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AR226-3142 CONFIDENTIAL SPONSOR ElfAtochemS.A. Cours Michelet La Defense 10 92091 Paris-la-Defense CEDEX France IFM recherche 3 'i.e. w wnu DE 5 jio OOP f ycG SOCW MKERfr - ; 700S WlU.X 788 OBO^i;BCS EVREUX TEST SUBSTANCE STUDY TITLE ACUTE DERMAL IRRITATION IN RABBITS STUDY DIRECTOR Xavier Manciaux STUDY COMPLETION DATE 13 December 1999 PERFORMING LABORATORY err Centre International de Toxicologie BP 563 - 27005 Evreux - France LABORATORY STUDY NUMBER C.n,pan,S^e-.Ooesn..c.--------^ 18749TAL CENTRE INTERNATIONAL DE TOXICOLOGIE B. P. 563 27005 Evreux Cedex Tel.: -33 2 32 29 26 26 Fax : +33 2 32 67 87 OS France 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 10 2.3.1 Preparation and selection of the animals 10 2.3.2 Study design 10 2.3.3 Application of the test substance 10 2.3.4 Chronology of the study 10 2.4 CUTANEOUS EXAMINATIONS 10 2.5 DESCRIPTION AND EVALUATION OF CUTANEOUS REACTIONS 11 2.6 INTERPRETATION OF RESULTS AND CLASSIFICATION OF SUBSTANCES 11 2.6.1 Interpretation of the results 11 2.6.1.1 Criteria for irritation 11 2.6.1.2 Criteria for corrosion 11 2.6.2 Classification of the test substances 12 . 2.6.2.1 Irritant substances 12 2.6.2.2 Corrosive substances 12 2.7 PROTOCOL ADHERENCE 12 2.8 ARCHIVING 13 . 3. RESULTS 14 4. CONCLUSION . 14 company Sanitized. Does nol contain TSCA ^. ^;u/:>njoyiNO. 15/4^ 1/ujl^l^^^^R^iiAiocnem :>.A. 3 Table 1: Individual cutaneous examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for the first animal (application for 3 minutes) 15 Table 2: Individual cutaneous examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal (application for 4 hours) 16 APPENDICES 1. Test article description and analytical certificate 2. Diet formula 17 18 21 and 22 ^nys.""^"^" WW^'^ -rc.-ftC^ ^,SC.CK CIT/Study No. 18749 TALJ|f--------tlt Atochem S.A. 4 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. . Decret N 90-206 du 7 mars 1990 concemant les Bonnes Pratiques de Laboratoire (Journal Officiel du 9 mars 1990), Ministere de 1'Industrie et de 1'Amenagement du Temtoire. . 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 (OJNo.L15ofl7.1-87). 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: 13 December 1999 OTHER SCIENTISTS INVOLVED IN THIS STUDY For Pharmacy: P.O. Guillaumat Doctor of Pharmacy For Toxicology: C. Pelcot Study Supervisor r-^^^ain-ESCACB. ^S?^^'""" CIT/StudyNo. 18749T, IfAtochemS.A. 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 10 December 1999 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 CTT 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. ^ y S ^ r ^ e \_^~__--_------------ L. Valette-TaIbi .Date: 13 December 1999 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. Company Sanitized. Does not contain TSCA CB1 SUMMARY M 1992) guidelines. The study was Laboratory Practice Regulations. la-Defense, France, the potential of the test substance to induce skin irritation was evaluated in rabbits uly 1992) and EC (92/69/EEC. B.4, 31st July conducted in compliance with the principles of Good Methods The study design was established according to available information on the test substance and the above guidelines. In the first instance, the test substance was applied for periods of 3 minutes and 4 hours to a single male New Zealand White rabbit. Since the test substance was not severely irritant on this first animal, it was then applied for 4 hours to two other animals. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank. ^ The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. The mean values of the scores for erythema and oedema were calculated for each animal. Results After a 3-minute exposure (one animal): No cutaneous reactions were observed. After a 4-hour exposure (three animals): A very slight erythema was noted in two animals on day 1; it persisted up to day 3 in one of them. No other cutaneous reactions were observed during the study. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.7 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema. Conclusion Under our experimental conditions, the test substanc non-irritant when applied topically to rabbits. According to the classification criteria laid down in Commission Directive 93/2 I/EEC (27th April 1993) adapting to technical progress for the eighteenth time Council Directive 67/548/EEC, the test substance was considered non-irritant. ^spany Sanitized. Goes no ^w" w- RESUME fll^^m^BHI^UlJipres , A la demandejig_ElfAtochem S,A Paris-la-Defense, France, les proprietes irritantes du produit application cutanee ont ete evaluees chez Ie Lapin selon "les lignes directrices de l'OCDE(n 404, 17 juillet 1992) et de la CEE (92/69/EEC. B.4, 31juilletl992). L'etude a etc realisee confonnement aux regles de Bonnes Pratiques de Laboratoire. / .< Methode L'etude a ete realisee selon les informations disponibles sur Ie produit et les lignes directrices mentionnees ci-dessus. Dans un premier temps. Ie produit a ete applique pendant 3 minutes et 4 heures sur 1 seui lapin male New Zealand White. Le produit n'etant pas fbrtement irritant sur ce premier animal, il a ensuite ete applique pendant 4 heures sur 2 autres animaux. Une dose unique de 0,5 ml de produit non dilue a ete appliquee sur une surface de peau tondue d'un des flancs. Le produit a ete maintenu en contact avec la peau au moyen d'un pansement semi-occlusif. Les reactions cutanees ont ete observees environ 1 heure, 24, 48 et 72 heures apres 1'enlevement du pansement. La moyenne des scores a ete calculee pour 1'erytheme et pour 1'oedeme pour chaque animal. Resultats Apres une exposition de 3 minutes (1 animal): Aucune reaction cutanee n'est observee pendant 1'etude. Apres une exposition de 4 heures (3 animaux): Un erytheme tres leger est note chez 2 animaux au jour 1 ; il persiste jusqu'au jour 3 chez 1 animal. Aucune autre reaction cutanee ri'est observee durant 1'etude. Les scores moyens calcules pour chaque animal apres 24, 48 et 72 heures sont de 0,0; 0,7 et 0,0 pour 1'erytheme et de 0,0; 0,0 et 0,0 pour 1'oedeme. Conclusion Dans nos conditions experimentales, le produit non irritant par voie cutanee chez le Lapin. lest considere Selon les criteres de classification decrits dans la Directive 93721/CEE (27 avril 1993) portant dix-huitieme adaptation au progres technique de la Directive 67/548/CEE, le produit est considere non irritant. JRwnpanSyanitized. Does hoi contain T.qnA CB' 1. INTRODUCTION The objective of this study was to evaluate the potential of the test substanc induce skin irritation following a.feingle topical application to rabbits. In the assessment of the toxic characteristics of a test substance, determination of the irritant and/or corrosive effects on the skin 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 skin to the test substance. This study was conducted in compliance with: . OECD guideline No. 404, 17th July 1992, . EC Directive No. 92/69/EEC, B.4.31st July 1992. 2. MATERIALS AND METHODS 2.1 TEST SUBSTANCE 2.1.1 Identification The test substanceBUU----Rised in the study was supplied by Elf Atochem S.A. The test substance was identified as follows: . na- mpero: tocol and labelIiCng-^||^U^H^II^B^lHrfl| ---- ^^ . batch number - protocol and labeIlingUJ^ ^ . Elf Atochem filing number 1392/99 . description: amber liquid . container one smoked glass flask . 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 in analytical certificate (presented in appendix 1) provided by the Sponsor. The pH of the test substance, as mentioned on the test article description, was 5 1. 2.1.2 Formulation procedure The test substance was used undiluted. ^afimy. Sanitized. Does nol contain TSCA cm CIT/Study No. 18749 TALf^lHEIf Atochem S.A. 9 ^ 4 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. Breeder Elevage des Dombes, 01400 Chatillon-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 2.8 0.1 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: 183C . relative humidity: 30 to 70% . light/dark cycle: 12h/12h . 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 Villemoisson- ' sur-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 libltum. 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. ^gp^^ffia-IB^^"'----6^.^ \*---- CIT/Study No. 18749 TAlJH------^Hp^ Acochem S.A. 10 2J TREATMENT 2.3.1 Preparation and selection of the animals The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined. Only animals with healthy intact skin were used. 2.3.2 Study design The study design was established according to available information on the test substance and the OECD (No. 404) and EC (92/69/EEC, B.4) guidelines. As possible irritant effects were anticipated, the test substance was evaluated on a single animal (No. 900) in the first instance. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank. Since the test substance was not severely irritant on this first animal, it was then applied for 4 hours to two other animals (Nos. 47 and 48). 2.3.3 Application of the test substance Doses of 0.5 ml of the undiluted test substance were placed on a dry gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals. The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. The untreated skin served as control. No residual test substance was observed on removal of the dressing. 2.3.4 Chronology of the study Animal number Date of treatment (day 1) End of the observation period 900 6 July 1999 (application for 3 minutes and 4 hours) 47 8 July 1999 9 July 1999 11 July 1999 . July July 1999 48___________8 1999______________11 2.4 CUTANEOUS EXAMINATIONS The skin was examined approximately 1 hour, 24,48 and 72 hours after removal of the dressing. Following the OECD and EC guidelines: . when there was no evidence of dermal irritation after 72 hours, the study was ended. . when there was persistent cutaneous irritation after 72 hours, the observation period was extended to a maximum of 14 days (until day 15) 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. ^CompanySanitized. Does not contain TSCft CIT/Study No. 18749 TALf^^--------Elt Atochem S.A. 11 2.5 DESCRIPTION AND EVALUATION OF CUTANEOUS REACTIONS Dermal irritation was evaluated for each animal according to the following scoring scale: Erythema and eschar formation: ^ . no erythema........................................................................................................... 0 . very slight erythema (barely perceptible).............................................................. 1 . well-defined erythema........................................................................................... 2 . moderate to severe erythema................................................................................. 3 . severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4 Oedema formation . no oedema.............................................................................................................. 0 . very slight oedema (barely perceptible)................................................................. 1 . slight oedema (edges of area well-defined by definite raising)............................. 2 . moderate oedema (raised approximately 1 millimetre)....................................... 3 . severe oedema (raised more than 1 millimetre and extending beyond area of exposure)........................................................................................................... 4 Any other lesions were noted. 2.6 INTERPRETATION OF RESULTS AND CLASSIFICATION OF SUBSTANCES The results obtained were evaluated in conjunction with the nature and the reversibility of the findings observed. 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 2.6.1.1 Criteria for irritation A substance or a preparation is considered to be irritating to the skin if, when it is applied to - healthy intact animal skin for up to 4-hours, significant inflammation is caused and which persists for 24 hours or more after the end of the exposure period. 2.6.1.2 Criteria for corrosion A substance or a preparation is considered to be corrosive if, when it is applied to healthy intact animal skin, it produces full thickness destruction of skin tissue on at least one animal during the test for skin irritation, or if the result can be predicted, for example: from strongly acid or alkaline reactions. ytSSpar.y Sanitize'd. Does not contat'ri TSCA (.W CIT/Study No. I S749 TAL^^^------^f'ir Atochem ;S.A. 12 2.6.2 Classification of the test substances 2.6.2.1 Irritant substances - symbol Xi, indication of danger "irritant", - phrases indicating the nature of special risks: R 38: "Irritating to skin" Inflammation is significant if: . the mean value of the scores is two or more for either erythema and eschar formation or oedema formation. The same will be the case where the test has been completed using three animals if the score for either erythema and eschar formation or oedema formation observed in two or more animals is equivalent to the value of two or more, . it persists in at least two animals at the end of the observation period. Specific effects such as hyperplasia, desquamation, discolouration, fissures, eschar and alopecia should be taken into account. All scores obtained at each reading time (24, 48 and 72 hours) for an effect are used for calculating the respective mean values. 2.6.2.2 Corrosive substances - symbol C, indication of danger "corrosive", - phrases indicating the nature of special risks: . R 34: "Causes bums" If, when applied to healthy intact animal skin, full-thickness destruction of skin tissue occurs as a result of up to 4 hours exposure, or if this result can be predicted. . R 35: "Causes severe bums" If, when applied to healthy intact animal skin, full thickness destruction of skin tissue occurs as a result of up to 3 minutes exposure, or if this result can be predicted. 2.7 PROTOCOL ADHERENCE The study was performed in accordance with Study Protocol No. 18749 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. CIT/^tudy No. 1S74y 1ALJ||^^------^Bblt Atochem ^i.A. 1:5 2.8 ARCmVING The study documentation and specimens generated during the course of the study are archived at Crr, 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. Sanfflzed-Doeanolcon^nTSC^- Company CIT/Study No. 1S749 TM^B^----------fcli Atochem S.A. 14 3. RESULTS The observations recorded during the study are presented in tables 1 and 2. After a 3-minute exposure (one animal): No cutaneous reactions were observed. After a 4-hour exposure (three animals): A very slight erythema (grade 1) was noted in two animals on day 1; it persisted up to day 3 in one of them. No other cutaneous reactions were observed during the study. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.7 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema. 4. CONCLUSION Under our experimental conditions, the test substanceJ|B^^^BB^B|HHBI^^B^s non-irritant when applied topically to rabbits. L J According to the classification criteria laid down in Commission Directive 93/2 I/EEC (27th April 1993) adapting to technical progress for the eighteenth time Council Directive 67/548/EEC, the test substance was considered non-irritant. CoWpsny san-ti?^- Does no< contain TSCA n' CIT/Study No. 18749T It Atochem S.A. 15 Table 1: Individual cutaneous examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for the first animal (application for 3 minutes) Rabbit number Dermal Irritation Ih Dl Seoics 24h 48h D2 D3 Mean :Interpretation irritation (+) 72h score(1) (-) D4 900 Erythema 0 0 0 0 0.0 (-) Oedema 0 0 0 0 0.0 (-) Other * * * (1) 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 LTl/^tudyNo. lo749T. It Atochem S.A. 16 Table 2: Individual cutaneous examinations and mean values of the scores recorded at each reading (24.48 and 72 hours) for each animal (application for 4 hours) Rabbit number Dermal Secires Mean Interpretation (+) Ih 24h 48h 72h score (1) (-) Dl D2 D3 D4 900 Erythema 0 0 0 0 0.0 (-) Oedema 0 0 0 0 0.0 (-) Other * * 47 Erythema 1 1 1 0 0.7 (-) Oedema 0 0 0 0 0.0 (-) Other * * * 48 Erythema 1 0 0 0 0.0 () Oedema 0 0 0 0 0.0 (-) Other * * * * (1) 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 Company Sanitized. Does not conWn TC^A '" LTlYSitudy No. 1S749 'i'AiJHBU^^ Atocnem 5.A. l / APPENDICES HS&mpanSyanTiT?s3. Does Hoi contain TSCA CBt 1. Test article description and analytical certificate 9 .CompanySanitized. Does not contain TSCA CP' ui/Study NO. i iw i ,n /uut-nem O.A. if TOXICOLOGY DEPARTMENT CONFIDENTIAL April 99 elf atochem s.a, La defense 10, cours Michelet 92091 Paris-la-Defense, France TEST ARTICLE DESCRIPTION PHYSICAL AND CHEMICAL PROPERTIES Appearance pH Density Boiling point Flash point Solubility amber liquid 51 HOOkg/m3 at20C 98-100 C no flash point water: insoluble soluble in alcohols, aromatic hydrocarbons TOXICOLOGICAL INFORMATIONS AND USE SAFETY See safety data sheet_______________________ STORAGE AND DISPOSAL- Storage Expiry date Disposal in dark and at room temperature may 2000 incineration pgmpany jSanitized. Does not contain TSCA CS. CIT/Study No. 18749TAL/FORAFAC 1210/ElfAtochemS.A. elf atochem ^SSj /--n--->---s Elf Atochem S.A. Usine d Vaera-SBi'nl-Paul ZA Villan Saini Pau(. Riaux B.P. W 60870 Ricux (Franco) TA): 44 74.44.74 Fax ; 44.74.42.07 . TAlox : 140 <29 ATO VSP Villcra Stint Paul, Ic 9 Novcaibrc VW ^ ^ CEFariFICAT D'ANALYSE Lot IT Extratt Sec Tcrtio Bumnol Aery (amide Acidc acryliquc Test d'extinction UniKS % % % % 1 Rdsultat 30.3 Specification dc fabrication 291 31 Mdthodc d* analyse LCU 622 0.95 Oil LCU653 0,07 OaO.l LCU 658 0,1 Oa2 LCU 658 positif positif ' SA1021 L< Chcfdc Scnica: du Laborntoire SIWATUW: HOM: Rnheri Cnippu h-urc-ii I ip,r,l 3 w, m yog ^^ ,.^-^.. CIT/Study No. 18749 TA :lf Atochem S.A. 21 2. Diet formula ICempanySanitized. Does riot contain TSCA ^-i Cil/^tudylMo. l74y i r Atocnem s./\. ^ 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 % MINIBRALS (calc:ulated in mg/kg) Nat. CMV Cereals ...................................... Grain byproducts and legumes. Vegetable protein (soya bean meal, yeast) .............................. Vitamin and mineral mixture.... 43.8 49 4.2 3 P..................... .. Ca ................. K ................... Na ................. Me val. 3500 4500 11600 400 2100 val. 3500 4500 0 1600 100 Total 7000 9000 11600 2000 2200 AVERAGE ANALYSIS % Mn ................ 40 40 80 Fe 160 140 300 Calorific value (KcaVkg). Moisture........................... Proteins............................ Lipids............................... Carbohydrates (N.F.E.) Fibre ................................. Minerals (ash).................. 2200 10 13 2.7 49.3 17 8 Cu ................. Zn ................. Co .................. I Cl..................... ................... 12 30 0.1 0 500 15 45 1.5 0 3000 VITvAMINS (cal culated per kg) 27 75 1.6 0 3500 AMINO ACID VALUES (calculated in mg/kg) Vitamin A Nat. val. 2850 IU CMV val. 6500 IU Total 9350 IU Arginine..... Cystine ....... Lysine ........ Methionine. 6800 2100 4600 1600 Vitamin D3 Vitamin Bl Vitamin B2 Vitamin B3 30 IU 4.3 mg 3.8 mg 16 mg 1000 IU Omg Omg Omg 1030 IU 4.3 mg 3.8 mg 16 mg Tryptophan. Glycine........ FATTY ACID VALUES (calculated in mg/kg) 1400 5200 Vitamin B6 Vitamin B 12 Vitamin E Vitamin K3 Vitamin PP Folic acid 1 mg Omg 16 mg 6mg 55 mg Omg 1 mg Omg 10 mg 1 mg 5mg Omg 2mg Omg 26 mg 7mg 60 mg O'mg Palmitic acid ..... Palmitoleic acid. Stearic acid......... Oleic acid........... Linoleic acid ...... Linolenic acid.... 6400 0 600 6400 12100 2400 Biotin Choline Meso-Inositol Omg 850 mg Omg Omg 200 mg Omg Omg 1050 mg Omg Available under quality "Control Ref.: 112 C" UAR, 7 rue Gallieni, 91360 Villemoisson - Tel: 01.69.04.03.57 - Fax : 01.69.04.81.97 (Ref. Doc. UAR: 1992) 'JSoftipan;^. aritizeh', "Uoes not contain TSCA CBI