v~ 

~ 

CJ {~V 

~ 

L! 

COh;PAkY ; 

ASSESSN1ENi 'JF PRFMRX CliTANEOliS iRRITAhCY 

LN VOLUN'fEERS 

(QCCLUSIGI PATCH TRST) 

PRODliCT : 

(RBPORT : 

vcJi.'-

iS. .`'{•;lVRi?tiLIZ -c1ao 
~ 

_ - 

P' 

Witlll:llv 

P3ges 

1. INTROGUV'TION 3 

2. .9UTHE!tiTICATIdN OF 'i'N6 STODY 't 

3. rrETHavoLOCY 5 

3.1. iNCLUDED Sl'+BJECTS 5 

3, 2. TR6AThiENTS 5 

3.3. 2.SSESS°v!E.tiT OP ?RRITATIVE REACTIOtvS Ei 

4. rzESOLTS 6 

5. CONCLUSIOY 7 

SCOIiT:ti SCALr AND :At3LEfi ., :...................... ,.,..., aP:i:!tiIIS.\' 
1.INTROQOCT1oN 

At the renuest nP the C66SPANY 

„ we assessed in Volunteers, the possible primary 

cutaneous irritant eft'ect of the product : 

':o perform this trial, +Ne received on September the 22nd, 1992, a sample 

with the foilawing charncteriStics : 

Concainer : pl2stic flask 

Ruantity : about 100 ml 

ror_n : liquid 

Color : colourless 

pt{ = 5.5 

5 ml of this sampie were placed in a hermatically stoppered jlass £1ask. 

ir,entifiel 92.1476, in order co be stoied at room temperat re for three 

years at most. 
2.AL'THENTZCATION OF TfiE STU17Y 

I the undcrsisned, Corinne GUIBIIIIR, Study Directar, 

certify th3t the study (protoco7: BIOGIR S.A Rdt, H:Cv) was perfarmed 

accord=na to the internai proc°ducea establi.shed on the basis of uood 

CIia:1G Practices, under the respons±b;lity'. 

Tcchnical of Gdcxle AhSERT. 

Scien;:ifac secretary o: ctarie-Pascale HOUaUH''I'E. 

'''hi5 St:ac3; was carried out on the premises of the BZOGT_R S.A. Cutacteous 

Biomatrology Center 122, rue Croix de Seguey 33000 BGP:6w:";(iX. 

ii31 the doct:ments related to this sbudy are stored under the referetace 

in specral pcemiSes o: EIOGIf'i S.i, Labor,atory for three 

years. 

At tne end of this period, ti:e study docucents wi22 be, after spoasar 

agreement, either transfer.ed ici sponsor premises or destroyed. 

The present report is yade of 7 pages .aumbered T'rom i to 7 ana 1 appendix, 

CESTA.$. November the 9th, 19Q 

~ 

1 

J<-an-Fran4nis °L\(lid 

Veterinarian c^h.G 

SCIENI'IFIC DIitEC':i?R 

n 

'1'~ -0 

h#;? ri.e -.i t{ek' 

CEt T Crt AN 

Brigitte H=YLAs'iaT 

v.liALli f :YSSiJRrhC$ 

a 

~ 
3.w1ETHODDLOCY 

This study was perCqrmed between October the 13rd and the 16th, 1992, 

according to the esperimental protocol described below. 

3.1. INCLUDEA 5[IBSECTS 

8 females and 3 males were selected. They were from 21 to 42 years o1d 

(mean :.26). 

i111 subjects were detei-mined to be frce oz" any vi.sible ski ❑ disease in 

the area to be patched. 

tiol)ody was under treatmanr„ whicn could interfere with the results of the 

study or which could induce a risk for the volunteer. 

Subjects declared as "elegible" had signed an informeG consent statement. 

These informed consent statements are stored in special premises of 

BIOGIR S.A. 

3.2. TBBATMENTS 

The trial involved the appiicata:on of the test product under occlusice 

conditions (patch cest). 

We used aluminum cups of 8 mm in diaareter and of 20 pl in volume. Each 

cup represented about a50 mm 2 area_ ?`hey were affixed by two on an 

adhesive tape. 

The product was studiec9 20 t diluted. 

The salution was placed on a speczal absorbant paper disc, laid down in 

the alumznum cup. 

The patch caas applied to the ?eft upper bac:-c which had not received any 

previous treatment. , 

.1 2'; solution of sodium laucyl sul?s,te was used as positive cor.trol and 

was applicd che same :aa,v on a diffNrent skin area. The second cup 

containing distiiled seatcr .aas used as negati=.e control. 
3.3. ASSfiSSMENT OF IRRITATIVE Rfi,4GTI0NS 

24 hours ai'ter tie application, the patch was removed and the skin was 

examinated C(ir any dermal response 30 minutes later. 

The parameters Scored were : 

erythema dryness 

oedema . wrinkling 

vesicles glazing 

Scc,7ring of each parameter was in accordance wiLh the scale in nppendix. 

.a second reading was performed 24 hcurs iater in order to assess the 

reversibility ot' lesions or to note any zaossible delayed reactiozr. 

4. RESULTS 

They are given in Tables I ta 3 in appendix. 

The table 1 gis;es the scores obtained with the positive control and the 

table 2 those obtained wita the negative control (distilied water). 

Table 3 gives the scores obtained £or the test product. 

~ °ositive contr0l site : 

Clear reactian in all subjects. 

* NeAative eontrol site : 

tqo reaction in ali ,:uhjecrs. 

* Test nroduct 20 a di.luted treated site 

^:o rea.Ctlur, °n lU sub,jeuts. 

JPrry slight eryt''ema on Z%. ;aur ceading in :snly ' Subject {n" 3}. 
5. caNCLD5I0N 

Under the experinent8l conditzons of the trial, the product 

dermatologically tested 20 . diluted, induced in only one subject a 

treu;sient very sligght irritative react:ion. 

Such res»its allow us to consider that the prodiict is most Zikely not tu: 

irritating agenc. 

i 

Corinne r,UIgAUD 

Physician 

Cei-tificate o'r' Clinical PhaLrracology 

CESA6i graduated 
AAW 

APPENDIX 

Scoring sca'Les and tables 
n

('(i_'1(I ~ 

ERYTHE.'IP 

0 Yoi;e 

S1.ight ihace"lY perceptible pinkness of ;.1.1 the sitc or distinct eink.,aes;; o•,' par; 

of sitel. 

2- Distinct (disti-net pinkness of all site or weli-developed redness of part or" 

si.te i . 

S= Well-fleveloped (weli.-d?velaped redness of 3.tl s':te or st.rong deep r=dness o2 

¢8.r C Of s).tC; - 

Y= Strong !yt_ong 4eep redness/re,3-brown. 'Lurn liice'}. 

OfiDL+1A 

0 = Nona_ 

1= SSight ;up to S1Sght sws'11ir=g OP al1 .site or ciscinct.swei'_ing of o-rt c'" si:te? 

2= Distinct ;up to slight swellin.g of a.11 sit.e or '«el:c-develnped ,s.relli::g c;f parlof slte), 

3=we1,.i. - devEACjJe[1 iilg t0 +:el.l - d2S+eloGed SwE;llit?l of 31.~'. site or st2`oP.g sWt;='_1ng OE 

7a):t Of siCe; . z' = St;ong Ist:'Ong s`rie'?iinST Of C11 s].t°° . may eYt.end beVo7ld s)te). 

ycSxcLEs 

0 = Vone 

i= SZight ig few s:nall veszckes, < 1. mm diam, on less than 1/ ~ 's o" site). 

_ = Distintt (some small vesicies ,< 1 mm diwn, on ebouY-. 114 of sitel, 

_3 = Well-ri.eveloped (aome smat1 ve ,_cles, < 1 nn d:iam, on.?./L to 1 1 2 of si.te, or one 

large vesicl.=., 1-2 mm diam). 

4 = Strong (sUme small vesicles, < 1 mm:diam. on more than.1/2 of Site, or afe,s 

l.arge vesicSes, 1-2 3m di<:m). 

DR.'itiE SS 

0 = None 

1= S1igF:t (du17.ness ; mattness to al1 sS.te or pawder;= on par*_ of site}. 

2= Distinct {powdery on ali site or some scating/fla.c;ng on nart Of sitz). 

3= WeI?-develuped (scaiing/flraking an all site or thick sca?esiflakes on partof 

site). 

4- Strong (neavy scaiing/f3.aking or.. tihick scaleS/f?a.kes on ail site possi.bl.,; reea 

cracking). 

4,'RI\''Ki.1NG 

0 = :tione 

1= Sli.gtli: {gli'_d,1t '+erLlkling a[1 d'll sl.Ce or disti;lcL kTitifCling 4n pctC -, oF Sii.e}. 

2 - Distinct tdi..stinct wrinklin.g on .ai.l stte or w=il-developed wri*;ic;,in, an part of 

wite). 

i=. Y:e11-deveiotia:d ;wel'_-deteleped ,vr-ni::.int : tu riuses an,:? t-..u.s^zs :tn 2t_' ;. __ . 

str,^ng wr- nk?i.ng on aart of wite). 

'i Strong ;.,t.rqng.. rinkting to .orm ;eep an... high _i:igeti;.. 

Gi,,;Z7VG 

0 = None 

, ' SI.i.flht ;n1»gitl;i °hiny on a-.i sx = Dist nc.ly s.i;ny on ,osvr. ot ;;itc::i. 

'? = D 5__.,.c:. ,uistinc L ; shiny on sits :;r ,-_ sevG-_owd gloss.=..ess ..., . .. _ .. -_e. 

J = i~ei1-de•.e).oped (well-deveic, ~,ed glossiaesm • ~ :e ~.1 a iEe =ar. -.er r gios ~y~ , -mi _ «! a ., . 

site). 

:€ - Strong .vYry slc;s;:y;;hignly cePlect:.ve un a::'_ s_..:.,. 
IND3VID(;,4I: RES4?LTS - T.4BLE I 

?ROL'(;CT : SODITjld Lr1QR'?L SULFA'FE 2 d' diYuted 

_st RE:aplr;G 

~ SUB.7ECt'S ERYTHEp7,q ~ DEDEMA ~ VESICLES f S,°RINiiLING GLa?.ING ~ DRYNESS 

, z i I c ~ e o 0 

z ~ Q ~ 3 0 z 0 ~ S ~ p 0 ~ 0 0 

I , 3 i j c 0 If 

0 

o i ;: ; 0 

D 0 

'iSSEJ E-%DZtiG 

E ~ i 

0 

k ~ G 

r0 .. _ ~. V 

_.. ~ . _ C . . ~ 

. C 6 

1~ ~ 0~— ~ ~ 0 0 

p ~ 

2rd FiEADING 

SG33ECTS ~ ERYTHF~'7A QEIIEMA EVESICLES 4aRI'iKLING4 GLr1ZZNC ~ DRYNESS . 

i € 0 0 ~ p ~ p 

'— z ~ o p ; o o 

— ~ 

., o o p i 

f 

~ ~— G J 0 

0 

p ! p 

~ p p 0 p p 0 

p ~ 

~-----~?~~ 

~ ~ ~ , .... ' _._..` . , E . _.. . 

I 1, i 

0 

i r' ; r 

0 

~ 

0 

I a_ 
IND.IVIDUr'1L RESULTS - TABLE 2 

P;?ObUC'I : DISTILLED WATER 

25t REr1DING 

~BJECTS ~ EftYT}f&'~3A 1 GEDEetiLA V'ESICLES I t~ RINKLI~:G GI.AZING ~ DRI`fv'ESS j 7 i G ' O 6 ~ G C C ~ 

~ 

Q U o 0 

0 

G Q } 

0 

G 

. . .. 

k 5 D L Q ; 

- 

V f J 

_ 

! 6 0 ; 4 Q 

U 

f M1fISSED R :HDIP4G . . 

I { 

. ~... 

C, ~ U

..._. 

i j o i-U 0 

~ zi a ; ~; i ~ i , ; 

~ ~ h 

0

_ 

2nr3 ,E:ADING 

f SU$78CTS ERYTHEt~7.~; ~ DEDEtnfi ~ VESICLES ~ WBIIQKT.ING GLAZIRG DRYNESS 

S U 

' 

u G Q ~ G ~ U 

F--- 

~ 2 Q j 0 G ~ '<J 

---~ -- 

G C 0 ~ 

, 

3 0 

~ 4 j o o f o ~ o 0 i o 

r, Q 

L 6 :7 

4 ~ U I n i U i J 

0 1 

T i 

0 0 Q C ~ 0 

U p ~ , 

; 

~ 10 .^, f o o p I0 

~ 

~ ~ 

0 I 0 I ; 

i 
INDIt'IDUA.L RESULTS - TAELE 3 

'rRCDU_r.t' : --_.___._--_- . ~, (20 '~ dilu-'ed) 

15t REA'OTlG 

~ SUf3JECTS 

— 

~ ERYTH&N7A i 4EDt.d"'43 ~ VF'$ICLES ~ `n'RI:IKLING( GCSZIiiG .f DRYiJ-S ~S

~ 0 0 *0 ~ Q )~ 0 ( 0 

( c ~ G o o ; a 

~ 3 ~ 1 ~ ~ ~ { p 

G ~ 

4 j e 0 o 

~ 

l ~ 1 ~ G 

_ 

0 

5 C o 0 

f 

i 0 0 ~ 0 

a 0 0 ~O~ — 0 0 ~ 0 

~ h'LISSED READii2G 

G 0 ! 0 ~ 'J 0 L 

~ 

O 

Io c ; 0 j 

I 

G 

,f 0 0 j c c o 0 

2nd 8$ADIMG 

~ &UII7EGTS £RY3'HE2~G1 {. OEDEMA 4'ESICLES WRIIVKLING ~ GL9ZIiVG DRIRSFSS 

. 1 0 n 0 D a 4 ~ 

0 G ! 0 D 0 4 

~ ~ 0 ! u 0 ~ U 0 

~ 4 0 { ~ 0 0 ~ p 0 

0 0 0 

i 6 0 } ~ 0 0 

0 f G 

Q I 0 

! 

7 1 i 

0 f 0 

~