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Safety Assessment of
Polyquaternium-22 and Polyquaternium-39 as Used in Cosmetics

Status: Draft Final Report for Panel Review


Release Date: August 16, 2013
Panel Meeting Date: September 9-10, 2013

The 2013 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V.
Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A Hill, Ph.D. James G. Marks, Jr., M.D.; Ronald
C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A.
This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist.

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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Commitment & Credibility since 1976

Memorandum

To: CIR Expert Panel Members and Liaisons


From: Wilbur Johnson, Jr.
Senior Scientific Analyst
Date: August 16, 2013
Subject: Draft Final Report on Polyquaternium-22 and Polyquaternium-39

After reviewing the available data on these ingredients at the June 10-11, 2013 CIR Expert Panel meeting, the Panel issued
a tentative safety assessment for public comment with the conclusion that Polyquaternium-22 and Polyquaternium-39 are
safe in the present practices of use and concentration in cosmetics. The basis for this conclusion is stated in the CIR Report
History. Comments on the tentative report were received from the Personal Care Products Council.

Included for your review is the Draft Final Report, the CIR report history, Literature search strategy, Ingredient Data
profile, 2013 FDA VCRP data, Minutes from the June 10-11, 2013 Panel meeting, and comments on the tentative report
that were received from the Council (pcpc1 pdf file).

After reviewing the available data, the Panel needs to determine whether a final report on polyquaternium-22 and
polyquaternium-39 with a conclusion stating that these ingredients are safe in the present practices of use and concentration
should be issued.

__________________________________________________________________________________________
1101 17th Street, NW Suite 412, Washington, DC 20036
(Main) 202-331-0651 (Fax) 202-331-0088
(Email) cirinfo@cir-safety.org (Website) www.cir-safety.org
Distrbuted for comment only -- do not cite or quote
Distrbuted for comment only -- do not cite or quote

CIR History of:

Polyquaternium-22
Polyquaternium-39

A Scientific Literature Review (SLR) Notice was announced on August 11, 2011, and unpublished data from the
Personal Care Products Council (Council) were received during the 60-day comment period.

Draft Report, Belsito and Marks Teams/Panel: December 12-13, 2011

The SLR (now a draft report) was revised to include the following unpublished data received from the Council:

1. Summary information on studies of an oxidative hair dye containing 0.16% Polyquaternium-22


submitted on 10-21-2011;
2. Use concentration data on Polyquaternium-22 and Polyquaternium-39 from Council survey
submitted on 10-25-2011

The Panel tabled the draft report on polyquaternium-22 and polyquaternium-39, with the expectation that the report
would be expanded to include other polyquaternium ingredients. The Expert Panel also requested that industry
provide information on the acrylamide monomer content of polyquaternium-22 and polyquaternium-39.

Draft Report, Belsito and Marks Teams/Panel: June 10-11, 2013

In December of 2012, a memorandum from the CIR Director (pcpc1 pdf file) emphasizing the importance of having
a residual monomer/polymerization profile available on each of the 108 polyquaternium ingredients identified in the
International Cosmetic Ingredient Dictionary and Handbook was sent to the CIR Science and Support Committee,
FDA, and the Consumer Federation of America.. This letter was sent with the understanding that these data would
allow CIR to approach the concept of group expansion with complete information available. In response, a letter
from the CIR Science and Support Committee (pcpc2 pdf file) was received, stating that the information provided in
the memorandum is not sufficient for evaluation of the proposed grouping of all polyquaternium ingredients into one
report, or to determine whether a read-across approach for the ingredients is appropriate.

The Draft Report has been revised to include the following data on polyquaternium-22/polyquaternium-39 trade
name materials received from the Council: chemistry, acute oral toxicity, ocular irritation, dermal irritation
(animal), genotoxicity, and skin irritation and sensitization (human). These data were included in the Wave 2 data
submission prior to the December 2011 Panel meeting.

After reviewing the available data, the CIR Expert Panel issued a tentative safety assessment for public comment
with the conclusion that Polyquaternium-22 and polyquaternium-39 are safe in the present practices of use and
concentration in cosmetics.

Relevant residual monomer data on polyquaternium,-22 and polyquaternium-39 were provided at this meeting, and
the unreacted monomers content was considered low and below the level of toxicologic concern. Acrylic acid (< 50
ppm or < 1000 ppm) and dimethyldiallyl ammonium chloride (<1% or < 2%) were detected in both polymers, but
acrylamide monomer (< 1 ppm) was only detected in polyquaternium-39. The Panel acknowledged that there were
data gaps for both ingredients, including no available skin sensitization data on polyquaternium-22. However, it was
agreed that these polymers are large, highly polar molecules that would not be absorbed. Furthermore, though
dermal absorption is not likely, the Panel noted that concern over skin irritation/sensitization potential is not
warranted based on the negative skin irritation data on polyquaternium -22 and polyquaternium-39, and the negative
skin sensitization data on polyquaternium-39 that were provided.

Draft Final Report, Belsito and Marks Teams/Panel: September 9-10, 2013

Comments on the tentative report that was announced were received.


Distrbuted for comment only -- do not cite or quote
Distrbuted for comment only -- do not cite or quote

Polyquaternium-22 and Polyquaternium-39 Checklist for September, 2013. Analyst Wilbur Johnson
Repeated dose
Acute toxicity Irritation Sensitization
toxicity

Penetration
Skin

Enhancement
Penetration

ADME

Oral

Parenteral

Dermal

Inhale

Oral

Parenteral

Dermal

Inhale

Irritation
Ocular

Animal
Dermal Irr.

Human
Dermal Irr

Animal
Sensitization

Human
Sensitization

toxicity
Repro/Devel

Genotoxicity
y
Carcinogenicit

Phototoxicity
Polyquaternium-22 X X X X X
Polyquaternium-39 X X X X X
Distrbuted for comment only -- do not cite or quote

Ingre- Toxline ChemIDplus Multidatabase DART SciFinder RTECS


dients &PubMed (See legend*)
P-22 0 0 0 141 0
P-39 0 0 0 146 0
*Data in Table: Publications found; Multidatabase = HSDB, CCRIS, ITER, IRIS,
Gene-Tox, and LacMed

Searches Performed on7/28/2011


Search updated on 11/7/2011 using PubMed, Toxline, and SciFinder
Search updated on 5/3/2013 SciFinder
Search updated on 6/27/2013

INGREDIENTS
Polyquaternium-22 (P-22)
Acrylic Acid-Diallyldimethylammonium Chloride Polymer
53694-17-0

Polyquaternium-39 (P-39)
Acrylic Acid, Polymer with Acrylamide and Diallyldimethylammonium Chloride
2-Propen-1-aminium, N,N-Dimethyl-N-2-Propenyl-. Chloride, Polymer with 2-Propenamide and 2-Propenoic Acid
25136-75-8

Search Strings (NLM databases)

Polyquaternium-22 OR Acrylic Acid-Diallyldimethylammonium Chloride Polymer OR 53694-17-0

Polyquaternium-39 OR Acrylic Acid, Polymer with Acrylamide and Diallyldimethylammonium Chloride OR


25136-75-8

SciFinder Search Terms

Polyquaternium-22
Polyquaternium-39
Distrbuted for comment only -- do not cite or quote

Day 1 of the June 10-11, 2013 CIR Expert Panel Meeting Dr. Belsitos Team

Polyquaternium-22 and Polyquaternium-39

DR. BELSITO: Moving along, polyquat-22 and -39.


DR. ANDERSEN: We also got Wave 3 data on this.
DR. BELSITO: Yes. So we have no absorption data, and I thought that would
be nice except that Wave 3 suggests that acrylamide levels are low in both polyquat-22 and
polyquat-39.
DR. ANDERSEN: Acrylamide is not a monomer for -22.
DR. BELSITO: Right, okay. So is absorption an issue? Regardless, we don't
have sensitization at use concentration for polyquaternium-22. And I guess I had a question for
Wilbur because I couldn't find the hard data. The sensitization data that we have for
polyquaternium-39 as written would imply to me that that was neat, 100 percent, and I just want to
verify that.
And we also have only two Ames tests. We have no mammalian genotoxicity
and did that bother that along with a lack of absorption bother my teammates? That's all I had.
DR. LIEBLER: I think a lack of absorption is the dominant characteristic here.
These are huge molecules, large polar.
DR. BELSITO: So absorption not likely, large and polar? Impurities we're
okay with based upon Wave 3?
DR. LIEBLER: Wave 3, yes.
DR. BELSITO: Polyquaternium-22 use concentration and sensitization and
mammalian genotox, are you concerned for lack of that?
DR. LIEBLER: Not really in something that's this big and not going to be
absorbed.
DR. BELSITO: Cutaneous question genicity?
DR. KLAASSEN: It's not going to get into cells.
DR. BELSITO: Okay.
DR. LIEBLER: I really don't think so. I'm trying to remember the last time the
discussion -- I'm not sure if I'm remembering this right, but I think the Marks Team wasn't really
particularly concerned about that either. I was looking to see what Tom Slaga might have thought.
DR. BRESLAWEC: And this is one of those ingredients -- I think you've
mentioned some of them, but there's a decently long list of things where there is no data for them.
DR. LIEBLER: Right.
DR. BRESLAWEC: And for some of them it's for particular chain lengths, but
for some of them it seems to be broader.
DR. BELSITO: I'm not following you because we decided to limit it to just -22
and - 39.
DR. SNYDER: Yes, so there's just --
DR. BELSITO: So there's just two now.
DR. BRESLAWEC: So I guess for both of them then there's no absorption,
which we've been discussing and other things, too.
DR. BELSITO: And we have no animal or human sensitization for
polyquaternium- 22? I mean it hasn't been reported in the literature that I'm aware of to be an
issue. So lack of clinical reports, we've used that before.
DR. LIEBLER: In the discussion last time I think we were more concerned
about the monomer impurities and there was a question of whether acrylamide was a monomer
impurity or a monomer precursor to I think it's polyquat-22.
DR. BELSITO: Right, well we now know --
DR. LIEBLER: Polyquaternium-22, but it's not. I mean the Wave 3 data
indicates that. Acrylic acid is much less of an issue in terms of its reactivity, toxicity, and
carcinogenicity. And the levels of the monomeric products, the impurities, are low.
DR. BELSITO: So safe as used?
DR. LIEBLER: Yes.
DR. KLAASSEN: Yes.
Distrbuted for comment only -- do not cite or quote

DR. LIEBLER: It's a minor point, though, Wilbur, on the chemical structures.
It looked like there were a couple of pasted-in pictures from a couple of different sources. And
maybe what we should do is just, since we have the capability to draw those structures with the
same software, let's just redraw them and use them for the report from here on.
DR. BELSITO: So safe as used, and then in the discussion large and polar and
not likely to be absorbed to any significant extent. So lack of the mammalian genotox repro data
is not an issue for these.
DR. LIEBLER: Right.
DR. BELSITO: Got all that, Wilbur?
MR. JOHNSON: Yes.
DR. BELSITO: Other comments, questions? If not, chamomile, another botanical.
Distrbuted for comment only -- do not cite or quote

Day 1 of the June 10-11, 2013 CIR Expert Panel Meeting Dr. Marks Team

Polyquaternium-22 and Polyquaternium-39

DR. MARKS: You're welcome. Okay. Next ingredient is the polyquats,


polyquaternium 22 and 39. So, Wilbur, you didn't change the title on me, did you, on this one
then? Put something in there that wasn't in the memo?
Okay. So in December of 2011, the Panel tabled the draft report on
polyquaternium 22 and 39, with the expectations it would be expanded. Then there was concern
about unreacted monomers. Then we found out from industry that data on the monomers would
not be available for this expanded group, so we're at the point -- in our group we were going to go
with "safe conclusion" in December. There are large molecules not absorbed. The skin tox was
okay even if there was a residual monomer. We had the data to support that. We won't get the
monomer levels from the expanded group.
And I thought we'd issue a tentative report just where the 22 and the 39 were the
safe conclusions, so limit it to those two ingredient.
DR. SHANK: I agree.
DR. MARKS: We don't have Tom here, so I'll wait for Tom to come back.
Yeah, just got a memo this morning. Is there anything in there that will change that, Wilbur?
MR. JOHNSON: I don't think so.
DR. MARKS: There was a memo this morning?
MR. JOHNSON: Yes.
DR. HILL: On page -- from Halyna.
DR. MARKS: So unreacted monomers, acrylic acid, less than 1,000 parts per
million. So these are the residual monomers in 22 and 39. Is there anything that wouldn't -- to
me, the residual is still that we have safety testing to indicate that it's not a significant sensitizer
irritant, even if there's some residual monomer in that, ingredients that were tested.
So, Tom, what -- it would appear that we're going to limit the safety report on
polyquaternium 22 and the 39, and issue a tentative report with "safe." Ron Shank thinks that's
fine. Ron Hill, is that okay with you?
DR. HILL: I think it is. The only note I'd add here was that we really have no
real repeated toxicology at all, but then that's really only a concern if people didn't keep those
worrisome monomer levels down. And we're looking at less than one ppm per acrylamide, less
than 50 for dimethyl diallyl. So that's typical.
DR. MARKS: So, Tom, okay? Let's see, so it would be a tentative report with a
conclusion "safe." Sound good?
DR. SHANK: Good, uh-uh.
DR. MARKS: Any other discussion?
(No response.)
Distrbuted for comment only -- do not cite or quote

Day 2 of the June 10-11, 2013 CIR Expert Panel Meeting Full Panel

Polyquaternium-22 and Polyquaternium-39

DR. MARKS: So in December of 2011, a year and a half ago or so, we tabled
this report. Part of that was the -- look at the expanded list of polyquaternium ingredients and deal
with the un-reactive monomers. We found out that we would not get monomer levels from the
expanded group of polyquats. So our team felt we could move forward with a tentative safety
report on just two ingredients, the 22 and 39 with a safe conclusion.
DR. BERGFELD: That's a motion. Is there a second?
DR. BELSITO: Well, our team briefly discussed that we really didn't have
sensitization at use concentration for a polyquaturnium 22. I didn't think it was an issue, but just
want to give my panel members a chance to voice their opinion before I second your motion.
DR. BERGFELD: Dan, Paul, Kurt?
DR. MARKS: I'll just respond. These are large molecules and the reason we
thought they would be okay safe is they would not be absorbed.
DR. BELSITO: That's what we pointed out, too, that they're large and very
polar.
DR. MARKS: Yes.
DR. BELSITO: Okay.
DR. BERGFELD: No need for any discussion from that team?
DR. BELSITO: Okay, second.
DR. BERGFELD: Second. Okay, Marks' team?
DR. MARKS: That would be put in the discussion, obviously.
DR. BELSITO: Right.
DR. MARKS: That's an important point.
DR. BERGFELD: Any other comments to be added in any way? Seeing none
-- oh, Jim, you have a comment?
DR. MARKS: The only other thing is the issue with the monomers, these
substantive -- the skin tox looked okay, even if there was a residual monomer. So that can be put
in the discussion also.
DR. BERGFELD: Anything else? Seeing none, all those in favor please
indicate by raising your hand.
(Motion approved by show of hands)
DR. BERGFELD: This goes out as safe, the polyquats.
Distrbuted for comment only -- do not cite or quote

Safety Assessment of
Polyquaternium-22 and Polyquaternium-39 as Used in Cosmetics

Status: Draft Final Report for Panel Review


Release Date: August 16, 2013
Panel Meeting Date: September 9-10, 2013

The 2013 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V.
Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A Hill, Ph.D. James G. Marks, Jr., M.D.; Ronald
C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A.
This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist.

Cosmetic Ingredient Review


1101 17th Street, NW, Suite 412 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088
cininfo@cir-safety.org
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TABLE OF CONTENTS
INTRODUCTION ............................................................................................................................................... 2
CHEMISTRY...................................................................................................................................................... 2
Definition and Structure ................................................................................................................................... 2
Chemical and Physical Properties..................................................................................................................... 2
Method of Production ...................................................................................................................................... 3
USE .................................................................................................................................................................... 3
Cosmetic.......................................................................................................................................................... 3
Noncosmetic .................................................................................................................................................... 4
TOXICOKINETICS ............................................................................................................................................ 4
TOXICOLOGY................................................................................................................................................... 4
Acute Oral Toxicity ......................................................................................................................................... 4
Repeated Dose Toxicity ................................................................................................................................... 4
Ocular Irritation ............................................................................................................................................... 4
Skin Irritation and Sensitization ....................................................................................................................... 5
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY ................................................................................ 6
GENOTOXICITY ............................................................................................................................................... 6
CARCINOGENICITY ........................................................................................................................................ 6
SUMMARY ........................................................................................................................................................ 6
DISCUSSION ..................................................................................................................................................... 7
CONCLUSION ................................................................................................................................................... 7

1
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ABSTRACT: Polyquaternium-22 and Polyquaternium-39 are polymers that function as antistatic agents, film formers, and
hair fixatives in cosmetic products. These ingredients are being used at concentrations up to 2% (Polyquaternium-22, in a
rinse-off product) and up to3 % (Polyquaternium-39, in a rinse-off product). The unreacted monomers content of these
ingredients was considered low and of no toxicological concern. Limited data showed no skin irritation/sensitization. While
these ingredients were non-genotoxic in bacterial assays, mammalian genotoxicity, carcinogenicity, and reproductive and
developmental toxicity data were not available. These polymers, however, are large, highly polar molecules that would not
be absorbed, and neither local effects in the respiratory tract nor systemic toxicity are likely following product
application/exposure. The Expert Panel concluded that polyquaternium-22 and polyquaternium-39 are safe in the present
practices of use and concentration in cosmetic formulations.

INTRODUCTION

This tentative report reviews the available data relevant to the safety of polyquaternium-22 and polyquaternium-39
as used in cosmetics . These ingredients are polymers, each with a quaternary ammonium moiety. In the case of
polyquaternium-22, the monomers used to produce the polymer are acrylic acid and dimethyldiallyl ammonium chloride and,
for polyquaternium-39, those monomers used to produce the polymer are the same, with the addition of acrylamide. Given
the similarities, these ingredients were grouped together. In addition, both ingredients function as antistatic agents, film
formers, and hair fixatives in cosmetic products.

The Panel, in its safety assessment of polyacrylamide, had established a limit for acrylamide monomer of 5 ppm in
cosmetic formulations.1

The Panel previously issued final reports on the safety assessment of Polyquaternium-72, Polyquaternium-103 and
Polyquaternium-114, having concluded that these cosmetic ingredients are safe in the present practices of use and
concentration. This conclusion on Polyquaternium-7 was reaffirmed by the Panel during a re-review of the safety of this
ingredient in cosmetics in 2010.5 The Panel also determined that the amount of residual acrylamide in Polyquaternium-7 is
not of toxicological concern. The Panels conclusions on Polyquaternium-10 and Polyquaternium-11 were also confirmed.6,7

CHEMISTRY

Definition and Structure

Polyquaternium-22 (CAS No. 53694-17-0) is defined as a copolymer of acrylic acid, diallyldimethyl ammonium
chloride (DADMAC) and acrylic acid that conforms to the structural formula in Figure 1: 8 Another name for this copolymer
is acrylic acid-diallyldimethylammonium chloride polymer.

Polyquaternium-39 (CAS No. 25136-75-8) is defined as a polymeric quaternary ammonium salt of DADMAC and
acrylamide.8 The structural formula of this chemical is included in Figure 1.9 Other names for this polymeric quaternium
ammonium salt include acrylic acid, polymer with acrylamide and diallyldimethyl ammonium chloride, and 2-propen-1-
aminium, N,N-dimethyl-N-2-propenyl-, chloride, polymer with 2-propenamide and 2-propenoic acid.8

Chemical and Physical Properties

Specifications for polyquaternium-22 and Polyquaternium-39 are as follows:

Polyquaternium-2210

Appearance (viscose water clear liquid)


Solid (40 1%)
pH (2 to 5, for 1% aqueous solution)
Viscosity (3,000 to 7,500 cps, @ 25C)

Polyquaternium-3911

Appearance (clear viscose liquid)


Solid (9 to 11%)
pH (5.5 to 7.2)
2
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Viscosity (2,000 to 20,000 cps, @ 25C)

Polyquaternium-22

MerquatTM* 280 Polymer (molecular weight = 4.5 x 105) is a trade name for polyquaternium-22.12 It is described as
a clear to slightly hazy, yellow, viscous liquid with a mild, aldehydic odor. The total solids content is listed as 39 to 43% for
this material, and the pH range is 4.2 to 5.3. Another trade name for polyquaternium-22 is MerquatTM* 295 polymer
(molecular weight = 1.9 x 105).13 It is described as a clear, yellow viscous liquid with a mild, aldehydic odor. The total
solids content is listed as 35 to 40% for this material, and the pH range is 4.0 to 5.5.

Polyquaternium-39

MerquatTM* PLUS 3330 Polymer (molecular weight = 1.5 x 106) is a trade name for polyquaternium-39.14 It is
described as a clear, colorless viscous liquid with a mild, aldehydic odor. The total solids content is listed as 9.4 to 10.4% for
this material, and the pH range is 5.5 to 7.0.

Methods of Production

Polyquaternium-22

According to one source, the starting monomers in the manufacture of polyquaternium-22 are acrylic acid and
dimethyldiallyl ammonium chloride.15

Polyquaternium-39

Polyquaternium-39 is manufactured from acrylic acid, diallyl dimethyl ammonium chloride and acrylamide.15

Composition

Polyquaternium-22

Polyquaternium-22 is marketed at concentration ranges of 30-45% and 94%. The lower concentration-range
products are defined as aqueous solutions that may also contain preservatives.15 The higher concentration product is
describerd as a powder with residual moisture content. Typical residual unreacted monomers in this ingredient are: acrylic
acid (< 1000 ppm) and diallyldimethyl ammonium chloride (< 1%).

Polyquaternium-39

Polyquaternium-39 is marketed at the following three concentration ranges: 8-11.5%, 41-45%, and 92%.15 The
two lower concentration-range products are preserved aqueous polymer solutions. The highest concentration product is an
unpreserved powder. Typical unreacted monomers in this ingredient are: acrylamide (< 1 ppm), acrylic acid (< 50 ppm), and
diallyldimethyl ammonium chloride (< 2%).

USE

Cosmetic

The 2 ingredients reviewed in this safety assessment function as antistatic agents, film-formers, and hair fixatives in
cosmetic products.8 According to information supplied to the Food and Drug Administration (FDA) by industry as part of
the Voluntary Cosmetic Registration Program (VCRP) in 2013, both polyquaternium-22 (544 uses) and polyquaternium-39
(83 uses) were being used in cosmetic products.16 These data are summarized in Table 1. Polyquaternium-22 is used
primarily in hair dye products and other hair care products; lower use frequencies for polyquaternium-39 in these products
were reported. Results from a survey of ingredient use concentrations provided by the Personal Care Products Council (also
included in Table 1) in 2011 indicate that these 2 ingredients were being used at concentrations up to 2% (Polyquaternium-
22, in a rinse-off product) and up to 3 % (Polyquaternium-39, in a rinse-off product and in a leave-on product).17

3
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Cosmetic products containing polyquaternium-22 or polyquaternium-39 may be applied to the skin and hair, or,
incidentally, may come in contact with the eyes and mucous membranes. Products containing these ingredients may be
applied as frequently as several times per day and may come in contact with the skin or hair for variable periods following
application. Daily or occasional use may extend over many years.

Polyquaternium-39 is being used in face and neck creams, lotions, and powders at concentrations up to 3% and is
also being used in indoor tanning preparations (sprays, use concentration data not available). Because this ingredient is used
in aerosol/pump sprays or powders, it could possibly be inhaled. In practice, 95% to 99% of the droplets/particles released
from cosmetic sprays have aerodynamic equivalent diameters >10 m, with propellant sprays yielding a greater fraction of
droplets/particles below 10 m, compared with pump sprays.18,19,20,21 Therefore, most droplets/particles incidentally inhaled
from cosmetic sprays would be deposited in the nasopharyngeal and bronchial regions and would not be respirable (i.e., they
would not enter the lungs) to any appreciable amount.19,20 It should be noted that though it is possible that polyquaternium-
39 is being used in face and neck powders and that the indoor tanning preparation containing this ingredient is a spray
product, there is uncertainty as to whether polyqyaternium-39 is actually being used in sprays or powders.

Noncosmetic

Polyquaternium-39 is included among the substances that may be safely used as components of paper and
paperboard products that come in contact with aqueous and fatty foods.22

TOXICOKINETICS

Data on the absorption, distribution, metabolism, and excretion of Polyquaternium-22 or Polyquaternium-39 were
not found in the published literature.

TOXICOLOGY

Acute Oral Toxicity

Polyquaternium-22

The acute oral toxicity of polyquaternium-22 (MerquatTM* 280 Polymer) was evaluated using 10 healthy male
albino rats.23 The animals were dosed orally with 5 g/kg of the test material. Mortality and systemic observations were made
3 to 4 h post-dosing and daily thereafter for 7 days. All animals survived the study and it was concluded that the LD50 was >
5.0 g/kg.

Polyquaternium-39

The acute oral toxicity of polyquaternium-39 (MerquatTM PLUS 3330 Polymer) was evaluated using 10 healthy
male Wistar albino rats.24 The test protocol was identical to that in the preceding study, except for the 14-day observation
period after the initial 3 to 4 h observation period. All animals survived in good health, and it was concluded that the LD50
was > 5.0 g/kg and that the test material was non-toxic.

Repeated Dose Toxicity

Repeated dose toxicity studies on Polyquaternium-22 or Polyquaternium-39 were not found in the published
literature, and unpublished data were not submitted.

Ocular Irritation

Polyquaternium-22

In an ocular irritation study, polyquaternium-22 (MerquatTM* 280 Polymer, 0.1 ml) was placed in the conjunctival
sac of one eye in each of 6 rabbits.25 The eyes were not rinsed after instillation. Reactions were scored at 1, 2, and 3 days
post-instillation. All eyes appeared normal throughout the study, and the test material was classified as a non-irritant.
4
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The ocular irritation potential of an oxidation dye containing 0.16% Polyquaternium-22 (pH = 9.5 to 10) was evaluated in
vitro using the hen's egg test on the chorioallantoic membrane (HET-CAM test).26 The dye was tested at a concentration of
10% (0.016% active Polyquaternium-22), and was classified as a slight irritant (irritation scores of 2.38, 4.51, or 4.60). The
positive controls, sodium hydroxide (0.1 M) and sodium dodecyl sulfate (SDS, 1%), yielded scores of 19.98 and 10.21,
respectively. The negative control (0.9% sodium chloride) yielded a score of 0.

Polyquaternium-39

The ocular irritation potential of polyquaternium-39 (MerquatTM PLUS 3330 Polymer) was evaluated in a study
involving 6 healthy New Zealand albino rabbits.27 The protocol was identical to that used in the ocular irritation study on
MerquatTM* 280 Polymer discussed earlier in this section. There was no evidence of systemic effects at any time after test
substance instillation. All eyes appeared normal during the study and the test material was classified as a non-irritant.

Skin Irritation and Sensitization

Animal

Polyquaternium-22

In a skin irritation study, polyquaternium-22 (MerquatTM* 280 Polymer, 0.5 ml) was applied to abraded and intact
skin sites on the backs (clipped free of hair) of 6 healthy albino rabbits.28 The total dose applied was 1.0 ml/rabbit. The test
material was applied under an occlusive patch for 24 h, and reactions were scored at 24 h and 72 h post-application. None to
slight and none to severe erythema were observed at 24 h and 72 h post-application, respectively. The erythema observed
was more severe at abraded sites than at intact sites. There was no evidence of edema. A primary irritation index (PII) of 1.1
was reported, and the test material was classified as a non-irritant.

Polyquaternium-39

The skin irritation potential of polyquaternium-39 (MerquatTM PLUS 3330 Polymer) was evaluated in a study
involving 6 healthy New Zealand albino rabbits.29 The test protocol was identical to that used in the skin irritation study on
MerquatTM* 280 Polymer discussed earlier in this section. There was no evidence of erythema, edema, or abnormal systemic
signs during the study. The test material was classified as a non-irritant (PII = 0).

Human

Polyquaternium-22

The skin irritation potential of an oxidation dye containing 0.16% polyquaternium-22 (pH = 9.5 to 10) was
evaluated using 30 subjects (ages not stated).26 In a single, occlusive patch test, a 10% concentration of the dye (0.016%
active Polyquaternium-22) was applied for 24 h. Reactions were scored at 24 h, 48 h, and 72 h post-application, and the dye
was not predicted to be a skin irritant (OIS [not defined] = 0.07). The negative control (water) yielded a score of 0, and the
positive control (1% SDS) yielded a score of 0.92. The same test concentration of the dye was also applied to 30 subjects
(ages not stated) in a multiple patch test.26 Three 24 h applications of the dye were made to each subject and reactions were
scored according to the same schedule. The dye was not predicted to be a skin irritant (OIS = 0.07). Water (negative
control) yielded a score of 0 and 0.3% SDS (positive control) yielded a score of 0.50.

Polyquaternium-39

The skin irritation and sensitization potential of polyquaternium-39 (MerquatTM PLUS 3330 Polymer, clear liquid)
was evaluated in a human repeated insult patch test (HRIPT) using 154 adult subjects (131 women, 23 men; 18 to 79 years
old). The numbers of subjects that completed the induction and challenge phases were 153 and 150 subjects, respectively.
An occlusive patch (2 cm x 2 cm) moistened with the test material (~ 0.2 ml) was applied to the back for 24 h. Patch
applications were made on either side of the midline. Patches were applied on Mondays, Tuesdays, Wednesdays, and
Thursdays during induction. There were no patch applications on Fridays, Saturdays, or Sundays. Week #4 was the non-
treatment period, and the challenge phase began at week #5. Patches were applied to a new test site (24-h application) on
Monday through Thursday. No adverse skin changes were observed during induction. Erythema of negligible significance

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was observed on either 1 or 2 occasions on each of 2 subjects. Adverse skin effects were not observed during the challenge
phase. It was concluded that the test material did not induce skin irritation or sensitization.

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

Reproductive/developmental toxicity data on Polyquaternium-22 or Polyquaternium-39 were not found in the


published literature.

GENOTOXICITY

Polyquaternium-22

The genotoxicity of polyquaternium-22 (MerquatTM* 280 Polymer) was evaluated, with and without metabolic
activation, in the Ames test using the following bacterial strains: Salmonella typhimurium strains TA98, TA100, TA1535,
and TA1537, and Escherichia coli strain WP2 uvr A.30 The test material was evaluated at doses ranging from 100 to 5,000
g/plate. Positive responses were not observed during the study, and it was concluded that the test material was non-
genotoxic in this assay. Results were also negative in another study (same protocol and doses) on MerquatTM* 295 polymer.31

Polyquaternium-39

In another study, the genotoxicity of polyquaternium-39 (MerquatTM PLUS 3330 Polymer) was evaluated in the
Ames test according to the protocol in the preceding study, using the same Salmonella typhimurium strains.32 The test
material was non-genotoxic, with and without metabolic activation, over the range of doses tested.

CARCINOGENICITY

Carcinogenicity data on Polyquaternium-22 or Polyquaternium-39 were not found in the published literature.

SUMMARY

The starting monomers for polyquaternium-22 are acrylic acid and dimethyldiallyl ammonium chloride.
Polyquaternium-39 is manufactured from acrylic acid, diallyldimethyl ammonium chloride and acrylamide. Acrylic acid (<
50 ppm or < 1000 ppm) and dimethyldiallyl ammonium chloride (<1% or < 2%) are present in both polymers, but acrylamide
monomer (< 1 ppm) is present only in polyquaternium-39. Both ingredients function as antistatic agents, film formers, and
hair fixatives in cosmetic products.

According to information supplied to the Food and Drug Administration (FDA) by industry as part of the Voluntary
Cosmetic Registration Program (VCRP) in 2011, both ingredients were being used in cosmetic products. Polyquaternium-22
is used primarily in hair dye products and other hair care products; lower use frequencies for polyquaternium-39 in these
products were reported. Results from a survey of ingredient use concentrations provided by the Personal Care Products
Council in 2011 indicate that these 2 ingredients were being used at concentrations up to 2% (Polyquaternium-22, in a rinse-
off product) and up to 3 % (Polyquaternium-39, in a rinse-off product).

Polyquaternium-22 (MerquatTM* 280 Polymer) and polyquaternium-39 (MerquatTM PLUS 3330 Polymer) were classified as
non-toxic (LD50 > 5 g/kg) in acute oral toxicity studies.

MerquatTM* 280 Polymer and MerquatTM PLUS 3330 Polymer were classified as non-irritants when instilled into the
eyes of rabbits. An oxidation dye containing 0.16% Polyquaternium-22, tested at a concentration of 10% (0.016% active
Polyquaternium-22) in an in vitro HET-CAM test, was classified as a slight ocular irritant.

Both MerquatTM* 280 Polymer and MerquatTM PLUS 3330 Polymer were classified as non-irritants when applied,
under an occlusive patch, to the skin of albino rabbits. In single and multiple application occlusive patch tests, an oxidation
dye containing 0.16% polyquaternium-22, tested at a concentration of 10% (0.016% active Polyquaternium-22), was not
predicted to be a skin irritant in human subjects. In an HRIPT (occlusive patches), MerquatTM PLUS 3330 Polymer was
classified as a non-irritant and non-sensitizer.
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MerquatTM* 280 Polymer, MerquatTM* 295 polymer (also polyquaternium-22), and MerquatTM PLUS 3330 Polymer were non-
genotoxic in the Ames test when tested at doses up to 5,000 g/plate in the following Salmonella typhimurium strains:
TA98, TA100, TA1535, and TA1537. MerquatTM* 280 Polymer and MerquatTM* 295 polymer) were also non-genotoxic in
Escherichia coli strain WP2 uvr A when tested according to the same procedure. MerquatTM PLUS 3330 Polymer was not
evaluated for genotoxiciy in Escherichia coli strain WP2 uvr A in this study.

The following types of data on Polyquaternium -22 or Polyquaternium-39 were not found in the published literature:
toxicokinetics, repeated dose toxicity, reproductive and developmental toxicity, and carcinogenicity.

DISCUSSION

Relevant data on the composition of polyquaternium-22 and polyquaternium-39 were available. Given that the
polymers are very large, polar compounds, the CIR Expert Panel focused its attention on the unreacted monomer levels
which were given to be <1000 ppm acrylic acid and <1% dimethyldiallyl ammonium chloride for polyquaternium-22, and
<1 ppm acrylamide, < 50 ppm acrylic acid, and <2 % dimethyldiallyl ammonium chloride for polyquaternium-39. Residual
acrylamide monomers are a concern and the Panel had previously established a limit of 5 ppm in cosmetic formulations. In
this case, the level is <1 ppm in the ingredient and the ingredient is used at a maximum concentration of 3%, so, acrylamide
levels are well below the previously established level. Therefore, the Expert Panel considered these unreacted monomers to
be low and of no toxicological concern, given the low use concentrations for these ingredients.

While bacterial genotoxicity data were available and showed no evidence of genotoxicity, the Panel noted the
absence of mammalian genotoxicity, carcinogenicity, and reproductive and developmental toxicity data on both ingredients,
as well as the absence of skin sensitization data on polyquaternium-22. However, it was agreed that these polymers are large,
highly polar molecules that would not be absorbed, and, based on acute oral exposure studies, that systemic toxicity is not
likely. The Panel also noted that there is little skin irritation/sensitization potential, based on the negative skin irritation data
on polyquaternium-22 and polyquaternium-39 and the negative skin sensitization data on polyquaternium-39.

The Panel discussed the issue of incidental inhalation exposure from aerosol and pump sprays, and face and neck
powders, relating to the use of polyquaternium-39 in these products. Inhalation toxicity data were not available. However,
the Panel considered pertinent data indicating that incidental inhalation exposure to polyquaternium-39 in such cosmetic
products would not cause adverse health effects, including chemistry data and data characterizing the potential for these
ingredients to cause acute oral toxicity, dermal irritation, or sensitization. The Panel noted that 95% 99% of
droplets/particles produced in cosmetic aerosols would not be respirable to any appreciable amount. The potential for
inhalation toxicity is not limited to respirable droplets/particles deposited in the lungs. However, coupled with the small
exposures anticipated in the breathing zone and the concentrations at which the ingredient is used, the available information
indicates that incidental inhalation would not be a significant source of toxicological concern. A detailed discussion and
summary of the Panels approach to evaluating incidental inhalation exposures to ingredients in cosmetic products is
available at http://www.cir-safety.org/cir-findings.

CONCLUSION

The CIR Expert Panel concluded that, in cosmetic formulations, polyquaternium-22 and polyquaternium-39 are safe in the
present practices of use and concentration described in this safety assessment.

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Figure 1. Structural Formulas for Polyquaterniums -22 and -39. DADMAC is diallyl dimethyl ammonium chloride,
sometimes written as dimethyldiallyl ammonium chloride. w, x, and y are variables that indicate that these
compounds are polymers. Unless specified by a manufacturer, they have no standard definition. This is common
notation for polymers wherein the number and order of repeats is unknown.

Polyquaternium-22

Polyquaternium-39

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Table 1. Current Frequency of Use According to Duration and Type of


Exposure Provided in 201116,17

Polyquaternium-22 Polyquaternium-39
# of # of
Uses Conc. (%) Uses Conc. (%)
Exposure Type
Eye Area NR NR 1 1
Incidental Ingestion NR NR NR NR
Incidental Inhalation-sprays NR NR 1 NR
Incidental Inhalation-powders NR NR 3 0.8 to 3
Dermal Contact 10 0.2 47 0.1 to 3
Deodorant (underarm) NR NR NR NR
Hair - Non-Coloring 47 0.3 to 1 35 0.01 to 3
Hair-Coloring 487 0.03 to 2 1 0.3
Nail NR NR NR NR
Mucous Membrane 10 0.2 21 0.1 to 1
Baby Products NR NR 2 NR
Duration of Use
Leave-On 14 0.4 to 0.5 25 0.01 to 3
Rinse off 530 0.03 to 2 50 0.1 to 3
Diluted for (bath) use NR NR 8 NR
Totals/Conc. Range 544 0.03 to 2 83 0.01 to 3
NR = Not Reported; NS = Not Surveyed; Totals = Rinse-off + Leave-on Product Uses.
Note: Because each ingredient may be used in cosmetics with multiple exposure types,
the sum of all exposure type uses may not equal the sum total uses.

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References

1. Andersen, F. A. Amended final report on the safety assessment of polyacrylamide and acrylamide
residues in cosmetics. International Journal of Toxicology. 2005;24(2):21-50.

2. Andersen, F. A. Final report on the safety assessment of Polyquaternium-7. J.Am.Coll.Toxicol.


1995;14(6):476-484.

3. Elder, R. L. Final report on the safety assessment of polyquaternium-10. J Am Coll Toxicol.


1988;7(3):335-352.

4. Elder, R. L. Final report on the safety assessment of polyquaternium-11. J Am Coll Toxicol.


1983;2(5):161-178.

5. Fiume, M. Z. Bergfeld W. F. Belsito D. V. Hill R. A. Klaassen C. D. Liebler D. C. Marks J. G. Jr.


Shank R. C. Slaga T. J. Snyder P. W. and Andersen F. A. 2010. Re-review Summary on
Polyquaternijum-7.

6. Andersen, F. A. Annual Review of Cosmetic Ingredient Safety Assessments - 2005/2006. International


Journal of Toxicology. 2008;27(1):77-142.

7. Andersen, F. A. Annual Review of Cosmetic Ingredient Safety Assessments - 2002/2003. International


Journal of Toxicology. 2005;24(1):1-102.

8. Gottschalck, T. E. and Bailey J. E. Cosmetic Ingredient Dictionary and Handbook. 13th ed.
Washington, D.C.: Personal Care Products Council, 2011.

9. Nguyen BA Trading and Manufacturing Co.Ltd. Product data sheet. Polyquaternium-39.


http://nguyenbachem.com/en/images/stories/files/polyquaternium%2039-en.pdf. Date Accessed
11-4-2011.

10. Perman-Scess Equipment Co., Led. Polyquaternium-22. http://cosmeticrawmaterials.org/Cosmetic-


Ingredients/Polyquaternium-22.html. Date Accessed 11-4-2011.

11. Shandong Luyue Chemical Co., Ltd. Polyquaternium-39.


http://luyue.en.alibaba.com/product/388817186-209682850/Polyquaternium_39.html. Date
Accessed 11-4-2011.

12. Lubrizol. Technical data sheet MerquatTM 280 polymer (polyquaternium-22). Unmpublished data
submitted by the Personal Care Products Council on 11-22-2011. 2011. pp.1

13. Lubrizol. Technical data sheet MerquatTM 295 polymer (polyquaternium-22). Unpublished data
submitted by the Personal Care Products Council on 11-22-2011. 2011. pp.1

14. Lubrizol. Technical data sheet. MerquatTM PLUS 3330 Polymer (Polyquaternium-39). Unpublished
data submitted by the Personal Care Products Council on 11-22-2011. 2011. pp.1-2.

15. Personal Care Products Council. Information on polyquaternium-22 and -39. Unpublished data
submitted by the Personal Care Products Council on 6-10-2013. 2013. pp.1

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16. Food and Drug Administration (FDA). Information supplied to FDA by industry as part of the VCRP
FDA database. 2013. Washington, D.C.: FDA.

17. Personal Care Products Council. Concentration of use by FDA product category. Polyquaternium-22
and Polyquaternium-39. Unpublished data submitted by the Personal Care Products Council on
10-25-2011. 2011.

18. Rothe H, Fautz R, Gerber E, Neumann L, Rettinger K, Schuh W, and Gronewold C. Special aspects of
cosmetic spray safety evaluations: Principles on inhalation risk assessment. Toxicol Lett.
2011;205(2):97-104.

19. Bremmer HJ, Prud'homme de Lodder LCH, and van Engelen JGM. Cosmetics Fact Sheet: To assess the
risks for the consumer; Updated version for ConsExpo 4. 2006.
http://www.rivm.nl/bibliotheek/rapporten/320104001.pdf. Date Accessed 8-24-2011. Report
No. RIVM 320104001/2006. pp. 1-77.

20. Rothe H. Special aspects of cosmetic spray evaluation. 2011.

21. Johnsen MA. The Influence of Particle Size. Spray Technology and Marketing. 2004;24-27.

22. Food and Drug Administration (FDA). Components of paper and paperboard in contact with aqueous
and fatty foods. Polyquaternium-39. 21 CFR 176.170. 2010.

23. MB Research laboratories, Inc. Oral toxicity in rats . Merquat 280 (polyquaternium-22). Unpublished
data submitted by the personal Care Products Council on 11-22-2011. 1985. pp.1

24. MB Research laboratories, Inc. Single dose oral toxicity in rats. Merquat Plus 3330 (Polyquaternium-
39). Unpublished data submitted by the Personal Care Products Council on 11-22-2011. 1991.
pp.1-5.

25. MB Research laboratories, Inc. Eye irritation in rabbits. Merquat 280 (polyquaternium-22).
Unpublished data submitted by the Personal Care Products Council on 11-22-2011. 1985. pp.1

26. Personal Care Products Council. 2010. Summary information on studies of an oxidative hair dye
containing 0.16% polyquaternium-22. Unpublished data submitted by the Personal Care
Products Council on 10-21-2011.

27. MB Research laboratories, Inc. Eye irritation in albino rabbits. Merquat Plus 3330 (Polyquaternium-
39). Unpublished data submitted by the Personal Care Products Council on 11-22-2011. 1991.
pp.1-7.

28. MB Research laboratories, Inc. Primary dermal irritation in albino rabbits. Merquat 280
(polyquaternium-22). Unpublished data submitted by the Personal Care products Council on 11-
22-2011. 1985. pp.1-5.

29. MB Research laboratories, Inc. Primary dermal irritation in albino rabbits. Merquat Plus 3330
(Polyquaternium-39). Unpublished data submitted by the Personal Care Products Council on 11-
22-2011. 1991. pp.1-6.

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30. MA BioServices. Bacterial reverse mutation assay. Merquat 280 (polyquaternium-22). Laboratory
study number G98AP83.502. Unpublished data submitted by the Personal Care Products
Council on 11-22-2011. 1998. pp.1-42.

31. MA BioServices. Bacterial reverse mutation assay. MerQuat 295 (polyquaternium-22). Laboratory
study number G98AP84.502. Unpublished data submitted by the Personal Care Products
Council on 11-22-2011. 1998. pp.1-42.

32. Microbiological Associates, Inc. Salmonella/Mammalian-microsome plate incorporation mutagenicity


assay (Ames test) of Merquat Plus 3330 (Polyquaternium-39). Laboratory study number
TA031.501. Unpublished data submitted by the Personal Care Products Council on 11-22-2011.
1991. pp.1-39.

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2013 FDA VCRP Data


Polyquaternium-22
05A - Hair Conditioner 14
05D - Permanent Waves 1
05F - Shampoos (non-coloring) 18
05G - Tonics, Dressings, and Other Hair Grooming Aids 3
05I - Other Hair Preparations 11
06A - Hair Dyes and Colors (all types requiring caution
statements and patch tests) 424
06B - Hair Tints 57
06G - Hair Bleaches 3
06H - Other Hair Coloring Preparation 3
10A - Bath Soaps and Detergents 10
Total 544

Polyquaternium-39
01C - Other Baby Products 2
02A - Bath Oils, Tablets, and Salts 1
02B - Bubble Baths 3
02D - Other Bath Preparations 4
03G - Other Eye Makeup Preparations 1
05A - Hair Conditioner 4
05C - Hair Straighteners 2
05F - Shampoos (non-coloring) 16
05G - Tonics, Dressings, and Other Hair Grooming Aids 5
05I - Other Hair Preparations 8
06H - Other Hair Coloring Preparation 1
10A - Bath Soaps and Detergents 12
10E - Other Personal Cleanliness Products 1
11B - Beard Softeners 1
11G - Other Shaving Preparation Products 1
12A - Cleansing 12
12B - Depilatories 1
12C - Face and Neck (exc shave) 3
12D - Body and Hand (exc shave) 3
12F - Moisturizing 1
13B - Indoor Tanning Preparations 1
Total 83
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Distrbuted for comment only -- do not cite or quote

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