IOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY
`Volume 7, Number 3, 1988
`Mary Ann Liebert, Inc., Publishers
`
`3
`Final Report on the Safety
`Assessment of Polyquaternium-10
`
`Polyquaternium-10 is a polymeric quaternary ammonium derivative of hy-
`droxyethyl cellulose that is used in cosmetics as a conditioner, thickener, and
`emollient at concentrations of I 0.1 %-5%. Polyquaternium-10 has, at most,
`only a low potential to penetrate the stratum corneum but is adsorbed by ke-
`ratinous surfaces. The oral LDso of Polyquaternium-10 was not obtained at 16
`g/kg in rats. Inhalation, dermal, and ocular animal test data indicated, at
`most, only a low degree of toxicity at test concentrations of Polyquaternium-
`10 greater than that used in cosmetic products. Polyquaternium-10 with and
`without metabolic activation was not a mutagen in three separate assay sys-
`tems. Polyquaternium-10 was neither an irritant nor a human sensitizer when
`tested at 2.0%. Cosmetic products containing .up to 1 o/o Polyquaternium-10
`were not human irritants, sensitizers, or photosensitizers. On the basis of the
`information presented, it is concluded that Polyquaternium-10 is safe as a
`cosmetic ingredient in the present practices of use.
`
`P
`
`INTRODUCTION
`
`olyquaternium-10 is a cationic form of hydroxyethyl cellulose that adsorbs
`and sorbs well to proteinaceous surfaces. It is used in cosmetics as a condi-
`tioner, thickener, and emollient in hair care products, lotions, and makeup.
`
`CHEMISTRY
`Definition
`Polyquaternium-10, also known as Quaternium-I 9, is a polymeric quater-
`nary ammonium salt of hydroxyethyl cellulose reacted with a trimethyl ammo-
`nium substituted epoxide. There are various grades of Polyquaternium-10 with
`different average molecular weights generally ranging from 250,000 to 600,000.
`Polyquaternium-10 has three CAS numbers: 53568-66-4, 54351 -50-7, and
`55353-1 9-0. (1-3)
`
`Chemical and Physical Properties
`Polyquaternium-10 is a white granular powder with a characteristic amine
`odor. It is soluble in water and insoluble in alcohol and nonpolar organic sol-
`
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`ALCON 2051
`Apotex Corp. v. Alcon Research, Ltd.
`Case IPR2013-00428
`
`

`

`336
`
`COSMETIC INGREDIENT REVIEW
`
`vents. Polyquaternium-10 used in cosmetics has 0.5% maximum water insolu-
`bles, 1.7 to 2.2% nitrogen-containing components, 2% maximum ash (NaCI),
`and 6% maximum volatile material. The particle size specifications are 95%
`minimum through a 20 mesh filter and 85% minimum through a 40 mesh filter.
`The viscosity of a 2% aqueous solution (25°C) is between 60 and 150 centi-
`poises. ( 4 )
`Polyquaternium-10 alters the surface tension of aqueous solutions of ani-
`onic surfactants. Addition of 1 o/o and 2% Polyquaternium-10 lowered the sur-
`face tension of aqueous solutions of sodium lauryl sulfate, sodium tridecylben-
`zenesulfonate, and potassium l a ~ r a t e . ' ~ )
`
`Reactivity
`Polyquaternium-10 is a cationic, surface-active polymer that is adsorbed by
`keratinous surfaces, such as hair and skin (stratum corneum). The adsorption of
`the polymer was not readily affected by pH in the range of 4 to 10. It undergoes
`slow hydrolytic cleavage outside this pH range. Sorption of Polyquaternium-10
`to keratinous surfaces was decreased by the addition of electrolytes (salts), such
`as aluminum, iron, calcium, or sodium. Polyquaternium-10 is biologically de-
`gradable. The presence of ethyl alcohol or propylene glycol adds to the stability
`of Po I yq uate r n i u m- 1 0. ( 6 - 9 )
`
`Analytical Methods
`The most common analytical method for quaternary ammonium com-
`pounds is colorimetric testing following separation by acid extraction.(")
`
`Method of Manufacture
`Polyquaternium-10 is generally produced by reacting hydroxyethylcellulose
`with epichlorhydrin, followed by quaternization using trimethylamine. It i s
`stable within a pH rane of 4 to 8.
`
`Impurities
`Inorganic impurities of Polyquaternium-10 used in cosmetics include water
`(up to 0.5%), nitrogen (1.7 to 2.2%), and ash (NaCI up to 2%). Information was
`not available on organic impurities of Polyq~aternium-lO.(~) Epichlorhydrin was
`not detected in any of six different Polyquaternium polymers analyzed with an
`average detection limit of about 0.5 ppm.'") A maximum of 10.8 ppm Trimeth-
`ylamine w'as detected in lots of Polyquaternium-10 that were produced and sold
`during 1985.(12)
`
`USE
`Purpose in Cosmetics
`Polyquaternium-10 is used as a conditioner, emollient and viscosity con-
`troll ing agent in cosmetics. (3,13,14)
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`ASSESSMENT: POLYQUATERNIUM-10
`
`337
`
`Scope and Extent of Use in Cosmetics
`Polyquaternium-10 is used primarily in hair care products, skin cleansers,
`and skin moisturizers in concentrations of 10.1 %-5%. One hundred thirty-nine
`(1 39) of the voluntarily filed cosmetic product formulations were reported to the
`Food and Drug Administration to contain Polyquaterniurn-1 O.(”) The cosmetic
`product formulation data that are made available by the FDA are compiled
`through voluntary filing of such data in accordance with Title 21 part 720.4 of
`the Code of Federal Regulations.(’6) Ingredients are listed in prescribed concen-
`tration ranges under specific product type categories. Since certain cosmetic in-
`gredients are supplied by the manufacturer at less than 100% concentration, the
`value reported by the cosmetic formulator may not necessarily reflect the actual
`concentration found in the finished product; the actual concentration would be
`a fraction of that reported to the FDA. Data submitted within the framework of
`preset concentration ranges provide the opportunity for overestimation of the
`actual concentration of an ingredient in a particular product. An entry at the
`lowest end of a concentration range is considered the same as one entered at
`the highest end of that range, thus introducing the possibility of a 2- to 10-fold
`error in the assumed ingredient concentration (Table 1).
`Polyquaternium-10 has been generally or individually approved for use in
`cosmetic formulations marketed in Japan.(”)
`
`Surfaces, Frequency, and Duration of Application
`The hair care products containing Polyquaternium-10 are, for the most part,
`applied for a few minutes, then rinsed off. However, Polyquaternium-10 i5 in-
`corporated in these products for its “substantivity” (sorption) and would be ex-
`pected to remain in contact with the hair between treatments. Skin cleansers
`and moisturizers have the potential to remain in continuous contact with the
`skin and nails for extended periods of time.
`
`B I 0 LOGY
`Penetration, Sorption, and Permeation Through Stratum Corneum
`Approximately 1 ml of a 5% ( w h ) water solution of ‘‘C-Polyquaternium-10
`(uniformly labeled on the pendant side chain) was applied to the backs of 12
`Fischer 344 rats. The total dose of 4.0 ml/kg was occluded for the test period 1,
`3, and 24 h. Six rats were placed in Roth-type glass metabolism cages de5igned
`for the separate collection of urine, feces, and expired air for the entire 24-h ex-
`posure period. The remaining 6 exposed animals were killed, 3 at 1 h and 3 at
`6-h postexposure. Blood measured at 1 h and 3 h for the interim sacrifices and
`for the 6 material balance rats killed at 24 h had no radioactivity above back-
`ground. There was no radioactivity above background in any of 9 tissues exam-
`ined in the 6 animals that were killed at 24 h. Less than 0.02% of the adminis-
`tered dose was found in the urine and less than 0.1 o/o in the feces; no radioactiv-
`ity was recovered in COz. Of the 83.7% of the total dose that was recovered
`from the male rats, 75.2% was from the occlusive materials and 7.1 o/o was found
`
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`

`

`n
`
`0
`W
`W
`
`37
`
`-
`1
`1
`1
`1
`8
`
`5
`
`3
`-
`2
`-
`-
`1
`1
`7
`-
`
`-
`1
`5
`-
`
`81
`
`1
`-
`-
`-
`-
`3
`
`3
`
`1
`1
`-
`3
`1
`3
`3
`46
`5
`1
`9
`-
`1
`
`139
`
`8
`
`6
`1
`2
`3
`1
`6
`4
`62
`6
`1
`16
`5
`1
`
`349
`38
`260
`171
`219
`747
`
`832
`
`680
`148
`831
`16
`177
`180
`290
`909
`474
`265
`478
`397
`475
`
`50.1
`
`>O.l-7
`
`> 1-5
`
`concentration
`Unreported
`
`concentration range (%)
`
`No. of product formulations within each
`
`ingredient
`containing
`Total no.
`
`in category
`formulations
`Total no. of
`
`1981 TOTALS
`
`Other skin care preparations
`Wrinkle smoothers (removers)
`Skin fresheners
`Paste masks (mud packs)
`Night skin care preparations
`Moisturizing skin care preparations
`
`shaving preparations)
`
`Face, body, and hand skin care preparations (excluding
`
`liquids, and pads)
`
`Skin cleansing preparations (cold creams, lotions,
`Bath soaps and detergents
`Makeup bases
`Hair shampoos (coloring)
`Other hair preparations (noncoloring)
`Wave sets
`Tonics, dressings, and other hair grooming aids
`Hair shampoos (noncoloring)
`Permanent waves
`Hair sprays (aerosol fixatives)
`Hair conditioners
`Mascara
`Bubble baths
`
`Product category
`
`TABLE 1. Product Formulation Data for Polyquaternium-10''51
`
`

`

`ASSESSMENT: POLYQUATERNIUM-10
`
`339
`
`in or around the skin at the dose site. The fraction of the applied material that
`did penetrate the skin amounted to less than 1.5% of the administered radioac-
`tivity. The investigators noted the low total recovery of the applied radioactivity;
`however, if the data were normalized to 100%, less than 1.75% of the applied
`dose would have penetrated the skin. The authors concluded that Polyquater-
`ium-10 is unlikely to penetrate the human skin in toxicologically significant
`
`The anti-irritant effect of hydroxyl and quaternary ammonium compounds,
`including Polyquaternium-10, has been investigated in recent years. It has been
`hypothesized that the sorption properties of Polyquaternium-10 enable the
`polymer to block keratin reactive sites, thus reducing the topical and eye irritant
`effects of surfactants in shampoo and cleanser formulations.(20,2')
`Several studies have investigated the passage of Polyquaternium-10 and sur-
`factants, such as sodium lauryl sulfate, into and through isolated stratum cor-
`neum from the skin of fetal pigs, neonatal rats, and adult humans. The fetal pig-
`skin was frozen, and on warming, the stratum corneum was gently separated
`from the underlying epidermis. Neonatal rat skin was removed following death
`by CO, inhalation. The skin was placed in a desiccator jar and exposed to am-
`monia vapor for 1-3 h, then put in water to remove the epidermis from the der-
`mis. After 1 h the epidermis was recovered on a paper towel, and the mal-
`pighian layer was scraped off, leaving the stratum corneum to dry. The various
`preparations were exposed to ''C-Polyquaternium-l 0 andlor surfactant (in aque-
`ous solution) in vials or permeability cells(22) to quantify sorption and perme-
`ability and to evaluate the effects of the polymer on the preparations. The results
`indicated that Polyquaternium-10 slowly diffused into the outer layer of the
`stratum corneum (all three species) rather than forming multilayers on the sur-
`face. Although ionic surfactants did reduce polymer sorption, pretreatment of
`the stratum corneum with 1 o/o Poiyquaternium-10 greatly reduced the amount
`of surfactant that passed through the preparation. This reduction in permeation
`of surfactant supported the hypothesis that Polyquaternium-10 is an anti-irritant
`in the presence of ionic (i.e., irritant) surfactants. The kinetics of polymer/surfac-
`tant sorption and permeation indicated that the polymer did not act primarily as
`a barrier to penetration, but rather it helped to maintain the physical integrity of
`the stratum corneum preparation.
`Pretreatment of the stratum corneum of neonatal rats with Polyquaternium-
`10 slightly increased the hydration of the membrane and reduced swelling after
`su rfactant exposure. (2,9.23,24)
`
`ANIMAL TOXICOLOGY
`Oral Toxicity
`Three lots of Polyquaternium-10 were tested for acute oral toxicity by intu-
`bation in rats. Three studies at maximum doses of 16 g/kg, 13.1 glkg, 16 g/kg did
`not achieve the LD50.(25-27)
`The acute oral toxicity of 1 .O% Polyquaternium-10 in a shampoo and a con-
`ditioner was tested by gavage. The LD,, of the two formulations was not
`reached at 5 glkg.(28t29) Results are summarized in Table 2.
`
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`340
`
`TABLE 2. Acute Oral Toxicity
`
`COSMETIC INGREDIENT REVIEW
`
`Compound
`
`No. of rats
`
`Vehicle
`
`LDso
`
`Comments
`
`Reference
`
`10
`
`Corn oil
`
`>16 gikg
`
`3
`
`10
`
`Water
`
`Not reached
`
`Corn oil
`
`13.1 g/kg
`
`10
`
`Corn oil
`
`Not reached
`
`Water
`
`Not reached
`
`Corn oil
`
`> 16.0 gikg
`
`Water
`
`Not reached
`
`3/10 died; sluggish, wet
`fur and diarrhea on
`one day; low order of
`toxicity
`None died: sluggish at
`4 g k 3
`7/10 died: sluggish, wet
`fur, nose covered
`with blood on 1 day
`None died at 8 gikg;
`appeared normal
`None died at 2 gikg;
`appeared normal
`None died at 16.0 gikg;
`wet fur and diarrhea
`at 1 day
`None died at 4 gikg:
`animals sluggish
`
`Polyquaternium-10
`(Lot 1)
`
`Polyquaternium-10
`(Lot 1)
`Polyquaternium-10
`(Lot 2)
`
`Polyquaternium-10
`(Lot 2)
`Polyquaternium-10
`(Lot 2)
`Polyquaternium-10
`(Lot 3)
`
`Polyquaternium-10
`(Lot 3)
`
`Polyquaternium-10
`1 % in shampoo
`Polyquaternium-10
`1% in condi-
`tioner
`
`5
`
`5
`
`3
`
`10
`
`10
`
`Formulation
`
`> 5 gikg
`
`None died; nonfoxic
`
`Formulation
`
`> 5 gikg
`
`None died: nontoxic
`
`25
`
`25
`
`26
`
`26
`
`26
`
`27
`
`27
`
`_ _ _
`28
`
`29
`
`Inhalation Toxicity
`Inhalation tests of three lots of Polyquaternium-10 were conducted using in-
`dividual groups of 6 rats and an exposure period of 8 h. The rats were exposed
`to a substantial aerosol concentration that was prepared by placing 50 g of test
`material on a 200 cm2 tray for 16 h before testing in a sealed chamber and dur-
`ing the 8-h exposure period. A fan was operated intermittently to agitate the in-
`ternal chamber atmosphere. No signs of toxicity were observed during the ex-
`posure period.(25)
`
`Dermal Toxicity and Irritation
`Three lot samples of Polyquaternium-10 were tested individually using three
`groups of 5 rabbits each. No deaths occurred when 4.0 g/kg was applied di-
`rectly to the skin and the application site covered. Erytheme developed, but no
`other remarkable gross lesions were observed. The three lot samples were con-
`sidered, at most, slightly toxic. ( 2 5 - 2 7 )
`Three lots of Polyquaternium-10 were tested on the clipped uncovered in-
`tact skin of the abdomen of 5 rabbits at individual lot concentrations of 2%, 5%,
`
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`

`ASSESSME NT: POLYQU ATE RN I UM-10
`
`341
`
`and 10% (in water). At 2% concentration, no irritation was observed in 4 rab-
`bits, and moderate erythema was seen in 1 rabbit. At 5.0% concentration, no ir-
`ritation was observed in 3 rabbits, and moderate erythema was seen in 2 rab-
`bits. At 10% concentration, no irritation was observed in 2 rabbits, and moder-
`ate erythema was observed in 3 rabbits. The investigator termed the observed ir-
`ritation a trace reaction.(25-27)
`A shampoo containing 0.5% Polyquaternium-10 had a primary irritation in-
`dex (PII) of 5.37 (max. 8) in a study performed according to CFR Title 16:
`1500.3(~)(4) and 1500.41.(30) The test used 12 rabbits, dosed at 0.5 ml of the
`shampoo, with 6 having intact skin and 6 having abraded skin. The shampoo
`was a severe skin i r ~ i t a n t . ' ~ ~ . ~ ' )
`The dermal toxicity of a shampoo containing 0.5% Polyquaternium-10 was
`evaluated according to the procedures in the CFR Title 16:1500.3(~)(1)(ii)(c) and
`1500.40.(30) The product was tested on the clipped skin of 5 rabbits and 5 that
`were both clipped and abraded. The dermal LD,, of the formulation was greater
`than 2 g/kg.(28,3''
`A 21-day subchronic dermal toxicity study was conducted with a condi-
`tioner containing 1 '/o Polyquaternium-10. Five male and five female rabbits
`were given 0.5 ml undiluted product once a day for 21 consecutive days. The
`test material was applied to the clipped dorsal trunk of the rabbits, and the skin
`of 5 of 10 animals was abraded before application of the test material. The test
`material remained in contact with the skin 6 h daily, and sites were uncovered.
`A control group of 5 male and 5 female rabbits had tap water applied to intact
`and abraded skin. N o rabbits died during the test period, both groups had nor-
`mal weight gains, and no lesions were observed at necropsy. Initial and terminal
`hematological and urinalysis values were within normal range. The product was
`not a cumulative dermal toxin.(32)
`Six New Zealand rabbits were used to evaluate the primary skin irritation of
`a conditioner containing l o l o Polyquaternium-10. One-half (0.5) milliliter of the
`test material was administered to 1 intact and 1 abraded test site per animal. The
`clipped test sites were covered by occlusive patches for 24 h, and test sites were
`scored for irritation immediately after patch removal and 48 h later. The group
`PI1 was 0.0 (max. 8). The product was not a primary skin irritant(29) (Table 3).
`
`Ocular Toxicity
`Three lots of Polyquaternium-10 were tested for ocular toxicity, both as a
`dry powder and as an aqueous solution using groups of 5 animals. N o irritation
`was produced by the powder form of any lot. When applied as the aqueous
`solution, no irritation was produced by lot 1 at a 20% concgntration or by lot 2
`at a 5% concentration. A trace of irritation was produced by lot 3 at a 10% con-
`centration. ( 2 5 - 2 7 )
`A shampoo containing 0.5% Polyquaternium-10 was tested for ocular irrita-
`tion in two groups of 12 rabbits according to the procedures given in the CFR
`Title 16:1500.3(~)(4) and 1 500.42.(30) One group received full-strength instilla-
`tions of the shampoo; a second received instillation of a 5 % dilution. The eyes
`of half of the rabbits of each group were rinsed after product instillation. No irri-
`
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`

`29
`
`PI1 0.0 (max. 8); conditioner
`
`was not skin irritant
`
`n
`
`28, 31
`
`tant
`was classified as severe irri-
`
`PI1 5.37 (max. 8); shampoo
`
`for 24 h
`and abraded area; occluded
`0.5 rnl applied to each intact
`
`abraded skin
`6 with intact and 6 with
`
`CFR 16:1500.3(C)(4), 1500.41 ;
`
`1 .O%
`
`Direct
`
`Direct
`
`6
`
`12
`
`ternium-I0
`Polyqua-
`taining 1 .O%
`
`Shampoo contain-
`
`Conditioner con-
`quaternium-10
`ing 1 .O% Poly-
`
`________i_________________-_---______--
`
`27
`
`26
`
`25
`
`27
`
`26
`
`25
`
`bellies for 24 h
`
`No irritation in 3; moderate
`
`0.01 ml applied to clipped intact
`
`rabbit
`capillary injection in 1
`
`No irritation in 4; moderate
`
`logical results
`no remarkable gross patho-
`No deaths; erythema at 24 h;
`
`logical results
`no remarkable gross patho-
`No deaths; erythema at 24 h;
`
`logical results
`no remarkable gross patho-
`No deaths; erythema at 24 h;
`
`0.01 rnl applied to clipped intact
`
`bellies for 24 h
`
`skin. occluded for 24 h
`
`Applied directly to clipped intact
`
`skin, occluded for 24 h
`
`Applied directly to clipped intact
`
`skin, occluded for 24 h
`
`Applied directly to clipped intact
`
`No irritation in 2; moderate
`
`rabbits
`capillary injection in 3
`
`rabbits
`capillary injection in 2
`
`bellies for 24 h
`
`sion)
`
`0.01 ml applied to clipped intact
`
`10% (suspen-
`
`Water
`
`5 010
`
`Water
`
`2 010
`
`Water
`
`None
`
`None
`
`None
`
`5
`
`5
`
`5
`
`5
`
`5
`
`5
`
`Polyquaternium-10
`
`(Lot 3)
`
`(Lot 2)
`
`Polyquaternium-10
`
`(Lot 1)
`
`Polyquaternium-10
`
`(Lot 3)
`
`Polyquaternium-10
`
`(Lot 2)
`
`Polyquaternium-10
`
`(Lot 1)
`
`Polyquaternium-10
`
`Reference
`
`~
`
`Results
`
`Method
`
`Concentration
`
`Vehicle
`
`No. of rabbits
`
`Compound
`
`TABLE 3. Dermal Toxicity and Irritation
`
`W k
`
`

`

`ASSESSMENT: POLYQUATE RN IUM-10
`
`343
`
`tation was observed in the eyes of any animal. The full-strength shampoo was
`not an eye i ~ r i t a n t . ' ~ ~ , ~ ~ )
`Polyquaternium-10 was
`'The ocular irritation or a conditioner containing 1
`evaluated in 9 New Zealand rabbits. One-tenth (0.1) milliliter of the test material
`was instilled into one eye of each rabbit, and the other eye served as an un-
`treated control. The eyes of 3 rabbits were rinsed 15 sec after application of the
`test solution. No irritation was observed in rinsed or unrinsed eyes 1, 2, 3, 4,
`and 7 days after application of the product. The conditioner was not an eye irri-
`tant.'29) A summary of ocular test data is given in Table 4.
`
`MUTAGENICITY A N D GENOTOXICITY
`
`Polyquaternium-10 was tested in triplicate and at five concentrations for
`mutagenic activity in the Salmonella typhirnuriurn assay (Ames test) on TA-98,
`TA-100, TA-1535, TA-1537, and TA-1538 tester strains without and with meta-
`bolic activation. The metabolic activation was induced with S9 liver homoge-
`nate from male Sprague-Dawley rats pretreated with Aroclor 1254. In this
`setting, Polyquaternium-10 was not mutagenic in any of the five bacterial strains
`tested with and without metabolic a ~ t i v a t i o n . ' ~ ~ )
`Chinese hamster ovary (CHO) cells were exposed for 5 h to five concentra-
`tions of Polyquaternium-10 (0.1 2-0.285% in DMSO) without and with addition
`of S9 liver homogenate for metabolic activation (as in the Ames assay). Although
`some degree of mutagenicity was observed in both of the duplicate assays in the
`absence as well as in the presence of S9 homogenate, the response was not
`dose dependent. Polyquaternium-10 was thus considered to be nonmutagenic
`in the CHO test. In sister chromatid exchange (SCE) assays, Polyquaternium-10
`in CHO cells both with and without enzyme induction by S9 liver homogenate
`did not increase the frequency of SCE over the range of concentrations tested
`(0.14-0.23°/o).'34'
`Polyquaternium-10 was evaluated also for its genotoxic effect in the rat he-
`patocyte primary culture/DNA repair test in six concentrations between 0.0009
`and 0.23%. The results from duplicate samples indicate significant genotoxicity
`of this cosmetic ingredient at three of six doses. However, the measured activ-
`ity, which was not dose dependent, was determined with hepatocytes from a
`single preparation and quantitated by liquid scintillation counting rather than by
`
`the more reproducible quantitative aut~radiography.'~~) The results of this study
`do not allow a valid conclusion about the activity of Polyquaternium-10 in he-
`patocyte DNA repair test.
`Polyquaternium-10 was tested for its in vivo clastogenic activity in female
`Swiss mice by injecting single doses of 0.125, 0.25, and 0.4 g/kg, respectively,
`into the peritoneal cavity of 5 males and 5 females. Blood samples were col-
`lected 24, 48, and 72 h after the injection. Blood smears were prepared and
`stained for evaluating the possible presence of micronuclei. No statistically sig-
`nificant increases in micronucleated polychromatophilic erythrocytes were re-
`ported. ( 3 4 )
`
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`
`
`
`

`

`W rn
`
`P
`P
`W
`
`Direct application, 3 eyes rinsed
`
`conditioner
`
`0.1 rnl of
`
`terniurn-10
`Polyqua-
`taining 1 .O%
`
`Direct
`
`9
`
`Conditioner con-
`
`27
`
`27
`
`26
`
`26
`
`25
`
`25
`
`none in 4
`in 1 eye,
`
`tival sac
`
`sion)
`
`Trace irritation
`
`0.5 rnl single instillation into conjunc-
`
`10% (suspen-
`
`Water
`
`tival sac
`
`No irritation
`
`0.5 rnl single instillation into conjunc-
`
`Direct
`
`Powder
`
`tival sac
`
`No irritation
`
`0.5 rnl single instillation into conjunc-
`
`5 %
`
`Water
`
`No irritation
`
`0.5 rnl single instillation into conjunc-
`
`Direct
`
`Powder
`
`No irritation
`
`0.5 rnl single instillation into conjunc-
`
`tival sac
`
`2 010
`
`Water
`
`tival sac
`
`No irritation
`
`Single instillation into conjunctival sac
`
`Direct
`
`Powder
`
`5
`
`5
`
`5
`
`5
`
`5
`
`5
`
`Reference
`
`~
`
`Results
`
`Method
`
`Concentration
`
`Vehicle
`
`No of rabbits
`
`~~~
`
`Compound
`
`TABLE 4. Ocular Toxicity
`
`quaterniurn-10
`ing 0.5% Poly-
`
`Shampoo contain-
`
`(Lot 3)
`
`Polyquaterniurn-10
`
`(Lot 3)
`
`Polyquaterniurn-1 0
`
`(Lot 2)
`
`Polyquaterniurn-10
`
`(Lot 2)
`
`Polyquaterniurn-10
`
`(Lot 1)
`
`Polyquaterniurn-10
`
`(Lot 1)
`
`Polyquaterniurn-10
`
`28, 31
`
`No irritation at
`
`CFR 16:1500.3(C)(4) and 1500.42; half
`
`of test eyes were rinsed
`
`0.05%
`1 .O and
`
`dilution
`
`Direct and 5%
`
`12
`
`29
`
`irritant
`not an eye
`No irritation,
`
`unrinsed
`rinsed or
`centration,
`either con-
`
`

`

`ASSESSMENT: POLYQUATE RN IUM-10
`
`345
`
`CLINICAL ASSESSMENT OF SAFETY
`Primary Skin Irritation, Sensitization, and Photosensitization
`14 lot of Polyquaternium-10 was tested for primary skin irritation on 106 sub-
`jects. A 5% wlv solution in water was applied to the skin under occlusive
`patches for 48 h. No skin irritation was observed at 48 and 72 h after applica-
`
`t i ~ n . ' ~ ~ ) No irritation was observed when a 5% Polyquaternium-10 solution was
`applied daily under occlusive conditions for 21 days to 27
`Three separate lots of Polyquaternium-10 were tested by a repeated insult
`patch test (RIPT) protocol using 50 subjects. A 2% w/v solution in water was ap-
`plied to the skin on lintine disks under occlusive patches for 24 h. The treatment
`reaclion sites were scored at 24 h. Following a 24-h nontreatment period, the
`sites were again exposed to the test samples. A 2-week nontreatment period fol-
`lowed the 15th application. The test sites were evaluated and then treated in a
`similar manner and scored at 24 and 48 h. No evidence of either irritation or
`sensitization was observed in any subject when exposed to the three lot samples
`of Polyquaternium-I 0. (37-39)
`There was no irritation or sensitization when a 5% w/v solution of Polyqua-
`ternium-10 was used in an RlPT on 203
`A shampoo containing 0.5% Polyquaternium-10 was evaluated for primary
`and an RIPT.(42' One
`irritation and sensitization by a prophetic patch
`hundred subjects participated in the prophetic patch test, and no reactions were
`observed to either of the two closed patches applied. Fifty-three subjects com-
`pleted the RIPT, and no reactions were observed during induction or at chal-
`lenge. Photosensitization also was evaluated in these two studies by exposure of
`the sites to UV light during the induction phase of the RlPT study and during the
`challenge phase of the prophetic patch test. The undiluted shampoo was not a
`primary skin irritant, sensitizer, or photosensitizer.(3' 4 3 )
`1-he primary irritation, sensitization, and photosensitization of an undiluted
`sharripoo containing 0.5% Polyquaternium-10 was evaluated in an RlPT accord-
`
`ing to the procedures of Shelanski and S h e l a n ~ k i ' ~ ~ ) using a 25-member panel.
`The UV light was applied during the induction phase of the study. The shampoo
`was tested at full strength. The product was nonirritating, nonsensitizing, and
`no n p h o t ose n si t iz i n g . ( 4 4 )
`Forty-six panelists participated in an RlPT of a conditioning product contain-
`ing 1 '/o Polyquaternium-10. Patches containing 0.2 ml undiluted conditioner
`were applied to the inner arm or back of each subject on Mondays, Wednes-
`days, and Fridays for a total of 10 induction patches. After a 10-20 day nontreat-
`ment period, two challenge patches were applied simultaneously, one to the
`original test site and the other to an untreated site. One panelist had minimal
`erythema (score of + on a 0-4 scale) to induction patch 9, and another panelist
`had f reaction to induction patch 10. Two panelists reacted at challenge; 1
`had .k reactions at the 24-h reading of both challenge patches, and another had
`scores of 1 and 2, and 2 and 2 at the 24-h and 48-h readings of the original site
`patch and untreated site patch, respectively. After rechallenge, the same panel-
`ist had no reactions. The conditioner was not an irritant or sensitizer.(45)
`A controlled use study following CTFA guidelines(46) was performed using a
`shampoo containing 0.5% Polyquaternium-10. Eighty-three subjects participated
`
`
`
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`
`
`
`

`

`346
`
`COSMETIC INGREDIENT REVIEW
`
`in the 4-week study, which required daily product use. The scalp, neck, face,
`and hair of each subject were examined for irritation. The shampoo was nonirri-
`tating under the conditions of this t e ~ t . ' ~ ' . ~ ' ) Results are summarized in Table 5.
`
`Moderation of Skin Irritants
`An extensive study was undertaken to determine the capacity of Polyquater-
`nium-10 to moderate reactions to skin irritants. The first phase of the study ex-
`
`Polyquaternrum- I0
`concentration i%)
`
`Comments
`
`Referent?
`
`TABLE 5. Clinical Assessment of Safety
`
`Jest type"
`
`No of
`suhlecth
`
`RlPT
`
`RI PT
`
`RlPT
`
`50
`
`50
`
`50
`
`Product type
`
`Polyquaternium-10
`(Lot 1 )
`
`Polyquaternium-10
`(Lot 2 )
`
`Polyquaternium-10
`(Lot 3)
`
`_
`
`
`
`_ _ _ _ _ ~ _
`Prophetic
`patch
`test
`
`100
`
`Shampoo
`
`RI PT
`
`53
`
`Shampoo
`
`RlPT
`
`25
`
`Shampoo
`
`RlPT
`
`46
`
`Conditioner
`
`0.5
`
`0.5
`
`0.5
`
`1
`
`No reactions; not
`an irritant or
`sensitizer
`N o reactions; not
`an irritant or
`sensitizer
`N o reactions; not
`an irritant or
`sensi tizer
`
`No reactions; not
`an irritant, sen-
`sitizer, or pho-
`tosensitizer
`N o reactions; not
`an irritant, sen-
`sitizer, or pho-
`tosensitizer
`N o reactions; not
`an irritant, sen-
`sitizer, or pho-
`tosensitizer
`Two minimal re-
`actions during
`induction, one
`minimal and
`one moderate
`reaction at
`challenge; re-
`challenge to
`moderate reac-
`tor was nega-
`tive; not an
`irritant or sen-
`sitizer
`No reactions; not
`an irritant
`
`37
`
`38
`
`19
`
`43
`
`43
`
`44
`
`45
`
`31, 47
`
`Con-
`trolled
`use
`
`83
`
`Shampoo
`
`0.5
`
`<'See text for details of experimental procedure.
`
`
`
` at Novartis Global on February 18, 2014ijt.sagepub.comDownloaded from
`
`
`
`

`

`ASSESSMENT: POLYQUATERNIUM-10
`
`347
`
`amined the cutaneous toxicity and effects on wound healing of Polyquater-
`nium-10. The Polyquaternium-10 used in this study had a molecular weight of
`approximately 400,000. Six subjects were given single 0.1 mi intradermal injec-
`tions of 0.25% and 1 .O% aqueous Polyquaternium-10 into the back. The injec-
`tion sites were observed daily for 1 week, and no reactions were observed at the
`0.25'Y0 Polyquaternium-10 sites. The 1 .O%
`injections produced small (5 mm)
`inflarned nodules within 24 h. The nodules disappeared without residue within
`a few days.
`The effect of Polyquaternium-10 on wound healing was studied by applying
`1% or 2 % Polyquaternium-10 to raw blisters produced by 15% ammonia solu-
`tions. A single application or five daily applications enhanced wound healing if
`the 2% Polyquaternium-10 was allowed to dry before the site was bandaged. If
`the test site was bandaged before the polymer dried, healing was slower than
`untreated control sites. These studies suggest that Polyquaternium-10 protected
`the wound surface and promoted reepithelialization.
`The second phase of this study evaluated moderation by Polyquaternium-10
`of inflammatory reactions to sodium lauryl sulfoacetate, shampoos, a depilatory
`cream, Rhus (poison ivy) dermatitis, and soap. In all cases, pretreatment andlor
`concurrent treatment of the test site with Polyquaternium-10 resulted in less se-
`vere reactions to the irritants(48) (Table 6).
`
`SUMMARY
`
`Polyquaternium-10, a white granular powder, is a polymeric quaternary am-
`monium derivative of hydroxyethyl cellulose with cationic surface-active prop-
`erties. The product for cosmetic use varies in molecular weight from 250,000 to
`600,000. Polyquaternium-10 is soluble in water and insoluble in alcohol and
`nonpolar organic solvents. Results of studies in rats indicated that Polyquater-
`nium-10 has, at most, only a low potential to penetrate the stratum corneum. it
`is adsorbed by keratinous surfaces. The ingredient is used in cosmetics as a con-
`ditioner, thickener, and emollient in hair care products, lotions, and makeup
`products at reported ranges of concentration of 50.1 %-5%.
`Polyquaternium-10 with and without metabolic activation was assayed for
`mutagenicity in 5 S.
`typhirnuriurn tester strains, in Chinese hamster ovarian
`cells, for in vitro sister chromatid exchange in CHO cells, and for clastogenic ac-
`tivity in female Swiss mice. Polyquaternium-10 was negative for mutagenicity in
`these four short-term tests. In the rat hepatocyte primary culturelDNA repair
`test, genotoxicity was present but was not dose related.
`Polyquaternium-10 permeates and adsorbs into isolated stratum corneum
`obtained from fetal pigs, neonatal rats, and humans. LD,,s
`for lots of Polyquater-
`nium-10 in corn oil were not obta