Document OJk6R6D7jZED2ZmDpJxrMneVQ

AR226-3144 CONFIDENTIAL SPONSOR Elf Atochem S.A. Cours Michelet La Dfense 10 92091 Paris-la-Dfense CEDEX France )) ) ) IFMRecherche SU.C AO CAPITAL DE55500D0 f STUDY TITLE ACUTE EYE IRRITATION IN RABBITS STUDYDIRECTOR Xavier Manciaux STUDY COMPLETION DATE 27 January 2000 PERFORMING LABORATORY CIT Centre International de Toxicologie BP 563 - 27005 Evreux - France Company Sanitized. Does not contain TSC C{ LABORATORY STUDY NUMBER 18747 TAL CENTRE IN TERN A TIO N A L D E TO X IC O LO G IE B. P. 563 27005 vreux Cedex France Al .xtn 1 -30 7Q1C'1C. V^ll/OLUUy 1NU. lO/t / X CONTENTS STATEMENT OF THE STUDY DIRECTOR 4 OTHER SCIENTISTS INVOLVED IN THIS STUDY 4 STATEMENT OF QUALITY ASSURANCE UNIT 5 SUMMARY 6 RESUME 7 1. INTRODUCTION 8 2. MATERIALS AND METHODS 8 2.1 TEST SUBSTANCE 2.1.1 Identification 2 .1.2 Formulation procedure 2.2 TEST SYSTEM 2.2.1 Animals 2.2.2 Environmental conditions 2.2.3 Food and water '2.3 TREATMENT 2.3.1 Selection of the animals 2.3.2 Study design 2.3.3 Administration of the test substance 2.3.4 Chronology of the study 2.4 OCULAR EXAMINATIONS 2.5 DESCRIPTION AND EVALUATION OF OCULAR REACTIONS 2.5.1 Conjunctival lesions and discharge 2.5.2 Iris lesions 2.5.3 Comeal lesions . 2.6 INTERPRETATION OF RESULTS AND CLASSIFICATION OF SUBSTANCES 2.6.1 Interpretation of the results 2.6.2 Classification of the test substances 2.7 PROTOCOL ADHERENCE 8 8 8 9 9 9 9 10 10 10 10 10 10 11 11 11 11 12 12 12 13 2.8 ARCHIVING 13 3. RESULTS I4 4. CONCLUSION 14 . 0tcrt= i" ' fSC' ' CBI Table 1: Individual ocular examinations and mean values of the scores recorded at each reading (24,48 and 72 hours) for each animal 15 APPENDICES 1. Test article description and analytical certificate 2. Diet formula 16 17 20 and 21 Company Sanitized. Dess STATEMENT OF THE STUDY DIRECTOR The study was performed in compliance with the principles of Good Laboratory Practice as described in: . OECD Principles on Good Laboratory Practice (as revised in 1997), ENV/MC/CHEM (98) 17. . Dcret N 90-206 du 7 mars 1990 concernant les Bonnes Pratiques de Laboratoire (Journal Officiel du 9 mars 1990), Ministre de l'Industrie et de l'Amnagement du Territoire. . Council Directive 87/18/EEC of 18 December 1986 on the harmonization of laws, regulations or administrative provisions relating to the application of the Principles of Good Laboratory Practice and the verification of their applications for tests on chemical substances (OJ No. L 15 of 17.1.87). I declare that this report constitutes a true and faithful record of the procedures undertaken and the results obtained during the performance of the study. This study was performed at CIT, Centre International de Toxicologie, BP 563, 27005 Evreux, France. Toxicology X. Manciaux Study Director Doctor of Pharmacy Date: 27 January 2000 OTHER SCIENTISTS INVOLVED IN THIS STUDY For Pharmacy: P.O. Guillaumat - Doctor of Pharmacy For Toxicology: C. Pelcot Study Supervisor qmpan Sanitized. Ossa notcontain TSCA.GB1 c n / o r u a y ivo. io/-*/ i STATEMENT OF QUALITY ASSURANCE UNIT Type of inspections Protocol Report Inspections 4 June 1999 10 November 1999 Dates Reported to Study Director (*) 4 June 1999 7 December 1999 Reported to Management (*) 4 June 1999 14 January 2000 In addition to the above-mentioned inspections, at about the same time as the study described in the present report, "process-based" and routine facility inspections of critical procedures relevant to this study type were also made by the Quality Assurance Unit. The findings of these inspections were reported to the Study Director and to CIT Management. The inspections were performed in compliance with CIT Quality Assurance Unit procedures and the Good Laboratory Practice. The reported methods and procedures were found to describe those used and the results to constitute an accurate and complete reflection of the study raw data. D L. Valette-Talbi Date: 27 January 2000 Doctor of Biochemistry ' Head of Quality Assurance Unit and Scientific Archives (*) The dates indicated correspond to the dates of signature of audit reports by Study Director and Management. SUMMARY t A n h ^ q u esto fE lfA to ch err^ A ^ aris-Ia-D fen se, France, the potential of the test substance induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th February 1987) and EC (92/69/EEC, B.5, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Methods The study design was established according to available information on the test substance and the above guidelines. As no irritant effects were anticipated, a single dose of 0.1 ml of the undiluted test substance was instilled into the conjunctival sac of the left eye of three male New Zealand White rabbits. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test substance. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. Results Very slight or slight conjunctival reactions (very slight chemosis, very slight or slight redness of the conjunctiva and clear discharge) were observed in two animals from day 1 or 2; these reactions persisted up to day 2 in one animal or up to day 3 in the other one. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.3 for chemosis, 0.3, 0.0 and 1.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for comeal opacity. Under our experimental conditions, the test substanc slightly irritant when administered by ocular route to rabbits. However, according to the classification criteria laid down in Commission Directive 93/21/EEC (27th April 1993) adapting to technical progress for the eighteenth time Council Directive 67/548/EEC, the test substance is considered non-irritant. ISGA.CB1 S ai,, u ttr f .o 85*olco!' tair` RESUME A la demande de Elf Atochem S.A., Paris-la-Dfense, France, les proprits irritantes oculaires du p r o d u i f l |H B m H H H H H H H ^ |V j p r s application unique chez le Lapin ont t values (n405, 24 fvrier 1987) et de la CEE (92/69/EEC, B.5,31 juillet 1992). L'tude a t ralise conformment aux rgles de Bonnes Pratiques de Laboratoire. Mthode L'tude a t ralise selon les informations disponibles sur le produit et les lignes directrices mentionnes ci-dessus. Aucun effet irritant n'tant suppos, une dose unique de 0,1 ml de produit non dilu a t instille dans le cul de sac conjonctival de l'oeil gauche de 3 lapins mles New Zealand White. L'oeil droit n'a pas t trait et a servi de tmoin. Aucun rinage des yeux n'a t ralis aprs l'administration du produit. Les ractions oculaires ont t observes environ 1 heure, 24, 48 et 72 heures aprs l'administration. La moyenne des scores pour le chmosis, la rougeur de la conjonctive, les lsions de l'iris et l'opacit de la come a t calcule pour chaque animal. Rsultats Des ractions conjonctivales trs lgres ou lgres (chmosis trs lger, rougeur de la conjonctive trs lgre ou lgre et larmoiement) sont observes chez 2 animaux au jour 1 ; ces ractions persistent jusqu'au jour 2 chez 1 animal ou jusqu'au jour 3 chez l'autre animal. Aucune autre raction oculaire n'est observe au cours de l'tude. La moyenne des scores enregistrs pour chaque animal aprs 24, 48 et 72 heures est de 0,0 ; 0,0 et 0,3 pour le chmosis, 0,3 ; 0,0 et 1,0 pour la rougeur de la conjonctive, 0,0 ; 0,0 et 0,0 pour les lsions de l'iris et 0,0 ; 0,0 et 0,0 pour l'opacit comenne. Conclusion Dans nos conditions exprimentales, le produi lgrement irritant par voie oculaire chez le Lapin. st considr Cependant, selon les critres de classification dcrits dans la Directive 93/21/CEE (27 avril 1993) portant dix-huitime adaptation au progrs technique de la Directive 67/548/CEE, le produit est considr non irritant. Company Sanitized. Does not contain TSG.GB1 M flfc 'k 1. INTRODUCTION The objective of this study was to evaluate the potential of the test substanc to induce irritation following a single ocular administration in rabbits. In the assessment of the toxic characteristics of a test substance, determination of the irritant effects on the eyes of mammals is an important initial step. Information derived from this test serves to indicate the possible hazards likely to arise from exposure of the eyes, and associated mucous membranes, to the test substance. This study was conducted in compliance with: . OECD guideline No. 405,24th February 1987, . EG Directive No. 92/69/EEC, B.5, 31-st July 1992. 2. MATERIALS AND METHODS 2.1 TEST SUBSTANCE 2.1.1 Identification The test substanc ised in the study was supplied by Elf Atochem S.A. The test substance was identified as follows: . name: - protocol and labelling:J . batch number: - protocol and labelling^ "I. Elf Atoch;emmkfhilnin^^iujimumbebr" H H F J . description! . container: one pil;astic tlasK . date of receipt: 5 May 1999 . storage conditions: at room temperature and protected from light . expiry date: May 2000. Data relating to the characterization of the test substance are documented in a test article description and an analytical certificate (presented in appendix 1) provided by the Sponsor. The pH of the test substance, as specified by the Sponsor, was 5. 2.1.2 Formulation procedure The test substance was used undiluted. .wbi V 2.2 TEST SYSTEM 2.2.1 Animals Sex, species, strain: male New Zealand White rabbits. Reason for this choice: species generally accepted by regulatory authorities for this type of study. Breeden Elevage des Dombes, 01400 Chtillon-sur-Chalaronne, France. Number of animals: three animals were used, as recommended by the international guidelines. Identification: the animals were identified individually with a metal ear tag. Weight: on the day of treatment, the animals had a mean body weight standard deviation of 2.7 0.2 kg. Acclimatization: at least 5 days before the beginning of the study. 2.2.2 Environmental conditions The conditions in the animal .room were set as follows: . temperature: 18 3C . relative humidity: 30 to 70% . light/dark cycle: 12 h /12 h . ventilation: approximately 12 cycles/hour of filtered, non-recycled air. The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals. The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle. 2.2.3 Food and water During the study, the animals had free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France). Each batch of food was analysed by the supplier for composition and contaminant levels. The diet formula is presented in appendix 2. Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum. Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories. The results of these analyses are archived at CIT. ' No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome of the study. XV 23 TREATMENT 2.3.1 Selection of the animals The day before treatment, the eyes of each animal were examined in order to use only animals without any signs of ocular lesions. Animals showing signs of ocular irritation, ocular defects or pre-existing comeal injury were not used. 2.3.2 Study design The study design was established according to available information on the test substance and according to the OECD (No. 405) and EC (92/69/EEC, B.5) guidelines. As no irritant effects were anticipated, the test substance was evaluated in three animals. 2.3.3 Administration of the test substance A single dose of 0.1 ml of the undiluted test substance was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The right eye, which remained untreated, served as control. The eyes were not rinsed after administration of the test substance. 2.3.4 Chronology of the study Animal number 899 45 46 Date of treatment (day 1) 15 July 1999 15 July 1999 15 July 1999 End of the observation period 18 July 1999 18 July 1999 18 July 1999 2.4 OCULAR EXAMINATIONS . The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test substance. Following the OECD and EC guidelines: . when there was no evidence of irritation after 72 hours, the study was ended. . when there was persistent ocular irritation after 72 hours, the observation period was extended to a maximum of 21 days (until day 22) in order to determine the progress of the lesions and their reversibility. . when severe irritant effects were observed, the animals were killed on humane grounds. Any change in the animals'behaviour was noted. contait1 i/D IU U y iNU. i o / * t / i n 2.5 DESCRIPTION AND EVALUATION OF OCULAR REACTIONS Ocular reactions were evaluated for each animal according to the following numerical scale: 2.5.1 Conjunctival lesions and discharge Chemosis (lids and/or nictitating membranes) . no swelling................................................................................................................................. 0 . any swelling above normal (includes nictitating membranes)................................................. 1 . obvious swelling with partial eversion of lids.......................................................................... 2 . swelling with lids about half-closed................................................. 3 . swelling with lids more than half-closed................................................................................... 4 Redness (refers to palpebral and bulbar conjunctivae, cornea and iris) . blood vessels normal..................................................................................................................0 . a number of blood vessels definitely hyperemic (injected)....................................................... 1 . diffuse, crimson colour, individual vessels not easily discernible............................................ 2 . diffuse, beefy red ........................................................................................................................ 3 Discharge . absence of discharge............ .......................... 0 . slight discharge (does not include small amounts normally found in inner canthus).............................................................................................................................. 1 . discharge with moistening of lids and hairs adjacent to lids.....................................................2 . discharge with moistening of lids and hairs on wide area around the eye................................ 3 2.5.2 Iris lesions . normal................................................................................................................ . markedly deepened rugae, congestion, swelling, moderate circum-comeal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)......................................................................... 1 . no reaction to light, haemorrhage, gross destruction (any or all of these)...............................2 2.5.3 Comeal lesions Cornea (direct examination or, if necessary, with an Ultra-Violet lamp) To determine the presence or absence of comeal opacification and to evaluate the affected area, one or two drops of 0.5% sodium fluorescein solution can be instilled into the eye (however, this must not be performed before the 24-hour reading). If comeal opacification is difficult to determine, the eye can be examined under a UV lamp (a clear fluorescence is visible in the areas of opacification). Opacity (degree of intensity: area most dense taken for reading) . no ulceration or opacity............................................................................................................ 0 . scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible...................................................................................................... 1 . easily discernible translucent area, details of iris slightly obscured........................................ 2 . nacrous areas, no details of iris visible, size of pupil barely discernible.................................3 . opaque cornea, iris not discernible through the opacity...........................................................4 S^ed.D M anrfconB iaTSC S.G ES gompa-qg v^iisouiuy nu. 1U/-T/ m Area of opacity . one quarter (or less) but not zero....................... . . greater than one quarter but less than a half...... . greater than one half but less than three quarters . greater than three quarters up to whole area........ Any other lesions observed were noted. 2 3 4 2.6 INTERPRETATION OF RESULTS AND CLASSIFICATION OF SUBSTANCES The results obtained were evaluated in conjunction with the nature and the reversibility of the scores observed, whilst taking into account all the reactions of the treated animals. Classification of the test substance is based on the criteria laid down in Commission Directive 93/21/EEC of 27 April 1993 adapting to technical progress for the eighteenth time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. 2.6.1 interpretation of the results Criteria for irritation A substance or a preparation is considered irritant for the eyes if, when applied to the eye of the animal, significant severe ocular lesions are caused within 72 hours after exposure and which persist for 24 hours or more after treatment with the test substance. All the scores at each reading time (24, 48 and 72 hours) and for an effect are used for calculating the respective mean values. 2.6.2 .Classification of the test substances - Xi symbol, indication of danger "irritant", - phrases indicating the nature of special risks: R 36: "Irritating to eyes" Ocular lesions are significant if the mean score has any of the following values: . opacity of the cornea > 2, but < 3, . lesion of the iris > 1, but <1.5, _ . redness of the conjunctivae > 2.5, . oedema of the conjunctivae (chemosis) > 2. Or else, if the test is performed on three animals, if at least two of them show lesions equal to one of the following values: . opacity of the cornea > 2, but < 3, . lesion of the iris > 1, but < 2, . redness of the conjunctivae > 2.5, . oedema of the conjunctivae (chemosis) > 2. not contain TSCA CBf Company Sanitized- Doeo V^i I / O t u u y INC. 1 0 / * t / 1 A 3 u R 41: "Risk of serious damage to eyes" Ocular lesions are severe: if the mean score has any of the following values: . opacity of the cornea > 3, . lesion of the iris > 1.5. Or else, if the test is performed on three animals, if at least two of them show lesions equal to one of the following values: . . opacity of the cornea > 3, . lesion of the iris = 2. Or if they persist at the end of the observation period. If the test substance or preparation induces irreversible colouration of the eyes, the phrase R 41 should also be applied. 2.7 PROTOCOL ADHERENCE The study was performed in accordance with Study Protocol No. 18747 TAL and subsequent amendments, with the following deviations from the agreed Study Protocol: . the temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges specified in the protocol. These minor deviations were not considered to compromise the validity or integrity of the study. 2.8 ARCHIVING The study documentation and specimens generated during the course of the study are archived at CIT, 27005 Evreux, France, for 10 years after the end of the in vivo phase of the study. The archived study materials include: . protocol and possible amendments, . raw data, . correspondence, __ . final report and possible amendments. __ On completion of this period, the archived study materials will be returned to the Sponsor, or may be archived at CIT for a further period. Company 3. RESULTS The observations recorded during the study are presented in table 1. Very slight or slight conjunctival reactions were observed in two animals on day 1: a very slight chemosis (grade 1), a very slight redness of the conjunctiva (grade 1) and a clear discharge were noted. On day 2, a slight chemosis (grade 1) (one animal) and/or a very slight to slight redness of the conjunctivae (grade 1 or 2) (two animals) were still observed. On day 3, only a slight redness of the conjunctivae persisted in one animal. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.3 for chemosis, 0.3, 0.0 and 1.0 for redness of the conjunctiva, 0.0,0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. 4. CONCLUSION Under our experimental conditions, the test substanc slightly irritant when administered by ocular route to However, according to the classification criteria laid down in Commission Directive 93/21/EEC (27th April 1993) adapting to technical progress for the eighteenth time Council Directive 67/548/EEC, the test substance is considered non-irritant. no1coniai*1 V^ll/aiuuy 1NU. IO/H/ Lt\ Table 1: Individual ocular examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal Rabbit Region number of eye Description of ocular reactions 899 Conjunctivae Chemosis Redness Discharge Iris Comeal opacity Intensity Area Other Fluorescein 45 Conjunctivae Chemosis Redness Discharge Iris Comeal opacity Intensity Area Other Fluorescein 46 Conjunctivae Chemosis Redness Discharge Iris Comeal opacity Intensity Area Other Fluorescein (I) mean of scores on days 2, 3 and 4 h - hour D - day (+) irritant according to E.E.C. criteria (-) = non-irritant according to E.E.C. criteria * = None / - Fluorescein notused U - Fluorescein batchNo. 7239 Su = Residual test substance lh Dl 1 1 1 0 0 0 Su / 0 0 0 0 0 0 * / 1 I 0 0 0 0 * / Scores 24h 48h D2 D3 00 10 00 00 00 00 ** U/ 00 00 00 00 00 00 ** u/ 10 21 00 00 00 00 ** u/ Mean Interpretation irritation (+) 72h score (1) (-) D4 0 0.0 (-) 0 0.3 (-) 0 0.0 0 0.0 0 0.0 0 0.0 * / 0 0.0 0 0.0 0 0.0 (-) (-) (-) (-) 0 0.0 0 0.0 0 0.0 * / 0 0.3 0 1.0 0 0.0 (-) (-) (-) (-) 0 0.0 (-) 0 0.0 0 0.0 / (-) CC5Pan^ Sar^' isca e APPENDICES V 1. Test article description and analytical certificate contain TSCAC G0fflPan>' Saniti^ 0 Do nn not u i i / d t u a y in o . i o / 4*/ i 1 io TOXICOLOGY DEPARTMENT CONFIDENTIAL April 99 e lf a t o c h e m s .a . La dfense 10, cours Michelet 92091 Paris-la-Dfense, France TEST ARTICLE DESCRIPTION PHYSICAL AND CHEMICAL PROPERTIES Appearance Melting point Flash point Solubility TOXICOLOGICAL INFORMATIONS AND USE SAFETY See safety data sheet ISTORAGE AND DISPOSAL Storage Expiry date , Disposal____________ _ in dark and at room temperature may 2000 incineration rvCfcCQ! W i * / sftU U J l 1V i t W( f t A4 ' *L V l u elf atochem S Elf Atochem S.A. Uzir* <J* VaU t i-SaIN -P sJ ZA V<ifS Saint Paul * K*J> B.P. 20 608*0 Rp j i (Fwce| T4I : . Fa* : n .7 * .< :.0 T TAv. : n o <29 ATO VSP V ille n S*inl Paul, le J N ovem bre 1993 Lot H* Extrait Sec Point clair pf Taille des Particules Test d'application Cuir olophobe et hydrophobie Uai t % Rsultat Spcification Mthode de d'analyse fabrication LC U 622 c P U LC U 057 LC U 642 nm p P M ] LCU 672 LC U 674 m Le C hef de Service du Laboratoire SIGNATURE: SOM:Ruhen Gmppo Company Sanitized. Does net contain TSCA CBt JjpuFn.au 2. Diet formula contain T S C A.CSI Sanitized. Does not Company i. 11 0 Ref: 112 COMPLETE DIET RABBIT MAINTENANCE DIET Appearance: 4.5 mm diameter granules Conditioning: bags of 25 kgs Daily portion: in accordance with race and body weight, Rabbits 100-150 g, water ad libitum. FORMULA % MINERALS (calculated in mg/kg) Nat. CMV Cereals...................................... 43.8 val. val. Total Grain byproducts and legumes. 49 P.................... .. 3500 3500 7000 Vegetable protein (soya bean Ca ................ 4500 4500 9000 meal, yeast)..... ........................ Vitamin and mineral mixture.... 4.2 K .................. 11600 3 N a ................ 400 0 11600 1600 2000 M g................ 2100 100 2200 AVERAGE ANALYSIS % Mn ............... Fe.................. 40 160 40 80 140 300 Calorific value (Kcal/kg)......... 2200 Cu ................ Moisture.................................... 10 Zn ................. Proteins..................................... 13 C o ................. 12 30 0.1 15 27 45 75 1.5 1.6 Lipids........................................ 2.7 I .................... 0 0 0 Carbohydrates (N.F.E.) 49.3 C l .................. 500 3000 3500 Fibre.......................................... 17 Minerals (ash)........................... 8 VITAMINS (calculated per kg) - AMINO ACID VALUES Nat. CMV (calculated in mg/kg) val. val. Total Vitamin A 2850 IU 6500IU 9350IU Arginine.................................... Cystine...................................... Lysine....................................... Methionine................................ Tryptophan................................ 6800 Vitamin D3 2100 Vitamin B 1 4600 Vitamin B2 1600 Vitamin B3 1400 Vitamin B6 30 IU 4.3 mg 3.8 mg 16 mg 1 mg 1000 IU 0 mg 0 mg Omg 1 mg 1030IU 4.3 mg 3.8 mg 16 mg 2 mg Glycine...................................... 5200 Vitamin B 12 0 mg Omg Omg FATTY ACID VALUES (calculated in mg/kg) Vitamin E Vitamin K3 Vitamin PP 16 mg 6 mg 55 mg 10 mg - 1 mg 5 mg 26 mg 7 mg 60 mg Folic acid 0 mg Omg Omg Palmitic acid............................. Palmitoleic acid........................ Stearic acid................................ 6400 Biotin 0 Choline 600 Meso-Inositol 0 mg 850 mg 0 mg Omg 200 mg Omg Omg 1050 mg Omg Oleic acid.................................... o4uu Linoleic acid... 12100 Linolenic acid. 2400 Available under quality "Control Ref.: 112 C" UAR, 7 rue Gallieni, 91360 Villemoisson - T e l: 01.69.04.03.57 - Fax : 01.69.04.81.97 (Ref. Doc. UAR: 1992)