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J. Soc.Cosmet.hem., 0, 297-306 (September/October989)

The flex wash est:A methodor evaluatinghe mildness fpersonalwashingproductsDARCEE DUKE STRUBE, STEPHEN W. KOONTZ,RICHARD I. MURAHATA, and RICHARD F. THEILER,Unilever esearchnitedStates,nc., 45 RiverRoad,Edgewater,J07020.

Receivedovember, 1988.

SynopsisVarious linicalproceduresxist or determininghe mildness f personal ashing roducts.t is commonto useseveral f theseevaluationmethodsn the development f a safety-and-claimupportpackage. heutility of manyof the methodss limited by their susceptibilityo fluctuationsn weather onditions.nthispaperwe describe method, he flexwash est,which s not affected y changesn weather ndcanbeused sa highlyreproducible ethod or determininghe relative rritancy otentialof personal ashingproducts.he flex wash estconsistsf a sixty-secondash, hree imesdaily,of the antecubitalossaflexarea)of the arm. Washing s conductedor five consecutiveaysor until a moderate rythemicesponseselicited.Erythema s assessedrior to eachwashand four hoursafter he last daily wash.Twelvecommer-ciallyavailable ersonal ashing arswereevaluatedn thisstudy.The flex wash s a reproduciblelinicaltest hat distinguishesifferencesn the relative rritancypotentialof various yndet synthetic etergent)andsoapbarsand s independentf ambientweather onditions.

INTRODUCTION

A varietyof test proceduresxist for determining he relativemildness f personalcleansingroducts n humanskin (1-4). The overallcategoriesor the methodsn-cludepatch esting,exaggeratedse ests,and normaluse ests.Normal use estswithsoapbarshavebeenconducted1), but they require argepanelsizesn order o differ-entiatebetweenvarying evelsof performance. his can become ery expensive ndtime-consumingor routine screening f marketedproducts nd new formulations.Patch estmethodsike the soap hamberest 2) canbe useful n distinguishing iffer-encesn relative rritancypotential.However, he authors eport hat surfactantsanrespond ifferentlyunderoccluded ersus ormaluseconditions.Arm immersion 3)andhalf-face4) testsmorecloselyesembleealistic seconditions ut areweather-de-pendent.Due to weatherdependencyactors hat affectmost of these ests, clinicaltrialswith thesemethods re mostsensitive uring he cold, dry winter months.The datapresentedn this paperdemonstratehe reproducibility nd utility of the flexwash est o accurately iscriminatehe relative rritancypotentialof personal ashing

297


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298 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

productsegardlessf the ambientweather onditions. he studies eported erewereconductedn the New York-New Jersey rea.

MATERIALS AND METHODSFourteencommercially vailablepersonalwashingbars designated arsA-N) weretestedusing he flex wash est. Compositionalngredients f thesebarsasobtainedromthe label are provided n Table I. Bar A was includedas a reference incestudies e-portedby others 2) demonstratedhe mildness f this bar.The subjects eremaleand emale olunteersetween 0 and55 years ld. All subjectswere n generalgoodhealthwith no historyof dermatologic onditions.nformedcon-sentwasobtainedprior to the initiation of the test. The antecubital ossaeflex area)ofthe armswere ree of cutsand abrasions, ith no irritation presentat the onsetof thestudy.Twelve o twentysubjects ere andomly electedrom a groupof 200 for eachdirect comparisonf two bars.The test groupwas hen divided nto two subgroups,which werebalancedor handdominance.Group usedproduct1 on the left arm andproduct2 on the right, while group I used he same wo productsbut on oppositearms.

All wash reatmentswereconducted y the subjectundersupervisionn the laboratory.The sponge JAECE denti-Plugs,sizeD foam test tube plug) and the cleansing arwere moistenedwith tap water (approximately 00 ppm total hardness,maintained t92 ___ F) mmediately eforeuse.The sponge asstroked veroneof the test barsten timesby the studymonitorandplacedn the subject'sight hand.The left flexareawasmoistened ith tap water and gentlywashedor 60 seconds. he washing roce-dure was an elliptical motion with 120 strokesper minute. The flex areawas then

Table ICompositionof CommercialPersonalWashing Bars

Barcode Predominantngredients

EFGHIJKL

M

N

sodiumcocoyl sethionate, tearic cid, sodium allowate,water, sodium sethionate, o-conut acid, sodium stearatesodium allowate,potassium oap,watertriethanolamineoap,sodium allowate,glycerinsodium alowate,sodiumcocoate, ater, coconut cid, sodiumpolyacrylate, lycerin,cocoabuttersodiumcocoate, odium allowate,water, glycerin, coconut cidsodium allowate,sodiumcocoate, lycerin,water, coconut cidsodium allowate,sodium ocoate, ater, PEG-6 methylether, triclocarban, lycerindextrin,sodiumaurylsulfoacetate,ater,boricacid,urea,sorbitol,mineraloil, PEG-14Msodium allowate,sodiumcocoate,water, petrolatum,glycerinsodium allowate,sodiumcocoate,water, mineraloil, PEG-75, glycerin, anolinoilsodium allowate,sodiumcocoate,water, vegetable ilsodium allowate,sodiumcocoate,water, sodiumcocoglycerylther sulfonate, lycerin,coconut acidsodium allowate,sodiumcocoate, odium ocoglycerylthersulfonate, lycerin,coconut rpalm kernalacid, triclocarbon, olyquaternium-7sodium allowate,sodiumcocoylsethionate,water, sodiumcocoate, tearic cid, triclosan


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METHOD FOR SKIN IRRITATION 299

rinsed or approximately 0 seconds nderrunning ap water until all lather wasre-movedand then patteddry with a softdisposableowel. The procedure as epeated nthe right arm using he left handwith the otherproductbeing tested.The test siteswere treated hree timesdaily with 1.5 hoursbetweenwashingsor five consecutivedays.The test siteswereevaluated y a trainedexaminer or irritation immediatelyprior toeachwashand four hoursafter the third daily wash, or a total of 20 evaluations. iteswere gradedusing a seven-point coringsystem 0-3). Dryness s not scored n thismethodas lakesare removed y the application rocedure.Grade Description0 Normal, no erytherna+ Barelyperceptible rytherna1 Mild erythema,no edema

1 + Mild to moderate rythema,with/without edema2 Moderateconfluenterythema,with/without edema2 + Moderate o deeperytherna,edema3 Deep erythema,edema,vesiculationEachsitewas reated n the prescribed ethod or a maximumof fifteenwashes r untila moderate onfluent rythernic esponseGrade2) waselicited. When a gradeof 2 orgreater Figure la) wasattained, reatmentof the site wasdiscontinued. ontinuingtreatmentbeyond his point quickly results n a severe esponsend discomfort o thesubject.The remaining lex areawas washeduntil Grade 2 erythemawasattainedorfifteen treatments ompleted.Subjectswere restricted rom applyingany rnoisturizing roducts o their arms. Thisincluded he useof body otions,sunscreens,ndbathoils. Additionally,subjects ereinstructed ot to wash he testsiteswith soapduringbathing.Sunbathing asprohib-ited during the test week.STATISTICAL ANALYSISThe datawasanalyzed y four methods.When an endpointwas eached,hat scorewascarried hrough or all remainingevaluations.Mean total irritation scoreand standarddeviationwere calculatedor eachbar tested.This "meanerythemascore"wasused orgeneral ntercomparisonsetween estsand to providea graphicpictureof a bar'sper-formance uring the test week.For all statistical nalyses, hen a subject'sirst site reached n endpointscore, hescoresor bothsiteswerecarried hrough or all remaining valuations. owever, reat-ment of the remaining itewascontinued. he following tatisticalmethodswereused:1. A signtest utilizing the binomialequationwasused o evaluate ata for only thosesubjectswho reached n endpoint.This methoddeterminedwhich product reat-ment resultedn achievinghis endpoint irst for erythema; ryness asnot evalu-

ated. Subjectswho were able to completeall wash reatmentson both arms wereconsidered a tie.2. The Wilcoxon matchedpairs test wasused o compare rythemascores t the timeof first site termination egardlessf the numberof treatments.The Wilcoxon testwasalsoused o compare cores t eachobservationoint.


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300 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Figure la. The same anelist'sight flexarea hat waswashed ine imeswith barB. This flexexhibits nirritation score of 2.

3. A survival estwasconducted n the numberof washes sitewasexposedo prior totermination.

RESULTSIrritation due to the useof the testmaterialdevelops ver he five-day est period.Theclinical ppearancef the flex areaundergoingepeated ashingwith a cleansingar


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Figure lb. A panelist's eft flex area that has been washednine times with bar A. No indicationofirritation exists.

rangesrom normal Grade0), to deeperythemawith edema Grade3). A scoreofGrade2 is the termination oint in the flex wash est due to panelistdiscomfort.Acharacteristicesponseor Grade0 and Grade2 is shown n Figure 1.The skin's esponseo the treatment ncreasest different atesdepending n the rela-tive irritancypotentialof the bar. Table II provides summaryof four studies om-paringbarswith varyingdegrees f relative rritancypotential.The increasen mean


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302 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTSTable II

Summary f ErythemaScoresEvaluation number

Ave. # 4 8 12 16 20Test Washes (Day 1) (Day 2) (Day 3) (Day 4) (Day 5)

Bar A 19 2.0 4.5 4.5 6.5 6.5Bar H 18 4.5 7.0 10.0' 11.5 12.5Bar A 18 0.0 2.0 7.0 7.5 8.0Bar I 14 0.5 11.0'* 21.5'* 21.5'* 23.0**Bar A 20 0.5 1.5 3.0 3.5 6.5Bar B 10 4.0* 24.5** 31.0'* 32.0** 32.5**Bar A 20 0.5 1.0 4.0 7.0 9.5Bar E 12 3.0** 20.5** 26.5** 32.0** 32.5**All endpointscores f 2.00 or greaterwerecarried hrough or remaining valuations. aluespresentedreinformational nly. Statistical nalysis asperformed singa Wilcoxonmatched air test.* Significantly ifferentat p < 0.05.** Significantly ifferentat p < 0.01.total scoreshows he rate of developmentof the observed rritation. The averagenumberof washess the number hat could be conductedwith that productbeforeamoderate esponseGrade2) waselicited.Bar B develops responseuickly, with theaverage core pproachinghe maximum alueby the twelfthevaluationday3). Milderbars H and A exhibit a gradual ncreasen response ithout the sites reaching hemaximumendpoint core. he four-hour estperiodbetweenhe third dailywashandthe final daily evaluation llows he responseo develop, esulting n the highestdailyscore.Recovery f the test sitesoccurs uring the sixteen-hour vernight est periodbetween onsecutive ashdays.This results n plateausn the responseurve.GraphicrepresentationFigure2) shows he sigmoidal attern hat typicallybecomes oreprominent s the irritancypotentialof the bar increases.se of more rritatingbarsresults n fewer survivorsless han Grade 2) at any time. Figure 2 also shows hatrepetitive estingof a bar produceserysimilar esponseurvesn testsduringdifferentseasons.

This absencef seasonalariation nd he reproducibilityf the flexwash est s shownin Figure3. The graphshowshe mean otal erythema core btainedor two productsof different elative rritancypotentials vera fourteen-monthime period.Meanscoresfor barsA and B were5.7 --- 1.2 and 27.7 -+ 2.0, respectively.he percentof pan-elistscompletinghe study s alsoveryconsistent, ith 93% --- 6% completinghestudieswith bar A and 5% --- 3% completingestingwith bar B.Elevenmarketed ersonal ashing arsweredirectlycomparedo bar A using he flexwash est. The percentagef survivorsnd the meannumberof evaluationsompletedfor eachpersonalwashingbar is shown n Table III. Statisticalanalysisof the dataindicateshat all the bars estedweresignificantlymore rritating than bar A based nthe Wilcoxonmatched airs est. The sign and survival est alsoshowed ignificantdifferences etweenall comparisonsxceptA vs H. There were no caseswhere hesubjectseached n endpoint coren the bar A-H comparison. tatistical nalyses ereonly conducted n the bars hat weredirectlycompared.


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80,

100

20-

0 0 10EVALUATION

15 20

Figure 2. Rate of irritation developments shown s the percentsurvivorsless han Grade2) at eachevaluationime.Theproduct odesrebarH (I); barC (A); barB--March ((2));March C)),July O).Based n these ata, the irritancypotentialof thesebarsvariedsignificantly: arsA andH were he milderproducts; arsC andL weremore rritating;andbarsB, D, E, F, G,I, J, andK wereharsher.A comparisonf the ingredientsndicateshat barswith highlevelsof soapweremore rritating han he syndet synthetic etergent) r soap/syndetbars.The additionof smallamounts f glycerin, ocoa utter, mineraloil, andpetro-latum did not appear o significantly ecreasehe relative rritancypotential or theseproducts.

DISCUSSION

Repetitiveclinical evaluations f two commercially vailablepersonalwashingbars,barsA andB, demonstratehat the flex wash est s a reproduciblessayhat is mini-mallyaffected y localclimatic luctuations. arsA andB werechosenor comparisonsthroughouthe yearsince hey representhe mildestcommerciallyvailable ar and asoapbar of moderate arshness,espectively2). In elevenevaluationsf bar A, thepercentagef subjectsompletingll fifteenwashes as93% -+ 6%. Similarly, n fiveevaluations f bar B, the percentage f subjects ompletingall fifteen washeswas5% -+ 3%. Althoughsomevariationof responseccurred,t is mainly attributable ointerpanel ariability ince ubjects erenot screenedor soap ensitivity. he standarddeviationwas ess han 10% betweenests onductedt different imesof the year.We


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304 JOURNALOF THE SOCIETYOF COSMETICCHEMISTS

32,

JAN MAR APR JUN JUL AUG OCT NOVmONTHS

Figure 3. Seasonalomparisonsf mean otal irritationscores uringvariousmonthsare shown or bar A(solid) and bar B (crosshatch).believe he testmethod educeshe influencesf stratumcorneum ydration nd turn-overdue to the sponge pplication rocedure nd thereforemakes he test essweather-dependent.We have ound hat the flex wash s capable f significantly iscriminating etweenmildercleansingystemshan s typically chievableith a chamberest.Thisresult sillustrated n Table IV, which compareshe relativedifferencesbservedor the flexwashanda modified oap hamberest 6) for threesoapbars.Using the flex washone observestatistically ignificant ifferenceshat are not seenusinga modifiedsoapchamber est. Furthermore,he modifiedsoapchamber est isreported o be assensitive s the test previously esigned y Frosch nd Kligman (7).Current rends o developmilderactivesystemsor personal leansingnd the ability tomoreeasilydiscriminate etweenhese ormulationss an importantaspect f anyclin-ical testingregime. We find that the flex wash s capable f discriminating mallerdifferencesn irritationpotential,while goodcorrelationo the soap hamber est canbe foundwhen the differencesn irritation potential or two products re large e.g.,soap ersus yndetbars).As an example, n these tudieswe chose arA asa referencetandard inceFrosch ndKligmandemonstratedhat this productwas he mildestof 18 bars ested n the soapchamberest 2). Utilizing the flexwash,barA wasalso ound o be superiorn mild-ness o the eleven bars tested, which in overall terms correlateswell with results re-


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Table IIIThe MildnessAttributesof PersonalWashingBarsUsed n the Flex Wash Test

Mean total Mean number ofBar erythema core % Survivors* evaluationsompleted**

BarA 5.7 -+ 1.2 93 -+ 6 19Bar H 11.0'** 83 18Bar L 18.4'** 31 14'**Bar C 20.4*** 26 14'**Bar K 25.4*** 15 7***Bar E 24.4*** 12 12'**Bar G 27.8*** 12 8***BarJ 26.1'** 7 9***Bar B 27.7 + 2.0*** 5 -+ 3 10'**Bar I 27.6*** 0 9***Bar F 28.6*** 0 8***Bar D 29.4*** 0 7***

* Data representshe average umberof panelists ompleting15 washes.** Data representshe average umber f evaluationsmaximum f 20) the panelistsompletedn eachexperimentor a particularproduct.*** Significantly ifferent p < 0.05) frombar A usinga survivalest or the meannumberof evaluationscompletednda Wilcoxonmatched air test or the mean otalerythemacores.

ported or the soap hamberest.BarsB, C, G, J, andK wereclassifieds"slightlyirritating" n the original oap hamberest.BarsH and wereclassifiedmoderatelyirritating." However, while many of the differences mongproducts n both thechamberestand lexwasharenot significantlyifferent, omemovementn the rankorder rom testto testwouldbe expected.In conclusion,he lexwashest sa reliablemethodorevaluatingherelativerritancy

Table IVA Comparison f ErythemaScoresor Three Bar Soaps sing a ModifiedSoapChamberTestand the Flex Wash

Modifiedsoap hamberest Erythema score Significance*Bar G 1.09 N.S.Bar M 1.09 N.S.Bar N 0.94 N.S.Flex wash

Mean end pointerythema Significance**Bar GBar NBar MBar N

5.832.2O p 0.011.691.18 p < 0.08

* Comparisonsf means singDuncan'sMultiple RangeTest.** Statistical nalysis f rank scores sing he Wilcoxon2 sample est.


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306 JOURNAL OF THE SOCIETYOF COSMETICCHEMISTSpotentialof personal ashing roducts. he test s reproduciblecross rangeof localseasonalariations.Product esting, asperformedn the flex wash est, allowsnaturallather developmentrom the bar and closelymimicsproductconcentrationsuringhomeusage.Subject ompliances excellent ince seof the flex areaallows he panelistto follow a normalcosmetic nd skin care egimenon the faceand hands.The method susefulas a screeningest when evaluatingmild surfactants nd other mildness gents,with directionalityevidentby the third day of the test. While the test hasbeende-signed o discriminate malldifferencesn irritationpotential, t lacks he ability toseparate roducts ased pondryness.

ACKNOWLEDGMENTSThe authorswish to thank Ms Joan Barrowsand Ms DoloresBorowski or their tech-nicalexpertise, nd Dr. Gary Grove or his consultationn the statistical nalysis f thedata.

REFERENCES(1) S. H. Peck,J. Morse,T. Cornbleet,E. Mandel, and . Kantor, Soap--Neutral vs alkaline,Skin, 1,261 (1962).(2) P. Frosch ndA.M. Kligman, The soap hamberest--A newmethod or assessinghe irritancyofsoaps,J.Am. Acad.Dermatol., , 35-41 (1979).(3) J. D. Justice,J. J. Travers,and L. J. Vinson,Testingdetergentmildness,SoapChem.Specialties,37(8), 53-56 (1961).(4) P. J. Frosch, Irritancy f SoapsndDetergent ars," n PrinciplesfCosmeticsor theDermatologist,.Frosch nd S. N. Horwitz, Eds. (C. V. MosbyCo., St. Louis, 1982), pp. 5-12.(5) M. F. Lukacovic,F. E. Dunlap, S. E. Michaels,M. O. Visscher,and D. D. Watson, Forearmwashtest to evaluate he clinical mildnessof cleansingproducts, . Soc.Cosmet. hem., 39, 355-366(1988).(6) S. W. Babulak,L. D. Rhein, D. D. Scala, . A. Simion,andG. L. Grove,Quantitation f ery-thema n a soap hamberestusing he Minolta Chroma Reflectance) eter: Comparisonf instru-mental esultswith visual ssessments,. Soc.Cosmet.hem., 7, 475-479 (1986).(7) G. L. Grove, personal ommunication.

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