Document 2bLn2vQp4Eo90v1RJd3mj075

3v i-r~~ S> l ***S5S? Ur*<!i AR226-2995 i Baugy, June 24 1993 STUDY NO 92Q085 E SAFETY STUDY IN THE RAT BY ORAL ROUTE Sponsor : ELF ATOCHEM SA Tours Iris La Dfense 10, Cedex 42 92091 PARIS LA DEFENSE - FRANCE Company Sanitized. Does fot contain TSC CB T'Vl 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 Dfense 10, Cedex 42 92091 PARIS LA DEFENSE - FRANCE I 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 3me Cycle o sMatre en Pharmacologie Date i / ----f r * -- -- Signature Head of Toxicology Department : C. AUDEVAL-GERARD Docteur Vtrinaire CES d'Ophtalmologie Study Director : L. BAUDET Ingnieur Biochimiste Quality Assurance : C. VIGIER i Signature CJ The authentic results of the experiment form the basis of the present report. Company Sanitized. Does nof contain TSCA CERB - STUDY No 920085 E 3 This report consists of 31 pages numbered from 1 to 31 including 4 appendices. CONTENTS I. SUMMARY II. EXPERIMENTAL PROTOCOL ADOPTED 11.1 II.2 II.3 II.4 II.5 II.6 II.7 II.8 II.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 DEVIATION FROM PROTOCOL No 9 2 .0 4 .1 0 .0 4 III.2 DATES OF STUDY III.3 MORTALITY III.4 PERCENTAGE MORTALITY III.5 CLINICAL MONITORING III.6 WEIGHT CHANGES - MEAN RESULTS III.7 AUTOPSY EXAMINATION III.8 CONCLUSION APPENDIX 1 Protocol no 9 2 .0 4 .1 0 .0 4 APPENDIX 2 Technical data and analytical certificate concerning compound APPENDIX 3 Analytical certificate concerning foodstuff APPENDIX 4 Analytical certificate concerning water Page 4 5 6 6 7 8 9 9 10 10 10 10 10 10 11 12 12 12 13 13 14 16 16 17-23 24-26 27-29 30-31 Company sanitized. Does not contain TSCA c . CERB - STUDY No 920085 E I. SUMMARY The aim of this study ;erify that the maximum administrable oral dose of compounc^ js a suspension in distilled water, i.e 2000 mg/kg, a_c_c_o_rd__inag'to Directive 67/54'---/E--E--C----d--id---n--o--t 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 c o m p o u n c | j H I H ^ f l i H l ^ s 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 n o te^ d u m ^ he 14-day period following the administration of c o m p o u n d j H ^ m ^ l - mean body weight in animals treated with compound differ significantly from that of the control animals, id not - no macroscopic organ or tissueabnorm alitie^^ere seen at autopsy of the animals treated with c o m p o u n d Q m ^ H H m ^ n d sacrificed after a 14-day observation period. In conclusion, u n d e i^ h ^ ) m e r im e n t a ^ o n |t o n ^ ^ ^ ^ ^ ^ ^ ^ ^ M ^ ^ ^ ^ L f the dose of 2 0 0 0 mg/kg did not cause any mortality in the male and female Wistar Rat. Company Sanitized. Does noi contain TSC A CBI CERB - STUDY No 920085 E II FXPFRIMENTAL PROTOCOL ADOPTED Company Sanitized. Does not contain T SC A C B P CERB - STUDY No 920085 E b 11.1 AIM The aim of the study was to verif e dose o ^ 0 0 ^ T T a /k a of the compound|_________________ _ J f m ^ j n d e r acceptable conditions of gavage, did not cause mortality of 50 % or more in rats. II.2 METHOD : Qualitative and quantitative evaluation of the toxic effect^seer^ollow in^sm gle administration of the dose of 2000 mg/kg of c o m p o u n c ^ H I H H H ^ ^ ^ o o k place in the male and female Rat in accordance with the general requirements of OECD guidelines and requirements of 6 7 /5 4 8 E.E.C. Guideline. The protocol n 9 2 .0 4 .1 0 .0 4 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 S N -S83/25. - EEC Guideline 8 7 /1 8 . This guideline refers to recommendation C C 81/30 Appendix 2 of the OECD. - Food and Drug Administration : GLP 21 CFR Part 58 dated December 2 2 , 1978 and amendments of April 11, 1980 and September 4, 1987. aTtffzeS.'Offeso 'cWam 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 CBI CERB - STUDY No 920085 E 11.4 ANIMALS : - SPECIES : SPF (Specific Pathogen Free) Wistar Rat. - ORIGIN : CHARLES RIVER - 7 6 4 1 0 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 : 2 2 .0 4 .1 9 9 2 . 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 A 04 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 Vtrinaires, 216 rue Louis Mallet, J 8 0 1 4 BOURGES CEDEX, FRANCE for analysis. 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 no! contain T SC A C V CERB - STUDY No 920085 E a H R ADMINISTRATION OF COMPOUND : C o m p o u n d (||^ ^ H H I^ m Q w a s 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 2 0 0 0 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 : 6 g of c o m p o u n d i M H I H ^ l w e r e weighed. Distilled w a t e i^ /a ^ h e n 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. Il.fi WEIGHING : Animals were routinely weighed on the following days: - day of randomization, on D -1, - fasting on D 1, day of administration, - on days D4, D7 and D14 during the study. TK5si;tfot ;or3'r* e.w CERB - STUDY No 92085 E 11.7 CLINICAI 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 macroscopically (liver, spleen, kidneys, stomach, lungs, heart). All animals surviving at the end of the 14-day observation period were autopsied on D 1 5 and the main organs as cited above were studied macroscopically. II-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. Com pany Sanitized. Does not contain T S C A C tf CERB - STUDY No 920085 E III. RESULTS CERB - STUDY No 920085 E 111-1 DEVIATION FROM PROTOCOL No 9 2 .0 4 .1 0 .0 4 : - 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. . III-2 DATES OF STUDY : Date of start of study : D1 = 28.0 4 .1 99 2 . Date of end of study : D 1 5 = 12.05.1992. III.3 MORTALITY (expressed in %) : mg/kq MALE RATS 0 2000 D1 + Imm. < 3 h MORTALITY KINETIC D2 D3 D4 D5 D6 D7 D14 <8h 0 0 0 000000 0 0 0 0 000000 0 FEMALE RATS 0 2000 0 0 0 000000 0 0 0 0 000000 0 + Imm. : Immediate Company Sanitized. Does not contain TSCA CBI CERB - STUDY No 920085 E 1114- PERCENTAGE MORTALITY : DOSE mg/kg VOLUME ml/kg C Q N C E ^ g A T jO N ^ 0 2000 10 * 10 0 20 MORTALITY PER 5 RATS (%) MALES FEMELLES 00 00 * : distilled water. No mortality was recorded during the study. Ill B Cl IN1CAL MONITORING : No symptomatology was recorded durii the 14-day period following administration of compound! ] CompanyBanifeiS. Tfoss mremr^n rs'es.m i CERB- STUDY No 920085 E III.6 WEIGHT CHANGES (a) - 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 c o m p o u n d f ip H IH B B H |) d id not differ significantly from that of the control animals. Company Sanitized. Does nol contain TSCA CBf CERB - STUDY No 920085 E TABLE I BODY WEIGHT CHANGE - MEAN RESULTS (g) PERCENTAGE WEIGHT VARIATION / D- 1 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 200OMG/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 p.100 in comparison with control group (p > 0.05). percentage weight variation / D--1. U ses'lfo t'contain TSCA CBI 'CO CERB - STUDY No 920085 E 111.7 AUTOPSY EXAMINATIONS : No macroscopic organ and t i s s u ^ w e r e seen at autopsy of the animals treated with c o m p o u n d y |m ^ H H B f J a n d sacrificed after a 14-day observation period except some congestive points noted on the thymus in control female no 92 03 0 7 . Ill B CONCLUSION : At request of ELF A T O C H E I ^ ^ ^ a f e t v study in the Rat by oral dosing was undertaken on c o m p o u n c f l m m m m ^ ^ Under experimental conditions adopted, compounf w _____ administered orally at the dose of ------------- -, ^ S D ^ g /l^ ^ ^ n o ^ a iis ^ n ^ m o r ta lity in the male and female Wistar Rat. Z'Z*'r c;Bs CERB - STUDY No 920085 E APPENDIX 1 Protocol no 9 2 .0 4 .1 0 .0 4 Company Sani!szed. D o ss noi contain T SC C B CERB - PROTOCOL No 9 2 .0 4 .1 0 .0 4 Page 1 of 6 TRIAL : m am m i Safety study in the rat by oral route SPONSOR : ELF ATOCHEM SA La Dfense 10, Cedex 42 92091 PARIS LA DEFENSE-FRANCE SITF OF TRIAL: CENTRE DE RECHERCHES BIOLOGIQUES Chemin de Montifault 1 8 8 0 0 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 not contain TSC A CPU (1 MCERB - PROTOCOL No 92.04.10.04 ) Page 2 of 6 Safety study in the rat by oral dosing I- AIM : Verify that oral administration in the Rat of the dose of 2 0 0 0 mg/kg of the c o m p o u n d f M H H J H H M } under acceptable conditions of gavage, does not cause m o rta J rt^ o ^ b ^ ^ ro o r 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 e ffe c ts ^ ^ ^ ^ ^ ^ w jn o s in g le administration of the dose of 2000 mg/kg of c o m p o u n d |fl[|^ ^ H ^ H H P J takes place in the male and female Rat in accordance with the general requirements of OECD guidelines and requirements of 6 7 /5 4 8 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 3 1 , 1983, official text No. 1 065 ; reference S N -S83/25. - EEC Guideline 8 7 /1 8 . This guideline refers to recommendation C C 81/30 Appendix 2 of the OECD. - Food and Drug Administration : GLP 21 CFR Part 58 dated December 22, 1 9 78 and amendments of April 11, 1980 and September 4, 1987. III. COMPOUND FORAPERLE 3 2 1 : DATA SUPLIED BY THE SPONSOR : The substance information sheet and the analytical certificate were received on April 10 1992. DATA TO B SUPPLIED BY THE SPONSOR : '' Please fill in the test substance information sheet. AMOUNT OF COMPOUND TO BE SUPPLIED : 10 ml of compound study. will be necessary for carrying out this omp?.;' finnttzeUi, '0'oesst 'contain TS'C CB ?0 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 groupsi, 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 no! contain TSC A Cffl CERB - PROTOCOL No 92.04.10.04 Page 4 of 6 - FOOD : UAR A 04 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 sajnple is taken every three months and sent to the Direction des Services Vtrinaires, 2 1 6 rue Louis Mallet, 18014 BOURGES CEDEX, FRANCE for analysis. A water analytical certificate is included in the study report. i\/-7 ADMINISTRATION OF COMPOUNC^B ^ ^ I B B ^ C o m p o u n d H I ^ H ^ H f l Q i s administered to animals fasting of food since the previous cfey (approximately 16 hours). It is administered to the animals distributed into groups by single dose, by gavage, using a cannula of appropriate SZ6 . . 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) Group 2 : and d femaies) 2CCC my/kg of compound 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. Com pany Sanitized. Does not contain T SC A CBI CERB - PROTOCOL No 92.04.10.04 Page 5 of 6 \A3 WEIGHING : 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. They are then examined clinically at least once a day for 14 days. 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 D 1 5 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 with standard operating procedures at the Centre. C<$lriPdriy'SartHTzWia. D'oes Hoi j CERB - PROTOCOL No 92.04.10.04 Page 6 of 6 VIII- RECORDS. : The protocol, any possible amendements, the raw data, the report, correspondence and a sample of the compound are stored for five years at CERB - 18800 BAUGY, 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. Company Sanitized. Does not contain TSC C B CERB - STUDY No 920085 E APPENDIX 2 Technical data and analytical certificate concerning compound tfewpany Sanitize": dues no! contain TSCA CBi SERVICE DE TOXICOLOGIE CONFIDENTIEL Avril 1992 elf atochem sa La Dfense 10, cdex 42 92091 Paris-La Dfense France FICHE D'INFORMATIONS IDENTIFICATION Nom commun Nom chimique Origine; n de lot N d'archivage (CAL) PROPRIETES PHYSICO-CHIMIQUES INFORMATIONS TOXICOLOGIQUES ET PRECAUTION D'EMPLOI Aucune information disponible.._______ . CONDITIONS DE CONSERVATION ET DE DESTRUCTION Conservation Stabilit Destruction : A l'obscurit et l'abri de la chaleur. : Stable jusqu'en Avril 1993 dans ces conditions de stockage : Incinration. _ Company Sanitized. Does rieonlan TSCA CB elf atochem sa 4, cours Michelet, cedex 42 92091 Paris La Dfense 10 France BULLETIN D'ANALYSE ATO0 2 ^ ^ v r i l 1992 Jean-Franois Rgnier Service de Toxicologie y "'ou^&r.v vnt*,:'' CB? CERB - STUDY No 920085 E APPENDIX 3 Analytical certificate concerning foodstuff j FICHE d e CONTROLE CONTROL SHEET ALIMENT A04C -10 N " LOT: 11219 FOODSTUFF UTILISATEUR user 23 NOMBRE DE SACS DANS LE LOT : 561 1400 * CENTRE CHEMIN RECHERCHES BIOLOGIQUES DE MONTIFAULT Number of bags in the lot DATE LIMITE DE VENTE conseille 19.03.92 18800 BAUGY last selling date DATE LIMITE D'UTILISATION : 19.06.92 last utilization date CONTROLE D'HOMOGENEITE : consistency check CONTROLE COMPOSITION CENTESIMALE centesimal composition control CONTROLE DE LA QUALITE PHYSIQUE PHYSICAL QUALITY CONTROL Diamtre des pellets 16,13 diameter of pellets Longeur des pellets 24,0 Length of pellets Rsistance l'crasement 20,7 crushing strength Rsistance l'abrasion 98,8 scratch resistance Fines <1 dust Poids moyen 5,4 Medium weight +0,05 -3,1 +1,3 +0,7 mm mm K g / cm2 ' / a CONTROLE DE LA QUALITE NUTRITIVE NUTRITIVE QUALITY C0NTR0L Tmoin d'incorporation mlange minral (Na) : incorporation counter sample minerai mixture (Na) Tmoin d'incorporation prmlange oligo-lments (Mn) : incorporation counter sample trace element premixing CMn) Tmoin d'incorporation prmlange vitamines (Vit.A) : incoroorat ion counter sample vitamin A premixing E a u .......................................... 12,4 water Proteines .......... 17,7 protein L i p i d e s ............. 3,2 lipids Glucides (E.N.A.).. 58,0 carbohydrates (NFE) dont A m i d o n .... 40,8 of which starch C e l l u l o s e .......... cellulose Minraux totaux. .-. 5,2 dont C a ...... of wh ich P ...... N a ....... K ........ M n ...... V i tami ne V i tami ne 8400 52 63 00 00 6500 91 5500 / mg/kg mg/kg mg/kg mg/kg mg/kg UI/kg mg/kg i.'aftfzati.'Does noContain TSC& en Company Saniftzed. Does nh /*- ^ CONTROLE DES CONTAMINANTS BACTERIOLOGIQUES b a c ter io 1ogi c a 1 Germes revivifiables... regenerating germs Col if o r m e s ............. E.Col i .................. Anarobies S . R ......... S a l m o n e l l a ............. < 10 /g 0 /g 0 /g 0 /g 0 /25g MYCOTOXIQUES mycotoxic 23 af latoxines... < O c h r a t o x i n e s .. < Z a r a l n o n e ... < Strigmatocystine. < 1 12 50 30 Pg/kg Pg/kg Pg' kg Pg/kg PESTICIDES pesticides Organo-chlors organoch1or ides L i n d a n e ............. ... < 1 Pg/kg a H C H ................ ... < 1 Pg/kg H e p t a c h l o r e ......... .. . < 1 pg/kg d d t ............... ... < 1 Pg/kg DDE ................. .. . < 1 Pg/kg D i e l d r i n e ........... ... < 1 pg/kg E n d o s u l f a n .......... ... < 1 Pg/kg PCB ..... .......... ... < 1 Pg/kg Autres O.Chlors .... .. . < 1 pg/kg Other O.Chl. METAUX LOURDS Heavy metals P l o m b ................ ... 1ead M e r c u r e ............. ... Mercury A r s e n i c ............. ... Arsenic C a d m i u m ............. ... cadmium Slnium ........... ... selenium 259 49 301 73 164 Pg/kg pg/kg pg/kg pg/kg pg/kg Organo-phosphors organophosphates M a l a t h i o n ..... Pyrimiphos C H 3 .. Chlorpyriphos CH3 D i m thoate..... P h o s a l o n e ....... Autres O . P H .... others O.PH . 495 105 85 <5 <5 <5 Pg/kg Pg/kg Pg/kg Pg/kg Pg/kg Pg/kg DERIVES NITROSES N i tro-compounds N 0 3 ......... ...... N 0 2 ......... ...... NDMA ...... ...... N D E A ........ N D B A .............. N D P A ........ N P i p ....... ...... N P y ......... ..... 108 6,8 0,5 0,3 < 0,05 < 0,05 mg/kg mg/kg Pg/kg Pg/kg ag/kg Pg/kg Pg/kg Pg/kg N DES SACS : 850 a 874 soit 625 KG (BL.2380) nb of bags C O N T R O L E (S ) SPEC.IFIQUE(S) sur demande : Irradi 10 kGy specific test(s) on request REMARQUES : Conforme aux normes du N C T R . ': 6 FEVRIER 1992 Michel HU/jiRD DIRECTEUR SCIEif TIFIQUE Assurance Qualit Scienti fie Manager Quality Insurance .vLUiii 5Ot/rt CjJ CERB - STUDY No 920085 E APPENDIX 4 Analytical certificate concerning water n0t containTSCACB' S ^ e d . ^ 09 Con^"r"f cfnCrai ou 'J\ORATO(RE DPARTEMENTAL VTRINAIRE agr par le Ministre de la sant J1 I RESULTAT D'ANALYSE D'EAU Turbidit en U Jackson Rsistivit pS/cm PH Oxydabilit KMn04 mg/1 Duret en "Franais TA .C en "Franais Ammoniaque en mg/1 Nitrites en mg/1 Nitrates en mg/1 Sulfates en mg/1 Chlorures en mg/1 Fer en mg/1 Manganse en mg/1 Fluor en mg/1 - 0 .3 642 7 .4 0 .8 IO 2S 0 O 59 56 22 0 < 2U 6 .5-9 <5 < 0.5 < 0.1 < 50 < 250 < 200 < 0.2 < 0.05 < 1.5 Conformes thermotolrants/100ml Streptocoques fcaux/100ml Coliforme s / 100ml Dnombrement des bactries arobies revivifimes 3 7 ' C/ml ' ' 22*C/mI Spores de bactries anarobies sulfi to-rductr ices/20m I ' ` /100m l Salmonelles Staphylocoques pathognes *:Selon decretN89-3 et suivants., <5 O O O <1 <1 i\ O 0 0 0 Bourges,le: Mardi 25 Fvrier 1992 Le Directeur du Laboratoire Jean Marie GUF.R ATTD C&npriSanH'/e. L'eus so rentam ISCr. t-is O -i