Document 99xbN1z8ZbMaGYQy9BKwjvvgR

OCTANOL/WATER PARTITION COEFFICIENT TEST SUBSTANCE Identity:N2-(N-methylperfluorooctanesulfonamido)-eatchryyllatem;ay alsobe referredto as N-MEFOSEA, or MEFOSEA. (2-Propenoicacid,2[[(heptadecafluorooctyl)sulfonyl]methylaminoe]settehry,ClAS 25268-77-3) Remarks: Materialisan amber, waxy solid.The testlaboratoryidentifietshe compound as "T-5869"(Batch2408). Sample purityisgivenas "95%". The remaining5% ofthe productwas not characterized. METHOD Method: OECD GLP (YIN): Yes Year completed: Analytical: HPLC 117 & EEC-Directive92/69 EEC, Annex 1994 withSpectrophotometridcetector V, PartA.8 Remarks: Testingused sixsubstances withknown log P. valuesas references.These substances were used to calibrattehe efutiontime inunitsof log POW. Reference substance Benzylalcohol Toluene 1,4-dichlorobenzene Fluoranthene(98%) Dibenzyl(99%) 2,4-DDT (99%) log POW 1.1 2.7 3.4 4.7 48 6.2 A stock solutionofthe testsubstance was prepared by dissolving287 mg in50.0 mL acetonitrilaend sonicatingfor2 minutes. The stocksolutionwas diluted10 timeswithmobile phase, resultinignthetestsolution(574 mg/L). Mobile phase isa 75/25 (v/v)solutionofacetonitri/lMeillipore-wQater respectively. RESULTS Substance Reference chemicals Benzylalcohol Toluene 1,4-dichlorobenzene log Pow 1.1 2.7** 3.4** Fluoranthene 4.7** Dibenzyl 4.8** 2,4-DDT 6.2** Test substance Peak 1 (majorcomp.) 5.6* Peak 2 5.4* Peak 3 5.3* Several smallpeaks -0.7/5.2* Interpolatferdomtheregressiolniney: = 0.288x- 0.730(r--9O7.2,n=6) logP,,valuesaccordingtotheOECD guidelines. CONCLUSIONS This study estimatesthe logPow forMEFOSEA. Submitter: 3M Company, Environmental Laboratory,P.O. Box 33331, St.Paul, Minnesota,55133 DATA QUALITY ReliabilityK:limischranking2 -perOECD. HPLC methods enables partitiocnoefficientso be estimatedinthe logP. range between 0 and 6. -Notox statesimpuritieasre of minor importance inHPLC method, however OECD states,HPLC method islesssensitiveto the presence ofimpuritieisnthe testsubstance than the Shake Flaskmethod. Nevertheless,insome cases impuritiecsan make the interpretatiofnthe resultsdifficudlute to uncertaintyin peak assignments. Mixtureswhich resultinan unresolvedband, upper and lower limitosf log P.,.should be stated.Duplicateanalysisshould be reportedin ordertoshow confidenceinthe measurement (logP. values shouldfallwithina range of +/-0.1 log units)- data providedmean valuethereforecan'tshow confidence.pH of eluant iscriticoafl ionizablecompounds. The study did not includeany fluorochemicalsamong the referencesubstances. Withoutfluorochemicalreferencecompounds, itisnot known whether the same relationshibpetween the capacityfactork'and Kow existsforcompounds with perfluoroalkyplortionsas exitsfornonfluorinaterdeferencematerialssuch as those used inthisstudy.The referencecompounds should have been also injectedindependentlyto insureappropriateretentiontime assigned toeach referencecompound. Reference substances were injectedtwice,however only the mean retentiontime data isgivenforthe referencesubstances thus repeatabilitoyfthe retentiontimes isnot clear.Itwas not demonstrated thatthe testmaterialwas solubleinthe acetonitrislteocksolutionor inthe mobile phase. No demonstrationthatthe major components ofthe testsubstance are detectableat UVk = 210 nm. UV adsorptionspectraisneeded ofthe purified main components ofthe testsubstance.Assumptions are made thatthe major peak from the HPLC ofthe testsubstance isthe major component. No attempt was made toconfirmthis(e.g.Mass spec analysistoshow the materialdetected has the appropriatemass). Itisnot known whether the major components even come offthe column. Some k'values reportedare calculatedincorrectly. REFERENCES Study conducted atthe requestof 3M Company by NOTOX Safety& EnvironmentalResearch B.V.,The Netherlands,April7, 1994. OTHER Last changed: 5/17/00 REPORT DETERMINATION OF THE PARTITION COEFFICIENT (N-OCTANOL/WATER) OF T-5869,t BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) RECEIVED NOV -9 1994 3m TOXICOLOGY T-5869 NOTOX Project 121286 STATEMENT OF GLP COMPLIANCE NOTOX S.V., Is-Hertogenbosch, The Netherlands The study described in this report was conducted in compliance with the most recent edition of: The OECD Principles of Good Laboratory Practice which are essentially in conformity with: The United States Food and Drug Administration. Title 21 Code of Federal Regulations Part 58. The United States Environmental Protection Agency (FIFRA). Title 40 Code of'Federal Regulations Part 160. The United States Environmental Protection Agency (TSCA). Title 40 Code of Federal Regulations Part 792. Study Director: Drs. R. de Vries Date: ................. Page 2 T-5869 NOTOX Project 121286 QUALITY ASSURANCE STATEMENT NOTOX B.V., Is-Hertogenbosch, The Netherlands. Study procedures were subject to periodic inspections and general non study specific processes were also inspected at periodic intervals. This report was audited by the NOTOX Quality Assurance Unit and the methods and results accurately reflect the raw data. DATES OF QAU INSPECTIONS/ AUDITS REPORTING DATES 25 March 1994 28 March 1994 21 April 1994 25 March 1994 28 March 1994 21 April 1994 Quality Assurance Manager C.J. Mitchell B.Sc. Date:Oct - o t, Page 3 T-5869 REPORT APPROVAL STUDY DIRECTOR: MANAGEMENT: NOTOX Project 121286 Drs. R. de Vries .......................... Date: J.A.M.W. van Helvoirt Section head Physico Chemistry pp. r.@ona C. Enninga ........................ec.h.nicalDirector Date: ,g 6 1CJCJ4 T Page-..4. T-5869 NOTOX Project 121286 PREFACE Sponsor Study Monitor Testing Facility Study Director Study plan TEST SUBSTANCE Identification Description Batch Purity Storage conditions Stability under storage conditions Expiry date 3M Belgium - Chemical EBC Canadastraat 11 B-2070 ZWIJNDRECHT Belgium Mr. R.H. Cox NOTOX B.V. Hambakenwetering 3 5231 OD Is-Hertogenbosch The Netherlands Drs. R. de Vries Start: 30 March 1994 Completed: 07 April 1994 T-5869 Cream solid 2408 95% At room temperature in the dark Stable January 01, 1996 Page 5 T-5869 NOTOX Project 121286 PURPOSE AND PRINCIPLE The purpose of the study was to determine the partition coefficient of the test substance between n-octanol and water. The partition coefficient(n-actanollwater)(POW) is defined as the ratio of the equilibrium concentrations in a two phase system consisting of n-octanol and water. The retention time of a substance in a reversed-phase High Performance liquid Chromatography (HPLC) chromatographic system is related to its partitioncoefficient(n-octanol/water). The HPLC method is useful for log Pow values between 0 and 6. Using the HPLC method, impurities are of minor importance. The HPLC method must also be applied if the test substance is a mixture of compounds but is not applicable to strong acids and bases, metal complexes, substances which react with the eluent or surface-active agents. GUIDELINES The study procedure described in this report was based on the following guidelines: Organization for Economic Co-operation and Development (OECD), OECD Guideline for Testing of Chemicals..guideline no. 117: NPartition coefficient (n-octanol/water) High Performance Liquid Chromatography (HPLC) methodu (adopted March 30, 1989). European Economic Community (EEC), EEC-Directive 92/69 EEC, Annex V, Part A, Methods for the determination of physica-chemical properties, A.8: 'Partition coefficientu. EEC Publication no. L383, December 1992. ARCHIVING NOTOX B.V. will archive the following data for at least 10 years: protocol, report, test substance reference sample and raw data. Page 6 T-5869 NOTOX Project 121286 TEST SYSTEM AND RATIONALE A High Performance Liquid Chromatograph with a spectrophotometric detector. The stationaryphase was bonded silica C18. The mobile phase was 75/25 (v/v)acetonitrile/waterB.oth HPLC instrumentatioannd conditionsare describedin the section "methodof chemicalanalysism. The test systemwas recognizedby the internationalguidelines(OECD, EEC). REFERENCE SUBSTANCES Six chemicalsfor which log P,w has been reportedwere used to calibrate the elutiontime in unitsof og Pow. The mixtureof referencesubstances consistedof: Reference substance - benzylalcohol(p.a.,Merck) - toluene(p.a.,Merck) - 1,4-dichlorobenzen(ez.s.,Merck) - fluoranthene(98%, GC, AldrichChemie) - dibenzyl (99%, GC, Aldrich Chemie) - 2,4-DOT (99%, HPLC, Riedel de Hadn, Seelze, FRG) log POW values according to the OECO guideline. log POW, 1.1 2.7 3.4 4.7 4.8 6.2 PERFORMANCEOF THE TEST Preparationof the solutions Solutionsof the referencesubstanceswere prepared in methanol (HPLC-grade, LabscanLimitedCo., Dublin,Ireland)at a concentrationof 1.5-2g/l. A mixture of the referencesubstanceswas preparedby adding125 ul of each solutionto a volumetricflask.Subsequently,this flaskwas made up with mobilephase to a final volumeof 25.0 ml. For the determinationof.to (retentiontime of the unretardedcomponent),a solutionof formamide(p a., Merck, Darmstadt,FRG) in methanolwas prepared at a concentrationof 1.7 g/l and thereafterdiluted10 timeswith mobile phase. A stock solution of T-5869 was preparedby dissolving287 mg test substance in 50.0 ml acetonitrile(2 minutes sonication).The stock solutionwas diluted10 times with mobi.lephase,resultingin the test solution. Page 7 T-5869 NOTOX Project 121286 Performance of the test The solutions were injected in the following sequence: the mixture of reference substances, mobile phase, the formamide solution, the test solution (in duplicate), mobile phase, the mixture of referencesubstances and the formamide solution. Temperature of measurement The temperature of the mobile phase was recorded several times during the measurements. METHOD OF CHEMICAL ANALYSIS The conditions used for the High Performance Liquid Chromatographic method are described below: Analysis Column Mobile phase Flow Detection Injection volume LiChrospher 100 RP-18; 125 x 4 (I.D.) mm; d 5 um (Merck, Darmstadt, FRG) 79@/25(v/v) acetonitrile (HPLC-grade, Labscan Limited Co., Dublin, Ireland)/Milli-Qwater (Millipore Corp., Bedford, MA, USA) 1 ml/min UV at X= 210 nm 10 ul Instrumentation HPLC Pump Autosampl.er Detector Integrator Series 410 LC (Perkin Elmer, Norwalk, CT, USA) ISS-200 (Perkin Elmer) SpectroManitor 3100 (LDC Analytical, Riviera Beach, FL, USA) SP 4290 (Spectra Physics, San Jose, CA, USA) DATA HANDLING Using High Performance Liquid Chromatography, especially large log Pow values can be accurately determined,from the chromatographicretention a a. To this end, the capacity factor (k ) was used, since it is proportionalto the partition coefficient. The capacity factor was calculatedfrom the retention of the substance concerned (tr) and the unretardedcomponent (to): k' = (tr- to)/to From the results of the reference substances,a plot of log Pow (x-value) versus log k' (y-value) was constructed, using linear regressionanalysis. The log k value of each component of the test substance was compared with the log k' values of the reference substances with known log Pow values. - Page 8 T-5869 NOTOX Project 121286 RESULTS Representative HPLC chromatograms of the test solution, the blank (mobile phase), the mixture of reference substances and the formamide solution are shown in Figures 1 to 4. In the HPLC chromatograms of T-5869, using detection at 210 nm, one large and 2 small test*substance peaks were observed. In addition, many small test substance peaks were observed between approximately 1 and 6 minutes. It was assumed that the large peak derived from the major component of test substance whereas the small peaks derived from impurities. The to was determined to be 0.90 minutes as a mean value,of both measurements (i.e 0.89 and 0.90 minutes). The mean values of the retention times, k' values, log k' values, log P w and Pow values are summarized In Table 1. The plot of log Pow (x-va?ue) versus log k' (y-value) from the reference substances is shown in Figure 5. Table 1 Results of the test. Substance trl k log k' 109 POW POW benzylalcohol toluene 1,4-dichlorobenzene fluoranthene dibenzyl 2,4-DOT. test substance peak I (major comp.) peak 2 peak 3 several small peaks 1.14 0.274 -0.563 1.1 2.24 1.503 0.177 2.7 2.89 2.229 0.348 3.4 5.67 5.330 0.727 4.7 4.07, 3.547 0.550 4.8 9.12 9.190 0.963 6.2 7.75 6.96 6.60 1-6 7.659 6.777 6.374 0.12/ 5.67 0.884 0.831 0.804 -0-93/0.75 5.6 2 5.4 2 5.3 2 -0.7/5.2 2 3.98xlO5 2.5lxlO5 2.00xlO 0.2/1.58xlO-5 N2ote Mean value of the retention times of both chromatograms. Interpolated from the regression line: y - 0.288x - 0.730 : The calculations were performed using not rounded values. (r.0.972, nm6) The temperature of the mobile phase was 20.2-20.-60Cduring the measurements.' Page 9 T-5869 CHANNEL R NOTOX Project 121286 INJECT 07-04-94 e8:03:58 !.;TORCDTO BIN !50 54 4. 1 33F9.4.N2,23 BATH SAVED TO BIN Sg 38196/121286 -ILE i. METHOD S. 07-04-94 08:03:58 RUN 7 INDEX* 7 PERK# 2 3 4 5 6 7 8 9 io 11 12 13 14 15 16 17 i-q19 20 21 22 23 'n4 ARERY. 0.041 0.209 0.098 3.425 0.121 0.251 0.498 0.189 0.25 A-.428 0.839 0.899 3.097 0.092 1.652 1.125 4.167 0,248 0.47,2 1.217 0. 8q 13. Fi76 11.364 55, '-Z9 RT AREA SC 0.-15 1321 02 0.25 6658 02 0.34 3122 A2 A-94 A09239 OR 0.79 3874 05 1.02 seii 06 1.1 15893 06 1.29 6033 06 1.47 7978 06 1.58 13948 06 1.72 26774 06 2.03 28669 07 2.48 98772 08 2.93 2936 06 3.@i5 " 52708 03 '-Z8. 35886 02 4.13 132925 0 4..93 7895 02 5.23 02 5.59 38811 02 5.88 28393 02 6.61 41708--(02 f;.97 3f;2494 @t' 7-77 1-1Ffr794;t-4 iffietPS= i. BIN 50 Figure 1 HPLC chromatogram of the test solution of 574 mg/l T-5869 in mobile phase. Column Mobile phase Flow Detection Injection volume LiChrospher 100 RP-18; 125x4 (I.D.) mm; dp=5 Jim 75/25 (v/v) acetoni-trile/Milli-wQater 1 ml/min UV, at X = 210 nm 10 pl 1 Note: All the peaks between 0 and approximately I minute and some of the peaks between approximately I and 2 minutes were also observed In the chromatograns of the blank (see Figure substance. 2). Therefore it was assumed that these peaks did not derive from the test P6hp-,in T-5869 NOTOX Project 121286 CHANNEL 8 INJECT 07-04-94 IR9:34:t34 ';TORED TO BIN 56 17 2 DATA SRVED TO BIN ER 0 56 38196/121286 FILE 1. METHOD ANRLYST: KRH -=RK# ARER% 1 2 3 4 5 6 7 8 70TAL 1.543 10.515 3.853 55.335 7.768 6.901 2.509 11.576 100. 07-04-94 09:34:04 0. RUN 13 INDEX 13 RT 0.15 iB.25 0. '-4Z r4.F,2 0. r,7 0.99 1.18 1.-r%i APER sc 877 02 5976 02 2190 A2 3144q S@@ 4415 03 3922 02 1426 03 A579 01 56834 CH= "A" PS= 1. BIN 56 Figure 2 HPLC chr omatogram of a blank (mobile phase). Column Mobile phase Flow Detection Injection volume LiChrospher 100 RP-18; 125x4 (I.D.) mm; dp=5 um 75/25 (v/v) acetonitrile/Milli-Qwater 1 ml/min UV, at X = 210 nm 10 ul Page 11 T-5869 I-7HANNEL A NOTOX Project 121286 INJECT 07-04-q4 Aq:SA:17 :;Tn-REDTO SIN # 57 . . ..................................... 1.14 f .98 F4- 91 i FER 0 (@7 DATA SRYED TO BIN # 57 3S196/121286 FILE i. METHOD ANALYST: KRH PERK# ARERY. I O.e23 2 0.145 3 0.06 4 0.879 5 0.073 6 0.139 7 8.977 8 0 112 9 .1,L3:1.7 0.013 -10.567 12 15.524 13 '-ZS.584 14 0.316 15 13.272 TOTAL 100. 07-04-94 09:50:17 0. RUN 14 INDEX 14 RT 0.14 0.25 0.34 0.53 0.79 0196 1.14 1.61 2.24 2.61 2.89 4.08 5.68 6.98 9.13 iL31 A2 7019 02 2917 02 42751 08 3542 05 6771 06 436774 03 5460 Ot@ 55A-i;40 Fli rl1 02 514173 03 755334 01 1877339 01 15361 01 645770 01 4865613 rH= uR" PS= IBIN 57 Figure 3 HPLC chromatogram of the mixture of reference substances in mobile phase. Column Mobile phase Flow Detection Injection volume LiChrospher 100 RP-18; 125x4 (I.D.) mm; dp=5 lim 75/25 (v/v) acetonitrile/Milli-wQater 1 ml/min UV, at X = 210 nm 10 ul - Page 12 T-5869 NOTOX Project 121286 R-HANNEL A INJECT 107-04-q4 07:37:44 4 1. 421--13.8577 2.97 3T.31.-665 DATA SAVED TO BIH 49 !;TORED TO BIN 49 .89 28196,,1121286 1%7-134-94 07:-k7:44 rH= FILE 1. METHOD 0. RUN 6 INDEX 6 ANALYST: 'PEAK# KRH FIRERV. RT AREA BC 1 0.35 0.16 2624 92 2 1.189 0.27 8926 02 3 0.79 5930 02 4 10.44 .55 78363 08 5 1.884 0.78 14143 06 6 54-548 0.89 4A-.Q437 08 7 6.246 .1-11 )179 A-5 8 0.12 1.42 8<)q C45 9 --@.094 1.87 23224 02 10 0.424 2.97 3IS5 03 li 20.915 3.65 1!7i-qR,9 01 TOTAL loo.. 7ciFI599 S= BIH 49 Figure4 HPLC chromatogram of a formamide solution of 0.2 g/l in mobile phase. Column Mobile phase Flow Detection Injection volume LiChrospher 100 RP-18; 125x4 (I.D.) mm; dp=s Jim 75/25 (v/v)acetonitrile/Milli-wQater 1 ml/min UV, at X = 210 nm 10 ul Page 13 T-5869 NOTOX Project 121286 13/04/94 TRJ Pow 1.000 ------ 4 -- - -- -- -- - -- - -- - -- - -- -- - -- - -- -- - - -- -- - - - -- -- -- -- - -- - - - - - - - - - - - - - - - - - - - - - - - - 0 0.800 -------0 ...................-.-.-.--.------------.-.-............ o 9 0.600 -------i------------------------------------------------ ---------0 0.400 k --------------------%-o------------4@ -------------------------------------------o 0.200 -----.-.--...........6.,.--:----------------------------------------------- 0.000 0.0 1.0 2.0 3.0 4.0 5.0 6.0 log Pow Figure 5 Plot of log Pow (x-value)versus log k' (y-value)from the reference substances. Page 14