Document jma3Jg18g2xbyLZVRpgEq1MDk

AR&A6 _ lA & r T elomer Research Program 1200 South Hayes Street Arlington, Virginia 22202-5050 Tet (703)413-1100 d. 5264 Fac (703)4136111 DAiK iN ASAHI LASS COMPANY Clariant 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 Ui jam 0 7 0 T Jrn w -- trn z< so c o m cn CO 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 Tetomer 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. 000003 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- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test with the Saturated Solution acc. to OECD-Guideline No. 203 for Testing of Chemicals (1992) Sponsor Telomer Research Project A sahi G lass A to fin a C lar ian t Da ik in In d u s t r ie s Ltd Dupont Author Dirk Scheerbaum Testing Facility D r .U .N o a c k -L a bo r a to r iu m FR ANGEWANDTE BIOLOGIE Kthe-Paulus-Str. 1 D-31157 Sarstedt Laboratory Project ID Project-No. Study-No. 020109CK FAZ84111 Page 1 of 32 Study Completed August 07, 2002 Original 7 of 7 000004 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- Page 2 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 Statement of GLP Compliance Title Guideline Test Item 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution OECD-Guideline for Testing of Chemicals No. 203 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro(Batch number: P00/001) T e st F acility D r .U .N o a c k -L a b o r a t o r iu m f r a n g e w a n d t e B io lo g ie Kthe-Paulus-Str.1, D-31157 Sarstedt Phone: (+49) 050 66 / 706 70, Fax: (+49) 050 66 / 706 789 E-mail: info@noacK-lab.de Deviations from GLP Principles 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. August 07, 2002 (Dirk Scheerbaum, Study Director) August 07, 2002 (Thomas Geffke, Scientist) August 07, 2002 (Dr. Udo Noack, Head of Testing Facility) ooooos 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 3 of 32 Project-No. 020109CK Study-No. FAZ84111 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution OECD-Guideline for Testing of Chemicals No. 203 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro(Batch number: P00/001 ) Dirk Scheerbaum The study was verified as follows: inspection study plan process based report dates 2002-03-12 2002-04-02 2002-04-08 2002-04-11 2002-04-12 2002-07-15 date of report 2002-03-12 2002-04-02 2002-04-08 2002-04-11 2002-04-12 2002-07-15 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. August 07, 2002 run Mohrmann-Kalabokidls 000006 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-heptadecafluoro- Page 4 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203 Study-No. FAZ84111 Personnel Involved Study Director: Dirk Scheerbaum (Biologist) Scientist: Thomas Geffke (Chemical Engineer) Responsible for concentration control analysis Technical Staff: Christian Rebl Quality Assurance Unit: Gudrun Mohrmann-Kalabokidis (Biologist) Deputy: Susanne Becker (Biologist) Director of the Testing Facility: Dr. Udo Noack (Biologist) 000007 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-heptadecafluoro- Page 5 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 Table of Content Title Page Statement of GLP Compliance Statement of Quality Assurance Unit Personnel Involved Table of Content List of Tables and Figures Page 1 2 3 4 5 6 1 2 3 4 4.1 4.2 5 6 7 8 8.1 9 9.1 9.2 9.2.1 9.2.2 9.2.3 9.2.4 9.2.5 9.3 9.4 9.5 10 11 Summary Characterisation Data of the Test Item Method Results Preliminary Test Definitive Test Validity Criteria Conclusions Literature / References Physicochemical Data Water Quality Measurements 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 Curves Chromatograms Certificate of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Analysis GLP-Certlflcate of D r .U .N o a c k -L a b o r a t o r iu m 7 9 10 15 15 15 17 17 17 18 18 19 19 21 21 21 22 22 23 24 25 26 31 32 ooooos 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- Page 6 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 List of Tables Tab. 1: Tab. 2: Tab. 3 Tab. 4: Tab. 5: Tab. 6: Tab. 7: Tab. 8: Tab. 9: Tab. 10: LC-Values with 95 % Confidence Intervals Cumulative Mortality in [%] in the Preliminary Test Observations in the Test Vessels Cumulative Mortality in [%] in the Test Vessels LC0-, LC100-, NOEC-Values (0 - 96 h) LC5o-Values with 95 % Confidence Intervals Water Parameters 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- List of Figures Fig. 1: Fig. 2: Fig. 3: Fig. 4: Fig. 5: Fig. 6: Calibration Curve of Standard - concentration range 0.01 - 0.06 mg/L Calibration Curve of Standard - concentration range 0 .1 -1 0 mg/L Calibration Curve of Standard - concentration range 0.1 - 0.6 mg/L Chromatogram of Standard Chromatogram of Test Item Chromatogram of Control Page 8 15 15 16 16 16 18 22 23 24 Page 25 26 26 28 29 30 000009 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- Page 7 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203________________________Study-No. FAZ84111 1 Summary The acute toxicity of the test item 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- (Batch no.: POO/001) to fish (zebrafish) was determined according to the OECD-Guideline for Testing of Chemicals No. 203 (1992) from 2002-04-02 to 2002-04-06 at D r .U .N o a c k -L a b o r a t o r iu m FOR A n g e w a n o t e B io l o g ie , 31157 Sarstedt, Germany. A static limit test was conducted with the saturated solution. The test vessel was coated with the test item for 14 days before the test started. Duration of the test was 96 h. 30 test organisms were exposed to the saturated solution and the control. For the preparation of the saturated solution a suspension with a nominal loading of 100 mg/L was shaken for 96 h and centrifuged. The clear supernatant was used for the test. All effect values are based on the initially measured concentration of the test item. GC-MS analysis was carried out from the test item and the control vessel at test start and end (for results see part 9.2). The initially measured concentration of 1-Decanol, 3,3,4,4,5,5,6,6, 7,7,8,8,9,9,10,10,10-heptadecafluoro- was 0.18 mg/L. At the end of the test the concentration of the test item was 0.0063 mg/L. Sorption to the glass walls of the test vessels is unlikely as the walls were already pre-coated for 14 d before the test has started. The acute toxicity of the test item 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8, 9,9,10,10,10heptadecafluoro- is summarised in the following table: O O O O IO 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- Page 8 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203_______________________Study-No. FAZ84111 Tab. 1: LC-Values with 95 % Confidence Intervals (based on initially measured concentrations) Test duration [h] 24 48 72 96 LC5o [mg/L] >0.18 mg/L >0.18 mg/L >0.18 mg/L > 0.18 mg/L p = 95 % [mg/L] not applicable not applicable not applicable not applicable LC100 = Lowest test item concentration with 100 % mortality after 96 h LC0 = Highest test item concentration with 0 % mortality after 96 h NOEC (0-96 h) = No observed effect concentration >0.18 mg/L 0.18 0.18 Water quality parameters of pH-value and oxygen-saturation measured after 0, 24, 48, 72 and 96 h were determined to be within the acceptable limits. oooou. Dr . .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-heptadecafluoro- Page 9 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203 Study-No. FAZ84111 2 Characterisation Data of the Test Item TEST ITEM 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- Batch Number P00/001 CAS RN 678-39-7 Chemical characterization 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecane-1-ol (EINECS) Purity C8-perfluoroalkylethanol: 99.3 % (ala), sum perfluoroalkylethanol 99.9 % (a/a) Appearance Yellowish solid wax Water solubility 134 gg/L at 12 degree C, Std 29 gg/L, n=8 (DuPont, 2002) 137 gg/L at 25 degree C, Std 53 gg/L, n=17 (DuPont, 2002) Stability in water Stable at test conditions Density 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. 000012 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- Page 10 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 3 Method TEST GUIDELINE TYPE AND PURPOSE TEST SYSTEM Reason for the selection of the test system Origin Holding Water Feeding Food OECD-Guideline for Testing of Chemicals No. 203 (1992) 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 zebrafish in a limit test with the saturated solution. Danio rerio (zebrafish) Gnathostoma, Pisces, Osteichthyes, Teleostei, Clupeiformes, Cyprinidae According to the guideline Danio rerio is suitable for this kind of study. A q u a r iu m a m A e g i, Feldstr. 7, D-30159 Hannover All fish used in the test will originate from the same delivery of the supplier. Holding was performed at the test facility at 23 2 C and diffuse light (0.1-10 pE/m2s, natural photoperiod). The water was changed at least once per week. No disease treatment was administered. The dissolved oxygen concentration was more than 80 % of the air saturation value. Only zebrafish with at least 12 days of acclimatisation and mortality < 5 % within the last 7 days before the study starts was used in the test. Tap water of local origin was used for holding and testing. The water was filtered on activated charcoal and aerated for at least 24 h to remove chlorine. Nominal water parameters: Total hardness: 4 0 - 180 mg C aC 03/L pH-value: 6.0 - 8.0 The water is analysed once a year acc. to German tap water regulation. Food was provided 3 times per week. The amount of food was 4 % of the fish body weight per feeding day. The test fish will not be fed until 24 h before the test started. Trouvit 40 / 2; M il k iv it , D-86666 Brgheim 000013 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 11 of 32 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203________________________Study-No. FAZ84111 TEST ITEM 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Pretreatment of The test item was heated to 50 C before weighing for homogenisation. TEST CONDITIONS Coating o f the Test vessels A coating phase of 14 days was carried out. Preparation 100 mg 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- /L dilution water (total volume 5 x 2 L) were shaken in a rotating shaker with 20 rpm for 96 h at 20 C. 2 L brown glass flasks were used. After phase separation about 10 L per test replicate were transferred from the clear liquid phase to the glass aquarium and covered with glass tops. Dilution water was used for the preparation of the coating solution. Coating period The readily filled and closed aquarium was stored at nominally 23 2 C for 14 days. At the end of the coating period the aquarium was emptied and used for the test. Preparation of the test medium (saturated solution) 100 mg 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- /L dilution water (total volume 5 x 2 L) were shaken in a rotating shaker with 20 rpm for 96 h at 20 C. 2 L -brow n glass flasks were used. This suspension was centrifuged for 20 min at 3000 rpm. 10 L per test replicate of the clear saturated solution was transferred to the glass aquarium. The preparation method has been chosen with regard to the test item properties and in accordance with the relevant guidance documents (OECD 2000, BAUA 2001). CONTROL 30 fish in dilution water (without test item) were tested under the same test conditions as the test replicates. REFERENCE ITEM No reference item is recommended for this test according to the guideline. TEST METHOD A static limit test was performed with one application at the test initiation. 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- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 12 of 32 Project-No. 020109CK Study-No. FAZ84111 Test duration Test vessel Test volume Aeration Dilution water Number of test fish Loading, length of fish Replicates Introduction of fish Feeding of test fish Water temperature Dissolved oxygen concentration Light intensity Photoperiod 96 h Glass-aquaria loosely covered by glass tops were used. The test volume was 10 L per vessel. Gentle aeration was provided. Same as for holding. 30 zebrafish was used per test concentration and control. Fish density in the tanks was less than 1 g fish per liter test solution. Average body length at the test start: 2.77 cm Average body weight at the test start: 0.29 g Measuring values were determined with fish from the same batch but not used in the test. One replicate per test concentration and control. Fish were introduced randomly to individual replicates. The fish will not be fed during the test. 23 2 C Not less than 60 % of air saturation value. 0.1 -1 0 p E /m 2 s A natural photoperiod occurred during the test. KIND AND FREQUENCY OF MEASUREMENT AND OBSERVATIONS Water quality measurements pH-value, temperature and oxygen saturation were measured in all vessels at the beginning of the test and every 24 h. Total hardness of the water was determined at the beginning out of the test control. During the test the room temperature was recorded continuously with a thermohygrograph. Dr.u .Noack-Laboratorium fr angewandte Biologie Report Page 13 of 32 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203_______________________ Study-No. FAZ84111 Criteria of effects Observation intervals Measurement of fish size Fish were considered dead if there was no visible movement (e.g. gill covers movement) and if touching of the caudal peduncle produced no reaction. Records were kept of visible abnormalities (e.g. loss of equilibrium, swimming behaviour, respiratory function, pigmentation, etc.). Observations were made after 24, 48, 72 and 96 h. At test start body weight and total length of a representative number of 7 test fish was determined. These fish will not be used for testing. DETERMINATION OF THE TEST ITEM Sampling and storage The test concentration level and control were analytically verified by gas chromatography with mass spectrometric detection (m/z = 463 and 395) at test start and test end. For details see part 9.1. 40 mL test solution were transferred to 50 mL glass flasks closed with glass plugs and stored at 2 - 7 * in the dark until analysis (test start for 3, test end for 2 days). EVALUATION The concentrations leading to 0 and 100 % mortality (LC0 and LC10o) as well as the no effect level (NOEC) after 96 h were determined directly from the test results. LC50-values have not to be calculated in a limit test. COURSE OF THE STUDY The definitive study was performed as a limit test with the saturated solution as single test concentration. One control with water (without test item) was tested under the same conditions as the test group. In the test concentration and control 30 fish were tested. The test fish were not fed during the test. After 24, 48, 72 and 96 h mortality and behaviour of the test fish were observed. Measurements and observations were carried out as described above. 000016 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- Page 14 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 VALIDITY CRITERIA DEVIATIONS FROM THE GUIDELINE DEVIATIONS FROM THE STUDY PLAN REPORTING ARCHIVING - 0 2 - saturation S: 60 % - Mortality in the control < 10 % None None The final report is issued as paper copy (6 originals) and an electronic record (1 original). 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 S tu d y p la n (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 were retained in a safe-deposit by Volksbank Sarstedt, D-31157 Sarstedt. 000017 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203_____________________ Page 15 of 32 Project-No. 020109CK Study-No. FAZ84111 4 Results 4.1 P relim inary Test Tab. 2: C u m u la tiv e M o rta lity in [% ] In th e P re lim in a ry T e s t (n = 5) Concentration Effect** 24 Test Duration [h] 48 72 96 Saturated Solution <1, 0 0 0 0 Control (1) 0 0 0 0 ' The number in brackets correspond to the following observation: (1) = Normal behaviour 4.2 D efinitive Test Symptoms of toxicity during the test are given in table 3. The cumulative mortality at each time of observation is shown in table 4. The test item concentration level caused no mortality. Therefore the NOEC was laid down as 0.18 mg/L (based on the initially measured concentration). Tab. 3 O b se rva tio n s in th e T e st V essels Initially Measured Concentration Effect*1 24 Test Duration [h] 48 72 96 0.18 mg/L (1) 30/30 30/30 30/30 30/30 Control (1) 30/30 30/30 30/30 29/30 (E) - / - - / - - / - 1/30 1 The n u m b e r in b ra cke ts co rre sp o n d to the fo llo w in g o b se rva tio n : ( 1) = Normal behaviour (E) = Exitus letalis (M ortality) 000018 Dr. .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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 16 of 32 Project-No. 020109CK Study-No. FAZ84111 Tab. 4: C um ulative M o rta lity In [%] in the Test Vessels Initially Measured Concentration 0.18 mg/L Control 24 0 0 Test Duration [h] 48 72 00 00 96 0 3 Tab. 5: LC0-, LC 10#-, NOEC-Values (0 - 96 h) Based on Initially Measured Concentrations LC-ioo = Lowest test item concentration with 100 % mortality after 96 h LC0 = Highest test item concentration with 0 % mortality after 96 h NOEC (0-96 h) No observed effect concentration > 0.18 mg/L 0.18 mg/L 0.18 mg/L Tab. 6: LCso-Values w ith 95 % C onfidence Intervals Based on Initially Measured Concentrations Test Duration [h] 24 48 72 96 LCso [mg/L] >0.18 mg/L > 0.18 mg/L > 0 .1 8 mg/L >0.18 mg/L p = 95 % [mg/L] not applicable not applicable not applicable not applicable 000019 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- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203_______________ Page 17 of 32 Project-No. 020109CK Study-No. FAZ84111 5 Validity Criteria The study met the validity criteria of the guideline: 0 2 - saturation was > 60 % Mortality in the control was 3 % 6 Conclusions In this study 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- did not cause any effects to zebrafish after 96 h when tested at the initially measured concentration of 0.18 mg/L. The NOEC (0 - 96 h) is 0.18 mg/L (initially measured concentrations). 7 Literature / References (1) OECD-guideline 203 for testing of chemicals. Fish, Acute Toxicity Test. Adopted July 17, 1992 (2) OECD (2000): Guidance document on aquatic toxicity testing of difficult substances and mixtures. OECD series on testing and assessment no. 23 (3) BAUA, Bundesanstalt fr Arbeitsschutz und Arbeitsmedizin (2001): Leitfaden fr Anmeldungen neuer Stoffe nach dem Chemikaliengesetz. 3. berarbeitete Auflage. (4) DuPont, Determination of physico-chemical parameters of Perfluorooctylethanol, CAS No. 678-39-7, Unpublished results, Update Feb. 15, 2002 000020 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- Page 18 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84111 8 Physicochemical Data 8.1 W ater Quality Measurements Tab. 7: W ater Parameters day 0 Initially measured Concentration 0.18 mg/L Control day 1 0.18 mg/L Control day 2 0.18 mg/L Control day 3 0.18 mg/L Control day 4 0.18 mg/L control OxygenSaturation [%] 100 100 94 90 94 94 94 93 90 88 pH-Value 7.42 7.46 6.98 6.93 7.43 7.47 7.31 7.45 7.77 7.81 Temperature Total Hardness [C] 21.5 21.1 [mg/L as C aC 03] 71 21.9 21.8 21.0 21.0 21.0 21.0 21.1 21.2 000021 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Page 19 of 32 Project-No. 020109CK With the Saturated Solution acc. to OECD 203 _____ Study-No. FAZ84111 9 GC - Analysis of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9, 10,10,10-heptadecafluoro- 9.1 M e th o d METHOD OF DETERMINATION 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-heptadecafluorowere carried out via gas chromatography on a Fused Silica CPSIL 8 capillary column using external standards. Detection was performed with a mass selective detector (MS). Gas chromatograph Autosampler Detector Software : CP-3800, V a r ia n : CTC Combi PAL, CTC A n a l y t ic s : MS, Saturn 2000, V a r ia n : Saturn GC/MS Workstation 5.51, VARIAN Reagents fert.-butyl methyl ether 99.8 %, Batch 423370/1 31101, F l u k a 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 [C/min] -- 10 30 Temperature tC] 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 000022 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-heptadecafluoro- Page 20 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203______________________ Study-No. FAZ84111 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 (9 concentrations each) and used for calibration. For calibration range see part 9.2.1. 40 mL of the sample were extracted with 4.0 mL fert.-butyl methyl ether. The extraction step encloses an enrichment by factor 10. After phase separation the extract was 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 quantification 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 = Wo.o5 / (2 f) T Wo.os f = Peak symmetry = Peak width at 5 % of peak height [m m ] = 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 1-Decanol, 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. 000023 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 21 of 32 Project-No. 020109CK Study-No. FAZ84111 9.2 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. 9.2.1 Linearity The analytical system gave linear response in the range of 0.1 - 10 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 curves and chromatograms obtained for standard and test item are given in figures 1 - 6. For determination and detection limits see part 9.3. 9.2.2 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). 000024 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 22 of 32 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203 _____ Study-No. FAZ84111 9.2.3 Precision (Repeatability) The results of the repeatability tests are provided in the table below. Tab. 8: R e pe atab ility o f In je ctio n s o f T est Item P eak area [ mV *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- heptadecafluoro(m/z = 69+395+463) 0.1 m g /l 0.6 mg/L 2098 2098 1978 1958 2341 2094.6 152.5 12141 13563 13291 13597 13500 13218.4 613.9 7.3 4.6 9.2.4 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. 000025 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- Page 23 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203________________________Study-No. FAZ84111 9.2.5 A ccu racy Tab. 9: Mean Recovery Rate o f F o rtifie d Sam ples 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 0.23 121 116 0.21 0.21 106 106 0.21 0.22 106 111 0.21 0.21 106 106 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 000026 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 24 of 32 Project-No. 020109CK Study-No. FAZ84111 9.3 Results Tab. 10: C o ncentrations o f the A ctive Ing re dient 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10, 1 0 ,1 0 -h e p ta d e c a flu o ro - Sampling Date Start of Analysis Test Item Replicate No. Saturated solution 1 2 Control LOQ [mg/L] LOD [mg/L] linearity ( r2 ) 2002-04-02 Test Start 2002-04-05 2002-04-06 Test End 2002-04-08 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] 0.14 0 . 0 0 6 3 2' 0.16 0 . 0 0 6 4 2' 0.21 0 . 0 0 6 2 2' 0.19 < LOQ < LOQ 0 . 0 0 6 3 2> < LOQ < LOQ 0.027 0.009 0.9996 M ean1' [mg/L] 0.18 calc. cone. LOQ LOD 1) 2) = calculated concentration, accumulation factor taken into account = Limit of quantitation = Limit of detection = concentrations from the test end were not taken into account for mean value = see explanation below Explanation of data reporting The concentrations calculated at the test end are based on 10fold enriched samples. As the concentrations in the enriched samples were all above the LOQ of 0.027 mg/L (e.g. 0.063 mg/L) the sample concentrations in the test can be calculated dividing these concentrations by 10. This delivers figures (e.g. 0.0063 mg/L) which are below the LOD and have to be reported as calculated figures under GLP. These calculated values are no artefacts. If the concentration in the enriched samples would have been below the LOQ (e.g. 0.027 mg/L) a division by 10 would not be allowed and the test concentration at the end of the test would be given as < LOQ. 000027 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 25 of 32 Project-No. 020109CK Study-No. FAZ84111 9.4 Calibration Curves The calibration curves shown were established for different concentration ranges and at different times Calibration Curve of Fluowet (2002-04-04) Fig. 1: C a lib ra tio n C urve o f S tan dard - co n c e n tra tio n range 0.01 - 0.06 m g/L (dated 2002-04-04) 000028 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- Page 26 of 32 F ish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 ______ Project-No. 020109CK Study-No. FAZ84111 Calibration Curve of Fluowet (2002-04-10) 500000 450000 400000 _ 350000 300000 S i 250000 S 200000 < 150000 100000 50000 0 Cone. [mg/L] Fig. 2: C a lib ra tio n C urve o f S tandard - c o n c e n tra tio n range 0.1 - 1 0 m g/L (dated 2002-04-10) Calibration Curve of Fluowet (2002-06-19) Fig. 3: C a lib ra tio n Curve o f S tandard - c o n c e n tra tio n range 0.1 - 0.6 m g/L (dated 2002-06-19) 000029 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 27 of 32 Project-No. 020109CK Study-No. FAZ84111 The first calibration curve was established 2002-04-04 but the concentration range (0.01 - 0.06 mg/L) was not broad enough to be used for all tests running. Therefore the second curve (2002-04-10) which covers a much wider range (0.1 - 10 mg/L) was used for the calculations in this test. The concentration calculations using the two different curves do not differ more than 10 % from each other. The calibration curve from 2002-06-19 with a concentration range of 0.1 - 0.6 mg/L shows that the GC/MS system has a good stability over a long period of time. 000030 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- Page 28 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203 Study-No. FAZ84111 9.5 Chromatograms Targai Compound fU port tar <Mfmm84110.1 l_1.SMS Sample ID: Instrument 10: Measurement Type: Acquisition Date: Calculation Date: Sample Type: Irj. Sample Note: Divisor: 8411 0.1 I Area 10.04.02 13:21 11.04.02 08:08 Calibration 1,000000 Operator. Last C alibration: Calibration Type: Data Fila: Method: 11.04.02 0&08 External Standard cV.,8411 0.1 i ta rn e \... 18411 repZmth M ultiplier: 1,000000 Parameter Compound Number Retention Time RT Offset Peek Name CAS Number Status Quan tons Ares Haight Amount (RF) Fit Calibration EquationI Baseline Code Spadflcettpn 4,918 +/- 0,200 68+395+483 >10 >*700 Linear, Include, None Actual 1 4,911 min. 0,00676 min. Fiuowet 878-39-7 4368 2263 44124,941 971 y * +4,412Se+4x +0,0 66 Stato Pa Pass Pan Fig. 4: Chrom atogram o f Standard 0.1 m g/L (dated 2002-04-10) 000031 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- Page 29 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Saturated Solution acc. to OECD 203 Study-No. FAZ84111 TarpaiCompoundRapedfar81hemFA2B4111EOLISMS Sampi ID; lns(rumnt C : Meaauramant Type; Acquiation Dal: Calculation Date: Sampi Type: inj. Sampl Notes: Divisor. FA24111 EG L I Area 08.04.02 13:31 11.04.02 10:35 Analysis 1,000000 Parameter Compound Number Ratantiori Tim RT Offset Peek Nam CAS Number Status Quen ions Area Height Amount Fit Calibration Equation BaeeHneCcxIe Specification 4,918 +/- 0,200 69+395+463 >10 > 0,000 >700 Linear, Ignore, None St** andErar: U:Ueerdrffnedendpciits. Oparator. Last Calibration: Calibration Type : Data File: Method; 11.04.02 08:08 External Standard c \...fa rW 1 1 t 011 cV..\8411 jap2 .m th M ultiplier. 1,000000 Actual 4,914 min. 0,00393 min. Fkjowst 678-39-7 U 787 279 0,033 980 yBB* +4,1459e+4x -572,0248 Statea Pass Paaa Pase Fig. 5: C hrom atogram o f Teat Hem Saturated solution at the test end (dated 2002-04-08) 000032 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 30 of 32 Project-No. 020109CK Study-No. FAZ84111 T w g tl Compound Report ta r# 1 f*xnFAZ84111_2 EKtr.SM S Sampf* ID: Instrument ID: Meaeunament Type: AcqutM on Data: Calculation Data: Sample Type. Inj. Sample Notes: D iviso r FAZ84111J2 EK tr Area 0aD4.CC 12:49 11.04.02 10:31 Analysis 1,000000 Parameter Compound Num ber Retention Time RT Offset Peak Name CAS Number Status Quart tana Area Haight Amount Fit Calibration Equationi BaeeUneCode S ca rifica tio n 4,918 * 1- 0,200 09+395+463 >*10 > 0,000 >*700 Linear, Ignora, Nona O perator Last Calibration: Calibration Type: Data File: Method: 11.04.02 08:08 Extam ri Standard c \... faz84111_2a Id c\...\8411_rsp2.m th M ultiplier: 1,000000 Actual 1 5,073 min. 0,15453 min. Fluowat 678-39-7 M 0 0 0,000 473 y * +4,1459a+4x-572,0248 S tatai Pass Fail Paaa Fail S i f t * and Errcr: M rM ta hg pa *- Fig. 6: Chromatogram o f C ontrol at test end (dated 2002-04-08) 000033 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 31 of 32 Project-No. 020109CK Study-No. FAZ84111 10 Certificate of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- Analysis ClaiUAt GmbH. Wrfc Gendorf CQG / QuUU um uugcm cnt D-84504 BurgUrcben T u : * + 4 9 79 / 2675 C lariant 1 Inspect, ion certificate according to EN10204-3.1B Date: 13.11.2001 Page: 1 / 1 Our c on s i g n m e n t Material Mar.erial~no. a t c . i Mo. 1-Decanol, 3 ,3 ,4 ,4 ,5 ,5 ,6 ,6 ,7 ,7 ,8 ,8 , 9,9,10,10, l-heptadeca fluoro :04705 PCO/001 o f v n i r r '..n? r o n 5 i cir,Tnt i s a p a r t , t h e f c i i o w . n g ' a l u e i :ey conr.ui.T r. :> ". g r e e d p r o d u c t s p e c i f i c a t i o n ;a r n t i v. -mecrodSpecj. Creation Reuui t J a p i - i K " / :.>l 5 cm P e r i l u o r o a l k y i e t h a n o l C a p i l l a r y GC Sum ? e r f i u o r a l k y l b u t a n o l C a p i l l a r y ZC Sum ? e r f l u c r a 1 '<y I s c h e n e Tap i i La r y CC Water concent K a r l " i s c h e r DIN 3 1 7 7 7 N-Mechy_pvrrolidone content Capu l l a r y DC >- 97, 5 > 9 8 , Q <- 1,0 <- C, 5 < 0 , 2 < 0 , 2 99,3* a/a] 99,91[a/aj < 0,1%[a/aj < 0,11[a/al <0,11 < 0, 1% The acc vs p a r t i c u l a r s do no t r e l e a s e th e cu s to m er from t h e o b l i g a t i o n c a rr y cut an in sp ec tio n t f poods received. to garcr.er - W orxsitjpector 000034 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Saturated Solution acc. to OECD 203 Page 32 of 32 Project-No. 020109CK Study-No. FAZ84111 11 GLP-Certificate of Dr.U.Noack-Laboratorium n N le d e rs ic h ils c h e * UimmMminMMtum Gute Laborpraxis/Good Laboratoty Practice GLP-Bascheinlgung/Statement of GLP Compliance (gemtiO/aeoordlng to 18 b Abt.1 Chemlkallengesetx) Eine GLP-Inspektkxi zur berwachung der Einhaltung der GLP-Grundstttze gemSS Chemikallengewlz bzw. Richtlinie M/320/EG wurde durchgefhrt ln: Assessment ofconfom ltyw tth OLP ecccrctnflto ChemksUengesatz and Directive S8/320/EEC et: X Prfeinrichtung ! T o ri fa d ity O P rfStan d o rt / Teat site D r. U. NOACK LABORATORIUM f r angewandte 8iologie Kthe-Paulue-Str. 1 D-31157 Sarstedt D r. U. NOACK LABORATORY o f applied biology K#the-Pulus-Str. 1 D-31157 Sarstedt <Uwen-- d e st a i n rn to tw ie und Adr-- -- lUrequSocal rem and mjekm m) Prfungen nach Kategorien/Areas o f Expertise tgam U /saadng CMnfVW VdU Nr. SJTOECO g u M ra ) 1 - Prfungen zur Bestimmung der physikalisch-chem ischen Eigenschaften und Gehattabestlmmungen 3 - Prfungen zur Bestimmung der erbgutverandem den Eigenschaften (in vitro und In vivo) 4 - Um welttoxikologlache Prfungen zu Auswirkungen auf aquatische und terrestrischa Organismen 5 - Prfungen zum Verhalten im Boden, im W arner und In der Luft, Prfungen zur Bioakkum ulation und zu r M etabolisierung 6 - Prfungen zur Bestimmung von Rckstnden 7 - Prfungen zur Bestimmung der Auswirkungen auf Meaokoamen und natrliche kosysteme Datum der Inspektion / Date o f Inspection (Tag-MonabJahr/ day.montti.yaar) 25. - 27. Juni 2001 f June 25* - 27*. 2001 29. August und 21. September 20011 August 29* and September 21" , 2001 befindet Ich im nationalen GLPberwaehungsveriahnwi und wird regefmAJUg auf Einhaltung der GLP-Grundaat berwacht Auf der Grundlage de* fnapeWtonabertchtea wird hiermit besttigt. dass in dieser PiOWiMfchtunpt f saem PrOfstendart die oben genannten PrOfengen unter Einhaltung der GIP-Grunds itz * dufthgefDhit werden kennen. T i above mentioned leat tadhy / tart aba ia includaci tn the national G IP Complance Programme and la impeded on a regular beala. Based on the inspection report Hcan be confirmed, tat this tost fe d tty / at ta is able le oonduct the aforementioned atudiea In compliance wHh the Principe of GLP. ooooas