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# SafePharm Laboratories

EMULGEN B-66: ACUTE EYE IRRITATION IN THE RABBIT SPLPROJECTNUMBER: 140/1100

STUDYSPONSOR: Kao Corporation Division of Product Safety Safe 匂

I & Environmen 

### ta1 Research Center 2606 ,Ak ab 組 e , Ichikairnachi Haga TOCHIGI 321-3497 JAPAN
140.1100.docIJS AUTHOR: A Sanders

TESTFACILITY: Safephann Laboratories Limited P.O. Box No. 45 DERBY DE12BT U.K Tel 

### 巴:p hone: (01332) 792896 Facsimile: (01332) 799018SPL PROJECTNUMBER: 140/1100 PAGE2 QUALITY ASSURANCEREPORT Thi s study ザ pe is classed ぉ short-term. 官 le s 旬nd 紅 d test method for this study type (“ General Study Plan" 血 OECDterr凶nology) was reviewed for compliance once only on initial production. 

### In

spection of the routine and repetitive procedures 也a1 con ぬ 旬te the study is carried out as a con 出 uous process designed to encomp ぉ s 也emajorph ぉ es at or about the 也ne this study was in progress. 百註s report hぉ been audited by Safepharm Quality Assurance U 凶 t 

### , and is consider 官 d to be an accurate account of 世 le da 臼 generated and ofthe proced 町巴 s followed. In each c ぉ e ,也.e outcome of QA evaluation is reported to the Study Director and Management on the day of evaluation. Audits of study documentation

### , and process inspections appropriate to the 句

!p



### e and sched 

### uI e ofthis 託udy were as follows: 15 August2001 19 March 2002 07 March 2002 05 March 2002 Standard Test Method Compliance Audit Test Material Preparation

13 

### , 20 March 2002 

## S 08 April 2002 Ani mal Preparation Dosing 

## S Date of QA Signature Assessment of Response Draft Report Audit Final Report Audit 

## S Evaluation specific to 白 

### is study 

# 以ム

For Safepharm Quality Assurance Unit*

•Authorised QA Signatures: DATE:

Head ofDep 紅 白len t: JRPateman CBiol MIBiol DipRQAFRQA JMCrow 也er MIScTMRQA 

## 26 APR 2002

Deputy Head ofDepar町lent Senior Audit S 阻ff: JVJohnson BSc MRQA; G Wren ONCMRQA; R Hurst MRQASPLPROJECTNUMBER: 140 /1 100 PAGE3 

### GLPCOMPL lAN 

### CESTATEMENT 百 

### le work described wぉ 

### performed in compliance with UK GLP standards (Schedule 1 , 

### Good Laboratory Practice Regulatio llS 

### 1999 (SI 1999/3106)). 百 

### lese Regulatio llS紅

### 'e in accordance with GLP standards published as OECD Principles on Good Laboratory Practice (revised 1997 

### , ENV 

### IMC/CHEM(98) 17); and 紅 

### e in accordance wi 由, 

### and implement , 

### the req 凶

### rements of Directives 87/18AEC (ぉ 

### amended by Directive 1999111 厄 

### C) and 88/320 厄 

### EC (as amended by Directive 1999/12 厄C). 

### Th 

### ese intemational standards are a 

## ∞ eptable to the Regulatory agencies of 也 

### e following countries: Australi 

### a, Aus位 

### i 

### a, B 巴 

### Igium 

### , Canad 

### a, the Czech Republic 

### , Denmark

### , Finland

### , France 

### , Germany 

### , Gr

### eece 

### ,Hungary 

### ,Iceland

### , Ireland

### ,Israel 

### ,Italy 

### , Japan

### ,Republic of Korea 

### , Luxembo 町 

### g 

### , Mexico 

### , Th 

### e Netherlands 

### , New Zealand

### , Norway 

### , Poland

### , Portugal 

### , Sloveni 

### a, Sp 垣見 

### Sweden

### , Switzerland

### , Turkey 

### , the United 

### Kin gdom 

### ,

andthe U 凶

### t巴

### d States of 

### Am erica 

### η lI 

### s report ぬ 

### lly and accurately reflects 也 

### e proced 出 回 

### used and data generated.

# '""'-..,ミ?と~一一 DATE:

# .........2.~..A**P. R**  ..

# Z~Q2 ASanders Study DirectorSPLPROJECT NUMBER: 140 /1100 PAGE4


### CONTENTS QUALITY ASSURANCEREPORT GLPCOMPLIANCE STATEMENT CONTENTS SUMMARY 

### 1. INTRODUCTION



### 3. TESTMATERIAL 2.1 Description

### , Identification and Storage Conditions 2.2 Preparation ofTest Materi aI 

### 2.3 Measurement of pH METHODS 3.1 

### Ani m aI 

### s and 

### Ani mal Husbandry 3.2 Procedure 3 

### .3 Interpretation of 

### Rc巴sults ARCHIVES 9La'34aTF3rokoroζ

り勺 j弓 J 勺,勺 jooay 

### 2.

4. 5. RESULTS 10 6. CONCLUSION 10 Table 1 

### In dividu aI 

### Scores and 

### In dividu aI 

### Total Scores for Ocular Irri 

### tation 11 Table 2 

### In dividu aI 

### To 凶 

### Scores An 

### d

Gr 

### oup Mean Scores For Ocular Irri 

### tation 12 Appendix 1 

### Ini ti aI 

### Pain Reaction 13 Appendix 2 Draize ScaI 

### e for Scoring Ocular Irri 

### tation 14 Appendix 3 Modified 

### Ka y and CaI 

### andra 

### In terpretation ofEye Irri 

### tation Test 15 Appendix 4 Statement of GLP Compliance 

### in Accordance with 

### Directive 88/320 厄 

### EC 16SPL PROJECT NUMBER: 140/1100 PAGE5 

### EMULGENB ・ 

### 66: ACUTEEYE IRRITATION11可 

### THERABBIT 

### SUMMARY 

### lnlroduction. Th e

study w ぉ 

### performed to assess the irritancy potenti aI 

### of the test material to 出 E 

### eye of 由巴 

### New ZeaI 

### and 

### Whi te rabbit. 

### Th e

method was designed to meet the requirements ofthe follow 泊

### g

• OECD Guidelines for the Testing of ChemicaI 

### s No. 405 

### “ Acute Eye IrritationlCoITosion" (adopted 24 February 1987)

• Commission Directive 92/69 厄 

### ECMe 血 

### od B5 Acute Toxicity (Eye Irritation) 

### Result. A single application of the test materi aI 

### to 也

### e non-irrigated eye of せ 

### rree rabbits produced moderate conjunctiv aI 

### i凶 匂

### .tion. All eyes appe 眠 

### d norm aI 

### at the 48 ・ 

### hour observation. 

### Conclusion. 百 

### le test material produced a maximum group mean score of 10.0 and was classified as a 

### minimaI irritant (Class 3 on a 1 to 8 s

### caI e) to the rabbit eye according to a modified Kay and CaI 

### andra classification system. 

### Th e

test materi aI 

### did not meet 也巴 

### criteria for classification as irritant according to EU labelling regulations Commission Directive 93/21AEC.SPL PROJECTNUMBER: 14011100 PAGE6


### EMULGENB・ 

### 66: ACUTEEYEll 主Rl 

### TATION IN THE RABBIT 1. 

### INTRODUCTION Th 

### e

study was performed to 拙 巴 

### ss 也

### e 凶 回 

### cy potential of 也

### e test material following a single applicationto the rabbit eye. Th 

### e

methodwas designed to meet the requirements of 出 

### e following:

• OECD Guidelinωfor the Testing of Chemicals No. 405 

### “ Acute Eye Irri 

### tationlCoITosion" (adopted 24 February 1987)

• Commission Directive 92/69AEC Method B5 Acute Toxicity (Eye Irritation) 百 

### le albino rabbit has been shown to be a suitable model for 也1S 句 

### rpe of study and is recommended in 吐 1巴 

### testme白 

### od. Th 

### e

results of the study 紅 

### 'eb 巴



### lieved to be of value in predicting 也 

### e lik 巴



### Iyeye 註討旬且 

### cy potential of the test material to m 釦 . 百

### le study was performed between 04 March 2002 and 10 March 2002. 2. TEST MATE Rl 

### AL 2.1 Description

## , Identification and Storage Conditions Sponsor' 

### s identification Description Batch number Date received Storage conditions EMULGENB-66 li 

### め t brown slightly turbid viscous liquid 2376 31 December 2001 room temperature inthe dark Data relating to 也

### e identity 

### , purity 釦 

### d stability of the test material l由 也

### e responsibili 旬。 

### f 也E 

### Sponsor. 2.2 Preparation ofTest Material For the purpose ofthe study the test material w ぉ 

### used ぉ 

### supplied The absorption of the test material was not determined.l , SPLPROJECTNUMBER: 140/1100 PAGE7 

### 2.3 Measurement of pH 百 

### le pH of a 90% v/v aqueous prep 制 

### tion of せ 

### le test material was determined 

### 戸 or to commencement ofthe study and found to be approximately 8.5. 3. METHODS 3.1 

### An imals and 

### An imal Husbandry τbree New Zealand Whi 

### te rabbits were supplied by David Percival Ltd 

### , Moston

### , Sandbach

### , Cheshire 

### , UK.. At 也

### es 泊

### rt ofthe study the animals were in the weight r 

### 佃.g e of 2.0 to 3.5 kg and were twelve to sixteen weeks old. 

### Aft er an acclimatisation period of at least five days each animal was given a number u 且

### ique wi 也

### in the study which w ぉ 

### wri 世 

### en wi 仕 1 

### a black indelible marker-pen onthe inner surface of 也 

### ee 紅 

### andon也

### e cage labe l.



### τ1:t e 創出

### nals were individually housed in suspended metal cages. Free access to mains drinking water and food (Certified 

### Ra bbit Diet (Code 5322) supplied by PMl 

### Nutrition lnternational 

### , No 仕



### inghanl 

### , UK.) W ぉ 

### allowed throughout the study. Th 

### e diet and drinking water were considered not to contain any contaminant of a level 也 

### at rnight have affected 也 

### e purpose or integrity of 也

### e study. Th 

### e

tempera 旬 

### re and relative humidity were set to achieve 1 並

### lits of 17 to 23 0 

### C 飢 

### d 30 to 70% respectively. 

### An y 0 

## ∞ asional deviations 企 

### om these t 紅 

### gets were considered not to have affected 白 

### purpose or integrity of the study. The rate of air 

### exchange was at 

### least fifteen changes per hourand也 

### e ligh 出 

### gw ぉ 

### con 甘

### olled by a time switch to give twelve hours continuous light (06:00 to 18:00) andtwelve hours darkness. The animals were provided with environmental enrichment items which were considered not to contain釦 

### y contanlinant of a 1 巴



### vel 白紙 

### rnight have affected the purpose or integrity of the 山 

### dy. 3.2 Procedure Immediately before 吐 

### le start of the test 

### , both eyes of 也 

### e provisionally selected test rabbits were ex alllIn 

### ed for evidence of ocular irritation or defect with the aid of a light so 町 

### ce from a

standard ophthalrnoscope. Dnly animals 企 

### ee of ocular danlage were used. lnitially 

### , a

single rabbit was treated. Avolume of 0 .1 lnl 

### of 也

### e test material was placed into 由 E 

### conjunctival sac of the right eye 

### , formed by gently p 叫 

### ling the lower lid away from 批 

### eyebal l. 百 

### le upper and lower eyelids wer 巴 

### held together for about one second inunediately after 仕切回 

### ent ,r-**~** SPLPROJECT NUMBER: 140/1100 PAGE8 to prevent loss of せ le test material , 釦d 也en released 百 1e left eye remained un 出 ated and was used for control purposes. Immediately after adminis回 tion of 吐 1e test mat 巴 rial , 組 assessment of the initial painreactionwas made according to 也 e six point scale shown inAppendix 1. 

### Aft er consideration of 也e oc

### u1ar responses produced in the first 仕eated aninlal 

### , two additional 祖 国 als were 困 ated. Assessment of oc 叫 紅 damage/irri 旬.t ion was made approximately 1 ho 町 組d 24 

### , 48 and 72 hours followi 時 間 atment 

### , according to 也e numerical evaluation given in Appendix 

### 2 

### , (企omDraize JH 

### (1 977) "Dermal 姐 d Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity ofHousehold Substances 

### , National Academy ofSciences 

### , Washington DC p 

### .48 to 49) An yotheroc叫紅巳 ffects were also noted. Exan 由1ation of 也e eye was facilitated by the use of the light source 企 omastand 紅 d ophthalmoscope. 3.3 Interpretation of Resu 

### It s The numerical values corresponding to each ru 由nal 

### , tissue and observation time were recorded. The data rela 出 gto 吐 1e ∞ 勾 unctivae were designated by the letters A (redness) 

### , B(chemosis) 飢 d C(disch 紅 ge) ,也ose relating to the iris designated by the 

### 1 出 er D and those relating to 血 e cornea by 也巴 letters E(degree of opacity) and F 

### (訂'ea of cornea involved). For each tissue the score w,ぉ calculated ぉ follows: Score for coniunctivae Score for iris Score for cornea 

### (A+B+ C)x 

### 2 Dx5 (E xF) x 5 Using the numerical data obtained a modified version of the system described by KayJ H and CalandraJ C 

### , J. Soc. Cosme 

### t. Chem. 

### , 1962 13 281-289 (see Appendix 3) was used to classi 今也E oc

### u1紅紅rit 組 cy potential of 也 e test material. This was achieved by adding together 也e scores for 也e corne 

### a, iris and conjunctivae for eachtime point for each rabbi 

### t. The group means ofthe total scores for each observation were calc

### u1ated. 百 1e highest of 出巴 se group means (the maximum group mean score) toge出巴r with the persistence of the reactions enabled classification of the eye 1m 阻 ncy potential ofthe test material. If evidence of irreversible oc

### u1ar damage is noted

### , the test material will be classified as corrosive to the eye.「
、、一 SPLPROJECT NUMBER: 140 /1100 PAGE9 

### 4. ARCHIVES Unless ins 住

### uctedotherwise by the Sponsor 

### , all original da 包 釦

### d 由 

### e final report will be retained in the Safepharmarchives for five ye 紅 

### s 

### , after which instructions will be sought as to fur 血



### er retention or disposal.SPLPROJECTNUMBER: 140!1l 00 PAGE 10


### 5. RESULTS 

### In

dividual and group mean scores for ocular irritation 紅 

### e given in Table 1 and Table 2. Nocorneal or iridial effects were noted during the study. Moderate conjunctival 討 

### itation was noted in all 回 

### ated eyes one ho ぽ 

### after 仕切回 

### ent wi 白 

### minimal coniunctival re 也



### less at the 24-hour observation. All treated eyes appeared normal at 白 

### e 48-hour observation. 6. CONCLUSION 百

### le test material produced a maximum group mean score of 10.0 and was classified as a M 別勘仏

### L 

### IRRl TANT (CLASS 3ON A 1 TO 8SCALE) to 也

### e rabbit eye according to a modified Kay and Calandra classification system. 立

### le test material did not meet the criteria for classification as 註 

### ri 1an 

### t according to EU labelling re

### gu1ations Commission Directive 93/21AEC.Table 

### 1 EMULGEN B-66: ACUTE EYE IRRITATION IN THERABBIT Individual Scores and Individual Total Scores for Ocular Irritation IPR=2 IPR=2 Rabbit Number and Sex 165 Male 109 Male Time After Treatment 24 48 72 24 48 72 Hour Hours Hours Hours Hour Hours Hou 悶 Hours CORNEA E = Degree of Opacity 

# 。 。 。 。 。 。 。 。 F = Area of Cornea Involved 

# 。 。 。 。 。 。 。 。 Score (E x F) x 5 

# 。 。 。 。 。 。 。 。 IRIS D 

# 。 。 。 。 。 。 。 。 Score (Dx 5) 

# 。 。 。 。 。 。 。 。 CONJUNCTIVAE A = Redness 2 

# 。 。 2 

# 。 。 B = Chemosis 

# 。 。 。 。 。 。 C = Discharge 2 

# 。 。 。 2 

# 。 。 。 Score (A + B

+

C) x 2 10 2 

# 。 。 10 2 

# 。 。 Total Score 10 2 

# 。 。 10 2 

# 。 。

IPR= Initial pain reaction SPL PROJECT NUMBER: 140/1 100 IPR=2 III Male 24 48 72 Hour Hours Hou l' s Hours 

# 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。
2 

# 。 。 。 。 。 2 

# 。 。 。 10 2 

# 。 。 10 2 

# 。 。

PAGE 11SPL PROJECT NUMBER: 140/1100 PAGE 12 EMULGEN B-66 : ACUTEEYE IRRIT A

TIONIJ 可 THERABBIT Table2 Individual Total Scores And GroupMean Scores For Ocular Irritation Rabbit Number In dividual Total Scores At and Sex 1 Hour 24 Hours 48 Hours 72 Hours 165 Male 10 2 

# 。 。 109 Male 10 2 

# 。 。 111 Male 10 2 

# 。 。 Group Total 30 6 

# 。 。 Group Mean Score 10.0 2.0 

# 。。 。 .0SPL PROJECT NUMBER: 140/1100 PAGE I3 EMULGENB ・ 66: ACUTEEYE IRRITATION IN THE RABBIT 

### Appendix 1 Initial Pain Reaction Wh en the material is insti 

### Il ed in 吐 

### le eye 白 

### ere may be 組 凶

### tiallocal pain reaction. 百 

### le reaction will be graded as fo 

### Il ows: Class Reaction by

### An imal Descriptive Rating 

# 。 No response No initial pain Afew blinks 0 凶 

### y 

### , normal wi 血

### inoneortwo Practically no 泊

### itial pain mmutes 

### 2 Rabbit blinks and 往

### ies to open eye 

### , but Slight initial pain reflex closes it 3 

### Rabbit holds eye shut and puts press 町 

### 'eon Moderate initial pain lids 

### , may rub eye 

### wi 也 

### paw 

### 4 

### Ra bbit holds eye shut vigorously 

### , may squeal Severe initial pain 

### 5 R且 

### bbit holds eye shut vigorously 

### , may Ve 巧

r 

### severe initial pain squeal 

### , claw at eye 

### , jump and try 

### to escape Th 

### ere is often no correlation betweenthe initial pain and the subsequent eye irritation.PAGE 14 SPLPROJECTNUMBER: 140!ll OO EMULGEN B-66: ACUTE EYE IRRITATIONINTHE RABBIT
Draize Scale for Scoring Ocular Irritation Appendix2 CONJUNCTIV AE 

### 1. 0123 Redness (refers to palpebral and bulbar conjunctivae excluding cornea 四 d iris) Vessels normal Vessels definitely i町ected above normal More diffuse , deeper crimson red, individual vessels not easily discemible Diffuse beeぢ red (A)

nu' 且今,&吋‘ JA

値 T Chemosis Noswelling An y

swelling above nonnal (in c1ud 田 nic凶 加 g membrane) Obvious swelling with parti 剖 eversion of lids Swelling with lids abOUI half closed Swellingwi 血 lids half closed 10 completely closed 

## 。)

Discharge No discharge An y 阻 ount different from normal (does oot include small 町 noun. 匝 observed in inner c 血血us of normal animals) Discharge with moistening ofthe lids 皿 dhai 目 just adjacent to lids Discharge wi 也 moistening of 曲 e lids 四 dh 司1S a considerable 町田町'O und 出 eeye THE TOTAL SCORE = (A 

### +

B 

### + c) x 2 MAXIMUM TOTAL =20 

# 。

2 3 (c)

IRIS 

### 2. 

# 。

2 Values Normal Folds above norm a1. congestion, swelIi ng , circumco四 国 1 injection (any or all ofthese or combination of any thereo f) iris still rea 凶 ng to light (sluggish reaction is positive) No reaction to ligh t, haemorrhage , gross destruction (四y or all of 曲 目 e) THE TOTAL SCORE = D x 5 (D)

MAXIMUM TOTAL 

## =

10

AU'I ヲ白司 3SAT CORNEA Degree ofOpacity (most dense area used) Noopacity Scattered or diffuse 町 eas , details of iris clearly visible E 白 ily discemible 回 nslucent areas , details ofiris slightly obscured Opalescent areas , no details ofiris visible , size ofpupil barely discemible Opaque. iris not discemible 血 rough 由 e opacity Area of Cornea Involved (E) 3. -1234
MAXIMUM TOTAL 

## =

80 

## σy One quarter (or less) but not zero Greater 白田 one quarter but less th 四 half Greater than halfbut less 出回 three quarters Greater th 四 three quarters , up to whole area THE TOTAL SCORE = (E xF) x 5 MAXIMUM TOTAL SCORE POSSffiLE = 110



### 、SPL PROJECT NUMBER: 140/1100 PAGE 15 EMULGEN B-66: ACUTE EYE IRRITATIONIN THE RABBIT 

### Appendix3 Modified 

### Ka y and Calandra Interpretation of Eye Irritation Test
MAX 町四JM DESCRIP 百 ONRAτlNG MEAN PERSISTENCE OF SCORE SCORE (ANDCLASS)
0.0 toO.5 Groupm 田 nto 阻 I score at 24 hours = 0 Non-Iπltant (1) Groupm 担 n to 阻 1 score at 24 hOll 回 >0 Pr富山田lI ynon-irritant (2) 0.5 t02.5 Groupm 田 n tO 回 1 score at 24 hou 目 -0 hMircutm 回 al11y u

mn imtant (2) Groupm 田 nlO 凶 E 回 reat 24 hours > 0 1π1 包 nt (3) 2.5 to 15 Groupm 国 n 阿 国 I score at 48 hours = 0 Minimal irri 飽nt (3) Groupm 国 nto 阻 I score at 48 hours > 0 Mild irri 回 t (4) 15t025 Groupm 阻 nto 也1s co 悶 at 72ho 四 百 -0 Mild irri 凶 nt (4) Groupm 田 nto 阻 I score at 72 hour 宮 >0 Moderate 町 出nt (5) Mo 陪白血 halfof 曲 e individual 同 国 11 sco 陀 S Moderate 町出血 (5) at 7 days 10 or less Groupm 田 nto 飽1s ∞

re at 7 days More 血 叩 ha!fofthe individual to 凶 scores 25to 50 at 7 days >10 but no individual to 凶 s ∞

re Mode 汀 ate irrt 泊 目 (5) 200fl 田 S at 7 day!l > 30 Moreth 四 h a1fofthe individual to凶 scor ,田 at 7 days >10 血 d any individual sco 陪 at 7 Severe irri 也nt (6) days> 30 Groupm 田 n tO 也Is回 目 at 7 days >20 Severe irritant (6) Moreth 叩 halfofthe individual 10凶 500 毘 S Severe iπi 阻 nt (6) a17 days 30 or les 市 Groupm 田 nto 凶 score al 7 da'戸 Morelh 血 halfofthe individual to 凶 scores 50to 80 at 7 days > 30 bUl no individual total scores Severe irri 回 t (6) 40 or less at 7 days >60 More 出 叩 halfofthe individual to 阻 1s四 回S al 7 days > 30 and individual total score at Very severe irritant (7) 7

days >60 Groupm 田 nto 回 1 score at 7 days > 40 Very severe irri 也nt (7) More th 血 h aJ fofthe individual to 組J sco 陀 S Very severe irritant (7) at 7 days 60 or 1 田 S Groupm 田 n total score at 7 days Moreth 叩 half ofthe individual to凶 scores 80tol00 at 7 days > 60 but no individual to 阻 1 score Very severe i 而 阻nt (7) 800rl 田 S at 7 days > 100 More 白 血 half ofthe individual total scores at 7 days > 60 and individual to 凶 s∞ re at Ex tremely severe irritant (8) 7

days > 100 Groupm 田 nto 回 1 score at 7 days > 80 Extremely severe irritant (8) Grollpm 田 n to 也J score at 7 days Very severe irri 包 nt (7) 100 to 110 80 or less Groupm 国 nto 凶 s∞ re at7 days >80 Extre 江 nely severe irri 旬nt (8)SPLPROJECT NUMBER: 140/1100 PAGE 16 

### Appendix4 Statement of GLPCompliance in 

### Accordance with 

### Di rective 88/320 

### lEEC 44 ・金 品、‘ }14' L 噌通慮党副甲、 、‘司言問

A 

## TE 白島屋
w 4 4 堅調盟国国 EE E

』 M 回訓電 ド邑.湖町民間身 弔 '



### THE DEP 

### AlITMENT OF BEALTI 王 

### OF 'I賢

### E GOVERNMENT OFl 百 

### E 四 回

### ED 玄 副 

### GDOM GOOD LABORATORYPRACOCE sll 訂宜勘1El'o"T OF 

### co r.置喧.IANCE 副 ACCORDANCE 布団富田100 斑ヨ:IVE1I&'3:曲 EEC LABORAτORY 宜主STTYPE SafePbum Labora 師時国LId S Il劃曲wB 回旬回 F 白 色 Lon doD lIoad SIJar喧胸 w h ぬ, ydlire 

### D

E7 

### 1 2G 

### D AnaIY曲剖 ch 佃 耐7 Eo吋周 E 皿回包lFm Eo吋m 盟国国凶 T 。温city M 国 q 聞編守 F町JlCh emTe 由 TOD 奮叫句E

DATE OF INSPECTION 21Fd 買司副ヲ Z 邸 ぬ A _gcncral IOSpeCtiOD for -compliance with the Pri ncipl 目 。 f Good La bo. 回田町 y P阻&ri田 W

出 C 由Ti ed 叫 E 昌 也c above laboratory 邑 pan of UK GLP Comp1i llD ce Pro gr四 lme. AI 血 e time of 由 e inspection 00 deviations Wc陪 found -of 四百1 白 聞t 田 昭 nitude 10 a町田 t 曲 e validity of non-<:lini 白 I s lU dies perfon 祖国副曲 E 日 fadIi ties. 

# 本 ... 五一一 ♀......

### SAFEPHARM LABORATORIES LTD
E l¥侃 

### JLGENB ・ 

### 66: ACUTEEYEIRRITATIONIN THE RABBIT SPL PROJECTNUMBER: 140/1100



### 1

verifシ 也

### at 也

### 1S 1S an exact copy of the original report which is located in 也 

### e 

### Archives of Safephann Laboratories Ltd. 

### , Derby 

### , UK. 

# ¥

ASanders Stud y

Director DATE:

## ...........?J.A**P. H...?~~?** **・.,.**