Document o35b7jNOngjxrbRVmMz0a64R

RECEIVED hDDT w rir Telomer Research Program 1200 South Hayes Street Arlington, Virginia 22202-5050 Tet (703)413-1100 ext 5264 Fatc (703)4138111 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 30 o 33 3C 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 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 L). smythe TRP Administrator This document does not contain TSCA CBI. 000036 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 Water Accommodated Fraction (WAF) acc. to OECD-Guideline No. 203 for Testing of Chemicals (1992) Sponsor Telomer Research Project Asahi Glass Atofina C l a r ia n t Daikin Industries Ltd Dupont Author Dirk Scheerbaum Testing Facility Dr .U .N oack-Laboratorium FR ANGEWANDTE BIOLOGIE Kthe-Paulus-Str. 1 D-31157 Sarstedt Laboratory Project ID Project-No. Study-No. 020109CK F A Z 8 4 1 12 Page 1 of 32 Study Completed August 07, 2002 Original 7 of 7 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-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Water Accommodated Fraction (WAF) acc. to OECD 203 Page 2 of 32 Project-No, 020109CK Study-No. FAZ84112 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 W ater Accommodated Fraction (W AF) 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) Test Facility D r .U .N oack-Labo rato rium fr a n g ew a n d te Bio log 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 W e 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 August 07, 2002 (Dirk Scheerbaum, Study Director) (jJ b (Thomas Geffke, Scientist) August 07, 2002 (Dr. Udo Noack, Head of Testing Facility) 000038 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-DecanoI, 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 3 of 32 Project-No. 020109CK Study-No. FAZ84112 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 Water Accommodated Fraction (WAF) 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 Gudfun Mhrmann-Kalabokidis 000039 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 4 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 Water Accommodated Fraction (WAF) acc. to OECD 203______ Study-No. FAZ84112 Personnel Involved Study Director: Dirk Scheerbaum (Biologist) Scientist: Technical Staff: Thomas Geffke (Chemical Engineer) Responsible for concentration control analysis Christian Rebl Quality Assurance Unit: Gudrun Mhrmann-Kalabokidis (Biologist) Deputy: Susanne Becker (Biologist) Director of the Testing Facility: Dr. Udo Noack (Biologist) 000040 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 Water Accommodated Fraction (WAF) acc, to OECD 203 Page 5 of 32 Project-No. 020109CK Study-No. FAZ84112 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 W ater 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-Certificate of Dr .U.Noack-Laboratorium 7 9 10 15 15 15 17 17 17 18 18 19 19 21 21 21 22 22 23 24 25 28 31 32 000041 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanal, 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 6 of 32 Project-No. 020109CK Study-No. FAZ84112 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-, LC-loo-, NOEC-Values (0 - 96 h) LC50-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- Page 8 15 15 16 16 16 18 22 23 24 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 25 26 26 28 29 30 000042 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 7 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______Study-No. FAZ84112 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.: P00/001) 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 -Labo ra to rium F r A n g e w a n d te B io l o g ie , 31157 Sarstedt, Germany. A static limit test was conducted with the water accommodated fraction (W AF). 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 water accommodated fraction and the control. For the preparation of the water accommodated fraction (W AF) a suspension with a nominal loading of 100 mg/L was shaken for 96 h. After phase separation the clear liquid phase 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 0.14 mg/L. At the end of the test the concentration of the test item was below the detection limit of 0.009 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: 000043 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 8 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 Tab. 1: LC-Values with 95 % Confidence Intervals (based on initially measured concentrations) Test duration [h] 24 48 72 96 LCso (mg/L] > 0.14 mg/L > 0.14 mg/L > 0 . 1 4 mg/L > 0.14 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 LCo = Highest test item concentration with 0 % mortality after 96 h NOEC (0-96 h) = No observed effect concentration > 0.14 mg/L 0.14 mg/L 0.14 mg/L W ater 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. 000044 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 9 of 32 Project-No. 020109CK Study-No. FAZ84112 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-oi (EINECS) Purity C8-perfluoroalkylethanol: 99.3 % (ala), sum perfluoroalkylethanol 99.9 % (a/a) Appearance Yellowish solid wax W ater solubility 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 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. 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-heptadecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Water Accommodated Fraction (WAF) acc. to OECD 203 Page 10 of 32 Project-No. 020109CK Study-No. FAZ84112 3 Method TEST GUIDELINE TYPE AND PURPOSE TEST SYSTEM Reason for the selection of the test system Origin Holding W ater 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-heptadecafluoro- to zebrafish in a limit test with the water accommodated fraction (W AF). D anio rero (zebrafish) Gnathostoma, Pisces, Ostelchthyes, Teleostei, Clupeiformes, Cyprinidae According to the guideline D anio rerio is suitable for this kind of study. AQUARIUM am AEGI, 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 a C 0 3/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; Mil k iv it , D-86666 Biirgheim 000046 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 11 of 32 Project-No. 020109CK Study-No. FAZ84112 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 of 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 (water accomodated fraction, W AF) 100 mg 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafluoro- /L dilution water (total volume 5 x 2 L) were shaken In a rotating shaker with 20 rpm for 96 h at 20 C. After phase separation 10 L per test replicate were transferred from the clear liquid phase (representing the W AF) to the glass aquarium. The preparation method was 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 TEST METHOD No reference item is recommended for this test according to the guideline. A static limit test was performed with one application at the test initiation. 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-heptadecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Water Accommodated Fraction (WAF) acc. to OECD 203 Page 12 of 32 Project-No. 020109CK Study-No. FAZ84112 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 W ater 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 - 10 pE / m2 s A natural photoperiod occurred during the test. KIND AND FREQUENCY OF MEASUREMENT AND OBSERVATIONS W ater 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 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 13 of 32 Project-No. 020109CK Study-No. FAZ84112 Criteria of effects 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.). Observation intervals Observations were made after 24, 48, 72 and 96 h. Measurement of fish size 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 EVALUATION 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. 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). 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 water accommodated fraction 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. 000049 d r .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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 14 of 32 Project-No. 020109CK Study-No. FAZ84112 VALIDITY CRITERIA DEVIATIONS FROM THE GUIDELINE DEVIATIONS FROM THE STUDY PLAN REPORTING ARCHIVING - 0 2 - saturation 2 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 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 were retained in a safe-deposit by Volksbank Sarstedt, D-31157 Sarstedt. 000050 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 15 of 32 Project-No. 020109CK Study-No. FAZ84112 4 Results 4.1 Preliminary Test Tab. 2: Cumulative Mortality in [%] in the Preliminary Test (n = 5) Concentration Effect'1 24 Test Duration [h] 48 72 96 W ater Accommodated (1) 0 0 0 0 (1> I 0Fraction Control 0 00 1 The number in brackets correspond to the following observation: (1) = Normal behaviour 4.2 Definitive 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 water accommodated fraction caused no mortality. Therefore the NOEC was laid down as 0.14 mg/L . Tab. 3: Observations in the Test Vessels Initially Measured Concentration Effect'1 24 Test Duration [h] 48 72 96 0.14 mg/L (1) 30/30 30/30 30/30 30/30 Control (1) 30/30 (E) - / - 30/30 - /- 30/30 -/- 29/30 1/30 * The number in brackets correspond to the following observation: ( 1 ) = Normal behaviour (E) = Exitus letalls (Mortality) 000051 dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 16 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 Tab. 4: Cumulative Mortality in [%] in the Test Vessels Initially Measured Concentration 0.14 mg/L Control 24 0 0 Test Duration [h] 48 72 00 00 96 0 3 If O O _] Tab. 5: LC0-, LC100-, NOEC-Values (0 - 96 h) Based on Initially Measured Concentrations LC100 = Lowest test item concentration with 100 % mortality after 96 h Highest test item concentration with 0 % mortality after 96 h NOEC (0-96 h) No observed effect concentration > 0.14 mg/L 0.14 mg/L 0.14 mg/L Tab. 6: LCso-Values with 95 % Confidence Intervals Based on Initially Measured Concentrations Test Duration [h] 24 48 72 96 LC50 [mg/L] > 0.14 mg/L > 0 . 1 4 mg/L > 0.14 mg/L > 0 . 1 4 mg/L p = 95 % [mg/L] not applicable not applicable not applicable not applicable 000052 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoroFish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Water Accommodated Fraction (WAF) acc. to OECD 203 Page 17 of 32 Project-No. 020109CK Study-No. FAZ84112 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 the water accommodated fraction of 0.14 mg/L . The NOEC (0 - 96 h) is 0.14 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 000053 _________________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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 18 of 32 Project-No. 020109CK Study-No. FAZ84112 8 Physicochemical Data 8.1 Water Quality Measurements Tab. 7: Water Parameters Initially measured Concentration day 0 0.14 mg/L control day 1 0.14 mg/L Control day 2 day 3 day 4 0.14 mg/L control 0.14 mg/L control 0.14 mg/L control OxygenSaturation [%] 100 100 93 90 94 94 94 93 91 88 pH-Value 7.38 7.46 7.04 6.93 7.48 7.47 7.42 7.45 7.64 7.81 Temperature Total Hardness [#C] 21.7 21.1 [mg/L as C a C 0 3] 71 21.9 21.8 21.1 21.0 21.2 21.0 21.2 21.2 000054 Dr .U.Noack-Laboratorium fr Angewandte Biologie Report Page 19 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 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 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-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, Varan : CTC Combi PAL, CTC A n alytic s : MS, Saturn 2000, V aran : Saturn GC/MS Workstation 5.51, V a ran Reagents fert.-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 (Va r a n ), 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 ml Heating rate rc/m in] -- 10 30 Temperature rc ] 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 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-heptadecafluoro- Page 20 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 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 ferf.-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 ferf.-butyl methyl ether. 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 = W 0.o5 / (2 f) T W o .o5 f = Peak symmetry = Peak width at 5 % of peak height [mm] = 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. 000056 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 Water Accommodated Fraction (WAF) ace. to OECD 203 Page 21 of 32 Project-No. 020109CK Study-No. FAZ84112 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 curve 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). 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- Page 22 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 9.2.3 Precision (Repeatability) The results of the repeatability tests are provided in the table below. Tab. 8: 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- heptadecafluoro(m/z = 69+395+463) 0.1 mg/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, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10 heptadecafluoro- was 1.8. 000058 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 23 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 9.2.5 Accuracy Tab. 9: 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 0.23 121 116 0.21 106 0.21 106 0.21 0.22 106 111 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 000059 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 24 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test With the Water Accommodated Fraction (WAF) acc. to OECD 203 Project-No. 020109CK Study-No. FAZ84112 9.3 Results Tab. 10: Concentrations of tha 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. WAF 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] 0.13 < LOD 0.17 < LOD 0.13 0.12 < LOD < LOD < LOD < LOD < LOD < LOD 0.027 0.009 0.9996 Mean1) [mg/L] 0.14 calc. cone. LOQ LOD WAF 1) = calculated concentration, accumulation factor taken into account = Limit of quantitation = Limit of detection = water accommodated fraction = concentrations from the test end were not taken into account for mean value, because they were < LOD 000060 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 25 of 32 Project-No. 020109CK Study-No. FAZ84112 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: Calibration Curve of Standard - concentration range 0.01 - 0.06 mg/L (dated 2002-04-04) 000061 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 Water Accommodated Fraction (WAF) acc. to OECD 203 Page 26 of 32 Project-No. 020109CK Study-No. FAZ84112 Calibration Curve of Fluowet (2002-04-10) 500000 450000 400000 ^ 350000 ? 300000 3 250000 200000 < 150000 100000 50000 0 0 2 4 6 8 10 Cone. [mg/L] Fig. 2: Calibration Curve of Standard - concentration range 0.1 -10 mg/L (dated 2002-04-10) Calibration Curve of Fluowet (2002-06-19) Fig. 3: Calibration Curve of Standard - concentration range 0.1 - 0.6 mg/L (dated 2002-06-19) 000062 ________________ 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 27 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 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 - 1 0 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. 000063 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 28 of 32 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptsdecafluoro- Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Water Accommodated Fraction (WAF) acc. to OECD 203________Study-No. FAZ84112 9.5 Chromatograms T 9 M C nnvoui*R xxtfcrN 1fiom M 110.11 15M 3 Sample ID: Iratiument ID: Measurement Type: Acquitftfon Date: Calculation Date: Sample Type: Inj. Sample Nolee: Divisor. 6411 0.1 1 Area 10.04.02 13:21 11.04.0208:08 Calibration 1,000000 Operator Last Calibration: Calibration Typs: Date File: Method: 11.04.02 08:08 External Standard e\... 8411 0.1 i 1.am c\... \8411 _rap2.mth Mumper: 1,000000 Parameter Compound Number Retention Time RT Offset PsekNama CAS Number Status Quart Iona Area Haight Amount (RF) Fit Calibration Equation BaaMine Code S a d flM tlB n 4,918 +/- 0,200 09+395+463 >10 >700 linear, Inducts, None Actual 1 4,911 min. Ao,00676 min. Fluowet 078-30-7 4368 2283 44124,941 971 y = +4,4125e+4x+0,0 BB Stafcia Paaa Peas Peas Fig. 4: Chromatogram of Standard 0.1 mg/L (dated 2002-04-10) 000064 Dr.U.Noack-Laboratorium for Angewandte Biologie Report Page 29 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 Target C o n po uid FUpcrt ter 11 from FA2B4112 E W AF I.SM 3 Sample ID: Inetiument ID: Masauremam Type: Acquisition Date: Calculation Dale: Sampi Type: Inj. Semple Note: Divisor FAZ84112EWAFI Area 08.04.0214:56 11.04.0210:37 Analysis 1,000000 Parameter Compound Number Retention Time RT Offset Peak Name CAS Number Statue Quan Ions Area Haight Amount Fit Calibration Equation Baseline Code Soectfication 4.018 +/- 0,200 60+303+483 >=10 >= 0,000 >=700 Linear, Ignora. Nona Operator Last Calibration: Calibration Type: Data File: Method: 11.04.0206:08 External Stnden! c\... faz84112awaf c\... \8411_rap2.mth Multiplier: 1,000000 Actual 1 4,913 min. 0,00503 min. Fluowet 878-30-7 M 0 0 0.000 387 y = +4,14S8e+4x -572,0246 Status Pass Fall Pass Fat StauaandEncra: M : M a tin g peak. Fig. 5: Chromatogram of Test item W ater accommodated fraction (WAF) at the test end (dated 2002-04-08) 000065 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 30 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 T M Compound R q x r t tar 1 t o m FA2B4111.2 E Ktr.SMS Sample ID: Instrument D : Meeaurament Type: Acquisition Oats: Calculation Data: Sampia Type: lnj. Sample Note: Divisor: FAZ84111J2 EKtr Aree 0604.02 12:49 11.04.021031 Analysis 1,000000 Parameter Compound Number Retention Time RT Offset Peek Name CAS Number Status Quart Iona Area Height Amount Fit Calibration Equation Baseline Code Spudficaipn 4,918 +/- 0.200 89+395+463 >10 =0,000 >=700 Linear,. Ignore, None Operator: Last Calibration: Cteibratlon Type: Data File: Method: 11.04.02 08:08 External Standard ct...feza411f 2 a kt c:\...\8411_rep2.mth Multiplier Actual 1,000000 5,073 min. 0,15453 min. Fluowet 678-39-7 M 0 0 0,000 473 y +4,1469e+4x 572,0248 Statua Pass Fail Peas Peril Staua and E acre Fig. 6: Chromatogram of Control at test end (dated 2002-04-08) 000066 Dr.U.Noack-Laboratorium fr Angewandte Biologie Report Page 31 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 Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 10 Certificate of 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10 heptadecafluoro- Analysis CUriam GmbH, Werk Gendorf CQG / QuaLitiuunsiU|emeftt D-44J04 S u rfa ire ben Fax: * * 4 9 B679 ; 2676 ^ ^ C la ria n t Inspeccin certificate according to EN10204-3.1B Date: 13.11.2001 Page: 1 / 1 Oar consignment M aterial M aterial-no. Sit NO. 1-Decanol, 3 ,3 ,4 ,4 ,5 ,5 ,6 ,6 ,7 ,7 ,8 ,8 ,9 ,9 ,1 0 ,1 0 , 10-h e p ta d e caflu o ro 104705 : POO/OUl an :vu oaten, u: wn L:r ri? ronaignment is a part, the fol lowing values cfcr.erxir.ea m e y conr.ai.r '*..7 v/u* agreed product specification. m.scecci cn ctarat" a : c - m e t n o c i S p e c i f i c a t i o r i Result J a p i - u a c y ,C Sam Fer f i u o r o a l S ty le th an o l C a p i l l a r y GC Sam P a r f l u o r a i J i y l b a t a n o l C a p ! 1 U r y GC 2 Pec f I'dor s i '<ylathene C a p i l l a r y GC Water content K a r l f . o t h e r DIN 51777 N-Methyipyrrolidone content C a p i l l a r y GC >- 97,5 >- 98,0 <-l, Q <-C, 5 < -0 ,2 <-0,2 A O 99, JM a / a ] 9 9 ,9%{a/aj < 0 ,l*[a/a] < 0 ,1 %[a/a] < 0, U 7!~.e a b o v e c a r t e cu l a r s do n o t r e l e a s e t h e c u s t o m e r fro m Che o b l i g a t i o n carry cut an cr.scecti.on of roods received. to Ms. 3 a urng a r t n e r - W o r i t s i r . s p e c t o r 00006V d r .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 32 of 32 Fish (Zebrafish), Acute Toxicity Test, Static, 96 h, Limit Test Project-No. 020109CK With the Water Accommodated Fraction (WAF) acc. to OECD 203_______ Study-No. FAZ84112 11 GLP-Certificate of Dr.U.Noack-Laboratorium n N lad ersSchsische* Gute Laborpraxis/Good Laboratory Practice GLP-Bescheinigung/Statament of 6 L P Compliance (gem H/according to $ 19 b Ab1 Chemlkallengeaetz) Eine GLP-lnspektk>n zur berwachung der Einhaltung der QLP-Grundeatze gemtH Chemlkallangesetz bzw. Richtlinie 88S32CVEG wurde durchgefOhrt In: A w eum ent o f conformity with OLP according to Chemkabengesetz end Directive 88/320/EEC a t X Prfeinrichtung /T e s t facility Prfstandort / T est site D r. U. NOACK LABORATORIUM fr angewandte Biologie Kflthe-Paulus-Str. 1 D -31157 Sarstedt D r. U. NOACK LABORATORY of applied biology KfMhe-Paulus-Str. 1 D -31157 Sarstedt {U ovam ooh e d h e ri Baaafcfm une und A dreaseU iequIvocaf nam e and addraaa) Prfungen nach Kategorien/Areas c f Expertise lamMDmmtOrnmw-au*Mr.S.3TOECOguM an) 1 - Prfungen zur Bestimmung der physikalisch-chemischen Eigenschaften und Gshattsbestimmungen 3 - Prfungen zur Bestimmung dsr srbgutverindem den Eigenschaften (In vitro und in vivo) 4 - Umwelttoxikologische Prfungen zu Auswirkungen auf aquatische und terrestrische Organismen 5 - Prfungen zum Verhalten 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 dsr Auswirkungen auf Mesokosmen und natrliche kosysteme Datum der Inspektion / Date of Inspection (Tas.MonatJahr I day.menSi.yesr) 25. - 27. Juni 2 0 0 1 1 June 2 5 * - 2 7 *. 2001 29. A ugust und 2 1 . Septem ber 2001 / A ugust 2 9 * and Septem ber 21" , 2001 D i* genannte Prfeinrichtung/Per iwnnhi flrtfe towdart befindet sich im naBanalen GLPOberweehungeverfehren und wird rogslm iaiQ auf Einhaltung dar GLP-G rundsite* berwacht Aul dar Grundlage das Inspekttonsberichtes wird hiermit besttigt, dass in dieser PrQWnrtchtung/cUaaam Prttfetandert die oben genannten Prfungen unter Einhaltung der GLP-Grondeite# durcbgefOhrt werden knnen. NiedersAcheiaches UmwettroinletBrtum Referat 33 Archivstrae 2 30169 Hannover The above mentioned test fadWty leet eite is induded In the national GLP Complance Programme and is inspected on a regular bask. Based on the Inspection report it can be confirmed, that this teat facility / test ehe ia able to conduct the aforementioned etudiee in oompftanc* wfth the Principles o f GLP. 11. MARE2002 Im Auftrge Dr. Braedt OOO