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Baugy, June 24 1993
STUDY NO 920085 E
SAFETY STUDY IN THE RAT BY ORAL ROUTE
Sponsor: ELF ATOCHEM SA
Tours Iris
La Defense 10, Cedex 42 92091 PARIS LA DEFENSE -
FRANCE
Sewpany Sanitized. Does not contain TSCA CW
CERB - STUDY No 920085 E
STUDY COMPOUND
: Safety study in the Wistar rat by oral route.
SPONSOR SPONSOR CONTACT ADDRESS
: ELF ATOCHEM SA. : Mr REGNIER : La Defense 10, Cedex 42
92091 PARIS LA DEFENSE - FRANCE
-OCATION OF STUDY
: 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
o/-i_i^j^(-f 3 Date
Signature
Head of Toxicology Department :
C. AUDEVAL-GERARD Docteur Veterinaire CES d'Ophtalmologie
3^|0^p5
Date [
Signature
Study Director :
L. BAUDET Ingenieur Biochimiste
3>0- C6S-3'
)ate
^O^r-g^fe SignapjfT-^^ ^
Quality Assurance : C. VIGIER
^-^xL^^S
Signature ^
The authentic results of the experiment form the basis of the present report.
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Company Sanlfeed. Does not conta.n TSCA ^
3 CERB - STUDY No 920085 E
This report consists of 31 pages numbered from 1 to 31 including 4 appendices.
CONTENTS ,
I.
SUMMARY
II.
EXPERIMENTAL PROTOCOL ADOPTED
11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9
11.10
11.11 11.12
AIM METHOD
COMPOUND ANIMALS ADMINISTRATION OF COMPOUND WEIGHING CLINICAL MONITORING OF ANIMALS AUTOPSY DATA ENTRY OF RESULTS REPORT QUALITY ASSURANCE RECORDS
III
RESULTS
111.1 111.2 111.3 111.4 111.5 111.6 111.7 111.8
DEVIATION FROM PROTOCOL No 92.04.10.04
DATES OF STUDY MORTALITY PERCENTAGE MORTALITY CLINICAL MONITORING WEIGHT CHANGES - MEAN RESULTS AUTOPSY EXAMINATION CONCLUSION
Page
4
6 6 7 8 9 9
10 10 10 10 10 10
11
12 12 12 13 13 14 16 16
APPENDIX 1 Protocol no 92.04.10.04
APPENDIX 2 Technical data and analytical certificate concerning
compound APPENDIX 3 Analytical certificate concerning foodstuff APPENDIX 4 Analytical certificate concerning water
17-23
24-26 27-29 30-31
**
CompanySanitized. Does not contain TSCA
CERB - STUDY No 920085 E
I. SUMMARY
The aim of this study (Ijmj^^a^^asJ^zerify that the maximum administrable
oral dose of compounq[t^^BH^^lB^s a suspension in distilled water, i.e
2000 mg/kg, according to Directive 67/548/EEC did not cause mortality of 50 %
or more in rats. If this were not the case, a lower dose was to be administered.
2000 mg/kg of compouncujIH^^^BIHBjs a suspension in distilled water,
were administered orally in a volume of 10 ml/kg.
A group of control animals dosed under the same conditions as the animals treated with 10 ml/kg of distilled water served as a reference.
Animals were monitored daily for 14 days after administration of compound.
Animals were weighed on days D-1, D1, D4, D7 and D14.
Under the experimental conditions adopted, essential experimental findings were :
- no mortality was recorded during the study,
- no symptomatology was noted during__the 14-day period following the
administration of compound|l|^----------^Bl
R\ (^^"^----l - mean body weight in animals treated with compound f_________^ id not
Jy
differ significantly from that of the control animals,
- no macroscopic organ or tissue abnormalities were seen at autopsy of the
animals treated with compoundQUmjHand sacrificed after a 14-day
observation period.
the dose of 2000mg/kgaidno^aiise^nymortaiity in the male and female
Wistar Rat.
Company Sanitized. Does not contain T8CA CBf
CERB - STUDY No 920085 E II. EXPERIMENTAL PROTOCOL ADOPTED
Company Sanitized. Does not contain TSCA CBF
CERB - STUDY No 920085 E
0
11.1 AIM :
The aim of the study was to verif^ha^raladministrgtiQiui^j^Bg^^
Q^QQQma/kq of the compound||H^H||UIHIHIHHHRBRH^H^
flBHHHM^inder acceptable conditions of gavage, did not cause mortality of
50 % or more in rats.
II.2 METHOD :
compouncfBHHiU^0^ Qualitative and quantitative evaluation of the toxic effectsseenfollowing^ngle
administration of the dose of 2000 mg/kg of
place in the male and female Rat in accordance with the general requirements of
OECD guidelines and requirements of 67/548 E.E.C. Guideline.
The protocol n 92.04.10.04 signed by the legal responsible for the sponsor of
the study and by the experimenters may be found in appendix 1.
The study was carried out in accordance with Good Laboratory Practices as
published by:
- the French Ministry of Social Affairs and National Solidarity : State Secretariat for Health. Guideline concerning Good Laboratory Practices (GLP) in the area of experimental toxicology. Guideline dated May 31, 1983, official text No. 1065 ; reference SN-S83/25.
- EEC Guideline 87/18. This guideline refers to recommendation CC81/30 Appendix 2 of the OECD.
- Food and Drug Administration : GLP 21 CFR Part 58 dated December 22, 1978 and amendments of April 11, 1980 and September 4, 1987.
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CERB - STUDY No 920085 E
11.3 COMPOUND :
The technical data and the analytical certificate concerning the compound are supplied with the study report in Appendix 2.
- Name
- Batch No
- Record number (CAL)
- Origin
ELF ATOCHEM SA.
- Date received
Saturday April 18 1992.
- Amount
1 bottle of 107 g.
- Appearance
- Storage conditions
: The compound was stored at room temperature, sheltered from light, in its original packaging.
Company Sanitized. Does not contain TSCA CB1
CERB - STUDY No 920085 E
11.4 ANIMALS : - SPECIES : SPF (Specific Pathogen Free) Wistar Rat.
- ORIGIN : CHARLES RIVER - 76410 ST AUBIN LES ELBEUF-FRANCE
specialized breeding station. - AGE : over 6 weeks at the time of administration. - SEX : Male and female animals. Females were nulliparous and non-gravid. - NUMBER : Five males and five females per dose. - ACCLIMATIZATION : For 5 days before random distribution into treatment
groups, in the area where the experiment was to take place.
- DATE OF DELIVERY : 22.04.1992. - DISTRIBUTION BY GROUP : The day prior to the study, on D-1, animals were
randomized into the different treatment groups on the basis of the criterion of body weight. Randomization was separate for each sex. - IDENTIFICATION : They were identified in accordance with standard operating procedures at the Center. - HOUSING : Five male or female animals from each treatment group were kept per cage of standard size, on dust-free white wood shavings as bedding, sterilized by irradiation.
These cages were placed in an air-conditioned animal house (18-22C) kept at a constant relative humidity of between 45 % and 65 %, in which recycled
filtered air was changed approximately ten times per hour. The artificial daylight cycle was 12 hours light and 12 hours darkness.
FOOD : UAR A04 C-10 (subjected to quality control and sterilized by
irradiation). An analytical certificate may be found with the study report in Appendix 3. DRINKING WATER : Softened tap water distributed 'ad libitum' in polycarbonate feed bottles with a stainless steel teat. A water sample was taken every three months and sent to the Direction des Services Veterinaires,
216 rue Louis Mallet, ,18014 BOURGES CEDEX, FRANCE for analysjs. The
water analytical certificate in Appendix 4 corresponds to the sample taken at the closest date of the start of the present study.
company Sanitized. Does not contain TSCA C'
CERB - STUDY No 920085 E
11.5 ADMINISTRATION OF COMPOUND :
CompoundlJII^BHUUIJwas administered to animals fasting of food since
the previous day. It was administered to the animal by single dose, by gavage, using a cannula of appropriate size.
After administration of compound, animals remained deprived of food for a period of 3 to 4 hours approximately.
- DOSE ADJUSTMENT :
The dose administered was expressed in mg/kg and adjusted to the weight of the animal determined just before administration.
- NUMBER OF DOSES :
The dose of 2000 mg/kg was administered in accordance with acceptable
conditions of gavage under the study conditions.
- FORM OF ADMINISTRATION :
The compound was administered as a suspension in distilled water. - VOLUME ADMINISTERED :
The volume administered was 10 ml/kg of body weight. - METHOD OF PREPARATION :
^^IHIH^^^H 6 g of compound|HliHHHm^were weighed. Distilled .water was then
added in sufficient amount to obtained a 30 ml preparation.
suspension was obtained.
^^^^^^^^^^^
Control animals were dosed with 10 ml/kg of distilled water under the same conditions as treated animals.
II.6 WEIGHING :
Animals were routinely weighed on the following days:
- day of randomization, on D-1, - fasting on D1, day of administration, - on days D4, D7 and D14 during the study.
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11.7 CLINICAL MONITORING OF ANIMALS :
Animals were regularly monitored on the day of administration. They were then examined clinically at least once a day for 14 days.
Findings were routinely noted using clinical case report form individual for each animal.
11.8 AUTOPSY:
All animals dying during the course of the study were autopsied as rapidly as possible and their main organs examined macroscopicaliy (liver, spleen, kidneys, stomach, lungs, heart).
All animals surviving at the end of the 14-day observation period were autopsied on D15 and the main organs as cited above were studied macroscopicaliy.
11.9 DATA ENTRY OF RESULTS :
All results were recorded as and when obtained using forms identified by the study number.
11.10 REPORT:
The experimental report included all findings noted during the course of the study, and in particular information concerning : - obervation of animals, - recording of mortality and of its causes, - body weight change, - macroscopic examination of the main organs.
11.11 QUALITY ASSURANCE :
The Quality Assurance unit ensured that working procedures relative to this type of study were strictly complied with by periodic inspections at random over the course of the year.
Data in the experimental report were audited by the Quality Assurance Unit, in accordance with standard operating procedur.es at the Centre.
11.12 RECORDS:
The protocol, the raw data, the report, correspondence 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.
All the end of this period. CERB will contact the sponsor in order to jointly
determine to either :
- continue storage of records,
- return the data to the sponsor,
- destroy the data.
Company Sanded. Does not contain TSCA C^
CERB - STUDY No 920085 E RESULTS
ft
vsss.-. SAA aSw:'^ 'SCA CB1
CERB - STUDY No 920085 E ?
1-1 DEVIATION FROM PROTOCOL No 92.04.10.04 :
Housing : 5 male or female animals from the same treatment group were kept per cage
of standard size, on an ABSORB PLUS vegetable bedding (particle size 8/10) following a new bedding selected by CERB.
Form of administration : The compound was administered as a suspension in distilled water and not as a solution.
Weighing : Animals were weighed on D4 and not on D3.
111.2 DATES OF STUDY :
Date of start of study : D1 = Date of end of study : D15 =
28.04.1992. 12.05.1992.
111.3 MORTALITY (expressed in %) :
[----MB] D1
mg/kg
+lmm. <3h
MALE RATS
0
0
0
2000
0
0
MORTALITY KINETIC D2 D3 D4 D5 D6 D7 D14
<8h
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
FEMALE RATS
0
2000
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
+ Imm. : Immediate
Company Sanitized. Does not contain TSCA CBI
CERB - STUDY No 920085 E
.4 PERCENTAGE MORTALITY :
DOSE mg/kg
VOLUME ml/kg
CQNCEMTRATION,
AsfiflUBUHBll
^/Toffin^--
0
10 *
0
2000
10
20
MORTALITY PER 5 RATS (%)
MALES FEMELLES
0
0
0
0
* : distilled water.
No mortality was recorded during the study.
III.5 CLINICAL MONITORING :
aNdominsiysmtrapttioomn aotfolcoogmy powuansd. frl--eco--rd--ed--^d--uri--ng--ltlhe
14-day
period
following
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CERB - STUDY No 920085 E
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111.6 WEIGHT CHANGES (g) - Mean results :
Mean body weights and mean percentage variations in body weight of animals during the course of the trial are shown in table I overleaf.
Mean body weight in animals treated with compoundjHIHBIHH^Jdidnot
differ significantly from that of the control animals.
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.C- ompany Sanded. Does not contain TSCA CB
CERB - STUDY No 920085 E
TABLE I
BODY WEIGHT CHANGE - MEAN RESULTS (g)
PERCENTAGE WEIGHT VARIATION / D-l
RATS
DOSES
MALES
D--1
D4
D7
D14
OMG/KG
2000MG/KG
count
mean
stdev
sem
%
count
mean
stdev
sem
%
5
199. 8 5. 4 2. 4
5
199. 6 3. 8 1. 7
NS
5
229 .8 5 .5 2 .5
15 .0
5
228 .8 1 .6 0 .7
NS
14 .6
5
250 .0 7 .2 3 .2
25 .1
5
250 .8 5 .8 2 .6
NS
25 .7
5
302. 8 13. 7 6. 1 51. 6
5
299. 6 10. 9 4. 9
NS
50. 1
DOSES
FEMALES
D-l . D4
D7
D14
OMG/KG
2000MG/KG
count
mean
stdev
sem
%
count
mean
stdev
sem
%
5
156. 2 2. 9 1. 3
5
156. 2 3. 3 1. 5
NS
5
174. 4 4. 1 1. 8
11. 7
5
174. 8 5. 9 2. 7
NS
11. 9
5
180 .8 4 .9 2 .2
15 .7
5
182 .4 5 .2 2 .3
NS
16 .8
5
204. 6 6. 5 2. 9
31. 0
5
206. 2 6. 6 3. 0
NS
32. 0
stdev
sem NS
standard deviation. standard error mean. non-significant difference at threshold of 5 in comparison with control group (p > 0.05). percentage weight variation / D-l.
p.100
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CERB - STUDY No 920085 E
111.7 AUTOPSY EXAMINATIONS :
compoundmfUfJand No macroscopic organ and tissueabnormajities.were seen at autopsy of the
animals treated with
sacrificed after a 14-day
observation period except some congestive points noted on the thymus in control
female no 920307.
111.8 CONCLUSION :
S^ At request of ELF ATOCIjEM
a safety study in the Rat by oral dosing was
undertaken on compound||HB||BHHy)
20uff?g7k^iffTo^auseanymortality in the male and female Wistar Rat.
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CERB - STUDY No 920085 E APPENPIX 1
Protocol no 92.04.10.04
Company Sanitized. Does nol contain TSCA C.W
CERB - PROTOCOL No 92.04.10.04
TRIAL :
'Safety study in the rat by oral route
SPONSOR:
ELF ATOCHEM SA La Defense 10. Cedex 42 92091 PARIS LA DEFENSE-FRANCE
Page 1 of 6
SITE OF TRIAL: CENTRE DE RECHERCHES BIOLOGIQUES Chemin de Montifault
18800 BAUGY-FRANCE
APPROBATION :
SPONSOR CONTACT :
Mr REGNIER
22.04.92
Date
Signed
RESPONSIBLE STAFF FOR CERB :
Scientific and Technical Director :
S. RICHARD
14.04.92
Date
Signed
Head of Toxicology Department : C. AUDEVAL-GERARD
14.04.92
Date
Signed
Study Director : L. BAUDET
13.04.92
Date
Signed
Quality Assurance : C. VIGIER
14.04.92
Date
Signed
Company Sanitized. Does nol contain TSCA CF<
CERB - PROTOCOL No 92.04.10.04
Page 2 of 6
Safety study in the rat by oral dosing
I- AIM :
Verify that_pral administration in the Rat of the dose of 2000 mg/kg of the
coiripound||Bl|HI|IBiy^ under acceptable conditions of gavage, does not
cause mortantyo^bO % or more in rats. If this is not the case, a dose of 200 mg/kg is to be administered.
II- METHOD :
Qualitative and quantitative evaluation of the toxic effects^eer^ollowing single
administration of the dose of 2000 mg/kg of compoundHlH^I^HBfrjtakes
place in the male and female Rat in accordance with the general requirements of
OECD guidelines and requirements of 67/548 E.E.C. Guideline.
The study is carried out in accordance with Good Laboratory Practices as published by:
- the French Ministry of Social Affairs and National Solidarity : State Secretariat for Health. Guideline concerning Good Laboratory Practices (GLP) in the area of experimental toxicology.
Guideline dated May 31, 1983, official text No. 1065 ; reference SN-S83/25. - EEC Guideline 87/18. This guideline refers to recommendation CC81/30
Appendix 2 of the OECD.
- Food and Drug Administration : GLP 21 CFR Part 58 dated 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 :
10 ml of compound^^BBlUm----^wbiell necessary for carrying out this
^oimp?.";- '^m'fee'6', 'Ooes 7K?rebtriaif! TSCA CBi
2C
CERB - PROTOCOL No 92.04.10.04
Page 3 of 6
IV-4 ANIMALS:
- SPECIES : SPF (Specific Pathogen Free) Rat Wistar.
- ORIGIN : From the CHARLES RIVER - 76410 ST AUBIN LES ELBEUF- FRANCE
specialized breeding station.
- AGE : over 6 weeks at the time of administration.
- SEX : Male and female . Females are nulliparous and non-gravid.
- NUMBER : Five males and five females per dose.
- ACCLIMATIZATION : For at least 5 days before random distribution into treatment groups, in the area where the experiment is to take place.
- DISTRIBUTION BY GROUP : The day prior to the study, on D-1, (not before D-3 ie 72 hours before the study) animals are randomized into the different treatment groups on the basis of the criterion of body weight.
- IDENTIFICATION : Animals identified by cage, separately, by picric acid tagging.
- HOUSING : Five male or female animals from the same treatment group are
kept per cage of standard size, on dust-free white wood shavings as bedding, sterilized by irradiation.
These cages are placed in an air-conditioned animal house (18-22C) kept at a constant, relative humidity of between 45 % and 65 %, in which recycled
filtered air is changed approximately ten times per hour. The artificial daylight cycle is 12 hours light and 12 hours darkness.
Company Sanitized. Does noi contain TSCA CW
2i
CERB - PROTOCOL No 92.04.10.04
Page 4 of 6
- FOOD : UAR A04 C-10 foodstuff (subjected to quality control and sterilized
by irradiation). An analytical certificate is included in the study report.
- DRINKING WATER : Softened tap water distributed 'ad libitum' in polycarbonate feed bottles with a stainless steel teat. A water sample is taken
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.
I'V-2 ADMINISTRATION OF COMPOl
CompoundjI^^^UB^fQis administered to animals fasting of food since the
previous day (approximately 16 hours). It is administered to the animals distributed into groups by single dose, by gavage, using a cannula of appropriate
size. After administration of compound, animals remain deprived of food for a period of 3 to 4 hours approximately.
IV-2-1- Dose adjustment :
The dose administered is expressed in mg/kg and adjusted to the weight of the animal determined just before administration.
IV-2-2 Number of doses :
2 doses including the zero dose (controls) are carried out during the study.
Group 1 : 10 rats (5 males and 5 females) : Controls (Dose 0)
2:I1^0HUH^I^IpjThis Group
rats (5 males and 5 females) 2000 mg/kg of compound dose is administered in accordance with
acceptableconditions of gavage under the study conditions.
IV-2-3 Form of administration :
The compound is administered as a solution in distilled water.
Control animals are dosed with the vehicle only under the same volume as the treated animals.
IV-2-4 Volume administered :
10 ml/kg of body weight.
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Company Sanitized. Does Hoi contain TSCA CBl
^ /'
CERB - PROTOCOL No 92.04.10.04
V-3 WEIGHING :
Page 5 of 6
Animals are routinely weighed on the following days:
- day of randomization ; - fasting on D1, day of administration, - on days D3, D7 and D14 during the study.
IV-4 CLINICAL MONITORING OF ANIMALS :
Animals are regularly monitored on the day of administration. examined clinically at least once a day for 14 days.
They are then
Findings are routinely noted using clinical case report form individual for each animal.
IV-5 AUTOPSY :
All animals dying during the course of the study are autopsied as rapidly as possible and their main organs examined macroscopically (liver, spleen, kidneys, stomach, lungs, heart).
All animals surviving at the end of the 14-day observation period are autopsied on D15 and the main organs as cited above are studied macroscopically.
All organs showing obvious evidence of general pathology are fixed in an appropriate agent for possible subsquent histopathology (not included in
estimate).
V DATA ENTRY OF RESULTS :
All results are recorded as and when obtained using forms identified by the study number.
VI REPORT :
The experimental report includes all findings noted during the course of the study, and in particular information concerning : - obervation of animals, - recording of mortality and of its causes, - body weight change, - macroscopic examination of the main organs.
VII QUALITY ASSURANCE :
The Quality Assurance unit ensures that working procedures relative to this type of study are strictly complied with by periodic inspections at random over the course of the year.
Data in the experimental report are audited by the Quality Assurance Unit, in accordance v\/ith standard operating procedures at the Centre.
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CERB - PROTOCOL No 92.04.10.04
VIII- RECORDS :
Page 6 of 6
The protocol, any possible amendements, the raw data, the report, correspondence and a sample of the compound are stored for five years at CERB
- 18800BAUGY, FRANCE.
At the end of this period, CERB will contact the sponsor in order to jointly determine to either :
- continue the storage of the records, - return the data to the sponsor, - destroy the data.
IX - PLANIFICATION :
Date of start of study : Week of April 27 1992. Date of end of study : At the end of the study. Date of submission of draft report : 1rst fortnight of June 1992 Date of submission of the English summary : at the final report submission.
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Company Sanitized. Does nol conta'n TSCA CBT
CERB - STUDY No 920085 E
(-
APPENDIX 2 Technical data and analytical certificate
concerning compound
^
%o?parsy'Sari!ti^eci^c?yenclCCT{c"nfSCAC8i
SERVICE DE TOXICOLOGIE
CONFIDENTIEL
Avril 1992
^
elf atacMem sa
La Defense 10, cedex 42 92091 Paris-La Defense France
FICEE D'INFORMATIONS
IINFORMATIONS 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.
'Company Sanitized; Ooesmrt contain TSCA CBf
elf atochem sa
4, cours Michelet, cedex 42 92091 Paris La Defense 10
France
BULLETIN D'ANALYSE
A-rB
^^-fivril 1992
Jean-Francois Regnier Service de Toxicologie
"''.,0 fr'^-sriv ^c;"!('''.';.:"^"^ '!;'" c^nt?-:" ^'"A CB?
CERB - STUDY No 920085 E
APPENDIX 3 Analytical certificate concerning foodstuff
FIWE. DC CONTnOLE CONTROL SHEET
ALIMENT A04C-10 N" LOT: 11219
23
FOODSTUFF
UTILISATEUR
user
NOMBRE DE SACS DANS LE LOT :
561 a 1400 <
Number of bags in the lot DATE LIMITE DE VENTE conseillee
last selling date
DATE LIMITE D'UTILISATION :
last utilization date
19.03.92 19.06.92
CENTRE RECHERCHES BIOLOGIQUES CHEMIN DE MONTIFAULT 18800 BAUGY
CONTROLE D'HOMOGENEITE :
consistency check
CONTROLE COMPOSITION CENTESIMALE
centesimal composition control
CONTROLE DE LA QUALITE PHYSIQUE
PHYSICAL QUALITY CONTROL
Diametre des pellets diameter of pellets Longeur des pellets Length of pellets
Resistance a 1'ecrasement crushing' strength Resistance a 1'abrasion
scratch resistance
Fines
16,13 24,0 20,7 98,8
< 1
dust
Poids moyen
5,4
Medium weight
^0.05 ^3.1 -1,3
^0,7
mm nun
]\e/cm2
CONTROLE DE LA QUALITE NUTRITIVE NUTRITIVE QUALITY CONTROL
Temoin d'incorporation melange mineral (Na) : incorporation counter sample mineral mixture (Na) Temoin d'incorporation premelange oligo-elements (Mn) :
incorporation counter sample trace element premixing CMn)
Temoin d'incorporation premelange vifamines (Vit.A) :
incorporation counter sample vitamin A premixing
wEaateur ................
12
Proteines protein
.........
17
L1iippidisdes............
Glucides (E.N.A.)..
58
carbohydrates (NFE)
dont Amidon....
40
of which starch
Cellulose..........
eellulose Mineraux totaux.--.
asn
ol-'
dont wh i ch
Ca......
P.
^
Na............
K. ......
VMi nfc.a.m.i.n..e
Vi Lamine
8400 5600 2300 6500
91
5500
/
mg/kg mg/KS mg/kg mg/Kg
ITlg/lvg
UI/!<S
ll|':;/'".g
So^paRyB'aTSiHzaa.',Ooes noil frontain TSR& r:w
Company Sanitized. Does nh i<n"*n'~ -res^n
BACTERIOLOGIQUES
bacteriological
Germes revivifiables...
regenerating germs
Coliformes.............
EAn.aCeroobliie.s...S....R...................
Salmonella.............
PESTICIDES
pesticides Organo-chlores organcchlorides
La indane................ HeHpCtaHc.h.l.o..r.e........................
DOT.................... DDiDeEld.r..i.n..e............................
Endosulfan.............
APuCtreBs . .0...C. .h. .l.o.r.e. .s. .............
Other O.ChI.
METAUX LOURDS
Heavy inetais
Plealod mb..................
Mercure................
Mercury
AArrsseneicnic................
Cadmium................
cadmium
Selenium selenium
..............
CONTROLE DES CONTAMINANTS
< 10 /g 0 /g 0 /g 0 /g 0 /25g
MYCOTOXIQUES
mycotoxic
aflatoxines...
<
1
Ochratoxines. .
< 12
Zearalenone...
< 50
Sterigmatocystine. < 30
< 1 Pg/kg < 1 Pg/kg
< 1 Pg/kg < 1 Pg/kg < 1 Pg/kg < 1 Pg/kg < 1 Pg/kg
< 1 Ug/kg < 1 Pg/kg
Organo-phosphores organophosphates
Malathion.....'.
Pyrimiphos CH3.. Chlorpyriphos CH3
Dimethoate...... Phosalone....... Autres O.PH.....
others O.PH
495
105
85
<
5
<
5
<
5
DERIVES NITROSES ;-<i tro-compounds
259 Pg/kg
N03. N02.
..............
108 6 ,8
49 Pg/kg
NDMA ...........................
0 ,5
0
301 Pg/kg
NDEA..............
<
,05
0
NDBA.............. .3
NDPA..............
<
0 ,05
0
73
Pg/kg
:
NPip.............. NPy...............
< <
,05 0 ,05
164 Pg/kg
29
Pg/kg Pg/kg
Pg^kg
Pg/kg
Pg/kg Pg/kg Pg/kg Pg/kg Pg/kg Pg/kg
ing/kg mg/kg Pg/kg Pg/kg
Pg/kg Pg/kg Pg/kg Pg/kg
N" DES SACS : 850 a 874 soit 625 KG (BL.2380) nb of bags CONTROLE<S) SPEC.IFIQUE(S) sur demande : Irradie a 10 kGy
specific test(s) on request
REMARQUES : Conforme aux normes du NCTR.
DATI)/: 6 FEVRIER 1992
J L = ^ .....
Michel HU^RD
DIRECTEUR SCIE^TIFIQUE
Assurance Qualite. Scientific Manager
Oua 1 i Ly I n:? LI i-a nee
'
'"^'V''?^" "
..
tesr--'-^'-'"
{ -. r .'
^..i.t.tilt t ui/^ ^'i^t
CERB - STUDY No 920085 E ", !~' ,ju APPENDIX 4 Analytical certificate concerning water
..,...,...----"
LABORAT01RE DEPARTEMENTAL VETER1NAIRE
31
RESULTAT D'ANALYSE D'EAU
agree par Ie Ministere de la sante
Nd'AaaIysc: 920279 *Typc d'analyse: B3+ 12P
N d'Ordrc: 39(^
Prclcvement d*cau parvenu Ic:
Effecftiepan CE.R.B. Originc: Robmefderevier
lieu: CONVENnbNh?ELLERATS
Commune: BAUGY
Lundi 17Fevrier 1992
Agent le client
Physicochimic
Turbidite en U Jackson Resistivile pS/cm PH
Oxydabilite KMn04 mg/1 Ourete en 'Francais T^\.C en 'Francais Ammoniaque en mg/1 Nitrites en mg/1 Nitrates en mg/1 Sul fates en mg/1
1Chlorures en mg/I
Fer en mg/1 Manganese en mg/1 Fluor en mg/1
Resultats Nonacs* Bacteriologic
Resaltats
0.3
<2U Coliformes thermotolerants/ 100ml
0
6-42
Streptocoques fecaux/IOOm!
0
7.4 6,5-9 Coliformes/100ml
0
0.8
<5
Denombrement des bacteries
10
aerobies reviviflables a 37'C/ml
<I
2S
a 22'C/mI
<l
0
< 0.5 Spores de bacteries anaerobies
0
< 0.1 sul fi to-reductrices/20m 1
0
59
< 50
/100ml
56
< 250 Salmonelles
22
< 200 Staphylocoques pathogenes
:
0
< 0.2
< 0.05
< 1.5
<5 ^sSeIon decret N"89-3 et survans<
Nonnes* 0 0
0-95%
i\
0 0 0 0
Bonrgcs.lc: Mardi 25 Fevrier 1992
Le Directeur du Laboratoire
Jean Maric GUERAUD
'e?on<p3riySaiui^fca^i^us Sios ccntah-i rs=:^ CKs