOL DIMETHACRYL 3 12H - Paste Masks (mud packs)
LAURYL METHACRYLATE/SODIUM METHACRYLAT 1 12F - Moisturizing
SODIUM ACRYLATES/C10-30 ALKYL ACRYLATE C 1 04E - Other Fragrance PreparationSODIUM ACRYLATES/C10-30 ALKYL ACRYLATE C 1 11A - Aftershave LotionSODIUM ACRYLATES/C10-30 ALKYL ACRYLATE C 4 12F - Moisturizing
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