Document DMjYweRn16jb66Zv2bp6Ew5Ro

3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Study Title 104-Week Dietary Chronic Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) in Rats (Covance Study No.: 6329-183) Analytical Laboratory Report Title Determination of the Presence and Concentration of Perfluorooctanesulfonate (PFOS) in Liver and Serum Specimens of Crl:CD(SD) IGS BR Rats Exposed to Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) Data Requirement Not Applicable Author 3M Environmental Laboratory Study Completion Date At signing Performing Laboratories Liver and Serum Analyses 3M Environmental Laboratory Building 2-3E-09, 935 Bush Avenue St. Paul, MN 55106 Project Identification 3M Medical Department Study: T-6295.4 Covance In-Life Study: 6329-183 Analytical Report: FACT TOX-002 3M Laboratory Request No. U2121 Total Number of Pages 181 3M Environmental Laboratory Page 1 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 This page has been reserved for specific country requirements. 3M Environmental Laboratory Page 2 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 GLP Compliance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration of Petfluorooctanesulfonate(PFOS) in Liver and Serum Specimensof Crl:CD@(SD)IGS BR Rats Exposed to Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) Study IdentificationNumber: T-6295.4, FACT TOX-002, LRN-U2121 This study was conducted in compliance with United States Food and Drug Administration (FDA) Good Laboratory Practice (GLP) Regulations 21 CFR Part 58, with the exceptions in the bulleted list below. Exceptions to GLP compliance: 0 There were two study directorsin this study. This study was designed astwo separate studies. The in-life phase study was considerteodend at the generationand shipment of specimens. The analytical study was consideretod start at the receipotf these specimens for analysis. This resulteind having two separate study directors, one for each phasoef the same study. However, since the technical performanceof each phase was entirely separate, neoffect is expected from this exception. 0 Changes in the raw data entries were not all madein accordance with21 CFR 58.130 (e). 0 Specimen stability storage will not be determined. One of the control matrices (rabbit liver) was not identified in accordance with 21 CFR 58.120 (a)(2). The electronic data systemsin use have not been validated and thereis not an electronic audit trailof corrections currently available (21 CFR 583.01 (e)). Authenticated hard copiesof chromatograms and associated documents will be considered as the original raw data. 0 Characterization of the analytical standards is underway, but was not completed at the time this datwaas assembled (21 CFR 58.105 (a)).When Certificatesof Analysis for all remaining lotosf PFOS are available, an amendmentto this report will be issued. Lot No. 59909of THPFOS will not be characterizefdor purity since quantitiesof this standard are exhausted. . L Represenfative Sponsor 3M Environmental Laboratory ' - d l i , f J !- I Date Page 3 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 GLP Study-Quality Assurance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration of Perfluorooctanesulfonate(PFOS) in Liver and Serum Specimensof Crl:CD@(SD)IGS BR Rats Exposedto Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) Study Identification Number: T-6295.4, FACT TOX-002, LRN-U2121 This'study has been inspected by th3eM Lab Quality Assurance Unit (QAU) as indicated in the following table. The findings were reportteodthe study director and laboratory management. Inspection Dates Phase Date Reportedto Management Study Director 11/I 1/99 Extraction 11/30/99 11/30/99 08/28/00 - 09/18/00 10/05/00- 10/06/00, 10/16/00 - 10/20/00, 10/30/00- 10/31/00 11/01/00 - 11/03/00 - 11/02/00 11/03/00, 11/06/00- 11/07/00 01/08/01 - 01/11/01 Data Data Data Data Draft Report 09/19/00 11/02/00 11/06/00 11/08/00 01/12/01 09/19/00 ~ ~~ 11/02/00 1I /06/00 11/08/00 01/12/01 LKJ 1 , QAU Represethytive Date 3M Environmental Laboratory Page 4 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table of Contents GLP Compliance Statement..............................................................................................3 GLP Study--Quality Assurance Statement .......................................................................4 Study Personnel and Contributors.....................................................................................9 Introduction and Purpose ..................................................................................................10 Test System .................................................................................................................10 Specimen Collection and Analysis ................................................................................10 Specimen Receipt and Maintenance .................................................................................11 Chemical Characterization ................................................................................................11 Dose Confirmation Analyses ........................................................................................12 Method Summaries ...........................................................................................................12 3M Environmental Laboratory.......................................................................................12 Preparatory Methods ...............................................................................................12 Analytical Methods ...................................................................................................13 Analytical Equipment ...............................................................................................14 Deviations..................................................................................................................... 14 Data Quality Objectives and Data Integrity........................................................................15 Data Summary, Analyses, and Results .............................................................................15 Summary of Quality Control Analyses Results..............................................................15 Statement of Data Quality ............................................................................................16 Summary of Specimen Results ....................................................................................16 Statistical Methods and Calculations .................................................................................16 Statement of Conclusion ...................................................................................................17 Reference .........................................................................................................................17 Appendix A: Identification of Test Article and Control Matrices .........................................18 Appendix B: Protocol, Amendments, Deviations ...............................................................19 Appendix C: Extraction and Analytical Methods ................................................................42 FACT-M-1.0, Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Liver for Analysis using HPLC-Electrospray/Mass Spectrometry (8 pages).....................................................................................................43 FACT-M-3.0, Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry (8 pages).....................................................................................................51 ETS-8-4.1, Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages).........................................................................................................................59 ETS-8-6.0, Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Liver for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages).........................................................................................................................73 3M Environmental Laboratory Page 5 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 FACT-M-2.0, Analysis of Fluorochemicals in Liver Extracts Using HPLCElectrospray/Mass Spectrometry (8 pages).......................................................................87 FACT-M-4.0, Analysis of Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry (8 pages) ............................................................95 ETS-8-5.1, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (9 pages) ....................103 ETS-8-7.0, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry, (10 pages) .....................114 Appendix D: Data Summary Tables ..................................................................................126 Appendix E: Data Spreadsheets .......................................................................................156 Appendix F: Example Calculations ....................................................................................172 Appendix G: Interim Certificates of Analysis......................................................................174 Appendix H: Report Signature Page .................................................................................181 3M Environmental Laboratory Page 6 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 List of Tables Table 1. Test System Population Demographics for Study (6329-183) ............................10 Table 2. Characterization of the Analytical Reference Materials Used in Study FACT TOX-002 ....................................................................................................12 Table 3. Negative Ions Monitored in 3M Laboratory Analyses..........................................14 Table 4. Characterization of the Control Matrices Used for Sera Analyses in Study FACT TOX-002 ....................................................................................................18 Table 5. Characterization of the Control Matrices Used for Liver Analyses in Study FACT TOX-002 ....................................................................................................18 Table 6. Identification of the Test Article in Study FACT TOX-002 ....................................18 Table 7. FACT TOX-002 Data Summary of PFOS Concentration--Serum (g/mL).........127 Table 8. FACT TOX-002 Data Summary of PFOS Concentration--Liver (g/g) ..............128 Table 9. Week 4 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 ....................................................................................................129 Table 10. Week 4 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 ....................................................................................................130 Table 11. Week 14 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 ....................................................................................................131 Table 12. Week 14 Reported PFOS Levels in Sera Female Rats in Study FACT TOX-002 ....................................................................................................132 Table 13. Week 53 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 ....................................................................................................133 Table 14. Week 53 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 ....................................................................................................133 Table 15. Day 719 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 ....................................................................................................134 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 ....................................................................................................135 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 (continued) .................................................................................136 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 (continued) .................................................................................137 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 ....................................................................................................138 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 (continued) .................................................................................139 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 (continued) .................................................................................140 3M Environmental Laboratory Page 7 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 18. Week 106 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 ....................................................................................................141 Table 19. Week 106 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 ....................................................................................................141 Table 20. Week 4 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 ....................................................................................................142 Table 21. Week 4 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................143 Table 22. Week 14 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 ....................................................................................................144 Table 23. Week 14 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................145 Table 24. Week 53 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 ....................................................................................................146 Table 25. Week 53 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................147 Table 26. Day 719 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................148 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 ....................................................................................................149 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 (continued) .................................................................................150 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 (continued) .................................................................................151 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................152 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 (continued) .................................................................................153 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 (continued) .................................................................................154 Table 29. Week 106 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 ....................................................................................................155 Table 30. Week 106 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 ....................................................................................................155 3M Environmental Laboratory Page 8 3M Medical Department Study: T-6295.4 Study Personnel and Contributors Study Director John L. Butenhoff, Ph.D., Study Director 3M Corporate Toxicology - Medical Department 3M Center, Building 220-2E-02 St. Paul, MN 55144-1000 651-733-1962 Sponsor Marvin T. Case, D.V.M., Ph.D., Sponsor Representative 3M Corporate Toxicology - Medical Department 3M Center Building, 220-2E-02 St. Paul, MN 55144-1000 Analytical Chemistry Laboratories Liver and Serum Analyses 3M Environmental Laboratory (3M Lab) Kristen J. Hansen, Ph.D., Principle Analytical Investigator Analytical Report: FACT TOX-002 LRN-U2121 3M Lab Contributing Personnel Lisa A. Clemen Kelly J. Dorweiler* Mark E. Ellefson Sara E. Estes* Barb A. Gramenz* Sarah A. Heimdal* Cari S. Hewitt* Marlene M. Heying* Megan C. Holloway* Joy D. Jenkins *Contract lab professional service employees Harold O. Johnson Ognjenka Krupljanin* Kelly J. Kuehlwein* Glenn M. Langenburg* Sally A. Linda* Ian A. Smith* Kathleen M. Stock* Bob W. Wynne* Richard D. Youngblom* Location of Archives All original raw data, protocol, and analytical report have been archived at the 3M Environmental Laboratory. The test article and analytical reference standard reserve samples, as well as the specimens pertaining to the analytical phase of this study are archived at the 3M Environmental Laboratory. 3M Environmental Laboratory Page 9 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Introduction and Purpose The purpose of the study is to determine the presence and concentration of PFOS in liver and serum specimens collected from Covance Study No.: 6329-183 titled: 104-Week Dietary Chronic Toxicity and Carcinogenicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS, T6295) in Rats, initiated on 22 May 1998. Test System 360 males and 360 females were used as the test system. Table 1 outlines the rat population demographics and dosage levels for study 6329-183. The test system species and strain selected was the Crl:CD(SD) IGS BR rat received from Charles River Laboratories, Inc., identified using an implanted microchip device. At the initiation of treatment the rats were approximately 6-8 weeks of age and weighed between 100-300 g. Table 1. Test System Population Demographics for Study (6329-183) Number of Animals Study Group Male Female Dietary Levels (ppm) Group 1 Control 70 70 0 Group 2 Low 60 60 0.5 Group 3 Mid 60 60 2.0 Group 4 Mid-High 60 60 5.0 Group 5 High 70 70 20.0 Group 6 High Recovery 40 40 20.0 Specimen Collection and Analysis Sample specimens were collected by Covance (study 6329-183) and sent to the 3M Environmental Laboratory for analysis. On week 4 and week 14, 50 liver and 50 serum specimens were collected from Groups 1-5 males and females. On week 53, 39 liver and 19 serum specimens were collected from Groups 1 and 5 males and females. On day 719, 9 liver and 9 serum specimens were collected from Group 3 females. At the time of terminal sacrifice week 105), 164 liver and 164 serum specimens were collected from Groups 1-5 males and females. At the time of recovery sacrifice (week 106), 27 liver and 27 serum specimens were collected from Group 6 males and females. The number and type of specimens collected for analyses in the analytical phase of this study are presented below. Specimens Collected from Study Groups 1 through 5 (through 4/21/00): Serum Specimens--292 specimens Liver Specimens--312 specimens Specimens Collected from Study Group 6 (Recovery) on 4/24/00 and 4/27/00: Serum Specimens--27 specimens Liver Specimens--27 specimens 3M Environmental Laboratory Page 10 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Blood specimens were allowed to clot at room temperature and separated by centrifugation. Serum was then harvested and stored in a freezer at -60C to -80C until shipped to the 3M Environmental Laboratory. Liver specimens collected from each animal were flash frozen in liquid nitrogen and then stored in a freezer at -60C to -80C until shipped to the 3M Environmental Laboratory. Liver and sera specimens were shipped to the 3M Environmental Laboratory frozen and on dry ice. Sera and liver specimens were extracted beginning on May 27, 1998 using an ion pairing reagent and either ethyl acetate or methyl-tert-butyl ether (MtBE). Liver specimens were homogenized prior to the extraction procedure. Specimen extracts were analyzed using high-pressure liquid chromatography-electrospray/tandem mass spectrometry (HPLC-ESMSMS) in the multiple reaction monitoring mode. PFOS levels were quantitated by external calibration of extracted curves. Analytical details are included in this report. Specimen Receipt and Maintenance The 3M Environmental Laboratory received liver and serum specimens collected at predetermined time points during and at the end of the in-life phase of Covance Study No. 6329-183 from May 1998 through May 2000 from Covance. All specimens were received frozen on dry ice and were immediately transferred to storage at -20C 10C. Control matrices used in liver and sera analyses performed during TOX-002 were obtained from commercial sources and are presented in Appendix A (see Tables 4 and 5). Specimens analyzed at the 3M Environmental Laboratory will be maintained for a period of 10 years and will be stored at the laboratory at -20C 10C. Chemical Characterization Chemical characterization information on the test article used in this study is presented in Appendix A (see Table 6). Chemical characterization information on the analytical reference materials used in this study is presented in tabular form (Table 2) below. 3M Environmental Laboratory Page 11 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 2. Characterization of the Analytical Reference Materials Used in Study FACT TOX-002 Reference Material / Formula Acronym Source Potassium Perfluorooctanesulfonate C8F17SO3-K+ KPFOS 3M Specialty Chemicals 3M Specialty Chemicals 3M Specialty Chemicals 1H, 1H, 2H, 2HTetrahydroperfluorooctanesulfonic acid C8H4F13SO3H THPFOS ICN Biomedics, Inc. ICN a Used for analysis of week 4 and week 14 sera samples. b Samples were not corrected for purity. TBD--to be determined N/A--not applicable. This lot is exhausted and cannot be characterized. Expiration Date 08/31/00 2010 2010 01/01/2010 01/01/2010 Storage Conditions Ambient temperature Ambient temperature Ambient temperature (dry) Ambient temperature Ambient temperature Chemical Lot Number 171 193a 215a 53406 59909 Physical Description White crystalline powder White powder White powder Brown waxy solid Brown powder Purity 86.4% 88.0%b TBD TBD N/A Dose Confirmation Analyses Dose preparation methods and analysis were performed by Covance, using a validated analytical method provided by the Sponsor (MP-M383-MA), and are reported separately (Reference Covance 6329-183). Method Summaries Following is a brief description of the methods used during this analytical study by the 3M Environmental Laboratory. Detailed descriptions of the methods used in this study are located in Appendix C. As the present study progressed, more advanced methods evolved and earlier methods were used with deviations until amendments to the protocol were written. Protocol and method deviations are located in Appendix B of this report. 3M Environmental Laboratory PREPARATORY METHODS FACT-M-1.0. "Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Liver for Analysis Using HPLC-Electrospray/Mass Spectrometry". This method was used for week 4 specimens extracted on 6/11/98 and week 14 specimens extracted on 8/6/98. FACT-M-3.0, "Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Serum for Analysis using HPLC-Electrospray/Mass 3M Environmental Laboratory Page 12 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Spectrometry". This method was used for week 4 specimens extracted on 5/27/98 and week 14 specimens extracted on 7/27/98. ETS-8-4.1, "Extraction of Potassium Perfluorooctanesulfonate or other Fluorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry". This method was used for week 53 specimens extracted on 11/10/99, and day 719, week 105, and week 106 specimens extracted on 5/1/00 and 5/2/00. ETS-8-6.0, "Extraction of Potassium Perfluorooctanesulfonate or other Fluorochemical Compounds from Liver for Analysis using HPLC-Electrospray/Mass Spectrometry". This method was used for week 53 specimens extracted on 11/10/99 and 1/25/00, day 719 specimens extracted on 5/16/00 and 5/18/00, week 105 specimens extracted on 5/16-18/00 and 5/22/00, and week 106 specimens extracted on 5/16/00 and 5/18/00. An ion-pairing reagent was added to the specimen and the analyte ion pair was partitioned into ethyl acetate (FACT-M-1.0 and FACT-M-3.0) or MtBE (ETS-8-4.1 and ETS-8-6.0). The extract was transferred to a centrifuge tube and put onto a nitrogen evaporator until dry. Each extract was reconstituted in 1.0 mL of methanol, and then filtered through a 3 cc plastic syringe attached to a 0.2 m nylon filter into glass autovials. ANALYTICAL METHODS FACT-M-4.0, "Analysis of Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry". With the exception of week 4 sera specimens, data was worked up according to ETS-8-5.1 or ETS-8-7.0 and following control of bias documentation included in study binder. ETS-8-5.1, "Analysis of Potassium Perfluorooctanesulfonate or other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry". Sera run 7/15/98 was accepted despite the failure of the continuing calibration checks. Since compliance with method ETS-8-5.1 was in the protocol, deviations from it, including this one are also protocol deviations. A method deviation has been written. ETS-8-7.0, "Analysis of Potassium Perfluorooctanesulfonate or other Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry". The analyses were performed by monitoring one or more product ions selected from a single primary ion characteristic of PFOS using HPLC-ES/MS/MS. For example, molecular ion 499, selected as the primary ion for PFOS (C8F17SO3-) analysis, was fragmented further to produce ion 99 (FSO3-). The characteristic product ion 99 was monitored for quantitative analysis. 3M Environmental Laboratory Page 13 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 ANALYTICAL EQUIPMENT The actual analytical equipment settings used in the present analytical phase of this study varied slightly during actual data collection. The following is representative of the analytical equipment settings used during the analytical phase of this study. Liquid Chromatograph: Hewlett-Packard Series 1100 Liquid Chromatograph system Analytical column: Keystone BetasilTM C18 2x50 mm (5 m) Column temperature: Ambient Mobile phase components: Component A: 2mM ammonium acetate Component B: methanol Flow rate: 300 L/min Injection volume: 10 L Solvent Gradient: 13.5 minutes Time (minutes) 0.0 8.5 11.0 12.0 13.5 %B 40% 90% 90% 40% 40% Mass Spectrometer: Micromass API/Mass Spectrometer Quattro IITM Triple Quadrupole system Software: Mass LynxTM 3.1, 3.3, and 3.4 Cone Voltage: 30-60 V Collision Gas Energy: 25-45 eV Mode: Electrospray Negative Source Block Temperature: 150C 10C Electrode: Z-spray Analysis Type: Multiple Reaction Monitoring (MRM) Table 3. Negative Ions Monitored in 3M Laboratory Analyses Target Analyte Primary Ion (AMU) Product Ion (AMU) PFOS THPFOS 499.0 427.0 80.0, 99.0, 130.0 80.0 Deviations As the analytical phase of this study progressed, method parameters were evaluated to improve analyses. Earlier methods were used with deviations until amendments to the protocol were written. 3M Environmental Laboratory Page 14 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Data Quality Objectives and Data Integrity The following data quality objectives (DQOs) were indicated in the method performance section of ETS-8-5.1, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry and ETS-8-7.0, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry: Linearity: The coefficient of determination (r) equal to or greater than 0.980. Limits of Quantitation (LOQ): The LOQ for PFOS is 5.55 ng/mL for serum and 26.9 ng/g for liver in the respective method performance sections, however, the LOQ for a given run is based upon the concentration of the lowest acceptable standard in the run. Acceptable Matrix Spike Recoveries: 70-130% for sera / 50-150% for liver. Data Summary, Analyses, and Results Data quality objectives for the analytical phase of this study outlined in the 3M Lab methods ETS-8-5.1 and ETS-8-7.0 (see Appendix C) were met with the exceptions noted in this report. Summary of Quality Control Analyses Results Linearity: The coefficient of determination (r) of the standard curve was 0.985. Calibration Standards: With the exception of the week 4 sera data, quantitation of the target analytes was based on linear regression analysis of two extracted matrix curves weighted 1/x bracketing each group of samples. Calibration standards were not diluted and were spiked to be within the linear range of the instrument. Week 4 sera data was evaluated using an unweighted curve. High or low points on the curve may have been deactivated to provide a better linear fit over the curve range most appropriate to the data. Low curve points with peak areas less than two times that of the extraction blanks were deactivated to disqualify a data range that may have been significantly affected by background levels of the analyte. Occasionally, a single mid-range curve point that was an obvious outlier may have been deactivated. Quantitation of PFOS was based on the response of one or more specific product ions using the multiple response-monitoring mode of the instrument (see Appendix C, Analytical Methods). Limits of Quantitation (LOQ): The LOQ is equal to the lowest acceptable standard in the calibration curve (defined as a standard within 30% of the theoretical value), and is at least two times the analyte peak area detected in the extraction blanks. For both liver and sera analysis, the LOQ decreased over the course of the study as methods improved. The highest LOQs in both analyses occurred in the week 4 analysis and were 23.2 ng/mL (sera) and 27.8 ng/g (liver). Blanks: All blanks were below the lower limit of quantitation for PFOS. To simplify analyses that were complicated by endogenous levels of fluorochemicals in unexposed rat sera and liver, rabbit sera and liver were selected as a suitable surrogate matrix for blanks, curves, and CCVs. Precision: Not determined for this study. 3M Environmental Laboratory Page 15 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Matrix Spike Recoveries: Rat sera from 18 control animals were spiked prior to extraction. PFOS was spiked at approximately 75 ng/g, 100 ng/g, and 250 ng/g levels. With two exceptions, all Matrix Spike/Matrix Spike Duplicate (MS/MSD) were recovered at 30% of expected values. One MS, analyzed with the week 4 samples had a recovery of 167%; one MS analyzed with the week 53 samples was recovered at 131%. These high recoveries were confirmed. Because the remaining 16 spikes were acceptable, the high recoveries do not indicate serious analytical deficiencies. Rat liver from 20 control animals were spiked prior to extraction. PFOS was spiked at approximately 100 ng/g and 250 ng/g levels. Thirteen of the 20 spikes were within 50% of the expected value; seven were outside of this range. Four of the deviant spikes, analyzed with the day 719 samples, were mistakenly prepared from G3 and G6 animals instead of from control animals (G1). The high levels of PFOS in the tissue of these test animals obscured the relatively low level of material spiked (spike was <3% of endogenous). This mistake in preparation invalidates these results as indicators of method QC. Two of the remaining deviant spikes were analyzed with the week 4 samples and one deviant MS was analyzed with the week 53 samples. Because 13 of 16 matrix spikes that were prepared correctly were acceptable, the deviant recoveries do not indicate serious analytical deficiencies. All matrix spikes were prepared at levels approximate to G1 samples. Surrogates: The surrogate (THPFOS) was added to all specimens and standards before extraction, as stated in the methods. THPFOS was spiked into samples at concentrations within the linear range when samples were analyzed without dilution. Prior to May 5, 2000, THPFOS was not used for quantitation, but was used to monitor for gross instrument failure (see Appendix C, Analytical Methods). In analyses performed after May 5, 2000, the surrogate response of each analytical run was verified to determine that it did not vary more than 50% from the mean within each analytical run. At no time was THPFOS used for quantitation as an internal standard. No problems were observed with these data. Statement of Data Quality It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Summary of Specimen Results Specimens from Control Animals: Low levels of PFOS were often detected in the sera and liver of the control animals. Specimens from Dosed Animals: Detailed specimen data tables are presented in Appendices D and E. Statistical Methods and Calculations Statistical methods were limited to the calculation of means and standard deviations. All specimen results were used to calculate the mean values; the LOQ value was used for specimens with <LOQ results. See Appendix F for example calculations used to generate the liver and serum specimen data in FACT TOX-002. 3M Environmental Laboratory Page 16 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Statement of Conclusion Under the conditions of the present studies, PFOS was observed in the sera and liver of rats dosed with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) during the in-life phase of the study. Reference Covance Study No.: 6329-183, 104-Week Dietary Chronic Toxicity and Carcinogenicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Rats 3M Environmental Laboratory Page 17 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Appendix A: Identification of Test Article and Control Matrices Table 4. Characterization of the Control Matrices Used for Sera Analyses in Study FACT TOX-002 Control Matrix Rabbit Serum Rabbit Serum Rat Serum Rat Serum Source Expiration Date Storage Conditions Lot # Physical Description Sigma 2010 Frozen 47H4641 Rabbit Serum Sigma 2010 Frozen 118H8418 Rabbit Serum Sigma 2010 Frozen 17H9306 Rat Serum Sigma 2010 Frozen 19H89292 Rat Serum Table 5. Characterization of the Control Matrices Used for Liver Analyses in Study FACT TOX-002 Control Matrix Rabbit Liver Rabbit Liver Rabbit Liver Rabbit Liver Source Expiration Date Storage Conditions Lot # Physical Description N/R--not recorded CHW 2010 Frozen F00014 Rabbit Liver CHW 2010 Frozen F00016 Rabbit Liver N/R 2010 Frozen N/R Rabbit Liver CHW 2010 Frozen F00007 Rabbit Liver Table 6. Identification of the Test Article in Study FACT TOX-002 Test Article Chemical Name Source KPFOS Perfluorooctane sulfonic acid potassium salt 3M ICP/PCP Division Expiration Date 08/31/01 Storage Conditions Ambient temperature Chemical Lot # 217 Physical Description White crystalline powder Purity 86.9% 3M Environmental Laboratory Page 18 3M Medical Department Study: T-6295.4 Appendix B: Protocol, Amendments, Deviations Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 19 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratorv Protocol - Analytical Study Phase 104-Week Dietary Chronic Toxicity Study withPerfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295) in Rats In-Vivo Study Reference NumberC: ovance # 6329-183 Study Number: AMDT - 112296.1 Test Material: T-6295 Name and Address of Sponsor: 3MToxicologSyervices Building 220-2E-O2,3M Center St. Paul, MN 55144-1000 Name and Address of Testing Facility: 3M Environmental Technology and Services 935 Bush Avenue St. Paul, MN 55106 Proposed Experimental Start Date:May 25, 1998 Proposed Experimental Termination Date:December 31,2001 Method Numbers and Revisions FACT-M-1.0, Extraction ofPerfluorooctanesulfonatefrom Liver for Analysis using HPLC-ElectrosprayMass Spectrometry FACT-M-2.0, Analysis of Liver Extracts for Fluorochemicals using HPLC- Electrosprayhlass Spectrometry FACT-M-3.0, Extraction of Perfluorooctanesulfonatefrom Sera for Analysis using HPLC-Electrosprayhdas Spectrometry FACT-M-4.0, Analysis of Sera Extracts for Fluorochemicals usiHngPLC- Electrosprayhlass Spectrometry Author: Lisa Clemen Krih J. Hansen,PhD Study Director Date Study Director Management v Andrew M. Seacat, PhD Dat6 Sponsor Representative 3M Environmental Laboratory Page 1 of 5 Page 20 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 1.0 PURPOSE 1.1 According to this analytical protocol, the3M Environmental Laboratory will analyze the tissue and fluid samples from the Covance study number 638239,-"1104-Week Dietary Perfluorooctane Sulfonic Acid PotassiumSalt (PFOS T-6295) inRats." The collected data will be provided to the sponsor for iunstehe assessment of toxicological effects of the test material when administeredin the diets of rats forat least 104 weeks. 1.2 Data collected in the Environmental Laboratory will be considerednon-quantitative screening data until future studies have been conducted to determianbesolute recoveries of specific or general fluorochemical compounds. 2.0 REGULATORY COMPLIANCE 2.1 This analytical phase of the study will be conductedin accordance withthe FDA Good Laboratory Practices Regulations 21 CFR 58, with fthoellowing exceptions: 2.1.1 The analytical phaseis being conductedas a separate study and therefore has a separate Study Director, protocol, anfdinalreport, from those listed in the(ha.nce protocol 6329-183. 2.1.2 The characterization of the reference material, includingpurity, identity, and stability, are the responsibility otfhe sponsor. 2.1.3 Sample storage stability will not be determined. 3.0 TEST MATERIALS 3.1 Control, and reference Materials and Matrices 3.1.1 Analytical Reference Material: T-6295, from 3M ICPRCP Division 3.1.2 Analytical Reference Matrix: Rat liver, from Covance and rat serum, from Sigma Chemical Company. 3.1.3 AnalyticalControlMaterial: None. 3.1.4 Analytical Control Matrix: Rat liver, from Covance and rat serum, from Sigma Chemical Company. 3.2 Number of Test and Control Samples:Throughout the course of the study, liver and serum from 580 test animals and 140control animals will be madaevailable. Samples will be analyzed as requested by the sponsor orthe study director. Otherbiological tissues (kidney, bile, dermal application site, and cellular fraction) will abveailable for analysis if deemed appropriate. 3.3 Identification of Testand Control Samples: The samples will beidentified using the Covance animal identification number that consisotsf a letter andfive-digit number, plus the tissue identity and day identity (serum). 3.4 Purity and Identity of Reference Material:To be determined bySponsor. 3.5 Stability of Reference Material: To be determined by Sponsor. 3M Environmental Laboratory Page 2 of 5 Page 21 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3.6 Storage Conditions for Reference Materials: Reference materials will be stored at room temperature (3.1.l), and samples will be stored at -20 h 10C (3.1.2, 3.1.4). Test and Control samples will be receivedaccording to AMDT-S-10-0. 3.7 Disposition of Specimens: Biological tissues and fluids will be retained per GLP Regulation for the time period required forstudies longer than 28 days. 3.8 Safety Precautions: Refer to appropriate MSDS. Wear appropriate laboratory attire. Use caution when handlingknives for cutting tissue samples. 4.0 EXPERIMENTAL - Overview 4.1 The tissues from animals dosed as described (Covance# 6329-183), will be available for analysis for fluorine-containing compounds. At the discretion of the Study Director, aseries of analytical tests can be performed.All high dose and control sera and livers will be analyzed initially using HPLC-electrospray mass spectrometry to identify fluorine-containing compounds of interest presentin the sera and liver (if any). The screening fororganic fluoride in liver via combustion may be performetdo present definitive data forfluorine in the liver. Based on the findings from these analyses, additional samples, tissues,or fluids may be analyzed at the discretion of the Study Director to determine the presence of fluorochemicals in these matrices. 5.0 EXPERIMENTAL - Methods 5.1 Methods (attached): 5.1.1 FACT-M-1.0, "Extraction of Perfluorooctanesulfonatefrom Liver for Analysis using HPLC-Electrosprayhlass Spectrometry" 5.1.2 FACT-M-2.0, "Analysis of Liver Extracts for Fluorochemicals using HPLCElectrosprayMass Spectrometry" 5.1.3 FACT-M3.0, "Extraction of Perfluorooctanesulfonate fiom Serum for Analysis using HPLC-Electrosprayhlass Spectrometry" 5.1.4 FACT-M-4.0, "Analysis of Serum Extracts for Fluorochemicals using HPLCElectrospray/Mass Spectrometry" 6.0 DATA ANALYSIS 6.1 Quality Control: Matrix spikes will be extracted and analyzedto determine accuracyof the method. Also, continuing calibration checks will be analyzedto determine response bias. 6.2 Transformations: Any transformationsperformed on data collected duringthe analytical phase of the study will be documented in the final report. 6.3 Statistics: At the discretion of the Study Director,statisticsused may include regression analysis of serum concentrationswith time, averages, and standard deviations of concentrations for thedifferent dose groups. If necessary, simpletests such as the Student's t-test may be applied todetermine statistical difference. Any statistical analysis performed will be documented inthe final report. 6.4 Data Reporting: A final data package will be submitted to 3M Toxicology Services. The data package will includethe following with additionaldata included as deemed appropriate. 3M Environmental Laboratory Page 3of 5 Page 22 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 6.4.1 A s u m m a r y of individual sample results, reported as a concentration(weightlweight, weightlvolume) of fluoride per tissue or fluid, or as the mass of a specific fluorochemical (HPLC-electrospray masspectrometry)per unitof tissue or fluid. 6.4.2 A s u m m a r y of quality control results (continuing calibrationchecks, method blanks, instrumentblanks, matrix spikes, and matrixspike duplicates). 6.4.3 Certified copies or originals of the written validated methods. 6.4.4 Certified copies or originalsof sample identificationsheets sent from Covance. 6.4.5 Certified copies or originals of study specific raw data. 6.4.6 A s u m m a r y of key personnelinvolved with the analyticalphase of the study. 6.4.7 A signed QAU statement listing the dates of inspections and reports of findings to management andStudy Director. 7.0 MAINTENANCE OF RAW DATA AND RECORDS 7.1 The following raw data and records (or certified copies thereof) will be maintained in the study folder in the archivesaccordingto appropriateSOPs. 7.1.1 7.1.2 7.1.3 7.1.4 7.1.5 7.1.6 7.1.7 Approved protocol Approved methods Data summaries Study correspondence Shipping records Raw data Electronic copies of data 7.2 Supporting records to be retained separately fromthe study folder in the archives accordingto 3M ET & S S SOPs, will include, but not necessarilbye limited to the following: 7.2.1 7.2.2 7.2.3 7.2.4 7.2.5 7.2.6 Approved validation reports Training records Calibration records Instrument maintenance logs Standard operating procedures, equipment procedures, and methods Appropriate specimens 8.0REFERENCES 8.1 Approved AMDT standardoperatingprocedures. 8.2 Approved ETSstandard operatingprocedures. 9.0ATTACHMENTS 9.1 FACT-M-1.0, Extractionof Perfluorooctanesulfonatefrom Liver for Analysis using HPLCElectrosprayhfass Spectrometry Page 4 of 5 3M Environmental Laboratory Page 23 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 9.2 FACT-M-2.0, Analysis of Liver Extracts for Fluorochemicals using HPLCElectrosprayiMass Spectrometry 9.3 FACT-M3.0, Extraction of Perfluorooctanesulfonatefrom Serum for Analysis using HPLCElectrosprayiMass Spectrometry 9.4 FACT-M-4.0, Analysis of Serum Extracts for Fluorochemicals using HPLCElectrosprayiMass Spectrometry 3M Environmental Laboratory Page 5 of 5 Page 24 3M Medical Department Study: T-6295.4 351 EnvironmentTalechnology and Services PO Box 3333 I St. Paul, M N 55 133-333I 6127786442 Analytical Report: FACT TOX-002 LRN-U2121 Study Title 104-Week Dietary ChronicToxicity Study with PerfluorooctaneSulfonic Acid Potassium Salt (PFOS T-6295) in Rats PROTOCOL AMENDMENT NO.I Amendment Date: December 13,1999 Performing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project identification ET&SS FACT-TOX-002 LIRN u2121 3M Environmental Laboratory 3M Environmental Laboratory Page 25 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 - ~~~~~ LR~~ N-U2121 Protocol FACT Tox-002 Amendment Number 7 This amendment modifies the following portion(s) of the protocol: 7. PROTOCORLEADS: The following methods will be used: FACT-M-1.0, Extractionof Perfluorooctanesulfonate from Liver for Analysis usingHPLCElectrosprayMass Spectrometry FACT-M-2.0, Analysisof Liver Extracts for Fluorochemicalsusing HPLCElectrosprayMass Spectrometry FACT-M-3.0, Extraction of Perfluorooctanesulfonatefrom Sera for Analysis using HPLCElectrosprayMass Spectrometry FACT-M-4.0, Analysis ofSera Extracts for Fluorochemicalsusing HPLC-ElectrosprayNass Spectrometry AMENDTO READ: The following methods will be used: ETS-8-4.1, Extraction of Potassium Perfluorooctanesulfonateor Other Fluorochemical compounds fromSenun for Analysis Using HPLC-ElectrosprayNass Spectrometry ETS-8-5.1, Analysisof Potassium Perfluorooctanesulfonateor Other Fluorochemicals in Serum Extracts Using HPLC-ElectrosprayMass Spectrometry ETS-8-6.0, Extraction of Potassium Perfluorooctanesulfonateor other Fluorochemical Compounds from Liver foAr nalysis using HPLC-ElectrosprayMas Spectrometry ETS-8-7.0, Analysisof Potassium Perfluorooctanesulfonateor Other Fluorochemicals in Liver Extracts Using HPLC-ElectrosprayMass Spectrometry REASON: The methods originally listed were superseded during the course of the study. Andrew M. Seacat, Ph.D., Sponsor Representative Kristen J. Hansen, Ph.D., Study Director 3M Environmental Laboratory 3M Environmental Laboratory e Date /2/zQl q f Date Page 26 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Study Title 104-Week Dietary Chronic Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS T-6295)in Rats PROTOCOL AMENDMENT NO.2 Amendment Date: 20 January 2000 Performing Laboratory 3M Environmental Technology & Safety Services 3M EnvironmentalLaboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project Identification ET&SS LRN-U2121 FACT TOX-002 Covance Study: 6329-183 3M Medical Department Study: T-6295.4 3M Environmental Laboratory 3M Environmental Laboratory Page 27 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Protocol LRN-U2121 Amendment Number 2 This amendment modifies the followingportion(s)of the protocol: 7. PROTOCOL READS: There is no independent sectionof the protocol that addresses sample retention. AMENDTO READ: Specimens willbe maintained in the 3M Environmental Laboratory specimen archives. Any specimens sentto sub-contract laboratories wilbl e returned to the 3M Environmental Laboratory upon completion of analysis and submissiontheofsubcontract laboratory(s) final report. Specimens analyzed at sub-contract laboratories will be returned with the following documentation:the signed original chainof custody and records of storage conditions whilethaetsub-contract facility. REASON: To define in detail the appropriate disposition of specimens analyzed at subcontract laboratories. 2. PROTOCORLEADS: Section 7 states that the following rawdata and recordswill be retained in the study folder in the archives accordingto AMDT-S-8: Approved protocol and amendments; approved methods; data summaries; study correspondence; shipping records; raw data; and electronic copiesof data. Additionally, Section7 states that supporting records to be retained separately from the study foldienrthe archives according to AMDT-S-8 will include at least the following: Approved validation reports; training records; calibration records; instrument maintenance logs; Standard Operating Procedures, Equipment Procedures, and Methods; and appropriate specimens. AMENDTO READ: Section 7 states: "The original data, or copies thereof,will be available at the 3M Environmental Laboratoryto facilitate audits of the study durinitgs progress and before acceptance of thefinal report. When the final report is completeda,ll original paper data, including: approved protocol and amendmentst,udy correspondence, shipping records, raw data, approved final report, and electronic copoief sdata will be retained in the archives of the 3M Environmental Laboratory. Ail corresponding training records, calibration records, instrument maintenance logs, standard operating procedures, equipment procedures, and methodswill be retained in the archives of the facility performing each analysis." REASON: To direct subcontract laboratories in the dispositioonf the items listed above. 3M Environmental Laboratory 3M Environmental Laboratory Page 28 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Protocol LRN42121 Amendment Number2 3. PROTOCOL READS: . The study director for the present study was identifiinedthe protocol as Kristen J. Hansen, Ph.D. AMENDTO READ: The roleof study director for the present study was reassignetod John L. Butenhoff, Ph.D., as of20 January 2000. The previous study director, Kristen Hansenh, as been reassigned to the roloef Principle Analytical Investigator. REASON: The roleof study director was reassignedin an effortto ensure compliance with Good Laboratory Practice Standards that outline study personnreeql uirements (refer to 21 CFR Part 58). 4. PROTOCOL READS: The sponsorfor the present study was identified as AndreMw. Seacat, Ph.D. AMENDTO READ: The role of sponsor forthe present study was reassignetdo Marvin T. Case, D.V.M., Ph.D., as of20 January 2000. REASON: The change was made at the requeosft the sponsor. 3M Environmental Laboratory 3M Environmental Laboratory Page 29 3M Medical Department Study: T-6295.4 Amendment Approval Analytical Report: FACT TOX-002 LRN-U2121 Protocol LRN42121 Amendment Number2 Anxeew M. Seacat, Ph.D.,Outgoing Sponsor Representative Kristen J. Hansen, Ph.D.,Outgoing Study Director Date / / - f%h -zood Date lo F&/, Marvin T. Case, D. K M , Ph.D., Incoming Sponsor Representative 2zfk.f) Date John L. ButenhoB Ph.D.,Incoming Study Director Date 3M Environmental Laboratory 3M Environmental Laboratory Page 30 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Study Title 104-Week Dietary Chronic Toxicity Study with PerfluorooctaneSulfonic Acid Potassium Salt (PFOS T-6295) in Rats PROTOCOL AMENDMENT NO.3 Amendment Date: November 21,2000 Performing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project ldentification ET&SS LRN-U2121 FACT TOX-002 Covance 6329-183 3M Medical Department Study: T-6295 . 3M Environmental Laboratory 3M Environmental Laboratory Page 31 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Protocol FACT TOX-002 Amendment No. 3 This amendment modifiesthe following portion(s)of the protocol: 1. PROTOCOL READS: 1.2 Data Collected in the Environmental Laboratory will be considered non-quantitative screening data until futurestudies have been conductedto determine absolute recoveriesof specific or general fluorochemical compounds. AMENDTO READ: 1.2 If matrix spike studies provide accurate representationof recovery of endogenous levels of PFOS,the 3M Environmental Laboratory will provide semi-quantitativdeata for sera and liver samples collected from test animals. REASON: Due to improved analytical methods, the decision was matdoechange the purposeof the study results from non-quantitative to semi-quantitative. 3M Environmental Laboratory 3M Environmental Laboratory Page 32 3M Medical Department Study: T-6295.4 Amendment Approval Analytical Report: FACT TOX-002 LRN-U2121 Protocol FACT TOX-002 Amendment No. 3 L A I,/ Te-4- Marvin T. Case, D. V.M.,Ph.D., SponRsoerpresentaDtivaete 3 7 & d 2a3-cr John Lf Butenhoa Ph.D., StudDyaDteirec'tbr 3M Environmental Laboratory 3M Environmental Laboratory Page 33 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation 1. Identification Study I Project No. ...T......OX-0....02 (LIM.S...#. U-2..1_2_.1...).... Dtyepveiation a SOP X Method .-___.__I__ CI EquPiprmoceendture (Check one) _...-_I ____-__-._I____ .___".I_.____ 0 Prot_oco_l __0 _Ot.her: _ _ _ - _ ~ - I _ Document number ETS-8-7.0 ~ Date(s) of occurrence i 7/6/98,5/25/00,5/26/00, 6/12/00,6/14/00, i 6113/00,5/19/00, 5/22/00 11. Description _ Requ_ired ~ procedurelprocess: Section 10.1.2: Analyze a method blank and a matrix blank prior to ecaclihbration curve. Actual procedurelprocess: On several occasions, the blanks were either a) analyzed afterthe calibration curvesor b) not .l^a._n._a_ll^y-lzed__ at a. ll for a.particular MS m _ _ _ _ I "_-__.l.l---._-~I_-._-__ .. . Deviation written. Ill. Actions Taken (such as amendment issued,SOP revision, etc.) _ _ -.._.___I_ I Recorded by I IV. Impact on Study / Project (completed by Study Director or Project Lead) ....... ............ .. . -- -....... All blanks were analyzed atleast once during the course of the study. When blanks were run after the calibration curve, all control-of-bias practices were followed. In the instances where blanks were not m at all, the samples being analyzed were well abovtehe typical run LOQ. In addition, the vast majority of samples runwithout blanks were high level dilutions.The function of the blank is to determine if contamination was introduced during extractioann; y low-level contaminationwould be inconsequential to extracts requiringdilution. This deviation . has no . _ _ . ................ adverse a_ _f_fect. on the_ study data. ._ _. ........... ............................... -. .-. ....................... --.....-- - , ................................ ............. ......... ...- ............... ......... ... ~ ~ ................................... -........ ............. ........................ S pV S' M : ~ a r vCare SLdd D i e . e c G ; John B u L h a F C Deviation No. I (assigned by Study Directoror Project Lead at the end of study or project) Attachment A: Record of Deviation 3M Environmental Laboratory ETS-4-8.0 Page 34 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation 1. Identification 1.... Study / Project No. I. .. ......... Deviation Type (Check one) IIDocument Number 3LT- ... ~ . 773%-0 0 2 tl SOP tl Protocol ......... . ldtMethod 0 Equipment Procedure IJ Other: - _- ; Date(s) of occurrence 1 ................................... ................................... ......................................... 3M Environmental Laboratory Page 35 3M Medical Department Study: T-6295.4 I Study / Project No. Record of Deviation 1. identification CI Protocol 0 Other: Analytical Report: FACT TOX-002 LRN-U2121 I Required Procedure/process: s- ._I-.-__I_._. ............. ..1.__1111...1..1__................................ .......................................................................... I...___ Recorded - _L.--__ By , Date .. .......... ................................................ j Form ETS-4-8.0 3M Environmental Laboratory (assibgyned Deviation No. Study Director or Project Lead at the end of study or project) Page 36 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation I Study / Project No. Covance StudyNuIm. bIdere:n6t3i2fi9c-a@tsi3o/n3M Project Number Tox002 I ...................................................................................................................................... 1 , ......U....t.C.................................................................................... a SOP J DeviaTtiyopne Method Cl Equipment Procedure ..................................................................................................................................................................................................................................................... 0 b o(Cnhe)eck Protocol Other: I I ........................................................................................................................ ........................................................................................................................... ! of Document Number: FACT-M-4.0 Date(s) occurrence: 07/23/98 II 11. Description: Required Procedure/process:Method FACTs-tMate.4s.0, .................................................... ............................................................................................................................................................................................. 10.3.1 Analyze a mid-range calibration standaradfter every tenth sample. If a significant change (rt 30%) in peak area occurs, relative to thineitialstandard curve, stop therun.Only those samples analyzed beforethe last acceptablecalibrationstandard will be used. The remaining samplesmust be reanalyzed. ..................................................................................................................................................................................................................................................... 1 Calibration cheinckthsis data packet (c0o7l1le5c9t8edb on amelia) are not with in the *30% I .......................................................................................................................................... .?................................................................................................. criteria. . . .. .. ........................ .... I Actual Procedure/process: Calibration checks within &40%criteria will be accepted for this ............................................................................................................................................................................................................................................... data set. The 97 ppb standard pointsat the beginning and end of therun are excluded from ............................................................................................................................................................................................................................................ the calibration curve due to the analyst adding the wrong amount of standard. This error . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . appears in both curvaensd is th. e. r.e.fo. re verified. Del.e. t.i.o.n. .o. f. .th. .e. .9.7. .ppb curve. p.oin. t .ca.us.ed. . .......t..h....e....c...a...l..i.b....r..a..t..i..o...n.....c...u...r..v....e...t...o....h...a...v...e.....a....g...r...e..a...t..e...r....*......v...a...l..u...e.....a...n...d......a...n...o....v...e...r..a...l..l...b...e...t..t..e...r...f...i.t...t..o.....t..h...e....p....o...i..n...t..s........................ I 111. Actions Taken: (such as amendment issued, SOP revision, etc. :). . . . . . . . . This method deviation, increasingthe criteria range for this data set is the only action that will ............................................................................................................................................................................................................................................ need to be taken. ................................................................................................................................................................................................................................................ ...T....h...i..s....n...e...w......d....a...t..a....s...e...t...w....i..l..l...b....e....u...s...e..d......f..o...r....f..i..n...a...l.....r..e...s...u...l..t.s......................................................................................................................... .......................................................................................................................................................................................... Recorded By: Harold Johnson ., ......................................................... Date: ! September 5,2000 IV. Impact on Study/ Project .................................................................................................................................................................................................................................................... I.......................................................................................................................................................................................... I Authorized BY (Stua$ Director /Project k,&6a d ) . t/J,-. w . A * ,, *.cv\ '.W'Jc ......................................................... ; Date /r& 9w+ Form ETS-4-8.0 ' cafe Deviation No. (assigned by Study Director or ProjectaLtead the end of study or project) 3M Environmental Laboratory Page 37 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation 1. Identification - I __ ___ . Study / Project No. (Check one) a Protocol @ Other: Document Number .................................................................................................................. dl CFR 53.1ao h ) 01) . 1 Date(s) of occurrence I I O d 2 J 1LiLi 11. Description: !..n..e.d..-.....- Actual Procedure/process: --.---_-____- ____ .......... L_ l.-i, . _ r i l e ........ .. lana...-.... . . . .d ......... S p . n . . m R e p L e A e !.@- .. ... ...... &&.Ar h Recorded By M IV. Impact on Study/ Project I Date i - Authorized By 9-p 3M Environmental Laboratory Form ETS-4-8.0 _.._..-._____._.-_.____I Project Lead) . -. , Date Deviation No. 5 (assigned by Study Director or Project Lead at the end of study or project) 3M Environmental Laboratory Page 38 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Number Record of Deviation I. Identification Deviation Type (Check one) Document 9.-Lt..-mx..--.CQ.aO~~~..Lll-lP.~,a9=..18_3 0 SOP 0Method IY EquipmPeronctedure Protocol Cl Other: - Date(s)-.ce_ I ! I~ilo/?7 11. Description: Ill. Actions Taken: (such as amendment issued, SOP revision, etc.) - ~ * s _ D ~ ~ h a ~ ~ ~ - . - .._.__ w r ~ ~ - ~ ~ ~ ~ ~ ~ . ~ ~ Recorded By A&JJn& IV. Impact on Study/ Project iI Date I 1 lalor[qq 3M Environmental Laboratoly F o ET~S-4-8.0 3M Environmental Laboratory Deviation No. b (assigned by Study Director or PraLotejeacdt the end of study or project) Page 39 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation 1. Identification I .. --...... Study / Project No. - C b ? ! k ~ ~ ! ? _ & ... . a Deviation Type __..._I__.._..__._..___) SOP OV.G_nCe_..-.d3.X~~-~8~ .__ CI Method CI EquipmPeronct edure I .. ........ .A_ct_ual Procedure/process: M-~~Q.L!IJ...LD IAU ~-l.ed.-.. ,.._-_-___.__-__ . ... Ill. Actions Taken: (such as amendment issued, SOP revision, etc.) . n.Li d . h ....&V~L.. ~ . U . L uUrijL-.&/-hd D - L - , Recorded By I ~ IV. Impact on Study/ Project 1 i I Date &l 9 ? .___......._..._...._.._-___....._I...._._.I-._....._.._._L.._I~.._... I .. . . . ~ Authorized By (Study Director - --- /Project Lead) I . - II I Date I 3M Environmental Laboratory FOKWETS-4-8.0 I DeviNaoti.on f Y (assigned by Study Director or ProjecLtead at the end of study or project) 3M Environmental Laboratory Page 40 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Record of Deviation 1. Identification Study I Project No. -~-..______ x . - ~ ~ ~ - _c_ 3eviation Type (Check one) . cl___ SOP 0 Protocol . . BMethod Cl Equipment Procedure 0 Other: __c_ ___ Document Number 7 5 - 8- 03-0 I - ____.___C. _.- I Date(s) of occurrence 3/00 11. Description: 8\00 Required Procedure/process: ........ . Ill. Actions Taken: (such as amendment issued, SOP revision. etc.) IV. Impact on Study/ Project 3Mknvironmkntal Laboratory F o ET~S-4-8.0 3M Environmental Laboratory Deviation No. 0 (assigned by Study Director or Project Lead at the end of study or project) Page 41 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Appendix C: Extraction and Analytical Methods This appendix includes the following methods: FACT-M-1.0, Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Liver for Analysis using HPLC-Electrospray/Mass Spectrometry (8 pages) FACT-M-3.0, Extraction of Potassium Perfluorooctanesulfonate or Other Anionic Fluorochemical Surfactants from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry (8 pages) ETS-8-4.1, Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages) ETS-8-6.0, Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Liver for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages) FACT-M-2.0, Analysis of Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry (8 pages) FACT-M-4.0, Analysis of Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry (8 pages) ETS-8-5.1, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (9 pages) ETS-8-7.0, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry, (10 pages) 3M Environmental Laboratory Page 42 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 43 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 44 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 45 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 46 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 47 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 48 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 49 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 50 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 51 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 52 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 53 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 54 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 55 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 56 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 57 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 58 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 59 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 60 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 61 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 62 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 63 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 64 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 65 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 66 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 67 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 68 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 69 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 70 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 71 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 72 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 73 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 74 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 75 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 76 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 77 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 78 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 79 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 80 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 81 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 82 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 83 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 84 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 85 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 86 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 87 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 88 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 89 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 90 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 91 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 92 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 93 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 94 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 95 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 96 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 97 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 98 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 99 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 100 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 101 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 102 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 103 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 104 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 105 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 106 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 107 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 108 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 109 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 110 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 111 3M Medical Department Study: T-6295.4 Study #: FACT-TOX-002 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Lab -- Method Modification Method: ETS-8-5.1 "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicalsin Sera Extracts Using HPLC-ElectrosprayAMass Spectrometry" Section modified: Effective date of modifications: 10.3.2, 14.5.1, add sections 14.3.2-14.3.6 April 26, 1999 Section 10.3.2 Method reads: 10.3.2 Analyze a mid-rangecalibration standard after every tenth sample,with aminimum of one per batch. Modify method to read: 10.3.2 Analyze a mid-range calibration standard at least after every ten samples, with a minimum of one per batch. Section 14.5.1 Method reads: 14.5.1 Continuing calibration verificationpercent recoveriesmust be within & 30% of the spiked concentration. Modify method to read: 14.5.1 At least one continuingcalibrationverificationper ten samples must show apercent recovery within +l-30% of the spiked concentration. Section 14.3.2 Method reads: NA Modify method to read: 14.3.2 The second (bracketing)calibration curve maybe deactivatedif instrumental drift affects the data. The first curve and acceptablecalibration checks shall bracket usable data. 3M Environmental Laboratory Page 112 3M Medical Department Study: T-6295.4 Study #: FACT-TOX-002 Analytical Report: FACT TOX-002 LRN-U2121 Section 14.3.3 Method reads: NA Modify method to read: 14.3.3 Calibration standards with peak areas less than 2 timetshe curve matrix blank should be deactivated to disqualify a datarange that maybe affected by background levels of the analyte. Section 14.3.4 Method reads: NA Modify method to read: 14.3.4 Low or high curve points may be deactivated to optimize a linear range appropriate to the data. Section 14.3.5 Method reads: NA Modi@ method to read: 14.3.5 A curve point may be deactivated if it deviates more than 30% from the theoretical value when the curve is evaluated over a linearrange appropriate to the data. Section 14.3.6 Method reads: NA Modify method to read: 14.3.6 A valid calibration curve must contain at least 5 active points. Signatu Signature of Sponsor and date L 2 J ! 2% Signature of Study Director anddate 3M Environmental Laboratory Page 113 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 114 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 115 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 116 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 117 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 118 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 119 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 120 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 121 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 122 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 123 3M Medical Department Study: T-6295.4 Study #: FACT-TOX-002 Analytical Report: FACT TOX-002 LRN-U2121 31111 Environmental Lab -- Method Modification Method: ETS-8-7.0 "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Liver Extracts Using HPLC-ElectrosprayMass Spectrometry" Section modified: Effective date of modifications: 10.3.2, 14.5.1, add sections 14.3.2-14.3.6 July 22, 1999 Section 10.3.2 Method reads: 10.3.2 Analyze a mid-range caliiration standard after every tenth sample, with a minimurn of one per batch. Modify method to read: 10.3.2 Analyze a mid-range calibration standard at least after every ten samples,with a minimumof one per batch. Section 14.5.1 Method reads: 14.5.1 Continuing calibration verificationpercent recoveries mustbe within f 30%of the spiked concentration. Modify method to read: 14.5.1 At least one continuing calibrationverification per ten samples mussthow a percent recovery within +l-30% ofthe spiked concentration. Section 14.3.2 Method reads: NA Modify method to read: 14.3.2 The second (bracketing)calibration curvemay be deactivated if instrumentaldrift affects the data. The fnst curve and acceptable calibration checks shall bracket usable data. 3M Environmental Laboratory Page 124 3M Medical Department Study: T-6295.4 ~~ Study #: FACT-TOX-002 Analytical Report: FACT TOX-002 LRN-U2121 Section 14.3.3 Method reads: NA Modify method to read: 14.3.3 Calibration standards with peak areas less tha2n times the curvematrix blank should be deactivated to disqualify daata range that may be affected by background leveolsf the analyte. Section 14.3.4 Method reads: NA Modify method to read: 14.3.4 Low or high curvepoints may be deactivated to optimize alinear range appropriateto the data. Section 14.3.5 Method reads: NA Modify method to read: 14.3.5 A curve point may be deactivatedif it deviates more than30% from the theoretical value when the curve is evaluated over a linear range appropriatteo the data. Section 14.3.6 Method reads: NA Modify method to read: 14.3.6 A valid calibration curve must contain at least 5 active points. 1 Signalire of PAI and date Ill27 /In, Signatureof Sponsor anddate 9 2 LLi&+g Signature of Study Director anddate / 3 d !&&f / 3 b ? 2oeo 3M Environmental Laboratory Page 125 3M Medical Department Study: T-6295.4 Appendix D: Data Summary Tables Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 126 3M Medical Department Study: T-6295.4 3M Environmental Laboratory Table 7. FACT TOX-002 Data Summary of PFOS Concentration--Serum (g/mL) Timepoint Sex Group 1 Control Average SD Group 2 Low Average SD Group 3 Mid Average SD Group 4 Mid-High Average SD Week 4a Week 14a Male Female Male Female <LOQb (n = 5) 0.0259 0.00663 (n = 5) <LOQc (n = 5) 2.67 4.58 (n = 5) 0.907 0.0619 (n = 5) 1.61 0.207 (n = 5) 4.04 0.801 (n = 5) 6.96 0.993 (n = 4d) 4.33 1.16 (n = 5) 6.62 0.499 (n = 5) 17.1 1.22 (n = 5) 27.3 2.34 (n = 5) 7.57 2.17 (n = 5) 12.6 1.73 (n = 5) 43.9 4.90 (n = 5) 64.4 5.48 (n = 5) Group 5 High Average SD 41.8 7.92 (n = 5) 54.0 7.34 (n = 5) 148 13.8 (n = 5) 223 22.4 (n = 5) Group 6 High Recovery Average SD Week 53 Day 719 Week 105 Week 106 Male Female Male Female Male Female Male Female 0.0249 0.0182 (n = 5) 0.395 0.777 (n = 5) 0.0118 0.0104 (n = 11) 0.0836 0.134 (n = 24) 1.31 1.30 (n = 10) 4.35 2.78 (n = 15) 20.2 13.3 (n = 9) 7.60 8.60 (n = 17) 22.5 23.5 (n = 25) 75.0 45.7 (n = 15) 146 33.5 (n = 4) 220 44.0 (n = 5) 69.3 57.9 (n = 22) 233 124 (n = 25) 2.42 5.09 (n = 10) 9.51 8.70 (n = 17) Analytical Report: FACT TOX-002 LRN-U2121 a Not corrected for purity of the standard material. b LOQ--Limit of Quantitation = 0.00910 g/mL c LOQ--Limit of Quantitation = 0.0457 g/mL d C92987F sample spilled during extraction, no sample remaining for analysis. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Page 127 3M Medical Department Study: T-6295.4 3M Environmental Laboratory Table 8. FACT TOX-002 Data Summary of PFOS Concentration--Liver (g/g) Timepoint Week 4a Week 14a Week 53 Day 719 Week 105 Week 106 Sex Male Female Male Female Male Female Male Female Male Female Male Female Group 1 Control Average SD 0.104 0.0673 (n = 5) 0.107 0.0486 (n = 5) 0.459 0.0573 (n = 5) 12.0 22.4 (n = 5) 0.635 1.04 (n = 10) 0.923 1.77 (n = 10) Group 2 Low Average SD 11.0 2.31 (n = 5) 8.71 0.552 (n = 5) 23.8 3.45 (n = 5) 19.2 3.77 (n = 5) Group 3 Mid Average SD 31.3 5.84 (n = 5) 25.0 6.11 (n = 5) 74.0 6.16 (n = 5) 69.2 3.46 (n = 5) 0.114 0.148 (n = 11) 0.185 0.184 (n = 24) 7.83 7.34 (n = 10) 12.9 6.81 (n = 15) 55.1 31.5 (n = 9) 26.4 20.4 (n = 17) Group 4 Mid-High Average SD 47.6 12.5 (n = 5) 83.0 14.1 (n = 5) 358 28.8 (n = 5) 370 22.3 (n = 5) 70.5 63.1 (n = 25) 131 61.4 (n = 15) Group 5 High Average SD 282 45.3b (n = 5) 373 44.1b (n = 5) 568 107 (n = 5) 635 49.0 (n = 5) 435 96.9 (n = 9) 560 180 (n = 10) Group 6 High Recovery Average SD 189 141 (n = 22) 381 176 (n = 25) 3.12 5.97 (n = 10) 12.9 10.4 (n = 17) Analytical Report: FACT TOX-002 LRN-U2121 a Not corrected for purity of the standard material. b The values in this mean were tentative It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Page 128 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 9. Week 4 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92506M <LOQ Group 1 Control C92524M C92526M C92529M <LOQ <LOQ <LOQ C92546M <LOQ C92574M 0.910* Group 2 Low C92575M C92610M C92613M 0.989* 0.944* 0.852* C92618M 0.842* C92646M 3.97* Group 3 Mid C92650M C92652M C92668M 2.85* 4.80* 5.98* C92678M 4.04* C92715M 8.46* Group 4 Mid-High C92718M C92731M C92734M 9.89* 4.03* 7.69* C92744M 7.81* C92752M 29.0* Group 5 High C92759M C92779M C92793M 40.7* 49.5* 42.7* C92798M 47.0* Note: Not corrected for purity of the standard material. LOQ--Limit of Quantitation = 0.00910 g/mL * Continuing calibration verifications did not meet 30% criteria; data may be biased low. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 129 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 10. Week 4 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL Group 1 Control C92861F C92864F C92914F C92919F 0.0227 0.0309 0.0347 0.0193 C92926F 0.0216 C92982F 1.69* Group 2 Low C92941F C92945F C92950F 1.67* 1.89* 1.38* C92969F 1.44* C92996F 6.84* Group 3 Mid C93006F C93008F C93031F 5.75* 6.85* 6.65* C93045F 6.99* C93058F 15.3* Group 4 Mid-High C93067F C93070F C93075F 13.2* 11.6* 10.8* C93084F 12.1* C93114F 62.8* Group 5 High C93123F C93142F C93144F 52.4* 56.4* 42.7* C93159F 55.8* Note: Not corrected for purity of the standard material. * Continuing calibration verifications did not meet 30% criteria; data may be biased low. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 130 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 11. Week 14 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92509M <LOQ Group 1 Control C92511M C92521M C92528M <LOQ <LOQ <LOQ C92532M <LOQ C92593M 4.70 C92600M 4.58 GrLoouwp 2 C92616M 4.09 C92621M 4.13 C92627M 2.69 C92640M 15.9 C92645M 16.9 GrMouidp 3 C92662M 16.1 C92676M 17.9 C92684M 18.8 C92713M 49.1 C92714M 37.2 MGirdo-uHpig4h C92719M 41.6 C92722M 43.3 C92728M 48.2 C92765M 139 C92777M 145 GrHoiugph 5 C92789M 149 C92799M 136 C92812M 171 Note: Not corrected for purity of the standard material. LOQ--Limit of Quantitation = 0.0457 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 131 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 12. Week 14 Reported PFOS Levels in Sera Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92880F 0.332 Group 1 Control C92887F C92898F C92903F 10.8 0.252 1.62 C92905F 0.333 C92944F 5.90 C92962F 8.21 GrLoouwp 2 C92967F 7.23 C92978F 6.50 C92987F * C92993F 28.7 C93000F 26.7 GrMouidp 3 C93018F 25.1 C93023F 25.4 C93035F 30.6 C93051F 56.7 C93064F 64.5 MGirdo-uHpig4h C93071F 71.3 C93085F 62.3 C93109F 67.3 C93111F 229 C93127F 210 GrHoiugph 5 C93143F 258 C93155F 220 C93169F 199 Note: Not corrected for purity of the standard material. * Sample spilled during extraction, no sample remaining for analysis. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 132 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 13. Week 53 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92504M 0.0278 Group 1 Control C92512M C92534M C92562M 0.0149 0.0251 0.0529 C92570M <LOQ C92778M 96.6 Group 5 C92795M 162 High C92796M 171 C92817M 154 LOQ--Limit of Quantitation = 0.00395 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Table 14. Week 53 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92876F 0.0310 Group 1 Control C92889F C92899F C92923F 1.78 0.0656 0.0891 C92930F <LOQ C93112F 240 C93120F 144 GrHoiugph 5 C93154F 223 C93163F 245 C93171F 250 LOQ--Limit of Quantitation = 0.00395 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 133 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 15. Day 719 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 Dosage Group Group 3 Mid Specimen ID C92991F G3 Day 719 C93003F G3 Day 719 C93007F G3 Day 719 C93011F G3 Day 719 C93022F G3 Day 719 C93039F G3 Day 719 C93040F G3 Day 719 C93047F G3 Day 719 C93048F G3 Day 719 PFOS g/mL 15.1 13.0 30.9 3.57 2.02 27.6 43.8 21.9 24.3 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 134 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92503M 0.0148 C92505M 0.0161 C92510M 0.0285 C92513M 0.0127 Group 1 Control C92514M C92518M C92541M 0.0325 <LOQ <LOQ C92542M <LOQ C92544M <LOQ C92551M <LOQ C92569M <LOQ C92577M 0.309 C92583M 0.212 C92590M 2.55 C92597M 1.95 Group 2 Low C92598M C92601M 0.230 3.94 C92602M 1.39 C92619M 0.461 C92623M 2.05 C92626M 1.48 C92631M 8.98 C92633M 14.3 C92637M 1.81 C92641M 15.1 C92642M 6.05 C92643M 2.75 C92644M 1.21 Group 3 Mid C92649M C92653M C92657M 8.63 0.487 5.20 C92659M 14.4 C92660M 1.66 C92669M 3.13 C92674M 35.3 C92682M 4.77 C92683M 2.72 C92690M 2.83 LOQ--Limit of Quantitation = 0.00428 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radiolabeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 135 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 (continued) Dosage Group Specimen ID PFOS g/mL C92691M 4.48 C92693M 7.71 C92694M 74.2 C92695M 75.6 C92696M 38.7 C92698M 12.1 C92699M 73.3 C92700M 28.8 C92702M 3.14 C92704M 10.9 C92705M 23.0 C92708M 9.72 MGirdo-uHpig4h C92716M 13.5 C92717M 3.01 C92724M 12.8 C92726M 38.8 C92730M 6.72 C92735M 24.4 C92736M 4.10 C92739M 5.72 C92740M 35.7 C92742M 2.28 C92747M 45.7 C92748M 3.66 C92750M 3.40 LOQ--Limit of Quantitation = 0.00428 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radiolabeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 136 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 16. Week 105 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 (continued) Dosage Group Specimen ID PFOS g/mL C92753M 35.8 C92757M 196 C92761M 27.3 C92762M 130 C92774M 10.4 C92775M 11.1 C92776M 108 C92780M 67.4 C92782M 16.7 C92786M 27.5 Group 5 C92788M 118 High C92791M 21.4 C92792M 18.0 C92800M 64.2 C92802M 169 C92803M 141 C92804M 127 C92808M 37.2 C92809M 6.02 C92814M 89.2 C92815M 11.9 C92818M 90.1 LOQ--Limit of Quantitation = 0.00428 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radiolabeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 137 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92866F 0.624 C92867F 0.225 C92868F 0.0467 C92869F 0.306 C92871F 0.00650 C92873F 0.0602 C92874F 0.0427 C92877F 0.100 C92881F 0.0258 C92882F 0.0483 C92885F <LOQ (1) Group 1 Control C92890F C92892F 0.0675 0.0140 C92895F 0.0233 C92896F 0.0407 C92897F 0.0443 C92906F 0.0795 C92907F 0.0176 C92909F 0.0402 C92911F 0.0687 C92912F 0.0311 C92913F 0.0575 C92925F <LOQ (2) C92927F 0.0229 C92936F 8.72 C92938F 0.349 C92946F 9.08 C92953F 6.64 C92957F 5.67 C92960F 1.70 C92964F 5.97 GrLoouwp 2 C92970F 1.73 C92973F 1.34 C92974F 4.06 C92975F 3.72 C92983F 6.81 C92984F 2.78 C92986F 5.24 C92988F 5.76 LOQ--Limit of Quantitation = (1) 0.00428 g/mL, (2) 0.00848 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 138 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 (continued) Dosage Group Specimen ID PFOS g/mL C93059F 103 C93060F 89.5 C93062F 102 C93063F 171 C93072F 114 C93077F 38.0 C93078F 25.9 MGirdo-uHpig4h C93079F 72.8 C93080F 73.6 C93081F 70.5 C93090F 99.1 C93098F 5.17 C93101F 117 C93102F 11.4 C93107F 33.2 LOQ--Limit of Quantitation = (1) 0.00428 g/mL, (2) 0.00848 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 139 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 17. Week 105 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 (continued) Dosage Group Specimen ID PFOS g/mL C93113F 403 C93115F 286 C93124F 160 C93125F 353 C93133F 242 C93135F 274 C93137F 143 C93139F 375 C93140F 3.85 C93146F 51.5 C93149F 432 C93151F 139 GrHoiugph 5 C93153F 121 C93157F 28.6 C93158F 287 C93161F 103 C93162F 446 C93164F 321 C93165F 165 C93166F 189 C93168F 339 C93174F 304 C93177F 248 C93178F 216 C93179F 190 LOQ--Limit of Quantitation = (1) 0.00428 g/mL, (2) 0.00848 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 140 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 18. Week 106 Reported PFOS Levels in Sera of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C92821M 8.32 C92823M 0.533 C92827M 0.0303 C92829M 0.0243 Group 6 High Recovery C92833M C92834M 0.0795 0.0138 C92848M 14.9 C92851M 0.0331 C92853M 0.210 C92856M <LOQ LOQ--Limit of Quantitation = 0.00482 g/mL It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Table 19. Week 106 Reported PFOS Levels in Sera of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/mL C93181F 5.76 C93182F 1.69 C93183F 5.68 C93184F 1.64 C93185F 11.8 C93190F 31.6 C93192F 16.8 C93197F 9.35 HigGhrRoeucpo6very C93198F 8.63 C93201F 27.0 C93202F 10.1 C93205F 0.0594 C93209F 6.57 C93211F 12.3 C93216F 2.85 C93219F 2.39 C93220F 7.44 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 141 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 20. Week 4 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92506M <LOQ Group 1 Control C92524M C92526M C92529M 0.169 0.186 <LOQ C92546M <LOQ C92574M 12.4 C92575M 9.67 GrLoouwp 2 C92610M 8.54 C92613M 14.2 C92618M 9.94 C92646M 40.7 C92650M 26.1 GrMouidp 3 C92652M 31.2 C92668M 32.0 C92678M 26.7 C92715M 53.5 C92718M 59.6 MGirdo-uHpig4h C92731M 26.7 C92734M 49.8 C92744M 48.3 C92752M 219* C92759M 264* GrHoiugph 5 C92779M 342* C92793M 286* C92798M 298* Note: Not corrected for purity of the standard material. LOQ--Limit of Quantitation = 0.0552g/g * Results were outside the range of the curve and should be considered estimates. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 142 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 21. Week 4 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g Group 1 Control C92861F C92864F C92914F C92919F 0.0817 0.0738 0.184 0.0700 C92926F 0.126 C92982F 9.09 C92941F 7.99 GrLoouwp 2 C92945F 9.40 C92950F 8.43 C92969F 8.67 C92996F 28.9 C93006F 14.6 GrMouidp 3 C93008F 29.7 C93031F 27.1 C93045F 24.8 C93058F 107 C93067F 83.9 MGirdo-uHpig4h C93070F 77.0 C93075F 70.7 C93084F 76.7 C93114F 435* C93123F 360* GrHoiugph 5 C93142F 395* C93144F 317* C93159F 359* Note: Not corrected for purity of the standard material. * Results were outside the range of the curve and should be considered estimates. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 143 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 22. Week 14 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92509M 0.440 Group 1 Control C92511M C92521M C92528M 0.542 0.492 0.403 C92532M 0.418 C92593M 24.6 C92600M 19.3 GrLoouwp 2 C92616M 27.2 C92621M 21.2 C92627M 26.6 C92640M 82.7 C92645M 73.5 GrMouidp 3 C92662M 68.3 C92676M 68.3 C92684M 77.4 C92713M 375 C92714M 372 MGirdo-uHpig4h C92719M 377 C92722M 308 C92728M 356 C92765M 722 C92777M 618 GrHoiugph 5 C92789M 559 C92799M 456 C92812M 485 Note: Not corrected for purity of the standard material. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 144 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 23. Week 14 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92880F 1.02 Group 1 Control C92887F C92898F C92903F 52.0 0.697 5.26 C92905F 1.18 C92944F 18.9 C92962F 17.7 GrLoouwp 2 C92967F 24.8 C92978F 14.5 C92987F 19.8 C92993F 69.0 C93000F 71.1 GrMouidp 3 C93018F 67.4 C93023F 64.9 C93035F 73.9 C93051F 355 C93064F 361 MGirdo-uHpig4h C93071F 355 C93085F 373 C93109F 408 C93111F 692 C93127F 619 GrHoiugph 5 C93143F 621 C93155F 675 C93169F 569 Note: Not corrected for purity of the standard material. It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 145 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 24. Week 53 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92501M 0.0326 C92504M 0.358 C92507M 0.301 C92512M 0.283 Group 1 Control C92517M C92523M 0.761 0.529 C92534M 0.359 C92540M 0.106 C92562M 3.52 C92570M 0.103 C92751M 559 C92754M 486 C92755M 486 C92778M 279 GrHoiugph 5 C92790M 405 C92795M 554 C92796M 427 C92817M 403 C92820M 316 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 146 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 25. Week 53 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92862F 5.66 C92876F 0.131 C92889F 2.08 C92894F 0.276 Group 1 Control C92899F C92910F 0.217 0.198 C92917F 0.246 C92922F 0.0580 C92923F 0.154 C92930F 0.215 C93112F 296 C93116F 534 C93117F 514 C93120F 430 Group 5 C93130F 504 High C93138F 565 C93147F 619 C93154F 424 C93163F 883 C93171F 830 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 147 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 26. Day 719 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Group 3 Mid Specimen ID C92991F C93003F C93007F C93011F C93022F C93039F C93040F C93047F C93048F PFOS g/g 43.6 51.7 97.2 13.2 9.02 79.7 94.1 53.3 53.8 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 148 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 Dosage Group Group 1 Control Group 2 Low Group 3 Mid Specimen ID C92503M C92505M C92510M C92513M C92514M C92518M C92541M C92542M C92544M C92551M C92569M C92577M C92583M C92590M C92597M C92598M C92601M C92602M C92619M C92623M C92626M C92631M C92633M C92637M C92641M C92642M C92643M C92644M C92649M C92653M C92657M C92659M C92660M C92669M C92674M C92682M C92683M C92690M PFOS g/g 0.152 0.106 0.511 0.0663 0.233 <LOQ 0.0283 0.0342 0.0291 <LOQ 0.0690 1.60 1.64 3.89 17.2 2.02 21.6 10.0 1.39 13.4 5.61 41.5 51.2 3.82 3.35 23.9 18.5 4.32 54.0 2.85 19.8 61.4 10.6 17.4 59.0 38.2 16.9 21.5 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 149 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 (continued) Dosage Group Group 4 Mid-High Specimen ID C92691M C92693M C92694M C92695M C92696M C92698M C92699M C92700M C92702M C92704M C92705M C92708M C92716M C92717M C92724M C92726M C92730M C92735M C92736M C92739M C92740M C92742M C92747M C92748M C92750M PFOS g/g 27.7 30.5 208 195 120 18.9 164 69.1 13.1 65.3 67.7 51.6 85.8 13.7 46.1 95.0 18.0 73.7 15.1 35.6 155 7.16 170 11.5 6.80 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 150 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 27. Week 105 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 (continued) Dosage Group Group 5 High Specimen ID C92753M C92757M C92761M C92762M C92774M C92775M C92776M C92780M C92782M C92786M C92788M C92791M C92792M C92800M C92802M C92803M C92804M C92808M C92809M C92814M C92815M C92818M PFOS g/g 113 329 80.2 175 39.4 35.0 320 163 53.1 98.6 385 69.0 54.8 159 409 411 330 119 23.3 358 72.0 352 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 151 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Group 1 Control Specimen ID C92866F C92867F C92868F C92869F C92871F C92873F C92874F C92877F C92881F C92882F C92885F C92890F C92892F C92895F C92896F C92897F C92906F C92907F C92909F C92911F C92912F C92913F C92925F C92927F PFOS g/g 0.907 0.367 0.108 0.250 <LOQ 0.254 0.151 0.271 0.0904 0.228 <LOQ 0.248 0.0490 0.113 0.116 0.158 0.328 0.0346 0.113 0.206 0.0667 0.183 <LOQ 0.161 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 152 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 (continued) Dosage Group Group 2 Low Group 4 Mid-High Specimen ID C92936F C92938F C92946F C92953F C92957F C92960F C92964F C92970F C92973F C92974F C92975F C92983F C92984F C92986F C92988F C93059F C93060F C93062F C93063F C93072F C93077F C93078F C93079F C93080F C93081F C93090F C93098F C93101F C93102F C93107F PFOS g/g 10.5 1.72 15.3 20.1 14.5 4.94 20.1 6.69 5.08 15.8 13.5 27.0 8.58 13.2 17.2 183 133 242 133 167 152 61.7 113 149 118 186 19.2 193 40.0 79.8 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 153 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 28. Week 105 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 (continued) Dosage Group Group 5 High Specimen ID C93113F C93115F C93124F C93125F C93133F C93135F C93137F C93139F C93140F C93146F C93149F C93151F C93153F C93157F C93158F C93161F C93162F C93164F C93165F C93166F C93168F C93174F C93177F C93178F C93179F PFOS g/g 373 378 174 444 403 582 281 446 9.20 131 575 292 234 76.8 617 212 695 510 411 394 462 493 623 396 328 LOQ--Limit of Quantitation = 0.0107 g/g It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 154 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Table 29. Week 106 Reported PFOS Levels in Liver of Male Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C92821M 9.68 C92823M 1.91 C92827M 0.144 C92829M 0.117 Group 6 High Recovery C92833M C92834M 0.382 0.203 C92848M 17.9 C92851M 0.363 C92853M 0.431 C92856M 0.0332 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. Table 30. Week 106 Reported PFOS Levels in Liver of Female Rats in Study FACT TOX-002 Dosage Group Specimen ID PFOS g/g C93181F 4.32 C93182F 2.10 C93183F 9.08 C93184F 1.69 C93185F 15.9 C93190F 22.8 C93192F 15.0 C93197F 8.65 HigGhrRoeucpo6very C93198F 6.18 C93201F 19.2 C93202F 17.0 C93205F 0.132 C93209F 14.9 C93211F 42.6 C93216F 14.7 C93219F 4.96 C93220F 19.5 It is not possible to verify true recovery of endogenous analyte from tissues without radio-labeled reference material. The only measurement of accuracy available at this time, matrix spike studies, indicated that the sera data are accurate to 30%; liver data are accurate to 50%. 3M Environmental Laboratory Page 155 3M Medical Department Study: T-6295.4 Appendix E: Data Spreadsheets Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 156 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 104 Week Dielary Chmnic Tortcity and Carcmogenicity Studwyith PemuMmcme SulfonicAcid PolvsiumSalt (PFOS T4295) in Rae 104 Week Dielary Chmnic Toxicity Study wiPthemuamocmc SulfonicAcid Pomsium Salt (PFOS T4295) inRats T4295 (FFOS) Analytical Report: FACT TOX-002 LRN-U2121 FACT-M-10 Excel 97 3M Environmental Laboratory WEEK 4 RAT SERA Group Dose Sanpk Y InlUnl LO1 215 I PFOSStd I PFOSPurlhi I PFOS I PFOS QC-75 ppb Conhnl 0 0 mgkg C92524M C92526M C92529M C92864F C92914F C92919F N2926F Gmup 2 C92574M Low Dose C92575M 0.5 mgkg C92610M C92613M C92618M 91.1 C92982F C92941F C92945F C92950F C92969F Group 3 C92MM Mtd Do% C92650M 2.0 mgkg C92652M C92668M C92678M C92996F C93w6F C93008F C9303IF C93045F Cmup 4 C92715M Mid-egh Dow C92718M 5 0 mgkg C92731M C92734M C92744M C93058F C93067F C93070F C93075F C93084F Group 5 C92752M Htgh Dose C9275YM 20 mgkg C92779M C92793M C92798M C93114F C93123F CY3142F 1 I C93144F C93159F Original PFOS LOQ (4 88 ng/mL, 9.81 ng/mL) Carrecuon factonnot applicablefor MSIMSD 1 ND =Not Detemmed 0.9275 NA 92.6 0.9275 ND 1.57 1 0.9275 ND 0.9275 0.9275 0.9275 0.00 0.9275 ND 1 0.9275 ND I 0.9275 ND I 20.8 I 0 9275 ND 3 1 23 I 0 9275 NTJ 20 49.0 1 0.9275 ND 20 53.3 I I 0.9275 I ND I 20 I 50.9 0.9275 0 9275 0.9275 0.9275 ND 89.8 0.9275 ND I 0.9275 ND 20 74.6 1.38 I 0.9275 77.N5 D 20 144 1 0.9275 ND 50 85.5 3 97 1 0.9275 ND 50 61.4 2.85 1 0.9275 ND 4.80 50 I03 12 8 1.61 0 207 K+ mfomation on 10104 00. LAC 10/04/00 PFOS = Pemuorwcmeaulfonatc * Dam entered,Conunumg calibration venftcations did not meet +I-30% criteria. LAC 09105100 2/13/01 Page 157 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covancdt 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 3M Study Title: Covance Study Title: Product Number(Test Substance): Matrix: Method/Revtsion: Analytical Equipment System Number: Instrument SnftwardVersion: Filename: R-Squared Value: Slope: Y-Intercept: Date of ExtractionlAnalyst: Date of AnalysidAnalyst: Date of Data ReductiodAnalyst: Sample Data WEEK 14 RAT SERA REWORK 104 Week Dietary Chronic Toxicity and Carcinogenicity Study 104 Week Dietary Chronic Toxictty Study with Pefluorooctane T-6295 (.PFOS), Rat Serum - Curve linear regression, I/X weighted FACT-M-3.0 & ETS-8-5.1 Amelia 062498 MassLynx 3.3 See Attachments See Attachments See Attachments See Attachments 07/28/98IAS O ~ / Z Y / Y X . O X / I ~ / Y R , nHwOl 7U/M~ xEE WOI/W. ounuw IAS Lot 193 with Perfluororrmne Sulfonic Acid PotassSiuamlt (PFOS T-6295) In Rafs Sulfonic Acid PotassiuSmalt (PFOS T-6295) inRats Filenames Blks Grp 1 M Grp 1 F Grp 1 F Grp 2 Grp 3 Grp 4 Grp 5 M Grp 5 F MS,MSD PFOS A072998(H)2-3& 71-72 072998013-17 O ~ Z Y Y R ~24Z.2I 5, 8l498012-l3 814YR016-26 8 1498029-40 81498043-54 8149R064-68 08179825-29 81498071-72 Dilutions I11 111 111 1/25 1/25 1/50 1/1w 1/250 1/5w 1/1 Group Dose Sample # Initial Vol. mL PFOSStd Correction Factor PFOSPurity Correction Factor PFOSConcePnFtrOatSion Dilution Conc. Factor ofPFODSev. Method Blk HZ0 Blk-l I 0.9275 ND 1 0 . W <LO(Q0.045u7g/mL) HZ0 Blk-2 1 0.9275 ND I Matrix Blk Rabbit Serum Blk-l I 0.9275 ND 1 <LOQ (0.0457 ug/mL) Rabbit Serum Blk-2 I 0.9275 ND I Q C - I W ppb TN-A-l902-MS 1 NA NA 1 Rat Serum TN-A-1902-MSD 1 NA NA 1 10 7 ?Z, Group 1 CY25OYM 1 0.9275 ND 1 Control C92511M 1 0.9275 ND 1 0.0 ppm CY2521M 1 0.9275 ND I in D m Group 2 CY252RM 1 0.Y275 ND I C92532M I 0.9275 ND 1 CWXXOF 1 0.9275 ND I C92887F 1 0.9275 ND 25 CY2898F I 0.9275 ND I C92903F I 0.~275 ND 25 C92905F 1 0.9275 ND 1 I C92593M I 1 I 0.9275 I ND I 25 i%f 1I ~. I I 17.5 <LOQ(0.0457ug/mL) 360 I 0.332 I0.R 0.252 70.0 1.62 0.333 204 4.70 Low Dose 0.5 ppm in Diet CY26WM C92616M C92621M 1 0.927s ND 25 198 4.58 I 0.9275 ND 25 I77 4.09 I ND 0.9275 25 I79 4.13 C92627M C92944F 1 ND 0.9275 25 117 0.801 2.69 I 0.9275 ND 25 256 5.90 C92Y62F 1 0.9275 25 ND 356 8.21 C92967F 1 0.9275 ND 25 314 7.23 C92978F C92987F I 0.9275 ND 25 282 6.50 1 ND 0.9275 25 ** ** Group 3 C92640M I 0.9275 ND 50 344 15.9 Mid Dose C92645M 1 0.9275 ND 50 367 16.9 2.0 ppm C92662M I 0.9275 ND 50 350 16.1 in Diet C92676M I 0.9275 ND 50 387 17.9 C92684M I 0.9275 ND 50 408 18.8 CY2993F 1 0.9275 ND 50 62 1 28.7 CY3WK)F 1 0.9275 ND 26.7 50 579 CY~~IXF I 0.9275 ND 25.1 50 543 C93023F I 0.9275 ND 25.4 50 549 C93035F I 0.9275 ND 50 663 30.6 Group 4 C92713M 1 0.9275 ND I00 532 49 1 Mid-High Dose CY2714M 1 0.Y27.3 ND I (W) 403 37.2 5.0 ppm C92719M 1 0.9275 ND IO0 45 1 41.6 in Diet C92722M I 0.9275 ND loll 46Y 43.3 C92728M I 0.9275 ND IOI) 522 48.2 CY3051F C93064F 1 0.9275 ND Io0 614 56.7 I 0.Y275 ND I w 699 64.5 CY307 IF 1 0.9275 ND I(K) 773 71.3 CY3085F 1 0.9275 ND I(I0 675 62.3 C931OYF I 0.9275 ND IO0 729 67.3 Group 5 C92765M I 0.9275 ND 250 fIn2 139 High Dose 20 ppm C92777M C92789M 1 0 9275 ND 250 629 I45 1 0.9275 ND I49 250 645 in Diet C9279YM 1 0.9275 ND 250 588 136 CY28lZM 1 0.9275 ND 250 740 171 C93111F I 0.9275 ND 500 496 229 CY3127F I 0.9275 ND 5(M) 456 211) C93143F I 0.9275 ND 500 559 258 I I I I C93155F I 0.9275 ND 500 477 220 C9316YF 1 0.9275 ND 500 432 199 -rigind PFOS LOQ (49.3 n.dmL) u.miated 111reflect K+ information on IO/M/(H).LAC l()/M/W Correction faclarsnnt applicable forM S N S D QCdata ND =Not Determined PFOS = Perfluor~,octanesulf~,na~ ** Sample spilled during extraction,no sample remining for analysis. Date EnterediBy: 02/09/(X).09/07/W LAC DVaeterified By: 08/24/00 KJH Mean Std. PFOS Udfi Rsn RPDMS/MSD N(u0<gA./L0m4OL5Q7) N(u0<gA./L0m4OL5Q7) 108% I %> <LOQ(0.0457 u mL) + -t-4.04 --t- 14.3 0.993 -t- 7.13 --+ t- t-4.90 PurityEntererWerified: OYIIUW LAC, Y/IUW MMH Original PFOS LOQ = 25 ng/mL updated to reflect purity informationon IO/(I4/W. LAC 1O/WW ETS-X-5.1 Excel 97 3M Environmental Laboratory 2/13/01 Page 158 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 3M StudyTitle: Covance Study Title: Product Number(Tes.1 Substance): Matrix: MethodRevision: Analytical Equipment System Number: Instrument SoftwardVenion: Frlename: R-Squared Value: Attachments Slope: Y-Intercept: Date of ExtractiodAnalyst: Date of AnalysidAnalyst: Dale af Data ReductiodAnalyst: Sample Data I YVEEK53 RATSERA Group I Dose Sample # 1 0 4 Week Dietary Chronic Toxicity and Carcinogenicity Study with Perfluomwtane Sulfonic Acid PotassiumSalt (PFOS T-6295) in Rats I O 4 Week Dietary Chmnic Toxicity Study with Perfluororctane SulfoniAccrd Prrtassium Salt (PFOS T-6295) in Rats T-629.5 (PFOS) Rat Serum Filenames ETS-X-4.1 and ETS-X-5.1 SOUP020199 Blanks PFOS S121499043-45.63-65 Dilutions 111 MassLynx 3.3 See Attachments See See Attachments Grp 1M GrplF Grp 1 F Grp 5 M I 1 1599019-25 1 l1599oZ6,2X-32 1214YY057 112299Ol7-20 111 I11 1/2 1/200&2(XN) See Attachmenu 11/10/99SEE l1/15/99. l1/19/99,11/22/99. 11/24/YY IAS, 12/15/99 IAS Crp 5 F MS. MSD Box 99-220 IIZ~YYOI~-IY 1/1 121495K)58-59 I/I 11/16/99. l1/22/99. 11/23/99, 11/29/99 IAS. 12/13/YYMMH I7 Lot 1 I I I I 1 I I 1 Initial I PFOSStd I PFOSPurity I PFOS I PFOS I Concentration I Vol. Correction Correction Dilution Conc. ofPFOS Mean PFOS 1 I RSD Std. Dev. C928XYF CYZXYYF C92923F C92930F 0.7W 0.~275 Group 5 C9277XM 0.8W 0.9275 High Dose C9279SM 0.XW 0.9275 20 ppm in Diet C9279hM CY2817M CY31 12F O.6OO n.xw 1 .m 0.9275 0.9275 0.9275 C9312OF 1. o w 0.9275 C93154F 0.000 0.9275 C93163F 0.900 C93171F 0.9W 0.9275 -riginal PFOS LOQ (4.93 ng/mL, 9.76 ng/mL) updatedto reflect K+ and pulity information on NA = Not Appicable PFOS = Perfluorooctanesulfc,nate * Second analysis canfirmed high result. LAC 08/24/00 Dale Entered/By: 11/22/99. 11/24/99 GMULAC, lUl/YY GML, 12/30/99 MMH Date Verified By: 08/31/00 KJH PurityEntemWerified1: 0/04/00LAC, lO/()4/0()KJH 0.X640 0.8640 O.XMO O.Xh40 n.xm n.xw 0.8Mo 0.86441 0.8640 o.nw IO/M/M. LAC I 200 2w 2W 2W 2WI) 200 2000 0.9275 2MX) Z(XX1 IO/O4/00 3.93 <LOQ (0.00395 ug/mL) 482 96.6 x06 I62 640 171 767 154 150 240 x97 144 125 223 245 138 140 250 0.395 146 I 197 0.777 23.0 33.5 20 o 44.0 220 ETS-X-5 1 Excel 97 3M Environmental Laboratory TOX-(X)2-sera183-3N 2/13/01 Page 159 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 3M StudyTitle: Covance Study Title: P r d u c t Numher(Tes1 Suhstance): Matrix: Methodmevision: ANAlytical Equipment System Numher: Instrument SoftwareJVersion: FileNAme: R-Squared Value: Slope: Y-Intercept: Dates of ExtractiodANAlyst: Dates of ANAlysidANAlyst: Date of D a u ReductiodANAlyst: Sample Data )AY 719 RAT SERA Group Dm Sample # Initial VOl. Sumgate verified OliginSdhriQ Correction PFOShriQ Correction mL Factor Factor Gmup 3 C92YYIFG3Day719 1.00 NA 0.9949 0.8640 mdkg/day C93lX)3FG3 Day719 1.0(1 NA 0.9949 0.8640 CY3007F G3 Day719 0.80 NA 0.9949 O.Xh40 C93011FG3 Day719 NA 0.75 0.9949 0.8640 C93022FG3 Day719 (1.85 NA 0.9949 O.RMO CY3039F G3 Day719 I.Il0 NA 0.9949 0.8640 ~ 9 3 0 4 0 D~ a~y7319 o.80 NA 0.9949 0.8640 C93047FG3 Day719 0.85 NA 0.9949 0 Rh40 C93048F G3 Day719 0.75 NA 0.9949 (1.8640 lriginal PFOS LOQ (24.R ng/mL, 4.93 np/mL) updated to reflect purity mformation on I(NM/W. LAC m/o4/(x) NA = Not Applicable Date EnteredlBy: DatVcerified By: PurityEntererWerified: 5/11/~1,5/12/00. 5/18/(N, 5/IY/OO, (VX100,6/1Y/(M), 11117/lM)MMH/CSH&AC OR/31/(X) KJH, I1/21/00 MMH I O / M / ~ X ) LAC, IO/M/00 KJH PFOS Dilution Factor 50 50 50 50 50 50 2lX) 50 50 PFOS Conc. ng/mL. 348 299 569 61.7 39.5 637 201 429 420 FileNAme (optional) D051(KXX)54 D051(XXX)55 D05100005X D051(XKK)59 D05100(X)60 WSInIXXKI R0531OCO30 DOSlMXX)6S DOSIlXMX)66 Concentration of PFOS ug/mL or % Rec 15.1 13.0 30.9 3.57 2.02 21.6 43.6 21.9 24.3 ug/mL 20.2 MS/MSD RPD ETS-8-5.1 Excel 97 3M Environmental Laboratory Page 160 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 Sample# igmal PFOS LOQ (4.93 NA = Not Appliahle CY2503M C92505M CY2510M CY2513M CY2514M CY2518M C92541M CY2542M CY2544M C92551M C92569M C928MF CY2867F C92868F C92869F C92871F C92873F C92874F CYZX77F 02881P CY2882F CY2885F C928YQF C92892F CYZUYSF CY28%F CY2X97F CY2W)OF CY2907F CY2'wL)F C92911F C92912F CY29 13F CYZY2SF CY2927F CY2577M CY2583M C925YQM C925Y7M CY2598M CYZ60lM CY2h" CY261YM C92623M CY2626M C92936F C92938F CY2946F CY2953F C929S7F CYZYNIF CY2964F CY2970F C92Y73F CY2974F CYZY7SF CY2Y83F CY2984F CY2986F C929XRF CY2631M CY2611M C92637M C92MIM C92MZM CY2643M CY2WM CY2MYM C92653M C92657M CY265YM C92hhnM C92MYM C92674M CY2682M CY2683M CY2690M "L, 9.76 " U l m L ) up& lnltlsl Vol. mL OM 0.85 0.84 0 82 0.85 0.70 0.74 034 0.78 0.70 n.m 0.87 0.90 n.yx 0.85 n us 0.n7 0.95 0 76 0.89 0.96 I .a0 100 0.85 n 8s 0.73 I .M 0 SI 1.00 0.w I .00 1.00 0.w 1 .M 0.43 100 0.85 0.81 0.4 0.81 0.75 I .00 I.0 0.92 0.83 0.70 100 1.00 0.75 0.85 0 95 0." 0 95 IM 0.98 I .00 n.85 0 75 0.33 0.85 0.74 0.90 0.75 1.00 0.82 I .M O.w 0 78 0.96 0.35 1.00 0.90 - SUITOgSte - verined NA NA NA NA NA NA NA NA NA - NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA - NA NA NA NA NA NA NA NA NA NA - NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA - NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA - NA NA mat,"" an Ollglnsl Puruy COWeCtlO" F.ctOr n 9949 0.9949 0.9~49 O.YY~Y 0.~49 O.YY~Y 0.9949 0.9WY 0.9949 0.9949 0.9949 0.W49 0 9949 0 W4Y 0.9949 n.9~4~ 0.~49 O.YY~Y nY Y ~ Y 0.9949 0.W4Y 0.~49 0.9949 0.9949 n9 4 9 0.949 n.wY 0.~49 0.W4Y 0949 0.9949 0.9949 0.9949 0.W4Y 0 9949 O.YY.W O.YY~Y 0.~49 0.~49 0.9949 0949 0.9949 0.W49 0.9949 0.949 0.~49 0.9949 0.9949 0.9949 0.~49 0.~49 0.W4Y O.YY~Y 0.994~ 0.WY n.Yw 0.9949 0.W4Y 0.~49 n w49 0.~94~ O.YY~Y 0.9949 0.9949 0.9949 0.W4Y 0.~49 n.9949 0.W49 0.W49 n.wy 0.9949 0.9949 0.949 0.9Y49 0.W4Y n w49 4/00, LAC 1wo. 0.8640 0 8640 0.8640 0.8640 0.8640 -PFOS - COW. wdd 10 9 IS 8 27.6 12.0 31.8 000 3.28 3.10 0.360 - 0.820 3.N 705 197 48.4 307 6.74 68.0 41.8 Y7 9 25 :I 52.8 0.M 69.2 15 5 26.9 46.8 43.1 77.9 14.8 46.3 M.1 35 8 59 6 -3.62 26 4 320 244 127 225 226 367 64.0 43.0 - 177 171 201 37.0 174 535 651 196 515 I69 147 421 407 784 313 -603 561 776 IW 17x 257 627 47.5 139 163 561 108 258 36 7 25 2 4nfi 495 - 53.3 52.1 0.0285 0.0127 0.0325 < LOQ (0.00428 ug/mL) < LOQ (0.0042U ug/mL) < LOQ (000428 ug/mL) < LOQ (0 00428 ug/mL) < LOQ (0.00428 ug/mL) < LOQ (0.00428ug/mL) 0.624 0 225 0.M7 0.306 o.oo6sn 0.ohoz 0 0427 0 IM o.ozsn 0.0481 c LOQ (0.00428 ug/mL) 0.0675 0.01411 0 0233 0.~07 0.0443 o.07~5 0.0176 0.0402 0 MX7 0.0311 0.0575 <LOQ (0.00848uglmL) 0 0229 n.3w 0.212 2.55 1.95 0 230 3.94 1.39 0 461 2.05 1.48 8.72 0.349 9.08 6.64 5 67 1.70 5.97 1.73 1.34 4.06 3.72 6.81 2.78 5 24 5 76 8.98 14.3 I81 15.1 6.m 2.75 1.21 8.63 0 487 5.20 14.4 I .M 3.13 35 3 4.77 2.72 2.83 Ma" PFOS f RSD Std. Dmv. MSMSD RPD 00118 87.6 0.0104 - 161 0 134 i 99.0 1.30 61 8 4.35 2.78 113 7m 8.60 ETS-8-5.1 Excel 97 3M Environmental Laboratory 2/13/01 I O 0 6 AM Page 161 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covancd 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 CY26Y3M IIYI CY2694M 1tm CY26YSM CY2696M CY269RM II.Y1 NA n.wY IM NA n y94v CY26WM 0.70 NA n WY CY2lMM n 7s NA n WY c927n2~ n Y(I NA n WY CY27MM 0.19 NA n WY CY~~SM 0.73 NA n.wY CY2108M n 67 NA n WY CY2116M 0.75 NA n WY CY211lM C92124M CY212hM 1.M NA nw 4 ~ n.85 NA n YWY n 7s NA n 9949 CY213OM n WY 1IXl IM IIW II~ 1011 IM 1") 2M 20 20 100 20 o In 10 CY213SM I1 9949 200 CY2136M C9213YM C5W4OM C92742M 0.~949 100 n WY IO 0 9w9 n WY Irn 100 CY2141M C92148M CY~~S~M CY~OSYF 0.9949 IM n VWY IIW n YWY 100 n WY SM CY3(MOF C~3n62F CYJO~~F CYXll2F CY307lF CY3OlRF CY3lllYF CY3llROF CY30RIF CYmF CYWRF CY3101F I19 w Y 5IXl n.wY IIXXI n.wv lOo(1 n WY 500 n MY IM n.mY sn 0.WY stn n YWY SIYI n.wv sw n WY 200 n~ 9 4 ~ IMI n.wY 100 CY3102F CY310lF CY2153M I1W Y n 9949 n WY 100 SI) 2Imm CY2lSlM CY2161M ll.81 NA 0.W9 n 65 NA n~ 9 4 ~ IIMXI 2m CY2162M IM NA 1) 9 9 4 Y CY2174M ].MI NA n we CY2115M 11.85 NA n 9949 C92116M 0.Y6 NA n WY CY~~M 10 NA 0.WY CY2lR2M n 57 NA n.vw CY2186M n YI NA n 9949 CY27RRM n.nn NA n.wy 2w so so 2000 2m sn 511 21m CY2lVIM CY2192M CY2RMM CY2802M CY2803M tl.Y3 NA 1I.WY n.m NA n WY OYI NA n.wY n 92 NA n YWY 0.75 NA n.wy 511 2000 200 Ilnn 2000 CV2RMM CY2RnRM CY2RWM CY2R14M I).RR NA I1 9 9 4 Y an6 NA n WY 0 65 NA n.wY 0 RS NA 0.S94Y 200 in sn 2MXl 4.79 2000 2000 20 21m 2000 21m 2Wl 21m 2000 2nm sn 2Irnl llxxl 21m 20 14 2WW 20(m 200 2WI 2Ml 2000 2oMl 2ooo CY3114F 20 CY31llF 2000 CY317RF 2lxuI 2000 Original PFOS LOQ ugdatul1 0 rrnsc, pY"ty lnbrmnl 75.5 Mn 740 423 140 5Y I 248 12 6 YR 9 96.8 375 584 241 626 335 54 I YR 5 35 5 65 R 349 26.3 3M 42 I 33 3 IRY 175 111 1Y7 223 436 (62 168 IS3 I27 5711 SY 5 202 ~ns 635 165 IY6 111.2 1s I 23Y 217 i YY 1R.R 220 511 54 4 4SY 6 62 136 17Y 60 7 MS 736 WI I 43.7 441 218 148 Y1.Y 203 I39 ISR 78.11 162 5Y.S 2Y 6 IW Rl1.I 6Y 1 11 I&5 4W 257 1x5 Y47 76 11 I Rn 175 128 I24 IW 771 2 14 li 6 1R.7 12.1 71.1 28 8 3.14 In.Y 23 n 9.72 13.s 3 01 12 R 38.8 6.72 24 4 4 In 5 12 17 7 2.28 4< 1 1.66 3 40 103 RY 5 102 171 114 3R.O 2s Y 72 R 13 6 70 s WI 5 11 117 33 2 I 10s 22.5 23 5 -75 n 649 45 1 61.4 16.7 21.5 21.4 1R.O M2 121 37 2 6.02 E l 5XY2 R3.6 S1.Y 353 242 274 446 321 I65 IRY 339 31Y 248 216 ETS-8-5 I Erusl Y l 3M Environmental Laboratory Page 162 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 Analytical Report: FACT TOX-002 LRN-U2121 3M Study Title: CovanceStudy Title: Product Numkr(Test Substance): Matrix: MethdRevision: ANAlytical Equipment System Number: Instrument SoftwareNersion: Filename: R-Squared Value: Slope: Y-lnten'ept: Dales of ExuactiodAnalyst: Dates of AnalysidAnalyst: Dale nf Data ReductiodAnalyst SamDle Data VEEK 106 RAT SERA 4 Group I Group h Sample# C92821M C92823M C92827M C9282YM CY2833M C92834M CY2848M C92851M CYZX53M C93183F C93184F CY3185F C93190F C93192F C93197F C93198F C93201F CY3202F C93205F C93209F C932lIF C93216F C93219F 104 Week Dietary Chronic Toxicityand Carcinogenicity Study with Perlluorooctane Sulfnnic Acid PotasiumSalt (PFOS T-6295) in Rats 104 Week Dietary Chronic Toxicity Study with Pertluorooctane Sulfonic Acid PotassiumSal1 (PFOS T-6295) in Rats T-6295 (PFOS) Rat Serum ETS-8-4.1 & ETS-8-5.1 Ruby IOMYY, Davey 070799 MassLynx 3.3,3.4 See listing to the right See Attachmenu See Attachments See Attachments OS/OI/~),OS/O~(X)SAUKIWRWW o w w . w n m . os/w/w,ns/ln/w, n s m w , O S / ~ ( Y O O , o 7 / ~ "xW/ wAS 05/04/00, ns/ns/oo,OS/I I/W,05/30/00, 07/31/00. I I/I~/(KI IASIMMH T Initial Val. mL 0.82 0.84 0.96 0 93 0.66 0.69 0.80 0.84 O.X4 0.90 0.86 0.86 1.00 0.82 0.95 0.76 0.95 1.00 O.81 0.79 0.77 1).78 0.87 0.88 1.W 0.85 - Surrogate lriginal Puri Verified Correction Factor NA 0.994~ NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.w49 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.9949 NA 0.~949 NA 0.~949 NA 0.9949 on I(Y(W00. 4C lO/(W0(1 Lot 171 P F O S Puritv Correction Factor n.86.w - PFOS FileNAme - Conc. ng/d 393 (optional) R0526"36 25.8 R0526"37 33.6 R053 10003I 26.0 R053100032 60.4 R053100035 I I .o R0531(M)o36 686 R052h(XW 32.0 R053100037 203 D07ZX(XW)17 - 3.65 R053100038 285 R0526"SO 83.5 R052h(XX)51 327 R052MXKI54 77.6 R052h(XX)55 647 R052h00056 553 Do72RO(X118 918 R052h(KK)58 538 R052h(KK)61 403 ROS2MXN62 492 Do72800019 447 ROSZh(XNM 53.3 R0531OW3Y 329 R052fKW68 623 R052h00069 I64 R052fMO70 -1I7 428 R052h(XX)7l R052h(XX)72 Concentration ofP F O S u g / d or % Rec 8.32 0.533 0.0303 0 0243 0.0795 0.0138 14.9 n 0331 0.210 c LOQ (0.00428 ug/mL) 5.76 1.69 5.68 1.64 11.8 31.6 16.8 9.35 8.63 27.0 10.1 0.0594 6.57 12.3 2.85 2.39 7.44 NA = Not Applicable DaEtentered/By: Date Verified/ By: PurityEntemVVerified: (K/OR/W, 06/19/00, 08/14/W11,/14/0101,/17/W O8/31/W KJH. 11/21/W MMH 1 0 / 0 4 / 0 0 LAC, 10/04/00 KIH CSHLAC Mean PFOS ug/d 2.42 9.51 RSD Std. Dev. MS/MSD RPD 211 5.W 91.5 8.70 ETS-8-5.1 Excel 97 3M Environmental Laboratory TOX-Ol12-seralR3-3N 2/13/01 1o:a7 AM Page 163 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covancdt 6329-183 3M Study TiUe: Covance Study TiUe: 104 Week Diclary Chmnic Toxicity anCd arcinogenicityStudy withPectlunmctane Sulfonic Acid Pomsium Salt (PFOS T-6295) inRats IM Week Dielary ChmnlcToxicity Study wilh fe'ctluomocmaneSulfonic AcidPolas~lumSalt (PFOS T4295) in Rau Roduct Number(TaI Subslance): T(-P62F9O5S) MaviX: Rat Lwer Filename: See List to Rlght MeUlod/Revsim: FACT-M-I 0 & ETS-8-70 R-Squared Value See Amchments Analytical EqutpmcntSystem NumMbaedrelineMlA09m8e. lia062498 Instnunem S o f t w d m i o n : Mau3Lynr 3 D m of ExtradonlAnalysl. 6/11N8 IASRWW Slope: Y-Intercept: See Atlacachments See Attachments Date of AdysidAnalyht: 07106/98,07/14/98KJWMEE Date of Dam RedudonlAnalyst 02102100 IAS Sample Data EEK 4 RAT LIVER REWORK Lot 193 Gmr DoJe Ssnpk I InlUal WL I Tolal Mass of LI*er PFOS Std COWsUon I Facto. M&cd Elk H20 B k - l l.W NA 0.9275 H20 Blk-2 I.Ow0 NA 0 9275 Matrix Elk RlbbttLwaBIk-l 1.W NA 0 9275 RabbitLwaBlk-2 l.W NA 0 9275 QC - 100 ppb C92506M-MS NA 1.0108 NA C92506M-MSD 1.0108 NA NA Gmup 1 C92506M 1.0108 NA 0.9275 I ziii;: I I I NA Conr0m.91998 C92524M 0.9275 0.0 ppm 1.0287 NA 0.9275 207 0.186 1 inDiet I 10117 NA C92546M I 1W34 I NA 0.9275 0.9275 0.00 I 0.00 I C92861F 1.0140 NA 0.9275 89.4 1 186 0.00 dCQ(0.0552 uglg) OW dCQ(00552 uglg) 81.7 0.0817 0.104 1.0172 C92864F NA 0.9275 80.9 1 73.8 I C92914F I 1.0186 I NA I 0.9275 202 1 184 1.0145 C929l9F NA 0.9275 76.06.0700 I 70.0 C92926F 1 0092 NA 0.9275 137 I 124 0.0738 0.184 0.126 0.0486 0 I07 Gm1u2p.42 0.9928C92574M 12376 NA33.3 0.9275 398 NA L a w 1D.0o1s8e7 C92575M 9.67 %70 33.3 0.9275 319 33 278 3 8539 8.54 465 333 14248 14.2 33.3 326 9937 9.94 11.0 33.3 9.20993 9089 33.3 7.92961 7988 33.3 309 9398 9.40 3 33 277 8429 8.43 8669 282 33.3 8.67 8.71 444 100 40692 40.7 283 100 26094 26 1 337 31.2100 31167 346 32.0 100 31975 289 100 313 1 100 I I00 26736 3 26.7 28866 I 28.9 14641 14.6 31 1 29.7 100 29691 27.1 100 27099 100 24847 24.8 25.0 I00 53503 53.5 100 5%32 59.6 26.7 100 26740 49 100 49826 8 100 12 48285 47.6 48 3 100 106760 107 908 100 83858 83.9 826 100 76985 77 0 100 706M) 70 7 14.1 83.0 76.7 100 76723 200 218558 219 264 200 263670 1835482 200 341904 1533 200 285921 286 200 297613 298 282 200 434951 435 1943 200 3Mw)89 360 2134945 200 394644 C93144F 1.0102 NA 0.9275 1728 200 317269 317 C93159F 1.0130 NA 0.9273573 1959 200 358782 359 IKinal PFOS LOO (59.5 nK/K) "&led to refleC1 k t mfomation 00 101M100. LAC O I WOO NA=Not Applicable Date Entered/Analyst: Date VenfkUA'Analyac Punty EnleredNenfied O U LA~C lo1031W KJH 1OlW,O3 LAC Analytical Report: FACT TOX-002 LRN-U2121 646 0.0673 45 4 21 1 2.31 6.33 0.552 18.7 5.84 1 24.4 6.11 26 2 5 I7 0 16.1 45.3 11.8 44.1 FACT-M-2.0 Excel 97 3M Environmental Laboratory 2113101 1011 AM Page 164 3M Medical Department Study: T-6295.4 AMDT# 112296.1 Covance# 6329-183 3M Study TiUe: Covance StudyT i k Fmduct NumWTest Subs-). MalriFi.ilename: MekdRevision. Analytical Equipment Syrlcm Number instnunem SoftwareNerrion: Date ofExtractiodhdyst: Date ofAnalysidAnalys1: Date of Dam ReducuodAnalyst Sample Data IW Week Dietary Chmnic Toricxty and CarcinogeniciStytudy with PemuomoclaneSulfonic Acid Polass!um Sdl (PFOS T4295)in Rals IW Week Dietary Chmnic Toxicity Studywllb Pcmuomoctane SulfonzcAcid PolassiumSalt (PFOS T-6295) inRats T-6295 R a t Liver See LIS 0 Right FACT-M-I.O& ETS-8-7.0 R-SquaredValue: S e t Attachmcnls MadelmeMIO98. Amelta 062498 Slope: See Atracbmenls MassLyor 3.3 Y-Inapt: See Atmhmenls 08/06/98 S A H 08/10/98.08/14/98.08/17/98 MEFAWOJ OUO3/W[AS WEEK 14 RAT LIVER REWORK 193 Lot Analytical Report: FACT TOX-002 LRN-U2121 Grovp 4 C92713M 1 OM8 NA 0.9275 406 Mid-Hqh Dose C92714M I .w NA 0.9275 403 5.0 ppm C92719M I M5O NA 0.9275 409 in Diu C92722M I ow5 NA 0.9275 336 C92728M 1.00I1 NA 0.9275 384 C93051F 0.9944 NA 0.9275 381 C93061F I0103 NA 0.9275 393 C93071F 1 WOI NA 0.9275 383 C93085F 1.0038 NA 0.9275 404 C93109F 1.0022 NA 0 9275 441 Gm"p 5 C92765M 0.9983 NA 0.9275 777 High Dose C92777M 1.0067 NA 0.9275 670 20 ppm C92789M 0.9920 NA 0.9275 598 in Dtb C92799M 1.x45 NA 0.9275 494 C92812M 1.0064 NA 0.9275 526 C93111F 0.9982 NA 0.9275 745 C93127F 1.0056 NA 0 9275 672 C93143F 1.0136 NA 0.9275 679 C93155F 1.0125 NA 0.9275 737 C93169F 0.9981 NA 0.9275 612 Onginal PFOS LOQ (61 3 ng/mL) updatedLo reflect k+ mfmation on 10104100.LAC10104100 PFOS = P d u o r m e s u l f o m k PFOSA = PemuomxL8m%sulfoni& PFOSAA = Perfluomoclanc\ulfonamldoacelatc EtFOSE = NarrowRange N-Ethyl PemuoraKmneaulfonmido ethyldcohol Correction F a c m not applicable to MSIMSD QC data ETS-8-7.0 Excel 97 3M Environmental Laboratory 1WO 375 374738 IWO 372357 372 loo0 377202 377 1WO 308422 308 8.05 IWO 35M119 356 358 28.8 IWO 355218 355 loo0 360819 361 1WO 355 354845 IWO 373 373393 6.03 lWO 408111 408 22.3 370 loo0 722350 722 loo0 617695 618 loo0 559277 559 1WO 456225 456 18.8 loo0 485214 485 568 107 IWO 692038 692 IWO 619486 619 loo0 621011 621 IWO 674725 675 7.72 IWO 569017 569 635 49 0 NA = No( Apphcabk Dale EnWAnalyst: 02109100 LAC Dale VdledlANilyst: 10/031w KJH Purity EnteredNerified: 101W00 LAC 2/13101 l o l l AM Page 165 3M Medical Department Study: T-6295.4 3M Study Title: Covance SNdy 'IiIitle. Rodun N u m W e s t Substance): Matrix: MahodlRevtsion: Analyucal Equipmen1System Number: Insmunent SoftwareNezsion: Date of ExlrmiodAnalyst. Date of AnalysisJAnalyst: Date of Data RedudidAnalysl: Sample Data AMDT# 112296.1 Covancd 6329-183 104 Week Dietary Chronic Toncity and Carcinogelucily Study with Pemunoonane Sulfaluc Acld PoIassium Salt (PFOS T-6295)in Rats 104 Week Dietary Chronic Toxicity SNdy with P d u m m a n e SulfonicAcid Potassium Salt (PFOS T-6295) inRats T-6295 Rat Liver Filename: See L i s to Right ETS-8-6.0 and Em-8-7.0 R-Squared Value: See Anafhmenfs swpo20199 Slope: See Aaxhmenfs MassLynx 3.3 Y-Intercept: See AnaEhments I 1 / 1 ImS, 01/25/00MCWSAL 11/15/99. 11/19/99 ll/2U99IAS/"H, 11/24/99GML, l2/16/99IAS 11/16/99. 11/22/99, 11/23/99[AS. 12/1/99 MMH. 12/17/99, 11/20/00 IAS/KJH WEEK 53 RAT LIVER Group Dose SnmpkY Melhal Blk HZ0 Blk-9 H20Blk-IO Malrix Blk Rabblt Liver Blk-9 Rabblt Liva Blk-IO QC C92517M-250ppb-MS9 C92876F-250 ppb-MSD10 Group 1 C92501M Conlrol C92504M 0.0 ppm C92507M in Diet C92512M C92517M Malfs C92523M C92534M C92540M C92562M C92570M Group 1 C92862F Conuol C92876F 0.0 ppm C92889F in Diet C92894F C92899F FelllolS C9291OF C92917F C92922F C92923F C92930F Gmup 5 C92751M High Dose C92754M 20 PPm in Diet C92755M C92778M C92790M Mal- C92795M C92796M C92817M C92820M Group 5 c93112F High Dose C93116F 20 ppm in Diel C93117F C93120F C9313OF FLmd'S C93138F C93147F C93154F C93163F C93171F Original PFOS LOQ (26.9 ng/g. 61.3 nug, 12.3 nug) updatl Colrection FadomnM applicable to MSMSD QC data PFOS = Pertluormaawulfonate NA = Not Applicable Initial W L g 1.oooO 1.oooO I .mo I .oooO 0.9979 0.9937 1.0185 I.W5 0.9916 0.9982 1.0192 0.9909 1.x65 1.0043 1.0017 1.0099 1.0085 OS937 0.9965 1.0128 0.9979 1.0171 1.0066 1.0083 1.0118 I .0028 1.0034 0.9907 1.0139 0,995 1 1.0111 1.0179 0.9930 0.9950 1.0019 1.o040 0.9931 0.9943 l.oo04 0.9912 0.9945 1.W40 0.9967 l.0141 0.9oOo ,retled K+ and Lot 171 Total M w PFOS Std PPuFFrOOitSSy PFOS of Liver Correction Corntion Conc. Dilution Factor 0.9275 I 0.9275 1 0.9275 0.8640 1 0.9275 0.8640 I IO NA NA NA 338 I NA 0.9275 0.8640 41.5 1 NA 0.9275 0.8640 45 I 1 NA 0.9275 0.8640 372 I NA 0.9275 0.8640 352 1 NA 0.9275 0.8640 96.8 IO NA 0.9275 0.8640 65.4 IO NA 0.9275 0.8640 45 I 0.359 I NA 0.9275 0.8640 133 I NA NA I 0.9275 0.9275 I 0.8640 0.8640 I 440 130 IO 1 NA 0.9275 0.8640 712 IO NA 0.9275 0.8640 163 1 NA 0.9275 0.8640 259 IO NA 0.9275 0.8640 349 I NA 0.9275 0.8640 27 I I NA 0.9275 0.8640 25 1 I NA 0.9275 0.8640 309 1 NA 0.9275 0.8640 73.0 1 NA 0.9275 0.8640 195 I NA 0.9275 0.8640 269 I NA I 0.9275 I 0.8640 I 280 2500 NA 0.9275 ~ 0.8640 240 2500 I NA 0.9275 0.8640 246 2500 NA 0.9275 0.8640 139 2500 NA 0.9275 0.8640 204 2500 NA 0.9275 0.8640 282 2500 NA 0.9275 0.8640 212 2500 NA NA I 0.9275 0.9275 1 0.8640 0.8640 I 200 158 2500 2500 NA 0.9275 0.8640 148 2500 NA 0.9275 0.8640 265 2500 NA 0.9275 0.8640 255 2500 NA 0.9275 0.8640 215 2500 NA 0.9275 0.8640 250 2500 NA 0.9275 0.8640 280 2500 NA 0.9275 0.8640 310 2500 NA 0.9275 0.8640 211 2500 NA NA 0.9275 0.9275 1 0 8640 0.8640 I 447 373 2500 2500 y information on 10/04/00. LAC IO/W00 Date EnteredAnalys: 11/24199 LAC, 12/2/99 GML0.1/24/00MMH1,1/20/00 LAC DateVenfldAnaly1s0t:/03/K00JH, 11/21/00 MMH Purity E n W e r i f i e d : IOIMMO LAC, I O / W 0 0 KJH 358 301 283 76 1 529 359 106 3519 103 5657 131 208 1 276 217 198 246 58.0 154 215 558532 485592 485843 2791 39 404861 554138 426888 403197 315897 296060 533843 513715 430218 504367 564538 619098 423936 883325 830454 Filenames Blanks Grp 1M GrplF GrpSM Grp 5 F MS, MSD Box 99-222 0.358 0.301 0.283 0.761 0.529 0.106 3.52 0.103 5.66 0.131 2.08 0.276 0.217 0.198 0.246 0.0580 0.154 0.215 559 486 486 279 405 554 427 403 316 296 534 1 619 424 883 830 Analytical Report: FACT TOX-002 LRN-U2121 PFOS 121699046-47,92-93 111999015261-5689,9067-76 1I191929106599-0,63.77-87 112499088-99 112499100-115 121699060 PFOSA NA NA NA NA NA NA 163 0.635 1.04 191 0.923 1.77 22 3 435 96.9 32.2 560 180 ETS-8-7.0 Excel 97 3M Environmental Laboratory 2/13/01 10:11 AM Page 166 3M Medical Department Study: T-6295.4 3M Study Title: Cov- Study Ti&. ProductNurnWTest Subslance): Mamr: MeUadlRevision. Analytical Equipment System Number: I n s m a t SoftwareNasion: Date of ExtractiodAnalyst: Date of AnalysiJANJyst: Date of Dam RedudodAnalybt Sample Data NAY 719 RAT LIVER Sampk# '.t MebudBL OS160H2081k-5 05160HZOBL-6 05180-HZOBP.5 05180-HZOBL-6 05220BHZ081k-3 05220C-HZOBIk-4 AMDT# 112296.1 Covancdt 6329-183 I 0 4 Week Dielary C h n l c Toxicityand Carcinogeninly Study wilb PemuomoCLvleSulfonicAcid Pamiurn Salt (PFOS 104 Week Dielary Chronic Toxicity Studwyith Pemuomocme Sulfonic Acid Pmasiwn Salt (PFOS T-6295)in Rals T-6295 Rat LWer Filename: See Below ETS-84.0 and FIS-8-7.0 R-SquareVd alue: See Atfachmenb Amelia 052498 Slope: See Atrachmenls Masslynx 3.4 Y-Intercept: See Atechmenls 05/16/W,05/181WSAUKJK OSRMO,05/24/00,05/25/00.06/12/00,06/14/00,07128/00. 07/31/00IASMMH 05/30KAl,06/15/00. 06/16/M, 07/311W. 08/01/00 IASlMMH Lot 171 InlUd wt. Tohi Mssr Or$inai Purity PFOS Pudly PFOS g of Liver C-tb" CWaCUO" conr I: FXtOr NA 1.00 NA 0.9949 NA 1.00 NA 0.9949 NA 1.00 NA 0.9949 NA 1.00 NA 0.9949 NA I .00 NA 0.9949 08640 NA 1.00 NA 0.9949 0 8640 Matrix Blk RBUlS160-LiverBP-S NA 1.00 NA 0.9949 0.8640 0.00 RBLOSIM-LI~UBL~ NA RBLOS180-LtvuBL-5 NA 1 .00 NA I .w NA 0.9949 0.8640 0.W 0.9949 0.8640 0.00 RBL05180-LiverBL-6 NA I .00 NA 0.9949 0.8640 0.570 RBLQ522W-LiverBP-3 NA 1.00 NA 0.9949 RBUlS2200-LiverBIk-4 NA 1.00 NA 0.9949 C9?503M Gl-MS-250ppb3 NA 1.0161 NA NA C92503MGl-MSD-25 b 3 NA 1.0161 NA NA C92MSM GI-MS-250ppb-5 NA 0.9927 NA NA NA 0 9927 NA NA NA 0.9665 NA NA NA 0.9665 NA NA NA 1.0055 NA NA NA 379 C92868FGl-MSD-25&&6 NA 1.0055 NA NA NA 433 C925lOMGl-MS-250ppb-6 NA 0 9973 NA NA NA 803 NA 0.9973 NA NA NA NA 1.oM4 NA NA NA 492 NA 1.0024 NA NA NA 517 I C92821M GdMSD-250ppb-5 NA NA O.Wo0 NA 0.9900 NA NA NA NA NA 319 309 CmuD 3 1 C9299iF NA 1.W24 NA 0.9949 0.8640 504 Mid Dose C93W3F NA 0.9967 NA 0.9949 0.8640 593 2.0 ppm C93007F NA 1.0010 NA 0.9949 0.8640 1121 in Diet C93011F NA I 0018 0.9949 0.8640 153 C93022F NA Iwo8 0.9949 0 8640 104 C93039F NA 1.0030 0.9949 0.8640 921 C93040F NA 0.9967 0.9949 0.8640 1080 C93047F NA 1.0016 0.9949 0 8640 615 NA I 0020 0 9949 0 8640 620 on1OMKMl LA 0 T-6295) inRals PFOS MbUo" 100 PFOS Cek.Cau. %R 0.643 0.00 0.W 0.W OW O.W 0.00 0.00 0.00 0.495 0.00 0.00 177 230 377 359 389 488 253 306 217 380 5430 1923 6423 5914 43639 51692 97210 13222 9018 79737 94108 53315 53775 Analytical Report: FACT TOX-002 LRN-U2121 Fikrume Concentratlo" MIs" (OPthld) dPFOS PFOS udg or 6 R e Do61400077 c LOQ (0.0107udg) A Do61400078 c LOQ (0.0107ug/g) A052XKy)60 c LOQ (0 0107 ug/g) AOSZuM073 c LOQ (0.0107 uglg) Do61400088 Do614wo89 Do61400079 c LOQ (0 0107 uglg) < LOQ (0 0107 uglg) < LOQ (0.0107 ug/g) Do61400080 c LOQ (0.0107 ug/g) A0522woM < LOQ (0.0107 uglg) A052200074 < LOQ (0.0107udg) D o 6 1 4 w 0 9 0 c IOQ(0.0107 ug/g) w614MxWl c LOQ (0.0107uglg) CLOP(0.0107 uglg) A073100018 60% A073100019 78% 69% A052200020 126% A052uM021 12m 123% A0512W060 126% AC412ooo61 158% 142% W728oM55 85% A052200025 102% 94% W728oM56 728 A052uM076 126% 99% Do614MK)45 18168 *a DO614oM46 26506 *I 2233% Do614wo47 213441 *a Do614oM48 1965% *a 2049% AOSZ5000lS 43 6 A052500016 51.7 A052500017 97.2 A0525wo18 13.2 A052500019 9.02 A052500022 79.7 A052500023 94.1 A052500024 53 3 A052500025 53.8 55.1 RSD std. Dt". MSlMSD RPD NA NA NA NA 26% 5% 22% 20% 55% 37% 8% 57.2 31.5 ETS-8-7.0 Excel 97 3M Environmental Laboratory 2/13/01 IOIZAM Page 167 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 ns18n ~ 2 0 ~ k . s 0518DH208k-6 ns~~1n~w~k-3 NA NA 11.9949 C92aWF NA NA C92892F C92895F NA C92896F NA NA C92897F NA C929MF C929117F NA CY2909F NA C929llF NA CY2912F conrmcd LOW C92913F NA C9292SF NA CY2927F NA elcup 2 C92577M NA Lnw D w C92i83M NA n.5 ppm CY259OM NA in Diel C9259lM NA C92SYIIM NA Malu CY2601M NA C~ZII~M NA C92619M NA C92623M NA CY2626M NA <;",up 2 CY2936F NA lnv u w CYXllRF NA 0.5 ppm CV29MF NA NA I"Diel C92953F CY2YSlF NA FMaler C92YfdF NA C929ii4F NA C9297OF NA NA CY2913F NA CY2974F C9297JF NA C92983F NA NA CY2984F CYB86F NA CY298RF NA OnginalPFOS LOQ I I 2 3 ngll) updated LDm f l d punty inrormatlnn M IM)4/(Xl.LA 0.9949 0.9949 11.9949 11.9949 Told Mnsa "r LI"= K NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11.9949 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA PIA NA NA NA NA NA *A NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Orl&d h r l t y C"rrstk" FM". 0.9949 11 9949 0.9949 0.9949 n 9949 u.9949 n 9949 n 9949 n 9949 n 9949 119949 0 9949 NA NA NA NA NA NA NA NA NA NA NA NA 119949 0.9949 Il.YY49 0.994~ 0.9949 0.9949 n 9949 0.9949 11.9949 n 9949 0.9949 n 9949 0.9949 n.9949 11.9949 0.9949 0.9949 n 9949 0.9949 0.9949 ll.9949 11.9949 0.9949 119949 11.9949 n 9949 n 9949 0.9949 n 9949 09949 I19949 11.9949 0 9949 n 9949 (1.9949 D.9949 0 w.49 (I.9949 0.9949 n 9949 0.9949 0 9949 n.9949 11 9949 I1 9949 0.9949 n 9949 1,9949 n 9949 0 9949 n 9949 n 9949 0 9949 n 9949 L n t 171 P Wh l l g CV-tl"" F&Ol O.8640 n 8640 n 8640 0.8640 n 8640 n 8640 11.8640 n 8640 n 8641 0.8640 118640 n 8Mo NA NA NA NA NA NA NA NA NA NA NA NA NA 135 379 413 Y65 122 75 9 131 IIS I82 I 384 389 I RFll sld. De". MSMSD RPV NA NA NA NA 26% S% 221, 55% 37% 8%) 131) 11 148 I 72 IS 3 20 I 14.5 4 94 211 I 8 (8 13 2 I v9.4 11 1% 91.8 7 34 52 7 6 x1 3M Environmental Laboratory Page 168 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 'EEKI05 RAT LIV Crnup DMcthal B k Ma!m Bk w RBUlS2ZWLiverBlk-4 C92S03M Gl-MS-U@pb-3 C92503M GI-MSD-BOpph3 CY25MMGI-MS-25Opph-5 C92505M GI-MSD-25Opph-S C918MF~Gl-MS-250pphl C92SMF-GI-MSD-ZMppb-4 CY2868FGI-MS-L'iOpph-6 C92633M C9263lM CY2641M C92642M CY2643M C92f44M C92649M CY2653M C926SlM CY2659M CY2MOM CY2MYM CY2614M C92682M C92683M CY16YCIM C 9 1 9 IM CY2693M CY2694M C9269M C92696M CYlm8M CYIWM C92lMM CY2702M C927MM C9llQ'iM C92108M C91116M C92111M C92124M C92126M C92130M C92735M C92136M N213YM CY214DM CY2142M C9274,M ~~2748~ CY27SOM C930SYF CYVW C931K2F CYIlK3F C91012F CY30llF C93018F CY3019F C910HOF C93081F CY3lNOF C931NRF C93101F C931112F NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA R InmMyl. u c + Tnt.1 M u "r LI*- NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA n 9949 n.9949 n 9949 0 9949 0.9949 n 9949 0.9949 11 9949 11.9949 0 9949 0.9949 11.9949 0.9949 n.9949 0.9949 0.9919 n.9~4~ 11.9949 n 9949 0 9949 11.9949 0.9949 n YY49 0.9949 n 9949 0 9949 119949 n9 9 4 ~ a 9949 nY Y ~ Y ll.994Y n 9949 0 9949 11 9949 11.9949 0 9949 n.9~4~ 11.9949 NA NA NA NA 0 HMO n 8640 11 8WI 0 8640 n.864) n.8m 0.wi41 o 8640 n.nw 0.8640 0.8640 0 8f40 n 8640 0.8641 n HMO 11.8640 n n6w n 8640 1I.RMO 0 8640 08640 11 H M O I1 8640 0.864) n nMo I)." n 8610 n~ M O 11 8640 0 8640 n8 ~ o n 8w1 D am 0 8640 n 8Mo n.8640 o nMo M-" PMS PJK RSII Sld. Der. MSrmSD RPD NA NA AOSl2IIMl6 DlK1400MS 3.82 3 35 23.9 18 S 4 32 54 11 XY.4 111 'i 63 I 4hl 61 4 3M Environmental Laboratory Page 169 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Matrix B1k w s-pk I CP2MWM N2814M CYZRISM C92RIRM CWII3F CY31 ISF CY3124F CY312SF CY3133F CY313SF CY3137F CY1139F CV3140F CY3146F CY314YF LYI1SlF CY3IS3F CY3ISlF C931SRF CV3161F CY1162F C93lMF LP316SF CY31 66F CY316RF CYllllF CY1177F su-.,e VlIilkd NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA HA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 1 NA NA NA Inn nm. wc ~ n m TnW M a r + ,#U"U NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 0rIgh.I p.r(ty cnrndion F.&V n WAY 0 W4Y 0.9949 nYY~P 0 YY4Y n 9949 0 W4Y nW ~ Y 0.~4~ 0 W4Y 0 9949 ,I 9949 NA NA NA NA NA NA NA NA NA NA NA NA NA NA ".W4Y n 9949 nM Y nW ~ Y u W4Y 0 9949 0.9949 IIYWY n 9949 0.9949 0.949 0.W4Y ll.YY4Y 0.WY ll.Y94Y n 994Y 0 9949 0 9949 n 9949 11.9949 0Y94Y 0 9949 u W4Y 0.W4Y n949 OY94Y 11 W4Y 0.W4Y 0 W4Y n vp1Y n.994~ 11.994Y 11.WY I, W4Y lI.994Y 0 W4Y 0 W4Y n w49 0 994Y 00949 I19949 0.994Y n 9949 0WIP U.WY 0w 4 Y NA NA NA 0 864" -PW! Cnc %? 0.IKl 0.w 0.00 -0 In O.w 0.in O.w 0.00 0.s70 ow 0.m -3s7 411 -4Y6 478 - 12s I35 - 379 433 -~ 0 3 966 - 492 SI7 -319 3w -261 765 1x6 4w 88.6 81.4 734 37s 121 227 YIS IM 127 3% Y3.6 917 762 271 lMl Ed7 -I% 812 RS.8 872 401 1113 9w 13s M3 W9 21.1 304 132 6R7 141 11s 143 4116 161 118 976 913 In.% 113 Is4 -RR6 7Y2 - P W S Cd.. C""C A n.w OW no0 0.w 0.W 0.00 ow ow 11 I", 0 4YS - n no n w 177 230 177 3SY 3RY 488 2S3 3M 217 I80 s430 7923 6423 (914 113104 32W66 80173 174603 3Y1W 349~0 320170 169214 s3101 98636 384592 6R9S4 54772 IS8184 4118544 4111SY 330049 118664 L1316 3S7R73 7lYYR 3S1Y3R 373041 377647 173716 4441llR 4027M S81680 2RORllS 445619 YlYR 13Irx3 s7s132 291713 233S44 76847 617048 2122111 6Y4Rl2 S099SY 410860 3938R" 46lSY2 493,138 - 622690 3YSSlS 328294 329 80 2 175 39.4 35.11 I2ll 163 (3 I 98 6 3RS 6Y I, (4 R ISY 4M 411 3311 IY 23 3 l<S 72.0 352 373 178 I74 444 403 582 281 446 Y 20 131 57s 292 234 16 R 617 212 69s SI0 411 394 462 493 LU 3% 11" NA NA NA NA 268 IC 22% 20% SS% 3706 8% 74 9 IRY 141 46 I 116 3M Environmental Laboratory Page 170 3M Medical Department Study: T-6295.4 S"V.te Vdld NA NA NA NA NA NA NA NA 0.994Y NA I1 W4Y NA NA NA NA NA NA NA NA NA n Yyzl NA II.YM5 NA ll.YM5 NA IWS5 NA I.WS5 NA 1, YV79 NA n 9973 NA I *I24 NA NA NA NA Gnuup 6 CYZR2lM CY2R23M CY2827M LY2R2YM NA NA NA NA NA NA NA NA NA NA NA 0.~49 NA lI.YY4Y NA 0 PMP CY2833M NA CYZRYM NA CYZR4RM NA CYZRSIM NA CYZRJ3M NA CYZR56M NA CY3IRIF NA CY31R2F NA CY31RlF NA 0.994Y n W4Y 0.994Y llY94Y CY3lR4F NA CYIIRSF NA R.YWY LY1190F NA LY11Y2F NA N31Y7F NA CYIIYRF NA CY12OIF NA CY32MF NA 0.9949 I1 W4Y OW4Y R.WIY nYWY cY32iISF LY32IWF CY32llF C93216F CY32IYF CY322OF I "@a I"reklpuntymf"mY(l0 ZYlW LACnR114M NA NA NA NA NA NA M I Mm LAC I 0 9949 n W4Y 0.949 11.9949 n 994Y NA n YW Analytical Report: FACT TOX-002 LRN-U2121 R.D Sld.Der. M W S D RPD NA NA NA NA 203, S% 229, 211% SS% 37% 8% 1,411 n 0132 4.12 2 In Y OR I OY ISY 22 R !in R 65 h.lX IY 2 17 n n 132 14.Y 42 6 14 7 4 Y6 IY2 3 12 5 Y7 3M Environmental Laboratory Page 171 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Appendix F: Example Calculations Formula Used for Sera Analyses in Study FACT TOX-002 AR (ng/mL) DF SC FV (mL) 1.0 g PC = Reported Concentration (g/mL) EV (mL) 1000 ng OPC Calculation Used for Group 3, Day 719, Animal ID C92991F 348 ng/mL 50 0.9275 1 mL 1.0 g 0.864 = 14.0 g/mL 1 mL 1000 ng 0.9949 AR-- Analytical result from MassLynx summary DF-- Dilution factor SC--PFOS salt correction constant (0.9275) FV--Final extract volume (1.0 mL unless otherwise noted) EV--Volume of sera extracted PC--PFOS purity correction factor (86.4% for lot 171) OPC--Original PFOS purity correction factor (99.49%) Formula Used for Liver Analyses in Study FACT TOX-002 AR (ng/g) curve (1) SC DF 1.0 g PC = Reported Concentration (g/g) specimen 1000 ng (1) curve is assumed to be: 1 g liver 5 mL H2O Calculation Used for Group 3, Week 105, Animal ID C92631M 480 ng/g 1 g/ 5 mL 100 1.0 g 0.864 = 41.5 g/g 1.0036 g/ 5mL 1000 ng 0.9949 AR-- Analytical result from MassLynx summary curve--Density of the liver standard curve, assumed to be 1g liver/ 5 ml water specimen--Density of the liver specimen (g specimen/ 5 mL H2O) DF-- Dilution factor PC--PFOS purity correction factor (86.4% for lot 171) OPC--Original PFOS purity correction factor (99.49%) 3M Environmental Laboratory Page 172 3M Medical Department Study: T-6295.4 Standard deviations were calculated using the equation: SD = nx2 - (x)2 n(n -1) Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 173 3M Medical Department Study: T-6295.4 Appendix G: Interim Certificates of Analysis Analytical Report: FACT TOX-002 LRN-U2121 3M Environmental Laboratory Page 174 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Cm& Analytical Laboratorks, Inc. State College,PA 16801 Fax:(814)231-1253 or(814)231-1580 INTERIM CERTIFICATE OF ANALYSIS Revision 1(9/7/00) Centre Analytical Laboratories COA Reference #: 023-018B 3M Product: PFOS, Lot 171 Reference #: Sk009 Purity: 86.4% Test Name Specifications Purity' `: ,,:!,.,I, ,: Result 86.4% Appearance Identification NMR Metals (ICPIMS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium2 5. Nickel 6. Iron 7. Manganese Total % Impurity (NMR) Total % Impurity (TLoCta/Ml %S)Impurity c (GUMS) RelatedCompounds- t POAA Residual Solvents(TGA) Purity by DSC InorganicAnions (IC) 1. Chloride 2. Flu&ride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate" OrganicAcids ' (IC) t 1. TFA 2. PFPA 3. HFBA 4. NFPA Elemental Analysis": 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine White Crystalline Powder :,,: " ,,,, 1. TheoreticalValue = 17.8% 2. TheoreticalValue = 0% 3. TheoreticalValue = 0% 4. TheoreticalValue = 5.95% 5. TheoreticalValue = 60% Conforms Positive 1. 0.017wt./v/t.% 2. 0.007 wt./wt.% 3. 1.355 wt.lwt.% 4. 6.552 wt.lwt.% 5. 0.003 wt./W.% 6. 0.004 wt.lwt.% 7. <O.OOl wt./wt.% 1.00 wt./W.% 10.60 wt.lwt.% None Detected 0.30 wt.lwt.% None Detected Not Applicable' 1. co.015 wt./u&% 2. 0.27 wt.lwt.% 3. <0.040 wt./wt.% 4. <0.009 wt./wt.% 5. <0.006 wt.lwt.% 6. <0.007 wt.lwt.% 7. 8.82 wt.lwt.% 1. co.1 wt./wt.% 2. co.1 wt.lwt.% 3. co.1 wt.lwt.% 4. co.25 wt./wt.% 1. 12.08wt./wt.% 2. 0.794W./wt.% 3. 1.61 wt.lwt.% 4. 10.1 wt./wt.% 5. 50.4wt./wt.% COA023.OlSB Page1of 3 3M Environmental Laboratory Page 175 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Cmtre Analytical Laboratories, Inc. State College, PA 16801 Fax:(814)231-1253 or(814)231-1580 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-018B Date of Last Analysis: 08/31/00 Expiration Date: OS/3l/O1 Storage Conditions: Frozen i-10C Re-assessmentDate: 0X/31/01 `Purity = 100% - (sum of metal impurities, 1.39% +LC/MS impurities, 10.6O%+Inorganic Fluoride, 0.27%+NMR impurities, l.OO%+ POAA, 0.30%) Total impurity from all tests = 13.56% Purity = 100% - 13.56% = 86.4% `Potassium is expected in this salt form and is therefore not considered an impurity. 3Purity by DSC is generally not applicable to materials of low purity. No endotherm was observed for this sample. 4Sulfur in the sample appearsto be converted to SO4 and hence detected using the inorganic anion method conditions. The anion result agreeswell with the sulfur determination in the elemental analysis, lending confidence to this interpretation. Based on the results, the SO4is not considered an impurity. `TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric acid Nonofluoropentanoic acid Pentafluoropropanoic acid 6Theoretical value calculations based on the empirical formula, C8F1+03X+ (MW=538) This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). COA023-0 1SB 3M Environmental Laboratory Page2 of 3 Page 176 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Cmtrc Analytical Laboratories, Inc. State College, PA 16801 Fax: (814)231-1253or(814)231-1580 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-018B LUMS Purity Profile: I Imnuritv I wt./wt. % I C? Total 1.63 I 10.60 Note: The C4 and C6 values were calculated using the C4 and C6 standard calibration curves, respectively. The C5 value was calculated using the averageresponse factors from the C4 and C6 standard curves. Likewise, the C7 value was calculated using the average response factors from the C6 and C8 standard curves. Prepared By: ./N Daw S. Bell Reviewed Bsz@e Laboratories Phb Date .f/b Laboratory Manager, Centre Analytical Laboratories COA023-OlSB 3M Environmental Laboratory Page 3 of 3 Page 177 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Centre Analytical laboratorks, Inc. State College, PA 16801 Fax:(814)231-1253or(814)231-1580 Purity' INTERIM CERTIFICATE OF ANALYSIS Revision I(9/7/00) Centre Analytical Laboratories COA Reference #: 023~OlSA 3M Product: PFOS, Lot 217 Reference #: SD-018 TestName Purity: 86.9% Specifications ,i ,,,:,::,:, ,,,,,i,;, Result 86.9% IAdpepnetiafircaanticoen White Crys,t.alline Powder Conforms NMR Metals (ICPiMS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium' 5. Nickel 6. Iron 7. Manganese Total % Impurity (NMR) Total % Impurity (LUMS) Total % Impurity (GUMS) Related Comuounds- POAA I Residual Solvents(TGA) Purity by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate" OrganicAcids ' (IC) 1. TFA 2. PFPA 3. HFBA 4. NFPA Elemental Analvsis? I 1. Carbon2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine ,, 1. TheoreticalValue = 17.8% 2. TheoreticalValue = 0% 3. TheoreticalValue = 0% 4. TheoreticalValue = 5.95% 5. TheoreticalValue = 60% Positive 1. 0.005wt./wt.% 2. 0.001wt./v&% 3. 1.439wt.lwt.% 4. 6.849wt.lwt.% 5. <O.OOlwt./wt.% 6. 0.005wt./wt.% 7. <O.OOlwt./W% 1.93wt.iwt.% 8.41wt.lwt.% None Detected 0.33 wt./wt.% None Detected Not Applicable' 1. co.015 wuvt.% 2. 0.59wt.lwt.% 3. co.040 wt.lwt.% 4. <0.009 wt./wt.% 5. CO.006wt.lwt.% 6. co.007 wt.lwt.% I. 8.76wt.ht.% 1. co.1 wt.lwt.% 2. co.1 wt.iwt.% 3. 0.10wt./wt.% 4. 0.28wt.lwt.% 1. 12.48wt./n&% 2. 0.244wt.iwt.% 3. 1.74wt.Iwt.% 4. 8.84wt.lwt.% 5. 54.1wt.lwt.% COA023-OlBA Page1of 3 3M Environmental Laboratory Page 178 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 Cmtre Analytical laboratorks, Inc. State College, PA 16801 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-OISA Dateof Last Analysis: OS/31100 ExpirationDate: 08/31/01 StorageConditions: FrozenClO"C Re-assessmenDtate: 08/31/01 `Purity = 100%- (sumof metalimpurities,1.45%+LCMS impurities,8.41%+Inorganic Fluoride,059%+NMR impurities,1.93%+organicacidimpurities,0.3S%+POAA, 0.33%) Totalimpurity from all tests= 13.09% Purity = 100%- 13.09%= 86.9% `Potassiumis expectedin this saltform andis thereforenot consideredanimpurity. 3Purityby DSC is generallynot applicableto materialsof low purity. No endothermwas observedfor this sample. 4Sulfurin the sampleappearsto be convertedto SO4andhencedetected~usintghe inorganicanionmethodconditions.The anionresultagreeswell with the sulfur determinationin the elementaal nalysis,lendingconfidenceto this interpretation. Based onthe results,the SO4is not consideredanimpurity. `TFA HFBA NFPA PFPA Trifluoroaceticacid Heptafluorobutyricacid Nonofluoropentanoicacid Pentafluoropropanoiaccid "Theoreticalvaluecalculationsbasedon theempiricalformula, CsFi$OsX'(MW=538) Thiswork wasconductedunderEPAGoodLaboratoryPracticeStandards(40 CFR 160). COA023-018A 3M Environmental Laboratory Page2of 3 Page 179 3M Medical Department Study: T-6295.4 Analytical Report: FACT TOX-002 LRN-U2121 CentrE Analytical Laboratories, Inc. State College, PA 16801 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-018A LCiMS Purity Profile: Impurity c4 c5 C6 c7 Total wt./wt. % 1.22 1.33 4.72 1.14 8.41 Note: TheC4 andC6 valueswerecalculatedusingthe C4 andC6 standardcalibration curves,respectively.TheC5 valuewascalculatedusingthe averageresponsefactors from the C4 andC6 standardcurves. Likewise,the C7 valuewascalculatedusingthe averageresponsefactorsfrom theC6 andC8 standardcurves. PreparedBy: RevieweBd~~~~~~~"i""""' Laboratories ~~~~ LaboratoryManager,CentreAnalyticalLaboratories COAOS018A 3M Environmental Laboratory Page 3 of 3 Page 180 3M Medical Department Study: T-6295.4 Appendix H: Report Signature Page Analytical Report: FACT TOX-002 LRN-U2121 y&*.. - &($y John L. Butenhoff, Ph.D., Studyoirector 2/ GI Date Kristen J. HansenP,h.D., PrincipaAlnalyticalnl vesfigator Date William K. ReaPghe.Dn,., LaborMataonryager Date 3M Environmental Laboratory Page 181