Document rxppRy8nzwm5zMyMxa5bk40q7

ftkA .6 _ 32.6A *444 AfOiiL- 3 * 6 ^ W A ter Solubility DuPont report number 12718 Test Guideline(s) OECD 105 (adopted 12 May 1981). Authors Mary A. Kaiser, Ph.D. (study director) Daryl P. Cobranchi, Ph.D. Robert C Buck, Ph. D. Study Completion Date 16 July 2002 Report Date 27 December 2002 Test Facility DuPont Corporate Center for Analytical Sciences Experimental Station 402/5321 (and Glasgow 300) Wilmington, DE 19880-0402 Sponsor Telomer Research Panel c/o Rand Corporation /****'**, 1Telomer Research Program Company Sanitized. Does not contain TSCA CB1 1 2 Table of Contents Title P age................................................................................................................................................... 1 Table o f Contents...................................................................................................................................... 2 1.0 Summary............................................................................................................................................ 2 2.0 General Study Information...................................................................................... 3 3.0 Materials and Methods.................................................................................................................... 4 3.1 Test Guidelines............................................................................................................................. 4 3.2 Chemical System ..........................................................................................................................4 3.2.1 Test Substance........................................................................................................................... 4 3.3 Test Conduct..................................................................................................................................6 3.4 Parameters Observed................................................................................................................... 7 3.5 Result A nalysis.......................................................................................................................... ..7 3.6 Validity Criteria o f the Study...................................................................................................... 7 3.7 Guidelinel Deviations.................................................................................................................. 7 4.0 Results and Discussion.....................................................................................................................8 5.0 Conclusions.............................................................................. 8 6.0 Retention o f Records.......................................................................................................................9 7.0 Disposal o f Test Item.............................................................. 9 8.0 Reference...................... 9 Tables Figures Appendices W Ater Authors Mary A. Kaiser, Ph.D. (study director) Daryl P. Cobranchi, Ph.D. Robert C Buck, Ph. D. 1.0 Summary Test System: The water solubility ofpHHHHHBHHHHHRHHaHHHHHPHwas determined in aqueous solution at 12 C, 25 C, 37 C and 60 C using a 2Telomer Research Program Company Sanitized. Does no! contain TSCA CBI 2 variation o f OECD method 105. The experimental mixture was shaken for at least three days and the test substance concentration determined at various intervals via gas chromatography mass spectrometry. Findings: The solubility in water was 134 pg/L (+/-29 pg/L) at 12 C ; 137 (47-53 pg/L) at 25 C; 318 pg/L b (4/-176 pg/L) at 37 C, and 225 pg/L (4/- 51 pg/L) at 60 C. Conclusions: The solubility o( C to 60 C is very low (134 to 318 pg/L). in water from 12 2.0 General Study Information Study Objectives The objectives o f this study were to: Determine the water solubility between 12 C, 25 C, 37C, and 60 C in pure water. Determine the effect o f pH on water solubility at 12 C, 25 C, 37C and 60 C. Test System Justification The test system was selected by the sponsor. Study Personnel Test Facility Name DuPont Corporate Center for Analytical Sciences Building 300, Glasgow, Delaware, 19714-6101 USA Management: Study Director: Marianne Marsi, Ph.D. Mary A. Kaiser, Ph.D. DuPont Company 3Telomer Research Program Company Sanitized. Does not contain TSCA CB 3 /""""N Principle Investigator: Technical Personnel: Daiyl P. Cobranchi, Ph.D. DuPont Company Corporate Center for Analytical Sciences Barry W. Wolstenholme Study Execution Dates Study Initiation Date: Experimental Start Date: Experimental Completion Date: Study Completion Date: 15-Jun-2001 15-Jun-2001 28-June 2002 12-July 2002 3.0 3.1 3.2 3.2.1 Materials and Methods Test Guidelines The solubility in water of a substance is specified by the saturation mass concentration o f the substance in water and is a function of temperature. The solubility in water is specified in units o f weight per volume of solution. The Si-unit is kg/m3; g/1 may also be used. Chemical System Test Substance ^ The test substance was obtained from ClariantG m bh (Germany) and w a s H J H p ure via gas chromatography. The major impurity was tentatively identified a sK jfiH fljB jj^ H ro a se d on the mass spectral fragmentation pattern. Name: Synonym: Active substance(s) CAS Name: CAS Number(s): 4Telomer Research Program Company Sanitized. Does not contain TSCA CB1 4 Structure: / ""n H Number Lot Number: EMSE Sample Number: Concentration, nominal: Concentration, analyzed: Certificate o f Analysis Date: Date Received: Vapor pressure: Stability: Appearance/Color: Storage Conditions: H-24691 E93386-63 03-Apr. 2001 15-June 2001 0.023 mm Hg Stable at ambient room temperature White solid Room temperature; keep tightly closed 3.2.2 Test Vehicle The test substance was dissolved in ultrapure water (17.6MQ-cm). 3.2.3.1 Test Units Test vessels were 2 mL (nominal) borosilicate glass vials, 12 mm outer diameter by 32 mm length. Vial caps were blue caps with Teflon fluoropolymer resin and redrubber septum caps. 3.2.3.2 Test Conditions Test solutions were kept closed during the dissolution and shaking process. 5Telomer Research Program Company Sanitized. Poe, not contain TSCA CB! 5 3.3 Test Conduct The water solubility o f t h e k j ^ ^ ^ ^ ^ ^ ^ ^ ^ H p i s t u d y material was determined at 12C, 25, 37C and 60CT7 Excess test substance was placed in a 2-mL gas chromatography sample vials and shaken at constant temperature for 24 hours on a shaker table. The test substance concentration was measured at various time intervals by gas chromatography with mass spectrometric detection ((Electron Impact (El) detection, m/z =463). In the second method used to determine water solubility, approximately 100 m g <'^ ^ 1 # ' ^ ad * s ta n te d je re w cap 2-mL glass gas chromatography vial. The vial was coated with excessBpBA placing the open vial on a warm surface to melt the test substance and condense the study substance onto the cooler upper surfaces of the vial. The vial was then removed from the warm surface and allowed to come to room temperature. Ultrapure (conductivity o f 17.6 M Q-cm) water was added to the vial so that no headspace was available. The silicone-rubber side o f the vial cap was turned to cover the vial before sealing. The vial was placed on a thermostated, insulated shaker table at the temperature of interest. The table rotation rate was set at approximately 100 rpm for at least four days. A sample was removed to a temperature-chromatographic autosampler tray and the test substance was determined by GC/MS. This method is much faster than the first method and gives the same result. Details of the GC/MS experiment Vials: Target DP (dual purpose) Vials, 1.8 mL capacity, borosilicate glass, 12 mm outer diameter by 32 mm length, National Scientific, Inc., 205 East Paletown Road, Quakertown, PA 18951 USA, catalog number C4000-1. Vial caps: Target DP (dual purpose) blue caps with Teflon and red-rubber septum, National Scientific, Inc., 205 East Paletown Road, Quakertown, PA 18951 USA, catalog number C4000-51B Helium: 99.999% pure, plumbed with stainless steel and copper tubing, MG Industries, Newark, DE USA. Gas Chromatograph and Mass Spectrometer: HP (now Agilent) Series II Plus gas chromatograph and HP (now Agilent) 5972 mass selective detector (MSD) with a 100-sample autosampler tray and HP (now Agilent) 7673 GC injector tower, Agilent Technologies, 2850 Centerville Road, Wilmington, DE 19808, USA. Gas chromatograph's septa: Merlin-Microseal, Merlin Instrument Company, Half Bay, CA 94019 USA, part number 310. VWR cooling unit, 1310 Goshen Parkway, West Chester, PA 19380 USA, model 1160A. Nalgene polypropylene volumetric flasks, from VWR, 1310 Goshen Parkway, West Chester, PA 19380 USA. Thermolyne Bigger Bill orbital shaker set at 300 rpm, VWR, 1310 Goshen Parkway, West Chester, PA 19380 USA, with temperature-controlled table and tray. Shaker connected to a Brinkmann RM-6 6Telomer Research Program Company Sanitized. Doss not contain TSCA CB 6 cooling unit, Brinkmann Instruments, Inc., One Cantiague Road, PO Box 1019 Westbury, NY 11590 USA. GC/MS conditions: Oven temperature: 80C for one minute, increased at 20C/minute to 300C and held for 10 minutes. Run time 22 minutes. Injector: splitless, 225C, purge flow 50.0 mL/minute, purge time 0.70 minutes, saver flow 20 mL/minute, 3 sample washes, no pump (quiescent), lpL injection size, (10 pL Agilent syringe), three post injection washes with JT Baker ultraresi-analyzed cat. # 9263-03) methanol, sampling depth 10.0 mm above the nominal position. Solvent delay: 5.0 minutes (i.e., detector turned on after five minutes) Ions: 463.0,131.0, 95.0, 69.0, 31.0 (preferred) El at 70 eV Column: Restek RTX-200 (trifluoropropylmethyl polysiloxane), 60 meter, 250 pm diameter, 1.00 pm film thickness, catalog number 15056, Restek Corporation, 110 Benner Circle, Bellefonte, PA 16823 USA. Initial flow set at 1.4mL/minute, constant flow, initial inlet pressure 25.89 psi, average velocity 31 cm/sec. Limit of Detection (LOD) approximately 20 ppb; limit of quantification (LOQ) approximately 50 ppb. 3.4 Parameters Observed The peak area or height was measured for the test substance saturated in the aqueous solution at specific temperatures. 3.5 Result Analysis The peak height or peak area obtained for the test substance was compared to the same parameter of a standard carefully preparred in methanol. 3.6 Validity Criteria o f the Study The test results were considered valid if the peak areas o f the standards run before and after the test substance were within 5% o f the parameter measured. 3.7 Guideline Deviations Deviation 1 Deviation 2 Concerning: Deviation: Reason: Impact on Study Concerning: Deviation: Addition of the test substance to the vessel The test substance was coated on the wall of the test vessel. The "excess" test substance formed needle like structures, which interfered with the chromatographic injection. None Choice o f test method The "flask" method recommended for 7Teiomer Research Program Company Sanitized. Does no! contain TSCA CBI 7 Reason: Impact on Study: compounds having solubility > 1 0 ppm was used rather than the "column elution method" which is recommended for compounds having solubility < 1 0 ppm. The "column elution method" is less reliable that the "flask" method for volatile compounds. None 4.0 Results and Discussion Table 1 summarizes the solubility data versus temperature. The solubility atpH 3, pH 11 and autogeneous pHJ5.8) at 12 C weremeasured with no significant difference in the s o l u b i l i t y t h e pH range. Table 2 through 7 summarize the m ea su re^ a ^ ^ o tu M tt^ ersu s pH determinations. The solubility in water at 12 C is 134 pg/L (+/-29 pg/L); 137 pg/L (+/-53 pg/L) at 25 C; 318 pg/L (+/-176 pg/L) at 37 C, and 225 pg/L (+/- 51 pg/L) at 60 C. Varying pH from 3 to 11 had no impact on the solubility measurement. 5.0 Conclusions The solubility o: 60 C. fis in the 100 to 250 pg/1 range from 12 C to 8Te!omer Research Program Company Sanitized. Does no! contain TSCA CBI 8 6.0 Retention of Records Study documents and materials will be stored in the archives of the DuPont Experimental Station including but not limited to: study protocol; any protocol and/or report amendments or addenda or deviations; all raw data; one original signed copy o f the final report; laboratory-specific or site-specific raw data such as personnel files, instrument, equipment, refrigerator, and/or freezer raw data. 7.0 Disposal of T est Item After issuance of the final report, the remaining test substance will be stored at the DuPont Glasgow site until its expiration date and then destroyed by burning, unless other arrangements are made between the sponsor and the Test Facility. 8.0 Reference 1. OECD Guidelines for the Testing o f Chemicals / Section 1: PhysicalChemical properties Test No. 105: Water Solubility, adopted 12 May 1981. (published July 1995) Table 1 Water Solubility versus Temperature (C) at Autogeneous pH 12 25 37 60 n = number of tests 134 137 318 225 9Telomer Research Program 29 8 53 17 176 10 51 10 Company Sanitized. Does no! contain TSCA 9 Table 2 Water Solubility versus pH at 12C fiH 3 autogeneous pH = 5.8 11 n = number of tests Solubility (na/mL) 227 104 74 Std. Dev. (na/mU 109 57 29 n 6 6 5 lOTelomer Research Program Company Sanitized. Does no! contain TSCA CB 10 Table 3 Water Solubility Raw Data : Autogeneous pH 5 .8 ,12C Slope Intercept 238.61 6555.5 Std Dev n t 95% UCL 95% LCL 29 8 2.3646 158 109 Average 134 ppb Samole Area 1 36,712 2 32,865 3 38,141 4 28,037 5 44,510 6 37,270 ......... 7............ 0 8 51,133 9 38,660 10 0 Cone. (PPb) 126 110 132 90 159 129 0 187 135 0 Peak Area used for quantitation n = number of determinations UCL = Upper Confidence Level (ppb) LCL = Lower Confidence Level (ppb) llTeiom er Research Program Company Sanitized. Does not contain TSCA CBI 11 Table 4 Water Solubility Raw Data : Autogeneous pH 5.8, 25C Slope Intercept 2.9948 0 Std Dev n t 95% UCL 95% LCL 53 17 2.1199 164 109 Average 137 ppb S e ti Set 2 Sample Peak Heiaht Peak Heiaht 1 511 2 470 3* 4 414 5 640 6 397 7 459 8 170 9 203 10 * 595 543 * 320 405 282 608 209 180 544 Cone (PPb) 185 169 123 174 113 178 63 64 182 Peak Height used for quantitation *Peak too high to measure. Solid probably included in injection. n = number of determinations UCL = Upper Confidence Level (ppb) LCL = Lower Confidence Level (ppb)_______________________ 12Telomer Research Program company Sanitized. Doss ne! csoja'n 7SCA CBf / 12 Table 5 Water Solubility Raw Data : Autogeneous pH, 37C Slope 10.0332 Sample Area Intercept 642.42 Std Dev n t 95% UCL 95% LCL 176 10 2.2622 444 192 Average 318 ppb 1 4207 2 4624 3 2498 4 3205 5 2055 6 2660 7 1828 8 3991 9 5870 10 7366 Peak Area used for quantitation n = number of determinations UCL = Upper Confidence Level (ppb) LCL = Lower Confidence Level (ppb) Cone. {qpM 355 397 185 255 141 201 118 334 521 670 13Telomer Research Program Company Sanitized. Does no? contain TSCA CB 13 Table 6 Water Solubility Raw Data : Autogeneous pH, 60C Standard run before and after each sample. Std Dev n t 95% UCL 95% LCL 51 20 2.09302 249 201 Average 225 ppb Set 1 Set 2 Sample Area Area 1 486500 366225 2 289001 266224 3 319066 273785 4 225266 226886 5 275743 263277 6 335225 240121 7 206398 190197 8 180304 326588 9 301712 343656 10 285294 212958 Cone. (PPb). 297 196 219 175 214 236 171 228 288 227 Peak Area used for quantitation n = number of determinations UCL = Upper Confidence Level (ppb) LCL = Lower Confidence Level (ppb) 14Telomer Research Program Company Sanitized. Does no! oonta'nTS C A C B I 14 ^jnnus Table 7 Water Solubility vs. pH Raw Data at 12C Std Dev n 95% UCL 95% LCL pH 3 average Sample pH 109 3 63 3 234 3 219 3 3 227 ppb Peak Heiaht Cone, (ppb) 30 284 18 170 12 114 23 217 44 416 17 161 . .. Std Dev n 95% UCL 95% LCL pH 5.81 average Sample pH Peak Heiaht" Cone, loob) 57 5.81 11 104 6 5.81 23 217 5.81 9 85 107 5.81 7 66 100 5.81 8 76 5.81 8 76 104 ppb Std Dev n 95% UCL 95% LCL Sample pH Peak Height Cone, (ppb) 29 11 6 57 5 11 8 76 11 4 38 76 11 1087* * 71 11 12 114 11 9 85 'rejected due to probable solid introduction pH 11 average 74 ppb Peak Area used for quantitation n = number of determinations UCL = Upper Confidence Level (ppb) LCL = Lower Confidence Level (ppb) 15Telomer Research Program Company Sanitized. Does ne? contain TSC CB1 15 Appendix A Chemical Analysis Summary H-24691 Analysis Summary The subject material was analyzed by gas chromatography using a standard method to e s s e ^ its composition. This analysis show e^hat the material com p ris e d B M B bf the subject material. The b>a,anc^ A H n was not _________________ ""at a limit of quantitation of ).02%. Further analysis by GOVMS suggests mat t h 4 H B i is a single impurity, whose chemical structure is| Finally, the subject material was evaluated by High Performance Liquid Chromatoarapy - Tanrtom Maco gnortmmghv (i for the presence of at a detection limit of '0.1 ppm. Neither material was observed to be preseriET Based upon these analyses, we conclude that methods are in hand to determine and confirm the composition of H-24691 to be as follows: / rm^. Material Wk%_(+0.3) 16Telomer Research Program 'Mnnanv n ''** nn< rnr Appendix B Solubility Determination- Modified ASTM Procedure 1. A concentrated (-50% w/w) solution o f 8-2A in GC grade methanol was prepared. 2. Approximately 200 pL were placed into a standard screw-cap GC vial. 3. The open vial is placed in a warm location to evaporate the solvent. 4. After the methanol had evaporated, the 8-2A was observed to collect on the upper surfaces o f the GC vial. 5. The vial was then removed and allowed to cool to room temperature. 6. Ultrapurel 8 M il water was carefully added to the vial, filling it all the way to the top (little or no headspace). 7. The septum was turned upside down so that the silicone rubber side was facing towards the solution. 8. The vials were then capped and placed in a temperature controlled shaker table operating at -1 0 0 rpm. 9. The vials were shaken for a minimum o f 4 days prior to analysis. 10. The vials were then removed to the GC/MS auto-sampler tray, temperature controlled. 11. The GC/MS was calibrated against 8-2A samples prepared in methanol. 17Telomer Research Program Company Sanitized. Doss not contain TSCA CBS 17