TS-K784YD

Attachment

10 PAGE

1 OF

6 PAGES STUDY SPONSOR:

CBI STUDY TYPE: TEST ITEM: STUDY NUMBER: INTRODUCTION The study was performed

to assess
the irritancy potential

of the test item following single, 3-Minute

, 1 and 4-Hour, semi
-o cc luded applications

to the intact rabbit skin (General Study Plan 540-17). This study was designed

to be compatible
with the procedures indicated

by the following internationally accepted guidelines

and recommendations: • OECD Guidelines

for the Testing

of Chemicals

No. 404 "A cute Dermal Irritation/Corrosion

" (a dopted

24 April2002) • Method

B4 Acut

e Toxicity (Skin Irritation)

of Commiss

io n Regulation
(EC) No. 440/2008 Initial considerations In the absence

of data suggesting

that the test item was unlikely

to produ

ce severe irritation/corro

s ion, an ex vivo pre-screen

test, the Transcutaneous

E
l ectrica

l Resistance Assay, was performed.

The results

of the pr e-sc reen test indicated
that the test item was considered

not to be corrosive

to the skin and the in vivo test was performed

. The results

of the Transcutaneous Electrical Resistance Assay

ar e given

in the Appendix

. Experimental Starting Date: Experimental Completion
Date:

04 June
20 14 11 Jul
y 2 014 Test item characterization

data are the responsibility

of the Sponsor. All raw data will be retained inL..Ic_

8 _ 1 _______________

__.TS-K784YD

Atta

c hme

n t 10 Report



### Page2 

## METHOD 3-Minute

and 1-Hour semi-occluded applications

(0.5 mL) of the tes

t item were administered

to the intact skin of one rabbit. Skin reactions were recorded

1, 24, 48 and 72 hours after administration. A sing
le 4-Hour, semi-occluded application

(0.5 mL) of the test item was administered

to the intact skin
of two rabbits.
Skin reactions were recorded

1, 24, 48 and 72 hours after administration. 

## RESULTS Individual

sk in reactions following

the 3-Minute

and 1-Hour exposure periods

are given

in Table

1 and individual
skin reactions following

a 4-Hour exposure period
are given

in Table

2. 3-Minute

and 1-Hour semi-occluded applications

of the test item

to the intact skin of one rabbit produced

no evidence

of skin irritation. A single 4-Hour, semi occluded

app lication

of the test item

to the intact skin of two rabbits produced

no ev iden ce of skin irrit ation

. 

## CONCLUSION The test item produced

a primary irritation index
of 0.0 and was

c la ssified

as non-irritant

to rabbit skin according

to the Draize classification scheme.

No corrosive effects were noted.TS-K784YDAttachment10ReportPage3ThisstudywasconductedinafacilityoperatingtoGoodLaboratoryPracticewithintheUKnationalGLPmonitoringprogramme,butthestudyreporthasnotbeenauditedbytheQAUnit.NoformalclaimofGLPcomplianceismadeforthisstudy.Thisreportisanaccuraterecordofthestudyanditsoutcome....................... A..:..Date:APoolesStudyDirectorTS-K784YDAttachment10ReportPage4TABLESTable1IndividualSkinReactionsFollowing3-Minuteand1-HourExposuresIndividualScoresObservationTimeRabbitNumberandSexSkinReaction(followingpatch74394Maleremoval)3-MinuteExposure1-HourExposureImmediately001Hour00Erythema/Eschar24Hours00Formation48Hours0072Hours00Immediately001Hour00EdemaFormation24Hours0048Hours0072Hours00TS

- K784YD

Attachment

10 Report

Page

5 Table2 Individual
Skin Reactions Following 4-Hour Exposure Individual Scores Observation
Time Skin Reaction (following patch

Rabbit Number
and Sex

Total removal)

74394 Male

74488 Female Immediately

0

0

(0) 1 Hour

0

0

(0) Erythema/Eschar

24 Hours

0

0

0 Fonnation

48 Hours

0

0

(O) 72 Hours

0

0

0 Immediately

0

0

(0) 1 Hour

0

0

(0) Edema Fonnation

24 Hours

0

0

0 48 Hours

0

0

(O) 72 Hours

0

0

0 Sum

o f2 4 and 72-Hour Readings

(S)

:

0 Primary

Irr

i tation Index (S/4)

0 / 6 = 0.0 Classification

NON-IRRITANT Primary Irritation Classification Index 0

N on -irritant >0-2

Mild initant > 2-5 Moderate irritant >5-8

Severe

irr itant ( )

= Total values not used for calculation

of primary irritation indexAttachment10ReportPage6APPENDIXTRANSCUTANEOUSELECTRICALRESISTANCEASSAYIntroductionTheskincorrosivitypotentialofthetestitemwasassessedusingtheTranscutaneousElectricalResistanceAssay.Thisinvolvedtheapplicationofthetestitemtotheepidermalsurfaceofskindiscs,obtainedfromahumanelykilledyoungWistar(RccHanTM:WIST)strainrat.MethodsThepreparedpeltfromtheratwasusedforskindiscpreparation.TheintegrityofthepeltwasconfirmedusingaQualityControltest.Onlyacceptablepeltswereusedtosupplyskindiscsforuseintheassay.Thetestitemwasappliedtotheepidermalsurfaceofthreeskindiscsforacontactperiodof24hours.Attheendofthecontactperiodthetestitemwasremovedusingajetofwarmtapwater.Corrosivesubstancesproduceanirreversiblelossofnormalstratumcorneumintegrityandfunction,thisismeasuredasareductionintheinherenttranscutaneouselectricalresistance.Testitemsthatgiveameanelectricalresistanceof5knorlessareconsideredlikelytobecorrosiveinvivo.Thetranscutaneouselectricalresistancewasmeasuredusingalowvoltagealternatingcurrentelectronicdatabridge.ResultsTheresultsaresummarizedasfollows:TestItemContactPeriodMeanElectricalResistance(StandardDeviation)24Hours14.2kn(±1.3)ConclusionFollowingassessmentofthedatathetestitemwasconsideredunlikelytohavethepotentialtocausecorrosioninvivo.