Document RJqyN7QzBVwMzN53N5qVQqbY8
AR226-2992
Baugy, June 17, 1993
STUDY NO. 920083 E
PRIMARY CUTANEOUS IRRITATION
Sponsor: ELF ATOCHEM SA La Defense 10 Cedex 42 92091 PARIS LA DEFENSE FRANCE
.Company Sanitized, Does not contain TSCA ^''l'
TRIAL COMPOUND
: Cutaneous primary irritation index.
SPONSOR SPONSOR CONTACT ADDRESS
SITE OF TRIAL
: ELF ATOCHEM SA.
: MrREGNIER
: La Defense 10 Cedex 42 92091 PARIS LA DEFENSE - FRANCE
: CENTRE DE RECHERCHES BIOLOGIQUES Chemin de Montifault 18800 BAUGY - FRANCE
RESPONSIBLE STAFF FOR CERB :
Scientific and Technical Director
S. RICHARD Pharmacien Docteur de 3eme Cycle MaTtre en Pharmacologie
oiL?.?:^---)
Date
Signature
Head of Toxicology Department
C. AUDEVAL-GERARD Docteur Veterinaire CES d'Ophtalmologie
3^-o.[-|-0--6.(|.-^^
Date
LM^
--.-^s=^-:
Signature
Study Director : C. BESSON DUT de Biologie Appliquee
3^/^/t
Date
Signature
Quality Assurance :
C. VIGIER
^ M ^ Date
Signature VJ
The present report is based upon the authentic experimental results obtained.
'Company'Sanit'^ed, Daes "sof 00^3^1 T'C^A -"*>
^ i \^\^ i iiu. c/^-woo c J
This report consists of 33 pages numbered from 1 to 33 including 5 appendices.
SUMMARY
CONTENTS
Page
4
II.
EXPERIMENTAL PROTOCOL ADOPTED
5
11.1
INTRODUCTION
6
11.2
AIM
6
11.3
METHOD
6
11.4
COMPOUND
7
11.5
ANIMALS
7
11.6 APPLICATION OF COMPOUND
8
11.7 CLINICAL MONITORING OF ANIMALS
9
11.8
CALCULATION OF CUTANEOUS IRRITATION INDEX
9
11.9
STEPS OF THE STUDY
10
11.10 CLASSIFICATION
10
II. 11 DATA ENTRY OF RESULTS
11
11.12 REPORT
11
11.13 QUALITY ASSURANCE
11
11.14 RECORDS
11
III.
RESULTS
12
111-1 DEVIATION FROM PROTOCOL N 92.04.10.02
13
111.2 DATES OF TRIAL
13
111.3 CUTANEOUS TOLERANCE
13
IV.
CONCLUSION
APPENDIX 1 APPENDIX 2
APPENDIX 3
APPENDIX.4 APPENDIX 5
Protocol n 92.04.10.02
Technical data and Analytical certificate
concerning compound Analytical certificate concerning foodstuff
Analytical certificate concerning water _ Results data sheet
16
17-23 24-26
27-28 29-30 31-33
company Sanitized. Does not conlam TSCA Cffl
>^L-I ILJ - \J I W I 11U. O^HJUOJ t:
I. SUMMARY The aim of this study was objective determination in the Rat
properties and/or degree of corrosion induced by compoundj
following single cutaneous application.
0.5 ml of compouncplBHBBmjwere applied to the right flank of each of
three rabbits. The leftflank served as a control for the trial. A dressing held the compound in place for 4 hours on the flank of each animal. Any possible lesions were evaluated approximately one hour after removal of the dressing, then 24 hours, 48 hours and 72 hours later. Mean indices were calculated from results obtained from each rabbit at times 24 hours, 48 hours and 72 hours. Cumulative means of mean indices were : . Erythema : 0. . Edema : 0. Mean indices per rabbit, for the three times together were :
. Erythema : 0 in all animals. . Edema : 0 in all animals.
In conclugi/oasn,focuonmd ptooubnedn)o._n_-irritan_t _fo_r _th_e_s_kin of the Rabbit.
D
1"oyRpimy^an;ite'g. Voes w? com^n TSca f':^'-
CtMB - SIUUY No. 920083 E J II. EXPERIMENTAL PROTOCOL ADOPTED
^CompanySanitized. Does not conta?" T<f.'
CbMB - a IUUY No. 920083 E
U
11.1 INTRODUCTION
The protocol used for study of cutaneous primary irritation, complied with
requirements of OECD Guideline No. 404 (May 12, 1981) and EEC Directives (67/548, 79/831, 83/467, 84/449) and enabled full evaluation of the reversible
or irreversible nature of the effects seen.
II.2AIM
The aim of the study was objective determination in the Rabbj^^he^mtant
application.
II.3 METHOD
JiBHBHBrJ10 DermaHmtationand/or corrosion following cutaneous application of compound the back of the Rabbit were evaluated by grading of the
' cutaneous irritation reactions seen, using a predetermined score system. This method is not applicable to substances with a pH below 2 or above 11.5, with a predictable cutaneous corrosive action.
The protocol n 92.04.10.02 signed by the responsible of the sponsor and by
the experimenters may be found in appendix 1.
A pre-study was carried out using one rabbit. Results showed no irritation, the study was continued in two other rabbits.
|^
This study took place in accordance with rules of Good Laboratory Practices as
published by :
- The French Ministry of Social Affairs and National Solidarity : State Secretariat Responsible for Health Instructions concerning Good Laboratory Practices (GLP) in the field of experimental toxicology. Instruction of May 31. 1983, Official Text No. 1065 ; Reference SN-S83/25.
- Directive 87/18/EEC, this directive referring to Recommendation CC81/30 Appendix 2 of the OECD.
- The Food and Drug Administration : GLP 21 CFR Part 58 of December 22, 1978 and amendments of April 11, 1980 and September 4, 1987.
I
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II.4 COMPOUND
The technical data and the analytical certificate concerning the compound are attached to the study report in Appendix 2.
- Name
- Origin and batch number
- Record number (CAL)
- Origin
: ELF ATOCHEM SA
- Date received - Amount - Appearance
-pH
: Saturday April 18 1992
: 1 bottle of approximately 107 g
s-
II.5ANIMALS
SPECIES : New Zealand Albino Rabbit.
ORIGIN : CEGAV specialized breeding establishment (Les Hautes Noes, Saint
tei,
Mars d'Egrenne, 61350 PASSAIS LA CONCEPTION, FRANCE).
WEIGHT : Between 1.5 kg and 2.5 kg at the start of the trial.
SEX : female.
NUMBER : 3.
DATE OF DELIVERY : On 01.04.1992.
ACCLIMATIZATION : For at least 5 days before the trial, in the zone where the experiment was to take place. Animals were selected on the basis of their
general condition.
IDENTIFICATION : Animals were identified individually by ear clipping.
HOUSING : Animals were kept in cages of standard size. Excreta were eliminated by unrolling plastified brown paper which was placed under the
cages. These cages were kept in an air-conditioned (170C-21C1C) animal house, kept
at relative humidity between 45 per 100 and 65 per 100, apart from during cleaning, in which non-recycled filtered air was changed approximately ten times per hour. The artificial daylight cycle was 12 hours light and 12 hours
darkness.
i?
TSSftSjSwL..';
CERB - STUDY No. 920083 E
0
- FOOD : UAR 112. An analytical certificate concerning this foodstuff is provided with the study report in Appendix 3.
- DRINKING WATER : Tap water distributed ad libitum in polycarbonate feeder bottles with a stainless steel teat. A water sample was obtained every three months and sent to the Direction des Services Veterinaires, 216 Rue Louis Mallet, 18014 BOURGES Cedex, FRANCE for analysis.The water analytical certificate in Appendix 4 corresponds to the sample obtained on the date closest of the start of 'the study. .
II.6 APPLICATION OF COMPOUND
CompoundlBIU^^fpj^as applied to the dorsal cutaneous region. For this
purpose, on the day prior to application, the dorsal region of each rabbit was carefully shaved over two symmetrical zones, measuring at least 14 cm x 5 cm, in relation to the vertebral axis. An AESCULAP FAVORITA II GT 104 electric trimmer was used, avoiding any damage to the skin. Any animal with damaged skin was eliminated from the study at the time of application.
The left flank of each of the animals was left intact.
A dose of 0.5 ml of compound^^B^BIHH^was applied to the right flank of
each of the animals. The non-treated flank of each animal served as a control for the trial.
Compoun^dj--yf----------j_----Bj--mwf as deposited on a gauze square of approximately
6 cm2. The side of the gauze in contact with the compound was applied to the
skin.
This gauze square was protected by a swab held in place with a URGOPORE microporous and non-allergic non-occlusive dressing, and the whole being held in place by COHEVET coalescent elastic and cohesive hypoallergenic tape. Dressings were held in place for 4 hours after application.
The day of application was taken as D1 of the study.
A SCpmpanySanitized. Does not contain TSC^ '*'
9 CERB - STUDY No. 920083 E
11.7 CLINICAL MONITORING OF ANIMALS
ADDroximatel^one hour after removal of the dressing and of compound
JBm----jR:hen 24 hours, 48 hours and 72 hours later, possible cutaneous
lesions which may have appeared on the right flank of each of the animals were evaluated using the following score system.
ERYTHEMA AND ESCHARS FORMATION
No erythema
0
Slight erythema (scarcely visible)
1
Clearly visible erythema
2
Moderate to marked erythema
3
Severe erythema (reddish purple) with
formation of slight eschars (deep lesions)
4
FORMATION OF EDEMA
No edema
0
Very slight edema (scarcely visible)
1
Slight edema (contours well defined,
visible swelling)
2
' -
Moderate edema (thickness approximately 1 mm) 3
Severe edema (thickness more than 1 mm
and area greater than that of application)
4
11.8 CALCULATION OF CUTANEOUS IRRITATION INDEX
|p Mean indices are calculated from results obtained for each rabbit at times 24 hours, 48 hours and 72 hours.
The following are noted :
- for each parameter, mean of indices for each rabbit for the three times
(= mean index per parameter, per animal for the three times = Mi)
The maximal theorical score is 4 (erythema/edema).
- for each parameter, the cumulative mean (= sum of mean indices for the
three animals / 3 = sum of Mi/3). The maximal theorical score is 4 (erythema/edema).
Company Sanitized. Does not contain TSCA r
CERB - STUDY No. 920083 E
11.9 STEPS OF THE STUDY :
A pre-study was carried out using one rabbit. Results showed, no irritation, therefore the study was continued in two other rabbits.
II. 10 CLASSIFICATION
The compound^UU^BH'iwas classified irritant or non irritant on the
basis of irritation indices obtained in accordance with the Directive 83/467/EEC proposed by the Official Gazette of the European Community.
Compound is found to be irritant if:
- cumulative mean (Cm = sum of Mi/3) is higher or equal to the values indicated in table I for at least one parameter.
- or if, for at least one parameter, mean indices (Mi) are higher or equal to the values indicated in the table I in at least 2 animals.
TABLE I
PARAMETER Erythema Edema
THRESHOLD IRRITATION VALUE
2 2
IDpmpany Sami'zeei Hoe's Hot eon^n ^~SQK CSif
CERB - STUDY No. 920083 E
11.11 DATA ENTRY OF RESULTS All data were recorded as and when obtained using files classified by the study number. 11.12 REPORT The report of experiment included all findings noted during the course of the study, and in particular: - cutaneous reaction observed,
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11.13 QUALITY ASSURANCE The Quality Assurance Unit ensured that working procedures relating to this type of study were strictly adhered to, by periodic inspections of random, over the course of the year. Data included in the report of the experiment were audited by the Quality Assurance Unit, in accordance with standard procedures at the Centre. 11.14 RECORDS The protocol, raw data. the correspondance, the report and a sample of the compound have been stored for five years at CERB, 18800 BAUGY, FRANCE, starting from the date of the final report. h. At the end of this period, CERB will contact the sponsor in order to jointly determine to either : - continue the records, - return the data to the sponsor, - destroy the data.
ft
CERB - STUDY No. 920083 E f ! <RESULTS
Company Sanitized. Does not contain TSCA fw
CERB - STUDY No. 920083 E
J
111.1 DEVIATION FROM PROTOCOL N 92.04.10.02 :
No deviation from the protocol was recorded during the study. The study was performed according to protocol n 92.04.10.02.
111.2 DATES OF TRIAL
- Date of start of the pro-study : 23.04.1992. - Date of end of the pre-study : 26.04.1992.
- Date of start of the main study: 28.04.1992. - Date of end of the main study : 01.05.1992.
111.3 CUTANEOUS TOLERANCE
The results of findings are shown in Tables II (irritation indices at 24 hours, 48 hours and 72 hours and mean indices per parameter) and III (cumulative
means for the three animals) as well as in the results sheet included in Appendix 5.
Cutaneous application of compound J^^HHII^BB)0^80^ no irritation
reaction.
IpoffipanySanNzea. Uoes pfo? confab TSCA CBt
CERB - STUDY No. 920083 E
TABLE
^ Irritation indices
(24h - 48h - 72h evaluations) and mean indices per parameter
Rabbit No
920457
24H
ER = 0 ED = 0
920458
ER = 0 ED = 0
920459
ER = 0 ED = 0
ER = erythema ED = edema
EVALUATION TIME
48H
ER = 0 ED = 0 ER = 0 ED = 0 ER = 0 ED = 0
72H
ER = 0 ED = 0 ER = 0 ED = 0 ER = 0 ED = 0 ,'
MEAN INDEX
(Mi)
ER = 0 ED = 0 ER = 0 ED = 0 ER = 0 ED = 0
ERYTHEMA EDEMA
TABLE III
Cumulative means for the three animals
Sum of mean indices of three animals
0
0-
Cumulative mean (sum/3) = CM
0
0
'
-
\L-...
CERB - STUDY No. 920083 E
-j
- Cumulative means (Cm) of mean indices were : . Erythema : 0. . Edema : 0. - Mean indices per rabbit (Mi), for the three times together were . Erythema : 0 in all animals. . Edema : 0 in all animals. Classification of the compound is ; non-irritant compound for the skin of the Rabbit.
Pompany Sanitized. Does not contain TSCA C?"
CERB - STUDY No. 920083 E
IV. CONCLUSION
Cutaneous primary irritation following application of compound was evaluated in the Rabbit. . UndeiL-thfi--experimental conditions adopted, the classificatioji of compound
...^ Compaq s8""^0
-T-^./^ K ^'^ '
n^s no1, contain-^-
CERB - STUDY No. 920083 E
APPENDIX 1
Protocol n 92.04.10.02
CERB - PROTOCOL N 92.04.10.02
TRIAL
Cutaneous primary irritation index.
SPONSOR:
ELF ATOCHEM
La Defense 10 - Cedex 42 92091 PARIS LA DEFENSE
Page 1 of 6
SITE OF TRIAL
: CENTRE DE RECHERCHES BIOLOGIQUES
Chemin de Montifault
18800BAUGY, FRANCE
APPROBATION :
SPONSOR CONTACT :
Mr REGNIER
22/04//92
Date
Signed
RESPONSIBLE STAFF FOR CERB :
Scientific and Technical Director :
S. RICHARD Pharmacien, Docteur de 3eme Cycle MaTtre en Pharmacologie
16/04/92
Date
Signed
Head of Toxicology Department :
C. AUDEVAL-GERARD Docteur Veterinaire
16/04/92
Date
Signed
Study^Director :
C. BESSON
14/04/92
Date
Signed
Quality Assurance : C. VIGIER
16/04/92
Date
Sianed
SCjompanySanitized. Does not contain TSCA'
The aim of the study is objective determination in the Rabbit of the irritant properties and/or degree of corrosion caused by compoundf following its single cutaneous application.
II METHOD
flfBHHH^0 Dermal irritation and/or corrosion following cutaneous application of compound the back of the Rabbit are evaluated by grading of the 'cutaneous irritation reactions seen, using a predetermined score system.
The protocol used for study of cutaneous primary irritation, complies with
requirements of OECD Guideline No. 404 (May 12, 1981) and EEC Directives (67/548, 79/831, 83/467, 84/449) and enables full evaluation of the reversible
or irreversible nature of the effects seen.
This method is not applicable to substances with a pH below 2 or above 11.5, with a predictable cutaneous corrosive action.
i")
rfy
A pre-study is carried out using one rabbit. If results shows no irritation or only slight irritation, the study is continued in
two other rabbits. If results reveals an irritant effect (grade S 3 erythema and/or edema), the prestudy can be continued until D8 and D15 to indicate the possible reversibility of lesions, though the study is not repeated in two other rabbits.
This study took place in accordance with rules of Good Laboratory Practices as published by :
- The French Ministry of Social Affairs and National Solidarity : State Secretariat Responsible for Health Instructions concerning Good Laboratory Practices (GLP) in the field of experimental toxicology.
Instruction of May 31, 1983, Official Text No. 1065 ; Reference SN-S83/25.
- Directive 87/18/EEC, this directive referring to Recommendation Appendix 2 of the OECD.
CC81/30
- The Food and Drug Administration : GLP 21 CFR Part 58 of
December
22, 1978 and amendments of April 11, 1980 and September 4, 1987.
III. COMPOUND FORAPERLE 321 :
DATA SUPLIED BY THE SPONSOR :
The substance information sheet and the analytical certificate were received on April 10,1992.
DATA TO. BE SUPPLIED BY THE SPONSOR : please fill in the test substance
^..^
information sheet.
AMOUNT OF COMPOUND TO BE SUPPLIED : 5 ml of compound]
are required for the study.
' -^Roil"' e^^^a. Hoes fto'-rtctnainTSCAl?.-""
CERB - PROTOCOL N 92.04.10.02 .
Page 3 of 6
IV - GENERAL CHARACTERISTICS OF STUDIES :
IV-1 ANIMALS
- SPECIES : New Zealand Albino Rabbit.
- ORIGIN : From CEGAV specialized breeding establishment (Les Hautes Noes, Saint Mars d'Egrenne, 61350 PASSAIS LA CONCEPTION, FRANCE).
f- WEIGHT : Generally between 1.5 kg and 2.5 kg at the start of the trial.
- SEX : male or female.
- NUMBER : 3.
- ACCLIMATIZATION : For at least 5 days before the trial, in the zone where the experiment is to take place. Animals are selected on the basis of their
general condition.
- - IDENTIFICATION : Animals are identified individually by ear clipping.
- HOUSING : Animals are kept in cages of standard size. Excreta are eliminated by unrolling plastified brown paper which is placed under the cages. These cages are kept in an air-conditioned (17C-21 C) animal house, kept at relative humidity between 45 per 100 and 65 per 100, apart from during cleaning, in which non-recycled filtered air is changed approximately ten times per hour. The artificial daylight cycle is 12 hours light and 12 hours darkness.
- FOOD : UAR 11 2 foodstuff. An analytical certificate concerning foodstuff is included in the study report.
Company Sanitized. Does nol contain TfiCA fW
CERB - PROTOCOL N 92.04.10.02
Page 4 of 6
- DRINKING WATER : Tap water distributed ad libitum in polycarbonate feeder bottles with a stainless steel teat. A water sample is obtained every three months and sent to the Direction des Services Veterinaires, 216 Rue Louis Mallet, 18014 BOURGES Cedex, FRANCE for analysis. A water analytical
certificate is included in the study report.
IV-2 APPLICATION OF COMPOUND
Compouncu|H|^B^^m)ls applied to the dorsal cutaneous region. For this
purpose, 6T^ the day prior to application, the dorsal region of each rabbit is carefully shaved over two symmetrical zones, measuring at least 14 cm x 5 cm,
in relation to the vertebral axis. An AESCULAP FAVORITA II GT 104 electric trimmer is used, avoiding any damage to the skin. Any animal with damaged
skin is eliminated from the study at the time of application.
The left flank of each of the animals is left intact.
A dose of 0.5 g of compound|HBlHHB|Tis applied to the right flank of
each of the animals. The non-treated flank of each animal serves as a control
for the trial.
The substance is deposited on a gauze square of approximately 6 cm2. The side of the gauze in contact with the compound is applied to the skin.
This gauze square is protected by a swab held in place with a URGOPORE microporous and non-allergic non-occlusive dressing, and the whole being held in place by COHEVET coalescent elastic and cohesive hypoallergenic tape. Dressings are held in place for 4 hours after application.
The day of application is taken as D1 of the study.
Steps of the study :
A pre-study is carried out using one rabbit. If results shows no irritation or only slight irritation, the study can be continued in two other rabbits.
If results reveal an irritant effect (grade > 3 erythema and/or edema), the prestudy can be continued until D8 and D15 to indicate the possible reversibility of lesions, though the study is not repeated in two other rabbits.
IV-3 CLINICAL MONITORING OF ANIMALS
Approximately one hour after removal of the dressing then 24 hours, 48 hours and 72 hours later, possible cutaneous lesions which may have appeared on the right flank of each of the animals are evaluated using the following score system. Observation can be continued until D8 and D15 if signs of irritation persist at 72 hours.
eristsss?;. D-.,c': Fib' contain T-S&A Grti
CERB - PROTOCOL N 92.04.10.02 ERYTHEMA AND ESCHARS FORMATION
Page 5 of 6
No erythema
0
Slight erythema (scarcely visible)
1
Clearly visible erythema
2
Moderate to marked erythema
3
Severe erythema (reddish purple) with
formation of slight eschars (deep lesions)
4
FORMATION OF EDEMA
No edema
0
Very slight edema (scarcely visible)
1
Slight edema (contours well defined,
visible swelling)
2
Moderate edema (thickness approximately 1 mm) 3
Severe edema (thickness more than 1 mm
and area greater than that of application)
4
IV-4 CALCULATION OF CUTANEOUS IRRITATION INDEX
Mean indices are calculated from results obtained for each rabbit at times 24 hours, 48 hours and 72 hours.
The following are noted :
- for each parameter, mean of indices for each rabbit for the three times
(= mean index per parameter, per animal for the three times = Mi)
The maximal theorical score is 4 (erythema/edema).
- for each parameter, the cumulative mean (= sum of mean indices for the
three animals / 3 = sum of Mi/3), The maximal theorical score is 4 (erythema/edema).
IV-5 CLASSIFICATION
The compoundflUBI^IBtis classified irritant or non irritant on the basis
of irritation indices obtained m accordance with the Directive 83/467/EEC proposed by the Official Gazette of the European Community.
Compound is found to be irritant if :
' -
- cumulative mean (Cm = sum of Mi/3) is higher or equal to the values indicated in table I for at least one parameter.
- or if, for at least one parameter, mean indices (Mi) are higher or equal to the values indicated in the table I in at least 2 animals.
B)
company Sanitized. Does not contain TSCA C"'
CERB - PROTOCOL N 92.04.10.02
23
Page 6 of 6
PARAMETER
THRESHOLD IRRITATION VALUE
Erythema
2
Edema
2
V- RESULTS
A!! data are recorded as and when obtained using files classified by the study number.
VI - REPORT
The report of experiment includes all findings noted during the course of the study, and in particular:
- irritation reaction observed, - cutaneous irritation indices, - classification of the studied compound.
VII - QUALITY ASSURANCE
The Quality Assurance Unit ensures that working procedures relating to this type of study are strictly adhered to, by periodic inspections of random, over the course of the year.
Data included in the report of the experiment are audited by the Quality Assurance Unit, in accordance with standard procedures at the Centre.
VIII - RECORDS
The protocol, any possible amendments, raw data, the correspondance and the report, and a sample of the compound are stored for five years at CERB, 18800 BAUGY, FRANCE, starting from the date of the final report.
At the end of this period, CERB will contact the sponsor in order to jointly determine to either :
- continue the records, - return the data to the sponsor, - destroy the data.
IX - PLANIFICATION :
Date of start of study : Week of April 27, 1992. Results by telex : at the end of the study. Date of submission of the draft report : end of May 1 992. Date of submission of the English summary : at the final report submission.
"-:o.?ip?iyS^hd -^-nytw-i^ s st:'^ ^
CERB - STUDY No. 920083 E
APPENDIX 2 Technical data and Analytical certificate
concerning compound
iCpmpany Sanitized. Does not contain TSCA CBI
SERVICE DE TOXICOLOGIE
COHFIDENTIEL Avri'1. 1992
eif^atochehi sa
La Defense 10, cedex 42 92091 Paris-La Defense France
FICHE D'INFORMATIONS
IMFORMATIOMS TOXICOLOGIQUES ET PRECAUTION D'EMPLOl
__ Aucune information'disponible.
CONDITIONS DE CONSERVATION ET DE DESTRUCTION
Conservation
Stabilite
Destruction
: A 1'obscurite et a 1'abri de la
chaleur.
: Stable jusqu'en Avril 1993 dans ces
conditions de stockage
: Incineration.
Mla^e^ Poe. not contain TSC^^
elf atochem sa
4, cours Michelet, cedex 42 92091 Paris La Defense 10
France
BULLETIN D'ANALYSE
^^fiVril 1992
Jean-Francois Regnier Service de Toxicologie
CERB - STUDY No. 920083 E
APPENDIX 3 Analytical certificate concerning foodstuff
^)
Company Sanitized. Does nol contain TSCA CBl
Ket. AUMENT CQMPLET
LAPINS - ENTRETIEN
Granules: <i.s ^
Ration joumaliere du Lapin: suivant la race.-de 100 a 150 g -- Eau a volonte.
FORMULE %
Cereales, "sucre .,..-......---
42,8
Issues" et legumineuses-.......
49
Pirpteines'vegetales (tourteaux)
4.2
Compose .nuneral
vitaminise
-
-
4
ANALYSE MOYENNE % .
Valeur calorifique (Cal/kg)
.2-200
" Eau "..:.-.-...---.....-Protides ---..--.--....--
".Upides ----..-..-.-.---."
'. Glucides '(Emuy- "'i,'...... -. ^Cellulose ^Weende) ''.-..--..
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(calcutes.en'nig/kg')
App. Nrt.
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TOTAUX
P .;..-.......-... <100
Ca
4.500
3500
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------ K ................. 10.600
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I.ISO
1350
j Mg .............. 2.100
130
TO
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'7.600
1
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10.600 3.100 Z230
160
1-40
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15
27"
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CERB - STUDY No. 920083 E
APPENDIX 4 Analytical certificate concerning water
CONSEIL
GCNERAi. OU
er
LABORATOIRE DEPARTEMENTAL
VETERIN.MRE
'gree par Ie Minislere de la srnte
Nd'Analyse: 920794 *Typc (Tanalyse: C7B3
RESULTAT D'ANALYSE D'EAU
N d'Ordre: 1236
Prelevemcnt d'eau parvenu Ie: Lundi 11 Kfai 1992
Effectuepan C.E.R.B. Origine:
Agent
lieu: ZONE PROTEGEE LATIN COULOIR PROPRE
Commune: BAUGY
Physicochimie
Turbi'dite en U Jackson Conduclivite pS/cm
.PH Oxydabilite KMn04 mg/1 Durete en 'Fran^ais T.A.C en "Francais Ammoniaque en mg/1 Nitrites en mg/1 Nitrates en mg/1 |5ulfates en mg/1 Bi~hlorures en mg/1 Fer en mg/1 Manganese en mg/1 Fluor en mg/1
Resultats Nonncs* Bacteriologie
: 0.3
652
7.S
:
I
: 37 25
0
0
57
65
: 20
:
0
<2U
6.5-9 <5
< 0.5 < 0.1 < 50 < 250 < 200 < 0.2 < 0.05 < 1.5
Colifbrmes thermotolerants/100ml Streptocoques fecaux/ 100ml Colifbrmes/ 100ml Denombrement des bacteries aerobies reviviriables a 37'C/ml
a.22'C/ml Spores de bacteries anaerobies sulfito-reductrices/20m]
/100ml
Salmonelles
Staphylocoques pathogenes
<5
*:SeIon decret N89-3 et suivants.
Resultats
0 0 2
< i
2.
0
Normes*
0 0
0-95%
.-
s1 0 . 0 0 0
Boorgcs.lc: Lundi 18 Mai 1992
Adj. Dir. du Laboratoire
Le Directeur du Laboratoire
Erick PRENGERE
Jean Mane GUERAUD
Company SanHized. Does nol contain TtfA i CpTnpa^Sanii^su/Doeahot-eo-ntelri-rS'CXCS?
CERB - STUDY No. 920083 E
APPENDIX 5 Results data sheet
CERB
CERT!^ co^pI-oOR;^^
IRRITATION PRIMAIRE CUTANEE
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HEURE DE DEBUT DE L'APPLICATION /
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ESPECE .-: Lapin Neo - Zeiandais
SEXE :-fflSAe. / femelle
DEBUT D'ETUDE : ?S.O<.<^
FIN D'ETUDE :- ^-0^
PARAPHE PARAPHE
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ESPECE ..: Lapin Neo - Zeiandais
SEXE : nterbe / femelle
DEBUT D'ETUDE FIN D'ETUDE
: 0 S.O^.^i' : " 'i. 0 $ 3 L.
PARAPHE : 3^45 / C (z)
PARAPHE : i^^O / CO
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