Document 37Q6Z2nDgKwkgGmRneDdVpXqx

..H M 01 N W M AR / AA3 Telomer Research Program 1200 South Hayes Street Arlington, Virginia 22202-5050 Tet (703)413-1100 ext 5264 Face (703)4138111 ^ Clariant (D lD K ) February 14, 2003 Mary F. Dominiak U.S. Environmental Protection Agency EPA East (Mail Code 7405M) 1200 Pennsylvania Avenue NW Washington, DC 20460 E-mail: dominiak.mary@epa.gov Dear Mary: The Telomer Research Program (TRP) and its member companies, Asahi Glass, Clariant, Daikin, and DuPont, are providing to U.S. EPA Docket# AR226 final reports on the acute hazard of 8-2 Telomer B Alcohol (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecan-1-ol; CAS No. 678-39-7) when tested with standard freshwater aquatic test species. These reports present the results of the acute aquatic toxicity testing conducted by an independent laboratory at the request of the TRP. These studies were conducted according to existing OECD test guidelines and in accordance with the provisions of the appropriate Good Laboratory Practices (GLP) regulations. The physical-chemical characteristics of the test substance indicate that the test substance is a "difficult" substance, as indicated in OECD Monograph 23 (Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures, OECD 2000), and the experimental designs selected for the acute aquatic toxicity testing were reflective of this observation. Common practices for testing these types of materials, and for evaluating the results from tests of these types of materials, were used during the conduct of the studies and the preparation of the study reports. The TRP and its member companies believe that the data gathered from these studies are consistent with the hypothesis that the 8-2 Telomer B Alcohol is of low to medium concern in terms of its potential for causing acute effects on aquatic species. If there are questions concerning the technical aspects of the studies submitted, please contact me so that I may direct your questions to the appropriate TRP member company personnel. Sincerely, Katie D. Smythe TRP Administrator This document does not contain TSCA CBI. 000035 Dr.u .Noack-Laboratorium fr Angewandte Biologie 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- Acute Immobilisation Test (48 h) to Daphnia magna STRAUS, Limit Test with the Water Accommodated Fraction (WAF) acc. to OECD-Guideline 202 I for Testing of Chemicals (adopted April 04,1984) Sponsor Telomer Research Project Asahi Glass Ato fin a C l a r ia n t Daikin In du str ies Ltd Dupont Author Martina Noack Test Facility D r .U .no a ck -laboratorium FR ANGEWANDTE BIOLOGIE Kthe-Paulus-Str. 1 D-31157 Sarstedt Laboratory Project ID Project-No. Study-No. 020109CK DAI84113 Study Completed September 25, 2002 Page 1 of 29 Original 7 of 7 000036 d r .U.Noack-Laboratorium fr Angewandte Biologie Report 1-Oecanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 2 of 29 Project-No. 020109CK Study-No. D A I84113 Statement of GLP Compliance Title Guideline Test Item Test Facility Deviations from GLP Principles 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS, Limit test with the Water Accomodated Fraction OECD 202 I for Testing of Chemicals (adopted April 04,1984) 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro(Batch No: P00/001) Dr .U.Noack-Laboratorium fr angew andte Biologie Kthe-Paulus-Str.1, D-31157 Sarstedt Phone: (+49) 050 66/706 70, Fax: (+49) 05066/706 789 E-mail: info@ noack-lab.de None We declare that this study was conducted and reported in compliance with the actual OECD principles of Good Laboratory Practice and the national GLP regulations as specified in the law in force, except deviations mentioned above. 25.09.2002 25.09.2002 kte. . lU kO U v (Martina Noack, Study Director) .... G /h .............. (Thomas Geffke, Scientist) 25.09.2002 (Dr. Udo Noack, Head of Testing Facility) 000037 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1 -Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 3 of 29 Project-No. 020109CK Study-No. DAI84113 Statement of the Quality Assurance Unit Title Guideline Test Item Study Director 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS, Limit test with the W ater Accomodated Fraction OECD 202 I for Testing of Chemicals (adopted April 04, 1984) 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro(Batch No: P00/001) Martina Noack The study was verified as follows: inspection study plan process based report dates 2002-03-12 2002-06-20 2002-07-17 2002-07-18 date of report 2002-03-12 2002-06-20 2002-07-17 2002-07-18 The reported results accurately and completely reflect the raw data of the study. Also methods, procedures, and observations are accurately and completely described in the report. The accordance of the study with its study plan and the principles of Good Laboratory Practice is guaranteed. 25.09.2002 000038 Dr.U.Noack-Laboratorium for Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,6,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 4 of 29 Project-No. 020109CK Study-No. DAI84113 Personnel Involved Study Director: Martina Noack (Biologist) Scientist: (Analytical part) Thomas Geffke (Chemical Engineer) Technical Staff: Anke Gehlert Quality Assurance Unit: Deputy: Gudrun Mhrmann-Kalabokidis (Biologist) Susanne Becker (Biologist) Director of the Test Facility; Dr. Udo Noack (Biologist) 000039 __________________ Dr.U.Noack-Laboratorium fr angewandte Biologie__________________ Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 5 of 29 Project-No. 020109CK Study-No. D AI84113 Table of Content Title Page Statement of GLP Compliance Statement of Quality Assurance Unit Personnel Involved Table of Content List of Tables 1 2 3 4 4.1 4.2 4.3 4.4 5 6 7 8 8.1 8.2 8.2.1 8.2.2 8.2.3 8.2.4 8.2.5 8 .3 8.4 8.5 9 10 Summary Characterisation Data of the Test Item Method Results Solubility of the Test Item Results of the Definitive Test Results of the Reference Item W ater Parameters Validity Criteria Literature / References Physicochemical data: pH-Values,DissolvedOxygen GC - Analysis of 1-Decanol, 3,3,4,4,5,5,6,6 ,7,7,8,8,9,9, 10,10,10heptadecafluoroMethod Method Validation Linearity Quantification Limit and Detection Limit Precision (Repeatability) Peak Symmetry Accuracy Results Calibration Curve Chromatograms Certificate of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Analysis GLP-Certificate of D r .U.Noack-Laboratorium Page 1 2 3 4 5 6 7 8 9 15 15 15 15 15 16 16 17 18 18 20 20 20 21 21 22 23 24 25 28 29 000040 Dr.U.Noack-Laboratorium fr Angewandte Biologie 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecaflluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Project-No. 020109CK Study-No. DAI84113 Tables List of Tables Table 1: Table 2: Table 3: Table 4: Table 5: Table 6: Table 7: Percentage Number of Daphnids Incapable of Swimming after 24 and 48 h of Exposure W ater Parameters at the Beginning of theTest W ater Parameters at the End of Test (48 h) W ater Parameters of the Dilution W ater Repeatability of Injections of Test Item Mean Recovery Rate of Fortified Samples Concentrations of the Active Ingredient 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro Page 7 17 17 17 21 22 23 List of Figures Figures Fig. 1: Fig. 2: Fig. 3: Fig. 4: Calibration Curve of Standard - concentration range 0.01 - 0.06 mg/L Chromatogram of Standard Chromatogram of Test Item Chromatogram of Control 24 25 26 27 000041 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 7 of 29 Project-No. 020109CK Study-No. D AI84113 1 Summary ln the acute immobilisation test with Daphnia magna (STRAUS) the effect of the water accomodated fraction with a nominal loading of 100 mg/L as limit concentration of the test item 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- (Batch number P00/001), was determined according to OECD Guideline 202 I. The limit test was conducted from 2002-06-18 to 2002-06-20 at D r .U.Noack-Laboratorium fr a ng ew andte Biologie D-31157 Sarstedt. A coating period of 14 days was carried out. The preparation method was chosen with regard to the test item properties and in accordance with the relevant guidance documents (OECD 2000, BAUA 2001). The study was conducted under static conditions over a duration of 48 hours. 20 test organisms were exposed to the water accommodated fraction and control. The water accommodated fraction was analytically verified by GC-analysis (for details see part 8). The mean measured concentration of the water accommodated fraction was 0.7 mg/L. In the tested water accommodated fraction of 100 mg/L (mean measured concentration 0.7 mg/L) no biologically significant effect was determined. Table 1: Percentage Number of Daphnids Incapable of Swimming after 24 and 48 h of Exposure (n = 20) Water accomodated fraction [mg/L] 100 Control 1. 0 0 IMMOBILISATION [%] 24 h Replicates 2. 3. 4. MV 000 0 000 0 MV Mean value 1. 20 0 48 h Replicates 2. 3. 4. 000 000 MV 5 0 A reference test is carried out once per month with potassium dichromate as reference item and the reference toxicity determined. The EC50-value of the reference item at 1.5 mg/L after 24 h was within the prescribed concentration range of 1.0 to 2.5 mg/L according to AQS, DIN Guideline 38412 L 30. Water quality parameters of pH-value and dissolved oxygen concentration measured at 0 and 48 h were determined to be within the acceptable limits. The validity criteria of the test guideline were fulfilled. 000042 Dr.U.Noack-Laboratorium fr Angewandte biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 8 of 29 Project-No. 020109CK Study-No. DAI84113 2 Characterisation Data of the Test Item TEST ITEM 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Batch Number P00/001 CAS RN 678-39-7 Chemical characterization Purity 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecane-1-ol (EINECS) C8-perfluoroalkylethanol: 99.3 % (ala), sum perfluoroalkylethanol 99.9 % (a/a) Appearance Water solubility Yellowish solid wax 134 pg/L at 12 degree C, Std 29 pg/L, n=8 (DuPont, 2002) 137 pg/L at 25 degree C, Std 53 pg/L, n=17 (DuPont, 2002) Stability in water Density Stable at test conditions Ca. 1.7 g/cm3 Expiry date Recommended storage Storage at testing facility Retention Identification parameter at testing facility Unlimited if stored under the recommended conditions. Room temperature (20 C), protected from moisture. Room temperature, protected from moisture and light. At least 1 g has been retained. Name, batch number and colour. The test item and the information concerning the test item were provided by the sponsor. 000043 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decano!, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 9 of 29 Project-No. 020109CK Study-No. D A I84113 3 Method TEST GUIDELINE TYPE AND PURPOSE OECD-Guideline for Testing of Chemicals No. 202 I "Acute Immobilisation Test of Daphnia magna STRAUS" adopted April 04,1984. Determination of the acute toxicity of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroto Daphnia magna STRAUS in a limit test with the water accomodated fraction. TEST SYSTEM T est organism Reason for the selection of test system Origin Breeder Culture Culture medium Feeding Daphnia magna STRAUS (Clone 5) Daphnia magna STRAUS belongs, in accordance with the study guideline, to the suitable Daphnia types and are bred in the test facility. Institut fr Wasser-, Boden- und Lufthygiene des Bundes gesundheitsamtes, Corrensplatz, 14195 Berlin, FRG Dr.U.Noack-Laboratorium, 31157 Sarstedt, FRG In 2-3 L glass vessels with approximatively 1.8 L culture medium (Elendt M4), at 21 C (temperatures of 20-25 C are tolerated), in an incubator, 16 h illumination, illumination strength max. 20 uE/m2/s (corresponding to 1200 lux). Brood daphnids were maintained in 100 % dilution water at the test temperature for at least 48 h prior to the test. Elendt M4, according to Elendt (1990), modified to a total hardness of 160 to 180 mg CaCCyL. 5x weekly ad libitum with a mix of Scenedesmus subspicatus and Chlorella vulgaris, with an algae cell density of > 108 cells/mL. Dr.U.Noack-Laboratorium fr Angewandte biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 10 of 29 Project-No. 020109CK Study-No. D A I84113 TEST ITEM Pretreatment TEST CONDITIONS Coating of the Test vessels Preparation Coating period Preparation of the test medium 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- The test item was heated to 50 C before weighing for homogenisation. A coating phase of 14 days was carried out. 100 mg 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- /L (total volume 1 L) were shaken in a rotating shaker with 20 rpm for 96 h at 20 C. 1 L -brown glass flasks were used. After phase separation (180 min) 20 mL per test replicate were transferred from the clear liquid phase to each replicate and covered with glass tops. Dilution water was used for the preparation of the coating solution. The readily filled and covered beakers were stored at nominally 18 22 C, 1 C constant for 14 days. At the end of the coating period the beakers were emptied and used for the test. 100 mg 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- /L (total volume 1 L) were shaken in a rotating shaker with 20 rpm for 96 h at 20 C. 1 L -brown glass flasks were used. After phase separation (195 to 210 min) 20 mL per test replicate of the clear liquid phase (representing the WAF) were transferred to each replicate. The preparation method had been chosen with regard to the test item properties and in accordance with the relevant guidance documents (OECD 2000, BAUA2001). CONTROL Dilution water without test item tested under same conditions as the test group. 000045 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 11 of 29 Project-No. 020109CK Study-No. DAI84113 REFERENCE ITEM CAS No. Purity Batch No. Stability under storage conditions Test concentrations Range of validity Test duration Potassium dichromate p.a. (Merck) 7778 - 50 - 9 100 % K 28974764 2006-02-28 0 .5 8 - 1 .0 - 1 .8 - 3 .2 - 5 .8 mg/L 1.0 mg/L < EC (24 h) < 2.5 mg/L 2002-05-28 to 2002-05-29 TEST METHOD Test duration Test vessels Volume of the study medium Dilution water Static 48 h, 2002-06-18 to 2002-06-20 Glass beakers (5 cm ID x 8 cm H), 50 mL volume were used. 20 mL Dilution water according to EEC 92/69 L383A C.2. Annex 2 was used: Component CaCI2- 2 H 20 M gS04 7 H 20 NaHCOa KCI pH-value Concentration [mg/L] 294.0 123.25 64.75 5.75 7.8 0.2 Number of study organisms per concentration and control Number of animals per test vessel 20 animals, divided into 4 (2*) parallel samples, each with 5 (10*) animals 5(10*) 000046 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3 ,3 ,4,4,5,5,6,6,7,7,818,9,9,1 0,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 12 of 29 Project-No. 020109CK Study-No. D A I84113 Number of parallel samples per concentration Age of test organisms Test temperature Illumination Photoperiod 4(2*) 2 - 24 h old 18 - 22 C, 1 C constant Diffuse light, illumination strength max 20 pmolm'2 s'1 (corresponding to 1200 lx) 16/8 h light/dark cycle COURSE OF THE STUDY The results of a first study were not comparable with the results of other study organisms (e.g. algae) with WAF and the studies concerning saturated solutions. As the incompatibility could not be explained the sponsor asked the contract laboratory Dr. U. Noack-Laboratorium to withdraw the first study and initiated instead a second study. The second study reported here does not show any inconsistent results.The second definitive study was performed as limit test with the water accomodated fraction to enable the determination of immobilization after 24 and 48 hours. A definitive study carried out previously was not reported. 2 to 24 h old daphnids were used for the definitive study. They were obtained by removing the mother animals twice within 22 h. Brood daphnids were maintained in 100 % dilution water at the test temperature for at least 48 hours prior to the test. 20 daphnids divided into 4 (2*) groups with 5 (1 0 *) animals per test vessel were used. Control replicates without test item were tested under the same conditions as the test groups. All test beakers were placed in an incubator (light/dark cycle 16/8 for 48 h at 20 1 C). The immobilisation of the daphnids was observed after 24 and 48 hours of exposure. The reference item was tested in five concentrations within the concentration range 0.58 to 5.8 mg/L. Observations, measurements and evaluation were carried out as described below. *) The information in brackets refer to the test of the reference item 000047 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 13 of 29 Project-No. 020109CK Study-No. DAI84113 TYPE AND FREQUENCY OF MEASUREMENTS AND OBSERVATIONS Equipment Prior to test start the water parameters of the dilution water (pH-value, dissolved oxygen concentration, temperature, conductivity and total hardness) were measured. At the beginning of the test the water parameters (pH-value, dissolved oxygen concentration) were measured in one additional replicate per concentration and control. After 48 h the water parameters were measured in all replicates per concentration and control. The temperature was recorded throughout the test with a hygrothermograph. The percentage immobility was determined in all test and control groups after 24 h and 48 h. Oxygen : Oximeter, Oxi 530 (WTW) pH value : pH-Meter inoLab pH Level 1 (WTW) Temperature : Hygro-thermograph (Lufft) Water hardness : Spectrophotometer, Cadas 100 LPG 158 (Dr. Lange) Fluorescence of algae : Chlorophyll-Fluorometer (Kleinfeld) Dispersion treatment: Rotating Shaker 3040, GFL Centrifuge: ZK 364, Z irbus STATISTICAL METHODS OF EVALUATION EC-values and statistical analyses The effects of the limit concentration as immobilisation in percent were determined directly from the test results. EC10and EC5o-va!ues were only calculated for the reference item. ECt0and EC^-values were calculated via probit analysis. Probits according to WEBER (1986). Calculation of the confidence intervals was carried out using standard procedures according to Breitig & T mpling (1982). SOFTWARE SigmaPlot rel. 2000 (2000), S pss C orporation 000048 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorO' Acute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 14 of 29 Project-No. 02Q109CK Study-No. DAI84113 VALIDITY CRITERIA The test is unacceptable if more than 10 percent of the control organisms are immobilised during the 48 h test period. The control daphnids should not be trapped on the surface of the water. The EC after 24 h of the reference substance should be in the range from 1.0 - 2.5 mg/L. The dissolved 0 2 concentration at the end should be > 5.21 mg/L (60 % of the air saturation value at the temperature used). The deviation of the pH-value from the initial value should not be more than 1 unit. DETERMINATION OF THE TEST ITEM DEVIATIONS FROM THE GUIDELINE DEVIATIONS FROM THE STUDY PLAN REPORTING The water accommodated fraction and control were analytically verified by gas chromatography with mass spectrometric detection (m/z = 463 and 395) at test start and test end. Additional replicates were set up for the analytical work. For details see part 8. None Purity was C8-perfluoroalkylethanol 99.3 % (ala). LOD and LOQ were 0.009 and 0.027 mg/L. respectively. These deviations had no impact on the quality and integrity of the study. The final report is issued as paper copy (6 originals) and an electronic record (1 original). ARCHIVING The following was retained in the archive of the test facility for the period as specified in the operative national GLP regulations: all raw data study plan (Original 1 of 2) final report paper copy (Original 1 of 6) all records performed by the quality assurance programme including master schedules sample of test item Microfilms will be retained in a safe-deposit by Volksbank Sarstedt, D-31157 Sarstedt. Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 15 of 29 Project-No. 020109CK Study-No. DAI 84113 4 Results 4.1 Solubility of the Test Item The test item was clearly dissolved throughout exposure. 4.2 Results of the Definitive Test The percentage immobility was determined in the tested limit concentration and the control after 24 h and 48 h. The immobilisation rates in % after 24 h and 48 h of exposure are given in Table 1. There is no biologically significant effect (2 10 %) neither in the tested limit concentration nor in control group. 4.3 Results of the Reference Item The percentage immobility for the reference item was determined after 24 h. The EC10ovalue was determined directly from the test results. The ECio and EC with 95 % confidence interval (Cl) were determined by probit analysis according to standard procedures. EC- values after 24 h of the reference item in mg/L were as follows: E C 10 EC E C 100 :0.9 : 1.5 (Cl 1 .3 -1 .7 ) : 5.8 The EC50 - value of reference item potassium dichromate after 24 h is within the prescribed concentration range of 1.0 - 2.5 mg/L of validity criteria according to AQS: DIN Guideline 38412 L 30. 4.4 Water Parameters The water parameters (dissolved oxygen concentration, pH-value) of test and control groups at the beginning of the test in one replicate per concentration and control and in all replicates after 48 h are listed in Tables 2 - 3. pH-value, oxygen concentration, temperature, conductivity and total hardness of the dilution water were measured prior to test start. The results are listed in Table 4. During the test the temperature was in the range of 18 - 22 C, 1 C constant. OOOOSO Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 16 of 29 Project-No. 020109CK Study-No. DAI84113 5 Validity Criteria The study was performed according to OECD Guideline 202 l/EEC Directive 92/69/EEC Method C.2. The validity criteria were fulfilled: - In the control group no Daphnia were immobilised or trapped on the surface of the water. The EC50-value after 24 h of the reference item was in the range of 1.0 to 2.5 mg/L. The dissolved 0 2 concentration was > 5.21 mg/L (60 % of the air saturation value at the temperature used). The pH-value did not vary by more than 1 unit. 6 Literature / References BAUA, Bundesanstalt fr Arbeitsschutz und Arbeitsmedizin (2001): Leitfaden fr Anmeldungen neuer Stoffe nach dem Chemikaliengesetz. 3. berarbeitete Auflage Breitig G. & T mpling W. (1982): Methoden der Wasseruntersuchungen Bd.II, VEB Gustav Fischer Verlag, Jena. DuPont, Determination of physico-chemical parameters of Perfluorooctylethanol, CAS No. 678-39-7, Unpublished results, Update Feb. 15, 2002 Elendt B. P. (1990): Selenium Deficiency in Crustacea, Protoplasma 154, 25 - 30 OECD-guideline 202-I for testing of chemicals. Acute Immobilisation Test of Daphnia magna STRAUS. Adopted April 04, 1984 OECD (2000): Guidance document on aquatic toxicity testing of difficult substances and mixtures. OECD series on testing and assessment no. 23 Weber E.(1986): Grundriss der biologischen Statistik, 9. Auflage OOOO Dr.U.Noack-Laboratorium for Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 17 of 29 Project-No. 020109CK Study-No. DAI84113 7 Physicochemical Data: pH-Values, Dissolved Oxygen Table 2: Water Parameters at the Beginning of the Test (measured in one replicate per concentration and control) Water accomodated fraction [mg/L] 100 Control pH-value 7.69 7.70 C>2-conc. [mg/L] 7.90 8.02 Table 3: Water Parameters at the End of Test (48 h) (measured in all replicates) Water accomodated fraction [mg/L] 100 Control 1 7.43 7.62 pH-v alues no. of r aplicate 23 7.50 7.52 7.64 7.60 4 7.50 7.61 O2-cone:. [mg/L] no. of r<aplicate 12 3 4 7.69 7.66 7.67 7.62 7.62 7.76 7.80 7.94 Table 4: Water Parameters of the Dilution Water Dilution water dated: 2002-06-18 pH-value 02-conc. 7.70 [mg/L] 8.02 Temp. [C] 21.0 Conduct. [pS/cm] 665 Total Hardness C3C03 [mg/L] 254 000052 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 18 of 29 Project-No. 020109CK Study-No. D A I84113 8 GC - Analysis of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- 8.1 Method METHOD OF D E T E R M IN A T IO N Equipment Analyses of various concentrations of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-w ere carried out via gas chromatography on a Fused Silica CP-SIL 8 capillary column using external standards. Detection was performed with a mass selective detector (MS). Gas chromatograph Autosampler Detector Software : CP-3800, Varian : CTC Combi PAL, CTC A nalytics : MS, Saturn 2000, Va rian : Saturn GC/MS Workstation 5 .5 1 , V a r ia n Reagents ferf.-butyl methyl ether 99.8 %, Batch 423370/1 31101, Fluka CONDITIONS OF ANALYSIS Column Injector Injector temperature Injection volume Temperature programme Chrompack CP-SIL 8 (Varian), 30 m, i.d.: 0.25 mm, LOW BLEED / MS, Film thickness: 0.25 pm Splitless (30 psi pressure puls) for 1 min 250 C 1 pL Heating rate [X/m in] -- 10 30 Temperature [X ] 40 90 220 Holding time [min] 0.0 1.0 5.0 Carrier gas Detector Ionisation mode Run time Retention time Helium 1 mL / min column flow MS Electron ionisation (El) 15.33 min approx. 4.9 min 000 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 19 of 29 Project-No. 020109CK Study-No. D A I84113 STANDARD PREPARATION OF STANDARDS PREPARATION OF SAMPLES Test item was used as standard. Two stock solutions of the standard of 200 mg/L were prepared in fert-butyl methyl ether, diluted (6 concentrations each) and used for calibration. For calibration range see part 8.2.1. 40 mL of the sample were extracted with 4.0 mL fert-butyl methyl ether. After phase separation the extract was diluted 1 :20 and injected directly into the GC/MS. METHOD VALIDATION Peak symmetry Repeatability Accuracy Quantification of the test item was calculated by peak area of the masses 69 + 395 + 463 (m/z) based on the external standards. The calibration procedure and the principle for the determination of detection and quantitation limits were adapted from DIN 32645. The method was validated as described below: Peak symmetries were calculated from chromatograms of analytical standards and test item according to the following equation: T = W 0.os/(2-f) T = Peak symmetry Wo,o5 = Peak width at 5 % of peak height [mm] f = first sector of peak width ( divided by the perpendicular line from the peak maximum ) [mm] 5 sub-samples of the highest and lowest concentration prepared from a single homogenous sample were analysed. Mean values, standard deviations and variations of coefficients were calculated. 5 samples with 40 mL water were spiked with an amount of 8 pg 1Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- (80 pL of 100 mg/L) to give a final concentration of 200 pg/L. Afterwards samples were extracted as described above. Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 20 of 29 Project-No. 020109CK Study-No. DAI84113 8.2 Method Validation The method was validated and tested with satisfactory results with respect to linearity precision (repeatability) peak symmetry accuracy determination limit and detection limit. 8.2.1 Linearity The analytical system gave linear response in the range of 0.1 - 0.6 mg/L of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-. The calibration curve and chromatograms obtained for standard and test item are given in Fig. 1 - Fig. 4. For limit of determination and limit of detection see part 8.3. 8.2.2 Quantification Limit and Detection Limit The limit of quantification (LOQ) and limit of detection (LOD) were calculated using the blind value method described in DIN 32645 "Nachweis- und Bestimmungsgrenze". The LOD was determined to be 0.009 mg/L and therefore the LOQ was 0.027 mg/L (threefold the LOD), see part 8.3. 000055 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 21 of 29 Project-No. 020109CK Study-No. DAI84113 8.2.3 Precision (Repeatability) The results of the repeatability tests are provided in the table below. Tab. 5: Repeatability of Injections of Test Item Peak area [pV*s] Serial No 1 2 3 4 5 Mean SD CV [%] 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafiuoro(m/z = 69+395+463) 0.1 mg/L 0.6 mg/L 4462 4237 4337 4443 4319 4359.6 93.0 24897 25433 25024 24913 25989 25251.2 466.1 2.1 1.8 8.2.4 Peak Symmetry The peak symmetry of the test item 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- was 1 .8. OOOOSG Dr.U.noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 22 of 29 Project-No. 020109CK Study-No. DAI84113 8.2.5 Accuracy Tab. 6: Mean Recovery Rate of Fortified Samples Fortified concentration of test item 0.1986 [mg/L] Replicate 1 Replicate 2 Replicate 3 Replicate 4 Replicate 5 Mean SD (N-1) CV% LOQ [mg/L] LOD [mg/L] Linearity correlation coefficient ( r2 ) 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10 -heptadecafluoro- calc. cone. RR [mg/L] [%] 0.22 111 0.24 121 0.23 116 0.21 106 0.21 106 0.21 106 0.22 111 0.21 106 0.21 106 0.21 106 110 5.3 0.027 0.009 4.8 0.9906 calc. cone. RR LOQ LOD SD (N-1) CV calculated concentration, accumulation factor taken into account Recovery rate related to the nominal concentration of the test item Limit of quantification Limit of detection standard deviation coefficient of variation 000057 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro Acute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 23 of 29 Project-No. 020109CK Study-No. DAI84113 8.3 Results Tab. 7: Concentrations of the Active Ingredient 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10, 10,10-heptadecafluoro- Sampling Date Start of Analysis Test Item Replicate No. Saturated solution Control LOQ [mg/L] LOD [mg/L] linearity ( r2 ) 2002-06-18 Test Start 2002-06-20 2002-06-20 Test End 2002-06-20 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafluoro- Calc. Cone. [mg/L] Calc. Cone. [mg/L] 0.83 0.74 0.81 0.71 0.87 0.85 < LOQ < LOQ 0.69 0.66 0.027 0.009 0.9972 < LOQ < LOQ Mean [mg/L] 0.70 calc. cone. LOQ LOD - calculated concentration, accumulation factor taken into account = Limit of quantitation = Limit of detection 000058 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 24 of 29 Project-No. 020109CK Study-No. D A I84113 8.4 Calibration Curve Fig. 1: Calibration Curve of Standard - concentration range 0.01 - 0.06 mg/L (dated 2 00 2 -0 6 -1 9 ) 000059 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Oecanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 25 of 29 Project-No. 020109CK Study-No. D A I84113 8.5 Chromatograms Print Date: 20 Jun 2002 08:56:55 Target Compound Raport For#1 ta n A4110.1 lm Sampln ID: Inatniment ID: Measurement Type: Acquisition Date: Calculation Date: Sample Type: In]. Sample Notes: Divlaor: 9411 0.1 I Area 10.06.02 17:31 20.06.02 08:35 CaKbration 1,000000 Operator \ m Laat Caibraaon: CaatmUon Type: Data Rie: Method: 20.06.02 08:35 External Standard e:V... VS411 0.1 i.sms c:\... \8411_rep2.mth M ultipler: 1.000000 Parameter Compound Number Retention Time RT Offset Peek Name CAS Number Status Quan Ions Area Height Amount (RF) Fit Calibration Equation Baseline Code SnadBcatlon 4,740 +7- 0,200 80+385+463 >10 >700 Unear, Include, None Actuel 1 4,744 min. Ao,00417 min. Flucwet 678-30-7 s a tin P ut 4288 2239 42850,077 029 y +4,2880e+4x -4,5475e-13 VB Pass Paaa 0.01 mg/L at test end (dated 2002-06-19) ooooo Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 26 of 29 Project-No. 020109CK Study-No. DAI84113 Tint Date: 27 Jun 2002 13:18:53 T ms* Compound Raport fo r #1 Pom DAMMI1 3 E W A P 1 1 J0 . Sample ID: Inatrumant ID: Measurement Type: Aoqutaltion Date: Calculation Data: Sample Type: Inj. Sample Notes: D ivisor: DAIM113E WAF1 1_20 Area 20.06.0212:34 27.06.02 13:1 Analysis 1:20 1.000000 ________ Parameter Compound Number Retention Time RT Offset Peak Name CAS Number Status Quan Ions Area Height Amount Fit Calibration Equation Baseline Code 4,744 +/- 0,200 80+305+463 > -1 0 0,000 >700 Linear, Ignore, Nona O pe rato r Laat CalfaraUon: CalbraHon Type: Data Fila: Method: 27.06.02 13:11 External Standard c:V... dal84113a waf1 c:\... \8411_rep2.mth MuMpllsr 1,000000 Actual 1 4,755 min. AO,01091 min. Fhrowet 675-39-7 U 15052 5009 0,354 985 y - +4,1386e+4x +415,9153 BB Statue -P m Pm Paae tut and Error: U: Umt definedondpaini. kCountj Q ia n Ion: 0&+3QO+463 marpad O A4113E W AF1 1_20JL3M 6 Rwnpfo dpoctwm to r S o ts 348 XT: 4.737 m irv DC BR 60 (8717*100% ) 0AIS4119E W AF11J20JLSJ4S i * I 7S%SO%~ 25% - 1M 231 0%- U ulL 160 ' 20 ' T5T Rforaneo Sparin jm te r Fluotiwd Bm tk 360 RT: 4.740 m in. o ld _ 1 0 i 100% - 406 iL 75% - m- 28% - 0%ri l Too 2A oar Bamate SpeeSun tar Seen: 340 RT: 4.767 m fct PC m hus 100%_ Rat K te a araa Spectrum lo r Ru d m I u -1-1- "Ali'....!s......ie....47..... !s....*!o.....'!'' ,,J. ` iio' ' ii ' sio Fig. 3: Chromatogram of Test Item Water accommodated fraction (WAF) at the test end (dated 2002-06-20) 000061 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Oecanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafIuoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 27 of 29 Project-No. 020109CK Study-No. DAI84113 n t D a ta : 2 7 J u r 2 0 0 2 1 3 :1 4 :1 2 Target C onpoaid R a pa i o r ti fro n DAW4113E M r 1 _ 2 0 J.S H * ample ID: wtrument ID: teasurement Type: .cqiHsition Date: alculabon Date: ample Type: lj. Sample Notes: Mvlsor: DAI84113E Ktr 1_20 Area 20.08.02 18:51 27.08.02 13:13 Analysis 1:20 1,000000 Parameter Compound Number Retention Time RT Offset Peak Name CAS Number Status Quan Ions Area Height Amount Fit Calibration Equation Baseline Code Specification 4,744 + /- 0,200 89+385+483 10 0,000 700 Linear, Ignore, None Operator: Last Calibration: CalbrW on Type: Data File: Method: 27.08.02 13:11 External Standard c:V.. dal84113e ktr 1 e:V.. \8*11_rep2.m th MulBpker: 1,000000 Actual 1 4,829 min. Ao,08488 min. Fluowat 878-39-7 M 0 0 0,000 218 y +4,1386e+4x +415,9153 StBtua Pass Fail Pass Fail M s and Error: M : M to in g pas*. 000062 Dr.U.Noack-Laboratorium for Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnla magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 28 of 29 Project-No. 020109CK Study-No. D AI84113 9 Certificate of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Analysis G iriaat Gm bH, Warfe Gendorf CDQ-MG50/4QuBagirigiluirucmh*eAna|*mnt F u : + 4-49 M 79 / 2676 C lariant inspection certificate a c c o r d i n g to E N 1 0 2 0 4 - 3 .IB Oate: 13.11.2001 Page: 1 / 1 O u r consignir.erv Material Material-r.o. iiaten Mo. i- D e c a n o l , 3 , 3 , 4 , 4 , 5 , 5 , 6 , 6 , 7 , 7 , 8 , 8 , 9 , 9 , 1 0 , 1 0 , 10-heptadeca fluoro '..04705 700/001 on oaten, of w n i t - r.n-:? -.'o'liuqn.Tenc is a part, the f o i i o w m q v a l u e s dfs-.* rifiir.eo. Iney conroxT. v.:> *.r:u n q r e e d p r o d u c t s p e c i f i c a t i o n . Zr. s ;" c; i ;n c-.-.ar a u :.; r.r. \ -met hoctSpeci fi c a tiori Result lapiixary um Perfluoroaikylechanol Capillary GC 3um Purfluocalfcy lbutanoi C a p u 11 a r y GC Sum Periluoral<yiachsne Capi1lary GC Water content Karl Fischer DIN 51777 M-Mechy 1pyrrolidcr.e content Cap i 1la ry GC A o >= 9 7 , 5 >- 98,0 <0, 5 <0, 2 <-0, 2 9 9 , J% [a/a] 9 9 , 9 % [a/a] < 0 , 1 3 [a/a] < 0,1% ia/aj <0,1% < 0, 1% The abeva particulars co not release the customer from the obligation carry cut an tr.spect ion of qc c a s rec e i v e d . to M.-5. SL.T.rtner - W c r < s i n s p e c t o r 000063 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,1O-heptadecafluoroAcute Immobilisation Test (48 h) to Daphnia magna STRAUS Limit-Test with the Water Accommodated Fraction, acc. OECD 202 I Page 29 of 29 Project-No. 020109CK Study-No. DAI84113 10 GLP-Certificate of Dr.U.Noack-Laboratorium n N M n U c lu iu lw a U inwaUml nls tsrtum Guta Laborpraxis/Good Laboratory Practica G LP-B esch aln lg u n g/S tatem en t o f G L P C o m p lia n ce (gemsryaccording to 19 b Abs.1 ChamlkallengMatz) Elno GLP-lnspsktion zur Obarwachung dar Elnhaltung dar GLP-Grundsatu gamM Chamlkallangasatz bzw. RlchUInla 88/320/EG wurda durchgafOhrt In: Assessment of conformity with GLP according to ChamlKaUangoaatz and Directiva 88/32CVEEC at: X Prfeinrichtung / Test fadllty Prfstandort / Test alte O r. U. NOACK LABORATORIUM fr angewandte Biologie Kthe-Paulus-Str. 1 D -31157 Sarstedt Or. U. NOACK LABORATO RY of applied biology Kthe-Pauhjs-Str. 1 D -31157 Sarstedt (Unvwwpch sslfasrs flarstchnung und Adr--is fU n s q u lv o o f nam and addraaa) Prfungen nach Katagorian/Araaa of Expertise (flamaB/apoondna ChamNAwV-OU* N r. S.3M36CD giSdanca) 1 - Prfungen zur Bestimmung der physikalisch-chemischen Eigenschaften und Gehaltsbestimmungen 3 - Prfungen zur Bestimmung der erbgutverndemden Eigenschaften (In vitro und In vivo) 4 - UmweHtoxikologiache Prfungen zu Auswirkungen auf aquatlscha und terrestrische Organismen 5 - Prfungen zum Verhallen Im Boden, Im W asser und In der Luft. Prfungen zur Bioakkumulation und zur Metabollsierung 6 - Prfungen zur Bestimmung von Rckstnden 7 - Prfungen zur Bestimmung dar Auswirkungen auf Mesokosmen und natrliche kosysteme Datum dar Inspektion / Data of Inspection (T a o .M o n a L Ja fir / d ay.m a n 1 li.ye a r) 25. - 27. Juni 2001 f June 2 5 * - 2 7 *. 2001 29. A ugust und 21. S eptem ber 2001 / A ugust 2 9 * and S eptem ber 2 1 *', 2001 Dia ganannta b a fin d a t ich im patterna lan berw ach u n g s v s rfs h re n u nd E in h a ltu n g d a r G LP -G ru n da A tza O bS fw aoftt. A u f d a r G ru n d la g a d a s In sp e ktlo n sb e rtch te e w ird h la rm lt b e s t tig t, dasa in d la s a r P rO fakirtch tun g / dlaeew i P rO fala n da rt d la o be n g e n a n n te n P rO funoan u n ta r E in h a ltu n g d a r G LP -G ru n dsA tza d u rch g e f h rt w a rd an knnen. T h a a bo va m e n tio n e d ta a t fa c ility / t a a t alta te in clu d e d in th e n a tio n a l G LP C om pN anc* P ro gram m e a nd ia In sp e cte d o n a re g u la r baala . B aaad o n th a Ina p actton re p o rt It ca n b a co n firm a d , th a t th is ta a t fa d y l ta a t a lia la a b fa to o o n d u ct th a a fo re m e n tio n e d s tu d ta s In co m p lia n ce vd th th a P rin cip ia s o f GLP. 000064