Document pe9oMjBnZqD439wQw8b3Z10gd

9) OECD 408-OPPTS 870.3100, 90-day oral toxicity (rodent), 418026 SAN ITlZED Study Title OEC 0 9 2003 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS SPONSOR'S STUDY NUMBER: T-7485.15 Data Requirement U S . Environmental Protection Agency Health Effects Test Guidelines; 90-Day Oral Toxicity in Rodents. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3100, August 1998. U.S. Environmental Protection Agency. Toxic Substances Control Act (TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160, July 2000. Author Raymond G. York, Ph.D., DABT (Study Director) Study Completed On 4 March 2003 (Final Report) Performing Laboratory Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 . SubcontractingFacilities Southern Research Institute 2000 Ninth Avenue South Birmingham, Alabama 35255-5537 Redfield Laboratories 100 East Boone Street P.O. Box 308 Redfield, Arkansas 72132 Laboratory Project ID Argus Research Protocol Number: 418-026 Page 1 of 443 ARGUS 4 18-026 Confidentiality Page This is a blank page to be inserted by the Sponsor. Page 2 ARGUS 41 8-026 GOOD LABORATORY PRACTICE STATEMENT This study was conducted according to U.S. Environmental Protection Agency (EPA TSCA) "Good Laboratory Practice Standards; Final Rule" (40 CFR Part 792). Any areas of noncompliance are documented in the study record. No deviations existed that affected the validity of the study. Sponsor: .------------------------------------------- .,Ph.D., DABT 3M Corporate Toxicology Date Page 3 ARGUS 4 18-026 Confidentiality Page This is a blank page to be inserted by the Sponsor. Page 4 ARGUS 41S-026 PROTOCOL 418-0261 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS SPONSOR'S STUDY NUMBER: T-7485.15 TABLE OF CONTENTS SUBJECT 1. SUMMARY AND CONCLUSION 1.1. Methods . 1.2. Results 1.3. Conclusion 2. DESCRTPTION OF TEST PROCEDURES 2.1. Conduct of Study 2.2. Test Substance Information 2.3. Vehicle Information 2.4. Test Substance Preparation and Storage Conditions 2.5. Test System 2.6. Husbandry 2.7. Methods 3. RESULTS 3.1. Mortality and Clinical Observations 3.2. Body Weights and Body Weight Changes 3.3. Maternal Absolute @/day) and Relative (g/kg/day) Feed Consumption Values PAGE 10 10 11 11 13 13 15 15 16 17 18 20 27 27 28 28 Page 5 SUBJECT ARGUS 4 18-026 PAGE 3.4. Motor Activity and Functional Observational Battery 28 3.5. Necropsy Observations 29 3.6. Terminal Body Weights, Organ Weights and the Ratio (%) of Organ Weight to Terminal Body Weight and Brain Weight 29 3.7. Hematology 30 3.8. Clinical Chemistry 30 3.9. Histopathology 30 REFERENCES 32 APPENDIX A - REPORT FIGURES 33 Figure 1. Body Weights - Male Rats 34 Figure 2. Body Weights - Female Rats 35 Figure 3. Motor Activity - Number of Movements - Male Rats 36 Figure 4. Motor Activity - Time Spent in Movement - Male Rats 37 Figure 5. Motor Activity - Number of Movements - Female Rats 38 Figure 6. Motor Activity - Time Spent in Movement - Female Rats 39 APPENDIX B - REPORT TAEiLES 40 Table 1. Clinical and Ophthalmological Observations - Summary - Male Rats 41 Table 2. Clinical and Ophthalmological Observations - Summary - Female Rats 43 Table 3. Body Weights - Summary - Male Rats 45 Table 4. Body Weight Changes - Summary - Male Rats 46 Table 5. Body Weights - Summary - Female Rats 47 Table 6. Body Weight Changes - Summary - Female Rats 48 Table 7. Absolute Feed Consumption Values (g/day) - Summary - Male Rats 49 Page 6 SUBJECT Table 8. Table 9. Table 10. Table 11. Table 12. Table 13. Table 14. Table 15. Table 16. Table 17. Table 18. Table 19. Table 20. Table 21. Table 22. Table 23. Table 24. Table 25. ARGUS 418-026 PAGE Relative Feed Consumption Values (&/day) - Summary - Male Rats 50 Absolute Feed Consumption Values (g/day) - Summary - Female Rats 51 Relative Feed Consumption Values (g/kg/day) - Summary - Female Rats 52 Motor Activity - Summary - Male and Female Rats 53 Functional Observational Battery - Summary - Male and Female Rats 57 Necropsy Observations - Summary - Male Rats 69 Necropsy Observations - Summary - Female Rats 70 Terminal Body Weights and Organ Weights - Summary - Male Rats 71 Ratios (%) of Organ Weight to Terminal Body Weight - Summary - Male Rats 72 Ratios (%) of Organ Weight to Brain Weight - Summary - Male Rats 73 Terminal Body Weights and Organ Weights - Summary - Female Rats 74 Ratios (%) of Organ Weight to Terminal Body Weight - Summary - Female Rats 75 Ratios (9%)of Organ Weight to Brain Weight - Summary - Female Rats 76 Hematology - Summary - Male Rats 77 Hematology - Summary - Female Rats 80 Clinical Chemistry - Summary - Male Rats 83 Clinical Chemistry - Summary - Female Rats 86 Clinical and Ophthalmological Observations - Individual Data - Male Rats 89 Page 7 ARGUS 418-026 SUBJECT PAGE Table 26. Clinical and Ophthalmological Observations - Individual Data - Female Rats 95 Table 27. Body Weights - Individual Data - Male Rats 100 Table 28. Body Weights - Individual Data - Female Rats 104 Table 29. Feed Consumption Values - Individual Data - Male Rats 108 Table 30. Feed Consumption Values - Individual Data - Female Rats 110 Table 31. Motor Activity - Individual Data - Male Rats 112 Table 32. Motor Activity - Individual Data - Female Rats 120 Table 33. Functional Observational Battery - Individual Data - Male Rats 128 Table 34. Functional Observational Battery - Individual Data - Female Rats 132 Table 35. Necropsy Observations - Individual Data - Male Rats 136 Table 36. Necropsy Observations - Individual Data - Female Rats 138 Table 37. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - Male Rats 140 Table 38. Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - Male Rats 144 Table 39. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - Female Rats 148 Table 40. Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - Female Rats 152 APPENDIX C - PROTOCOL AND AMENDMENT 156 APPENDIX D - DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY 193 APPENDIX E - CERTIFICATES OF ANALYSIS 196 APPENDIX F - ANALYTICAL REPORT 199 APPENDIX G - ENVIRONMENTAL AND HUSBANDRY REPORTS 216 Page 8 ARGUS 418-026 SUBJECT PAGE APPENDIX H - OPHTHALMOLOGY REPORT 245 APPENDIX I - POSITIVE CONTROL DATA 248 APPENDIX J - HEMATOLOGY AND CLINICAL CHEMISTRY REPORT 253 APPENDIX K - HISTOPATHOLOGY REPORT 32 1 APPENDIX L - QUALITY ASSURANCE STATEMENT 441 Page 9 ARGUS 418-026 TITLE: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS ARGUS RESEARCH PROTOCOL NUMBER: 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 1. SUMMARY AND CONCLUSION 1.1. Methods" Eighty Crl:CD@(SD)IGSBR VAF/Plus@rats were randomly assigned to four dosage groups, 10 rats per sex per group. The test substance, Potassium Perfluorobutane Sulfonate (PFBS or T-7485), or vehicle, aqueous 0.1% carboxymethylcellulose,was administered once daily for at least 90 days. The dosages were 0 (Vehicle), 60,200 and 600 mg/kg/day. The dosage volume was 10 mwkg, adjusted for the most recently recorded body weight. Observations for clinical signs of effects of the test substance and deaths were made daily before dosage and approximately 60 minutes after dosage administrationand on the day of sacrifice. Detailed clinical observations were conducted for all male and female rats once before the first dosage and at least once weekly thereafter. Ophthalmological examinations were performed for all rats prior to dosage and at termination of the study. Body weights for male and female rats were recorded weekly during the dosage period and at sacrifice. Feed consumption values were recorded weekly during the dosage period. A functional observational battery and motor activity assessment were conducted on five male and five female rats per group. All surviving rats were sacrificedby on the day following the last administration of the test substance. Rats were exsanguinated following sacrifice and blood was collected for hematological and clinical biochemical evaluations. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Selected organs were weighed and retained. All gross lesions were examined histologically. Histological examination was performed on all tissues from the 0 (Vehicle) and 600 mg/kg/day dosage groups and also on the nasal cavities and turbinates, stomachs and kidneys of the male and female rats in the 60 and 200 mg/kg/day dosage groups. a. Detailed descriptionsof all procedures used in the conduct of this study are provided in the appropriate sections of this report and in APPENDIX C (PROTOCOLAND AMENDMENT). Page 10 ARGUS 4 18-026 1.2. Results One male rat in the 600 mg/kg/day dosage group was found dead on study day (DS) 85. This death was considered unrelated to administration of PFBS because it was a single event. All other male rats and all female rats survived until scheduled sacrifice. The incidence of a red perioral substance and urine-stained abdominal fur were significantly increased in male rats in the 600 mg/kg/day dosage group. Chromorhinomhea occurred in two and three male rats in the 200 and 600 mg/kg/day dosage groups, respectively. All other clinical observations in the male rats and all clinical observations in the female rats were considered unrelated to the test substance. Body weights, body weight gains and absolute (g/day) and relative (g/kg/day) feed consumption values for the male and female rats were comparable among the four dosage groups and did not significantly differ. There were no statistically significant or biologically important differences for the male and female rats among the four dosage groups in the measures of motor activity or the measures of the functional observational battery (FOB). All male and female rats appeared normal at scheduled sacrifice. The absolute weights of the spleen and the ratios of the weight of the spleen to the terminal body weight and brain weight were reduced or significantly reduced in the male rats in the 60,200 and 600 mg/kg/day dosage groups. Organ weights and the ratios of the organ weights to the terminal body weights and brain weights for the female rats were unaffected by dosages of PFBS up to 600 mg/kg/day. Average values for red blood cells (RBC),hemoglobin concentration (HGB) and hematocrit (HCT) were reduced or significantly reduced in male rats in the 200 and 600 mg/kg/day dosage groups. All other hematological parameters for the male rats and all hematological parameters for the female rats were comparable among the four dosage groups. The average value for chlorine (CL) was significantly increased in male rats in the 600 mg/kg/day dosage group. Average total protein and albumin values were significantly reduced in female rats in the 600 mg/kg/day dosage group. All other clinical chemistry parameters were unaffected in either sex by dosages of PFBS as high as 600 mg/kg/day. No microscopic changes directly related to treatment were observed in any of the male and female rats given 60 or 200 mg/kg/day of PFBS for 90 days. Treatment-related microscopic changes were observed in the kidneys and stomach of the male and female rats of the 600 mg/kg/day dosage group. The treatment-related change in the ludneys consisted primarily of an increased incidence of the male and female rats of the high dosage group with hyperplasia of the epithelial cells of the medullary and papillary tubules and ducts in the inner medullary region. Other treatment-related changes included a lower incidence of focal papillary edema and papillary necrosis. Page 11 ARGUS 418-026 The treatment-related effect in the stomach consisted of an increased incidence of necrosis of individual squamous epithelial cells in the limiting ridge of the forestomach in the male and female rats in the 600 mg/kg/day dosage group. In some of these rats, the limiting ridge also appeared to have been thickened due to hyperplasia and hyperkeratosis of this squamous mucosa. Microscopic changes of an equivocal and uncertain nature were observed in the nasal cavity/turbinates at very low and sporadic incidences in male and female rats in the 200 and 600 mg/kg/day dosage groups. These changes were quite varied and occurred in the posterior (olfactory mucosa) region and included multifocal necrosis or atrophy of the olfactory mucosa, foci of adhesions of the olfactory mucosa between turbinates and between the turbinates and the lateral nasal cavity wall, foci of inflammation, focal hyperostosis of the turbinate bone and/or foci of olfactory epithelial hyperplasia. The nasal cavity/turbinates of most rats of all groups were histologically not remarkable. The varied and focal fiistomorphologic characteristics of these lesions in the nasal cavityhrbinates are not typical or consistent with a systemic toxic effect. Although the mechanism is unknown, many of these lesions are more suggestive of a local imtating effect on the nasal mucosal membranes. 1.3. Conclusion On the basis of these data, the no-observable-adverse-effect-level (NOAEL) for PFBS in male rats is less than 60 mg/kg/day. The 60,200 and 600 mg/kg/day dosages caused significant reductions in spleen weights and the ratios of the weight of the spleen to the terminal body weight and brain weight, the 200 and 600 mgkglday dosages were associated with increased adverse clinical observations and reductions in red blood cells, and hemoglobin concentration and hematocrit, and chlorine was significantly increased at the 600 mg/kg/day dosage. The NOAEL for PFBS in female rats is 600 mg/kg/day. The 600 mg/kg/day dosage was associated with significant reductions in average total protein and albumin values, but reductions were minor and the only changes observed at the 600 mg/kg/day dosage in the female rats. Alan M. Hoberman, Ph.D., DABT Date Director of Research Study Director Associate Director o h e s d i r c h Study Director Page 12 ARGUS 4 18-026 2. DESCRIPTION OF TEST PROCEDURES 2.1. Conduct of Study 2.1.1. Sponsor 3M Corporate Toxicology, 3M Center, Building 220-2E-02, St. Paul, Minnesota 55 144-1000 2.1.2. Testing Facility Argus Research, 905 Sheehy Drive, Building A, Horsham, Pennsylvania 19044-1297 2.1.3. Study Number 418-026 2.1.4. Sponsor's Study Number T-7485.15 2.1.5. Purpose of the Study The purpose of this study was to provide information on possible adverse effects on Crl:CD@(SD)IGS BR VAF/Plus@ rats resulting from repeated exposure to Potassium Perfluorobutane Sulfonate (PFBS) over an extended period of time covering postweaning maturation and growth well into adulthood. The study was designed to provide information on toxicity, indicate target organs and the possibility of accumulation, and may provide an estimate of a no-observed-adverse-effect level (NOAEL) of exposure that can be used in dosage selection for chronic studies and for establishing safety criteria for human exposure. 2.1.6. Study Design The requirements of the U.S. Environmental Protection Agency (EPA)"' were used as the basis for study design. 2.1.7. Regulatory Compliance This study was conducted in compliance with Good Laboratory Practice (GLP) regulations of the U.S. Environmental Protection Agency (EPA)'*'. There were no deviations from the GLP regulations that affected the quality or integrity of the study. Quality Assurance Unit findings derived from the inspections during the conduct of this study are documented and have been provided to the Study Director and the Testing Facility Management. Page 13 ARGUS 4 18-026 2.1.8. Ownership of the Study The Sponsor owns the study. All raw data, analyses, reports and preserved tissues are the property of the Sponsor. 2.1.9. Study Monitor Paul H.Lieder, Ph.D., DABT 2.1.10. Study Director Raymond G. York, Ph.D., DABT (Associate Director of Research) Argus Research, 905 Sheehy Drive, Building A, Horsham, Pennsylvania 19044-1297 2.1.11. Technical Performance John F. Barnett, B.S. (Director of Laboratory Operations) Joseph W. Lech, B.S. (Senior Research Associate) Craig M. Sonntag, B.S. (Laboratory Technician) Melissa A. Carl, B.S.A.G. (Necropsy Laboratory Technician) Christopher K. Ruppert, B.S. (Formulation Laboratory Technician) 2.1.12. Report Preparation Raymond G. York, Ph.D., DABT Jo Ann Frazee, M.S. (Study Coordinator) JoAnne M. Conklin, B.S. (Data Management Specialist) Jennifer M. Hughes (Report Administrator) 2.1.13. Report Review Valerie A. Sharper, M.S., Director of Study Management 2.1.14. Date Protocol Signed 14 December 2001 2.1.15. Dates of Technical Performance Rat Arrival 11 DEC 01 Ophthalmological Evaluations 12 DEC 01 Dosage Administration 18 DEC 01 - 20 MAR 02 Ophthalmological Evaluations 15 MAR 02 Sacrifice and Necropsy 18 MAR. 02 - 21 MAR 02 Page 14 ARGUS 4 18-026 2.1.16. Records Maintained The original report, raw data and reserve samples of each lot of bulk test substance and vehicle are retained in the archives of Argus Research. Any preserved tissues are retained in the archives of the Testing Facility for one year after the mailing of the draft final report, after which time the Sponsor will decide their final disposition. All unused prepared formulations were discarded at the Testing Facility. Unused bulk test substance will be returned to the Sponsor. 2.2. Test Substance Information 2.2.1. Description Potassium Perfluorobutane Sulfonate (PFBS or T-7485) - white powder 2.2.2. 5 Lot Number 2.2.3. Date Received and Storage Conditions The test substance was received on 13 December 2001 and stored at room temperature. 2.2.4. Special Handling Instructions Standard safety precautions (use of protective clothing, nitrile gloves, dust-mist/HEPAfiltered mask, safety goggles or safety glasses and a face-shield) were worn during formulation preparation and dosage. In addition, TyvekB sleeves were worn and preparation was conducted in a chemical fume food. A half-face respirator was worn when the bulk test substance was not being used in a chemical fume hood. 2.2.5. Analysis of Purity Information to document or certify the identity, composition, method of synthesis, strength and purity of the test substance was provided by the Sponsor to the Testing Facility. A Certificate of Analysis is available in APPENDIX E. 2.3. Vehicle Information 2.3.1. Description Aqueous 0.1% carboxymethylcellulose (CMC) (medium viscosity) prepared using reverse osmosis membrane processed deionized water (R.O. deionized water). Carboxymethylcellulose - off-white powder 2.3.2. Lot Number 120K0252 Page 15 ARGUS 4 18-026 2.3.3. Date Received and Storage Conditions The powdered carboxymethylcellulose was received from Sigma Chemical Company, St. Louis, Missouri, on 11 September 2001 and stored at room temperature. R.O. deionized water is available from a continuous source at the Testing Facility and is maintained at room temperature. 2.3.4. Special Handling Instructions Standard safety precautions (use of protective clothing, nitrile gloves, dust-mist/HEPAfiltered mask, safety goggles or safety glasses and a face-shield) were taken when handling the vehicle components and prepared vehicle solutions. 2.3.5. Analysis of Purity Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the vehicle that would have interfered with the results of this study. The expiration date for the carboxymethylcellulose is September 2005. 2.4. Test Substance Preparation and Storage Conditions ' Formulations (suspensions) were prepared approximately every 10 days at the Testing Facility. Prepared test substance and vehicle formulations were stored at 2C to 8C. 2.4.1. Sample Information R.O. deionized water a. A sample of the bulk test substance was retained on the last day of dosage administration and shipped for analysis. b. Duplicate samples were taken from each concentration from the first and last preparation on the day prepared. One sample from each duplicate set was shipped for analysis. The remaining samples were retained at the Testing Facility as backup samples. c. Southern Research Institute, Birmingham, Alabama. 2.4.2. Analytical Results Information to document the homogeneity of the test substance in the prepared vehicle over the range of concentrations used in this study and the stability data for prepared Page 16 ARGUS 418-026 formulations bracketing the range of concentrations in this study was provided by the Sponsor and is available in APPENDIX F. Results of analytical analyses are available in APPENDIX F. 2.5. Test System 2.5.1. Species Rat 2.5.2. Strain Crl:CDB(SD)IGS BR VAFPlusB 2.5.3. Supplier (Source) Charles River Laboratories, Inc., Kingston, New York 2.5.4. Sex Male and female 2.5.5. Rationale for Test System The Crl:CD@(SD)IGSBR VAFPIus@ rat was selected as the Test System because: 1) it is one mammalian species accepted for use in toxicity studies; and 2) it has been widely used throughout industry for toxicity evaluations. 2.5.6. Test System Data 2.5.6.1. Male Rats Number of Rats Approximate Date of Birth Approximate Age at Arrival Weight (g) the Day after Arrival Weight (g) at Study Assignment 50 05 NOV 01 37 days 126 - 157 175 - 199 2.5.6.2. Female Rats Number of Rats Approximate Date of Birth Approximate Age at Arrival Weight (g) the Day after Arrival Weight (g) at Study Assignment 50 05 NOV 01 37 days 104 - 152 146 - 171 Page 17 ARGUS 418-026 2.5.7. Method of Randomization Upon arrival rats were assigned to individual housing on the basis of computer-generated random units. After an acclimation period of six days, male and female rats were selected for study on the basis of physical appearance and body weights recorded during acclimation. The rats were assigned to four dosage groups (Groups I through IV), 10 rats per sex per group, using a computer-generated (weight-ordered) randomization procedure. The weights of the rats assigned to the study did not exceed 220% of the mean weight of each sex. In order to accommodate the necropsy schedule, rats were randomly assigned to sacrifice on four consecutive daysa. Five rats per sex per dosage group were randomly selected for functional observational battery. 2.5.8. System of Identification Rats were permanently identified using a MonelB self piercing ear tag (Gey Band and Tag Co., Inc., No. MSPT 20101). Male and female rats assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study. Cage tags were marked with the study number, permanent rat number, sex, test substance identification, generation and dosage level. 2.6. Husbandry 2.6.1. Research Facility Registration USDA Registration No. 14-R-0144 under the Animal Welfare Act, 7 U.S.C. 213 1 et seq. 2.6.2. Study Room The study room was maintained under conditions of positive airflow relative to a hallway and independently supplied with a minimum of ten changes per hour of 100%fresh air that had been passed through 99.97% HEPA filters. Room temperature and humidity were monitored constantly throughout the study. Room temperature was targeted at 66F to 77F (19C to 25C); relative humidity was targeted at 30% to 7 0 a b . 2.6.3. Housing Rats were individually housed in stainless steel, wire-bottomed cages. All cage sizes and housing conditions were in compliance with the Guidefor the Cure and Use of Laboratory Anirnald3'. a. See APPENDIX D (DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY), item 1. b. See APPENDIX G (ENVIRONMENTAL AND HUSBANDRY REPORTS). Page 18 ARGUS 418-026 2.6.4. Lighting An automatically controlled fluorescent light cycle was maintained at 12-hours light: 12-hours dark, with each dark period beginning at 1900hours EST. 2.6.5. Sanitization Cage pan liners were changed at least three times weekly. Cages were changed approximately every other week. 2.6.6. Feed Rats were given ad libitum access to Certified Rodent Diet8#5002 (PMI Nutrition International, Inc., St, Louis, Missouri) in individual feeders. Feed was removed the evening prior to scheduled sacrifice. 2.6.7. Feed Analysis Analyses were routinely performed by the feed supplier. No contaminants at levels exceeding the maximum concentration for certified feed or deviations from expected nutritional requirements were detected by these analyses. Copies of the results of the feed analyses are available in the raw data and in APPENDIX G. Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the feed that would have interfered with the results of this study. 2.6.8. Water Local water that had been processed by passage through a reverse osmosis membrane (R.O. water) was available to the rats ad libitum from an automatic watering access system and/or individual water bottles attached to the cages. Chlorine was added to the processed water as a bacteriostat. 2.6.9. Water Analysis The processed water is analyzed twice annually for possible chemical contamination (Lancaster Laboratories, Idancaster,Pennsylvania) and monthly for possible bacterial contamination (Analytical Laboratories, Inc., Chalfont, Pennsylvania). Copies of the results of the water are available in the raw data and in APPENDIX G. Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the water that would have interfered with the results of this study. Page 19 2.7. 2.7.1. Methods Dosage Administration ARGUS 4 18-026 a. The test substance was considered 100% pure for the purpose of dosage calculations 2.7.2. Rationale for Dosage Selection Dosage levels were selected by the Sponsor on the basis of a 28-day toxicology study conducted with the test substance. In that study, 900 mg/kg/day produced significant increases in the liver weight of male rats and significant increases in kidney weights of female rats. The no-observable-adverse-effect level (NOAEL) was 300 mg/kg/day. 2.7.3. Route and Rationale for Route of Administration The oral (gavage) route was selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered; and 2) it is one possible route of human exposure. 2.7.4. Frequency of Administration Male and female rats were administered the test substance or the vehicle once daily for 90, 91,92 or 93 days. Dosages were adjusted for the most recently recorded body weight and administered at approximately the same time each day". 2.7.5. Method of Study Performance Rats were observed for viability at least twice each day of the study. Rats were examined for clinical observations and general appearance weekly during the acclimation period. Observations for clinical signs of effects of the test substance and deaths were made daily before dosage and approximately 60 k 10 minutes after dosage administration and on the day of sacrificeb. Signs of toxicity were recorded as observed, including the time of onset, degree and duration, when applicable. Once before the first dosage and at least once weekly thereafter, detailed clinical observations were conducted for all male and female rats. These observations were made outside the cage in a standard arena at the same time each day of conduct. Effort was made to ensure that variations in the test conditions were minimal. Signs noted included, but were not limited to changes in skin, a. See APPENDIX D, items 2 and 3. b. See APPENDIX D, item 5. Page 20 ARGUS 418-026 fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g., lacrimation, piloerection, pupil size, and unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes (e.g., excessive grooming, repetitive circling), or bizarre behavior (e.g., self-mutilation, wallung backwards) were recorded. Ophthalmological examinations were performed by a veterinary ophthalmologist for all rats prior to dosage and at termination of the study. Results of the ophthalmological examinations are available in APPENDIX H. Body weights for male and female rats were recorded weekly during the acclimation and dosage periods and at sacrificea. Feed consumption values were recorded weekly during the acclimation and dosage periods. Feed left was recorded on the day before sacrifice. Rats were fasted overnight before sacrifice. On one occasion.during the course of the study, not earlier than week 11 of dosage, a functional observational battery and motor activity assessment were conducted on five male and five female rats per group. The FOB evaluation was conducted by an observer unaware of the group assignment of the rat. The following parameters were assessed: 1. Lacrimation, salivation, palpebral closure, prominence of the eye, pupillary reaction to light, piloerection, respiration, and urination and defecation (autonomic functions). 2. Sensorimotor responses to visual, auditory, tactile and painful stimuli (reactivity and sensitivity). 3. Reactions to handling and behavior in the open field (excitability). 4. Gait pattern in the open field, severity of gait abnormalities, air righting reaction, and landing foot splay (gait and sensorimotor coordination). 5 . Forelimb and hindlimb grip strength. 6. Abnormal clinical signs including but not limited to convulsions, tremors and other unusual behavior, hypotonia or hypertonia, emaciation, dehydration, unkempt appearance and deposits around the eyes, nose or mouth. The ability of this battery to detect the effects of positive control substances has been established (Testing Facility Positive Control Data) and is available in APPENDIX H. ~~ a. See APPENDIX D, item 4. Page 21 ARGUS 418-026 During the motor activity assessment, the movements of each rat were monitored by a passive infrared sensor mounted outside a stainless steel, wire-bottomed cage (40.6 x 25.4 x 17.8 cm). Each test session was 1.5 hours in duration with the number of movements and time spent in movement tabulated at each five-minute interval. The apparatus monitored a rack of up to 32 cages and sensors during each session. Groups were counterbalanced across testing sessions and cages. Data demonstrating that the test system is capable of detecting increases in activity produced by positive control substances (Testing Facility Positive Control Data) is available in APPENDIX I. 2.7.6. Gross Necropsy All surviving rats were sacrificed by carbon dioxide asphyxiation on the day following the last administration of the test substance (days 91 to 94 of study). Rats were fasted overnight before sacrifice. Rats were exsanguinated from the inferior vena cava immediately following scheduled sacrifice. Approximately 5 mL of blood was collected for hematological and clinical biochemical evaluations. The tubes containing the samples were labeled with the protocol number, Sponsor study number, rat number, group number, day of study, collection interval, date of collection, species, generation and storage conditions. Approximately 1 mL of blood was collected into EDTA-coated (lavender top) tubes and maintained on wet ice and refrigerated until shipment for analysis of the following hematologic parameters: erythrocyte count (RBC), hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), total leukocyte count (WBC), differential leukocyte count, platelet count (PLAT), mean platelet volume (MPV) and cell morphology. Two blood smear slides were prepared at the Testing Facility for each sample for measurements of differential leukocyte count. Approximately 1.8 mL of blood was added to a tube containing 0.2 mL of sodium citrate (blue top) (0.129 M). The contents were mixed and maintained on wet ice until the tubes were centrifuged (within 30 minutes of the collection time). The resulting plasma was transferred to 2.0 mL polypropylene tubes and immediately frozen on dry ice and maintained frozen (470C) until shipped for measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT). Approximately 2 mL of blood was collected into serum separator tubes and centrifuged. The resulting sera samples were transferred to 2.0 mL polypropylene tubes and immediately frozen on dry ice and maintained frozen (5-70C) until shipment for analysis of the following parameters: total protein (TP), triglycerides (TRI), albumin (A), globulin (G), albumidglobulin ratio (NG),glucose (GLU), cholesterol (CHOL), total bilirubin (TBILI), urea nitrogen (BUN), creatinine (CREAT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALK), calcium (CA), phosphorus (PHOS), sodium (NA), potassium (K) and chloride (CL). Page 22 ARGUS 418-026 Samples for hematology and clinical chemistry analyses were shipped to Redfield Laboratories, A Division of CRL-DDS, Redfield, Arkansas. Blood samples for hematology were shipped refrigerated on cold packs, slides were shipped at ambient conditions and clinical chemistry sera samples were shipped on dry ice. Results of these analyses are available in APPENDIX J. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Gross necropsy included an initial physical examination of external surfaces and all orifices, as well as an internal examination of tissues and organs in situ. In addition, the cranial, thoracic and abdominal cavities were examined. The lungs were perfused with neutral buffered 10% formalin. Gross lesions were retained in neutral buffered 10% formalin and examined histologically. Tissue trimming and histopathology will be performed under the supervision of or by a Board-Certified Veterinary Pathologist. Representative photographs of gross lesions are available in the raw data. The following organs were excised, trimmed and weighed prior to fixation as soon as possible after excision to avoid drying (paired organs were weighed as pairs): adrenals, brain, kidneys, heart, thymus, spleen, liver, testes, epididymides, ovaries and uterus. The following tissues or representative samples were retained in neutral buffered 10% formalin: adrenals, aorta, bone marrow (sternum), brain (cerebrum, cerebellum, medulldpons), epididymides, esophagus, eyes (with optic nerve), femur, heart, large intestines (colon, cecum, rectum), small intestines (duodenum,jejunum, ileum), kidneys, larynx, pharynx and nose, liver, lungs, lymph nodes (mandibular, mesenteric), mammary gland (with skin, female rats only), ovaries, pancreas, Peyer's patches, pituitary, prostate, salivary gland (mandibular), sciatic nerve, seminal vesicles, skeletal muscle, skin, spinal cord (cervical, mid-thoracic, lumbar), spleen, stomach, testes (fixed in Bouin's solution for 48 to 96 hours before being retained in neutral buffered 10%formalin), thymus, thyroidparathyroid, trachea, uterus, urinary bladder and vagina. Tissues to be examined histologically were routinely processed, embedded in paraffin, sectioned at 5 microns and stained with hematoxylin and eosin. Histological examination was performed on all tissues from the 0 (Vehicle) and 600 mg/kg/day dosage groups and the nasal cavities and nasal turbinates, stomachs and kidneys of the male and female rats in the 60 and 200 mg/kg/day dosage groups. Tissues to be examined histologically were shipped to Research Pathology Services, Inc., New Britain, Pennsylvania, for evaluation. Results of the histological evaluation are available in APPENDIX K. The male rat that died was examined for the cause of death on the day the observation was made. The rat was necropsied and examined to the extent possible as described for rats sacrificed according to schedule. Gross lesions were preserved in neutral buffered 10%formalin for possible future evaluation. Representative photographs of gross lesions are available in the raw data. Page 23 ARGUS 4 18-026 2.7.7. Data Collection and Statistical Analyses Data generated during the course of ths study were recorded either by hand or using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System, the Coulboum Instruments Passive bzfrared Motor Activity System, the Coulboum Instruments Auditoiy Startle System, the Coulbouni Instruments Spatial Delayed Alternation System, andor the passive avoidance software. All data were tabulated, summarized andor statistically analyzed using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System, Microsoft Excel [part of Microsoft Office 97 (version SR-Z)] and/or The SAS System (version 6.12). Page 24 ARGUS 418-026 The following schematic represents statistical analyses of the data. I. Parametric A. Bartlett's Test Tvpe of Testa It. Nonparametricb A. Kruskal-Wallis Test h 75% ties at any concentration) Significant at 1x_0.001 Not Significant Significant at ~ 0 . 0 5 Not Significant Nonparametric Analysis of Variance A Significant at ~ 0 . 0 5 Not Significant Dunn's Test 8. Fisher's Exact Test on Proportion of Ties (>75% ties at any concentration) Dunnett's Test 8. Analysis of Variance with RepeatedMeasures Significant at ~ 0 . 0 5 Not Significant A (Dosage) (Dosage x Block Interaction) Dunnett's Test One-way ANOVA for each block I Significant at ~ 0 . 0 5 I Dunnett's Test I Not Significant I l l . Test for Proportion Data Variance Test for Homogeneity of the Binomial Distribution a. Statistically significant probabilities are reported as either p10.05 or p10.01 b. Proportion data are not included in this category. c. Test for homogeneity of variance. Page 25 ARGUS 4 18-026 Test items in the FOB using interval scales, such as the grip-strength tests and the landing foot splay test, as well as body weight data and feed consumption values were analyzed as described under the Parametric heading of the schematic. Bartlett's Test of Homogeneity of Variances'*' was used to estimate the probability that the groups had different variances. A nonsignificant result (pO.001) indicated that an assumption of homogeneity of variance was appropriate, and the data were compared using the Analysis of Variance Tedg). If that test was significant (pg.05),the groups exposed to the test substance were compared with the control group using Dunnett's Test"'). If Bartlett's Test was significant @<O.OOl), the Analysis of Variance Test was not appropriate, and the data were analyzed as described under the Nonparametric heading of the schematic. When 75% or fewer of the scores in all the groups were tied, the Kruskal-Wallis Test"" was used to analyze the data, and in the event of a significant result @ g . 0 5 ) ,Dunn's Test'") was used to compare the groups exposed to the test substance with the control group. When more than 75% of the scores in any group were tied, Fisher's Exact Test(I3) was used to compare the proportion of ties in the groups. Data from the motor activity test, with repeated measurements within a session, was analyzed using an Analysis of Variance with Repeated Measures(14),as described under that heading in the schematic. A significant effect (p10.05)in that test can appear as effect of Concentration (a difference between groups in the total across all measurements in a session) or as an interaction between Concentration and Block (a difference between groups at specific measurement periods). If the Concentration effect was significant, the totals for the control group and the groups given the test substance were compared using Dunnett's Test. If the Concentration x Block interaction was significant, an Analysis of Variance Test was used to evaluate the data at each measurement period, and a significant result (p10.05) was followed by a comparison of the groups using Dunnett's Test. Test items in the FOB having graded or count scores were analyzed using the procedures described under the Nonparametric heading of the schematic. Clinical observation incidence data, as well as the descriptive and quantal data from the FOB, were analyzed as contingency tables using the Variance Test for Homogeneity of the Binomial Di~tribution''~). Page 26 ARGUS 4 18-026 3. RESULTS - 3.1. Mortality and Clinical Observations (Summaries - Tables 1 and 2; Individual Data Tables 25 and 26) 3.1.1. Male Rats One male rat (14890) in the 600 mg/kg/day dosage group was found dead on study day (DS) 85, before administration of the 85th daily dosage. Adverse clinical observations included red perioral substance and urine-stained abdominal fur on DSs 83 to 84 and decreased motor activity, cold to touch, ptosis, dehydration, brown substance around mouth and ungroomed coat on DS 84. Weekly body weight gains and feed consumption values were normal. Necropsy revealed thin walls of the stomach in the cardiac region, stomach and intestines distended with gas, red thymus and small spleen (0.34 g); all other tissues appeared normal. This death was considered unrelated to administration of PFBS because it was a single event and the sudden onset of adverse clinical observations indicates a possible injury. All other male rats survived until scheduled sacrifice. The incidence of a red perioral substance (slight to extreme in degree) and urine-stained abdominal fur were significantly increased @<O.Ol) in male rats in the 600 mg/kg/day dosage group. Chromorhinorrhea occurred in two and three rats in the 200 and 600 mg/kg/day dosage groups, respectively. All other clinical observations were considered unrelated to the test substance because: 1) the incidences were not dosage dependent; and/or 2) the observations only occurred in one rat in a group. These clinical observations included localized alopecia of the limbs and neck, discolored fur, swollen ears or snout, excess salivation, red substance in cage pan, decreased motor activity, dehydration, ptosis, brown substance around mouth, ungroomed coat, cold to touch, soft or liquid feces, scab on the neck, head or forelimb, ulceration on neck, chromodacryorrhea, missinghroken incisors and abrasion on neck or head. Ophthalmological examination of the male rats at study termination revealed one male rat in the 200 mg/kg/day dosage group with chromodacryorrhea of both eyes: all ophthalmological examinations were normal prior to dosage administration. 3.1.2. Female Rats All female rats survived to scheduled sacrifice. All clinical observations in the female rats were considered unrelated to PFBS because: 1) the observations were not dosage-dependent; and/or 2) the observations only occurred in one or two rats in a group. These clinical observations included missinghroken or misaligned incisors, localized alopecia of the limbs and back, chromodacryorrhea, urine-stained abdominal fur, red, slight perioral substance, excess salivation, swollen ears, rales, red substance in cage pan, soft or liquid feces, chromorhinorrhea, bent tail and abrasion on forepaw. Ophthalmological examination of the female rats prior to dosage administration revealed one female rat in the 60 mg/kg/day dosage group with iritis of the left eye; all ophthalmological examinations were normal at study termination. Page 27 ARGUS 418-026 3.2. . 3.2.1. - Body Weights and Body Weight Changes (Figures 1and 2; Summaries Tables 3 through 6; Individual Data - Tables 27 and 28) MaleRats Body weights and body weight gains for the male rats in all four dosage groups were comparable throughout the dosage period. Body weight gains were significantly reduced (pl0.0 1) on DSs 15 to 22 in the 60 and 200 mg/kg/day dosage groups but were not considered treatment-related because: 1) they were not dosage dependent; and 2) they occurred only once. 3.2.2. Female Rats Body weightsand body weight gains for the female rats in all four dosage groups were comparable throughout the dosage period. Body weight gain was significantly increased (plO.01) on DSs 43 to 50 in the . 60 mg/kg/day dosage group but was not considered treatment-related because: 1) it was . not dosage dependent; and 2) it occurred only once. 3.3. Absolute @/day) and Relative (g/kg/day) Feed Consumption Values (Summaries - Tables 7 through 10; Individual.Data - Tables 29 and 30) Absolute (g/day) and relative (g/kg/day) feed consumption values for the male and female rats were comparable among the four dosage groups and did not significantly differ. 3.4. Motor Activity and Functional Obsevational Battery (Figures 3 through 6 ; Summaries - Tables 11 and 12;Individual Data - ..Tables31 through 34) . There were no statistically significant or biologically important differences for the male and female rats among the four dosage groups in the measures of motor activity on DS 86. There were no statistically significant or biologically important differences among the four dosage groups in the measures of the fbnctional observational battery (FOB). There were no alterations in home cage behavior, autonomic functions (lacrimation, salivation, palpebral closure, prominence of the eye, pupillary reaction to light, piloerection, respiration, defecation and urination), sensorimotor functions [responses to visual, auditory, tactile and painful stimuli (reactivity and sensitivity)], excitability (reactions to handling and behavior in the open field), gait and sensorimotor coordination (gait pattern ' in the open field, severity of gait abnormalities, air righting reaction and landing foot splay) and forelimb and hindlimb grip strength and abnormal clinical observations - including but not limited to:. convulsions, tremors, unusual behavior, hypotonia or I Revised Page 28 ARGUS 4 18-026 hypertonia, emaciation, dehydration, unkempt appearance and deposits around the eyes. nose or mouth. Body weights recorded during the FOB for the male and female rats in the four dosage groups were Comparable and did not differ significantly. - 3.5. Necropsy Observations (Summaries Tables 13 and 14; Individual Data - Tables 35 and 36) The only necropsy observations in the male rat occurred in the male rat in the 600 mg/kg/day dosage group that was found dead and were previously described; all male rats appeared normal at scheduled sacrifice. All female rats appeared normal at necropsy. 3.6. Terminal Body Weights, Organ Weights and the Ratio (%) of Organ Weight to Terminal Body Weight and Brain Weight (Summaries - Tables 15 through 20; Individual Data - Tables 37 through 40) 3.6.1. Male Rats Terminal body weights for the male rats were comparable among the four dosage groups and did not differ significantly. The absolute weights of the spleen and the ratios of the weight of the spleen to the terminal body weight and the brain weight were reduced or significantly reduced ($50.05 orplO.O1) in the 60,200 and 600 mg/kg/day dosage groups. The weights of the epididymides, testes, brain, liver, kidneys, adrenals, thymus and hart and the ratios of these organ weights to the terminal body weights and the brain weights for the male rats were unaffected by dosages of PFBS up to 600 mg/kg/day. 3.6.2. Female Rats Terminal body weights for the female rats were comparable among the four dosage groups and did not differ significantly. The weights of the brain, liver, kidneys, adrenals, spleen, thymus, ovaries, uterus and heart and the ratios of these organ weights to the terminal body weights and the brain weights for the female rats were unaffected by dosages of PFBS up to 600 mg/kg/day. Page 29 ARGUS 418-026 3.7. Hematology (Summaries - Tables 21 and 22; Individual Data APPENDIX J) Average values for red blood cells (RBC),hemoglobin concentration (HGB) and hematocrit (HCT) were reduced or significantly reduced (p10.05or ~50.01i)n male rats in the 200 and 600 mg/kg/day dosage groups. Average values for leukocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, mean platelet volume, prothrombin time, activated partial thromboplastin, nucleated red blood cell count, segmented neutrophils, bands, monocytes, eosinophils, basophils, abnormal lymphocytes and other cells were comparable among the four dosage groups for male and female rats. The mean corpuscular hemoglobin concentration was significantly increased (pl0.05) in the 60 mg/kg/day dosage group female rats but was not considered treatment related because it was not dosage dependent. 3.8. Clinical Chemistry (Summaries - Tables 23 and 24; Individual Data - APPENDIX J) The average value for chlorine (CL) was significantly increased (plO.01) in male rats in the 600 mgkglday dosage group. Average total protein and albumin values were significantly reduced (pl0.05)in female rats in the 600 mg/kg/day dosage group. Average values for glucose, cholesterol, total bilirubin, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, calcium, inorganic phosphorus, triglycerides, sodium, potassium, globulin and the albumirdglobulin ratio were unaffected in either sex by dosages of PFBS as high as 600 mg/kg/day. 3.9. Histopathology (APPENDIXK) Compound-related microscopic changes were observed in the ludneys and stomach of the male and female rats of the 600 mgkglday dosage group. The primary treatment-related change in the kidneys consisted of an increased incidence of the male and female rats in the 600 mg/kg/day dosage group with hyperplasia of the epithelial cells of the medullary and papillary tubules and ducts in the inner medullary region. These tubules had a dark tinctorial appearance with increased amounts of small interstitial cells with prominent dark nuclei. Other treatment-related changes included a lower incidence of focal papillary edema and a single incidence of papillary necrosis in both kidneys of one male rat in the 600 mg/kg/day dosage group. The treatment-related effect in the stomach consisted of an increased incidence of necrosis of individual squamous epithelial cells in the limiting ridge of the forestomach in the male and female rats in the 600 mg/kg/day dosage group. This change was characterized by individual squamous epithelial cells with dark pyknotic nuclei surrounded by a clear cytoplasmic halo. This change was seen at a very low incidence in the rats of the other dosage groups, including a control female rat, but the increased incidence of this change, along with minimal or mild thickening of the mucosa of the Page 30 ARGUS 4 18-026 limiting ridge due to hyperplasia and hyperkeratosis, was considered to be treatmentrelated in the 600 mg/kg/day dosage group. Microscopic examination of the nasal cavity and nasal turbinates revealed a few equivocal microscopic changes that occurred at low and sporadic incidences in rats in the 200 and 600 mg/kg/day dosage groups. These changes occurred primarily in the posterior nasal cavityhrbinates and involved the olfactory mucosa. These histomorphologic changes included single or low incidences of multifocal necrosis or atrophy of the olfactory mucosa, focal acute/subacute or chronic inflammation, adhesions of the turbinate to either an adjacent turbinate or to the lateral nasal wall, focal hyperostosis of turbinate bone andor foci of olfactory epithelial hyperplasia. Foci of inflammation may occur spontaneously in the nasal cavity of rats, but in several of the above-mentioned lesions, the inflammation was associated with these other changes. The lesions in the nasal cavity/turbinates are of uncertain significance and origin mainly because they occurred only in the 200 and 600 mg/kg/day dosage groups at very low and sporadic incidences and were focal or multifocal in distribution. The nasal cavity/turbinates 'of most rats of all groups were histologically not remarkable. The varied and focal histomorphologic characteristics of these lesions in the nasal cavity/turbinates are not typical or consistent with a systemic toxic effect. Although the mechanism is unknown, many of these lesions are more suggestive of a local irritating effect on the nasal mucosal membranes. Page 31 ARGUS 4 18-026 REFERENCES 1. U.S. Environmental Protection Agency Health Effects Test Guidelines; 90-Day Oral Toxicity in Rodents. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3100,August 1998. 2. U.S. Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFRA/TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 16OPart 792, July 2000. 3. Institute of Laboratory Animal Resources (1996). Guidefor the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C. 4. Haggerty, G.C. (1989). Development of Tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. J. Amer. Col. Toxicol. 853-70. 5. Irwin, S. (1968). Comprehensive observational assessment: Ia. A systemic quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia (Berlin) 13:222-257. 6. Moser, V.C. (1989). Screening approaches to neurotoxicity: A functional observational battery. J. Amer. Col. Toxicol. 8:85-94. 7. O'Donoghue, J.L. (1989). Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Amer. Col. Toxicol. 8:97- 116. 8. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 9. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 10. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 11. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389. 12. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. 13. Siegel, S. (1956). Nonparametric Statisticsfor the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. 14. SAS Institute, Inc. (1988). Repeated measures analysis of variance. S A S / S T A P User'$ Guide, Release 6.03 Edition, Cary, NC, pp. 602-609. 15. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 240-241. Page 32 ARGUS 418-026 APPENDIX A REPORT FIGURES Page 33 PROTOCOL 418-026:ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANESULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) BODY WEIGHTS - MALE RATS 550 500 450 400 h 2 E l- % c3 350 w P 300 250 - - v 0 (VEHICLE) MGlKGlDAY A60 MGlKGlDAY - 17200 MGIKGIDAY e- 600 MGIKGIDAY a. Terminal body weight. 200 --, 150 - --T---i----r- 1 -- T- 7 -- r - - - I - - r --- I - - 1 I 1 8 15 22 29 36 43 50 57 64 71 78 85 a DAY OF STUDY PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANESULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) BODY WEIGHTS - FEMALE RATS 320 300 280 260 h 2 240 tI yi? w 220 ul 200 180 -v 0 (VEHICLE) MG/KG/DAY -A 60 MGlKGlDAY +I 200 MG/KG/DAY 0 600 MG/KG/DAY ~ a. Terminal body weight. 160 140 I - I-- 7 - 1 8 1--- T- - 1 - 1 - T-- 1 - I 7 1-1 15 22 29 36 43 50 57 64 71 78 85 I a DAY OF STUDY PROTOCOL 418-026: ORAL (GAVAGE) REPEATEDDOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSORS STUDY NUMBER: T-7485.15) MOTOR ACTIVITY - NUMBER OF MOVEMENTS - MALE RATS Figure 3 80 T-7 70 0 (VEHICLE) MGIKG/DAY 60 cn I50 2 W > 0 840 w m W 30 3 Z A 60 MGIKGIDAY C) 200 MGlKGlDAY I 600 MG/KG/DAY 20 10 0 0 20 40 60 80 100 TIME (MINUTES) PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) MOTOR ACTIVITY - TIME SPENT IN MOVEMENT - MALE RATS 250 ~ 200 - z W z w > 0 z Z 150 Iz- W 2 % a cn w 4 ch n 9 100 0 0 W ", 'Wz 50 -y3 - 0 (VEHICLE) MGlKGlDAY A 60 MGIKGIDAY (- t 200 MGlKGlDAY m- 600 MGlKGlDAY ~- 0 0 20 40 60 80 100 TIME (MINUTES) PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSORS STUDY NUMBER: T-7485.15) MOTOR ACTIVITY - NUMBER OF MOVEMENTS - FEMALE RATS 80 60 0 zI- w z Y cd 0 40 6 w LI 0 0 r1wy: m J z 20 0 (VEHICLE) MGIKGIDAY A ~~ 60 MGIKGIDAY i >- 200 MGlKGlDAY I- 600 MGlKGlDAY 0 0 20 40 60 80 100 TIME (MINUTES) PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE SO-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) MOTOR ACTIVITY - TIME SPENT IN MOVEMENT - FEMALE RATS 200 _ _ -_ - _ _~ zz - cn I- wZ 150 -5 w > 0 IZ 100 cn h zvn) z 0 0 W 50- F \ 0 _ _- 1 -- -7 --- - T - - - ~ 1- c? A . '' A r, / I'J A 1 -- - , A - -A a--+-y = ms;1 _- I? A -1 ~ ~_ T%'"-0 (VEHICLE) MGIKGIDAY A 60 MGIKGIDAY -t- ' 200 MGIKGIDAY I 600 MGIKGIDAY ARGUS 41 8-026 APPENDIX B REPORT TABLES Page 40 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 1 (PAGE 1): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - SUMMARY - MALE RATS LOCALIZED ALOPECIA: TOTAL LIMBS NECK 1121 3 112/ 3 01 0 541 2 54/ 2 o/ 0 FUR DISCOLORED ol 0 11 1 1/ 1 2/ 2 EAR ( S ): SWOLLEN 1 o/ 0 01 0 141 1 EXCESS SALIVATION 221 2 11 1 21 2 11 1 RED SUBSTANCE IN CAGE PAN o/ 0 01 0 o/ 0 11 1 DECREASED MOTOR ACTIVITY o/ 0 o/ 0 o/ 0 1/ lb DEHYDRATION o/ 0 01 0 o/ 0 1/ lb PTOSIS ol 0 01 0 o/ 0 1/ lb ________________________________________-------------------------------------------------------------------------------------------- STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. R a t 14890 was found dead on day 85 of study. v, * * Significantly different from the vehicle control group value (p.cO.01). P c-- M b m13 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 1 (PAGE 2 ) : CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - SUMMARY - MALE RATS GROUP _D-O-S_A_G-E_ _(_M_G/_K_G_/_DA_Y_)a_ _ _ _ _ _ _ _ _ _ _ _ _ _ MAXIMUM POSSIBLE INCIDENCE FOUND DEAD MOUTH: BROWN SUBSTANCE UNGROOMED COAT COLD TO TOUCH SOFT OR LIQUID FECES SCAB c NECK : ULCERATION P h, CHROMODACRYORRHEA INCISORS: MISSING/BROKEN SNOUT: SWOLLEN NECK OR HEAD: ABRASION OPHTHALMOLOGICAL EXAMINATION: PRIOR TO DOSAGE: ALL EYES APPEARED NORMAL TERMINATION: BOTH EYES: CHROMODACRYORRHEA 0 0 1 0 .................................................................................................................................... b STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. b N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. 4 v, a . Dosage occurred on days 1 through 9 0 , 91, 92, o r 93 of study. P b. Rat 14890 was found dead on day 85 of study. c- c . Neck, head, or r i g h t forelimb. oo 1m 3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 (PAGE 1): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - SUMMARY - FEMALE RATS MORTALITY 0 0 0 0 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 51/ 1 o/ 0 51/ 1 4/ 1 4/ 1 4/ 1 27/ 3 18/ 2 9/ 1 LOCALIZED ALOPECIA: TOTAL LIMBS BACK 119/ 2 119/ 2 o/ 0 23/ 2 23/ 2 o/ 0 s9/ 2 59/ 2 9/ 1 CHROMODACRYORRHEA 3/ 1 o/ 0 o/ 0 4/ 2 URINE-STAINED ABDOMINAL FUR o/ 0 o/ 0 o/ 0 3/ 1 RED, SLIGHT PERIORAL SUBSTANCE 1/ 1 o/ 0 o/ 0 I/ 3 EXCESS SALIVATION o/ 0 o/ 0 o/ 0 1/ 1 EAR ( S ) : SWOLLEN o/ 0 15/ 1 19/ 1 o/ 0 RALES 5/ 1 o/ 0 11/ 1 o/ 0 RED SUBSTANCE IN CAGE PAN o/ 0 o/ 0 2/ 1 o/ 0 SOFT OR LIQUID FECES I/ 1 o/ 0 I/ 1 o/ 0 CHROMORHINORRHEA 3/ 2 o/ 0 o/ 0 o/ 0 TAIL BENT 34/ 1 o/ 0 o/ 0 o/ 0 bc o / o / LEFT FOREPAW: ABRASION 5/ 1 0 0 Q / 0 CA ____________________-------------------------------------------------- STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. b MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. bm J PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 (PAGE 2 ) : CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - SUMMARY - FEMALE RATS OPHTHALMOLOGICAL EXAMINATION: PRIOR TO DOSAGE: LEFT EYE: IRITIS 0 1 0 0 TERMINATION: ALL EYES APPEARED NORMAL .................................................................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER O F OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. P P PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 (PAGE 1 ) : BODY WEIGHTS - SUMMARY - MALE RATS GROUP DOSAGE (MG/KG/DAY)a ___-__________________ RATS TESTED BODY WEIGHT (G) DAY 1 DAY 8 DAY 1 5 DAY 22 DAY 2 9 DAY 36 DAY 4 3 DAY 5 0 DAY 5 7 DAY 64 DAY 7 1 DAY 7 8 DAY 8 5 TERMINATION c I 0 (VEHICLE) _-_______________--------------- N lo MEANfS.D . MEANfS .D . MEANfS .D. MEANfS.D . MEANkS.D. MEANfS .D. MERNfS .D . MEANfS .D . MEANfS .D . MEANfS .D . MEANfS .D . MEANfS.D . MEANfS . D. MEANfS.D . 192.1 f 7.3 254.4 f 1 2 . 1 309.4 f 15.4 350.9 f 22.0 387.7 f 28.0 415.3 f 32.6 438.5 f 35.9 458.9 f 39.8 480.0 f 42.6 494.5 f 43.7 509.6 f 44.4 520.1 f 46.6 531.7 f 47.0 510.9 f 47.0 192.9 f 6.8 252.3 f 13.0 303.7 f 20.4 337.0 f 25.9 369.2 f 32.0 392.1 f 35.4 416.7 f 42.5 433.7 t 46.0 451.3 f 48.6 466.4 f 52.4 481.8 f 55.2 489.3 f 58.2 506.0 f 64.6 482.6 f 60.4 190.0 f 7.2 248.8 f 7.6 295.5 f 11.3 328.3 f 12.9 358.2 f 14.8 382.2 f 14.0 403.5 f 19.2 423.8 f 22.6 441.2 f 22.6 460.9 f 24.7 477.0 f 28.1 486.5 f 29.2 500.9 f 33.0 479.6 f 30.3 IV 600 10 193.1 f 7.2 255.4 f 10.2 304.5 f 11.2 343.5 f 14.4 373.5 f 18.7 402.3 f 20.7 423.8 f 28.0 446.3 f 30.0 462.3 f 34.6 478.9 f 37.7 495.2 + 40.9 502.7 f 41.7 DAY = DAY OF STUDY [ 1 = NUMBER O F VALUES AVERAGED. a. Dosage occurred on days 1 through 90, 91, 9 2 , or 9 3 of study. b. Excludes values for rat 1 4 8 9 0 , which was found dead on day 8 5 of study. c. Rats were fasted the evening prior to sacrifice. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 4 (PAGE 1): BODY WEIGHT CHANGES - SUMMARY - MALE RATS RATS TESTED N 10 10 10 lo BODY WEIGHT CHANGE (G) DAYS DAYS 1- 8 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 MEANfS .D . MEANfS .D . MEANfS .D . MEANfS .D . MEANfS .D . +62.3 f 6.6 +55.0 f 5.0 t41.5 f 7.5 t36.8 f 7.4 t27.6 f 8.0 +59.4 f 6.6 +51.4 f 9.3 +33.3 f 6.7** +32.2 f 7.5 t22.9 f 4.1 +58.8 f 6.2 +46.7 f 4.7 +32.8 f 4.9** +29.9 f 5.6 +24.0 f 4.4 +62.3 f 5.3 +49.1 f 7.9 t39.0 f 5.8 t30.0 f 5.6 t28.8 f 4.6 DAYS 36 - 43 DAYS 43 - 50 MEANfS .D . MEANfS .D. +23.2 f 6.7 t20.4 f 5.3 t24.6 f 8.1 +17.0 f 5.2 +21.3 f 7.6 +20.3 f 4.8 +21.5 f 9.2 t22.5 f 4.7 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 71 MEANfS .D . MEANfS .D. MEANfS .D. +21.1 f 6.2 t14.5 f 2.8 t15.1 f 6.1 t17.6 f 6.0 t15.1 f 9.1 +15.4 f 4.9 t17.4 f 2.6 t19.7 f 7.8 t16.1 f 7.1 +16.0 f 9.7 +16.6 f 6.2 +16.3 f 6.8 DAYS 71 - 78 MEANkS .D. t10.5 f 8.8 +7.5 f 6.4 +9.5 f 4.9 +7.5 f 5.0 DAYS 78 - 85 MEANfS.D. t11.6 f 6.9 +16.7 f 10.7 +14.4 f 6.8 t9.9 f 7.3 DAYS 85 TERMINATION C MEANfS .D . -20.8 f 8.1 -23.4 f 5.8 -21.3 ? 6.9 [ 91b -23.8 f 8.5 DAYS 1 TERMINATION C MEANfS.D . t318.8 f 42.6 t289.7 f 55.7 I 91b 4 m ...................................................................................... P c DAY(S) = DAY(S) OF STUDY [ 1 = NUMBER OF VALUES AVERAGED a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes a value for rat 14890, which was found dead on day 85 of study. c. Rats were fasted the evening prior to sacrifice. * * Significantly different from the vehicle control group value ( ~ ~ 0 . 0 1 ) . PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 5 (PAGE 1): BODY WEIGHTS - SUMMARY - FEMALE RATS GROUP DOSAGE (MG/KG/DAY)a ____________________- RATS TESTED N 10 10 10 10 BODY WEIGHT (G) DAY 1 DAY 8 DAY 15 DAY 22 MEANfS .D . MEANfS .D. MEANfS .D . MEANfS .D. 161.5 f 9.6 187.2 f 9.1 212.8 i 14.0 228.4 f 16.2 161.0 f 7.7 190.2 f 9.1 213.3 f 14.9 233.5 f 13.3 157.9 f 11.2 189.7 f 11.9 212.8 f 13.7 231.1 f 17.0 158.1 f 10.9 184.8 f 11.7 205.8 f 13.3 220.2 f 17.9 DAY 29 DAY 36 P 4 DAY 43 DAY 50 DAY 57 MEANfS .D. MEANfS.D . MEANfS .D. MEANfS .D . MEANkS . D. 242.3 f 18.4 255.5 f 21.5 266.2 f 21.9 272.2 f 22.3 277.4 f 21.1 246.9 f 14.4 261.0 f 15.6 265.6 f 17.9 277.8 f 18.0 283.5 f 19.2 248.9 f 21.4 261.4 f 22.3 269.9 f 23.7 277.2 f 25.8 286.6 f 29.2 233.2 f 15.6 246.6 f 14.4 257.3 f 15.9 263.2 f 16.6 267.5 f 19.4 DAY 64 DAY 71 MEANkS . D. MEANfS .D . 284.0 f 23.4 289.5 f 25.3 288.8 f 20.1 296.0 f 23.1 292.3 f 28.6 295.4 k 31.4 274.9 f 17.0 279.3 f 18.4 DAY 78 MEANf.5.D. 289.0 f 25.4 299.1 f 21.7 296.4 f 32.4 277.6 f 17.6 DAY 85 MEANfS .D. 295.7 f 22.7 306.6 f 20.8 306.5 f 31.7 281.6 f 21.4 TERMINATION b MEANfS.D. 276.5 f 24.0 286.0 f 21.5 ................................................................................ DAY = DAY OF STUDY a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Rats were fasted the evening prior to sacrifice. 284.8 f 30.1 .................... 264.6 i 19.5 -----__-______-____ 1 0 tm3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 6 (PAGE 1): BODY WEIGHT CHANGES - SUMMARY - FEMALE RATS BODY WEIGHT CHANGE (G) DAYS 1 - 8 . MEANfS D. DAYS 8 - 15 MEANfS.D. DAYS 15 - 22 MEANfS .D. DAYS 22 - 29 MEANkS .D. DAYS 29 - 36 MEANfS .D . P DAYS 36 - 43 MEANiS.D . 00 DAYS 43 - 50 MEANiS .D . DAYS 50 - 57 MEANiS .D . t25.7 f 7.3 t25.6 f 8.2 t15.6 f 4.9 t13.9 f 6.3 +13.2 f 7.2 +10.7 f 5.8 +6.0 f 3.8 +5.2 f 5.3 t29.2 f 7.8 +23.1 f 8.9 +20.2 f 5.8 t13.4 f 7.3 +14.1 f 5.9 +4.6 f 6.8 +12.2 f 4.7'' t5.7 f 1.4 +31.8 f 5.8 t23.1 f 3.5 +18.3 f 6.1 t17.8 f 7.2 t12.5 f 4.3 +8.5 f 4.1 +7.3 f 4.6 t9.4 f 5.2 +26.7 f 4.5 t21.0 f 7.4 +14.4 f 11.5 +13.0 f 10.7 +13.4 f 4.6 t10.7 f 5.7 t5.9 f 4.3 +4.3 f 6.1 DAYS 57 - 64 DAYS 64 - 71 DAYS 71 - 78 DAYS 78 - 85 DAYS 85 TERMINATION b MEANfS.D. MEANkS.D. MEANfS.D . MEANfS .D. MEANfS .D. t6.6 f 5.4 t5.5 f 4.3 -0.5 f 4.9 t6.7 f 8.2 -19.2 f 6.7 +5.3 f 7.6 + 7 . 2 f 7.6 +3.1 f , 3.6 t7.5 * 7.3 -20.6 f 3.3 +5.7 f 5.5 t3.1 f 6.1 t1.0 f 5.0 +10.1 f 4 . 2 -21.7 f 3.8 +7.4 f 4.7 +4.4 f 5.8 -1.7 * 9.0 +4.0 f 6.6 -17.0 f 4.2 DAYS 1 - TERMINATION b MEANfS .D. t115.0 f 21.0 t125.0 f 21.8 +126.9 f 23.5 t106.5 +_ 1 7 . 1 .................................................................................................................................... DAY(S) = DAY(S) OF STUDY a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Rats were fasted the evening prior to sacrifice. * * Significantly different from the vehicle control group value ( ~ ~ 0 . 0 1 ) . PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE I (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - MALE RATS GROUP DOSAGE (MG/KG/DAY)a ____________-__-__------- RATS TESTED I I1 I11 0 (VEHICLE) 60 200 ________________________________________---------------------------- lo 10 10 FEED CONSUMPTION (G/DAY) DAYS 1 - 8 MEANfS .D. 23.3 f 1.4 23.4 f 2 . 1 22.3 f 1.6 23.4 f 1 . 4 DAYS 8 - 1 5 DAYS 1 5 - 22 MEANfS .D. MEANfS.D . 26.2 f 1.6 26.8 f 2.1 26.6 f 2.9 26.3 f 2.6 24.8 f 24.5 f 1.8 1.2 25.9 f 1.6 26.0 f 2.0 DAYS 22 - 2 9 MEANfS .D. 21.6 f 2.4 26.9 f 2.8 25.2 k 1.3 26.5 f 1.6 DAYS 29 - 3 6 MEANfS.D. 21.0 f 2.9 26.0 f 2.7 24.8 f 1.2 - DAYS 36 4 3 MEANfS .D. 21.1 f 2.9 26.2 f 2.8 25.2 f 1.8 P v) DAYS 43 - 5 0 MEANfS .D. 21.5 f 3.0 26.9 f 3.5 26.1 f 3.1 DAYS 5 0 - 51 MEANfS .D . 21.5 f 2.1 26.9 f 3.7 25.6 f 2 . 1 DAYS 5 1 - 64 MEANfS .D. 21.2 f 2.6 26.6 f 3.4 25.8 f 2.2 DAYS 64 - I 1 DAYS I 1 - I 8 MEANfS .D. MEANkS .D . 27.3 f 2.3 21.3 f 2.6 26.9 f 3.4 27.1 f 3.4 25.8 f 2.5 25.1 f 2.2 DAYS I 8 - 85 MEANfS.D . 26.6 f 2.7 26.6 f 4.0 24.1 f 2.1 DAYS 1 - 8 5 MEANkS .D. 26.8 f 2.2 25.1 f 1.5 .................................................................................................. DAYS = DAYS OF STUDY [ 1 = NUMBER OF VALUES AVERAGED a. Dosage occurred on days 1 through 90, 9 1 , 9 2 , or 93 of study. b . Excludes values that were associated with spillage. c. Excludes values for rat 1 4 8 9 0 , which was found dead on day 8 5 of study. 26.0 f 1.6 [ 9lb 27.1 f 2.5 26.8 f 2.6 26.6 f 2.5 27.4 f 2.7 21.2 f 2.1 21.0 I 25.4 [ 26.1 [ f 9lb f 91 c f 91c 2.2 1.8 1.8 PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 8 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/I)AY) - SUMMARY - MALE RATS GROUP DOSAGE (MG/KG/DAY)a ......................................... --- RATS TESTED N 10 I1 I11 IV 60 200 600 ________________________________________---------------------------- 10 10 lo FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 8 DAYS 8 - 1 5 DAYS 1 5 - 22 DAYS 22 - 29 DAYS 29 - 3 6 DAYS 36 - 4 3 DAYS 4 3 - 5 0 DAYS 50 - 57 DAYS 57 - 64 MEANfS .D . MEANfS .D. MEANfS .D . MEANfS .D . MEANfS .D. MEANfS,D . MEANfS .D . . MEANfS .D MEANkS .D . DAYS 64 - 7 1 MEANfS.D . DAYS 7 1 - 78 MEANfS .D. DAYS 78 - 8 5 MEANfS.D . DAYS 1 - 85 MEANfS.D . 104.4 f 92.8 f 81.0 f 7 4 . 8 f. 67.2 f 63.6 f 61.3 f 58.6 f 55.9 f 54.5 f 53.1 f 50.6 f 65.2 f 4.3 5.6 4.9 4.8 5.3 4.8 4.4 3.2 2.6 3.1 3.2 3 .O 3.0 105.2 f 6.8 95.7 f 7.7 82.0 f 5.0 76.1 f 4.3 68.3 f 3.5 64.9 f 4 . 1 63.2 f 4.2 60.7 f 3.8 57.9 f 3.5 56.6 f 3.0 55.9 f 4.5 53.1 f 3.3 [ 8lb 66.8 f 3.4 [ 8lb 101.8 f 91.0 f 78.6 f 73.3 f 67.0 f 64.1 f 63.1 f 59.2 f 57.2 f 55.0 f 53.3 f 50.0 f 65.2 f 8.1 4.8 2.6 2.4 2.7 2.7 6.4 2.8 3.3 3.3 1.9 3.2 1.9 104.5 f 4.4 92.4 f 4.0 80.3 f 4.2 74.0 f 2.2 67.7 [ 65.5 f 9lb f 2.0 3.5 61.5 f 3.4 58.6 f 3.5 58.4 f 5.7 56.0 f 5.7 53.6 f 2.4 [ 9lb 50.5 f 4 . 5 [ 91c 65.6 f 2.7 [ 91c DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Dosage occurred on days 1 through 90, 91, 9 2 , o r 93 of study. b. Excludes values that were associated with spillage. b c. Excludes values for rat 1 4 8 9 0 , which was found dead on day 8 5 of study. 1m 3 PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 9 (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - FEMALE RATS GROUP DOSAGE (MG/KG/DAY)a ___________________r_____ RATS TESTED FEED CONSUMPTION (G/DAY) DAYS 1 - 8 DAYS 8 - 1 5 DAYS 1 5 - 22 DAYS 22 - 29 MEANfS .D. MEANfS .D. MEANfS.D. MEANfS .D . DAYS 29 - 3 6 DAYS 3 6 - 4 3 DAYS 4 3 - 50 DAYS 50 - 5 7 DAYS 5 7 - 64 MEANfS .D. MEANfS.D . MEANfS .D. MEANfS .D . MEANfS .D. DAYS 64 - 7 1 DAYS 7 1 - 7 8 MEANfS .D. MEANfS .D. DAYS 78 - 8 5 MEANfS.D . DAYS 1 - 8 5 MEANfS .D. 17.1 f 1.1 [ 9lb 19.0 f 2.1 18.9 f 2.5 18.6 f 1.5 18.6 f 1.6 19.0 f 1.5 1 8 . 2 f 1.1 18.0 f 1.3 18.2 f 1.8 18.0 f 1.6 17.7 f 1.3 17.4 f 0.9 1 8 . 3 f 1.1 I1 60 10 17.8 f 18.4 f 18.7 f 19.1 f 19.1 f 19.3 f 19.6 f 18.7 f 18.8 f 18.6 f 19.1 f 18.1 f 18.8 f 1.6 1.5 1.3 1.4 1.5 1.7 1.6 1.9 2.0 1.8 1.5 1.8 1.4 17.7 f 1.5 19.2 f 1.5 19.2 f 2.1 20.0 f 1 . 9 [ 91b 19.8 f 2.2 20.1 f 2.2 [ 9lb 19.7 f 2.2 19.4 f 2.1 19.0 f 1.7 [ 8lb 18.4 f 2.3 19.0 f 2.1 18.9 f 1.7 19.2 f 1.8 17.2 f 1.6 18.3 f 2.4 I 9lb 18.8 f 3.0 18.9 f 1.9 19.1 [ 18.5 [ 18.5 [ 18.2 [ 18.5 f 9lb f 8lb f 9lb f 9lb f 2.3 1.4 1.4 1.5 1.5 17.6 f 1.6 17.8 f 2.0 17.2 f 3.5 1 8 . 2 f 1.3 PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE i o (PAGE 1) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - FEMALE RATS RATS TESTED N 10 10 10 lo FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 8 MEANfS.D . DAYS 8 - 1 5 MEANfS .D. DAYS 1 5 - 22 MEANfS.D. DAYS 22 - 29 MEANfS.D . DAYS 29 - 3 6 MEANfS .D. DAYS 36 - 4 3 MEANfS .D . DAYS 4 3 - 5 0 MEANfS.D . DAYS 50 - 57 MEANfS .D. DAYS 5 7 - 64 DAYS 64 - 7 1 MEANfS.D . . MEANfS D. DAYS 7 1 - 78 MEANfS.D . DAYS 78 - 8 5 MEANfS .D. DAYS 1 - 8 5 MEANfS .D. 97.9 [ 94.9 f 4.0 9lb f 10.0 8 5 . 8 f 11.1 79.0 f 3.4 74.8 f 3.2 72.9 f 3.1 67.9 f 3.5 65.8 f 4.3 64.6 f 3.3 62.9 f 4.0 61.4 f 3.4 59.6 f 3.5 72.9 f 2.0 101.3 f 91.3 f 83.9 f 79.5 f 75.4 f 73.2 f 72.2 f 66.8 f 65.7 f 63.5 f 64.4 f 59.7 f 73.5 f 8.7 4.9 4.8 4.4 4.1 4.0 6.0 5.0 4.6 2.8 3.5 3.7 3.5 101.8 f 5.5 95.2 f 4 . 1 86.3 f 5.1 82.8 f 3.5 [ 9lb 77.5 f 5.4 75.3 f 2.7 [ 9lb 72.0 f 3.4 68.7 f 2.7 64.9 f 1.6 [ 8lb 62.8 f 5.7 64.5 f 4.4 62.9 f 4.6 74.9 f 2.6 100.1 f 6.5 93.9 [ 88.0 f 9.7 91b f 13.2 83.5 f 10.0 80.0 f 7.7 [ 9lb 73.4 f 2.8 [ 8lb 71.0 f 3.2 [ 9lb 68.5 f 3.2 [ 91b 68.1 f 4.0 63.6 f 3.7 63.7 f 6.0 61.5 f 11.7 75.3 f 3.8 DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED b a. Dosage occurred on days 1 through 9 0 , 91, 9 2 , o r 93 of study. b. Excludes values that were associated with spillage. PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLB 11 (PAGE 1 ) : MOTOR ACTIVITY - SUMMARY - MALE AND FEMALE RATS GROUP DOSAGE (MG/KG/DAY) I I1 0 (VEHICLE) 60 DAY 86 NUMBER OF MALE RhTS N 5 5 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCX 4 BLOCK 5 BLOCK 6 BLOCK 7 2 BLOCK 8 BLOCK 9 w BLOCK 10 w BLOCK 11 BLOCX 1 2 BLOCK 1 3 BLOCK 14 BLOCK 1 5 BLOCK 1 6 BLOCK 17 BLOCK 1 8 TOTAL MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. 61.8 f 61.2 f 55.4 f 60.4 f 47.2 f 56.4 f 27.2 f 21.4 f 14.0 f 11.2 f 10.0 f 5.4 f 3.4 f 1.4 f 12.0 f 12.2 f 2.4 f 1.6 f 464.6 f 7.0 8.8 6.3 8.8 13.1 13.7 23.4 21.6 11.7 17.8 15.5 11.0 3.0 1.7 20.8 18.8 2.9 2.1 87.2 68.6 f 10.3 68.4 f 7.4 68.2 f 4.7 53.6 f 19.2 45.8 f 24.6 44.2 f 27.8 30.0 f 25.4 28.0 f 28.3 30.4 f 26.4 15.8 f 19.1 10.6 f 17.0 7.6 f 10.2 9.2 f 18.9 3.2 f 5.0 16.8 f 24.5 4.6 f 10.3 0.4 f 0.9 0.0 f 0.0 505.4 f 162.1 TOTAL I SUM OF BLOCKS1 EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD.' I11 200 5 65.6 f 67.0 f 58.0 f 55.2 f 46.0 f 35.6 f 24.6 f 16.4 f 19.8 f 9.2 f 8.8 f 9.6 f 3.4 f 1.2 f 0.2 f 0.4 f 0.8 f 1.8 f 423.6 f 6.6 8.9 10.2 10.6 4.7 19.7 22.6 20.9 11.5 17.8 12.4 17.7 7.6 1.8 0.4 0.5 0.4 1.5 93.6 IV 600 5 65.8 f 15.7 70.0 f 7.3 61.2 f 11.2 37.0 f 16.4 46.6 f 26.0 45.8 f 27.6 42.0 f 30.6 31.2 f 36.3 47.4 f 30.0 29.4 f 27.1 15.2 f 11.4 12.8 f 18.3 10.0 f 22.4 7.0 f 14.0 5.6 f 7.2 8.2 f 11.3 0.4 f 0.5 0.2 f 0.4 535.8 f 227.6 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN FATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 11 (PAGE 2): MOTOR ACTIVITY - SUMMARY - MhLE AND FEMALE RATS GROUP DOSAGE (MG/KG/DAY) I I1 0 (VEHICLE) 60 DAY 86 NUMBER OF MALE RATS N 5 5 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 BLOCK 2 BLOCX 3 BLOCK 4 BLOCK 5 BLOCX 6 BLOCX 7 2 BLOCK e % BLOCX 9 BLOCK 10 , BLOCK 11 BLOCK 12 BLOCK 13 BLOCX 14 BLOCX 15 BLOCX 16 BLOCX 17 BLOCX 18 TOTAL MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. 204.6 f 35.0 156.8 f 39.6 112.0 f 28.8 99.8 f 20.5 68.0 f 49.4 80.6 f 22.5 43.8 f 65.9 27.6 f 39.7 11.2 f 11.0 16.6 f 31.8 9.0 f 17.0 6.0 f 12.9 1.0 f 1.4 0.6 f 1.3 20.2 f 41.9 12.4 f 22.6 2.0 f 2.9 1.2 f 1.8 873.4 f 110.2 194.6 f 24.9 178.2 f 23.9 114.0 f 28.2 89.8 f 51.6 72.8 f 37.0 78.2 f 64.0 40.8 f 37.6 34.8 f 36.4 51.6 f 47.6 25.4 f 33.9 17.6 f 36.6 10.6 f 15.8 11.4 f 24.9 1.2 f 2.7 15.0 f 20.9 7.4 f 16.5 0.2 f 0.4 0.0 f 0.0 943.6 f 328.7 TOTAL I SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. I11 200 5 184.2 f 153.8 f 120.6 f 71.6 f 65.0 f 50.4 f 33.8 f 18.0 f 20.6 f 12.4 f 10.6 f 9.8 f 6.2 f 0.6 f 0.2 f 0.0 f 0.0 f 1.2 f 759.0 f 36.5 46.0 40.4 24.1 10.6 40.3 28.7 30.6 13.2 27.2 16.8 20.8 13.9 1.3 0.4 0.0 0.0 2.2 84.4 IV 600 5 191.2 f 53.0 172.0 f 48.0 122.0 f 66.5 66.0 f 55.8 90.2 f 62.4 73.0 f 57.2 68.4 f 59.4 53.0 f 70.0 55.2 f 31.9 30.8 f 29.1 15.2 f 16.4 9.2 f 12.6 26.8 f 59.9 7.0 f 15.6 5.0 f 9.0 6.6 f 10.6 0.2 f 0.4 0.0 f 0.0 991.8 f 512.8 v, P e PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PPBS) IN RATS (SPONSOR'S STUDY NUMBXR: T - 7 4 8 5 . 1 5 ) TABLE 11 (PAGE 3 ) : MOTOR ACTIVITY - SuMMhRY - MALE AND FEMALE RATS GROUP DOSAGE (MG/KG/DAY) I I1 0 (VEHICLE) 60 DAY 86 " M B E R OF FEMALE RATS N 5 5 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 BLOCK 8 BLOCK 9 VI BLOCK 1 0 VI BLOCK 11 BLOCK 1 2 BLOCK 1 3 BLOCK 1 4 BLOCK 1 5 BLOCK 1 6 BLOCK 17 BLOCK 1 8 TOTAL MEAN f S.D. MEAN f S.D. M E A N f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. 62.4 f 8 . 1 66.2 f 8.0 54.8 f 16.0 57.6 f 10.4 37.0 f 25.8 34.0 f 20.9 31.0 f 41.6 27.6 f 33.1 14.4 f 17.6 15.2 f 19.8 18.8 f 19.0 6.2 f 11.2 6.4 f 5.7 4.2 f 1.3 3.0 f 3.1 3.0 f 5.6 1.0 f 2.2 1.8 f 3.5 444.6 f 138.5 60.8 f 3.6 59.6 f 16.4 48.2 f 17.4 35.4 f 32.5 37.4 f 32.4 25.0 f 26.2 21.8 f 27.6 39.6 f 22.9 46.0 f 25.2 .52.8 f 24.2 38.8 f 25.0 28.6 f 29.8 27.8 f 29.2 23.0 f 23.4 10.0 f 8.3 11.0 f 19.4 15.2 f 26.5 11.6 f 21.0 592.6 f 279.2 TOTAL = SUM OF BLOCKS1 EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. I11 200 5 71.6 f 7.4 56.6 f 7.4 48.0 f 18.2 38.2 f 31.9 41.8 f 30.0 29.2 f 27.7 22.2 f 25.1 25.2 f 33.5 25.4 f 32.6 21.8 f 26.1 16.8 f 33.2 23.2 f 30.6 32.0 f 36.8 20.8 f 26.7 21.2 f 26.9 16.2 f 31.9 7.2 f 13.3 10.0 f 13.9 527.4 f 347.4 IV 600 5 60.8 f 10.9 55.8 f 23.5 47.4 f 17.8 40.0 f 24.1 31.0 f 29.6 27.6 f 33.3 30.6 f 24.0 33.6 f 22.6 31.0 f 17.7 36.6 f 33.2 32.4 f 29.6 43.0 f 37.5 28.8 f 30.2 25.4 f 24.2 2.0 f 2.0 2.0 f 1.7 1.2 f 1.6 5.0 f 5.7 534.2 f 280.2 P Y PROTOCOL 418-026: 0- (GAVAGE) R E P U T E D DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERPLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 11 (PAGE 4): MOTOR ACTIVITY - SUMMARY - MALE ANIJ FEMALE RATS GROUP DOSAGE (MG/KG/DAY) I I1 0 (VEHICLE) 60 DAY 86 NUMBER OF F B M U E RATS N 5 5 TIME (SECONDS) SPENT IN MOVEMENT BLOCX 1 BLOCX 2 BLOCK 3 BLOCX 4 BLOCX 5 BLOCX 6 BLOCX 7 2 BLOCK 8 % BLOCX 9 BLOCX 10 o\ BLOCK 11 BLOCX 12 BLOCK 13 BLOCK 14 BLOCX 15 BLOCK 16 BLOCK 17 BLOCX 18 TOTAL MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S . D . MEAN f S.D. MEAN f S.D. MEAN f S . D . MEAN f S . D . MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. MEAN f S.D. 171.8 f 21.9 126.2 f 9.5 81.2 f 45.3 87.0 f 36.6 38.8 f 39.3 43.0 f 45.8 40.2 f 54.8 37.8 f 54.2 12.4 f 16.5 10.6 f 15.7 15.4 f 20.4 4.2 f 8.8 3.6 f 4.6 2.4 f 1.5 1.0 f 1.2 1.8 f 4.0 0.6 f 1.3 0.6 f 1.3 670.6 f 284.2 166.8 f 24.6 115.8 f 29.6 76.6 f 65.5 50.0 f 52.6 57.2 f 56.9 31.8 f 44.2 23.2 f 37.0 46.0 f 32.5 78.6 f 46.4 66.2 f 44.6 37.0 f 30.0 30.8 f 39.3 35.4 f 51.2 23.4 f 27.6 9.2 f 10.5 10.4 f 21.1 25.4 f 52.9 10.0 f 20.1 893.8 f 449.2 TOTAL = SUM OF BLOCKS; EACH BLOCX CONSISTS OF A 5 MINUTE PERIOD. I11 200 5 153.0 f 28.8 127.6 f 71.5 82.0 f 58.6 44.4 f 46.3 42.0 f 41.6 47.2 f 51.9 31.6 f 46.2 29.2 f 38.7 27.4 f 38.2 24.8 f 32.3 20.2 f 44.0 28.8 f 42.4 43.2 f 54.3 27.2 f 45.6 44.2 f 70.8 27.2 f 59.7 9.4 f 20.5 5.8 f 8.8 015.2 f 627.8 IV 600 5 139.6 f 31.0 91.0 f 42.2 87.4 f 68.7 48.6 f 38.6 42.0 f 42.4 37.8 f 50.5 43.8 f 20.5 31.2 f 22.9 40.2 f 32.9 43.8 f 41.4 42.4 f 42.3 43.2 f 40.5 28.4 f 41.3 19.4 f 20.5 0.0 f 0.0 0.2 f 0.4 0.8 f 1.8 3.2 f 6.0 743.0 f 379.1 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) HOME CAGE BEHAVIOR 1: Sleeping 2 : Awake, Immobile 3 : Normal movement 4 : Unusual posture 5: Unusual behavior ALTERATIONS (HOME CAGE) 1: None 5 2 : Stereotyped behavior 0 3 : Bizarre behavior 0 4 : Limb twitches/tremor 0. 5: Whole body tremor/spasm 0 6 : Unusual posture 0 I : Tonic-clonic seizure 0 REACTION TO REMOVAL (1) Sits quietly N 5 5 5 5 ( 2 ) Vocalization N 0 0 0 0 ( 3 ) Runs or freezes N 0 0 0 0 ( 4 ) Tail or throat rattles N 0 0 0 0 MEAN SCORE 1.0 1 .o 1.0 1.0 REACTION TO HANDLING ( 1 ) No resistance N 5 5 ( 2 vocalization N 0 0 ( 3 ) Tense N 0 0 ( 4 ) Squirming N 0 0 0 0 P +- .-----------------------------------M-E-A-N--S-C--O-R-E----------1--.-0--------------------1--.-0---------------------1-.-0----------------------1-.-0----------------------------------------Y n : = Category number for descriptive test item. 0 Id ( n ) = Score assigned to graded test items; mean score was calculated by multiplying each score by the number of rats with that score m and then dividing the sum of the products by the total number of rats PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) REARS IN OPEN FIELD MEANfS.D. 5.8 f 2.6 5.0 f 3.7 7.0 f 4.9 6.6 f 6.6 DEFECATION IN OPEN FIELD 1: None N 3 4 5 3 2: Feces normal N 2 1 0 2 3 : Soft or liquid feces N 0 0 0 0 URINATION IN OPEN FIELD (1) None N 4 5 5 5 % ( 2 ) Normal urination N 1 0 0 0 (3) Excess urination N 0 0 0 0 MEAN SCORE 1.2 1.0 1.0 1.0 LEVEL OF AROUSAL (1) Stuporous N 0 0 0 0 ( 2 ) Sluggish N 0 0 0 0 (3) Apparently normal N 4a 5 5 5 (4) Sudden darting N 0 0 0 0 (5) Freezing, vocalization N 0 0 0 0 MEAN SCORE 3.0a 3.0 3.0 3.0 ALTERATIONS (OPEN FIELD) P 1: None N 5 5 5 5 2: Stereotyped behavior N 0 0 0 0 P 3: Bizarre behavior N 0 0 0 0 0 c 4: Limb twitches/tremor N 0 0 0 0 5: Whole body tremor/spasm N 0 0 0 0 v) P - 6: Unusual posture N 0 0 0 0 .-7--:---T-o-n-i--c---c-l--o-n-i-c--s-e-i-z--u-r-e------------N-----------------0-----------------------0-----------------------0------------------------0-----------------------------------------90" n : = Category number for descriptive test item. mtd (n) = Score assigned to graded test items; mean score was calculated by multiplying each score by the number of rats with that score and then dividing the s u m of the products by the total number of rats a . Excludes a value that was incorrectly recorded. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED W S E 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 12 (PAGE 3): FUNCTIONAL OBSERVATIONAL BATTERY - SUMMARY - MALE AND FEMALE RATS MALE RATS N 5 5 GAIT PATTERN 1: Apparently normal 2 : Ataxic 3: Limbs splay or drag 4: Spastic, tip-toe 5: Duck-walk 6: Scissors gait 5 5 0 0 0 0 0 0 0 0 0 0 GAIT ABNORMALITY, SEVERITY cd (1) Normal gait N 5 5 ( 2 ) Slight N 0 0 ul (3) Moderate \o (4) Extreme N 0 0 N 0 0 MEAN SCORE 1.0 1.0 PALPEBRAL CLOSURE (1) Wide open N 5 5 ( 2 ) Slightly drooping N 0 0 ( 3 ) Half-closed N 0 0 (4) Completely shut N 0 0 MEAN SCORE 1.0 1 .o 5. 5 5 5 0 0 0 0 0 0 0 0 0 0 5 5 0 0 0 0 0 0 1.0 1.0 5 5 0 0 0 0 0 0 1.0 1.0 PROTOCOL 418-0215: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) LACRIMATION (1) No excess N 5 5 5 5 (2) Excess at eyelid margin N 0 0 0 0 ( 3 ) Margin persistently damp N 0 0 0 0 (4) Extends beyond margin N 0 0 0 0 MEAN SCORE 1.0 1.0 1.0 1.0 SALIVATION (1) No excess N 5 5 3 5 ( 2 ) Margin of mouth wet N 0 0 2 0 (3) 1/4 to 1/2 submandibular N 0 0 0 0 ( 4 ) Entire submandibular N 0 0 0 0 m MEAN SCORE 1.0 1.0 1.4 1.0 0 PILOERECTION N 0 0 0 0 ABNORMAL RESPIRATION N 0 0 0 0 APPEARANCE (1) Clean and groomed N 5 5 5 5 ( 2 ) Unkempt N 0 0 0 0 (3) Urine and/or fecal stain N 0 0 0 0 MEAN SCORE 1 .o 1.0 1.0 1.0 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TACTILE REACTION (1) None N 0 0 0 0 (2) Orienting N 5 5 5 5 ( 3 ) Startle N 0 0 0 0 ( 4 ) More energetic reaction N 0 0 0 0 ( 5 ) Attacks N 0 0 0 0 MEAN SCORE 2.0 2.0 2.0 2.0 AUDITORY REACTION (1) None N 0 0 0 0 (2) Orienting N 0 0 0 0 ( 3 ) Startle N 5 5 5 5 ( 4 ) More energetic reaction N 0 0 0 0 (5) Intense vocalization N 0 0 0 0 MEAN SCORE 3.0 3.0 3.0 3.0 TAIL- PINCH REACTION (1) None N (2) Orienting N ( 3 ) Startle 'N ( 4 ) More energetic reaction N (5) Attacks N and then dividing the sum of the products by the total number of rats P c. MALE RATS N 5 AIR RIGHTING RESPONSE (1) All feet land on ground N 5 (2) Lands on side N 0 (3) Lands on back N 0 MEAN SCORE 1.0 PUPIL RESPONSE TO LIGHT N 5 FORELIMB GRIP TEST Maximum (GI Average (G) MEANfS .D. MEANfS .D. 397.0 f 136.7 342.5 f 88.2 HINDLIMB GRIP TEST Maximum (G) Average (G) MEANfS .D. MEANfS . D. 432.0 f 379.0 f 152.9 119.8 LANDING FOOT SPLAY Average (CM) MEANfS.D. 10.3 f 3.1 5 5 0 0 1.0 5 553.0 f 254.6 482.0 f 212.0 483.0 f 441.0 f 123.2 113.6 11.5 f 2.4 5. 4 1 0 1.2 5 401.0 f 192.3 325.0 f 146.6 449.0 f 106.2 403.5 f 78.4 9.4 f 1.1 5 5 0 0 1.0 5 379.0 f 143.3 358.0 f 129.3 392.0 f 351.5 f 137.2 145.8 10.8 f 3 . 5 and then dividing the sum of the products by the total number of rats P c 90 0 1m 3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SYLFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) HOME CAGE BEHAVIOR 1: Sleeping 2: Awake, Immobile 3: Normal movement 4: Unusual posture 5 : Unusual behavior ALTERATIONS (HOME CAGE) 1: None N 2 : Stereotyped behavior N 3 : Bizarre behavior N 4: Limb twitches/tremor N 5: Whole body tremor/spasm N 6: Unusual posture N 7: Tonic-clonic seizure N REACTION TO REMOVAL (11 Sits quietly N 5 5 5 5 (2) Vocalization N 0 0 0 0 ( 3 ) Runs or freezes N 0 0 0 0 (4) Tail or throat rattles N 0 0 0 0 MEAN SCORE 1.0 1.0 1.0 1.0 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED WSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) REARS IN OPEN FIELD MEANf3.D. 10.8 f 3.1 9.6 f 4.4 7.8 f 3.5 9.2 f 2.6 DEFECATION IN OPEN FIELD 1: None N 5 5 5 2: Feces normal N 0 0 0 3 : Soft or liquid feces N 0 0 0 URINATION IN OPEN FIELD ( 1 ) None N 4 5 (2) Normal urination N 1 0 ( 3 1 Excess urination N 0 0 m MEAN SCORE .2 1.0 P 5 5 0 0 0 0 .o 1.0 LEVEL OF AROUSAL (1) Stuporous N 0 0 0 0 ( 2 ) Sluggish N 0 0 0 0 ( 3 ) Apparently normal N 5 5 5 5 ( 4 ) Sudden darting N 0 0 0 0 (5) Freezing, vocalization N 0 0 0 0 MEAN SCORE 3.0 3.0 3.0 3.0 ALTERATIONS (OPEN FIELD) 1: None N 5 5 5 5 2 : Stereotyped behavior N 0 0 0 0 3 : Bizarre behavior N 0 0 0 0 4 : Limb twitches/tremor N 0 0 0 0 5: Whole body tremor/spasm N 0 0 0 0 6: Unusual posture N 0 0 0 0 ._7_: _T_o_ni_c_-c_l_o_ni_c_s_ei_z_ur_e___-----N-----~~----~-0~-----~-~---------0-~-------------------0---~---------~------0-------------------------------~~------~------ n : = Category number for descriptive test item. (n) = Score assigned to graded test items; mean score was calculated by multiplying each score by the number of rats with that score and then dividing the sum of the products by the total number of rats PROTOCOL 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 12 (PAGE 9 : FUNCTIONAL OBSERVATIONAL BATTERY - SUMMARY - MALE AND FEMALE RATS FEMALE RATS N 5 5 5 5 GAIT PATTERN 1: Apparently normal 2 : Ataxic 3 : Limbs splay o r drag 4 : Spastic, tip-toe 5: Duck-walk 6: Scissors gait 5 5 5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 GAIT ABNORMALITY, SEVERITY (1) Normal gait N 5 5 5 5 ( 2 ) Slight N 0 0 0 0 ( 3 ) Moderate N 0 0 0 0 ( 4 ) Extreme N 0 0 0 0 MEAN SCORE 1.0 1.0 1.0 1.0 PALPEBRAL CLOSURE ( 1 ) Wide open N 5 5 5 5 ( 2 ) Slightly drooping N 0 0 0 0 ( 3 ) Half-closed N 0 0 0 0 ( 4 ) Completely shut N 0 0 0 0 MEAN SCORE 1.0 1.0 1.0 1.0 PROMINENCE OF THE EYE 1: Normal N 5 5 5 5 2 : Exophthalmos N 0 0 0 0 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) LACRIMATION (1) No excess N 5 5 5 5 ( 2 ) Excess at eyelid margin N 0 0 0 0 ( 3 ) Margin persistently damp N 0 0 0 0 ( 4 ) Extends beyond margin N 0 0 0 0 MEAN SCORE 1.0 1.0 1 .o 1.0 SAL1VATION ( 1 ) No excess N 5 5 5 5 ( 2 ) Margin of mouth wet N 0 0 0 0 ( 3 ) 1/4 to 1/2 submandibular N 0 0 0 0 % ( 4 ) Entire submandibular N 0 0 m MEAN SCORE 1.0 .o 0 .o 0 .o PILOERECTION N 0 0 0 0 ABNORMAL RESPIRATION N 0 0 0 0 APPEARANCE (1) Clean and groomed N 5 5 5 5 ( 2 ) Unkempt N 0 0 0 0 (3) Urine and/or fecal stain N 0 0 0 0 MEAN SCORE 1.0 1.0 1.0 1.0 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TACTILE REACTION (1) None N 0 0 0 0 (2) Orienting N 5 5 5 5 ( 3 ) Startle N 0 0 0 0 (4) More energetic reaction N 0 0 0 0 ( 5 ) Attacks N 0 0 0 0 MEAN SCORE 2.0 2.0 2.0 2.0 AUDITORY REACTION (1) None N 0 0 0 0 ( 2 ) Orienting N 0 0 0 0 (3) Startle N 5 5 5 5 ( 4 ) More energetic reaction N 0 0 0 0 ( 5 ) Intense vocalization N 0 0 0 0 MEAN SCORE 3.0 3.0 3.0 3.0 TAIL-PINCH REACTION ( 1 ) None N (2) Orienting N ( 3 ) Startle N (4) More energetic reaction N (5) Attacks N .-------_--_-_-------------------M-E-A-N--S-C-O--R-E----------2-.-0--------------------2-.-0---------------------2-.-0----------------------2-.-0-------------------------------- n: = Category number for descriptive test item. (n) = Score assigned to graded test items; mean score was calculated by multiplying each score by the number of rats with that score and then dividing the sum of the products by the total number of rats FEMALE RATS N 5 5 5. 5 AIR RIGHTING RESPONSE (1) All feet land on ground N 5 5 4 5 (2) Lands on side N 0 0 1 0 (3) Lands on back N 0 0 0 0 MEAN SCORE 1.0 1.0 1.2 1.0 PUPIL RESPONSE TO LIGHT N 5 5 5 5 FORELIMB GRIP TEST Maximum LG) Average (G) MEANiS .D. MEANiS .D. 328.0 i 111.6 268.5 i 96.0 301.0 f 65.4 271.0 f 67.0 323.0 f 152.2 295.5 f 138.7 337.0 i 212.1 289.5 i 182.7 HINDLIMB GRIP TEST Maximum (G) Average (G) MEANiS .D. MEANiS.D. 374.0 i 347.5 f 107.7 122.2 344.0 f 77.6 296.0 i 57.0 331.0 i 72.7 299.5 i 52.9 322.0 f 109.1 278.5 i 107.0 LANDING FOOT SPLAY Average (CM) MEANiS .D. 8.6 f 2.4 8.4 f 2.1 7.8 f 1.5 8 . 9 f 1.4 .--B-O--D-Y---W--E--I-G--H-T----(-G--)-----------------------M-E--A--N-+--S-.--D-.=----2-8--7-.--8----+-----2-1--.-8----------3--0-8--.-6------i-----2--1-.--3---------3-0--9-.--6------i------3--6-.--9---------2-7--6-.--6------+ n: = Category number for descriptive test item. 21.7 ( n ) = Score assigned to graded test items; mean score was calculated by multiplying each score by the number of rats with that score and then dividing the sum of the products by the total number of rats b m1 3 . PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 13 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - MALE RATS APPEARED NORMAL N 10 10 10 9 STOMACH : CARDIAC REGION, THIN WALLS N 0 0 0 IC STOMACH AND INTESTINES: DISTENDED WITH GAS N 0 0 0 1c THYMUS : RED N 0 0 0 IC SPLEEN: SMALL N 0 0 0 IC a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Refer to the individual clinical observations table (Table 25) for external observations confirmed at necropsy. c. Rat 14890 was found dead on day 8 5 of study. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 14 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - FEMALE RATS APPEARED NORMAL N 10 10 10 10 4 0 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 15 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - MALE RATS GROUP I I1 I11 DOSAGE -------- (MG/KG/DAY)a _-_______ _ ___- _ _ _ _ _ _ _ _ _ _-_- - . . 0. . .(.V.E.H.I.C. L. E. ). . . . . . . 60 200 --------------____-________________ RATS TESTED N 10 10 10 IV 600 --------_-_____________ 10 INCLUDED IN ANALYSES TERMINAL BODY WEIGHT EPIDIDYMIDES PAIRED N MEANfS.D . MEANfS.D. 10 510.9 f 47.0 1.65 f 0.18 10 482.6 f 60.4 1.46 f 0.10 10 479.6 f 30.3 1.58 f 0.17 9b 485.3 f 49.4 1.59 f 0.16 TESTES PAIRED BRAIN LIVER MEANfS.D . MEANfS.D. MEANfS.D. 3.54 f 0.68 2.28 f 0.13 14.48 f 1.76 3.38 f 0.22 2.28 f 0.11 13.83 f 2.67 3.56 f 0.24 2.25 f 0.09 13.50 1.28 3.53 f 0.57 2.29 f 0.10 14.78 1.78 KIDNEYS PAIRED ADRENALS PAIRED SPLEEN THYMUS MEANfS .D. MEANfS.D . MEANfS.D. MEANfS.D. 4.18 f 0.48 0.066 f 0.014 0.93 f 0.13 0.49 f 0.19 4.15 f 0.55 0.057 f 0.016 0.77 f 0.10** 0.48 f 0.17 3.93 f 0.30 0.068 f 0.013 0.83 f 0 . 0 6 * 0.38 f 0.10 4.18 f 0.33 0.061 f 0.010 0.80 f 0.11** 0.38 f 0.14 HEART MEANfS .D. 1.61 f 0.19 1.54 f 0.18 1.60 f 0.23 1.59 f 0.18 ________________________________________------------------------------------------------------------------- ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes values for rat 14890, which was found dead on day 85 of study. * Significantly different from the vehicle control group value ( ~ ~ 0 . 0 5 ) . ? * * Significantly different from the vehicle control group value ( ~ ~ 0 . 0 1 ) . !a bcCA PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 16 (PAGE 1): RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - MALE RATS GROUP DOSAGE (MG/KG/DAY)a ........................ RATS TESTED I I1 111 IV 0 (VEHICLE) 60 200 600 _ _ _ _ _ _ _ _ _ _ - _ _ _ - -_____ _ ___- _- -_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ____ __ _______ __ _ _ _ _ _ _ _ _ - - - _ - - _ _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ N lo 10 10 10 INCLUDED IN ANALYSES TERMINAL BODY WEIGHT EPIDIDYMIDES PAIRED TESTES PAIRED N MEANfS.D . MEANfS.D. MEANfS . D . 10 510.9 f 47.0 0.325 f 0.043 0.689 f 0.118 10 482.6 f 60.4 0.306 f 0.037 0.708 f 0.086 10 479.6 f 30.3 0.329 f 0.037 0.746 f 0.074 9b 485.3 f 49.4 0.332 f 0.054 0.733 f 0.142 BRAIN MEANfS.D. 0.451 f 0.046 0.479 f 0.054 0.473 f 0.042 0.474 f 0 . 0 6 0 LIVER KIDNEYS PAIRED ADRENALS PAIRED SPLEEN MEANfS.D. . MEANfS .D MEANfS.D. . MEANfS .D 2.832 f 0.198 0.818 f 0.058 0.013 f 0 . 0 0 5 0.181 f 0.018 2.846 f 0.273 0.859 f 0.053 0.012 f 0.004 0.158 f 0.015** 2.814 f 0.175 0.818 f 0.053 0.013 f 0 . 0 0 5 0.172 f 0.017 3.049 f 0.220 0.864 f 0.049 0.011 f 0.003 0.163 f 0.020* THYMUS MEANtS .D. 0.096 f 0.039 0.097 f 0.033 0.078 f 0.021 0.078 f 0.023 HEART MEANfS.D . 0.317 f 0.020 0 . 3 2 0 f 0.022 0.334 f 0.057. 0.328 f 0.037 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). RATIOS ( % ) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes values for rat 14890, which was found dead on day 85 of study. * Significantly different from the vehicle control group value (~50.05). * * Significantly different from the vehicle control group value (~50.01). PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 1 7 (PAGE 1) : RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - MALE RATS INCLUDED IN ANALYSES N 10 10 10 9b BRAIN WEIGHT EPIDIDYMIDES PAIRED MEANfS .D . MEANfS.D . 2.28 f 0.13 72.45 f 8.36 2.28 f 0.11 64.25 f 3.19 2.25 f 0.09 70.28 f 9.59 2.29 f 0.10 69.89 f 7.92 TESTES PAIRED MEANfS .D . 155.25 f 29.94 148.40 f 7.90 158.19 f 10.60 154.02 f 22.28 LIVER KIDNEYS PAIRED ADRENALS PAIRED 4 w SPLEEN MEANfS .D . MEANfS.D . MEANfS .D. MEANfS .D . 637.27 f 96.70 183.42 f 22.38 2.88 f 0.63 40.86 f 5.19 604.29 f 99.62 181.97 f 20.89 2.50 f 0.66 33.56 f 3.75** 600.60 f 70.64 174.55 f 16.32 3.04 f 0.63 36.74 f 3.07 649.12 f 96.48 183.46 f 18.64 2.69 f 0.49 34.92 f 5.64** THYMUS MEANfS .D. 21.66 f 8.84 20.88 f 7.19 16.90 f 4.84 16.98 f 6.35 HEART MEANfS .D. 70.89 f 9.95 67.32 f 7.10 71.07 f 10.38 69.77 f 10.16 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS ( G ) . RATIOS ( % ) = (ORGAN WEIGHT/BRAIN WEIGHT) x 100. a. Dosage occurred on days 1 through 90, 91, 92, o r 93 of study. b. Excludes values for rat 14890, which was found dead on day 85 of study. * * Significantly different from the vehicle control group value ( p ~ O . 0 1 ) . PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 18 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - FEMALE RATS ________________________________________-------------------------------------------------------------------------------------------- GROUP I I1 I11 IV DOSAGE (MG/KG/DAY)a 0 (VEHICLE) 60 200 600 ______-_________________________________-------------------------------------------------------------------------------------------- RATS TESTED N 10 10 10 lo TERMINAL BODY WEIGHT BRAIN LIVER MEANfS.D . MEANfS .D . MEANfS .D . 276.5 f 24.0 2.07 f 0.08 7.71 f 0.78 286.0 f 21.5 2.08 f 0.09 8.30 f 0.72 284.8 f 30.1 2.08 f 0.08 8.23 f 0.91 264.6 f 19.5 2.06 f 0.10 7.79 f 0.36 KIDNEYS PAIRED ADRENALS PAIRED MEANfS.D . MEANtS .D. 2.34 f 0.22 0.076 f 0.014 2.40 f 0.30 0.078 f 0.011 2.40 f 0.18 0.079 f 0.013 2.39 f 0.41 0.074 f 0.010 SPLEEN THYMUS OVARIES PAIRED UTERUS NON-GRAVID MEANkS.D . MEANfS.D . MEANfS .D . MEANfS . D . 0.58 f 0.09 0.35 f 0.07 0.136 f 0.019 0.64 f 0.16 0.59 f 0.11 0.34 f 0.13 0.136 f 0.020 0.76 f 0.26 0.57 f 0.07 0.38 f 0.10 0.139 f 0.025 0.64 f 0.14 0.65 f 0.11 0.36 f 0.09 0.129 f 0.018 0.80 f 0.21 HEART MEANfS .D . 0.97 f 0 . 0 8 1.02 f 0.07 0.99 f 0.10 0.98 f 0.12 ________________________________________-------------------------------------------------------------------------------------------- ALL WEIGHTS WERE RECORDED IN GRAMS (GI. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 19 (PAGE 1): RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - FEMALE RATS BRAIN LIVER KIDNEYS PAIRED ADRENALS PAIRED SPLEEN THYMUS OVARIES PAIRED UTERUS NON-GRAVID MEANfS . D. MEANfS .D . MEANfS.D . MEANfS.D . MEANfS .D. MEANfS .D. MEAN+S.D. MEANfS .D. 0.752 f 0.060 2.788 f 0.152 0.847 f 0.069 0.026 f 0.007 0 . 2 0 9 f 0.033 0 . 1 2 8 f 0.033 0.048 f 0.008 0.234 f 0.064 0.730 f 0.052 2.902 f 0.154 0.838 f 0.071 0.027 f 0.005 0.208 f 0.037 0.121 f 0.047 0.046 f 0.007 0.264 f 0.087 0.736 f 0.061 2.890 f 0.100 0 . 8 4 6 f 0.059 0.028 f 0.008 0.202 f 0.030 0.131 f 0.027 0 . 0 4 8 f 0.009 0.228 f 0.062 0.780 f 0.080 2.951 f 0.204 0.906 f 0.150 0.027 f 0.007 0.248 f 0.046 0.134 f 0.031 0.047 f 0.007 0.303 f 0.077 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 2 0 (PAGE 1): RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - FEMALE RATS BRAIN WEIGHT LIVER KIDNEYS PAIRED ADRENALS PAIRED SPLEEN THYMUS MEANfS .D. MEANfS .D . MEANfS .D. MEANfS .D. MEANkS .D. MEANkS .D. 2.07 f 0.08 372.75 f 37.36 112.96 f 9.64 3.68 f 27.82 + 0.76 4.22 17.07 f 3.53 2.08 f 0.09 399.29 f 33.37 115.32 f 11.72 3.76 f 0.58 28.51 f 4.88 16.60 f 6.22 2.08 f 0.08 395.19 f 36.04 115.28 f 8.85 3.78 f 0.62 27.49 f 3.68 18.10 f 4.58 2.06 f 0.10 379.04 f 21.60 116.22 f 18.95 3.58 f 0.47 31.74 _+ 4.77 17.30 f 4.58 OVARIES PAIRED MEANkS.D . 6.61 f 1.06 6.51 f 0.91 6.68 f 1.26 6.26 f 0.93 UTERUS NON-GRAVID MEANkS .D. 31.04 f 8.98 36.22 f 11.32 30.65 f 7.18 38.58 f 9.52 HEART MEANfS .D. 47.16 f 4.88 48.92 f 4.45 47.74 f 4.38 47.89 f 6.22 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (GI. RATIOS ( % ) = (ORGAN WEIGHT/BRAIN WEIGHT) x 100. a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED W S E 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 21 (PAGE 1): HEMATOLOGY - SUMMARY - MALE RATS (See the last page for abbreviations) GROUP DOSAGE (MG/KG/DAY)a I I1 0 (VEHICLE) 60 111 IV 200 600 RATS TESTED N 10 10 10 9b WBC (THSN/CU MM) MEANfS.D. 17.0 f 3.66 15.4 f 3.50 14.7 f 2.31 15.2 f 2.80 RBC (MILL/CU MM) HGB (GRAMS/DL) MEANf.5.D. MEANfS.D. 7.76 f 0.469 16.4 f 0.96 7.62 f 0.443 16.0 f 0.41 7.55 f 0.282 15.6 f 0.48* 7.19 f 0.481* 15.5 * 0.78* HCT ( % ) MEANf.9.D. 44.2 f 2.32 42.7 f 1.44 41.9 f 1.50* 40.9 rt 2.24** MCV (CU MICRONS) MEAN3S.D. 57.0 f 1.25 56.2 f 2.12 55.6 f 1.38 57.0 f 2.08 MCH (PIC0 GRAMS) MCHC ( % ) MEANfS.D. MEANfS .D 21.2 f 0.53 37.2 f 0.50 21.1 f 1.18 37.5 f 1.11 20.7 f 0.51 37.2 f 0.69 21.6 f 1.01 37.8 f 0.96 PLAT (THSN/CU MM) MEANfS.D. 1235 f 241.3 1160 f 175.6 1134 f 149.4 1202 f 165.0 MPV (CU MICRON) MEANfS .D . 7.7 f 0.35 8 . 0 f 0.65 8 . 0 f 0.64 7.6 f 0.51 ................................................................................................................................... a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes rat 14890, which was found dead on day 85 of study. * Significantly different from the vehicle control group value (pS0.05). * * Significantly different from the vehicle control group value ( ~ 5 0 . 0 1 ) . b m1 3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 1 (PAGE 2): HEMATOLOGY - SUMMARY - MALE RATS (See the last page for abbreviations) RATS TESTED N 10 10 10 9b PT (SECONDS) MEANfS.D. 13.7 f 0.41 14.2 f 0.45 14.1 f 0.68 14.2 f 0.80 APTT (SECONDS) NRBC COUNT MEANfS.D MEANS.D . 24.7 f 2.80 0 If 0.0 25.7 f 3.84 0 f 0.3 25.6 f 2.94 0 f 0.0 25.5 f 4.43 0 f 0.7 Lymphocyte (THSN/CU MM) MEAN+S.D. 13.6 f 3.93 12.6 f 3.66 12.2 f 2.34 13.0 f 2.62 Segmented (THSN/CU MM) MEANfS.D. 2.7 f 1.48 2.2 f 0.90 1.9 f 0.57 1.6 f 0.48 Bands (THSN/CU MM) MEANfS.D. 0.0 f 0.00 0.0 f 0.06 0.0 f 0.00 0.0 i 0.00 Monocytes (THSN/CU MM) MEANfS.D. 0.5 f 0.23 0.4 f 0.26 0.5 f 0.20 0.5 f 0.26 Eosinophil (THSN/CU MM) MEANIfS.D. 0.2 f 0.29 0.2 f 0.19 0.1 f 0.18 0.1 f 0.15 Basophils (THSN/CU MM) MEANfS.D. 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 Abnormal L (THSN/CU MM) MEANfS.D. 0 . 0 f 0.06 0.0 f 0.06 0.0 f 0.07 0.0 f 0.03 . O. t. h. e. .r. .(.T.H.S.N./.C.U. .M.M.) . . . . . . .M.E.A.N.f.S...D... . . . 0.0 f ..... . 0...0.0. . . . . . . . . . . . . .0. ..0. f .. .0...0.0. . . . . . . . . . . . . . . 0. .. 0. . f . . 0. .. 0. 0 . . . . . . . . . . . . 0. .. 0 . . f .. .0 .. 0. 0 . . . . . . . . . . . . . . . . . a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes rat 14890, which was found dead on day 85 of study. PROTOCOL 418-026: TABLE 21 (PAGE 3 WBC RBC HGB HCT MCV MCH MCHC PLAT MPV PT APTT NRBC Segmented Abnormal L Other ---__------ White Blood Cells (Leukocytes) Red Blood Cells (Erythrocytes) Hemoglobin Hematocrit (Packed Cell Volume) Mean Corpuscular Volume Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin Concentration Platelets Mean Platelet Volume Prothrombin Time Activated Partial Thromboplastin Nucleated Red Blood Cell Count Segmented Neutrophils Abnormal Lymphocytes Other Cells ________________________________________-------------- PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 2 (PAGE 1): HEMATOLOGY - SUMMARY - FEMALE RATS (See the last page for abbreviations) RATS TESTED N 10 WBC (THSN/CU MM) MEANk3.D. 12.2 f 3.95 RBC (MILL/CU MM) MEANfS.D. 7.17 f 0.315 HGB (GRAMS/DL) MEANfS.D. 15.9 k 0.61 HCT ( % ) MEAN*S.D. 43.3 f 1.85 MCV (CU MICRONS) MEANfS.D. 60.5 f 1.08 MCH (PIC0 GRAMS) MEANfS.D. 22.2 f 0.64 00 0 MCHC ( % ) MEANfS .D 36.7 f 0.69 PLAT (THSN/CU MM) MEANfS.D. 1119 f 88.2 10 11.5 f 3.10 6.95 f 0.226 15.8 f 0.57 42.1 f 1.56 60.6 f 1.47 22.7 f 0.65 37.4 f 0.54f 1157 f 195.8 10 12.1 f 3.77 7.16 f 0.309 15.6 f 0.69 42.7 f 2.14 59.5 f 1.50 21.8 f 0.61 36.7 f 0.51 1181 f 181.6 lo 13.5 f 3.94 6.95 f 0.297 15.3 f 0.82 41.2 f 1.71 59.2 f 1.21 22.0 f 0.75 37.1 f 0.70 1126 f 283.3 b N m PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 2 (PAGE 2 ) : HEMATOLOGY - SUMMARY - FEMALE RATS (see the last page for abbreviations) PT (SECONDS) MEAN3S.D. 13.3 f 0.29 APTT (SECONDS) NRBC COUNT MEANfS.D MEANfS . D . 21.2 f 2.41 0 f 0.0 Lymphocyte (THSN/CU MM) MEANfS.D. 10.3 f 3.76 Segmented (THSN/CU MM) MEANfS.D. 1.5 f 0.59 13.5 f 0.49 24.3 f 5.68 0 f 0.3 9.6 f 2.56 1.6 f 0.61 13.1 f 0.40 24.2 f 3.27 0 f 0.3 9.6 f 3.87 2.1 f 1.45 13.4 [ 24.5 [ 0 f 0.16 9lb f 5.17 9lb f 0.0 12.1 * 3.94 1.2 It 0.47 Bands (THSN/CU MM) MEANfS.D. 0.0 k 0.00 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 Monocytes (THSN/CU MM) MEANfS.D. 0.2 f 0.10 0.2 f 0.20 0.2 f 0.20 0.2 f 0.18 Eosinophil (THSN/CU MM) MEANfS.D. 0.3 f 0.15 0.2 f 0.16 0.2 f 0.17 0.1 f 0.10 Basophils (THSN/CU MM) MEANk3.D. 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 0.0 f 0.03 Abnormal L (THSN/CU MM) MEANfS.D. 0.0 f 0.08 0.0 f 0.00 0.0 f 0 . 0 3 0.0 f 0.00 Other (THSN/CU MM) MEANfS.D. 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 0.0 f 0.00 .................................................................................................................................... [ ] = NUMBER OF VALUES AVERAGED a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes values for rats that data was unavailable. P PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 22 (PAGE 3 ) : HEMATOLOGY - SUMMARY - FEMALE RATS ________________________________________---------------------- KEY TO HEMATOLOGY TABLE ............................................................................................................................... ABBREVATION TERMINOLOGY ________________________________________--------------------------------------------------------------------------------------- WBC White Blood Cells (Leukocytes) RBC Red Blood Cells (Erythrocytes) HGB Hernoglobin HCT Hematocrit (Packed Cell Volume) MCV Mean Corpuscular Volume MCH Mean Corpuscular Hemoglobin MCHC Mean Corpuscular Hemoglobin Concentration PLAT Platelets MPV Mean Platelet Volume PT Prothrombin Time APTT Activated Partial Thromboplastin NRBC Nucleated Red Blood Cell Count Segmented Segmented Neutrophils RATS TESTED N 10 10 la TP (G/DL) MEANfS .D . 6.6 i 0.33 6.5 f 0.16 6.4 f 0.19 A (G/DL) MEANfS .D . 4.1 f 0.17 4.1 f 0.19 4 . 0 f 0.11 GLU (MG/DL) MEANfS .D . 164 f 29.2 157 f 12.8 167 f 21.6 CHOL (MG/DL) TBILI (MG/DL) MEANiS .D . MEANfS .D . 54 f 0.1 + 12.9 0.03 51 f 0.1 * 14.9 0.00 45 f 8.4 0.1 f 0.00 BUN (MG/DL) MEANfS .D . 15 f 1.4 14 f 1.5 14 f 2.2 00 CREAT (MG/DL) w ALT (U/L) MEANfS .D . MEANfS . D . 0.3 k 0.05 42 f 5.8 0.2 f 0.05 45 f 7.1 0.3 f 0.06 41 f 4.6 AST (U/L) MEANfS .D . 84 f 11.2 90 f 10.9 88 f 7.5 ................................................................................................ a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes rat 14890, which was found dead on day 85 of study. 9b 6.5 f 0.50 4 . 0 f 0.26 166 f 13.8 53 f 14.4 0.1 f 0.00 15 f 1.4 0.3 f 0.05 43 f 7.8 91 f 12.7 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 3 (PAGE 2): CLINICAL CHEMISTRY - SUMMARY - MALE RATS (See the last page of table for abbreviations) ALK (U/L) MEANfS . D . 94 f 15.0 90 f 12.0 96 f 12.1 107 f 12.7 CA (MG/DL) MEANfS .D . 11.4 f 0.37 11.2 f 0.27 11.0 f 0.24 11.1 f 0.32 PHOS (MG/DL) MEANfS .D . 8.9 f 0.68 8.7 f 0.64 8.3 f 0.71 8.3 f 0.55 TRI (MG/DL) MEANfS.D . 6 0 k 32.3 58 f 21.0 50 f 11.6 47 f 13.7 NA (MMOL/L) 2 K (MMOL/L) (300 CL (MMOL/L) P MEANfS . D . MEANfS .D. MEANfS .D. 148 f 1.4 5.2 f 0.59 9 8 f 2.0 2.5 f 0.28 148 f 0.7 5.3 f 0.54 100 f 1.2 2.5 f 0.14 149 f 1.2 5.1 f 0.29 100 f 1.4 2.4 f 0.16 149 f 0.9 5.1 f 0.38 101 f 1.7** 2.4 f 0.37 A/G MEANfS .D . 1.7 f 0.23 1.7 f 0.14 1.7 f 0.13 1.7 f 0.23 ________________________________________---------------------------------------------------------------------------------------------- a. Dosage occurred on days 1 through 90, 91, 92, or 93 of study. b. Excludes rat 14890, which was found dead on day 85 of study. * * Significantly different from the vehicle control group value (~50.01). I 0 13 ch TP A GLU CHOL TBILI BUN CREAT ALT AST ALK CA PHOS TRI NA K CL G - - - - _A_/G- _ - - Total Protein Albumin Glucose Cholesterol Total Bilirubin Blood Urea Nitrogen Creatinine Alanine Aminotransferase Aspartate Aminotransferase Alkaline Phosphatase Calcium Phosphorus (inorganic) Triglycerides Sodium Potass ium Chloride Globulin Albumin/Globulin Ratio ______________________________ PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 24 (PAGE 1 ) : CLINICAL CHEMISTRY - SUMMARY - FEMALE RATS (See the last page of table for abbreviations) RATS TESTED N 10 INCLUDED IN ANALYSES N 10 lo 10 10 10 10 9b TP (G/DL) MEANfS .D . 7.2 f 0.40 7.2 f 0.34 A (G/DL) MEANfS .D. 4 . 9 rl. 0.38 4.8 f 0.29 GLU (MG/DL) MEANfS . D . 156 f 16.7 160 f 21.4 CHOL (MG/DL) TBILI (MG/DL) MEANfS .D . MEANfS .D. 16 f 11.8 0.1 f 0 . 0 0 6 9 f 10.0 0.1 f 0.03 BUN (MG/DL) MEANfS .D. 16 f 1.9 16 f 1.6 CREAT (MG/DL) ALT (U/L) MEANfS . D . MEANfS .D. 0.4 f 0.05 44 f 11.6 0.4 f 0.04 55 f 23.6 AST (U/L) MEANfS .D. 85 f 15.8 95 f 25.8 .......................................................................... a. Dosage occurred on days 1 through 90. 91, 9 2 , or 93 of study. b. Excludes a rat that did not have sufficient data. * Significantly diff-erent from the vehicle control group value (~10.05). 7.1 k 0.40 6.7 f 0.23* 4.7 f 0.31 4.4 f 0.23* 163 f 30.1 161 f 13.1 74 f 18.7 68 f 16.8 0.1 f 0.03 0.1 f 0.03 15 f 1.8 16 f 2.9 0.3 f 0.05 0.4 f 0.05 49 f 30.7 44 f 13.3 f f 94 51.0 96 - - - - - - - - - - _ _ _ _ _ _ r _ _ _ _ _ _ _ _ _ _ ._- 19.6 - - PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 24 (PAGE 2): CLINICAL CHEMISTRY - SUMMARY - FEMALE RATS (See the last page of table for abbreviations) PHOS (MG/DL) TRI (MG/DL) NA (MMOL/L) K (MMOL/L) CL (MMOL/L) G (G/DL) MEANfS .D. MEANfS .D . MEANfS .D . MEANfS .D . MEANfS .D. MEANfS.D . 8.2 f 1.35 36 f 7.1 146 k 1.5 6.3 f 0.76 101 f 2.5 2.4 f 0.17 8.0 f 1.39 45 f 19.0 146 f 0.9 5.9 f 0.62 101 f 2.3 2.4 f 0.22 7.9 f 41 + 1.17 9.2 146 f 1.2 6.2 f 0.60 102 f 2.2 2.4 f 0.28 8.4 f 0.80 42 f 13.5 145 f 1.1 6.2 f 0.63 102 f 1.1 2.3 f 0.26 TP A GLU CHOL TBILI BUN CREAT ALT AST ALK CA PHOS TRI NA K CL G - - _ _A_/_G _ _ _ _ - - _ - Total Protein Albumin Glucose Cholesterol Total Bilirubin Blood Urea Nitrogen Creatinine Alanine Aminotransferase Aspartate Aminotransferase Alkaline Phosphatase Calcium Phosphorus (inorganic) Triglycerides Sodium Potassium Chloride Globulin Alburnin/Globulin Ratio ........................................ PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 25 (PAGE 1): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - MALE RATS ________________________________________-------------------------------------------------------------------------------------------- GROUP I VEHICLE o (VEHICLE) MG/KG/DAY ________________________________________-------------------------------------------------------------------------------------------- RAT # DESCRIPTION ________________________________________-------------------------------------------------------------------------------------------- 14851 DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 17- 36) NECK: ABRASION (0.5 CM IN DIAMETER) DS( 24 ) DS( 31 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 37- 43) NECK: SCRB (0.2 CM IN DIAMETER) 14852 DS( 38 ) DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL FUR DISCOLORED 14853 14854 DS( 65 ) DS( 62- 68) CHROMODACRYORRHEA INCISORS: MISSING/BROKEN DS( 6 6 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14855 14856 DS( 8 0 ) DS( 38- 42) EAR ( S ) : SWOLLEN EXCESS SALIVATION DS( 38 ) DS( 51- 61) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL EXCESS SALIVATION DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 69 ) DS( 73 ) RED PERIORAL SUBSTANCE EXCESS SALIVATION 14857 DS( 77 ) DS( 77- 79) DS( 77 ) SOFT OR LIQUID FECES EXCESS SALIVATION EXCESS SALIVATION DS( 79 ) RED, SLIGHT PERIORAL SUBSTANCE DS( 91 ) EXCESS SALIVATION 14858 NO ADVERSE FINDINGS 14859 DS( 4 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14860 NO ADVERSE FINDINGS ________________________________________-------------------------------------------------------------------------------------------- ALL EYES APPEARED NORMAL PRIOR TO DOSAGE. ALL EYES APPEARED NORMAL AT TERMINATION UNLESS NOTED OTHERWISE. DS = DAY OF STUDY PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 25 (PAGE 2): ----___-_ CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - MALE RATS 14861 DS( 11- 15) NECK: ABRASION (0.4 CM IN DIAMETER) DS( 16- 35) NECK: ULCERATION (DID NOT EXCEED 1.0 CM IN DIAMETER) DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 20- 23) HEAD: SCAB (0.3 CM IN DIAMETER) DS( 24 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 31 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14862 DS( 55 SOFT OR LIQUID FECES DS( 61- 62) SOFT OR LIQUID FECES DS( 78 ) SOFT OR LIQUID FECES DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 8 0 ) SOFT OR LIQUID FECES 14863 DS( 52- 83) LOCAL1ZED ALOPECIA: LIMBS DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 8 0 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14864 DS( 11- 31) NECK: ULCERATION (1.0 CM IN DIAMETER) DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 19- 29) LOCALIZED ALOPECIA: LIMBS DS( 24 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 31- 36) NECK: SCAB (1.0 CM IN DIAMETER) DS( 31 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66- 67) HEAD: SCAB (0.5 CM IN DIAMETER) DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 72- 75) HEAD: SCAB (0.5 CM IN DIAMETER) DS( 73 HEAD: ABRASION (0.5 CM IN DIAMETER) DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 76- 78) HEAD: ABRASION (0.5 CM IN DIAMETER) DS( 77- 78) SOFT OR LIQUID FECES DS( 77- 92) LOCALIZED ALOPECIA: LIMBS a DS( 79- 86) HEAD: SCAB (0.5 CM IN DIAMETER) DS( 8 0 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL P DS( 87 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL IC-. DS( 91 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL m I 0 t3 o\ PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 25 (PAGE 3): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - MALE RATS 14865 DS( 91 FUR DISCOLORED 14866 DS( 61- 63) SOFT OR LIQUID FECES 14867 NO ADVERSE FINDINGS 14868 14869 DS( 91 ) DS( 42- 94) DS( 45 ) EXCESS SALIVATION LOCALIZED ALOPECIA: LIMBS a DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 6 6 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 80 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14870 NO ADVERSE FINDINGS .......................................................................................... ALL EYES APPEARED NORMAL PRIOR TO DOSAGE. ALL EYES APPEARED NORMAL AT TERMINATION UNLESS DS = DAY OF STUDY a . Observation confirmed at necropsy. __________-__-__- NOTED OTHERWISE. 0 chn , DESCRIPTION ________________________________________------------------------------------------------------------- 14871 DS( 78 ) EXCESS SALIVATION 14872 DS( 4 ) FUR DISCOLORED DS( 6- 7) LOCALIZED ALOPECIA: NECK DS( 8- 3 6 ) NECK: ULCERATION (DID NOT EXCEED 5.0 CM IN DIAMETER) DS( 10 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 20- 3 0 ) RIGHT FORELIMB: SCAB( S ) (DID NOT EXCEED 0.4 CM X 0.3 CM) DS( 24 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 30- 6 3 ) NECK: SCAB(S) (DID NOT EXCEED 0.8 CM X 0.4 CM) DS( 31 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 38 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 45 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 52 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14873 NO ADVERSE FINDINGS 14874 DS( 54 ) SOFT OR LIQUID FECES DS( 79 ) RED, SLIGHT PERIORAL SUBSTANCE DS( 91 ) RED, SLIGHT PERIORAL SUBSTANCE DS( 92 EXCESS SALIVATION a 14875 NO ADVERSE FINDINGS 14876 NO ADVERSE FINDINGS 14877 DS( 80 ) SOFT OR LIQUID FECES 14878 DS( 38- 42) SNOUT: SWOLLEN DS( 39- 41) CHROMODACRYORFWEA DS( 77 ) CHROMORHINORRHEA DS( 77- 92) CHROMODACRYORRHEA DS( 77- 93) INCISORS: MISSING/BROKEN a DS( 80 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) OPHTHALMOLOGICAL EXAMINATION: BOTH EYES: CHROMODACRYORRHEA 14879 NO ADVERSE FINDINGS 14880 DS( 69 ) CHROMORHINORRHEA P _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -w - 03 ALL EYES APPEARED NORMAL PRIOR TO DOSAGE. ALL EYES APPEARED NORMAL AT TERMINATION UNLESS NOTED OTHERWISE. b DS = DAY OF STUDY a. Observation confirmed at necropsy. m N PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBVTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 25 (PAGE 5): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - MALE RATS 14881 14882 14883 14884 14885 14886 14887 14888 14889 80 ) 80 ) 77- 79) 78 ) 78 1 78 1 79- 80) 62- 90) 66 1 73 ) 79 1 80 ) 87 ) 79 ) 79- 92) 80 1 87 ) 91 ) 69- 93) 71- 93) 73 ) 80 ) 87 ) 91 ) 91 1 91 ) 91 1 79 ) NO ADVERSE FINDINGS CHROMORHINORRHEA RED, SLIGHT PERIORAL SUBSTANCE RED, SLIGHT TO EXTREME PERIORAL SUBSTANCE CHROMORHINORRHEA FUR DISCOLORED RED SUBSTANCE IN CAGE PAN URINE-STAINED ABDOMINAL FUR LOCALIZED ALOPECIA: LIMBS DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT EXCESS SALIVATION DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT RED, MODERATE PERIORAL SUBSTANCE EAR (S) : SWOLLEN a DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT LOCALIZED ALOPECIA: LIMBS a URINE-STAINED ABDOMINAL FUR DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT DETAILED CLINICAL OBSERVATIONS APPEARED NOT CHROMORHINORRHEA FUR DISCOLORED RED, MODERATE PERIORAL SUBSTANCE DETAILED CLINICAL OBSERVATIONS APPEARED NOT NO ADVERSE FINDINGS RED, SLIGHT PERIORAL SUBSTANCE NO ADVERSE FINDINGS NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL b i L v, PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 25 (PAGE 6): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - MALE RATS .................................................................................................................................... GROUP IV HIGH DOSAGE GOO MG/KG/DAY ________________________________________-------------------------------------------------------------------------------------------- RAT # DESCRIPTION ___---____-_____________________________----------------------- 14890 DS( 83- 84) RED PERIORAL SUBSTANCE a DS( 83- 84) URINE-STAINED ABDOMINAL FUR DS( 84- ) DECREASED MOTOR ACTIVITY DS( 84 ) COLD TO TOUCH DS( 84 PTOSIS DS( 84 ) DEHYDRATION a DS( 84 ) MOUTH: BROWN SUBSTANCE DS( 84 1 UNGROOMED COAT DS( 85 ) FOUND DEAD .................................................................................................................................... ALL EYES APPEARED NORMAL PRIOR TO DOSAGE. DS = DAY OF STUDY a. Observation confirmed at necropsy. ALL EYES APPEARED NORMAL AT TERMINATION UNLESS NOTED OTHERWISE. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 26 (PAGE 1): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS GROUP I -_------________ - ----- VEHICLE 0 (VEHICLE) MG/M/DAY ..................................................................................................... 14891 DS( 8 0 - 84) RALES 14892 DS( 25- 29) LEFT FOREPAW: ABRASION (0.2 CM IN DIAMETER) 14893 DS( 42- 44) DS( 42- 92) CHROMODACRYORRHEA INCISORS: MISALIGNED a DS( 45 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 80 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14894 DS( 59- 92) TAIL BENT a DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 92 ) SOFT OR LIQUID FECES 14895 DS( 52- 92) LOCALIZED ALOPECIA: LIMBS a DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 77 ) CHROMORHINORRHEA DS( 77 ) RED, SLIGHT PERIORAL SUESTANCE DS( 80 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14896 NO ADVERSE FINDINGS 14897 NO ADVERSE FINDINGS 14898 DS( 92- 93) CHROMORHINORFUIEA ________________________________________-------_------------------------------------------------------------------------------------ ALL EYES APPEARED NORMAL PRIOR TO DOSAGE UNLESS NOTED OTHERWISE. ALL EYES APPEARED NORMAL AT TERMINATION. DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED W S E 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 6 (PAGE 2): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS VEHICLE o (VEHICLE) MG/KG/DAY LOCALIZED ALOPECIA: LIMBS a DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETXLED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL NO ADVERSE FINDINGS PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 26 (PAGE 3): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS -----_-______-__________________________---------------------------------------------------------------~~-------~-~----------~~~---- RAT # DESCRIPTION -_______________________________________-------------------------------------------------------------------------------------------- GROUP I1 LOW DOSAGE 60 MG/KG/DAY . .................................................................................................................................... 14901 DS( 77- 78) LOCALIZED ALOPECIA: LIMBS DS( 91 ) LOCALIZED ALOPECIA: LIMBS a DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14902 NO ADVERSE FINDINGS 14903 NO ADVERSE FINDINGS 14904 DS( 4 - 92) LOCALIZED ALOPECIA: LIMBS a DS( 4 1 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 10 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 24 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 31 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 38 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 45 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14905 NO ADVERSE FINDINGS 14906 NO ADVERSE FINDINGS 14907 NO ADVERSE FINDINGS 14908 ( PREDOSE) OPHTHALMOLOGICAL EXAMINATION: LEFT EYE: IRITIS 14909 DS( 19- 24) LOCALIZED ALOPECIA: LIMBS DS( 24 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14910 DS( 77- 91) EAR (SI : SWOLLEN DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL ________________________________________------------------- ALL EYES APPEARED NORMAL PRIOR TO DOSAGE UNLESS NOTED OTHERWISE. ALL EYES APPEARED NORMAL AT TERMINATION. DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 26 (PAGE 4): CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS ________________________________________-------------------------------------------------------------------------------------------- RAT # DESCRIPTION ________________________________________-------------------------------------------------------------------------------------------- GROUP I11 MIDDLE DOSAGE 200 MG/KG/DAY . ____-___________________________________---------------------- 14911 DS( 19- 24) LOCALIZED ALOPECIA: LIMBS DS( 24 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 61- 64) INCISORS: MISSING/BROKEN DS( 61- 64) INCISORS: MISALIGNED DS( 77- 91) LOCALIZED ALOPECIA: LIMBS a DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14912 DS( 64- 74) RALES DS( 66 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14913 DS( 91- 92) LOCALIZED ALOPECIA: LIMBS a 14914 NO ADVERSE FINDINGS 14915 NO ADVERSE FINDINGS 14916 DS( 79 ) SOFT OR LIQUID FECES 14917 DS( 75- 93) EAR ( S ) : SWOLLEN a DS( 80 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 87 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14918 NO ADVERSE FINDINGS 14919 DS( 78- 79) RED SUBSTANCE IN CAGE PAN 14920 NO ADVERSE FINDINGS ________________________________________--------------------- ALL EYES APPEARED NORMAL PRIOR TO DOSAGE UNLESS NOTED OTHERWISE. DS = DAY OF STUDY a. Observation confirmed at necropsy. ALL EYES APPEARED NORMAL AT TERMINATION. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 26 (PAGE 5 ) : CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS ________________________________________-------------------------------------------------------------------------------------------- RAT # DESCRIPTION .................................................................................................................................... GROUP IV HIGH DOSAGE 600 MG/KG/DAY . ________________________________________-------------------------------------------------------------------------------------------- 14921 NO ADVERSE FINDINGS 14922 DS( 82- 90) INCISORS: MISALIGNED DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14923 DS( 35- 91) LOCALIZED ALOPECIA: LIMBS a DS( 38 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 45 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 59 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 6 6 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 73 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 79 ) RED, SLIGHT PERIORAL SUBSTANCE DS( 79- 80) CHROMODACRYORRHEA DS( 80 ) DS( 80 ) EXCESS SALIVATION DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 80- 82) URINE-STAINED ABDOMINAL FUR DS( 83- 91) LOCALIZED ALOPECIA: BACK DS( 87 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14924 NO ADVERSE FINDINGS 14925 NO ADVERSE FINDINGS 14926 DS( 77 ) CHROMODACRYORRHEA 14927 DS( 92 ) DS( 33- 38) CHROMODACRYOWEA INCISORS: MISSINGfBROKEN DS( 38 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14928 DS( 46- 57) INCISORS: MISSING/BROKEN DS( 52 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL 14929 DS( 17 ) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL DS( 91 ) DS( 91- 92) DETAILED CLINICAL OBSERVATIONS APPEARED NOT NORMAL LOCALIZED ALOPECIA: LIMBS 14930 NO ADVERSE FINDINGS .................................................................................................................................... ALL EYES APPEARED NORMAL PRIOR TO DOSAGE UNLESS NOTED OTHERWISE. ALL EYES APPEARED NORMAL AT TERMINATION. DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 2 7 (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - MALE RATS .............................................................. o (VEHICLE) MG/KG/DAY - - - - - - - - - - - - _ _ DAY _____ 1 ___ _ - _ _ _ _ _ _8 _ _ _ _ _ _ _ _1_5_ _ _ 22 29 36 43 50 . 57 64 71 78 85 _______________________________________ 14851 180. 236. 289. 318. 347. 365. 388. 405. 426. 437. 446. 455. 459. 14852 202. 261. 310. 348. 377. 404. 429. 451. 473. 488. 501. 509. 516. 14853 191. 258. 316. 355. 401. 431. 459. 485. 516. 534. 557. 550. 569. 14854 190. 259. 321. 374. 419. 448. 482. 506. 533. 547. 556. 571. 577. 14855 185. 245. 294. 329. 359. 383. 400. 413. 427. 445. 460. 474. 480. 14856 201. 272. 331. 377. 418. 441. 468. 494. 508. 525. 543. 567. 581. 14857 191. 249. 305. 349. 381. 401. 410. 422. 436. 446. 460. 465. 482. 14858 198. 261. 322. 369. 406. 434. 457. 483. 511. 527. 533. 553. 567. 14859 186. 237. 286. 321. 353. 383. 407. 426. 448. 461. 485. 489. 513. 14860 197. 266. 320. 369. 416. 463. 485. 504. 522. 535. 555. 568. 573. TERMINAL BODY WEIGHT a 14851 0 14852 0 14853 444. 500. 543. 14854 554. 14855 460. 14856 548. 14857 458. 14858 552. 14859 483. 14860 567. ................................................................................................. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (GI. a. Rats were fasted the evening prior to sacrifice. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 27 (PAGE 2): BODY WEIGHTS - INDIVIDUAL DATA - MALE RATS b PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 2 7 (PAGE 3): BODY WEIGHTS - INDIVIDUAL DATA - MALE RATS - _ - - - _ _ _ _ _ _ _ _ DAY ___ _ 1 _ _ _ _ _ _ _ 8 _ _ _ _ _ _ 15 __ _ _ _ _-_- 22 _- -_-_--_-_- ~ _ 29 ___ _ _ _ _ _ 36 __ _ _ _ _ _ 43 __ _ _ _ _ _ 50 __ _ _ . _ _ _ 5 _ 7 _ _ _ _ 64 -_-____- ---_~ _- -_-___ 7__ _1 _ _ _ _ _ _ _ 7_ 8 _ _ _ _ _ _ _ _ 8_ 5 _ _ _ _ 14871 178. 234. 272. 309. 339. 362. 382. 405. 424. 451. 455. 468. 477. 14872 200. 250. 294. 325. 349. 380. 395. 415. 429. 452. 465. 478. 496. 14873 188. 240. 286. 309. 340. 363. 386. 403. 418. 440. 462. 474. 482. 14874 190. 258. 315. 354. 387. 402. 435. 458. 476. 506. 533. 546. 567. 14875 184. 244. 292. 328. 360. 383. 394. 410. 427. 436. 450. 461. 463. 14876 202. 254. 300. 329. 355. 380. 405. 430. 444. 448. 472. 484. 500. 14877 185. 247. 296. 333. 369. 396. 426. 449. 469. 490. 509. 519. 537. 14878 192. 257. 303. 332. 350. 372. 382. 392. 414. 436. 450. 448. 463. 14879 188. 253. 301. 335. 370. 399. 424. 450. 467. 485. 501. 505. 517. _ _ 14880 ___ _ _ _ _ 193. ___ _ _ 251. ___ _ 296. ___ _ _.-_3- 2-_-9-._- ._. ._. .3_.6.3_..._. ._. ._.3.8_.5.._. ._. ._. .4_.0._6. .._. .-. _ . . 426. -. ... . . . . . . 444. ..... . _ 4 _ 65. __ - _ _ 473. __ __ __- - - - - 482. ----- __ ___ _ 5_ 0_ 7_ . _ _ _ ._ PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 27 (PAGE 4 ) : BODY WEIGHTS - INDIVIDUAL DATA - MALE RATS c w 0 P c PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 28 (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - FEMALE RATS b PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 8 (PAGE 2) : BODY WEIGHTS - INDIVIDUAL DATA - FEMALE RATS DAY 1 8 15 22 29 36 43 50 . 57 64 71 78 85 - - - - - - - _ _ _ _ ___- _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - _- -_ -_ -_ -_ -_-_-_-_-_-_-_ - _ _ _ _ _ _ _ _ _ _ _ .-_ - - -_ - -_ _ _ _ _ _ - - 14901 150. 171. 180. 204. 221. 233. 228. 242. 256. 258. 252. 258. 272. 14902 175. 192. 219. 240. 253. 260. 279. 294. 292. 292. 308. 311. 313. 14903 159. 183. 209. 221. 226. 243. 248. 254. 254. 257. 265. 269. 273. 14904 14905 158. 155. 200. 184. 227. 202. 239. 230. 266. 242. 283. 264. 287. 264. 290. 278. 312. 277. 321. 299. 324. 300. 322. 297. 330. 320. 14906 162. 199. 225. 240. 243. 258. 268. 277. 281. 295. 309. 316. 321. 14907 160. 196. 227. 251. 261. 285. 286. 300. 306. 304. 320. 322. 323. 14908 167. 192. 205. 232. 254. 262. 266. 279. 286. 291. 290. 298. 312. 14909 154. 187. 225. 245. 255. 263. 272. 290. 296. 296. 306. 308. 312. 14910 170. 198. 214. 233. 248. 259. 258. 274. 275. 275. 286. 290. 290. TERMINAL BODY WEIGHT a _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -_ -. - - - - - - _ . 14901 249. 14902 294. 14903 256. 14904 313. 14905 298. 14906 302. 14907 304. 14908 284. 14909 292. 14910 268. ______________-_________________________--------------------------------------------------------------------- DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Rats were fasted the evening prior to sacrifice. 1 0 h, o\ PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 8 (PAGE 3): BODY WEIGHTS - INDIVIDUAL DATA - FEMALE RATS 14911 152. 186. 211. 229. 232. 249. 258. 264. 265. 267. 272. 274. 279. 14912 173. 200. 219. 231. 253. 257. 270. 276. 289. 302. 295. 288. 300. 14913 158. 188. 211. 228. 253. 268. 271. 276. 286. 296. 298. 293. 301. 14914 158. 199. 227. 248. 273. 287. 300. 302. 317. 326. 327. 332. 340. 14915 134. 171. 190. 210. 223. 230. 236. 246. 256. 258. 257. 265. 271. 14916 172. 212. 239. 265. 291. 304. 310. 328. 345. 341. 355. 360. 367. 14917 158. 186. 212. 242. 255. 268. 279. 286. 296. 298. 299. 305. 315. 14918 159. 187. 211. 225. 244. 257. 266. 273. 283. 288. 291. 291. 302. 14919 151. 176. 198. 209. 223. 234. 236. 238. 244. 249. 250. 248. 265. _ _ _ 1492 ___ 0 _ _ _ _ _ _ _ 16 __ 4. __ _ _ _ 192. ___ _ _ _ 210. ____ _ _ _ 224. ___ _ _ _ 242. _---- - - - - - 260; ---- - - - - - 27 --- 3 - . - - - - - - 283. ----- - - - - - 2 - 8 - 5 - . -- - - - - 298. ----- - - - - - 310. ----- - - - - - 308 _- -_- . -------_- _ 3 - 2 - 5. __ _ - - _ TERMINAL BODY WEIGHT a ................................................................................................................... c 14911 0 m 14912 14913 257. 284. 284. 14914 318. 14915 250. 14916 341. 14917 287. 14918 283. 14919 244. 14920 300. ................................................................................................................... DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Rats were fasted the evening prior to sacrifice. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBWANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 28 (PAGE 4): BODY WEIGHTS - INDIVIDUAL DATA - FEMALE RATS c 0 4 0 13 cn PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 2 9 (PAGE 1): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - MALE RATS 14851 14852 149. 165. 186. 182. 169. 187. 169. 194. 162. 190. 165. 200. 167. 197. 169. 190. 161. 188. 169. 183. 161. 180. 160. 171. 14853 14854 177. 174. 192. 192. 194. 192. 213. 206. 209. 201. 209. 208. 207. 208. 206. 215. 202. 208. 204. 202. 193. 209. 194. 201. 14855 14856 159. 169. 172. 184. 170. 183. 174. 184. 168. 177. 168. 180. 175. 185. 180. 186. 175. 194. 184. 190. 183. 200. 173. 191. 14857 14858 14859 151. 165. 153. 165. 205. 175. 173. 208. 185. 179. 207. 193. 164. 205. 195. 158. 208. 193. 157. 213. 199. 161. 213. 195. 165. 207. 197. 164. 204. 201. 165. 198. 205. 160. 197. 202. - - - - 1- - 4 8 - 6 - 0 - - - - - - . _ - - - - 1 - 70. --- - - _ 17 __ 7. __ _ _ 21 _- -_- 3 - . - - - - - - 2 - 1 - 5. __ _ _ _ 220. ___ _ __ __. 21 __ 0 _ . _ _ _ _ 220 ___ . _ _ _ _ 212. ____ _ _ _ _ 210. ____ _ _ _ 2 _ 13. ___ _. __ _ 21 __ 7. _- - - - _ 2_ 1_ 4_ ._ _ _ _ _ _ _ _ _ _ _ - - - - RAT - - - - # - - - - - - . - - - - GROUP -----_ I1 -_ _ _ _ _ _ _-_- _- - - - - - - - LOW -__ DOSAGE __-__ _ _ _ ____. __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 6 _ 0 _ MG/KG/DAY _________ _ _ _ _ _ _ _ _ _. -_-_____ _- -_- - _ c 14861 138. 150. 154. 155. 147. 145. 141. 140. 144. 143. 138. 143. 0 14862 174. 195. 200. 203. 200. 197. 202. 204, 201. 213. 206. 204. 00 14863 171. 199. 198. 195. 188. 200. 192. 188. 187. 196. 209. a 14864 156. 175. 179. 183. 171. 176. 183. 189. 191. 193. 190. 191. 14865 161. 187. 189. 198. 191. 195. 200. 201. 197. 202. 207. 223. 14866 165. 187. 181. 193. 198. 195. 198. 194. 181. 196. 192. 178. 14867 165. 182. 181. 180. 178. 184. 190. 190. 190. 185. 189. a 14868 181. 203. 196. 197. 183. 186. 200. 195. 189. 187. 197. 188. 14869 145. 165. 155. 160. 158. 156. 154. 153. 153. 151. 160. 152. 14870 186. 221. 208. 219. 208. 204. 224. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - -_- .- - - - - - - - - - 232. 228. 216. 212. 211. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. b t3 cn PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 29 (PAGE 2): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - MALE RATS 14871 165. 161. 165. 167. 161. 165. 157. 14872 134. 158. 161. 171. 185. 181. 227. 14873 157. 171. 166. 172. 171. 174. 166. 14874 161. 194. 192. 194. 183. 198. 201. 14875 150. 166. 174. 175. 168. 166. 166. 14876 157. 172. 166. 171. 165. 172. 177. 14877 148. 164. 172. 176. 171. 181. 189. 14878 175. 192. 170. 167. 170. 156. 163. 14879 157. 174. 172. 180. 183. 191. 197. 14880 160. 184. 177. 189. 180. 181. 186. - _ - - _ - - - -.-. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RAT # GROUP IV HIGH DOSAGE 162. 170. 161. 188. 185. 185. 170. 178. 178. 205. 213. 221. 162. 168. 160. 172. 158. 168. 188. 182. 189. 170. 177. 183. 195. 197. 183. _ _18_ 2_ ._ _ _ _ _ _ 1_ 8_ 1_ ._ _ _ - - - -17- 9- . 6 0 0 MG/KG/DAY 165. 179. 175. 213. 159. 177. 191. 168. 187. 187. 155. 184. 172. 208. 154. 175. 175. 142. 184. 181. 14881 151. 173. 170. 168. 165. 169. 160. 172. 173. 170. 166. 153. 14882 166. 191. 203. 205. a 200. 198. 199. 195. 187. 190. 182. 14883 163. 199. 188. 191. 198. 213. 207. 203. 213. 220. 212. 191. 14884 159. 170. 166. 173. 177. 180. 179. 183. 186. 185. 185. 176. 14885 168. 186. 192. 195. 193. 212. 207. 198. 205. 195. 205. 187. 14886 170. 181. 181. 189. 181. 183. 179. 180. 217. 217. a 192. 14887 172. 189. 182. 191. 184. 180. 181. 171. 180. 174. 185. 176. 14888 162. 177. 175. 180. 179. 181. 184. 195. 184. 188. 188. 179. 14889 149. 160. 163, 176. 169. 169. 166. 154. 159. 165. 170. 163. _ _ _ 14890 _____ _ _ _ _ _ _ 181. __--_ _ _ _ 187. ____ _ _ _ 204. ____ _ _ 190. ____ _ - - - 193. ------ - - - 210. -_- -_- -_---_- _ - 214. __-- _ _ 210. ---___- -_ _ _ _ 208. -___ _ _ 206. ____ _ _ _2__0_3_.-__ - _ _ b _- _ _ _ _ _ - - DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GTiAMS (G). a. Spilled feed precluded t h e c a l c u l a t i o n of t h i s value. b. R a t 14890 was found dead on day 85 of study. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 30 (PAGE 1): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FEMALE RATS - _ - - - - _ - _ _ _ _ _ _ _ _ _ _ _--- - -_-_- - - - - - - - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _- -_- _- ---_- _- --_ _ _ _ _ _ _ _ _ _ _ - ___-_- _______ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _._- _- -_-_-_- 14891 122. 129. 132. 135. 138. 132. 131. 137. 137. 136. 135. 123. 14892 131. 147. 143. 150. 153. 150. 139. 131. 147. 138. 127. 123. 14893 a 165. 177. 124. 136. 128. 119. 126. 123. 109. 119. 123. 14894 121. 139. 131. 130. 135. 147. 137. 138. 133. 139. 135. 125. 14895 107. 128. 132. 126. 129. 131.. 130. 118. 108. 122. 127. 117. 14896 125. 123. 120. 146. 131. 142. 125. 120. 139. 123. 122. 127. 14897 114. 122. 122. 130. 128. 130. 132. 136. 132. 135. 132. 130. 14898 125. 123. 120. 119. 121. 122. 123. 125, 119. 122. 116. 124. 14899 110. 115. 117. 117. 116. 115. 115. 109. 110. 109. 105. 108. 14900 124. 137. 130. 124. 116. 134. 127. 124. 123. 129. 123. 117. 14901 14902 14903 14904 14905 14906 14907 14908 14909 14910 116. 115. 115. 139. 129. 147. 118. 117. 124. 126. 114. 123. 122. 144. 127. 139. 133. 119. 144. 125. 122. 128. 116. 146. 136. 135. 135. 128. 141. 124. 127. 130. 118. 157. 134. 131. 136. 136. 139. 131. 123. 135. 130. 152. 141. 127. 147. 127. 139. 120. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. 120. 137. 121. 116. 143. 138. 122. 122. 123. 121. 119. 116. 152. 157. 159. 150. 145. 149. 132. 144. 128. 128. 130. 147. 144. 134. 132. 134. 126. 134. 129. 127. 147. 147. 150. 144. . - 1- 2- 2- .- - - _ _ 126. -__ _ _ _ 119. ___ _ _ _ 117. _- -- - - - - - 111. 129. 114. 138. 135. 121. 111. 112. 110. 143. 147. 142. 137. 137. 141. 137. 144. 141. 134. 138. 125. 123. 133. 125. 146. 141. 136. 122. 124. 112. - - - - - - - _ _ - - _ _ _ _ _- -_-_- - - - - PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 30 (PAGE 2): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FEMALE RATS 14911 14912 132. 121. 138. 129. 131. 121. a 134. 137. 119. a 135. 119. 144. 118. 139. 120. 135. 121. 102. 14913 14914 14915 14916 118. 127. 106. 142. 124. 145. 123. 155. 124. 148. 124. 165. 130. 153. 121. 165. 133. 153. 116. 163. 132. 158. 121. 166. 133. 145. 121. 171. 128. 151. 119. 161. 130. 144. a 151. 122. 142. 116. 153. 14917 14918 125. 118. 139. 133. 148. 131. 143. 142. 145. 142. 148. 142. 143. 141. 142. 142. 139. 129. 135. 134. 14919 118. 123. 120. 128. 125. 121. 120. 119. 117. 118. 14920 134. . - 1 - 3 - 3 - . - - - - 132. 143. - - - - - - - - - - _ 1_ 5_ 2_ ._ _ _ _ _ _ 1_ 4_ 5_ ._ _ - 143. - - - - - - _ _ _ 1_ 3_ 7_ ._ _ _ _ - - - -a- - - - - - - 148. - - - - - RAT # GROUP IV HIGH DOSAGE 600 MG/KG/DAY .......................................................................................................... 14921 101. 106. 106. 108. 109. 116. 112. 110. 119. 108. 14922 119. 125. 143. 128. 126. 129. 135. 129. 126. 119. 14923 123. 124. 131. 132. 149. 135. 142. 135. 137. 135. 14924 126. a 140. 141. a 133. 122, 126. 128. 121. 14925 122. 132. 130. 134. 150. 135. 134. 136. 134. 127. 14926 134. 141. 137. 130. 144. 144. 142. 142. 145. 146. 14927 14928 106. 130. 115. 138. 120. 137. 124. 142. 125. 153. 129. a 123. a 118. a 122. 141. 122. 123. 14929 110. 113. 172. 124. 115. 116. 123. 117. 111. 107. 14930 131. 161, 97. 158. 133. a 130. 133. 131. 128. .......................................................................................................... DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. 121. 124. 115. 150. 120. 152. 144. 140. 120. - 1 - 4 - 8 - . - - - - - 119. 137. 126. 131. 112, 150. 135. 137. 126, 1 - 5 - -0-,- - - - - _ . 117. 133. 106. 125. 133. 140. 101. 137. 116. 135. - - - - - - - - 110. 125, 59. 121. 138. 136. 128. 144. 112. 1 - 3 - 3 - . - - - - - - PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 31 (PAGE 1): MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP I 0 (VEHICLE) MG/KG/DAY RAT NUMBER 14851 14852 14057 14859 14860 DAY 86 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 BLOCK 8 BLOCK 9 '+ 3 BLOCK 10 BLOCK 11 BLOCK 12 BLOCK 13 BLOCK 14 BLOCK 15 BLOCK 16 BLOCK 17 BLOCK 18 TOTAL 63 70 66 52 58 61 70 70 51 54 64 51 60 53 49 63 55 70 48 66 49 65 48 46 28 73 54 67 49 39 57 35 1 37 6 40 21 0 46 0 2 18 24 25 1 0 11 1 42 2 13 0 0 36 1 0 0 0 25 2 1 5 8 2 1 1 0 0 4 2 1 0 49 4 6 15 0 44 2 0 0 2 7 3 0 0 2 0 5 1 503 459 515 530 316 TOTAL I SUM OF BLOCKS1 EACH BLOCK CONSISTS OF A MINUTE PERIOD. PROTOCOL 418-026: ORAL (GAVAGE) REPEhTED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 31 (PAGE 2): MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP I 0 (VEHICLE) MG/KG/DAY RAT NUMBER 14851 14852 14057 14859 14860 DAY 86 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 cd BLOCK 7 6 BLOCK 8 BLOCK 9 e BLOCK 10 w + BLOCK 11 BLOCK 12 BLOCK 13 BLOCK 14 BLOCK 15 BLOCK 16 BLOCK 17 BLOCK 18 TOTAL 226 163 242 17 2 220 138 161 185 100 200 162 99 91 98 110 115 85 115 71 113 53 150 54 66 17 100 45 95 91 72 159 31 0 27 2 24 18 0 96 0 0 12 21 23 0 0 9 0 73 1 6 0 0 39 0 0 0 0 29 1 0 3 2 0 0 0 0 0 3 0 0 0 95 1 5 10 0 52 0 0 0 1 I 2 0 0 2 0 4 0 993 719 959 895 741 TOTAL = SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. PROTOCOL 4 1 8 - 0 2 6 1 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTJdE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 1 (PAGE 3 ) : MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP I1 6 0 MG/KG/DAY RAT NUMBER 14862 14865 14867 14868 DAY 8 6 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 % BLOCK 8 BLOCK 9 + BLOCK 1 0 c , BLOCK 11 BLOCK 1 2 BLOCK 1 3 BLOCK 1 4 BLOCK 1 5 BLOCK 1 6 BLOCK 1 7 BLOCK 1 8 TOTAL 68 67 68 28 67 55 31 4 0 0 0 0 0 0 0 0 0 0 388 70 68 68 68 61 16 3 26 52 6 2 11 2 2 55 0 0 0 5 10 82 76 76 40 6 14 7 0 3 0 0 0 0 0 1 0 0 0 305 70 74 64 74 56 76 47 69 49 34 11 3 1 2 0 0 0 0 630 TOT= I SUM OF BLOCKS! EhCH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 14869 53 57 65 58 39 60 62 41 48 39 40 24 43 12 28 23 2 0 694 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUKBER: T-7485.15) TABLE 31 (PAGE 4): MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP I1 60 MG/KG/DAY RAT NUMBER 14862 14865 14867 14868 14869 DAY 86 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 219 192 199 154 BLOCK 2 174 142 19 5 17 6 BLOCK 3 106 140 91 e3 BLOCK 1 26 113 48 152 BLOCK 5 110 80 11 88 BLOCK 6 134 11 14 86 BLOCK 7 46 0 4 78 % BLOCK 8 BLOCK 9 L BLOCK 10 L BLOCK 11 1 30 0 71 0 2 0 0 0 82 1 79 0 63 0 5 BLOCK 12 0 8 0 7 BLOCK 13 0 1 0 0 BLOCK 14 0 0 0 0 BLOCK 15 0 43 0 0 BLOCK 16 0 0 0 0 BLOCK 17 0 0 0 0 BLOCK 18 0 0 0 0 - TOTAL 816 e39 566 1053 TOTAL SUM OF BLOCKSi EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 209 204 147 110 75 146 76 61 101 62 83 38 56 6 32 37 1 0 1444 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERPLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 31 (PAGE 5) : MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS - GROUP I11 200 MG/KG/DAY - U T NUMBER 14871 14875 14876 14877 14880 DAY 86 NUMBER OF MOVEMENTS BLOCK 1 63 68 59 62 76 BLOCK 2 67 54 73 64 77 BLOCK 3 65 62 40 60 63 BLOCK 4 43 49 63 52 69 BLOCK 5 44 42 46 44 54 BLOCK 6 44 10 20 47 57 BLOCK 7 57 1 36 22 7 % BLOCK 8 BLOCK 9 I- BLOCK 10 c o\ BLOCK 11 11 3 52 16 0 28 1 30 21 19 1 0 41 2 2 6 0 30 0 8 BLOCK 12 5 0 41 2 0 BLOCK 13 0 0 17 0 0 BLOCK 14 4 0 0 2 0 BLOCK 15 0 0 0 0 1 BLOCK 16 1 0 0 0 1 BLOCK 17 1 0 1 1 1 BLOCK 18 0 1 2 2 4 - TOTAL TOTAL SUM OF BLOCKS; EACH 440 291 BLOCK CONSISTS OF A 551 5 MINUTE 397 PERIOD. 439 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERPLUOROBUTANE SULFONATE (PPBS) IN RATS (SPONSOR'S STUDY NUMBER1 T-7485.15) TABLE 31 (PAGE 6): MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP I11 200 MG/KG/DAY IUT NUMBER 14871 14875 14876 14877 14880 DAY 86 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 187 224 126 2 03 181 BLOCK 2 107 14 0 11s 211 193 BLOCK 3 139 14 5 53 152 114 BLOCK 4 42 60 97 63 96 BLOCK 5 51 68 16 57 73 BLOCK 6 50 5 16 87 94 BLOCK 7 76 5 39 40 9 %- BLOCK 8 BLOCK 9 c BLOCK 10 BLOCK 11 7 0 72 11 0 23 0 36 18 26 0 0 61 1 0 6 0 40 0 7 BLOCK 12 2 0 47 0 0 BLOCK 13 0 0 31 0 0 BLOCK 14 3 0 0 0 0 BLOCK 15 0 0 0 0 1 BLOCK 16 0 0 0 0 0 BLOCK 17 0 0 0 0 0 BLOCK 18 0 0 1 0 5 TOTAL 693 647 8 13 843 799 TOTAL - SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERPLUOROBUTANE SULFONATE (PPBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 31 (PAGE 7): MOTOR ACTIVITY - INDIVIDUAL DATA - RATS GROUP IV 600 MG/KG/DAY RAT m E R 14883 14884 14885 14886 14888 DAY 86 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 Tdp BLOCK 8 % BLOCK 9 c BLOCK 10 BLOCK 11 BLOCK 12 BLOCK 13 BLOCX 14 BLOCK 15 BLOCK 16 BLOCK 17 BLOCK 18 TOTAL 59 51 54 86 79 69 61 67 81 72 64 62 69 69 42 57 31 51 28 18 46 70 61 53 3 67 41 65 56 0 38 28 64 79 1 14 0 68 73 1 57 49 48 83 0 5 29 58 55 0 9 15 29 23 0 1 0 20 42 1 0 0 50 0 0 3 0 32 0 0 1 4 18 5 0 0 0 27 4 10 0 0 0 1 1 0 0 0 1 0 490 441 781 739 228 TOTAL I SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PPBS) IN RATS (SPONSOR`S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLB 3 1 (PAGE 8 ) : MOTOR ACTIVITY - INDIVIDUAL DATA - MALE RATS GROUP IV 6 0 0 MG/KG/DAY 2 * % w \c O RAT NUMBER 14883 14884 14805 14886 DAY 8 6 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 252 121 233 162 BLOCK 2 234 124 212 142 BLOCK 3 224 69 155 85 BLOCK 4 137 22 115 38 BLOCK 5 164 86 13 0 71 BLOCK 6 131 31 124 79 73 17 135 117 BLOCK 8 16 0 159 90 BLOCK 9 63 62 69 82 BLOCK 1 0 4 30 63 57 BLOCK 11 10 8 43 15 BLOCK 1 2 0 0 23 23 BLOCK 1 3 0 0 134 0 BLOCK 1 4 0 0 35 0 BLOCK 1 5 0 2 21 2 BLOCK 1 6 0 0 25 2 BLOCK 1 7 0 0 0 0 BLOCK 1 8 0 0 0 0 TOTAL 1308 572 1676 965 TOTAL - SUM OF BLOCKS1 EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 14888 188 14 8 77 18 0 0 0 0 0 0 0 0 0 0 0 6 1 0 438 PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 2 (PAGE 1 ) : MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE RATS GROUP I 0 (VEHICLE) MG/XG/DAY RAT NUMBER 14891 14893 14896 14898 14899 DAY 86 NUMBER OF MOVEMENTS BLOCK 1 62 61 58 52 73 BLOCX 2 57 78 61 67 68 BLOCX 3 59 58 73 55 29 BLOCX 4 46 59 66 69 48 BLOCX 5 6 31 66 61 21 BLOCX 6 17 10 34 50 59 BLOCK 7 1 3 2 92 57 % BLOCX 8 BLOCX 9 c BLOCX 1 0 3 6 6 78 45 2 4 0 39 27 1 0 2 31 42 BLOCX 1 1 8 0 48 11 27 BLOCX 1 2 0 1 26 4 0 BLOCK 1 3 10 1 14 1 6 BLOCX 1 4 5 5 2 5 4 BLOCX 1 5 0 5 7 3 0 BLOCX 1 6 0 2 0 13 0 BLOCX 17 5 0 0 0 0 BLOCX 1 8 0 8 1 0 0 - TOTAL 282 338 466 63 1 506 TOTAL SUM OF BLOCKS; EACH BLOCX CONSISTS OF A 5 MINUTE PERIOD. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 32 (PAGE 2): MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE RATS GROUP I 0 (VEHICLE) MG/KG/DAY RAT NUMBER 14891 14893 14896 14898 14899 DAY 86 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 181 151 151 203 113 BLOCK 2 111 126 12 8 137 129 BLOCK 3 58 78 105 142 23 BLOCK 4 35 92 97 13 6 15 BLOCK 5 3 21 55 100 15 BLOCK 6 10 3 26 114 62 BLOCK I 0 0 1 101 93 % BLOCK 8 BLOCK 9 c BLOCK 10 1 1 5 12 5 51 0 2 0 35 25 0 0 0 18 35 BLOCK 11 3 0 50 I 17 BLOCK 12 0 0 20 1 0 BLOCK 13 5 0 11 0 2 BLOCK 14 3 3 0 4 2 BLOCK 15 0 1 3 1 0 BLOCK 16 0 0 0 9 0 BLOCK 17 3 0 0 0 0 BLOCK 18 0 3 0 0 0 - TOTAL 413 481 652 1139 708 TOTAL SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 2 (PAGE 3): MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE RATS GROUP I1 6 0 MG/KG/DAY RAT NUMBER 14902 14903 14904 14906 DAY 8 6 NUMBER OF MOVEMENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 % BLOCK 8 BLOCK 9 I- BLOCK 1 0 BLOCK 11 BLOCK 1 2 BLOCK 13 BLOCK 1 4 BLOCK 1 5 BLOCK 1 6 BLOCK 1 7 BLOCK 1 8 TOTAL 57 41 24 5 3 0 0 39 62 58 5 0 2 1 11 0 2 0 310 64 79 45 0 2 2 0 41 57 65 23 0 1 2 2 9 0 4 402 60 44 44 54 57 26 26 1 2 11 59 37 71 27 1 0 11 5 536 58 69 57 42 70 64 16 51 48 73 42 35 25 27 17 1 1 0 696 TOTAL I SUM OF BLOCKS: EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 14909 65 65 71 76 55 33 67 60 61 57 65 71 40 58 19 45 62 49 1019 PROTOCOL 418-026: ORhL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PPBS) IN RATS (SPONSOR'S STUDY NUKBER: T-7485.15) T-LE 32 (PAGE 4): MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE IUTS GROUP I1 60 MG/KG/DAY RAT m E R 14902 14903 14904 14906 14909 DAY 86 TIME (SECONDS) SPENT IN MOVEMF,NT BLOCK 1 151 160 198 139 BLOCK 2 97 102 95 119 BLOCK 3 15 41 47 100 BLOCK 4 1 0 60 62 BLOCK 5 1 0 71 133 BLOCK 6 0 1 18 107 BLOCK 7 0 0 11 17 % BLOCK 8 BLOCK 9 w BLOCK 10 42 36 118 103 51 109 0 66 0 77 9 114 BLOCK 11 0 13 59 42 BLOCK 12 0 0 25 33 BLOCK 13 1 0 123 16 BLOCK 14 0 0 36 16 BLOCK 15 4 1 0 22 BLOCK 16 0 4 0 0 BLOCK 17 1 0 6 0 BLOCK 18 0 2 2 0 TOTAL 482 572 760 1063 TOTAL - SUM OF BLOCKS; m c n BLOCK CONSISTS OF A 5 MINUTE PERIOD. 186 166 180 127 81 33 88 86 95 48 71 96 37 65 19 48 12 0 46 1592 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 32 (PAGE 5): MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE RATS GROUP I11 200 MG/KG/DAY RAT NUMBER 14912 14913 14915 14916 DAY 86 NUMBER OF MOVEEdENTS BLOCK 1 BLOCK 2 BLOCK 3 BLOCK 4 BLOCK 5 BLOCK 6 BLOCK 7 5 BLOCK 8 BLOCK 9 c BLOCK 10 BLOCK 11 BLOCK 12 BLOCK 13 BLOCK 14 BLOCK 15 BLOCK 16 BLOCK 17 BLOCK 18 TOTAL 72 59 73 78 45 58 55 65 55 25 56 34 67 1 37 13 59 22 3 46 37 0 1 46 11 2 0 44 1 37 3 6 0 58 0 5 1 30 0 15 0 0 3 5 2 3 44 0 3 13 74 0 2 4 39 0 0 5 48 0 0 0 8 0 1 2 2 0 1 8 7 0 357 327 453 357 TOTAL I SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 14 9 17 76 60 70 73 79 62 54 79 64 63 76 67 70 59 53 73 31 34 1143 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBSR: T-7485.15) TABLE 32 (PAGE 6): MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE RATS GROUP I11 200 MG/KG/DAY RAT NUMBER 14912 14913 14915 14916 14 9 17 DAY 86 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 185 133 133 130 BLOCK 2 241 82 63 100 BLOCK 3 12 6 37 46 38 BLOCK 4 91 0 26 8 BLOCK 5 65 14 1 27 BLOCK 6 57 0 0 53 BLOCK 7 e 1 0 40 % BLOCK 9 BLOCK 9 w BLOCK 10 0 69 0 79 0 34 1 2 0 0 0 13 BLOCK 11 0 0 1 1 BLOCK 12 0 6 39 0 BLOCK 13 3 8 107 0 BLOCK 14 1 1 28 0 BLOCK 15 0 3 54 0 BLOCK 16 0 0 2 0 BLOCK 17 0 1 0 0 BLOCK 18 0 5 3 0 - TOTAL 777 473 504 4 12 TOTAL SUM OF BLOCKS1 EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 184 152 163 97 103 126 109 74 58 77 99 99 98 106 164 134 46 21 1910 0 N m PROTOCOL 4 1 8 - 0 2 6 : ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 2 (PAGE 7 ) : MOTOR ACTIVITY - INDIVIDUAL DATA - FJ?.MALE RATS GROUP IV 6 0 0 MG/KG/DAY RAT NUMBER 14921 14924 14925 14929 14930 DAY 86 " B E R OF MOVEMENTS BLOCK 1 68 65 46 53 BLOCK 2 21 41 59 69 BLOCK 3 21 63 49 40 BLOCK 4 1 58 58 33 BLOCK 5 1 48 39 0 BLOCK 6 0 10 57 1 BLOCK 7 0 18 59 26 % BLOCK 8 BLOCK 9 w BLOCX 10 2 20 40 47 4 24 38 50 1 0 58 57 BLOCK 11 3 0 49 67 BLOCK 1 2 2 3 60 73 BLOCK 1 3 10 1 71 12 BLOCK 1 4 1 4 23 42 BLOCK 15 3 1 0 5 BLOCK 16 2 1 1 5 BLOCK 17 1 0 1 0 BLOCK 1 8 3 14 7 1 - TOTAL TOTAL SUM OF BLOCKS; EACH 144 BLOCK 377 CONSISTS OF A 5 115 MINUTE 581 PERIOD. 72 83 64 50 67 70 50 59 39 67 43 77 50 57 1 1 4 0 854 PROTOCOL 4 1 8 - 0 2 6 : O m (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 ) TABLE 3 2 (PAGE 8 ) : MOTOR ACTIVITY - INDIVIDUAL DATA - FEMALE FATS GROUP IV 6 0 0 MG/KG/DAY RAT KUMBER 14921 14924 14925 14929 14930 DAY 8 6 TIME (SECONDS) SPENT IN MOVEMENT BLOCK 1 107 177 126 120 BLOCK 2 16 102 113 110 BLOCK 3 27 188 69 29 BLOCK 4 0 75 93 19 BLOCK 5 0 61 50 0 BLOCK 6 0 3 97 0 BLOCK 7 0 34 68 48 % BLOCK 8 BLOCK 9 BLOCK 10 0 20 29 55 1 25 88 55 0 0 84 56 BLOCK 11 2 0 57 101 BLOCK 1 2 0 0 60 70 BLOCK 1 3 5 0 98 4 BLOCK 1 4 0 3 18 25 BLOCK 1 5 0 0 0 0 BLOCK 1 6 0 0 0 1 BLOCK 1 7 0 0 0 0 BLOCK 18 1 14 1 0 - TOTAL 159 702 1051 693 TOTAL SUM OF BLOCKS; EACH BLOCK CONSISTS OF A 5 MINUTE PERIOD. 168 114 124 56 99 89 69 52 32 79 52 86 35 51 0 0 4 0 1110 HOME CAGE BEHAVIOR 2 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 REACTION TO HANDLING 1 1 1 1 REARS IN OPEN FIELD 5 10 5 6 DEFECATION IN OPEN FIELD 2 2 1 1 URINATION IN OPEN FIELD 1 2 1 1 LEVEL OF AROUSAL 3 la 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 GAIT PATTERN 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 PROMINENCE OF THE EYE 1 1 1 1 LACRIMATION 1 1 1 1 SALIVATION 1 1 1 1 PILOERECTION 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 APPEARANCE 1 1 1 1 VISUAL REACTION 2 2 2 2 TACTILE REACTION 2 2 2 2 AUDITORY REACTION 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 FORELIMB GRIP TEST #1 220 335b 585 275 FORELIMB GRIP TEST #2 205 430b 2 90 320 HINDLIMB GRIP TEST #1 510 305b 430 275 HINDLIMB GRIP TEST #2 570 600b 315 265 LANDING FOOT SPLAY #1 11.3 14 .O 13.5 7.3 LANDING FOOT SPLAY #2 10.0 11.9 13.8 5.8 BODY WEIGHT (G) 463 520 484 1 1 1 3 1 1 3 1 1 1 1 1 1 1' 0 0 1 2 2 3 2 1 1 335 430 235 285 9.0 6.4 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 33 (PAGE 2): FUNCTIONAL OBSERVATIONAL BATTERY - INDIVIDUAL DATA - MALE RATS HOME CAGE BEHAVIOR 2 2 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 8 I 8 0 2 DEFECATION IN OPEN FIELD 1 1 1 2 1 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 2 PALPEBRAL CLOSURE 1 1 1 1 1 % PROMINENCE OF THE EYE 1 1 1 1 1 C-L LACRIMATION til 1 1 1 1 1 \o SALIVATION 1 3 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 1 1 la VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 300 645 675 865b 245 FORELIMB GRIP TEST #2 220 560 430 600b 280 HINDLIMB GRIP TEST #1 350 510 435 640b 295 HINDLIMB GRIP TEST #2 485 4 90 485 490b 230 LANDING FOOT SPLAY #1 7.2 11.5 14.2 14.9 11.2 LANDING FOOT SPLAY #2 8.1 12.2 13.1 11.2 10.8 a. Localized alopecia: right forelimb (2.5 cm x 0.5 cm). b. Vocalization to touch and aggression were observed during grip strength testing PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 33 (PAGE 3): FUNCTIONAL OBSERVATIONAL BATTERY - INDIVIDUAL DATA - MALE RATS HOME CAGE BEHAVIOR 2 2 2 2 1 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 14 10 5 4 2 DEFECATION IN OPEN FIELD 1 1 1 1 1 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE 1 1 1 1 I wc1 LACRIMATION 0 SALIVATION 1 1 1 1 1 2 1 1 2a 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 1 1 1 VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 lb 1 2 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 425 265 205 370 715 FORELIMB GRIP TEST #2 280 220 230 115 425 HINDLIMB GRIP TEST #1 400 355 320 3 90 390 HINDLIMB GRIP TEST #2 615 440 255 450 420 LANDING FOOT SPLAY #1 9.9 11.5 7.2 10.3 10.4 LANDING FOOT SPLAY #2 10.4 9.6 8.1 8.2 8.1 a. Slight, red perioral substance. b. Soft or liquid feces were observed during air righting response. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 3 3 (PAGE 4): FUNCTIONAL OBSERVATIONAL BATTERY - INDIVIDUAL DATA - MALE RATS HOME CAGE BEHAVIOR 2 2 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 15 1 12 5 0 DEFECATION IN OPEN FIELD 1 2 1 1 2 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE 1 1 1 1 1 LACRIMATION 1 1 1 1 1 SALIVATION 1 1 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 1 la 1 VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 400 425 365 140 510 FORELIMB GRIP TEST #2 335 465 380 140 420 c HINDLIMB GRIP TEST #1 620 345 410 280 270 0 HINDLIMB GRIP TEST #2 590 270 225 315 190 LANDING FOOT SPLAY #1 13.8 11.9 14.6 5.4 10.2 cn LANDING FOOT SPLAY #2 13.9 13.4 10.9 5.6 7.9 P 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 11 6 14 10 13 DEFECATION IN OPEN FIELD 1 1 1 1 1 URINATION IN OPEN FIELD 2 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVER1TY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE c w LACRIMATION h;, SALIVATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 la 1 1 Ib VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST # 1 4 85 340 135 105 320 FORELIMB GRIP TEST #2 315 255 325 170 235 HINDLIMB GRIP TEST #1 555 365 220 355 285 HINDLIMB GRIP TEST #2 550 3 55 270 195 325 LANDING FOOT SPLAY #1 12.6 10.5 8.1 6.4 7.3 LANDING FOOT SPLAY #2 9.4 12.2 6.1 5.9 7.5 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 34 (PAGE 2): FUNCTIONAL OBSERVATIONAL BATTERY - INDIVIDUAL DATA - FEMALE RATS ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 10 12 11 13 2 DEFECATION IN OPEN FIELD 1 1 1 1 1 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE c w LACRIMATION w SALIVATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 la 1 1 VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 250b 270 270 280 350 FORELIMB GRIP TEST #2 200b 165 2 90 220 415 HINDLIMB GRIP TEST #1 290b 255 200 300 195 HINDLIMB GRIP TEST #2 415b 390 360 340 215 LANDING FOOT SPLAY #1 10.7 10.1 5.1 7.4 8.4 LANDING FOOT SPLAY #2 8.9 8.5 4.2 10.4 10.2 a. Localized alopecia: both forepaws (2.0 cm x 0.5 cm). b. Soft or liquid feces were observed during grip strength testing PROTOCOL 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 34 (PAGE 3 : FUNCTIONAL OBSERVATIONAL BATTERY - INDIVIDUAL DATA - FEMALE RATS 1 2 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 3 12 6 10 8 DEFECATION IN OPEN FIELD 1 1 1 1 1 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE c w LACRIMATION P SALIVATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 1 1 la VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 2 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 435 320 140 315 190 FORELIMB GRIP TEST #2 455 3 55 125 475 145 HINDLIMB GRIP TEST #1 405 4 15 285 280 265 HINDLIMB GRIP TEST #2 2 55 335 290 230 235 LANDING FOOT SPLAY #1 9.6 9.5 5.9 9.5 7.3 LANDING FOOT SPLAY #2 8.7 8 .O 5.5 8.2 6.2 367 313 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) HOME CAGE BEHAVIOR 2 2 2 2 2 ALTERATIONS (HOME CAGE) 1 1 1 1 1 REACTION TO REMOVAL 1 1 1 1 1 REACTION TO HANDLING 1 1 1 1 1 REARS IN OPEN FIELD 10 5 10 12 9 DEFECATION IN OPEN FIELD 1 1 1 1 1 URINATION IN OPEN FIELD 1 1 1 1 1 LEVEL OF AROUSAL 3 3 3 3 3 ALTERATIONS (OPEN FIELD) 1 1 1 1 1 GAIT PATTERN 1 1 1 1 1 GAIT ABNORMALITY, SEVERITY 1 1 1 1 1 PALPEBRAL CLOSURE 1 1 1 1 1 PROMINENCE OF THE EYE c w LACRIMATION u-l SALIVATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PILOERECTION 0 0 0 0 0 ABNORMAL RESPIRATION 0 0 0 0 0 APPEARANCE 1 1 1 1 1 VISUAL REACTION 2 2 2 2 2 TACTILE REACTION 2 2 2 2 2 AUDITORY REACTION 3 3 3 3 3 TAIL-PINCH REACTION 2 2 2 2 2 AIR RIGHTING RESPONSE 1 1 1 1 1 PUPIL RESPONSE TO LIGHT 1 1 1 1 1 FORELIMB GRIP TEST #1 685 195 375 210 140 FORELIMB GRIP TEST #2 505 2 70 245 125 145 $ HINDLIMB GRIP TEST #1 410 275 205 220 170 0 c HINDLIMB GRIP TEST #2 475 2 95 390 115 230 LANDING FOOT SPLAY #1 12.5 9.1 8.1 7.5 7.8 v, P LANDING FOOT SPLAY #2 8.6 10.5 7.2 10.6 7.0 c PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 35 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - MALE RATS GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/ DAY) NUMBER NECROPSY ADMINISTERED .............................................................. .- I 0 (VEHICLE) 14851 DS 91 90 14852 DS 91 90 14853 DS 91 90 14854 DS 92 91 14855 DS 92 91 14856 DS 93 92 14857 DS 93 92 14858 DS 93 92 14859 DS 94 93 14860 DS 94 93 OBSERVATIONS a ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. I1 60 w Y u l 14861 14862 14863 14864 DS 91 DS 91 DS 92 DS 92 90 ALL TISSUES APPEARED NORMAL. 90 ALL TISSUES APPEARED NORMAL. 91 ALL TISSUES APPEARED NORMAL. 91 ALL TISSUES APPEARED NORMAL. 14865 DS 92 91 ALL TISSUES APPEARED NORMAL. 14866 DS 93 92 ALL TISSUES APPEARED NORMAL. 14867 14868 DS 93 DS 94 92 ALL TISSUES APPEARED NORMAL. 93 ALL TISSUES APPEARED NORMAL. 14869 DS 94 93 ALL TISSUES APPEARED NORMAL. 14870 DS 94 93 ALL TISSUES APPEARED NORMAL. .................................................................................................................................... DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table 25) for external observations confirmed at necropsy. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 35 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - MALE RATS IV 600 c w 4 14881 14882 14883 14884 14885 14886 14887 14888 14889 DS 91 DS 91 DS 92 DS 92 DS 92 DS 93 DS 93 DS 94 DS 94 90 ALL TISSUES APPEARED NORMAL. 90 ALL TISSUES APPEARED NORMAL. 91 ALL TISSUES APPEARED NORMAL. 91 ALL TISSUES APPEARED NORMAL. 91 ALL TISSUES APPEARED NORMAL. 92 ALL TISSUES APPEARED NORMAL. 92 ALL TISSUES APPEARED NORMAL. 93 ALL TISSUES APPEARED NORMAL. 93 ALL TISSUES APPEARED NORMAL. 14890 DS 85 84 FOUND DEAD ON DAY 85 OF STUDY (DEATH OCCURRED 20 HOURS AND 3 MINUTES AFTER DOSAGE ADMINISTRATION). STOMACH: CARDIAC REGION, THIN WALLS. STOMACH AND INTESTINES: DISTENDED WITH GAS. THYMUS: RED. SPLEEN: SMALL (0.34 G) . ALL OTHER TISSUES APPEARED NORMAL. ________________-___-----------------------------------~-------------- DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table 25) for external observations confirmed at necropsy. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 36 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FEMALE RATS (MG/KG/ DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a I VEHICLE) 14891 DS 91 90 ALL TISSUES APPEARED NORMAL. 14892 DS 91 90 ALL TISSUES APPEARED NORMAL. 14893 DS 92 91 ALL TISSUES APPEARED NORMAL. 14894 DS 92 91 ALL TISSUES APPEARED NORMAL. 14895 DS 92 91 ALL TISSUES APPEARED NORMAL. 14896 DS 93 92 ALL TISSUES APPEARED NORMAL. 14897 DS 93 92 ALL TISSUES APPEARED NORMAL. 14898 DS 94 93 ALL TISSUES APPEARED NORMAL. 14899 DS 94 93 ALL TISSUES APPEARED NORMAL. 14900 DS 94 93 ALL TISSUES APPEARED NORMAL. I1 60 14901 DS 91 90 ALL TISSUES APPEARED NORMAL. 14902 DS 91 90 ALL TISSUES APPEARED NORMAL. 14903 DS 91 90 ALL TISSUES APPEARED NORMAL. 14904 DS 92 91 ALL TISSUES APPEARED NORMAL. 14905 DS 92 91 ALL TISSUES APPEARED NORMAL. 14906 DS 93 92 ALL TISSUES APPEARED NORMAL. 14907 DS 93 92 ALL TISSUES APPEARED NORMAL. 14908 DS 93 92 ALL TISSUES APPEARED NORMAL. 14909 DS 94 93 ALL TISSUES APPEARED NORMAL. 14910 DS 94 93 ALL TISSUES APPEARED NORMAL. ________________________________________-------------------------------------------------------------------------------------------- DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table 26) for external observations confirmed at necropsy. GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED .............................................................. I11 200 14911 DS 91 90 14912 DS 91 90 14 913 DS 92 91 14914 DS 92 91 14915 DS 92 91 14916 DS 93 92 14917 DS 93 92 14918 DS 94 93 14919 DS 94 93 14920 DS 94 93 IV 600 14921 DS 91 90 14922 DS 91 90 14923 DS 91 90 14924 DS 92 91 14925 DS 92 91 14926 DS 93 92 14927 DS 93 92 14928 DS 93 92 14929 DS 94 93 14930 DS 94 93 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 3 7 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - MALE RATS EPIDIDYMIDES TESTES BRAIN LIVER KIDNEYS ADRENALS RAT TERMINAL BODY NUMBER WEIGHT PAIRED PAIRED PAIRED PAIRED ABS. REL. ABS. REL. ABS. REL . ABS. REL. ABS. REL. ABS. REL. WT. .__ _ % _ TBW ___ _ - WT. ---- - _ % - TBW __ _ _ _ WT. __ _ % TBW _______ _ _ _ W _- T . _ _ - __ _%_ _ _ _T_ B__W__ _____-__-W_T._._ _ _ % __ TBW _-_ _ _ _ _ WT. ____ _ _ % __ TBW ___ _ _ _ _ _ _ _ _ _ 14851 444. 1.54 0.35 1.79 0.40 2.36 0.53 12.26 2.76 3.83 0.86 0.077 0.02 14852 500. 1.49 0.30 3.57 0.71 2.12 0.42 14.81 2.96 4 .05 0.81 0.064 0.01 14853 543. 1.84 0.34 3.50 0.64 2.15 0.40 17.41 3.21 3.97 0.73 0.053 0.01 14854 554. 1.57 0.28 3.64 0.66 2.37 0.43 15.04 2.71 4.56 0.82 0.065 0.01 14855 460. 1.44 0.31 3.34 0.73 2.06 0.45 13.58 2.95 3.91 0.85 0.063 0.01 14856 548. 1.44 0.26 3.75 0.68 2.47 0.45 14.16 2.58 4.31 0.79 0.054 0.01 14857 458. 1.69 0.37 3.92 0.86 2.36 0.52 11.83 2.58 3.47 0.76 0.074 0.02 14858 552. 1.86 0.34 4.20 0.76 2.38 0.43 15.00 2.72 4.26 0.77 0.047 0.01 14859 483. 1.92 0.40 3.49 0.72 2.32 0.48 13.89 2.88 4.19 0.87 0.064 0.01 P 14860 567. 1.72 0.30 4.16 0.73 2.25 0.40 16.82 2.97 ............................................................................................. _ 5_ ._ 2_ 4_ _ _ _ _ _ 0.92 0.095 0.02 - - - - - - - - 0 SPLEEN THYMUS HEART RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. _ _ _ _ _ _ _ - _ WT. -_ _ % TBW __ _ WT. __ _ % TBW __ - - - WT. -- - % TBW ---- - - - - - - - - - . - - - - - - - - - - - - - - ~ - -- --- -- -- - - - - ~ - - - - - 14851 444. 0.73 0.16 0.43 0.10 1.40 0.32 14852 500. 0.89 0.18 0.59 0.12 1.74 0.35 14853 543. 0.87 0.16 0.71 0.13 1.84 0.34 14854 554. 0.88 0.16 0.29 0.05 1.82 0.33 14855 460. 0.80 0.17 0.22 0.05 1.36 0.30 14856 548. 1.04 0.19 0.30 0.05 1.53 0.28 14857 458. 0.88 0.19 0.72 0.16 1.37 0.30 14858 552. 1.11 0.20 0.52 0.09 1.72 0.31 14859 483. 1.03 0.21 0.40 0.08 1.54 0.32 14860 567. 1.10 0.19 0.74 0.13 1.81 0.32 b1 3 o\ PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 3 7 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( 2 ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - MALE RATS 14861 383. 1.26 0.33 2.89 0.75 2.05 0.54 9.14 2.39 3.24 0.84 0.050a 0.01 14862 534. 1.42a 0.26 3.44 0.64 2.25 0.42 15.96 2.99 4.41 0.82 0.047 0.01 14863 449. 1.38 0.31 3.49 0.78 2.23 0.50 13.70 3.05 4.07 0.91 0.046 0.01 14864 523. 1.42 0.27 3.42 0.65 2.39 0.46 15.11 2.89 4.20 0.80 0.054 0.01 14865 527. 1.53 0.29 3.47 0.66 2.45 0.46 17.71 3.36 4.65 0.88 0.085 0.02 14866 507. 1.58 0.31 3.77 0.74 2.29 0.45 13.38 2.64 4.89 0.96 0.041 0.01 14867 501. 1.52 0.30 3.26 0.65 2.20 0.44 14.62 2.92 4.49 0.90 0.085 0.02 i486a 476. 1.55 0.32 3.44 0.72 2.36 0.50 13.47 2.83 4.02 0.84 0.049 0.01 14869 380. 1.47 0.39 3.37 0.89 2.24 0.59 9.70 2.55 3.23 0.85 0.056 0.01 14870 546. 1.51 0.28 3.26 0.60 2.33 0.43 15.51 2.84 4.32 0.79 0.057 0.01 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ---_-_- ------- -.- _ _ _ _ - _ _ - - - _ _ _ _ - - _ _ _ _ _ _ _ _ _ _ _ _ SPLEEN THYMUS HEART RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW ________________________________________---.----------------- 14861 14862 14863 14864 14865 14866 14867 14868 14869 14870 383. 534. 449. 523. 527. 507. 501. 476. 380. 546. 0.58 0.84 0.77 0.81 0.86 0.87 0.82 0.80 0.64 0.67 0.15 0.16 0.17 0.15 0.16 0.17 0.16 0.17 0.17 0.12 0.09 0.53 0.49 0.36 0.54 0.68 0.47 0.61 0.40 0.63 0.02 0.10 0.11 0.07 0.10 0.13 0.09 0.13 0.10 0.12 1.30 1.59 1.56 1.48 1.68 1.78 1.54 1.51 1.18 1.73 0.34 0.30 0.35 0.28 0.32 0.35 0.31 0.32 0.31 0.32 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBTJTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 3 7 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - MALE RATS 14871 455. 1.40a 0.31 3.22 0.71 2.37 0.52 14.01 3.08 3.72 0.82 0.059 0.01 14872 475. 1.73 0.36 3.65 0.77 2.23 0.47 13.64 2.87 3.97 0.84 0.091 0.02 14873 462. 1.49 0.32 3.37 0.73 2.16 0.47 13.35 2.89 3.34 0.72 0.062 0.01 14874 544. 1.70 0.31 3.33 0.61 2.14 0.39 16.26 2.99 4.26 0.78 0.086 0.02 14875 448. 1.61 0.36 3.73 0.83 2.33 0.52 12.41 2.77 3.56 0.79 0.057 0.01 14876 480. 1.64 0.34 3.29 0.68 2.18 0.45 12.00 2.50 4.18 0.87 0.054 0.01 +d 14877 503. 1.56 0.31 3.62 0.72 2.29 0.46 14.45 2.87 4.25 0.84 0.059 0.01 14878 448. 1.39 0.31 3.84 0.86 2.37 0.53 11.92 2.66 4.03 0.90 0.064 0.01 14879 505. 1.37 0.27 3.72 0.74 2.30 0.46 13.28 2.63 3.91 0.77 0.074 0.01 R w 14880 476. 1.89 0.40 3.86 0.81 _ _. 2.17 ___ _ _ _ 0.46 ---- _ - _ 1-_3-_.- 6- 9- - - - - - 2.88 - - - - - - _ _ _ 4.05 ____ _ _ _ 0.85 __ - - 0.075 ---_ _ 0.02 .- - - - - - - HEART RAT TERMINAL BODY NUMBER WEIGHT .......................... ABS. WT. REL. % TBW ABS. REL. ABS. REL. WT. % TBW WT. % TBW - - - - _ _ _ _ _ _ - - _ _. ._._. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14871 455. 0.79 0.17 0.25 0.05 1.56 0.34 14872 475. 0.84 0.18 0.41 0.09 1.54 0.32 14873 462. 0.79 0.17 0.19 0.04 1.46 0.32 14874 544. 0.89 0.16 0.56 0.10 1.57 0.29 14875 448. 0.81 0.18 0.48 0.11 1.47 0.33 14876 480. 0.89 0.18 0.35 0.07 2.06 0.43 14877 503. 0.76 0.15 0.40 0.08 1.43 0.28 14878 448. 0.94 0.21 0.38 0.08 1.98 0.44 14879 505. 0.81 0.16 0.39 0.08 1.44 0.28 14880 476. 0.75 0.16 0.39 0.08 1.49 0.31 b ct n3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR`SSTUDY NUMBER: T-7485.15) TABLE 3 7 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - MALE RATS EPIDIDYMIDES RAT TERMINAL BODY PAIRED NUMBER WEIGHT ABS. REL. WT. % TBW .......................................... TESTES PAIRED ABS. REL. WT. % TBW BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW KIDNEYS PAIRED ABS. REL. WT. % TBW ADRENALS PAIRED ABS. REL. WT. % TBW 14881 443. 1.71 0.39 2.17 0.49 2.19 0.49 13.54 3.06 3.77 0.85 0.081 0.02 14882 528. 1.49 0.28 3.46 0.66 2.17 0.41 17.80 3.37 4.69 0.89 0.053 0.01 14883 578. 1.51 0.26 3.75 0.65 2.23 0.38 17.78 3.08 4.72 0.82 0.068 0.01 14884 464. 1.69 0.36 3.85 0.83 2.23 0.48 14.97 3.23 4.10 0.88 0.051 0.01 14885 530. 1.39 0.26 3.49 0.66 2.28 0.43 14.01 2.64 4.11 0.78 0.052 0.01 14886 423. 1.51 0.36 4.20 0.99 2.46 0.58 13.58 3.21 3.99 0.94 0.063 0.01 14887 465. 1.66 0.36 3.35 0.72 2.29 0.49 13.86 2.98 3.88 0.83 0.067 0.01 14888 468. 1.90 0.40 3.66 0.78 2.30 0.49 13.21 2.82 4.22 0.90 0.065 0.01 (3c 1144888990a 4_ 6_ 9_ . 11..3459 0_ ._ 3_ 2_ 33..8237 0- ._8_2 _ 22..3403 0- ._5_2 - 1154..6331 3_ ._ 0_ 5_ 43..8148 0_ ._ 8_ 9_ 00..015021 0- .- -0-1 P .......................................... _-____ -----_--_-______ w SPLEEN THYMUS HEART RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. _ _ _ _ _ _ _ _ _ _ _ _ - _ _ - - _ _ _ _ WT. ____ _ _ % _ TBW ___ _ _ _ _ WT __ . _ _ _ - % -- TBW ----- - - - WT. ----- - - - -- - - _ _ % _ _ T_ B_ W_ _ _ _ _ _ _ _ _ _ _ _ 14881 443. 0.78 0.18 0.37 0.08 1.78 0.40 14882 528. 0.79 0.15 0.37 0.07 1.80 0.34 14883 578. 1.02 0.18 0.70 0.12 1.86 0.32 14884 464. 0.90 0.19 0.39 0.08 1.40 0.30 14885 530. 0.74 0.14 0.24 0.04 1.39 0.26 14886 423. 0.72 0.17 0.35 0.08 1.40 0.33 14887 465. 0.81 0.17 0.42 0.09 1.50 0.32 14888 468. 0.63 0.13 0.41 0.09 1.59 0.34 14889 14890a 4_ 6_ 9_ . 0.77 0.34 0.16 _--- 0.22 0.24 0_ ._ 0_ 5_ ........................................................... 1.58 1.85 0_ ._ 3_ 4_ ALL WEIGHTS WERE RECORDED IN GRAMS (GI. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 a. R a t 14890 was found dead on day 85 of study; values excluded from group averages and statistical analyses. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 38 (PAGE 1): ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - MALE RATS ________________________________________-_-.----------------- GROUP I VEHICLE 0 (VEHICLE) MG/KG/DAY ________________________________________---..---------------- EPIDIDYMIDES TESTES LIVER KIDNEYS ADRENALS SPLEEN RAT BRAIN PAIRED PAIRED PAIRED PAIRED NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW ________________________________________-----------------------------------_-------------------------------------------------------- 14851 2.36 1.54 65.25 1.79 75.85 12.26 519.49 3.83 162.29 0.077 3.26 0.73 30.93 14852 2.12 1.49 70.28 3.57 168.40 14.81 698.58 4.05 191.04 0.064 3.02 0.89 41.98 14853 2.15 1.84 85.58 3.50 162.79 17.41 809.77 3.97 184.65 0.053 2.46 0.87 40.46 14854 2.37 1.57 66.24 3.64 153.59 15.04 634.60 4.56 192.40 0.065 2.74 0.88 37.13 14855 2.06 1.44 69.90 3.34 162.14 13.58 659.22 3.91 189.80 0.063 3.06 0.80 38.83 14856 2.47 1.44 58.30 3.75 151.82 14.16 573.28 4.31 174.49 0.054 2.19 1.04 42.10 14857 2.36 1.69 71.61 3.92 166.10 11.83 501.27 3.47 147.03 0.074 3.14 0.88 37.29 14858 2.38 1.86 78.15 4.20 176.47 15.00 630.25 4.26 178.99 0.047 1.97 1.11 46.64 14859 2.32 1.92 82.76 3.49 150.43 13.89 598.71 4.19 180.60 0.064 2.76 1.03 44.40 14860 2.25 1.72 76.44 4.16 184.89 16.82 747.56 5.24 232.89 0.095 4.22 1.10 48.89 ________________________________________-----------------------------------_-------------------------------------------------------- THYMUS HEART RAT BRAIN NUMBER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW ________________________________________-------------------------------------------------------------------------------------------- 14851 2.36 0.43 18.22 1.40 59.32 14852 2.12 0.59 27.83 1.74 82.08 14853 2.15 0.71 33.02 1.84 85.58 14854 2.37 0.29 12.24 1.82 76.79 14855 2.06 0.22 10.68 1.36 66.02 14856 2.47 0.30 12.14 1.53 61.94 14857 2.36 0.72 30.51 1.37 58.05 14858 2.38 0.52 21.85 1.72 72.27 14859 2.32 0.40 17.24 1.54 66.38 14860 2.25 0.74 32.89 1.81 80.44 .................................................................................................................................... c ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. tn PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 38 (PAGE 2) : ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - MALE RATS 14861 2.05 1.26 61.46 2.89 140.98 9.14 445.85 3.24 158.05 0.050a 2.44 14862 14863 14864 2.25 2.23 2.39 1.42a 1.38 1.42 63.11 61.88 59.41 3.44 3.49 3.42 152.89 156.50 143.10 15.96 13.70 15.11 709.33 614.35 632.22 4.41 4.07 4.20 196.00 182.51 175.73 0.047 0.046 0.054 2.09 2.06 2.26 14865 2.45 1.53 62.45 3.47 141.63 17.71 722.86 4.65 189.80 0.085 14866 2.29 1.58 69.00 3.77 164.63 13.38 584.28 4.89 213.54 0.041 14867 2.20 1.52 69.09 3.26 148.18 14.62 664.54 4.49 204.09 0.085 14868 2.36 1.55 65.68 3.44 145.76 13.47 570.76 4.02 170.34 0.049 14869 2.24 1.47 65.62 3.37 150.45 9.70 433.04 3.23 144.20 0.056 - - - 1 - 4870 ----- - - - - - 2.33 ----- - _ _ _ _ 1. __ 51 __ _ _ 6 _ 4.81 ___ _ _ _ 3.26 ___ - - - 1 - 3 - 9 - . - 9 - 1 -- - - - 1 - 5 - . - 5 - 1 - ~ - 665.66 ------- - - - - - 4 - . - 3 - 2 - - - - 1 - 8 - 5 - . - 4 - 1 - - - ~ ~ 0_~._-0_-5_-7_-_~ 3.47 1.79 3.86 2.08 2.50 2.45 RAT BRAIN THYMUS HEART NUMBER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW ____-___________________________________----------------------------------------~-------------- 14861 2.05 0.09 4.39 1.30 63.41 14862 2.25 0.53 23.56 1.59 70.67 14863 2.23 0.49 21.97 1.56 69.96 14864 2.39 0.36 15.06 1.48 61.92 14865 2.45 0.54 22.04 1.68 68.57 14866 2.29 0.68 29.69 1.78 77.73 14867 2.20 0.47 21.36 1.54 70.00 14868 2.36 0.61 25.85 1.51 63.98 14869 2.24 0.40 17.86 1.18 52.68 14870 2.33 0.63 27.04 1.73 74.25 0.58 28.29 0.84 37.33 0.77 34.53 0.81 33.89 0.86 35.10 0.87 37.99 0.82 37.27 0.80 33.90 0.64 28.57 0.67 28.76 _-_______________ _. p" 0 m1 3 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 38 (PAGE 3): ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - MALE RATS ---_____________________________________-------------------------------------------------------------------------------------------- GROUP I11 MIDDLE DOSAGE 200 MG/KG/DAY .................................................................................................................................... EPIDIDYMIDES TESTES LIVER KIDNEYS ADRENALS SPLEEN RAT BRAIN PAIRED PAIRED PAIRED PAIRED NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL . WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... 14871 2.37 1.40a 59.07 3.22 135.86 14.01 591.14 3.72 156.96 0.059 2.49 0.79 33.33 14872 2.23 1.13 77.58 3.65 163.68 13.64 611.66 3.97 178.03 0.091 4.08 0.84 37.67 14873 2.16 1.49 68.98 3.37 156.02 13.35 618.06 3.34 154.63 0.062 2.87 0.79 36.57 14874 2.14 1.70 79.44 3.33 155.61 16.26 759.81 4.26 199.06 0.086 4.02 0.89 41.59 14875 2.33 1.61 69.10 3.73 160.08 12.41 532.62 3.56 152.79 0.057 2.45 0.81 34.76 14876 2.18 1.64 75.23 3.29 150.92 12.00 550.46 4.18 191.74 0.054 2.48 0.89 40.82 14877 2.29 1.56 68.12 3.62 158.08 14.45 631.00 4.25 185.59 0.059 2.58 0.76 33.19 14878 2.37 1.39 58.65 3.84 162.02 11.92 502.95 4.03 170.04 0.064 2.70 0.94 39.66 14879 2.30 1.37 59.56 3.72 161.74 13.28 577.39 3.91 170.00 0.074 3.22 0.81 35.22 14880 2.17 1.89 87.10 3.86 177.88 13.69 630.88 4.05 186.64 0.075 3.46 0.75 34.56 ________________________________________-------------------------------------------------------------------------------------------- THYMUS HEART RAT BRAIN NUMBER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW .................................................................................................................................... 14871 2.37 0.25 10.55 1.56 65.82 14872 2.23 0.41 18.38 1.54 69.06 14873 2.16 0.19 8.80 1.46 67.59 14874 2.14 0.56 26.17 1.57 73.36 14875 2.33 0.48 20.60 1.47 63.09 14876 14877 2.18 2.29 0.35 0.40 16.06 17.47 2.06 1.43 94.50 62.44 14878 2.37 0.38 16.03 1.98 83.54 14879 2.30 0.39 16.96 1.44 62.61 14880 2.17 0.39 17.97 1.49 68.66 _-__________________--------------------------------------------------- ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) x 1 0 0 . a. Damaged during processing (weight not affected). PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 38 (PAGE 4): ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - MALE RATS _----___________________________________-------------------------------------------------------------------------------------------- GROUP IV HIGH DOSAGE 600 MG/KG/DAY _----___________________________________----------------------- RAT NUMBER BRAIN WEIGHT EPIDIDYMIDES PAIRED ABS. REL. WT. % BRW TESTES PAIRED ABS. REL. WT. % BRW LIVER ABS. WT. REL. % BRW KIDNEYS PAIRED ABS. REL. WT. % BRW ADRENALS PAIRED ABS. REL. WT. % BRW SPLEEN ABS. WT. REL. % BRW ________________r_______________________-------------------------------------------------------------------------------------------- 14881 2.19 14882 ' 2.17 1.71 1.49 78.08 68.66 2.17 3.46 99.09 159.45 13.54 17.80 618.26 820.28 3.77 4.69 172.15 216.13 0.081 0.053 3.70 2.44 0.78 0.79 35.62 36.40 14883 2.23 1.51 67.71 3.75 168.16 17.78 797.31 4.72 211.66 0.068 3.05 1.02 45.74 14884 2.23 1.69 75.78 3.85 172.64 14.97 671.30 4.10 183.86 0.051 2.29 0.90 40.36 14885 2.28 1.39 60.96 3.49 153.07 14.01 614.47 4.11 180.26 0.052 2.28 0.74 32.46 14886 2.46 1.51 61.38 4.20 170.73 13.58 552.03 3.99 162.20 0.063 2.56 0.72 29.27 14887 2.29 1.66 72.49 3.35 146.29 13.86 605.24 3.88 169.43 0.067 2.92 0.81 35.37 14888 2.30 1.90 82.61 3.66 159.13 13.21 574.35 4.22 183.48 0.065 2.83 0.63 27.39 14889 14890a 2.43 2.30 1.49 1.35 6_1_._3_2 3.83 3.27 157_ _._6_1 14.31 15.63 588_ ._ 8_ 9_ 4.18 3.84 172_.-0_2- 0.052 0.101 2.14 ---- 0.77 0.34 31.69 ----- ________________________________________------------------~--------------------------------~-----------------------~-----~---------- THYMUS HEART RAT NUMBER BRAIN WEIGHT ABS. REL. ABS. REL . WT. % BRW WT. % BRW .................................................................................................................................... 14881 2.19 0.37 16.89 1.78 81.28 14882 2.17 0.37 17.05 1.80 82.95 14883 2.23 0.70 31.39 1.86 83.41 14884 2.23 0.39 17.49 1.40 62.78 14885 2.28 0.24 10.53 1.39 60.96 14886 2.46 0.35 14.23 1.40 56.91 14887 2.29 0.42 18.34 1.50 65.50 14888 2.30 0.41 17.83 1.59 69.13 14889 14890a 2.43 2.30 0.22 0.24 9.05 ---_ 1.58 1.85 65- .-0-2_ _--______-------_----------------------------------------~~-------------- b ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. d a. Rat 14890 was found dead on day 85 of study; values excluded from group averages and statistical analyses. v1 P c-. 00 b td ch PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 39 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - FEMALE RATS 14891 295. 2.16 0.73 8.88 3.01 2.51a 0.85a 0.076 0.02 0.80 0.27 0.26 0.09 14892 321. 2.16 0.67 8.77 2.73 2.86a 0.89a 0.063 0.02 0.52 0.16 0.34 0.10 14893 14894 274. 295. 2.08 1.91 0.76 0.65 7.12 8.14 2.60 2.76 2.27 2.36 0.83 0.80 0.053 0.077 0.02 0.03 0.46 0.58 0.17 0.20 0 .'31 0.32 0.11 0.11 14895 273. 2.10 0.77 7.46 2.73 2.22 0.81 0.081 0.03 0.61 0.22 0.51 0.19 14896 278. 2.11 0.76 7.42 2.67 2.36 0.85 0.069 0.02 0.51 0.18 0.42 0.15 14897 269. 2.13 0.79 7.13 2.65 2.25 0.84 0.064 0.02 0.62 0.23 0.30 0.11 14898 266. 1.98 0.74 8.06 3.03 2.09 0.78 0.085 0.03 0.52 0.20 0.30 0.11 14899 230. 1.99 0.86 6.36 2.76 2.35 1.02 0.099 0.04 0.53 0.23 0.39 0.17 c 14900 264. 2.08 0.79 7.77 2.94 2.11 0.80 0.091 0.03 0.61 0.23 0.38 0.14 P ........................................................................................................ ._____C__________ 00 OVARIES UTERUS HEART RAT TERMINAL BODY PAIRED NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW ........................................................................................................ 14891 295. 0.130 0.04 0.46 0.16 0.93 0.32 14892 321. 0.132 0.04 0.45 0.14 1.01 0.31 14893 274. 0.100 0.04 0.65 0.24 0.91 0.33 14894 295. 0.158 0.05 0.88 0.30 0.94 0.32 14895 273. 0.148 0.05 0.43 0.16 0.87 0.32 14896 278. 0.167 0.06 0.56 0.20 1.08 0.39 14897 269. 0.119 0.04 0.74 0.28 0.88 0.33 14898 P 14899 ;a 14900 266. 230. 264. 0.145 0.127 0.139 0.05 0.06 0.05 0.85 0.63 0.72 0.32 0.27 0.27 1.08 1.07 0.97 0.41 0.46 0.37 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 39 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FEMALE RATS 14901 249. 1.94 0.78 7.71 3.10 2.02 0.81 0.082 0.03 0.53 0.21 0.28 0.11 14902 294. 2.23 0.76 8.37 2.85 2.82a 0.96a 0.077 0 . 0 3 0.49 0.17 0.08 0.03 14903 256. 2.05 0.80 7.49 2.92 2.00 0.78 0.069 0 . 0 3 0.51 0.20 0.41 0.16 14904 313. 1.99 0.64 8.90 2.84 2.43 0.78 0.074 0.02 0.56 0.18 0.31 0.10 14905 298. 2.12 0.71 8.64 2.90 2.27 0.76 0.062 0.02 0.53 0.18 0.27 0.09 14906 302. 2.12 0.70 8.83 2.92 2.58 0.85 0.096 0.03 0.59 0.20 0.31 0.10 14907 304. 2.00 0.66 8.74 2.88 2.60 0.86 0.095 0.03 0.61 0.20 0.42 0.14 2 14908 284. 2.11 0.74 8.19 2.88 2.30 0.81 0.070 0.02 0.61 0.21 0.56 0.20 % 14909 292. 2.19 0.75 9.19 3.15 2.82 0.96 0.080 0.03 0.88 0.30 0.35 0.12 C-L P 14910 268. 2.04 0.76 6.91 2.58 2.17 0.81 0.074 0.03 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . _ - - _ _- _- 0.62 - - - - - - - 0.23 ___ - - - _ 0.44 ---_ _ - _ -_0- .-1-6- - - \o OVARIES UTERUS HEART RAT TERMINAL BODY PAIRED NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW ....................................................................................... 14901 249. 0.093 0.04 0.64 0.26 1.09 0.44 14902 294. 0.129 0.04 1.22b 0.41 1.05 0.36 14903 256. 0,147 0.06 0.41 0.16 0.89 0.35 14904 313. 0.141 0.04 0.51 0.16 1.04 0.33 14905 298. 0.134 0.04 1.11 0.37 1.01 0.34 14 906 302. 0.151 0.05 0.74 0.24 1.05 0.35 14907 304. 0.153 0.05 0.59 0.19 1.11 0.36 14908 284. 0.119 0.04 0.70 0.25 0.99 0.35 14909 292. 0.160 0.05 0.72 0.25 1.03 0.35 14910 268. 0.128 0.05 0.94 0.35 0.89 0.33 I 0 13 PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBZPTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 3 9 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FEMALE RATS .................................................................................................................................... GROUP I11 MIDDLE DOSAGE 200 MG/KG/DAY .................................................................................................................................... BRAIN LIVER KIDNEYS ADRENALS SPLEEN THYMUS RAT TERMINAL BODY PAIRED PAIRED NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. . . . . . . . . . . . . . . . . . . . . . . . . . . .W.T... . . . .%. .T.B.W. . . . . . .W.T... . . . .%. .T.B.W. . . . . . W. T. .. . . . . .%. .T.B.W. . . . . . .W.T... . . . .%. .T.B.W. . . . . . .W.T... . . . .%. .T.B.W. . . . . . .W.T... . . . .%. .T.B.W. . . . 14911 257. 2.15 0.84 7.52 2.93 2.13 0.83 0.090 0.04 0.48 0.19 0.33 0.13 14912 284. 2.13 0.75 8.03 2.83 2.38a 0.84a 0.077 0.03 0.52 0.18 0.39 0.14 14913 284. 2.09 0.74 8.04 2.83 2.31 0.81 0.092 0.03 0.48 0.17 0.44 0.15 14914 318. 2.13 0.67 8.76 2.75 2.38 0.75 0.070 0.02 0.63 0.20 0.42 0.13 14915 250. 1.98 0.79 7.12 2.85 2.14 0.86 0.059 0.02 0.67 0.27 0.32 0.13 14916 341. 2.15 0.63 10.17 2.98 2.66 0.78 0.076 0.02 0.60 0.18 0.60 0.18 14917 287. 2.07 0.72 7.90 2.75 2.56 0.89 0.066 0.02 0.60 0.21 0.37 0.13 % 14918 283. 2.01 0.71 8.48 3.00 2.59 0.92 0.101 0.04 0.51 0.18 0.38 0.13 14919 244. 1.93 0.79 7.29 2.99 2.30 0.94 0.070 0.03 0.55 0.22 0.30 0.12 c 14920 300. 2.16 0.72 8.97 2.99 2.51 0.84 0.085 0.03 0.67 0.22 0.22 0.07 ch .................................................................................................................................... 0 OVARIES UTERUS HEART RAT TERMINAL BODY PAIRED NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... 14911 257. 0.109 0.04 0.75 0.29 0.96 0.37 14912 284. 0.151 0.05 0.47 0.16 1.02 0.36 14913 284. 0.138 0.05 0.56 0.20 0.86 0.30 14914 318. 0.126 0.04 0.50 0.16 1.06 0.33 14915 250. 0.091 0.04 0.67 0.27 0.88 0.35 14916 341. 0.149 0.04 0.47 0.14 1.11 0.32 14917 287. 0.173 0.06 0.57 0.20 0.93 0.32 14918 283. 0.169 0.06 0.84 0.30 1.14 0.40 14919 244. 0.145 0.06 0.71 0.29 0.92 0.38 14920 300. 0.137 0.04 0.81 0.27 1.05 0.35 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (GI. a. Fixed weight. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x l o o . i P CL 90 0 N o\ PROTOCOL 418-026: ORAL (GAVAGE)REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 3 9 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FEMALE RATS 14921 242. 14922 282. 14923 248. 14924 288. 14925 276. 14926 291. 14927 253. 14928 270. 14929 237. - - - 1 - 4 - 9 - - 3 - 0 _ _ _ _ _ _ _2_59_ ._ _ _ _ _ _ 1.92 1.92 2.07 1.99 2.08 2.08 2.10 2.03 2.22 2.16 0.79 0.68 0.83 0.69 0.75 0.71 0.83 0.75 0.94 0.83 7.01 2.90 2.14 0.88 8.08 2.86 1.97 0.70 7.97 3.21 2.89 1.16 7.98 2.77 2.12 0.74 7.46 2.70 2.30 0.83 8.30 2.85 3.25 1.12 7.77 3.07 2.02 0.80 7.56 2.80 2.54 0.94 7.93 3.34 2.22 0.94 - 7- .- 8- 0 - - - - - - 3 - . - 01 - - - . . . . 2.46 ..... . . . . . 0.95 ..... . . 0.059 0.02 0.50 0.21 0.074 0.03 0.63 0.22 0.092 0.04 0.69 0.28 0.074 0.02 0.52 0.18 0.071 0.02 0.60 0.22 0.079 0.03 0.77 0.26 0.063 0.02 0.87 0.34 0.073 0.03 0.64 0.24 0.066 0.03 0.69 0.29 - 0 - .- 0- 8- 4 - - - - 0.03 _---- - - - - 0.63 ---_ _._- -_- 0 - . - 2 - 4 - - - 0.28 0.42 0.26 0.29 0.42 0.43 0.23 0.51 0.32 0.39 _ _ _ _ - ~- - 0.12 0.15 0.10 0.10 0.15 0.15 0.09 0.19 0.14 0.15 - - - - - - - OVARIES UTERUS HEART RAT TERMINAL BODY PAIRED NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _-W---T-. _- - - _ - % - - TBW - - - - - - - - WT. - - - - - - - % - TBW . WT. % TBW _ _ _ _ _ _ __ _ __ _ __ _ __ _ __ _ __ _ __ _ _._ _ - - - - - - - - - 14921 242. 0.098 0.04 0.65 0.27 0.99 0.41 14922 282. 0.143 0.05 0.67 0.24 1.07 0.38 14923 248. 0.110 0.04 0.73 0.29 0.96 0.39 14924 288. 0.154 0.05 0.48 0.17 0.85 0.30 14925 276. 0.137 0.05 0.66 0.24 1.17 0.42 14926 291. 0.127 0.04 1.14 0.39 1.01 0.35 14927 253. 0.105 0.04 0.73 0.29 0.79 0.31 14928 270. 0.137 0.05 1.07 0.40 0.95 0.35 14929 237. 0.138 0.06 0.87 0.37 0.91 0.38 14930 259. 0.137 0.05 0.96 0.37 1.13 0.44 ________________________________________-------------------------------------------------------------------------------------------- ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBWANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 4 0 (PAGE 1): ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - FEMALE RATS 14891 2.16 8.88 411.11 2.51a 116.20a 0.076 3.52 14892 2.16 8.77 406.02 2.86a 132.41a 0.063 2.92 14893 2.08 7.12 342.31 2.27 109.13 0.053 2.55 14894 1.91 8.14 426.18 2.36 123.56 0.077 4.03 14895 2.10 7.46 355.24 2.22 105.71 0.081 3.86 14896 2.11 7.42 351.66 2.36 111.85 0.069 3.27 14897 2.13 7.13 334.74 2.25 105.63 0.064 3.00 14898 1.98 8.06 407.07 2.09 105.56 0.085 4.29 14899 1.99 6.36 319.60 2.35 118.09 0.099 4.97 - - - 1 - 4 - 9- - 0 - 0 - 2.08 7.77 373.56 2.11 ---__---___--____-__ 101.44 0.091 - - 4 - . - - 3 8 - - UTERUS RAT BRAIN NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. - _ _ _ _ _ _ _ _ _. -_- - - - - _ - - - - - _ WT. __- _ _ % _ BRW _-- _ _ WT. _____-_____ _ _ % _ BRW ____ _ _ _ _ _ _ _ _ _. __ _ _ _ _ 14891 2.16 0.46 21.30 0.93 43.06 14892 2.16 0.45 20.83 1.01 46.76 14893 2.08 0.65 31.25 0.91 43.75 14894 1.91 0.88 46.07 0.94 49.21 14895 2.10 0.43 20.48 0.87 41.43 14896 2.11 0.56 26.54 1.08 51.18 14897 2.13 0.74 34.74 0.88 41.31 14898 1.98 0.85 42.93 1.08 54.54 14899 1.99 0.63 31.66 1.07 53.77 14900 2.08 0.72 34.62 0.97 46.63 0.80 0.52 0.46 0.58 0.61 0.51 0.62 0.52 0.53 0.61 __--__ 37.04 24.07 22.12 30.37 29.05 24.17 29.11 26.26 26.63 2_ 9_ ._ 3_ 3_ _ 0.26 0.34 0.31 0.32 0.51 0.42 0.30 0.30 0.39 - - - 0 - . - 3 - 8 - - - 12.04 15.74 14.90 16.75 24.28 19.90 14.08 15.15 19.60 18.27 - - - - - - 0.130 6.02 0.132 6.11 0.100 4.81 0.158 8.27 0.148 7.05 0.167 7.91 0.119 5.59 0.145 7.32 0.127 6.38 - - 0- .- 1- 3- 9- - _ _ _ 6.68 _____ _ _ ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Fixed weight. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100 I 0 h m , PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 4 0 (PAGE 2 ) : ORGAN WEIGHTS AND RATIOS ( % ) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - FEMALE RATS c VI w 4 cn P PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'SSTUDY NUMBER: T-7485.15) TABLE 40 (PAGE 3) : ORGAN WEIGHTS AND RATIOS ( $ 1 OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - FEMALE RATS -------____-____________________________-------------------------------------------------------------------------------------------- GROUP I11 MIDDLE DOSAGE 200 MG/KG/DAY -------_________________________________---~-------------------------------~----~----------------~~~~~-~----------~-~--~ LIVER KIDNEYS ADRENALS SPLEEN THYMUS OVARIES RAT BRAIN PAIRED PAIRED PAIRED NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW WT. % BRW -------_________________________________-------------------------------------------------------------------------------------------- 14911 14912 14913 14914 14915 2.15 2.13 2.09 2.13 1.98 7.52 8.03 8.04 8.76 7.12 349.77 377.00 384.69 411.27 359.60 2.13 2.38a 2.31 2.38 2.14 99.07 111.74a 110.53 111.74 108.08 0.090 0.077 0.092 0.070 0.059 4.19 3.62 4.40 3.29 2.98 0.48 0.52 0.48 0.63 0.67 22.32 24.41 22.97 29.58 33.84 0.33 0.39 0.44 0.42 0.32 15.35 18.31 21.05 19.72 16.16 0.109 0.151 0.138 0.126 0.091 5.07 7.09 6.60 5.92 4.60 14916 2.15 10.17 473.02 2.66 123.72 0.076 3.53 0.60 27.91 0.60 27.91 0.149 6.93 14917 2.07 7.90 381.64 2.56 123.67 0.066 3.19 0.60 28.98 0.37 17.87 0.173 8.36 14918 2.01 8.48 421.89 2.59 128.86 0.101 5.02 0.51 25.37 0.38 18.90 0.169 8.41 14919 1.93 7.29 377.72 2.30 119.17 0.070 3.63 0.55 28.50 0.30 15.54 0.145 7.51 14920 2.16 8.97 415.28 2.51 116.20 0.085 3.94 0.67 31.02 0.22 10.18 0.137 6.34 ---_--__________________________________-------------------------------------------------------------------------------------------- UTERUS HEART RAT BRAIN NON-GRAVID NUMBER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW _---_______-_-____-_____________________-------------------------------------------------------------------------------------------- 14911 2.15 0.75 34.88 0.96 44.65 14912 2.13 0.47 22.06 1.02 47.89 14913 2.09 0.56 26.79 0.86 41.15 14914 2.13 0.50 23.47 1.06 49.76 14915 1.98 0.67 33.84 0.88 44.44 14916 2.15 0.47 21.86 1.11 51.63 14917 2.07 0.57 27.54 0.93 44.93 14918 2.01 0.84 41.79 1.14 56.72 14919 1.93 0.71 36.79 0.92 47.67 14920 2.16 0.81 37.50 1.05 48.61 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Fixed weight. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-026: ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS (SPONSOR'S STUDY NUMBER: T-7485.15) TABLE 4 0 (PAGE 4): ORGAN WEIGHTS AND RATIOS ( % I OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - FEMALE RATS 14921 14922 14923 14 924 14925 14926 14927 14928 14929 14930 1.92 1.92 2.07 1.99 2.08 2.08 2.10 2.03 2.22 2.16 7.01 8.08 7.97 7.98 7.46 8.30 7.77 7.56 7.93 7.80 365.10 420.83 385.02 401.00 358.65 399.04 370.00 372.41 357.21 361.11 2.14 1.97 2.89 2.12 2.30 3.25 2.02 2.54 2.22 2.46 111.46 102.60 139.61 106.53 110.58 156.25 96.19 125.12 100.00 113.89 0.059 0.074 0.092 0.074 0.071 0.079 0.063 0.073 0.066 0.084 3.07 3.85 4.44 3.72 3.41 3.80 3.00 3.60 2.97 3.89 0.50 0.63 0.69 0.52 0.60 0.77 0.87 0.64 0.69 0.63 26.04 32.81 33.33 26.13 28.85 37.02 41.43 31.53 31.08 29.17 0.28 0.42 0.26 0.29 0.42 0.43 0.23 0.51 0.32 0.39 14.58 21.88 12.56 14.57 20.19 20.67 10.95 25.12 14.41 18.06 0.098 0.143 0.110 0.154 0.137 0.127 0.105 0.137 0.138 0.137 RAT BRAIN UTERUS NON- GRAVID HEART NUMBER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW .......................................................................................................................... 14921 1.92 0.65 33.85 0.99 51.56 14922 1.92 0.67 34.90 1.07 55.73 14923 2.07 0.73 35.26 0.96 46.38 14 924 1.99 0.48 24.12 0.85 42.71 14925 2.08 0.66 31.73 1.17 56.25 14926 2.08 1.14 54.81 1.01 48.56 14927 2.10 0.73 34.76 0.79 37.62 14928 2.03 1.07 52.71 0.95 46.80 14929 2.22 0.87 39.19 0.91 40.99 1 4 93 0 2.16 0.96 44.44 1.13 52.31 .......................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. 5.10 7.45 5.31 7.74 6.59 6.10 5.00 6.75 6.22 6.34 - - - - - - - ARGUS 418-026 APPENDIX C PROTOCOL AND AMENDMENT Page 156 ARGUS 418-026 905 Ymhy Drinr, Mg. A Hodwrn, PA 19014 TJephonr (215) 4435710 T A (21~5)143-8587 -/e ARGUS RESEARCH Chades River Laboratories Dimvery and Development Services PROTOCOL NUMBER 418-026 SPONSOR'SSTUDY NUMBER: T-7485.15 STUDY TITLE: Oral (Gavage) Repeated Dose 90-Day Toxicity Study of Potassium Perfluorobutane Sulfonate (PFBS) in Rats PURPOSE: The purpose of this study is to provide information on possible adverse effects on Crl:CD@(SD)IGSBR VAF/PIu@ rats resulting from repeated exposure of Potassium Perfluorobutane Sulfonate (PFBS) over an extended period of time covering postweaning maturation and growth well into adulthood. The study should provide information on toxicity, indicate target organs and the possibility of accumulation, and may provide an estimate of a no-observed-adverse-effect level (NOAEL) of exposure that can be used in dosage selection for chronic studies and for establishing safety criteria for human exposure. TESTING FACILITY: Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 Telephone: (215) 443-8710 Telefax: (215) 443-8587 STUDY DIRECTOR: Raymond G. York, Ph.D., DABT Associate Director of Research Email: raymond.york@criver.com Address as cited above for Testing Facility. SPONSOR: 3M Corporate Toxicology 3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000 STUDY MONITOR: ., Ph.D., DABT 3M Corporate Toxicology 3M Medical Department Telephone: Telefax: Email: Page 157 ARGUS 4 18-026 REGULATORY CITATIONS: Protocol 41 8-026 Page 2 U.S. Environmental Protection Agency Health Effects Test Guidelines; 90-Day Oral Toxicity in Rodents. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3100, August 1998. U.S. Environmental Protection Agency. Toxic Substances Control Act (TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160, July 2000. REGULATORY COMPLIANCE: This study will be conducted in compliance with the Good Laboratory Practice (GLP) regulations cited above. All changes or revisions of this protocol shall be documented, signed by the Study Director and the Sponsor, dated and maintained with the protocol. The Testing Facility's Quality Assurance Unit (QAU) will audit the protocol, the raw data and the report, and will inspect critical phases of those portions of the study conducted at the Testing Facility in accordance with the Standard Operating Procedures of Argus Research. The final report will include a compliance statement signed by the Study Director that the report accurately reflects the raw data obtained during the performance of the study and that all applicable GLP regulations were followed in the conduct of the study. Should significant deviations from GLP regulations occur, each will be described in detail, together with how the deviation might affect the quality or integrity of the study. Should any portion of the study be conducted by a subcontractor or by the Sponsor, the QAU for this facility will conduct critical phase inspections and audit respective results and reports for that study portion according to the SOPS of that facility. Such critical phase inspection reports and report audits will be submitted by the facility to the Study Director. The dates of the inspections and report submissions will be incorporated into a QAU Statement generated by that facility and provided to the Testing Facility for inclusion in the final report. SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE: See ATTACHMENT 1 to the protocol. Page 158 ARGUS 4 18-036 TEST SUBSTANCE AND VEHICLE: Protocol 418-026 Page 3 Identification: Test Substance: Potassium Perfluorobutane Sulfonate (PFBS or T-7485). Lot number will be documented in the raw data. The Sponsor will provide to the Testing Facility documentation or certification of the identity, composition, method of synthesis, strength and purity of the test substance. Vehicle: Aqueous 0.1% carboxymethylcellulose (CMC) (medium viscosity) prepared using reverse osmosis membrane processed deionized water (R.O. deionized water). Lot number will be documented in the raw data. Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the vehicle that would interfere with the results of this study. Therefore, no analyses other than those mentioned in this protocol will be conducted. Safetv Precautions: Nitrile gloves, dust-mist/HEPA-filtered mask, appropriate eye protection and uniforrn/lab coat to be worn during formulation preparation and dosage. In addition, Tyvek sleeves will be worn and preparation will be conducted in a chemical fume hood. A half-face respirator will be wom when the bulk test substance is not being used in a chemical fume hood. The Material Safety Data Sheet (MSDS) is attached to the protocol (ATTACHMENT 2). Storaqe: Bulk Test Substance: Bulk Vehicle Components: Prepared Test Substance and Vehicle Formulations: Room temperature. Room temperature. 2C to 8C All test substance shipments should be addressed to the attention of Julian Gulbinski, Manager of Formulation Laboratory, at the previously cited Testing Facility address and telephone number. Shipments should include information concerning storage conditions and shipping cartons should be labeled appropriately. The recipient should be notified in advance of shipment. Page 159 ARGUS 418-026 FORMULATlON: Protocol 41 8-026 Page 4 Frequencv of Preparation: Formulations (suspensions) will be prepared approximately every 10 days at the Testing Facility. Detailed preparation procedures will be attached to this protocol (ATTACHMENT 3 ) . Adjustment for Purity: The test substance will be considered 100% pure for the purpose of dosage calculations. Testinq Facility Reserve Samples: The Testing Facility will reserve approximately 1 g sample of each lot of bulk test substance and vehicle used during the course of the study. Samples will be stored under the previously cited conditions. ANALYSES: Results of required analyses will be provided to the Testing Facility for inclusion in the study report. Samples additional to those described below may be taken if deemed necessary during the course of the study. Bulk Test Substance Samplinq: A sample (1 g) of the test substance will be taken on the last day of treatment and sent (ambient conditions) to the Sponsor for analysis. This sample will be sent to: Gregory S. Gorman, Ph.D. Staff Chemist Bioanalytical Chemistry Group Southem Research Institute 2000 Ninth Avenue South Birmingham, Alabama 35255-5537 Telephone: Telefax: Email: (205) 581-2725 (205) 581-2044 gorman@sri.org The recipient will be notified in advance of sample shipment. Page 160 ARGUS 418-026 PfOtOCOl 4 18-026 Page 5 Analvses of Prepared Formulations: Hornoqeneity: Homogeneity analyses of the prepared formulations will not be conducted. Information is on file with the Sponsor to document the homogeneity of the test substance in the prepared vehicle over the range of concentrations to be used in this study. This information will be provided to the Study Director for inclusion in the final report. Concentration: Concentration of the prepared formulations will be verified during the course of this study. Duplicate samples (2 mL each) will be taken from the first and last preparation on the day prepared. One sample of each set will be shipped for analysis; the remaining samples will be retained at the Testing Facility as backup samples. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Stability: Stability data for prepared formulations bracketing the range of concentrations in this study are on file with the Sponsor and will not be determined during the conduct of this study. This information will be provided to the Study Director for inclusion in the final report. Shippinq Instructions: Samples to be analyzed will be shipped (on cold packs) to Gregory S. Gorman, at the previously cited address. The recipient will b e notified in advance of sample shipment. DlSPOSlTlON: Prepared formulations will be discarded at the Testing Facility. All remaining bulk test substance will be returned to: 3M SMMG EHS&R 3M Center Building 236-15-10 St. Paul, Minnesota Telephone: Telefax: Email: 55144-1 000 ~. Page 161 ARGUS 4 18-026 Protocol 418-026 Page 6 TEST SYSTEM: SpeciedStrain and Reason for Selection: The Crl:CD@(SD)IGSBR VAF/PIu& rat was selected as the Test System because: 1) it is one mammalian species accepted for use in toxicity studies; and 2) it has been widely used throughout industry for toxicity evaluations. Number: Initial population acclimated: Population selected for study: - Sex: 50 virgin male and 50 virgin female rats. 40 male and 40 female rats (10 per sex per dosage group). Both male and female rats will be evaluated. Body Weiqht and Aqe: Male and female rats will be ordered to be approximately 35 days of age at receipt, at which time they will be expected to weigh from 80 to 140 g each. Actual body weights will be recorded the day after receipt and will be documented in the raw data. The weight ranges will be included in the final report. Source: Charles River Laboratories. Inc. The rats will be shipped in filtered cartons by air freight and/or truck from Charles River Laboratories, Inc., to the Testing Facility. Identification: Rats are permanently identified using MonelB self-piercing ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101). Male and female rats are assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study before administration of the first dosage. ANIMAL HUSBANDRY: All cage sizes and housing conditions are in compliance with the Guide for rhe Care and Use of Laboratory Animals"'. Page 162 ARGUS 4 15-026 Housinq: Protocol 41 8-026 Page 7 During the acclimation and study periods, the rats will be individually housed in stainless steel wire-bottomed cages. Room Air, Temperature and Humidity: The animal room is independently supplied with at least ten changes per hour of 100% fresh air that has been passed through 99.97% HEPA filters. Room temperature will be maintained as per the Test Guidelines [66"Fto 77F (19C to 25"C)I and monitored constantly. Room humidity will also be monitored constantly and maintained at 30% to 70%. Liqht: An automatically controlled 12-hour light:12-hour dark fluorescent light cycle will be maintained. Each dark period will begin at 1900 hours EST. The light cycle may be adjusted by the Study Director or designee if deemed necessary to accommodate scheduled laboratory activities. Any such adjustment will be documented in the raw data. Rats will be given Certified Rodent Diet0 #5002 (PMI Nutrition International) available ad libitum from individual feeders. Feed will be removed the evening prior to scheduled sacrifice. Water: Water will be available ad libitum from individual bottles attached to the cages or from an automatic watering access system. All water will be from a local source and passed through a reverse osmosis membrane before use. Chlorine will be added to the processed water as a bacteriostat; processed water is expected to contain no more than 1.2 ppm chlorine at the time of analysis. Water is analyzed monthly for possible bacterial contamination and twice annually for possible chemical contamination. Contaminants: Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the certified diet or in the drinking water at levels that would interfere with the results of this study. Therefore, no analyses other than those routinely performed by the feed supplier or those mentioned in this protocol will be conducted. RANDOMIZATION AND ACCLIMATION: Upon arrival, rats will be assigned to individual housing on the basis of computergenerated random units After acclimation for a minimum of five days, rats will be Page 163 ARGUS 418-026 Protocol 418-026 Page 8 selected for study on the basis of physical appearance and body weights recorded during acclimation. The rats will be assigned to dosage groups based on computergenerated (weight-ordered) randomization procedures. The weights of the animals assigned to the study should not exceed &O% of the mean weight of each sex. Five rats per sex per dosage group will be randomly selected for functional observational battery. In order to accommodate the necropsy schedule, rats will be randomly assigned to four replicates that will begin dosage and be sacrificed on consecutive days. ADMINISTRATION: Route and Reason for Choice: The oral (gavage) route was selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered; and 2) it is one possible route of human exposure. Method and Frequency: Male and female rats will be given the test substance once daily for 90 days. Rats will be sacrificed on the day following the last dosage. Dosages will be adjusted for the most recently recorded body weight and given at approximately the same time each day. Rationale for Dosaqe Selection: Dosage levels were selected by the Sponsor on the basis of a 28-day toxicology conducted with the test substance. In that study, 900 mg/kg/day produced significant increases in the liver weight of male rats and significant increases in kidney weights of female rats. The no-observable-adverse-effect level (NOAEL) was 300 mg/kg/day. Dosaqe Levels, Concentrations and Volumes: Concentration The test substance will be considered 100% pure for the purpose of dosage calculations Page 164 ARGUS 415-026 Protocol 4 18-026 Page 9 TESTS, ANALYSES AND MEASUREMENTS: Via biIity : All Periods: At least twice daily. Clinical Observations and/or General Appearance: Acclimation Period: Weekly. Dosage Period: Daily before dosage. Postdosage observations will be recorded approximately 60210 minutes after administration. These observations will be recorded at approximately the same time each day. Day of Sacrifice: Once. Signs of toxicity will be recorded as observed, including the time of onset, degree and duration, when applicable. Clinical observations may be recorded more frequently than cited above, if deemed appropriate by the Study Director and/or Sponsor's Representative. Detailed Clinical Observations - Male and Female Rats: Once before the first dosage and at least once weekly thereafter, detailed clinical observations will be conducted for all male and female rats. These observations will be made outside the cage in a standard arena at the same time each day of conduct. Effort will be made to ensure that variations in the test conditions are minimal. Signs noted should include, but not be limited to: changes in skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g., lacrimation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes (e.g., excessive grooming, repetitive circling), or bizarre behavior (e.g., self-mutilation, walking backwards) should also be recorded. 0phthaImoloqicaI Evaluation: Ophthalmological examinations will be performed by a veterinary ophthalmologist for all rats prior to dosage and at termination of the study. Page 165 ARGUS 4 18-026 Protocol 418-026 Page 10 Body Weiqhts (recorded and tabulated): Acclimation Period: Weekly (not tabulated). Dosage Period: Weekly and on the day before sacrifice. Sacrifice: Terminal weight. Feed Consumption Values (recorded and tabulated): Acclimation Period: Weekly (not tabulated). Dosage Period: Weekly. Day Before Sacrifice: Feed left recorded. Feed consumption values may be recorded more frequently if it is necessary to replenish the feed. These intervals will not be tabulated. Functional Observational Battery and Motor Activity: Functional Observational Battery: On one occasion during the course of the study, not earlier than week 11 of dosage, a functional observational battery (FOB)`*-'' and motor activity assessment will be conducted on five male and five female rats per group. The FOB, to be conducted by an observer unaware of the group assignment of the rat, will assess the following parameters: . 1. Lacrimation, salivation, palpebral closure, prominence of the eye, pupillary reaction to light, piloerection, respiration, and urination and defecation (autonomic functions). 2. Sensorimotor responses to visual, auditory, tactile and painful stimuli (reactivity and sensitivity). 3. Reactions to handling and behavior in the open field (excitability). 4. Gait pattern in the open field, severity of gait abnormalities, air righting reaction and landing foot splay (gait and sensorimotor coordination). 5 . Forelimb and hindlimb grip strength. 6. Abnormal clinical signs including but not limited to convulsions, tremors and other unusual behavior, hypotonia or hypertonia, emaciation, Page 166 ARGUS 418-026 Protocol 418-026 Page 11 dehydration, unkempt appearance and deposits around the eyes, nose or mouth. Evidence of the ability of this battery to detect the effects of positive control substances will be provided (Testing Facility Positive Control Data). Data will also be provided to document interobserver reliability if more than one observer is involved in the testing. Motor Activity: During the motor activity assessment, the movements of each rat will be monitored by a passive infrared sensor mounted outside a stainless steel wire-bottomed cage (40.6 x 25.4 x 17.8 cm). Each test session will be 1.5 hours in duration with the number of movements and time spent in movement tabulated at each five-minute interval. The apparatus will monitor a rack of up to 32 cages and sensors during each session. Groups will be counterbalanced across testing sessions and cages. Data will be provided to demonstrate that the test system is capable of detecting increases in activity produced by positive control substances (Testing Facility Positive Control Data). HEMATOLOGY AND CLINICAL CHEMISTRY: On the day of scheduled sacrifice, whole blood samples of approximately 5 mL will be collected from each rat (fasted) for hematological and clinical biochemical evaluations. Samples will be collected from the inferior vena cava immediately following sacrifice. Hematoloqv: Approximately 1 mL of blood will be collected into EDTA-coated (lavender top) tubes and maintained on wet ice and refrigerated until shipment for analysis of the following hematological parameters: Erythrocyte Count (RBC) Hematocrit (HCT) Hemoglobin (HGB) Mean Corpuscular Hemoglobin (MCH) Mean Corpuscular Hemoglobin Concentration (MCHC) Mean Corpuscular Volume (MCV) Leukocyte Count, Total (WBC) Leukocyte Count, Differential Platelet Count (PLAT) Mean Platelet Volume (MPV) Cell Morphology Two blood smear slides will be prepared at the Testing Facility for each sample for measurements of differential leukocyte count. All samples (refrigerated on cold packs) and slides (ambient conditions) will be shipped on the day of collection by overnight courier to arrive, if possible, on Tuesday through Friday. Approximately 1.8 mL of blood will be added to a tube containing 0.2 mL of sodium citrate (blue top) (0.129 M) tubes. The contents will be mixed and maintained on wet Page 167 ARGUS 418-026 Protocol 418-026 Page 12 ice until the tubes are centrifuged (within 30 minutes of the collection time). The resulting plasma will be transferred into 2.0 mL polypropylene tubes, labeled with study number, Sponsor's study number, rat number, dosage level, day of study, collection interval, date of collection, species, generation and storage. All samples will be frozen on dry ice and maintained frozen (2-70C) until shipment on dry ice by overnight courier for measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT). Clinical Chemistry: Approximately 2 mL of blood will be collected into serum separator tubes and centrifuged. The resulting sera samples will be transferred to 2.0 mL polypropylene tubes, labeled with study number, Sponsor's study number, rat number, dosage level, day of study collection interval, date of collection, species, generation and storage. Samples will be immediately frozen on dry ice and maintained frozen (570C) until shipment for analysis of the following parameters: Total Protein (TP) Triglycerides (TRI) Albumin (A) Globulin (G) Albumin/Globulin Ratio ( N G ) Glucose (GLU) Cholesterol (CHOL) Total Bilirubin (TBILI) Urea Nitrogen (BUN) Creatinine (CREAT) Alanine Aminotransferase (ALT) Aspartate Aminotransferase (AST) Alkaline Phosphatase (ALK) Calcium (CA) Phosphorus (PHOS) Sodium (NA) Potassium (K) Chloride (CL) Samples will be shipped (on dry ice) by Overnight courier to arrive on Monday through Friday. Shippinq Instructions - Hematoloqy and Clinical Chemistty Samples: Samples will be shipped according to the conditions described above to: Ms. Phyllis Powell Redfield Laboratories 100 East Boone Street P.O. Box 308 Redfield, Arkansas 72132 Telephone: (501) 397-2540 Telefax: (501) 397-2002 The recipient will be notified in advance of sample shipment. Page 168 ARGUS 4 18-026 Protocol 418-026 Page 13 SACRIFICE: Method of Sacrifice: Rats will be sacrificed by carbon dioxide asphyxiation. Scheduled Sacrifice: Male and female rats will be sacrificed on the day following the last administration of the test substance and necropsied as described below. Rats Found Dead or Moribund: Rats that die or are sacrificed because of moribund condition will be examined for the cause of death ormoribund condition on the day the observation is made. The rats will be necropsied and examined to the extent possible as described below. GROSS NECROPSY AND HISTOPATHOLOGY: Gross necropsy will include an initial physical examination of external surfaces and all orifices, as well as an internal examination of tissues and organs in situ. In addition, the cranial, thoracic and abdominal cavities will be examined. The lungs will be perfused with neutral buffered 10% formalin. Male and female rats will be sacrificed and examined for gross lesions. Gross lesions will be retained in neutral buffered 10% formalin and examined histologically. Tissue trimming and histopathology will be performed under the supervision of or by a BoardCertified Veterinary Pathologist. See ATTACHMENT 2 for tissues to be weighed and retained and histological evaluations to be conducted. All other tissues will be discarded. Page 169 ARGUS 4 18-026 PROPOSED STATISTICAL TESTS("'3): The following schematic represents statistical analyses of the data. Protocol 418-026 Page 14 I. Parametric TvDe of Test a I I . Nonparametricb A BarUett's Test A Significant at p ~ 0001 Not Significant I. Nonpamnelric I Analysis of Vanance Significant at p10.05 I Dunn's Test Not Significant Significant at ~ 0 . 0 5 I Dunnetrs Test Not Significant B. Fishefs Exact Test on Propomon of X e s ('75% Mal ry OncenMOnl B Analysis of Vanance with Repeated Measures Significantat E O 05 I Not Sgnificant (Dosage) Dunnetis Test (Dosage x Block interaction) One-way ANOVA b r e a c h block I SigniBcanr at p50 05 I Dunnetrs Test I Not Significant I l l . Test for Proportion Data Vanance Test for H o m o g e n e i t y of the B i n o m i a l Distribution a. Statistically significant probabilities are reported as either p I 0.05 or p 5 0.01 b. Proportion data are not included in this category. c. Test for homogeneity of variance. Page 170 ARGUS 415-026 Protocol 418-026 Page 15 Test items in the FOB using interval scales, such as the grip-strength tests and the landing foot splay test, as well as body weight data and feed consumption values will be analyzed as described under the Parametric heading of the schematic. Bartlett's Test of Homogeneity of Varianced6)will be used to estimate the probability that the groups had different variances. A nonsignificant result @>0.001)will indicate that an assumption of homogeneity of variance is not inappropriate, and the data will be compared using the Analysis of Variance Test'". If that test is significant @S0.05), the groups exposed to the test article/substance will be compared with the control group using Dunnett's Test@).If Bartlett's Test is significant @60.001),the Analysis of Variance Test is not appropriate, and the data will be analyzed as described under the Nonparametric heading of the schematic. When 75% or fewer of the scores in all the groups are tied, the Kruskal-Wallis Test(g'will be used to analyze the data, and in the event of a significant result @10.05),Dunn's Test'") will be used to compare the groups exposed to the test article/substance with the control roup. When more than 75% of the scores in any group are tied, Fisher's Exact Test'") will be used to compare the proportion of ties in the groups. Data from the motor activity test, with repeated measurements within a session, will be analyzed using an Analysis of Variance with Repeated Measures('*),as described under that heading in the schematic. A significant effect (p10.05) in that test can appear as effect of Concentration (a difference between groups in the total across all measurements in a session) or as an interaction between Concentration and Block (a difference between groups at specific measurement periods). If the Concentration effect is significant, the totals for the control group and the groups given the test articlehbstance will be compared using Dunnett's Test. If the Concentration x Block interaction is significant, an Analysis of Variance Test will be used to evaluate the data at each measurement period, and a significant result @S0,05) will be followed by a comparison of the groups using Dunnett's Test. Test items in the FOB having graded or count scores will be analyzed using the procedures described under the Nonparametric heading of the schematic. Clinical observation incidence data, as well as the descriptive and quantal data from the FOB, will be analyzed as contingency tables using the Variance Test for Homogeneity of the Binomial Distrib~tion''~). Alternate or additional statistical evaluations may be performed if deemed necessary or appropriate. Page 171 ARGUS 418-026 Protocol 418-026 Page 16 DATA ACQUISITION, VERIFICATION AND STORAGE: Data generated during the course of this study will be recorded either by hand or using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System, the Coulbourn lnstruments Passive lnfrared Motor Activity System, the Coulboum lnstruments Auditory Startle System, the Coulboum lnstruments Spatial Delayed Alternation System, and/or the passive avoidance software. All data will be tabulated, summarized and/or statistically analyzed using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System, Microsoft Excel [part of Microsoft Office 97 (version SR-2)] and/or The SAS System (version 6.12). Records will be reviewed by the Study Director and/or appropriate management personnel within 21 days after generation. All original records will be stored in the archives of the Testing Facility. All original data will be bound and indexed. A copy of all raw data will be supplied to the Sponsor upon request. Preserved tissues will be stored at the Testing Facility at no charge for one year af-ter mailing of the draft final report, after which time the Sponsor will be contacted to determine the disposition of these materials. RECORDS TO BE MAINTAINED: Protocol and Amendments. Test Substance, Vehicle and/or Reagent Receipt, Preparation and Use. Animal Acquisition. Randomization Schedules. Treatment (if prescribed by Staff Veterinarian). General Comments. Clinical Observations and/or General Appearance. Body Weights. Feed Consumption Values. Ophthalmological Evaluations. Functional Observational Battery Observations. Motor Activity Observations. Blood Sample Collection, Processing and Shipment. Gross Necropsy Observations. Organ Weights. Tissue Sample Collection, Processing and Shipment. Photographs (if required). Study Maintenance (room and environmental records). Feed and Water Analyses. Packing and/or Shipment Lists. Page 172 ARGUS 418-026 KEY PERSONNEL: Protocol 418-026 Page 17 Executive Director of Research: Mildred S.Christian, Ph.D., Fellow, ATS Director of Research: Alan M. Hoberman, Ph.D., DABT Associate Director of Research and Study Director: Raymond G. York, Ph.D., DABT Director of Operations and Compliance: Barbara J. Patterson, B.A. Director of Laboratory Operations: John F. Bamett, B.S. Director of Study Management: Valerie A. Sharper, M.S. Manager of Animal Operations: Dena C. Lebo, V.M.D. Chairperson, Institutional Animal Care and Use Committee: Theresa H. Woodard, D.V.M. Clinical Pathology Manager, Redfield Laboratories: Phyllis Powell, B.S., MT(ASCP) Consultant, Veterinary Pathology: W. Ray Brown, D.V.M., Ph.D., ACVP FINAL REPORT: ' The Study Director will provide periodic updates of study progress to the Sponsor. Draft summary tables of unaudited computer-recorded data may accompany these updates. Statistical analyses will not be performed on these interim data. A comprehensive draft final report will be prepared on completion of the study and will be finalized following consultation with the Sponsor. The report will include the following: Summary and Conclusion. Experimental Design and Method. Evaluation of Test Results. Appendices: Figures, Summary and Individual Tables Summarizing the Above Data, Protocol and Associated Amendments and Deviations, Study Director's GLP Compliance Statement, Reports of Supporting Data (if appropriate) and QAU Statement. The Sponsor will receive one copy of the draft report and two copies of t h e final report. INSTITUTIONAL ANIMAL CARE AND USE COMMIITEE STATEMENT: The procedures described in this protocol have been reviewed by the Testing Facility's Institutional Animal Care and Use Committee. All procedures described in this protocol that involve study animals will be conducted in a manner to avoid or minimize discomfort, distress or pain to the animals. The Sponsor's signature below documents the fact that information concerning the necessity for conducting this study and the fact that this is not an unnecessarily duplicative study may be obtained from the Sponsor. No alternative ( m wtro) procedures were available for meeting the stated purposes of the study. Page 173 ARGUS 418-026 REFERENCES: Protocol 4 18-026 Page 18 1. Institute of Laboratory Animal Resources (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C. 2. Haggerty, G.C. (1989). Development of Tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. J. Amer. Col. Toxicol. 8:53-70. 3. Irwin, S. (1968). Comprehensive observational assessment: la. A systemic quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia (Berlin) 13:222-257. 4. Moser, V.C. (1 989). Screening approaches to neurotoxicity: A functional observational battery. J. Amer. Col. Toxicol. 835-94. 5 . O'Donoghue, J.L. (1989). Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Amer. Cot. Toxicol. 8:97-116. 6. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 7. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 8. Dunnett, C.W. (1955). A muttiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 9. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Go., San Francisco, pp. 388-389. 10. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. 1 1 . Siegel, S. (1956). Nonparametric Statistics for the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. 12. SAS Institute, Inc. (1988). Repeated measures analysis of variance. SAS/STATTMUser's Guide, Release 6.03 Edition. Cary, NC, pp. 602-609. 13. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 240-241. Page 174 PROTOCOL APPROVAL: FOR THE TESTING FACILITY Alan M. Hoberman, Ph.D., DABT Director of Research ARGUS 3 18-026 Protocol 418-026 Page 19 Theresa H. Woodard, D.V.M. Chairperson, Institutional Animal Care and Use Committee FOR THE SPONSOR ---I---------------_- Ph.D., DABT Study Monitor and Sponsor's Representative Date Page 175 ARGUS 418-026 ATTACHMENT 1 SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE Page 176 ATTACHMENT 1 ARGUS 418-026 Protocol 418-026 Page 1 of 2 STUDY SCHEMATIC REPEATED DOSE 90-DAY TOXOCITY STUDY IN RATSa I Acclimation 1 I Test Substance Administration One Week i 90 Days b =Dosage Period. a. For additional details, see ';Tests, Analyses and Measurements" section of the protocol. b. All surviving rats sacrificed on the day following administration of the last dosage. Page 177 ATTACHMENT 1 ARGUS 4 18-026 Protocol 418-026 Page 2 of 2 SCHEDULE^ 11 DEC 01 11 DEC 01 - 17 DEC 01 Week of 10 DEC 01 18 DEC 01 - 20 MAR 02 Week of 11 MAR 02 18 MAR 02 - 21 MAR 02 12 JUN 02 Animal Receipt. Acclimation Period. Ophthalmological Evaluations. Dosage Administration. Ophthalmological Evaluations. Sacrifice and Necropsy. Draft Final Report. .................... a. The study initiation date is the date the Study Director signs the protocol Page 178 ~~~~ ~ ARGUS 418-026 ATTACHMENT 2 MATERIAL SAFETY DATA SHEET Page 179 ARGUS 418-026 VWAPILORINPGAEPSOSUIaE~:.:................................ N/A UIA VAPOR MNSITY: ................. n/A EvApoRAnffl RATE:.............. WlA SOLUBILITV IN WATER:. .......... 5 b SPECIFIC GRAVITY: .............. ca. 0.54 k i t e - 1 Bulk 0.ntity 7-8 PERCEHT VOLATfLE:. ............. NlA pH: ............................ 5.5 . 7.5 (9c Aqueous) VISCOSTPI: ..................... N/A BELTTffi POIKT: ................. 265 C lblpll APPEARANCE AND O W R : S o l i d , uhLtc, odorless, granular Page 180 ARGUS 4 15-026 --LE cormLI:n.r.r.S.....L.E..L.: ................ Won-F-blr MIA FLNmEU L mIGwmoII f E m W . UEL: ERANFI E.:............. WIA WA ~NaJIsIuNQmu: M t e r , C.&M dioxide, W C h r M , F w PME 2 FIRE F I m m PROCEDIRES: tku f u l l p r o t e c t i v e ~ U t h M g ,hclwtfng helmet, self-contained, poritivc pressurn o r p m r s u r r dcund h a t h i n g apparatus, bunker coat and pants, bands around ams. n s b t and lms, face Bask, and protective covering ?or erpoud areas of the hmad. FIRE AND ExPLosIols HA;uRDs: See HuardoUS D e c m p o s i t ~SeCtiCm t o r products of combustion. poLYHERIUTION: W a r d o u s polymrriration will not occur. HAzAmws DEcowosITIffl PRO#ICTS: Carbon mnoxide and Carbon Dioxide, Oxides of Sultur, Hydrogmn Fluoride. T O X I C Vapors. Gasms or P a r t i c u l ~ t e r . SPIU R E M : Observe prccmutionr ?rem other s e c t l m s . Ventfiate area. Collect s p i l l e d matwirl. Use net rwcpinQ CMpOund or water t o avoid dusturg. Clem up residue. Place i n a closed container. AECOmOlDED DISPOSAL: Incinerate in an i n d u s t r i a l o r c m e r c i a l ? a c u i t y in the presence o f a m b u s t i b l e m a t e r i a l . Corburtion p r o d u c t s u i l l include HF. Disposal a l t e r n a t i v e : Oisposc of waste product i n a t a c i l i t y pcnitted t o accept cheaicnl Wste. Page 181 C(SDS: L-nsa D e c n k r 08, 2000 cl~~ecw ARGUS 418-026 PAGE s EYE mm: I n d h t e l y f l u s h eyes wFth brgr amounts ot water. Get %mediate medical attention. SKfN QWTTACT: Hash a t t e c t e d area &th r o r p 8nd cater. INHAUTIOW: If s i p n r l 8 y ~ p t w SOCCUC. r Y O V h pamon t o t r e s h a i r . I f signs/sy.ptors c o n t i n u e , u.U 8 physician. If SCUUOWED: If. . a l l N d , c a l l a physician immediately. Only induce vomiting m t the Lnstruction of a p h y s i c h n . b v * r g i v e anything by mouth t o an unconscious person. EYE PROTEGTION: Avoid eym contact. The f O ~ s~houlQd be mrn combination, u appnapri8te. t o P r w e n t eye contact: gaggles. Ckmr s a t e t y ghssts d t h side s h i e l d s . of in Near vented SKIN PROTECTION: Avoid s k i n contact. Mar a p p r o p r b t e glover when handling t h i s material. A pair of gloves made t m m t h e toUaring maturial(s) am recmended: neoprene, n i t t f l e rubber. Use one or #re of the following personal p r o t e c t i o n items as necessary t o prevent s k i n contact: head covering, C O V e m l l S . P r o t e c t i v e gamcnts (other than gloves) should be made of either _ _ - - _ _ . _- - -_. _ __ - --- -_- - _- - -_- - - - - - - - of- -t h-e -fo_llo_uin_g m_at-er_ia- l_s._:-- -_- - -_- -_- - ___ -_- __- _ _ _ _ Abbrevutions: M I D :Nof Detarmincd N/A - Not Applicable CA - Approxuately Page 182 ARGUS 4 18-026 CSSW: L-7058 MYU-M December OS, 2000 MATE" PACE 4 Plm Tyvek or coated T p e k o r shflu dhpouble c o v c r d . REU)+EWED VENTIUTIW: P m v i d . approprhte local exhaust product i B heated. rrovidm approprmo locil e x h a u s t v v l t f l r t i o n m t t r a n s f o r point.. P r w f d c suffbiant v a n t U a t b n t o maintain a k i i m m b l o w recwrmded e x p u n Units. I f exh8mt Vmtmth ir not 8dOqIJate, use appmprlstr n r p l m t o y protoetion. RESPIRATORY P m o I : Avoid b m t h f n g O f li-8 m 8 t m r i d . A v o i d b r r r t h h g o f dust. Select ono of tho to- NIOSI appr0v.d mspir8tors b a r d on -me concentration of t o n t u l n a n t s and i n ~ C C O ~ ~ U I C wO ith QSHA regulations: half-mark dust M d m i s t rexpirator, t u l l - f a c e dust and mist r e s p i n t o r . P R E V E N T I ~OF ACCIDENTAL I'mESnON: Do not O a t , drink or smoke when u s i n g t h i s product. Mrh exposed a m u t h o m u g u y uith soap and h u t o r . Hash hands a f t e r h a a g end btwt eating. Do not ingest- RE- -: Stom w y t r a h e a t . when not in use. KHp c o n t r i n r r dry. Keep contamer c l o d FIRE AN0 D ( P L 0 s I ~AVOIDANCE: mt ~pplicablm. Nonflammable. OTHER PREmo)(ARy INfwuwnW: NO smoking: Smoking h i l o using t h i s product u n rcsult i n c o n t u b m t h n of t h e t O b 8 C C O and/or smoke 8nd lc8d t o t h e t o m t i o n o f the h8zardOUS d a c m p o r i t z o n p-cts mentioned m t h e R e 8 c t i V i t y ~ a t ar e c t i o n of t h i i HSDS. Stom work cuther toprrrtely frru, other clothing. tood and tobacco products. EXPOSURE LIMITS - SKIN NfYTATIffl: L i s t e d s u b s t a n c e s indicated with 'r' under SKIN refer t o t h e p o t r n t i r l c o n t r i b u t i o n t o the o v e r a l l exposure by t h e cutaneous route i n c l u d i n g aucoub rembranc and eye, e i t h e r by airborne o r , sort p a r t i c u l a r l y , by -- - di -- r - e - c - t - - c - o - n - t - a - ct -- ui -- t - h -- t - he --- sub ---- s - tan --- c _ e - . - - - V- -e-h-ic-le-s -ca.n -a l-t e_r s-k i-n- _-a- b-_s- _o r_-p_-ti_o-n_.- -. - _ -- _ Abbreviations: N l O - Not Determined N I A - Not Mplicablc CA - Approximately Page 183 ARGUS 418-026 EYE m A m : Pbdermtr Eye Xrrltatlon: S i c W / B f l p t o l S palm, tearing, a d hazy v b i o n . c8n i n c l u d e mdncss, smiling, SKIN CONTACT: Contact with the skin d u r i n O product Use i s not expected t o r r s u l t in signiticant Irritation. 1wnON: Single ~ v ~ m x p o r u r sab, ow m e o n e n d e d e u i d c ~ i s ,w y C8Ufe: I r r i t a t i o n (upper mrplmtory): tignsl8ymptmr can i n c l u d e tomnesa of the no8e and thfv-, coughing and sneezing. IF SWAUWD: May be h a r r t u l if6 m . Page 184 ARGUS 418-026 The intorration in t h b mtorir2 Wrty'Data Shnt (-) i s believed t o be correct as o t tho date mued. SM RWES NO WARRAHnES. EXPRESSED OR IHPLIED, INCLUDING. BUT ran unna~TO. NN rmm WWANTY OF MRC"TABILIlY OR FITNESS FWI A P A R n c u u A PllRpOsE OR tMRISf O f PERFOWWEE OR O F TRADE. U8.r h msponsiblo for d e t a r r i n i n g &tether the 3n p r o d u c t 1s ?it ?or a partitulmr purpose and s u i t a b l e ? o r u s e r ' s method o t use o r pppLLcttion. Qivsn t h e v a r i o t y o t ?actors that can 8 f f e C t ttte use and D p p l i C 8 t m o t 3)1 wet, tame o? which are u n i w l y u i t h i n tho u s e r ' I knowledge and control, it i s e s s e n t i a l t h a t t h e user r v a l u a t o t h o 3n produet to - t o m i n e chothcr it ir tit ?or a p a r t i c u l a r purpose and a u i t a b l e t o r user's method o t use o r a p p l i c a t i o n . prPVidr8 i n t o r r a t i o n Fn electronic t o r r as a s e r v i c e t o its c u s t m e r s . Due t o the mmoto p a r s i b u t y that e b c t r o n i c t r a n r f o r m8y havo r r s u l t e d i n e r r o r s , omissions o r alterations h t h h i n f o r r a t i o n , 3w makes no r e p r e s e n t r t l o n s as t o its COmplrten+tS o r a n u n c y . In addition, information obtained f m m I dat888So u y not be as c u r r e n t as t h e information i n t h e W S r v a i l a b l c d i r e c t l y frm 3M. Page 185 ARGUS 418-026 ATTACHMENT 3 TEST SUBSTANCE PREPARATION PROCEDURE Page 186 ARGUS 4 18-026 ATTACHMENT 3 Protocol 41 8-026 Version: 418-026(26 NOV 011 Page 1 of 2 TEST SUBSTANCE PREPARATION PROCEDURE Test Substance: PFBS Vehicle: Aqueous 0.1% CMC (medium viscosity) A. Purpose: The purpose of this procedure is to provide a method for the preparation of dosage suspensions of PFBS for oral (gavage) administration to rats on Argus Research Study number 418-026. B. General Information: 1. All suspension containers will be labeled and color-coded. Each label will specify the protocol number, test substance identification, Argus batch number, concentration, dosage level, preparation date, expiration date and storage conditions. 2. Suspensions will be prepared: - Daily Weekly -X Approximatelyevery ten days - For- days of use - By Sponsor 3. Suspensions will be prepared at a final dosage volume of 2mUkg. 4. Safety: - X Nitrile or neoprene gloves, uniform/lab coat, goggles or safety glasses with side shields - X - -X Dust-Mist Respirator if used in a chemical fume hood Half-Face Respirator if not used in a chemical fume hood Full-Face Respirator/Positive Pressure Hood X Tyvek Suit or tyvek apron and sleeves 5 . Dosage suspensions adjusted for YoActivity/Purity or Correction Factor: - Yes - Yo Activity - X No (Calculations based on 100%) - % Purity - Correction Factor 6. Sampling requirements: Cited in protocol 7 . Storage: Cited in protocol Page 187 ARGUS 418-026 ATTACHMENT 3 Protocol 418-026 Version: 418-026(26 NOV 011 Page 2 of 2 TEST SUBSTANCE PREPARATION PROCEDURE NOTE: Prior to test substance preparation accurately measure the required amount of the appropriate vehicle (R.O. deionized water should be used for calibration purposes) in a graduated cylinder, pour the required amount of vehicle into a beaker. Carefully mark each beaker at the meniscus. This mark will be used during the preparation to bring the test substance slurry up to volume. C. Dosage Suspension Preparation: 1. Weigh the required amount of test substance on a piece of weigh paper or into an appropriately sized mortar (see PREPARATION CALCULATIONS). 2. If weigh paper is used, transfer the test substance to an appropriately sized mortar. If necessary, grind the test substance into a fine powder. Slowly add a small amount of vehicle and grind. Continue to add vehicle slowly and grind the vehicle and the test substance together to form a fine slurry. Transfer the vehicle/test substance slurry to a marked beaker. 3. Rinse the mortar and pestle with additional vehicle to remove any remaining test substance. Transfer rinse to beaker. 4. Add additional vehicle to the beaker to bring volume up to the mark. Place on magnetic stir plate and agitate prior to and during administration and/or sampling. 5. Repeat steps (1) through (4) for each concentration. Clarification: No -Yes [see attached clarification form] Page 188 ARGUS 418-026 AlTACHMENT 4 TISSUES TO BE WEIGHED AND RETAINED FOR POSSIBLE EXAMINATION AND HISTOLOGICAL EVALUATION Page 189 ARGUS 4 15-026 ATTACHMENT 4 Protocol 418-026 Page 1 of 2 TISSUES TO BE WEIGHED AND RETAINED FOR POSSIBLE EXAMINATION The following organs will be weighed prior to fixation as soon as possible after excision to avoid drying (paired organs will be weighed as pairs): Adrenals Brain Kidneys Heart Thymus Spleen Liver Testes Epididymides Uterus Ovaries Target Organs The following tissues or representative samples will be collected from all male and female rats at necropsy and retained in neutral buffered 10% formalin. Adrenals Aorta Bone Marrow (sternum) Brain (cerebrum, cerebellum, medulldpons) Epididymides Esophagus Eyes (with optic nerve) Femur Heart Intestines, large (colon, cecum, rectum) Intestines, small (duodenum, jejunum, ileum) Kidneys Larynx, Pharynx and Nose Liver Lungs Lymph Nodes (mandibular, mesenteric) Mammary Gland (with skin, female only) Ovaries Pancreas Peyer's Patches Pituitary Prostate Salivary Gland (mandibular) Sciatic Nerve Seminal Vesicles Skeletal Muscle Skin Spinal Cord (cerivcal, mid-thoracic, lumbar) Spleen Stomach Testes' Thymus Thyroid/Parathyroid Trachea Uterus Urinary Bladder Vagina 'Testes will be fixed in Bouin's solution for 48 to 96 hours before being transferred to and retained in neutral buffered 10% formalin. Histological Evaluation Tissues to be examined histologically will be routinely processed, embedded in paraffin, sectioned at 5 microns and stained with hematoxylin and eosin. All gross lesions will be examined histologically. Page 190 ARGUS 418-026 ATACHMENT 4 Protocol 418-026 Page 2 of 2 Histological examination will be performed on all control and high test substance concentration group rats, and all target tissues from all rats. If lesions attributed to the substance by the Study Director and/or Veterinary Pathologist are observed in the rats exposed to the high test substance concentration, the same organs will be examined histologically in the rats exposed to the lower test substance concentrations. Should results from the control and high dosage groups warrant examination of the lower dosage groups and conduct of the quantitative evaluation, scheduled report dates will be adjusted accordingly. Additional costs will be incurred should these evaluations be required. Histopathological findings will be presented in a Contributing Scientist Report Shippinq Instructions: Retained tissues will be shipped (ambient conditions) to: W. Ray Brown, D.V.M., Ph.D., ACVP Veterinary Pathologist Research Pathology Services, Inc. 438 E. Butler Avenue New Britain, Pennsylvania 18901 Telephone: (215) 345-7070 The recipient will be notified in advance of sample shipment. Page 191 ARGUS 4 18-026 905 S k h y Drive, 4.A Honham, PA 19044 Tekphont. (2 IS) 14387I 0 rckfhx: (21s) 443-8587 -/- ARGUS RESEARCH Chartes River Laboruton'es Discovery and Development Services PROTOCOL 4 5 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PEWLUOROBUTANE SULFONATE (PFBS) IN RATS SPONSORS STUDY NUMBER: T-7485.15 Amendment 1 - 30 MAY 2002 1. Histolorrical Evaluation (page 2 of Attachment 4 of the protocol): [Effective Date: 2 1 May 20021 Histological evaluation will be performed on the nasal cavities and nasal turbinates, stomachs and kidneys of the male and female rats in the 60 and 200 mg/kg/day dosage groups (low and intermediate dosage groups) Reason for Change: This change was made to clarify that additional histological evaluations would be performed because lesions were found in rats of both sexes assigned to the 600 mg/kg/day dosage group. Study Director ---_--_____--- Date ., Ph.D., DABT Date Member, Institutional Arurnal Care Study Monitor and Use Committee Sponsor's Representative Any revisions to this finalized amendment must be made by subsequent amendment. Page 192 ARGUS 418-026 APPENDIX D DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY Page 193 ARGUS 4 18-026 DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY 1. On day 1 of study (DS l), (18 December 2001), rats were not assigned to four replicates but were scheduled to be sacrificed over four days to accommodate the necropsy schedule. This deviation did not adversely affect the outcome or interpretation of the study because the rats were administered the test substance for 91 to 94 days. 2 . The following rats did not receive the full dosage volume because the rat refluxed a portion of the test substance. Dosage . Dosage Day of Study Rat Dosage Volume Volume Refluxed" a. Approximate volume refluxed. These deviations did not adversely affect the outcome or interpretation of the study because the volume refluxed was small compared to the total dosage volume. 3. On DS 84 (11 March 2002), one 600 mg/kg/day dosage group female rat (14930) was administered the test substance 3 hours and 36 minutes late. This deviation did not adversely affect the outcome or interpretation of the study because the rat received the appropriate test substance on the intended day and it was a single event. 4. Postdosage observations were performed out of the range of 60 -t 10 minutes on the following dates. 1 1 1 1 1 1 1 Dosage Dosage ~ Group ( m g k g i a y ) Date Day of Study Number of Rats Range of *?:zed (minutes) I 0 (Vehicle) 20 DEC 01 3 2 +I 12 JAN 02 26 6 +1 to+4 18 JAN02 63 3 +1 03 MAR 02 76 10 +1 to+9 I1 60 03 MAR 02 76 9 + I to +9 Page 194 ~ ARGUS 4 1S-026 These deviations did not adversely affect the outcome or interpretation of the study because the extent of the deviation was less than ten minutes. 5 . Body weights were not recorded on the day before sacrifice for the following rats: IV . 600 19MAR02 92 21 MAR02 94 18MAR02 91 19MAR02 92 21 MAR 02 94 14873,14874 14875,14879, 14880 14881, 14882 14884, 14885 14888, 14889 14913, 14914, 14915 14918, 14919, 14920 14921, 14922 14924, 14925 14929, 14930 These deviations did not adversely affect the outcome or interpretation of the study because body weights were taken on the day of sacrifice. All deviations are documented in the raw data. Page 195 ARGUS 4 18-026 APPENDIX E CERTIFICATES OF ANALYSIS Page 196 - ARGUS 418-026 Centre Anahjtical Laboratoris, Inc. 3048 Research Onve-- - State College, PAmi -www.xentrelab.m Phone: (814) 231-8032 Fax: (814) 231-1253 w (814) 231-1580 CERTXFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-067 3M Product: PFBS, Lot #5 Purity' Appearance I Identification NMR 1. Calcium 2. Magnesium 3. sodium2 ' . 4. Potassium2 5. Nickel 6. Iron 7. Manganese Total % h p e t y (NMR) I Total % Impurity (La) Total % Impurity (GCrnS) Punty by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate White, crystalline solid Elemental Analysis': 1 . Carbon 2. Hydrogen 3 . Nitrogen 4. Sulfur 5 . Fluorine Theoreticd Value = 14.2% Theoretical Value = 0.0% Theoretical Value = 0% Theoretical Value = 9.5% Theoretical Value = 50.6% 98.2 % Confoms Positive I. 0.002wt/wt.% 2. <0.001 wt/wt% 3. 1.142 d w t % 4. 8.442 w t ~ w t % 5. <0.001 wtlwt.% 6. 0.002wtJwt% 7. <0.001 wtlwt% 0.9 wtJwt.% 0.774 wt/wt.% II None Quantified - .- 99.69% 1. co.015 wtfwt.% 2. 0.101wt./wt.% 3. <0.040 wt/wt.% 4. c0.009 wtlwt.% 5. C0.006 wtlwto/p I 6. ~0.006wtJwt-% 7. C0.078 wtJwt.% , 1. co.1 wt./wt.% 2. CO.1 w-tJwL% 3. cO.1 wtJwt.% 4. <0.25 wtlwt.% 1. 10.4 wtJw-t.% 2. 0.31 1 wt./wt.?'m 3. 3.94 wt/wt.% 4. 9.46 wt.iwt.% 5. 38.1 wt/wt.% COAO23-067 Page 197 Page 1 o f 2 ARGUS 4 18-026 - a C m t r ~Analytical Laboratori-. fnc 3048 ResearchDmre StateCollege;PA16801- - -w~~-t-an?blatErri Phone: (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 CERTIFICATE OF A.A&YSIS Centre Analytical Laboratories COA Reference #: 023-067 Date of Last Analysis: 08/31/01 Expiration Date: 08/31/03 Storage Conditions: Frozen 410C Re-assessment Date: 08/31/03 'purity = 100% 1.(Total NMR impurities, 0.90% + Total LUMS impurities, 0.774% + Total Metal impurities, 0.004% + Total Anion Impurities, 0.101 +Residual Solvents TGA., 0.02%) Total ixupurity from all tests = 1.799% Purity = 100% - 1.799% = 98.2% 2Potassiumand Sodium are present as counterions and thus are excluded fium the purity calculation. 3 "'heoretical value calculations based on the empirical formula, C+F$3O3Kt (MW=338.2) Prepared By: Scientist, Centre Analytical Laboratories \\at\m Date dmdL7 / ! b - Reviewed By: John Flahefi, / Date 'Laboratory Manager, Centre Analytical Laboratories COAO23-067 Page 2 of 2 Page 198 ARGUS 4 18-026 APPENDIX F ANALYTICAL REPORT Page 199 ARGUS 418-026 ANALYSIS OF DOSING SOLUTIONS USED AT ARGUS RESEARCH LABORATORY FOR SPONSOR'S STUDY NUMBER T-7485.15 (ARGUS RESEARCH LABORATORY PROTOCOL NUMBER: 418-026), SRI STUDY A536.1 STUDY ID: A536.1 SPONSOR STUDY NO. T-7485.15 (ARGUSRESEARCH LABORATORY PROTOCOL NUMBER: 418-026) Southern Research Institute 2000 Ninth Avenue South P.O.Box 55305 Birmingha~A~L~, 35255-5305 Study Initiation Date: 1/08/2002 Study Completion Date: 9/05/2002 Experimental Initiation Date: 3/18/2002 Experimental Completion Date: 3/19/2002 (1.7 SOUTHERNRESEARCH INSTITUTE Page 200 ARGUS 4 18-026 SUMMARY A total of 8 formulated dose samples including vehicles ranging in concentration fiom 0 to 60 mg/mL were analyzed by analytical method BACG-3533 to determine the concentration of perfluorobutanesulfonate(PFBS) in the formulated mixture. Formulation stability information is the responsibility of the sponsor. Samples were stored refigerated as per sponsor's shipping recommendations. Dose formulations were found to be within k 10% of the reported concentration except for two samples, 6 m g / d dated 12/17/01, and 60 m g / d dated 3/11/02. These two samples were found to have measured concentrations of 115% and 79% of target values, respectively. Page 201 KEY PERSONNEL Raymond G. York, PbD., D.A.B.T. Study Director Argus Research Laboratories Gregory S. Gorman, Ph.D. Manager Bioanalykal Chemistry Group Lara Cook, M.S. Research Associate 11 B i o d y t i c a l Chemistry Group ARGUS 418-026 Page 202 ARGUS 418-026 1.0 Objective The objective of this study was to determine the dose concentration of perfluorobutanesulfonate (PFBS) in the supplied dosing solutions received fiom the sponsor and to confirm the identity of the test solution. 2.0 Safety All necessary procedures to ensure safety of the analysts were based on information contained in the Material Safety and Data Sheets (MSDS), provided by the producer of the test article and the study director. 3.0 Compliance The study described in this final report was conductec in accordance with the EPA Good Laboratory Practice Standards (40 CFR Part 160 and 40 CFR 792). The final report accurately reflects the raw data obtained during the performance of the study. There were no adverse circumstances that affected the quality or integrity of the study. 4.0 Experimental 4.1 Analytical Procedures The sample preparation and analysis procedures as described in the analytical method BACG-3533 were employed for all analyses. Each sample was allowed to warm to room temperature, was sonicated for about 15 minutes and was then vortexed well before being sampled. An aliquot was taken from each and diluted as described in the method. Multiple calibration curves were prepared over a concentration range of 500 to 10,000 n g / d and analyzed along with the samples as described kthe method. The correlation coefficient for each curve was equal to or greater than 0.9982. 4.2 Results The results of the identity testing confixmed that the found spectra (LC/MS, FT-IR and I3CNMR results) were consistent with the submitted substance, PFBS. The results of the analysis are presented (Table I) corresponding to the sponsor's study number at the end of the report. Page 203 ARGUS 418-026 4.3 Calculations Calculations were performed using TurboQuan (Version 1.O). The amount of analyte in the diluted dose formulation samples (ng/mL) was back calculated using a calibration curve generated fiom a set of calibration standards containing the equivalent amount of CMC as in the diluted samples. The calibration curve was generated by a regression analysis to determine the best fit curve (e.g., linear, quadratic etc.) and amount of weighting. A quadratic fit with 1/X weighting was determined to be the best fit : y = n x 2 + bx + c where: y = Peak area response of test article x = Concentration of the test article in standards. a, b, c = Constants derived fiom the regression analysis. 5.0 Storage A copy of the h a l report and all raw data will be stored in the SRI archives. 6.0 Conclusion A total of 8 dose formulation samples ranging in concentration fiom 0 to 60 m g / d were analyzed by BACG-3533. With the exception of two samples, 6 m g / d dated 12/17/01, and 60 mg/mL dated 3/11/02, dose formulation sampleswere found to be within -C 10 % of the reported concentration. Page 204 ARGUS 418-026 Table I Dose Formulation Analysis of T-7485.15 in 0.1% CMC Sponsor Study Number T-7485.15 (Argus Research Laboratory Protocol Number:418-026) Page 205 7.0 Approvals :wk,M.S. Research Associate II Bioanalyticd Chemistry Group StafTChemist I3ioanalytm.l Chemistry Group _ I Tina Rogers,P h h Director Safety Assessment Department ARGUS 418-026 Y-6 - 0 L Date 9-L-ca Date Date I U AStrugduys!Rdierseecatorcrh Laboratories Page 206 ~________ ARGUS 418-026 QUALITY ASSURANCE STATEME" F d Report On: Analysis of Dosing Solutions Used at Argus Research Laboratory for Sponsor's Study Number T-7485.15 (Argus Research Laboratory Protocol Number: 418-026), SRI Study A536.1 Study No.: A536.1 Listed below are the phases andor procedures perfomed by Southern Research Institute that were inspected and audited by the Quality As~uranceUnit during the study described in the report. Findings were reported to the study Wctor and managementperiodically. PhasesProcedures Inspection/ Audit Date Date Management Date Study Director Notified Notified Protocol Review ,- Fourier-Transform Infrared spectroscopy I Data Audit and Draft Report Review 411 5/02 411 6/02 4115-19/02,4/22/02, 4/24-26/02,5/8/02, 6/20/02-6/2 1/02 4117/02 4117/02 612 1/02 6/26/02 6/26/02 8119/02 Protocol hendment A I 6/26/02 6/26/02 8119/02 Final Report 8119/02 8119/02 81 19/02 The results presented in this final report accurately reflect the raw data. Date Page 207 ARGUS 418-026 Page 1 of 8 ANALYTICAL METHOD Method No. : BACG-3533 .- Tide: Dose Formulation Analysis of Perfluorobutane SuIfonate in 1%Carboxymethyl Cellulose by HPLCIMass Spectrometry (HPLC/MS) 1.0 PRINCIPLE .. _ " - 2.0 Dose formulation samples of perfluorobutane sulfonate (PFBS)in 1 % carboxymethyl cellulose (CMC) are diluted down to 3200 n g / d and analyzed by HPLC/MS. Quantitation 'is based on an internal standard using back calculated values from a calibration curve encompassing a concentration range from 500 to 10,000 ng/mL and containing the same concentration of CMC as the dose formulations in the diluted _ o- m. REAGENTS AND SOLUTIONS The listed reagents or their equivalents m a y be used. 2.1 Neat Reagents 2.1.1 Water, deionized and organic free (fiorn in-house purification system; e.g., Ingalls 2 1oN) 2.1.2 Methanol, HPLC grade 2.1.3 Perfluorobutanesulfonate (analyte), as provided by the client 2.1.4 (internal standard), 97 % 2.1.5 Ammonium acetate, HPLC grade 2.2 Prepared Solutions Appropriate changes in the solutions may be made at the discretion of the analyst 2.2.1 5 mM Ammonium acetate in organic free water Page 208 ARGUS 418-026 Page 2 of 8 ANALYTICAL METHOD Method NO.: BACG-3533 Title: Dose Formulation Analysis of Perfluorobutane Sulfonate in 1%! Carboxymethyl Celluloseby HPLC/Mass Spectrometry @PLUMS) 2.2.1.1 For example, to prepare 4 liters, measure out ammonium acetate (e.g., 1.542 g) and add in organic-free water (e.g., 4 L). Mix well and filter through HPLC mobile phase filtration apparatus. 3.0 INSTRUMENTS, M A T E m , AND APPARATUS _ - The following or their equivalents may be used. 3.1 HPLC pump(s), autosampler, and single quadrupole mass spectrometer 3.2 Autosampler vials with inserts 3.3 Vortex mixers (e.g., touch mixer and IKA-Vibrax @ platform mixer) 3.4 HPLC mobile phase filtration apparatus 3.5 Filters for HPLC mobile phase filtration apparatus (e.g., Nylon-66, 0.20 pm) 3.7 Analytical balance 3.8 Volumetric flasks (e.g., 10 and 25 mL) 3.9 i 3 .-lo - 3.11 Disposable Pasteur pipets Micropipettor(s) with tips Culture tubes with teflon-lined caps 3.12 Assorted glassware and syringes Page 209 ANALYTICAL METHOD ARGUS 4 18-026 Page 3 of 8 T@. e: Dose Formulation Analysis of Perfluorobutane Sulfonate in 1%Carboxymethyl Cellulose by HPLC/Mass Spectrometzy @PLUMS) 4.0 _, PREPARATION OF STOCKS AND WORKING STOCKS Appropriate .changes in the concentrations of the solutions may be made at the discretion of the analyst. Actual dilutions will be documented on the preparation sheets. ..*- - -+.. LI - -)__ 4.1 ' Main Stock Solution of PFBS -1000 &mL - 4.i.i Prepare an lo00 pg/mL solution of PFBS in mobile phase (e.g., accurately weigh lLq__ 7a*bout 10 mg PFBS into a 10-mL volumetric flask). Add mobile phase to dissolve. ?-. . D(ei.lgu.t,ectuolttuhree mtuabrek).anAdlatedrdna1t0ivmelLy,ofwmeiogbhilethpehcaosem. pMouinxdwineltlo. aTnraanpspfreorptrhiaetesovluetsisoenl to a clean vessel if desired. 4.2 4.211 -_ - Spiking Stock Solution of PFBS -50 pg/mL Prepare an -50 p g f d solution of PFBS in mobile phase (e.& ,measure about 500 pL of -1OOO pg/mL PFBS into a 10-mL volumetric flask). Add mobile phase to dissolve. Dilute to the mark. Alternatively, weigh the compound into an appropriate vessel (e.g., culture tube) and add 10 mL of mobile phase. Mix well. Transfer the solution to a clean vessel if desired. 4.13'- I - - Stock Solution of Internal Standard , -200 pg/mL 4.3.7 +; ,C I. *,. i I Prepare an -200 pg/mL solution of in deionized organic-free water (e.g., accurately weigh about 10mg into a 50-mL volumehc flask). Add deionized organic- free water to dissolve and dilute to the mark with deionized organic-free water. Alternatively, weigh the compound into a an appropriate vessel (e.g. , culture tube) and add 50 mL of deionized organic-free water. Mix well. Transfer the solution to a clean vessel if desired. Page 210 ARGUS 418-026 Page 4 of 8 ANALYTICAL METHOD Mezhod No.: BACG-3533 Title: Dose Formulation Analysis of Perfluorobutane Sulfonate in 1%Carboxymethyl Cellulose by HPLCMass Spectrometry (HPLCRMS) 4.3 Working Stock Solutions of PFBS 4.3;1 To prepare working stock solutions, make the proper dilutions as shown in the following table. Prepare in IO-mL volumetric flasks or other appropriate glassware. If desired a modified dilution scheme canbe used and documented in the study records. .W o a g Stock Level WSL) A p p r o h t e Concentration -* (Jlgm Volume of Internal Standard (PL) Volume of PFBS spiking solution (PL) 500 200 10 lo00 200 20 3000 -- 3200 - . - 5Ooo 200 60 I 200 I 64 200 100 8000 200 160 L . loo00 200 200 Volume of mobile phase (PL) 790 780 740 736 1 700 640 600 Note: The mobile phase used for each standard curve should contain the same concentration of CMC as the samples. For example, the dilution factor of a 4 mg/mL sample is loo0 @nor to addition of IS). The mobile phase for a 4 mg/mL sample prepared in 1%CMC should contain 1/1OOO% CMC to account for the dilution. 5.0 PREPAlUTION OF SPIKED STANDARDS AND BLANKS Appropriate changes in the concentrations of the solutions may be made at the discretion of the analyst. Page 21 1 ARGUS 418-026 .. .. . Page 5 of 8 ANALYTICAL METHOD Mead NO. BACG-3533 -. - - - Titie: Dose Formulation Analysis of Perfluorobutane Sulfonate in 1% Carboxymethyl Cellulose by HPLCMass Spectrometry @PLUMS) 5.1 6. ..0 . Multiple (e.g., about three) sets of standards blanks (blank + IS) are analyzed with each set of unhown samples. A double blank (blank-IS) may also be analyzed if desired. Standards may be prepared as shown in the table in 4.3.1. - PREPARATION OF SAMPLES 6.1 All samples are to be diluted to approximately the middle of the curve (e.g. 3200 ng/mL). Dilutions are to be made with mobile phase. For example, for a 4 mg/mL - __-.-_s-ple, take 1mL and dilute with mobile phase in a 10 mL volumetric flask. Then taki 100 pL of the diluted sample and dilute that with mobile phase in a 10 mL -whmetric flask. Take 800 pL of the second dilution, place in & autosampler vial, add 200 pL of IS, mix, and analyze. 7.0 ANALYSIS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY MASS SPECTROMETRYIMASSSPECTROMETRY (HpLC/MS/MS) 7.1 7.1.1 - Conditions are to be optimized if necessary. T,C . . Analytical Column: . none G w d Column: Efution Flow rate: Injection volume: .Mobile phase: Fluofix 120E 10 mm x 2 mm lo00 pumin. 5 PL A: 5 m M ammonium acetate buffer B: methanol Elution Profile: Temperature : Isocratic 30%A : 70% B Ambient 7.1-2 PE Sciex API 150EX Single Quadrupole Mass Spectrometer Conditions Page 2 12 ARGUS 4 18-026 Page 6 of 8 ANALYTICAL METHOD Me&& NO. BACG-3533 - . Ti&&- Dose Formulation Analysis of Perfluorobutane Sulfonate in 1% Carboxymethyl Cellulose by HPLC/Mass Spectrometry (HPLC/MS) Software: PE Sciex TurboQuan - :Note: Values listed under 'MS/MS Acquisition Conditions" override parameters in this table. . Auxiliary Gas: Air (e.g., Grade 0.1) at 85 pounds per square inch -Parameter Ls NC TEM OR 1 - RNG Qo IQ 1 Sr RO1 IPE Value -SO00 0 450 -25 -170 10 11 16 11 300 2400 15 8 0 0 0 0 0 Page 213 .-. ._ _. . . ANALYTICAL METHOD ARGUS 418-026 Page 7 of 8 ,M&odjNo.: - --___ _ Pice.-_ BACG-3533 Dose Formulation Analysis of Perfluorobutane Sulfonate in 1% Carboxymethyl CWulose by HPLUMass SpecPometry (HPLC/MS) ! - - Masses requested: .- - I PFRS: i-I f - 200 i . - .. I b. - ii 200 -">. CULATIONS _ - --_ i - I--- i3.1 1 - 1 .:-$ I t - i i ! t # L 7i?3Ee end of the analytical run,review each chromatogram to ensure the retention - h e , peak shape, and peak height and peak area determination of the test article and EA -me IS are acceptable. The data may be smoothed as appropriate. For quantitation, use the ion profiles at the following mass-to-charge ratios: Analvte PFBS IQdhEk 299.2 tt - _ _ . li Plot the peak area response of PFBS divided by the peak area response of the IS .from all standards versus the concentration of the test article in the standards. Alternatively, thepeak heights may be used h e a d of peak areas. Obtain the best curve fit of the data (e.g., quadratic fit weighted with l/concentration of the test article or a atic fit). Note: The best curve fit m a y be dependent on the range of the standard and it m a y be necessary to have more than one standard curve for various gqcentration ranges using the following: * .. -. - y = ax2 + bx + c where y = Peak height response of PFBS divided by peak height response of -. the IS in Standards. ,-- x = Concentration of the PFBS in standards. Page 214 ARGUS 4 18-026 Page 8 of 8 ANALYTICAL METHOD Mead No.: - -. - _ ritre BACG-3533 Dose Formulation Analysis of Perfluorobutane Sulfonate in 1% Carboxymethyl Cellulose by HPLCMass Spectrometry (HPLC/MS) a, b, c = Constants derived from the regression analysis. 8.3 Using the standard curve, calculate the level of PFBS in each d o w n sample. Correct _ _ the results of samples for any dilutions. 9.0 - ACCEPTANCE AND RXJECTION CRITERIA __ _I__ 9.1 Refer to SOP SRI 91-3 for acceptance/rejection criteria except acceptable accuracy for standards is 80-12076 of theoretical. 10.0 REPORTING 10.1 Results of all analyses are tabulated, and the raw data, o r i w chromatograms, and reports are to be filed in the appropriate study file. Authors: 743-3mo Chemist III Date 7-/7-2000 Date Page 2 15 ARGUS 418-026 APPENDIX G ENVIRONMENTAL AND HUSBANDRY REPORTS Page 216 ARGUS 418-026 ARGUS Temperature and Relative Humidity Report Location: Room 05 Protocol Number: 418-026 Range of Dates: I f -De02001 13:20 to 21-Mar020020 8 5 9 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Mean (a SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (YO): Number of Points Low (%): Report Generated: 09-Jun-2002at 11:45 Temperature 66F to 79F Relative Humidity 30% to 70% 101 2395.25 2380 101 2395.25 2380 70.5 72.2 70.6 67.7 2380 0 0 (k 0.6) (100.0) (0.0) (0.0) 57.9 66.5 58.1 40.5 2380 0 0 (k 3.4) (100.0) (0.0) (0.0) COMMENTS: REVIEWED BY: DATE: (p/?/UZ Page 2 17 ARGUS 418-026 Page 1 of 2 Product Code Product Desc: Lab Number: Lot Code: Entered: CERTIFIED RODENT DIET MEAL LO123118-1 AUG 28 01 2A 8/30/2001 Assay PROTEIN FAT ACID (HYDRO ) 1 - ( Analysis 7 1 22.6 5.66 l O R G A N O P H O S P H A T E S * l ~O]RGANOPHOSPHATES IPPM I /Diazinon I Disulfoton ?, 11 I I LESS THAN 0 02 [ b c r , t - d H C ] LESS THAN 0 02 r i,I= LESS THAN 0 02 G-tI,-BHC LESS THAN 0 02 ri,wrln LESS THAN 0 02 nu: Jcnlor Liii~~iie LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 Alpha-BHC Chlordane DOT Dieldrin HCB Heptachlor Epoxide Methoxychlor PCB LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0 15 111I!). 'ILII7diet.coin/ceii i fic.d/pwa-spc002.asp 09/27/2001 Page 2 18 1:- I:I[v ,111 .- I,. I l I * I V S I(Aflatuxins (/LESSTHAN 5 PPB Frtr 3rlLlitional information, please contact: : :..i:;iwner Service at (314) 962-1310 - for assay methodology 2.. j i dorrance Haught at (314) 7684362 -- for nutritional interpretation L 8:..,(:.uiiond,IN Manufacturlng Plant at (765) 962-9561 -- all other questions ARGUS 415-026 Page 2 of 2 REVIEWED BY: DATE Page 219 09/27/200 1 Certified Papers Retrieval ARGUS 4 18-026 Page 1 of 2 PROTEIN II [FAT ACID (HYDRO.) II li-MERCURY PHO-SPHORUS LESS THAN 0 . 0 2 5 [ P P M I II 0 701 lORGANOPHOSPHATES[L~]~RGANOPHOSPHATES][PPM] I IlDiazinon Ethion Aldnn Beta-BHC DDE Delta-BHC Endnn Heptachlor Lindane Mirex LESS THAN 0.02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0.02 LESS THAN 0 02 LESS THAN 0 02 LESS THAN 0.02 LESS THAN 0 02 Alpha-BHC Chlordane I LESS THAN 0 02 1 LESS THAN 0 02 DDT LESS THAN 0 02 Dieldnn LESS THAN 0 02 HCB LESS THAN 0 02 Heptachlor Epoxide LESS THAN 0 02 Methoxychlor LESS THAN 0 02 PCB LESS THAN 0 15 Page 220 ARGUS 418-026 Certified Papers Retrieval Page 2 of 2 IAflataxin ]]Aflatoxins ~ILESS THAN s PPB No notes. For additional information. please contact: - 1 ) CustomerService at (314)962-1310 for assay methodology 2) Dr. Dorrance Haught at (314)7684362 -for nutritional interpretation - 3) Richmond, IN Manufacturing Plant at (765) 962-9561 all other questions The lcrm "LESSThan' IS urcd ID r i i n d y fhc l o w ~ lrimil d q w n u l r o o n orthe pmccdure under the conditions cnlplayed The use of the term 'Less Than' docs no1 m p l y that I ~ C C oI f m a l y s were pmrcnt $N.dlnflk- REVIEWED BY: wbi\O\ DATE ' http:/llabdiet.com/certifiecUpwa~spcOO2.asp Page 221 12/20/2001 7 -.-I ARGUS 418-026 Page I 01'2 . . . I ,`.I`:;I ,, I . .11: . I.,I!.'.IX I Product Code: Return to Certified Analysis Retrieval 5002M Product Desc: CERTIFIED RODENT DIET (MEAL) Lab Number: LO128869-2 Lot Code: JAN 01 02 36 Entered: 1212712001 Assay PROTEIN FAT ACID (HYDRO \ [FIBER (CRUDE) 1 ~ A Z y s i s l U n i t s Z1 i[-jl 56- 4.7111% I /CADMIUM [CALCIUM LEAD MERCURY PHOSPHORUS SELENIUM ~ 0 2 [PPM 1 LESS THAN 0 025- 06 2 8 F 1 0 296 `~RGANOPHOSPHATESI[PPMI[ORGANOPHOSPHATES][] i.'..I...lvI(0lsuifoton(yI I1Th1rnet F;TICIDES LESS THAN (10.02 LESS THAN Ilo.02 (IPPM \IPPM 1 l l AND J/;WFCIDES AND IAldrin L- Beta-BHC DOE Delta-BHC Endrin Heptachlor Lindane Mirex [(LESSTHAN 0 02 LESS THAN 0 02 /(Aloha-BHC 8 7 Chlordane II_LE_S- S THAN o 02 I (LESS THAN o 02 LESS THAN 0 02 DDT LESS THAN 0 02 LESS THAN 0 02 Dieldrin LESS THAN 0 02 LESS THAN 0 02 HCB LESS THAN 0 02 LESS THAN 0 02 Heptachlor Epoxide LESS THAN 0 02 LESS THAN 0 02 I LESS THAN 0 02 \Methoxychlor IPCB LESS THAN 0 02 LESS THAN 0 15 1/23/2002 Page 222 ARGUS 418-026 Ccrri ticd Papcrs Retrieval Page 1 of 2 Aflatoxin ]IAflatoxins I LESS THAN 5 w e No notes. For additional information, please contact: - 1) Customer Service at (314) 962-1310 -for assay methodology 2) Dr.Oorrance Haught at (314) 7684362 - for nutritional interpretation 3) Richmond, IN Manufacturing Plant at (765) 962-9561 all other questions Thc icmt 'Lcrr Than' IS used IO r t p b l y the lever l m t t of quint,1atio18or the procedure under the cotiditions cniployed The UY o i the !<mi "Lcrr Than' docs not miply 1 1 a t~mccs 01 ~ n i l y l cvcre prescul .. REVIEWED BY: . ... , . . , : DATE Page 223 1/23/2002 ARGUS 418-026 Lancaster Laboratories wherequalmisa science. Lancarter Laboratories Sample No. WW 3634413 Collected:06/20/2001 10:40 by EA Account Number: 02123 Submitted: 06/20/2001 16:30 Primedica Argus Reported: 06128/2001 at 14:28 57 Union Street Discard: 07/29/2001 Worcester MA 01608 Point #2 Formulation Lab 905 Sheehy Dr Bldg F Grab Water Sample Page I of2 UT No. 00224 00226 00228 00368 01504 0506 01505 Anrlyaza Namm Chloride Ortho-Phosphate as P Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Brormde 00178 00453 00454 00455 00469 00477 00478 00638 01902 01903 01904 01405 01906 01907 91908 01509 01910 01911 01912 01913 01914 01915 01916 @1517 01918 01519 PestacideslPCB`s in Water Gamma BHC - Lindane Heptachlor Aldrin oieldrin Endrin DDT Endrin Aldehyde Alpha BHC Beta BHC Delta BHC Heptachlor Epoxide ODE DDD Chlordane Toxaphene Endosulfan I Endosulfan XI Endosulfan Sulfate PCB-1016 PCB-1221 PCB-1232 PCB-1242 PCB-1248 eca-s:1 4 PCB-1260 01856 Herbicides i n Water Us Numlmr 16887-00-E 13265-44-i 14808-75-8 14797-55-8 16984-48-8 14757-65-0 n.a. k. IcIcraMd ICrauLt < 2.0 < 0.020 c 5.0 < 0.50 < 0.50 < 0.50 < 2.5 58-85-5 76-44-8 309-00-2 60-57-1 72-20-8 50-25-3 7421-93-4 319-84-6 315-85-7 315- 9 6-8 1024-57-3 72-55-5 72-54-8 57-74-4 8001-35-2 55P-98-8 33213-65-9 1031-07-8 12674-11-2 11104-28-2 11141-16-5 53465-21-4 12612-29-6 11057-64-1 :105i-82-5 < 0.0034 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.0034 < 0.094 < 0.0034 < 0.0094 < 0.0094 < 0.0054 < 0.0094 < 0.0054 0.28 c 3.8 < 0.0094 < 0.0094 < 0.028 < 0.94 < 0.94 < 0.54 < 0.94 < 0.94 < 0.94 5 0.54 Lancaner bborsroncr. Inc Aa RICSlMd a t as Qulatatrtion 2.0 0.020 5.0 0.50 0.50 0.50 i.5 Onit. mg/l lag11 mg/l mg/l mq/l mgll mq/l 0.0094 0.0054 0.0094 0.0094 0.0094 0.0094 0.094 0.0094 0.0094 0.0094 0.0094 0.0094 0.0054 0.28 3.8 0.0094 0.0094 0.028 0.54 0.94 0.54 0.94 0.94 0.54 0.54 ug/l ug/l ug/l uq/1 ug/l ug/1 ug/1 uq/1 ug/1 ug/1 ug/l ug/1 Ugll ug/l ug/1 ugl1 uq/1 ug/1 ug/1 ug/1 ug/1 uq/1 ug/1 ug/l ug/1 DiluUon hctor 5 1 5 5 5 5 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Page 224 ARGUS 418-026 Lancaster Laboratories where cpakylsa science. Larbcrster Laboratories Sample No. WW 3634413 Collected:06/20/2001 10:40 by EA Account Number: 0 2 4 2 3 Submitted: 06/20/2001 16:30 Primedica A r g u s Reported: 06/28/2001 at 14:28 5 7 Union Street Discard: 07/29/2001 Worcester M4 01606 Point #2 Formulation Lab 905 Sheehy Dr Bldg F Grab Water Sample Page 2 of2 CkT NO. Analysis N a 01857 01858 05286 05287 05288 05289 05290 05291 05292 05253 08103 2.4-0 2,4,5-TP 2.4,s-r Dalapon Dinoreb Dicamba MCPP MCPA 2.4-OP IDichlorpropl 2,4-0B Pentachlorophenol CkS lhrPkr 54-75-7 93-72-1 93-16-5 75-95-0 88-85-7 1918-00-3 93-65-2 94-74-6 120-36-5 94-82-6 87-86-5 Am Fmaavd Result < 0.40 < 0.045 < 0.0411 < 1.2 < 0.25 < 0.30 < ZOO. < 200. < 0.49 < 0.45 < 0.05 Comnonwealth of Pennsylvania Lab Certification Ho. 36-037 0.45 0.049 0.045 1.2 0.25 0.30 zoo. ZOO. 0.44 0.49 0.05 mts ug/1 ug/1 ug/l ug/l ug/l ug/1 ug/1 ug/l ug/1 uq/1 ug/1 Dilntrop hctor 1 1 1 1 1 1 1 1 1 1 1 c&T No. 00224 00226 00228 00368 01504 01506 01505 00178 01856 00816 00817 hnalyS&n N W Chloride Ortho-Phaiphate as P Sulfate Wit ra t e I J i t roqen Fluoride NltKAte Nitrogen B romlde Pcsticides/PCB's in Water Herbicides in Yater Water Sample Herbicide Extract Water Sample Pest. Extraction Laboratory mehod EPA 300.0 E P A 365.3 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 608 SW-846 8151A SY-846 8151A Chronicle Anrlysas Tzrral8 Data and f i w 1 06/21/2001 1J:ZS 1 06/21/2001 21:OO 1 06/21/2001 14:25 1 06/21/2001 14:.25 1 06/21/2001 14:25 1 06/21/2001 14:25 1 06/21/2001 14:25 1 06/21/2001 19:15 1 06/25/2001 16:12 1 06/22/2001 09:OO EPA 608 1 56/21/2001 04:45 Andy3 t Hark A. BuckWalter Daniel s. S m t h Nark A. Buckwalter Hark A. BuckWalter Hark A. Buckwalter Hark A. Buckwalter Hark A. BuckWalter Anita W. Dale Tiffany A. Leyda Deborah H. Zimmerman DLhtaM nctor 5 1 5 5 5 5 5 1 1 1 Amanda E. wade 1 Lanosier Labofatores.Inc 2415 New Holland Pike PO Box 12425 Lancaster, PA 17605.1425 ?:7-656-2300 Fax: 717-656-2611 2216 Rev. 9/11/00 Page 225 4IP Lancaster Laboratories where quahtyis a science. Laneaster Laboratories Sample No. W W 3671419 Collected:08/20/2001 10:55 by EA Submitted: 0 8 / 2 0 / 2 0 0 1 16:OO Reported: 09/12/2001 at 11:52 Discard: 10/13/2001 Point R 1 905 Formulation Lab Grab Semi-Annual Water Sample Account Number: 02423 Prirnedica Argus 57 Union Street Worcester MA 01608 Page 1 of 1 CaT No. 00259 01746 01749 01751 01755 01766 01772 07035 07036 Arulysis Nap. Hercury BdKlum cadmium Chronuum Lead Silver Zinc Arsenic TR Selenium TR CAS NuPbrr 7439-97-6 1440-39-3 7440-43-0 7440-47-3 7439-92-1 74 40-22-4 144p-66-6 7440-38-2 7782-49-2 L. R m i v r d Rmdt < 0.00020 < 0.100 < 0.0100 < 0.0300 0.100 < 0.0200 < 0.0250 < 0.0100 < 0.0100 As Recmzvrd u t Of Quantitation 0.00020 0.100 0.0100 0.0300 0.100 0.0200 0.0250 0.0100 0.0100 Uruts mg/l mq/l mg/l mg/l mq/l mo/l mg/l mq/l Dllutiom Yrctor 1 1 1 1 1 1 1 1 1 Cornanwealth of Pennsylvania Lab Certification No. 36-037 CXT No. 00254 01746 01749 01751 01755 01766 01772 07035 07036 01848 05713 Andysaa Name xercury Barium camnzum Chromium Lead Silver Zinc Arsenic TR Selenium TR WW SW846 ICP Digest recl WW SU046 Hg Digest (tot Laboratory mw SY-846 sw-846 sw-846 SU-046 SW-846 SW-E46 SW-846 sw-846 51-846 SW-846 7470.4 60108 60108 60108 60108 60108 60108 60108 60108 3005A Chronicle analysis Trial1 Oat0 and T i u 1 OBiZ7/2001 07:29 1 08/22/2001 02:47 1 08/22/2001 02:47 1 08/22/2001 0 2 : 4 7 1 08/28/2001 14:55 1 08/22/2001 02:47 1 08/22/2001 02:47 1 08/22/2001 02:41 1 08/22/2001 02:47 1 08/21/2001 15:30 SW-846 7470A 1 08/24/2001 21:17 Y -or4 -*) Analyst Damar). S. Valentir. David K. Beck David K. Beck D a v i d K. B e c k Jennifer Speck David K. Beck David K. Beck David K. Beck David K. Beck Liana C. Jones Nelli S . Harkaryan Dilution Trctor 1 1 1 1 1 1 1 1 1 1' 1 Page 226 2216 Rev. 9~11IW ARGUS 418-026 Lancaster Laboratories Mere qualityisamknce. Lancaster Laboratories Sample No. UU 3634414 Collected:06/20/2001 10:30 by EA Account Nunber: 0 2 4 2 3 Submitted: 06/20/2001 16:30 Reported: 06/28/2001 at 14:28 Discard: 01/29/2001 Point 13 Analytical Lab 905 Sheehy Dr Bldg B Grab Water Sample Primedica Argus 57 Union Street Worcester MA 01608 Page 1 of 2 UT NO. 00224 00226 00228 00368 01504 01506 Oi505 Rmalysas NIY Chloride Crtho-Phosphate as P Sulfate Nitrate Nitroqen Fluoride N i t r i t e Nitrogen Bromide 00178 00453 00454 00455 00469 00477 00478 00638 01902 01903 01904 01905 0'1906 01907 01908 01909 01310 01911 01912 01913 01314 01915 01916 01417 01918 G1919 Pesticides/PCB's i n water GaImna EHC - L i n d a n e Heptachlor Aldrin Cieldrin Endrin OD? Endrin Aldehyde Alpha EHC B e t a BHC Delta BHC Heptachlor Epoxide DOE 0 OD Chlordane Toxaphene Endosulfan Endosulfan Endosulfan PCB- 1 0 16 PCE- 1 7 2 1 PCB- 1 2 3 2 PCB- 1 2 4 2 PCB-1248 PCE- 1 2 5 1 PCB-1260 I I1 Sulfate 01856 Herbicides i n Water UJ Nubar 16887-00-6 14265-44-2 14808-79-8 14797-55-8 16984-48-8 14797-65-0 n.a. A. W i d hn3t c 2.0 < 0.020 c 5.0 < 0.50 < 0.50 < 0.50 < 2.5 58-89-9 76-44-8 309-00-2 60-57-1 72-20-8 50-25-3 7421-93-4 319-84-6 319-85-7 319-86-8 1021-57-3 72-55-9 72-54-6 57-74-9 8001-35-2 459-58-8 33213-65-9 1031-07-8 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29- 6 11057-69-1 11096-82-5 < 0.0095 < 0.0095 < 0.0095 C 0.0055 < 0.0095 C 0.0095 < 0.095 c 0.0035 < 0.0095 < 0.0095 < 0.0055 < 0.0095 c 0.0095 < 0.29 < 3.8 < 0.0095 < 0.0095 < 0.029 < 1.0 c 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 M E M E R 2525 New Holland Pike PO Boa 12425 bncastcr. PA 17605-2425 717-656-2300Fax 717-656-2681 b htmivrd Lrut of Quamutation 2.0 0.020 5.0 0.50 0.50 0.50 2.5 MLt3 mall mq/l mq/l mq/l mq/l mq/l m9/1 Oi~utim ?actor 5 1 5 5 5 5 5 0.0095 0.0095 0.0095 0.0095 0.0095 0.0095 0.09s 0.0095 0.0095 0.0095 0.0095 0.0095 0.0095 0.29 3.8 0.0095 0.0095 0.029 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ug/1 1 uqll 1 uq/1 1 uq/1 1 uq/l 1 uqll 1 uqll 1 uq/l 1 uq/1 1 ug/l 1 uq/l 1 "g/l 1 uq/l 1 uq/1 1 uq/l 1 ug/l 1 uq/1 1 uq/l 1 uq/l 1 ug/l 1 uq/l 1 uqll 1 uq/l 1 uqll 1 uq/l 1 t 2216 Rev. 91111W Page 227 ARGUS 418-026 Lancaster Laboratories whereq d y bascience. Lancaster Laboratories Sample No. WU 3634414 Collected:06/20/2001 10:30 by Account Number: 0 2 4 2 ? Submitted: 06/20/2001 16:30 Reported: 06/28/2001 at 14:28 Discard: 07/29/2001 Point # 3 Analytical Lab 905 Sheehy Dr Bldg B Grab Water Sample Primedica Argus 5 7 Union Street Worcester MA 01608 Page 2 of 2 CA? No. hnalyau Namm 01851 01858 05286 05287 05288 05289 05290 05291 05292 05293 08103 2,J-D 2.4.5-TP 2.4.5-2 Dalapcn Dinoseb Dicarnba KPP UCPA 2.4-DP IDiChlOrprop, 2.4-DEi Pentachlorophenol CAS Ntdms 44-75-7 93-72-1 53-7 6-5 15-99-0 88-85-7 1918-00-9 93-65-2 94-14-6 120-36-5 94-82-6 87-86-5 Aa mi& haul+ < 0.48 < 0.048 < 0.048 < 1.2 < 0.24 < 0.29 < 190. < 190. c 0.48 < 0.48 < 0.05 k IlrC.LVmd u t of Quantatataon 0.4B 0.048 0. 048 1.2 0.24 0.29 190. 190. 0.48 0.48 0.05 units uqil ug/l ug/1 ug/: uq/1 ug/l ug/l ug/l uq/l uq/l ug/l Commonwealth of Pennsylvania Lab Certification NO. 36-037 Dalutla Retor 1 1 1 1 1 1 1 1 1 1 1 CA!? no. 00224 00226 00228 00368 01504 01506 '21505 00178 01856 00816 00817 Analy8ia N . u Chloride ortho-Phaaphare 1s P Sulfate Nltrate Nitroqen Fluoride Nltrlte Nitrogen Bromide PesticideslPCa's in Yater Herbicides in Water Yater sample Herbicide Extract Water Sample P e s t . Extraction Laboratory neczhod EPA 300.0 EPA 365.3 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 608 SW-846 8151A SU-846 8151A Chronicle Myria Trial0 D a h . n d T i u 1 06/21/2001 14:39 1 06/zi/zooi zi:oo 1 06/21/2001 1 4 : 3 9 I 06/21/2001 14:39 1 06/21/2001 14:35 1 06/21/2001 1 4 : 3 9 1 06/21/2001 14:39 1 06/21/2001 20:05 1 06/25/2001 16:44 1 06/22/2001 05:OO EPA 608 1 06/21/2001 09:45 Andy. t Mark A. BuckWalter Daniel S. Smith Mark A . Buckwalter Mark A. Eiuckwalter Mark A . Buckwalter Mark A . Eiuckwalter Mark A. Buckwalter Anita n. Dale Tiffany A. Lcyda Deborah n. Zimennan Dilutiam -tor 5 1 5 5 5 5 5 1 1 1 hmanda E. Wade 1 242s NCW Holland Prke PO BOX nazs Llncaster PA 17MS-lJ25 777-656-1300 Fax: 717.656-2661 Page 228 ARGUS 418-026 Lancaster Laboratories WEqualrtyis a science. Lancaster Laboratories Sample No. WW 3671420 Collected:08/20/2001 10:50 by EA Submitted: 08/20/2001 16:OO Reported: 09/12/2001 a t 11:52 Discard: 10/13/2001 Point # 2 Analytical Lab 905 Sheehy Sample Semi-Annual Grab Water Account Number: 0 2 4 2 3 Primedica Argus 57 Union Street Worcester MA 016138 Page I of I CAT No. 00255 01746 01745 01751 01755 01766 01712 07035 07036 Analysra N ~ l s Mercury Barium Cadmium Chromrurn Lead Silver zinc A r s e n i c TR S e l e n i u m TR CAS Ihub.r 7439-97-6 7440-39-3 7440-43-9 7440-47-3 7 4 39-52- 1 7440-22-4 7440-66-6 7440-38-2 7782-49-2 Aa IIIcrivrd R.ault < 0.00020 < 0.100 < 0.0100 < 0.0300 < 0.100 < 0.0200 C 0.0250 < 0.0100 < 0.0100 As Rocmavud L r u t Of Quantitrtaon 0.00020 0.100 0.0100 0.0300 0.100 0.0200 0.0250 0.0100 0.0100 Una ta mall W/l mj/l mqll mg/l mg/l mg/l mg/l w/l Dalution Factor 1 1 1 1 1 1 1 1 1 CAT yo. 00259 01746 01144 01151 01755 01766 01772 07035 07036 oi84a 05713 Commonwealth of P e n n s y l v a n i a Lab C e r c i t i c a t i o n No. 36-033 -lyra. w- Mercury Barium Cadmium Chromurn Lead Silver Zinc Arsenic TR Selenium TR Ww 513846 ICP D i g e s t rec) W SW846 H q D i g e s t (tot Laboratory mud S1-946 51-846 SW-846 SU-846 sn-846 su-1146 SW-816 SX-84h SW-846 SW-946 7470A 60108 60108 60108 60108 6oioe 60108 60108 60108 3005A Chronicle Anrlyars T r i a l # D l t m md T i u 1 08/27!2001 07:?0 1 08/22/2001 02:53 1 08/22/2001 02:53 1 08/22/2001 0 2 : 5 3 1 08/28/2001 15:OO 1 08/22/2001 02:53 1 08/22/2001 02:53 1 0e122/2001 0 2 ~ 5 3 1 08/22/2001 C 2 : 5 3 1 08/21/2001 15:30 51-846 74101 1 08/24/2001 21:17 y -&+-D/ Analyst Canary 5. Valentin David K . Beck Oavid K . B e c k Davrd K . Beck Jennifer Speck David K . B e c k Oavid K . Beck David K . Beck David 1.. B e c k Liana C. Jones trelli S . Harkaryan niiutihctar 1 1 1 1 1 1 1 1 1 1 1 Page 229 1216 Rev r/11r00 ~ ~~ ARGUS 418-026 Customer: Attn: FAX # : - A " I C A L LABORATORIES, INC. P . 0 . Baa 319 M, PA 18914 (215) 723-6466 Argus Research, Inc. 905 Sheeby Dr. , Bldg. A Sample number: Date sampled : Horsham, PA 19044 Time sampled : Attn. Dena Lebo Date received: 215-443-8710 Sampled by : 4538-012/13/01 1500 12/13/01 AF Sample source: Rm. 19 Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards or this parameter. Parameter Mu! Result Coliform Bacteria, counts/100 m l c1 Noncoliform Bacteria, counts/100 m l Free Chlorine, mg/l e1 40 1.0 A l l results which are outside the "Maximum C o n t a m i n a n t L e v e l " (MCL) established under the "Safe Drinking Water A c t " are marked by asterisks ( * * ) - Symbol key: c - less than TNTC - too numerous to count ( > 2 0 0 ) mg/l - milligram/liter PA DEP #09-332 NJ DEP #77847 ,- Mary& E. Fedock/ President Page 230 ARGUS 418-026 ABALYl'ICAL LABORATORIBS, INC. p . 0 . Bax 319 aiiumtm, PA 18914 (215) 723-6466 Customer: Argus Research, Inc. 905 Sheehy D r . , Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : Sample source: Chern. Lab Sample number: 4538-01C Date sampled : 12/13/01 Time sampled : 1500 Date received: 12/13/01 Sampled by : AF - ..~3- 3- ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water rmpply, at the time of sampling, meets the EPA and DBP drinking water stwnrtards for this parameter. Parameter Coliform Bacteria, counts/100 m l c1 Noncoliform Bacteria, counts/100 m l Free Chlorine, mg/l cl <1 < 0.1 AU results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * I . <Symbo- llkeesys:than TNTC - t o o numerous to count ( > 2 0 0 ) mg/l - milligram/liter PA DEP #09-332 NJ DEP #77847 M a ~ Em. Fedock/ President Page 23 1 ARGUS 418-026 Lancaster Laboratories Wherequalityisa science. Lanca8t.r Laboratorio. Suuplo No. NW 3760419 Collected:01/16/2002 0O:OO by EA Submitted: 01/17/2002 15:lO Reported: 01/31/2002 at 06:49 Discard: 03/03/2002 Sample Point #l Analytical Lab Semi-Annual Grab Water Sample Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page I of3 AL--1 . CIT wo 00259 01746 01749 01751 01755 01766 01772 07035 07036 00224 00220 00360 01504 01506 07322 01505 Anrlymis NLY Mercury Barrum Cadmium Chmmiw Lead Silver Zinc Arsenic TR Selanzw TR Chlorade Sulfate Nitrate Nitrogen Fluoride Nitrxte Nitrogen Ortho-phosphate Bromrde 00170 00453 00454 00455 00469 00177 00470 00638 01902 01903 01904 01905 01906 01907 31908 01909 21910 31911 Pertacrdes/PCB'a i n water G a m 8 BWC - Lindane Heptachlor Aldozn Dieldrin Endrin p.p-DDT Endrrn Aldehyde Alpha BHC Beta BHC D d t a BnC Heptachlor Epoxide P IP-DDE p.p-DDD Chlordane Toxaphene Endoaultan I Endosulfan :I ~ 1 w9 a r 7439-97-6 7440-39-3 7440-43-9 7440-47-3 7439-92-1 7440-22-4 7440-66-6 7440-30-2 7702-49-2 16017-00-6 - 1 4 0 0 8 - 7 9 - 0 147 9 7 - 5 5 0 16964-40-0 1*797-65-0 14265-44-2 n.a. A8 Paeaived PO8dC c 0.00020 c 0.100 'e 0.0100 < 0.0300 < 0.100 c 0.0200 c 0.0250 < 0.0100 c 0.0100 -2n c 5.0 c 0.50 c 0.50 e 0.50 c 5.0 < 2.5 Received L i m i t of purncitation 0.00020 0. LOO 0.0100 0.0300 0.100 0,0200 0.0250 0.0100 0.0100 10 5.0 0.50 0.50 0.50 5.0 2.5 Dilution ?actor 1 1 1 1 1 1 1 1 1 < 5 5 5 5 5 5 50-09-9 76-44-0 309-00-2 60-57-1 77-20-8 50-29-3 7421-93-4 319- 04-6 319-05-7 319-86-E 1024-57-3 72-55-9 72-54-0 57-74-9 8001-35-2 9 1 5 3 9 2 1 9 3 8- -8 65 - 9 c 0.0099 c 0.0099 < 0.0099 c 0.020 c 0.020 c 0.020 c 0.020 c 0.0099 c 0.0099 < 0.0099 0.0099 c 0.020 c 0.020 $ 0.50 < 1.0 c 0.020 < 0.059 0.0099 0.0099 0.0099 0.020 0.020 0.020 0.020 0.0099 0.0099 0.0099 0.0099 0.020 0.020 0.50 1.0 0.020 0.059 ug/ 1 1 us/ 1 1 ug/l 1 ug/l 1 ug/ 1 1 ug/ 1 1 ug/ 1 1 ug/l 1 us/ 1 1 ug/l 1 ug/ 1 1 ug/ 1 1 ug/ 1 1 us/ 1 1 ug/ 1 1 ug/ 1 1 ug/l 1 Page 232 LZ16 Rev. 9/11/00 ... ARGUS 418-026 4IPLancaster Laboratories wherequ3lqKaxrence Lmca8t.r Laborrtoria8 Sample No. WW 3760419 Collected:01/16/2002 00:oO by .EA Account Number: 02423 submitted: 01/17/2002 1s:io Reported: 01/31/2002 at 0 6 : 4 9 Discard: 03/03/2002 Sample Point #1 Analytical Lab Semi -Rnnual Grab Water Sample Primedica A r g u s 5 7 Union Street Worcester MA 01608 AL- -1 UT no. 01912 01913 01914 01915 01916 01917 019111 01919 -1y.i. NU. Endosulfan Sultace PCB-1016 PCB- 1221 PCB-1232 PCB-1242 PCB-1248 PCB-1254 PCB-1260 01856 Herbicides in Water 01857 01858 05286 05287 052E8 05289 05290 05291 05292 05293 08103 2.4-D 2.4.5-TP 2.1.5-T Dalapon Dinoseb Dicamba UCPP UCPA 2.4-DP IDichlorpmpl 2.4-DS Pencachlorophenol w -or 1031-07-8 12674-11-2 11104-28-2 11141-16-5 53469-23-9 12672-29-6 - 11097-69-1 11096-82 5 A. E m c m i v d RmNl c 0.020 c 0.50 c 1.0 < 0.50 c 0.50 c 0.50 c 0.50 c 0.50 94-7 s - 7 93-72-1 93-76-5 75-99-0 88-85-7 1918-00-9 -93-65-2 94 74-6 120-36-5 94-82-6 87-86-5 c 0.49 c 0.049 < 0.049 c 1.2 c 0.24 c 0.29 200. c 200. c 0.49 c 0.49 < 0.05 The sample received for t h e mecals a n r l y r i s was rUb.IiCced in an upreserved container. Aa numivmd Limit ot Purneitation 0.020 0.50 1.0 0.50 0.50 0.50 0.50 0.50 Ilnit. ug/l ug/l ug/ 1 ug/ 1 ug/l ug/ 1 uq/ 1 ug/ 1 0.49 0.049 0.049 1.2 0.24 0.29 200. 200. 0.49 0.49 0.0s ug/ 1 ug/l ug/l us/ 1 ug/l us/ 1 ug/ 1 u511 ugll ug/ 1 ug/l Dilucion ?.CtOI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 UT NO. 00259 01746 01749 01751 J17S5 &alyia NLP. nercuq Sazium Cadmium Chromium Lead Laboratory Umtbod SU-846 sw-846 SW-846 sw-846 SW-846 7470A SO~OB 6010B SOLOB 60108 Chronicle Analysis Trial) DaCa and 1- 1 01/23/2002 20:59 1 01/25/2002 0 8 : ~ i 01/25/2002 08:28 1 01/25/2002 0 8 ~ 2 8 1 01/29/2002 07:50 hdy.t Nelli S Markaryan J~ oanne u Gates Joanne M Gates Joanne U Caces Joanne U Gates Dilution Pactor 1 1 1 1 1 Page 233 ARGUS 418-026 Lancaster Laboratories where q d t y i s a science. Lancastrr Laboratorims S-1. No. WII 3760419 Collected:01/16/2002 0O:OO by EX Submitted: 01/17/2002 lf:10 Reported: 01/31/2002 at 0 6 : 4 9 Discard: 03/03/2002 Sample Point #1 Analytical L a b Semi-Annual Grab Water Sample Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 XF-1 01766 01772 07035 07036 00224 00128 00368 01504 01506 07322 01505 00178 01856 00816 00817 01848 05713 Silver Zinc Arsenac TR Sclcnium TR Chloride Sulfate Nitrate Nitrogen Fluoride Nitrice Nitrogen Ortho-phosphate Bromide Pasticides/PCB's in Water Herbicides in Wacer Water Sample Herbicide mtracf Water Sample Pest. Extraction WW SW846 ICP Digest ( t o t rec) 'dW SW846 Hg Dlgest SW-846 60108 SY-846 60108 SW-846 60108 5 1 - 0 4 6 60108 EPA 300.0 EPA 3 0 0 . 0 EPA 3 0 0 . 0 EPA 300.0 EPR 300.0 EPA 3 0 0 . 0 EPA 300.0 EPA S O 8 SW-846 B l S l A SW-846 815l.A EPA 6 0 8 SW-846 3005A SW-846 74701 1 01/25/2002 08:'8 Joanne ?( Gdtea 1 1 01/2s/2002 0 8 : 2 8 Joanne U Gates 1 1 01/29/2002 37:SO Joanne 3 Gates 1 Oli25/2002 18:2S Joanne M Gates 1 1 01/18/2002 16:ll Mark A Buckvalcer 5 1 01/18/2002 16:11 Mark A BuckWalter 5 1 01/18/2002 16:ll mark A Buckwaltcr 5 1 01/18/2002 16:ll nark A Buckmalccr 5 1 O l / l 8 / 2 0 0 2 16:ll Mark A Buckwalter 5 1 01/18/2002 16:ll Mark A Buckwaiter 5 1 01/18/2002 16:ll Mark A Buckvalter 5 1 01/24/2002 09128 A n ~ c aU Dale 1 1 01/22/2002 21:43 T i f f u u / A Le* 1 1 01/22/2002 07:10 AmatIda E Wad. 1 1 01/21/2001 0 9 : O O Amanda E wad. 1 1 01/23/2002 21:30 au-xamaria Stipkuvits 1 1 01/23/2002 16:45 N e l h S Markarym 1 Page 234 2216 Rev. 9/11/00 1.. . - ARGUS 418-026 f l P Lancaster where qua/qisa Laboratories science. Lurcastor Lrbor8torims Samplm No. WlV 3760420 Collected:01/16/2002 0o:oo by EA Account Number: 02423 Submitted: 01/17/2002 15:io Reported: 01/31/2002 ac 06 :49 Discard: 03/03/2002 Sample Point #2 Formulation L a b Semi -Annual Grab Water Sample Primedica Argus 5 7 Union Street Worcesfer M A 01608 Page I of5 n--2 UT No. 00259 01746 01749 01751 01755 01766 01772 07035 07036 noam 00228 00368 01504 01506 07322 01505 Analysis Name nercuq Barium Cadmium Chromium Lmad Silver Zinc Arsenic TR Selenium TR Chloride Sulfate Nicrate Nierogen Fluoride N i t r i t e Nitrogen Orcho-phosphate Bromide 00178 00453 00454 00455 00469 00477 J04?8 00638 51902 01903 01904 51905 01906 31907 51908 01909 31910 01911 Pesticides/PCEi'r i n water Camma BHC - Lmdana Heptachlor Aldrin Dieldrin Endrin p.p-DDT Endrin Aldehyde Alpha BHC Beta BWC Delta BHC Hepeachlor Epoxide p.p-DDB p.p-DOD Chlordane ?oxaphene Endosulfan i Endosulfan 11 CAS M u b m r 7439-97-6 7440-39-3 7440-43-9 7440-47-3 7439-92-1 7440-22-4 7440-66-6 7440 -38-2 1782-49-2 16887-00-5 14EOE-79-8 14797-55-0 16984-4s-1 14797-65-0 14265-44-2 n.a. lu n.cmiv-4 Rmsul t < 0.00020 *, 0.100 c 0.0100 c 0.0300 c 0.100 c 0.0200 < 0.0250 c 0.0100 c 0.0100 2.0 c 5.0 c 0.50 c 0.so c 0.50 c 5.0 c 2.5 58-89-9 76-44-a 309-00-2 60-57-1 72-20-8 SO-29-3 7423-93-4 319-84-6 319-85-7 319-86-E 1024-57-3 72-55-9 72-54-8 57-14-9 8001-35-2 959-98-8 31231-65-9 c 0.0098 c 0.0098 c 0.0098 c 0.020 c 0.020 c 0.020 c 0.020 c 0.009E c 0.0098 c 0.0098 c 0.0098 c 0.020 c 0.020 c 0.49 < 1.0 c 0.020 c 0.059 As R m c m i v d L i d + of Quantitatian 0.00020 0,100 0.0100 0.0300 0.100 0.0200 0.0250 0 .OlOO 0.0100 2.0 s.0 0.50 0.50 0.50 5.0 2.5 Dilution Factor 1 1 1 1 1 1 1 r; 5 5 5 5 5 5 0.0098 0.0098 0.0098 0.020 0.020 0.020 0.020 0,0098 0,0098 0.0098 0.0098 0.020 0.020 0.49 1.0 0.020 0.059 ug/ 1 1 ug/ 1 1 ug/l 1 ug/ 1 1 ug/ 1 1 ug/L 1 ug/ 1 1 ug/ 1 1 ug/ 1 1 ug/l 1 ug/ 1 1 ug/ 1 * ug/ 1 ug/ 1 ug/ 1 1 uq/ 1 1 ug/ 1 1 Page 235 ARGUS 418-026 Lancaster Laboratories When?qwllty /s a suence. Laacaatmt Laboratorio8 S l m p h Wo. llW 3760420 Collected:01/16/2002 0 O : O O by EA Account Number: 02423 Submitted: 01/17/2002 15:lO Reported: 01/31/2002 a t 0 6 : 4 9 Discard: 03/03/2002 Sample P o i n t #2 Formulation Lab Semi-Annual Grab Water Sample Primedica Zugua 57 Union Street Worcester MA 01608 Page 2 of 5 FL--2 -U T NO 01912 01913 01914 01915 01916 01917 01918 01919 Aaalymim Y a m Endosulfan Sulface Pa-1016 PCB-1221 PCB-1232 PCB-1242 PCB-1248 KB-1254 PCB-1260 01856 Herbicides in Wacer 01857 01858 OS286 05287 05288 05289 OS290 OS291 OS292 OS293 08103 2.4-0 2.4.5-TP 2.4.5-t Dalapon Dinoreb nicunba WPP HCPA 2.4-DP IDicNorprop) 2.4-08 Pencachlorophcnol cu -r 1031-07-8 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 11096-82-5 u n.c.ir.d nrrvle c 0.020 * 0.49 < 1.0 c 0.49 c 0.49 c 0.49 c 0.49 < 0.49 94-75-7 93-72-1 93-76-5 75-99-0 88-85-7 1911-00-9 93-65-2 94-74-6 120-36-5 94-82-6 87-86-5 < 0.48 * 0.048 < 0.018 c 1.2 < 0.24 < 0.29 < 190. < 190. < 0.40 ' 0.48 < 0.05 The sample received Cor che metals analysis w a s submitted m an unpreserved container. & Racmirrd L i m i t of pureeieation 0.020 0.49 1.0 0.49 0.49 0.49 0.49 0.49 Uni Ca us/ 1 ug/l ug/l us/ 1 us/ 1 us/ 1 us/ 1 us/l Dilucion Factor 1 1 1 1 1 1 1 1 0.48 0.048 0.048 1.2 0.24 0.29 190. 190. 0.48 0.18 0.05 Uq/l 1 us/ 1 1 ug/1 1 ug/l 1 us/ 1 1 uq/ 1 1 ug/l 1 ug/l 1 us/ 1 1 us/ 1 1 ug/ 1 1 UT No. 30259 31746 01149 11751 01155 Analymia N w flercury garrum Cadmium Csromium Lead Laboratory hehd SW-846 SW-846 SW-846 SW-846 SW-846 7470A 60108 60108 60108 60108 Chronicle Anr1y.i. Trial) Oat. md T f M 1 01/23/2002 21:07 1 01/25/2002 08:33 1 01/21/2002 0 8 : 3 3 1 01/25/2002 0 8 : 3 3 1 01/29/2002 0 7 : 5 5 Anr1Y.C Ne111 S Markarym JoaNIe M Gates J O a N I e M Gates Joanne fl Gates Joanna f4 GICer Dilution raceor 1 1 1 1 1 Page 236 ARGUS 418-026 4 PLancaster Laboratories wherequa/@rs aXience. Laneastor Laboratorio8 Sampla No. WIQ 3760420 Collected:01/16/2002 0O:OO by EA Account Number: 02423 Submitted: 01/17/2002 1S:lO Reporced: 01/31/2002 at 0 6 : 4 9 Discard: 03/03/2002 Sample Point #2 Formulation Lab Semi-Annual Grab Water Sample Primedica Argus 5 7 Union Street Worceacer MA 01608 Page 3 of 2 m--2 01766 01772 07035 07036 00224 00228 00368 01504 01506 07122 01505 00178 01856 00816 00817 01848 05713 Silver Zanc xrsenic TR Selenium 1R Chloride Sulfate Nitrate Nitrogen Pluorade Nitrite Nitrogen Orrho-phospbte eromide PesticideslPCEi's in Water Herbicides in Water Water Sample Herbicide Excract Water Sample Peat. Extraction ww sua46 IC? Digest (tot reel w sw846 Hg Digest SW-846 60108 SW-846 6 0 1 0 8 SU-846 60108 SU-846 6 0 1 0 8 EPA 3 0 0 . 0 EPA 100.0 SPA 300.0 EPA 300.0 EPA 3 0 0 . 0 EPA 300.0 EPA 300.0 EPA 608 SU-816 81SLA sw-846 ais= PPA 608 SU-846 3005A SW-946 7 4 7 0 A 1 0 1 / 2 5 / 2 0 0 2 0 8 : 3 3 Joanne I4 Gates 1 1 0 1 / 2 5 / 2 0 0 2 08:31 Joanne U Gates 1 1 01/29/2002 07:55 Joanne U Gates 1 1 0 1 / 2 5 / 2 0 0 2 08:33 J O l M C I Gatea 1 1 0 1 / 1 8 / 2 0 0 2 1 6 : 2 5 nark A Buckwalter 5 1 0 1 / 1 8 / 2 0 0 2 1 6 : 2 5 nark A 8uckwaLter 5 1 0 1 / 1 8 / 2 0 0 2 1 6 : 2 5 nark A Buckvalcer 5 1 01/18/2002 16:25 nark A 8uckralter 5 1 01/18/2002 16:25 nark A Buckralter 5 1 0 1 / 1 8 / 2 0 0 2 1 6 : 2 5 nark A Buckralfer 3 1 0 1 / 1 8 / 2 0 0 2 1 6 : 2 5 nark A Buckvalter 5 1 01/74/2002 09:18 Anita n Dale 1 1 01/22/2002 22:16 TiffUrY A La+ 1 1 01/21/2002 01:30 w d a E Wade 1 1 01/21/2002 09:oo Amanda E Wade 1 1 0 1 / 2 3 / 2 0 0 2 21:30 mamaria Stipkovits I 1 0 1 / 2 3 / 2 0 0 2 1 6 : 4 S Nelli S narkaman 1 Page 237 ARGUS 418-026 ANALYTICAL LABORATORIBS, INC. P.0. Box 319 CBALFONT, PA 18914 (215) 723-6466 Customer: Argus Research 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-8587 Sample source: Chem. Lab Sample number: 4012-021 Date sampled : 01/03/02 0 Time sampled : 1440 Date received: 01/03/02 Sampled by : AF ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards or t h i s parameter. Earameter Mu Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 m l Total Chlorine, mg/l <1 c1 < 0.1 All results which are outside t h e "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * ) . c Symbo- llekseys :than TNTC - too numerous to count ( > 200) m g / l - milligram/liter PA DEP #09-332 NJ DEP # 7 7 8 4 7 @TJ9& Mary& E. Fedock/ President Page 238 ARGUS 418-026 ANAL?lTICAL LABORA'KIRIBS, P.O. Bax 319 CIEIALFONT, PA 18914 (215) 723-6466 INC. Customer: Argus Research 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-8587 Sample source: Room 19 Sample number: 4012-02D Date sampled : 01/03/020 Time sampled : 1440 Date received: 01/03/02 Sampled by : AP ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter Coliform Bacteria, counts/100 m l Noncoliform Bacteria, counts/100 m l Total Chlorine, mg/l 'M.cLi <1 Result <1 <1 0.2 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * I . Symbol key : C - l e s s than m c - too numerous to count ( > 200) mg/l - rnilligram/liter PA DEP #09-332 NJ DEP $ 7 7 8 4 7 A-f Mary& E. Fedock/ President Page 239 ARGUS 418-026 ANALYTICAL LABORATORIES, INC. P . O . Box 319 CElALFONT, PA 18914 (215) 723-6466 Customer: Argus Research 905 Sheehy D r . , Bldg. A Horsham, PA 19044 Attn. Dena Lebo Rttn: 215-443-8710 FAX #: 215-443-8587 Sample source: Chem. L a b Sample number: 4207-02A Date sampled : 02/21/02 Time sampled : 1200 Date received: 02/21/02 Sampled by : AF ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter KL Coliform Bacteria, counts/100 m l c1 Noncoliform Bacteria, counts/100 m l Total Chlorine, mg/l Result c1 cl c 0.1 3. All results which are outside the l'MaximumContaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * I . e Symb-ollkeesys:than TNTC - t o o numerous t o count ( 5 2 0 0 ) mg/l - milligram/liter PA DEP #09-332 NJ DEP #77847 *y42a Mary& E. Fedock/ President Page 240 ARGUS 418-026 ANALYTICAL LABORATORIBS, P . O . BOX 319 CBAwPoKT, PA 18914 (215) 723-6466 INC. Customer: Argus Research 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-8587 Sample source: Room 1 Sample number: 4287-02D Date sampled : 02/21/02 Time sampled : 1200 Date received: 02/21/02 Sampled by : AF ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DBP drinking water standards f o r this parameter. Parameter Kxl Coliform Bacteria, counts/100 m l el Noncoliform Bacteria, counts/loo m l Total Chlorine, mg/l Result cl <1 0 -4 All results which are outside the " M a x i m u m Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * I . Symbol key : C - less than TNTC - too numerous to count ( > 200) mg/l - milligram/liter PA DEP # 0 9 - 3 3 2 NJ DEP #77847 MaryaM E. Fedock/ President Page 241 __ ARGUS 418-026 ANALYTICAL LAwlRAToRIBS, P.O. Bar 319 (gALFoHT, PA 18914 (215) 723-6466 INC. Customer: Aryus Research 905 Sheehy Dr., Bldg. A Horsham. PA 19044 A t t n . Dena Lebo Attn: 215-443-8710 FAX #: 215-443-8587 *=rc Sample source: R o a n 9 Bldg. 905 Sample number: 4385-02B Date sampled : 03/14/02 Time sampled : 1030 Date received: 03/14/02 Sampled by : AF ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP dripking water standards for a i s parameter. Earametex XL Result Coliform Bacteria, counts/100 ml c1 Noncoliform Bacteria, counts/100 m l Free Chlorine, mg/l c1 <1 1.0 A l l results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * I . Symbol key: < - less than TNTC - too numerous to count ( > 2 0 0 ) mg/l - milligram/liter PA DEP #09-332 NJ DEP #77847 *&fJ$2&&/ Mary$& E. Fedock/ President Page 242 ARGUS 418-026 ANALYTIICAZ, IABORATORIBS, INC. P.O. Box 319 W N T , PA 18914 (215) 723-6466 Customer: Argus Research 905 Sheehy Dr., Sldg. A Horsham, PA 19044 At-. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-8587 Sample source: Formulation Bldg. 905 Sample number: 4385-02D Date sampled : 03/14/02 Time sampled : 1030 Date received: 03/14/02 Sampled by : AF Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for th+ parameter. * -.. Parameter 4 Coliform Bacteria, counts/100 ml Noncolifom Bacteria, counts/100 m l Free Chlorine, mg/l <1 <1 1.0 All results which are outside the "Maximurn Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * ) . - Symbol key : < - less than TNTC too numerous to count ( > 200) mg/l - milligram/liter PA DEP #09-332 NJ DEP #77847 ... . . -. .- Page 243 ARGUS 418-026 Explanation of Symbols and'Abbreviations me lbllowng dehes c o m m symbds and ebbreviafions used in rspomng tschntca/data: N.D. lNTC IU ,ihodcm C Cd none detected Too NumsrousTOCount International Units miwmhoJan degrees Celsius (diet) calories BYaL MPN CP Unltr Mu F Ib. Wow MinimumQuantitabonLevel Mort Probable Number ~ b a l t c h h p k t i n a t eunits nephelometric turbidity units degrees Fahrenheit pound@) m.q milliequivalcnts g gram(s) U9 miuognm(s) ml millilitcr(s) m3 cubic metar(s) k# mg I ul fib a5 umlml kilogam(S) miUigram(s) lihr(S) miaolirjS) fibers greater than 5 microns in length per mi < less than - The number following the sign is the limit ofauanb'tation.the smallest amount of analyte which can be reliably determirted using this specific test > greater than - PP" pa- per million One ppm is equivalentto o m milligram per kilogram (mglkg). or one gram per million grams. For aqueous liquids, pprn is usually taken to be quivalmt to milligramsper liter (mg/l), because one liter of water has a weight very dose to a kilogram. For gases or vapors, one ppm is equivalent to one microliter of gas per liter of gas. PPb Dry wolght buk parts per billion Results printed under thk heading have been adjustedfor mistun?content. This increases the arulyte weight concentration to approximate the value present m a similar sample without moisture. U.S. EPA dah qualiliers: Organic Qualifierr A B C D E J N P U X.YZ TIC is a possible aldolcondensation product Analyte was ako detected in the blank Pesticide result confirmed by GClMS Compound quantitated on a diluted sample Concentration ex-s tho calibration range of me instrument Estimated value Presumptive evidence of a compound (ncsonly) Concentration difference between primary confirmation columns >25% Compound was not detected Defined in case narrative Inorganic Qualifiers 8 Value is <CRDL. but 2IDL E Estimated due to interference 1111 Duplicateinjection pncision not met N Spike sample not within control limits S Method of standard additions (MSA) used for Cakulation U Compound was not detected W Post digestion spike out of control limb Duplicate analysis not within control limits + Correlationcoefficient for MSA <0.995 Tests resub relate only to the sample tested. Clients should bs aware that a critical step in a chemicalor microbiological analysis is the collection of the sample. Unless the sample analyzed is h l y representative of the bulk of materialinvoked. the test results wiU be meaningless. If y w have questions regardingthe proper techniques of collecting samples, please contad us. We cannot be held responsiblefor sample integrity, however, unless sampling has been performedby a member of our staff. This report shall not be reproduced except in full, without the written approval of the laboratory. - WARRANTY AND LIMITS OF LkBluTv In accepting analyticalwork. we warrant the accuracy of test resultsfor the sample as submitted. THE FOREGOING EXPRESS WARRANTY IS WCLUSIVE AND IS GIVEN IN LIEU OF ALL OTHER WARRANTIES. EXPRESSED OR IMPLIED. WE DISCLAIMANY OTHER WARFUNTIES. EXPRESSED OR IMPLIED, INCLUDINGA WARRANTY OF FITNESS FOR PARTICULAR PURPOSE AND WARRANlY OF MERCHANTABILITY. IN NO EVENT SHALL LANCASTER ' 4BORATORIES BE UABLE FOR-INDIRECT.SPECIAL, CONSEQUENTIAL. OR INCIDENTALDAMAGES INCLUDING, BUT NOT .TED TO, DAMAGES FOR LOSS OF PROFIT OR GOODWILL REGARDLESS OF (A) THE NEGLIGENCE (EITHER SOLE OR SURRENT) OF LANCASTER LABORATORIES AND (8)WHETHER LANCASTER LABORATORIESHAS BEEN INFORMEDOF THE POSSIBILITY OF SUCH DAMAGES. We accept no legal responsibility for me purposes for which the dicnl uses the lest results. No purchase order or other order for work shall bc accepted by LancarlerLaboratorieswhich indudes any conditions that vary from rhe Standard Terms and Conditions of LaneasterLaboratories and we herebyob~ec!to any umllidingterms contained in any acceptance or order submitted by dient. ARGUS 4 18-026 APPENDIX H OPHTHALMOLOGY REPORT Page 245 ARGUS 418-026 LIONEL F. RUBIN, V.M.D. 1116 Saint Andrews Road Bryn Mawr, PA 19010 (610) 520 9430 Argus Research 905 Sheehy Drive, Bldg. A Horsham PA 19044-1297 March 22, 2002 Attention: John F. Barnett Ophthalmoscopic examination of Protocol 418-026 rats was performed March 15, 2002 (terminal examination). The following abnormality was seen: 1) Chromodacryorrhea bilaterally in rat 14878 (group 3) No other abnormality was seen. There is no indication of compound related ocular disease. Lionel F. Rubin, V.M.D. Page 246 ARGUS 4 18-026 LIONEL F. RUBIN, V.M.D. 1116 Saint Andrews Road Bryn Mawr, PA 19010 (610) 520 9430 Argus Research 905 Sheehy Drive, Bldg. A Horsham PA 19044-1297 December 12, 2001 Attention: John F. Barnett Pretest ophthalmoscopic examination of Protocol 418-026 rats was performed December 12, 2001. The following abnormalities were seen: 1) lntravitreal hemorrhage in the left eye of female rat 1 2) Iritis unilaterally in the left eye of female rat 49 No other abnormality was seen. The rats with ocular abnormalities may be excluded from this study if convenient. Lionel F. Rubin, V.M.D. Page 247 ARGUS 418-026 APPENDIX I POSITIVE CONTROL DATA Page 248 -- ARGUS 418-026 Historical Control Data This Functional Observation Battery Standard Operating Procedure and Studies conducted to document the training and competencyof the technical staff and Motor Activity Negative Control Data and Positive Control Data are available at the Testing Facility. Page 1 Page 249 ARGUS 418-026 Summary Information for Functional Observation Battery Study Number - Title 012406- V d & h of F d d ObscnmtionalBattay and MotwActivity M ~ s r nUtsing PositiveTcst Substancs In-Life Start 12/89 Test Substance Dosage Information Numbs of m y k g Dosagd 50 1 7 physostigmine 0.75 15 I DDT 75 1 I 012-014-Nmmtox~tyEvaluation of Positive Control Substar~cepin CrkCD@BR VAF/F'b@ Rats 9/9 I acrykmidc 40 1 9 IDPN 200 1 3 carbaryl 75 5 I DDT 75 5 1 triadimefon 200 5 1 012-015 -Ncurotoxidty Evduatioa of DDT in Cd:CD@BR VAFPhU@ Rats 3/92 DDT 75 I I 012-017-Nmtoxiaty Evaluation of Positive COnhoI sub-cs in Crl:CD(BBR VAF/Pb@Rati -5/92 aclyklmide 40 IDPN 200 40 DDT 75 damphctaminc 4.0 012-022 - Neurotoxicity Evaluation of Carbarylin CrkCDBBRVAF/PhU@Rats 1002 carbaryl 40,200 5 1 012-031 - Neurotoxicity Evaluation of Positive Conhol Substances in Cr1:CDBBRVAF/PlusO Rats -7/93 amylamide 45 IDPN 250 40 DDT 75 d-amphdaminc 4 Page 2 Page 250 -- 012-056- Nmtoxkity EraluatiOnOf Positive ControlSubstancnin . <XL-CD@BRVAF/PhsQ Rats - 0 12-075 Neurotoxicity Evaluationof Positive Conirol Substances in CrlrCD@BRVAFPhrs@Rats 012-08I -N~mtoxiOityEvaiuation of PositiveControl Substances in C&CD@BR VAFPb@Rats 11/95 acrykmide 45 rnPN 250 hwl 40 DDT 75 d-ampheiamine 4.0 3/98 acryhmide 30 trimahyltill 8 MK-801 0.3 carbaryl 100 DDT 100 11/01 acrykmide 30 IDPN 250 d-amphctamine 40 buyl 100 DLYT 100 ARGUS 418-026 Page 3 Page 251 . Summary Information for Motor Activity Study - Titie In-Life Start 012-011-Th~Ass~~t0fM0tor Activity in N d and Adult Rodents wing Passive Infirarcd smsors 5/9 1 012-014- Ncurob~xiatyEvaluation of Positive Control Sobstances m Crtl=DFDBR VAF/Plw@ Rats 9i9 1 012-016-MotorActivityEvaluation in CrkCDBBR VAFiPb@ Rabr AdministeredC h l o ~ m a d nme d dAmphetamine (Positive Cmtrol Study) ARGUS 4 18-026 Test Substance Dosage Information mgkg Numba of -6 d-amphctaminc 0.75,l.S. 4 1 1 c h l o l p m ~ e 1.2.4 I 1 acrylami& 40 1 9 IDPN 200 I 3 haryt 75 5 I DDT 75 5 I tliadimcfon 200 5 1 012-058 - NcrPotoxidty Evaluation of Positive Control Substances m Crl:CDOBR VAFiPIustB Rats 4/96 45 d-amphdamhe 0.75 himdhyltin 8 MK-801 10 I 10 I. I 1 I 1 1 Page 4 Page 252 ARGUS 4 18-026 APPENDIX J HEMATOLOGY AND CLINICAL CHEMISTRY REPORT Page 253 ARGUS 418-026 STUDY ID: ARGUS #418-026 STUDY NO: 060-062 __ Animal ID UBC RBC THSN/CU HM MILL/CU HH ~ ~~ GROUP: I-H 1485 1 14852 14853 14854 14855 14856 14857 14858 14859 14860 22.4 15.4 23.5 14.0 15.5 17.9 18.7 16.2 12.4 13.9 8.38 7.85 7.91 7.37 7.82 8.38 7.85 7.80 7.45 6.80 MEAN SD N 17.0 3.66 10 7.76 0.469 10 HGB GRAHS/DL 17.1 16.3 16.4 16.0 16.4 18.3 17.0 16.6 15.4 14.8 16.4 0.96 10 GROUP: 2-M 14861 14862 14863 14864 14865 14866 14867 14868 14869 14870 HEAN SD N 17.3 16.1 13.7 16.1 14.3 17.1 14.4 13.1 22.9 9.4 15.4 3.50 10 7.28 7.29 8-06 7.53 7.05 7.24 7.43 7.89 8.41 7.99 7.62 0.443 10 16.6 15.7 16.4 16.0 15.6 16.3 15.4 16.2 16.3 15.6 16.0 0.41 10 HCT HCV HCH % CU MICRONS P I C 0 GRAMS 46.4 55.4 20.4 43.3 55.2 20.8 45.2 57.1 20.7 42.6 57.8 21.7 44.0 56.3 21 .o 48.1 57.4 21.8 45.5 57.9 21 -7 44.8 57.4 21.3 41.6 55.9 20.7 40.3 59.2 21 .8 44.2 57.0 21 -2 2.32 1.25 0.53 10 10 10 41.8 57.4 22.8 42.2 57.9 21.5 44.1 54.7 20.3 43.7 58.1 21.2 41 .O 58.1 22.1 42.3 58.4 22.5 41.5 55.9 20.7 42.7 54.1 20.5 45.8 54.5 19.4 41.9 52.4 19.5 42.7 56.2 21 .I 1.44 2.12 1 .I8 10 10 10 SEX: HALE HCHC % PLT THSN/CU MH 36.9 37.6 36.3 37.6 37.3 38.0 37.4 37.1 37.0 36.7 37.2 0.50 10 1711 1181 1532 1127 1718 875 1032 1197 1248 1328 1235 241.3 10 39.7 37.2 37.2 36.6 38.0 38.5 37.1 37.9 35.6 37.2 37.5 1.11 10 1106 991 1186 1108 1130 1032 1201 938 1476 1433 1160 175.6 10 Page 254 ARGUS 4 18-026 ~ _____ ~ ___^_____ Study Report for Hematology ~ ~___ INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD : TERMINAL _--_-------c---I----______________I_____--- STUDY ID: ARGUS #418-026 STUDY NO: 06&062 ________^____ _--_11---1------1---_--L-----------I---------------------------------- SEX: MALE Animal I D WBC RBC HGB HCT MCV MCH THSN/CU MM MILL/CU MM GRAMS/DL % CU MICRONS P I C 0 GRAMS -------------_______------------~--------------~----------------------------- GROUP: 3-M 14871 14.2 7.10 15.2 40.8 57.5 21.4 14872 14.7 7.77 15.5 40.9 52.6 19.9 14873 16.9 7.68 15.9 42.5 55.4 20.7 14874 14.1 7.75 15.4 42.2 54.5 19.9 14875 13.3 7.98 16.5 44.6 55.9 20.7 14876 14877 11.8 7.36 15.2 41.4 56.2 20.7 19.6 7.49 15.2 42.1 56.2 20.3 14878 14879 7 4880 14.9 7.63 16.2 43.5 57.0 21.2 15.7 7.14 15.1 39.2 54.9 21 .I 12.0 7.63 15.8 42.2 55.3 20.7 MCHC % PLT THSN/CU MM 37.3 37.9 37.4 36.5 37.0 36.7 36.1 37.2 38.5 37.4 1202 1122 1314 1240 973 882 1118 983 1173 1330 MEAN SD N 14.7 2.31 10 7.55 0.282 10 15.6 0.48 10 41.9 1 .so 10 55.6 I .3a 10 20.7 0.51 10 37.2 0.69 10 1134 149.4 10 GROUP: 4-M 14881 14882 14883 14884 14885 14886 14887 14888 14889 14890 HEAN SD N 13.3 17.3 20.7 11.8 15.8 14.1 15.9 11.9 15-.6- 15.2 2.80 9 7.48 6.96 7.04 7.12 8.01 7.83 6.81 6.69 6.7-3- 7.19 0.481 9 16.8 15.7 15.5 15.5 16.4 15.2 15.0 14.4 -- 1 4 . 6 15.5 0.78 9 44.0 40.1 39.8 41.7 44.2 41.5 40.9 38.1 - 37.9 40.9 2.24 9 58.8 57.6 56.6 58.5 55.2 53.0 60.0 56.9 -56.3 57.0 2.08 9 22.5 22.6 22.0 21 .8 20.5 19.4 22.0 21.5 21.7 I 21.6 1.01 9 38.2 39.2 38.9 37.2 37.1 36.6 36.7 37.8 38.5 -- 37.8 0.96 9 946 1073 1202 1096 1275 1429 1202 1143 1455 -- 1202 165.0 9 LABCAT HE4.43 Page 255 10-APR-2002 Study Report for Hematology INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD: TERMINAL ARGUS 418-026 Animal I D WBC REC HG B HCT MCV HCH THSN/CU HM MILL/CU HM GRAHS/DL % CU MICRONS PIC0 GRAMS ---------------____--------------------------------------------------------------- GROUP: 1-F I4891 9.8 6.90 16.3 43.3 62.7 23.6 I4892 9.7 7.38 16.0 43.6 59.1 21.7 14893 21.5 7.30 16.0 44.4 60.8 21.9 I4894 9.6 7.18 15.4 42.7 59.5 21.4 14895 16.3 6.96 15.7 42.9 61.7 22.6 14896 12.6 7.39 16.2 44.4 60.1 21.9 i4897 13.2 7.44 16.3 45.2 60.8 21.9 I4898 I4899 9.7 6179 15.5 40.6 59.8 22.8 10.1 7.66 17.0 46.1 60.2 22.2 14900 9.6 6.71 14.8 40.3 60.0 22.1 MEAN SD N 12.2 3.95 10 7.17 0.315 10 15.9 0.61 10 43.3 1.85 10 60.5 1 .oa 10 22.2 0.64 10 GROUP: 2-F 14901 14902 14903 14904 I4905 14906 14907 14908 14909 14910 MEAN SD N 8.4 10.1 11.9 15.5 7.2 13.5 15.8 12.1 12.8 7.5 11.5 3.10 10 7.20 6.58 6.89 7.a 6.92 7.27 6.99 6.61 6.87 7.10 6.95 0.226 10 15.6 15.0 16.1 16.2 15.7 15.8 16.6 14.8 15.5 16.3 15.8 0.57 10 42.5 40.1 42.4 43.8 40.8 42.7 44.0 39.8 41.2 43.8 42.1 1.56 10 59.0 60.9 61- 5 62.2 58.9 58.7 62.9 60.2 60.0 61.7 60.6 1.47 10 21.7 22.8 23.4 23.0 22.7 21.7 23.7 22.4 22.6 23.0 22.7 0.65 10 HCHC i! PLT THSN/CU MM 37.6 36.7 36.0 36.1 36.6 36.5 36.1 38.2 36.9 36.7 36.7 0.69 10 1052 1153 1092 1110 1214 1211 1192 1162 926 1079 1119 88.2 10 36.7 37.4 38.0 37.0 38.5 37.0 37.7 37.2 37.6 37.2 37.4 0.54 10 956 1139 1320 1435 891 1025 992 1307 1107 1402 1157 195.8 10 Page 256 ARGUS 418-026 ~ ~- GROUP: 3-F 14911 14912 14913 14914 14915 14916 14917 I 491a 14919 14920 ~ 7.3 11.7 12.2 9.3 19.9 15.6 11- 6 14.5 9.9 a. 5 MEAN SD N 12.1 3.77 10 GROUP: 4-F 14921 14922 14923 14924 14925 14926 14927 i 4928 14929 14930 MEAN SD N 6.4 9.5 12.1 19.2 10.5 12.8 16.4 15.4 17.0 15.8 13.5 3.94 10 7.16 7.02 7.00 6.85 7.83 7.19 7.18 7.49 7.14 6.76 7.16 0.309 10 7.48 6.83 6.48 7.02 7.11 6.62 6.70 7.11 7.02 7.16 6.95 0.297 10 16.2 14.6 15.2 15.2 16.9 16.2 15.4 15.8 15.9 15.0 15.6 0.69 10 16.0 15.8 14.5 16.1 15.5 14.3 14.0 16.0 14.8 16.0 15.3 0.82 10 43.3 40.4 40.7 41.1 47.4 44.4 41.9 43.1 43.2 41 .O 42.7 2.14 10 43.2 41 .a 38. a 41.9 42.0 39.6 38.5 42.7 40.5 42.8 41.2 1.71 10 60.5 57.5 58.2 60.0 60.5 61- 7 58.4 57.5 60.5 60.6 59.5 1 .50 10 57.8 61.2 59.9 59.7 59.1 59.8 57.5 60.0 57.7 59.8 59.2 1.21 10 22.6 20.8 21.7 22.2 21.6 22.5 21.4 21 .I 22.3 22.2 21 .a 0.61 10 21.4 23.1 22.4 22.9 21 .a 21.6 20.9 22.5 21.1 22.3 22.0 0.75 10 37.4 36.1 37.3 37.0 35.7 36.5 36.8 36.7 36.8 36.6 36.7 0.51 10 895 1180 1185 1280 1288 987 1535 1158 1030 1268 1181 181.6 10 37.0 37.8 37.4 38.4 36.9 36.1 36.4 37.5 36.5 37.4 37.1 0.70 10 1159 862 1622 743 1242 980 1327 a52 1441 1030 1126 283.3 10 Page 257 Study Report f o r Hematology ARGUS 4 18-026 STUDY ID: ARGUS #418-026 STUDY NO: 060-062 SEX: MALE Animal ID. MPV CU MICRONS PT seconds APTT seconds NRBC COUNT Lymphocyte THSN/CU tlH Segmented THSN/CU MM Bands THSN/CU MH Monocytes THSN/CU MM GROUP: 1 -M 14851 7.5 14852 8.2 14853 7.2 14854 7.2 14855 7.5 14856 8.0 14857 7.6 14858 7.7 14859 8.1 14860 7.5 13.9 14.2 13.9 13.7 13.4 14.1 12.8 13 :3 13.7 13.6 22.7 30.6 25.9 27.1 25.7 21.7 23.8 24.6 21 . I 23.8 0 20.2 0.7 0.0 0.7 0 10.6 3.9 0.0 0.8 0 21.2 1.6 0.0 0.2 0 11.8 2.1 0.0 0.7 0 13.2 1.7 0.0 0.5 0 13.2 4.1 0.0 0.5 0 12.5 5.6 0.0 0.6 0 12.2 3.1 0.0 0.6 0 9.5 2.4 0.0 0.4 0 11.4 1.7 0.0 0.8 MEAN SD N 7.7 0.35 10 13.7 0.41 10 24.7 2.80 10 0 13.6 2.7 0.0 0.5 0.0 3.93 1.48 0.00 0.23 10 10 10 10 10 ........................................................................ GROUP: 2-M 14861 7.7 14.7 34.0 0 14.5 1.9 0.0 0.5 14862 8.1 14.2 26.7 0 13.2 2.1 0.0 0.6 14863 7.9 14.2 29.5 0 11.9 I .4 0.0 0.4 14864 7.1 13.9 22.2 0 13.7 1.6 0.2 0.3 14865 7.0 14.9 27.9 0 9.6 4.4 0.0 0.1 14866 8.2 14.3 24.2 0 13.9 1.7 0.0 0.9 14867 8.2 14.6 23.1 0 11.5 2.6 0.0 0.3 14868 14869 9.2 13.7 23.0 8.1 13.9 23.9 1 10.6 1.4 0.0 0.5 0 20.4 2.5 0.0 0.0 14870 8.6 13.5 22.3 0 6.4 2.7 0.0 0.2 MEAN SO N 8.0 0.65 10 14.2 0.45 10 25.7 3.84 10 0 12.6 2.2 0.0 0.4 0.3 3.66 0.90 0.06 0.26 10 10 10 10 IO Page 258 ARGUS 4 18-026 GROUP: 3-M 14871 7.4 14872 9.5 14873 7.7 14874 8.4 14875 7.5 14876 8.2 148?7 7.7 14878 8.1 14879 8.0 14880 7.3 14.0 14.4 14.1 13.7 12.9 15.0 14.0 15:2 13.5 13.8 30.9 28.7 24.4 26.1 23.5 23.0 23.5 27.4 21.5 27.2 0 12.4 1.4 0.0 0.4 0 13.4 0.9 0.0 0.4 0 15.0 1.2 0.0 0.5 0 10.6 2.5 0.0 0.7 0 11.0 1.9 0.0 0.3 0 9.0 2.5 0.0 0.2 0 16.3 2.4 0.0 0.2 0 11.8 2.2 0.0 0.6 0 13.2 1.7 0.0 0.8 0 9.4 2.2 0.0 0.4 MEAN SD N 8.0 0.64 10 14.1 0.68 10 25.6 2.94 10 0 12.2 1.9 0.0 0.5 0.0 2.34 0.57 0.00 0.20 10 10 10 10 10 ---- ________________-___-1-___1_____1__----------- GROUP: 4-M 74881 7.0 15.2 32.1 0 9.8 2.3 0.0 1.1 14882 7.8 15.8 30.6 0 14.5 1.9 0.0 0.5 14883 7.6 14.2 31.3 0 17.8 2.1 0.0 0.4 14884 7.7 13.6 22.4 0 10.0 1.2 0.0 0.4 14885 8.5 13.5 21.4 0 14.1 1.4 0.0 0.3 14886 8.1 13.8 22.4 0 12.4 1.3 0.0 0.4 14887 7.9 13.6 22.5 2 13.4 2.1 0.0 0.3 14888 7.0 13.8 24.4 0 10.4 1 .I 0.0 0.5 14889 14890 7.2 - 13.9 -- 22-.8- - 0 14-.4- 1-.1- 0.-0- -0 . 2 MEAN SD N 7.6 0.51 9 14.2 0.80 9 25.5 4.43 9 0 13.0 1.6 0.0 0.5 0.7 2.62 0.48 0.00 0.26 9 9 9 9 9 (--I - Data U n a v a i l a b l e LABCAT HE4.43 Page 259 ARGUS 418-026 ~-~ _ _ _ ~ ~ ~ ~ _ ~~ ~~~ Animal I D MPV PT CU MICRONS seconds ~~ ~_. GROUP: I-F 14891 7.8 14892 7.3 14893 7.2 14894 7.3 14895 7.4 14896 7.9 14897 7.0 14898 7.7 14899 7.5 14900 6.5 13.2 13.2 12.8 13.0 13.4 13.6 13.2 13.1 13.3 13.8 MEAN SD ti 7.4 0.41 10 13.3 0.29 10 APTT seconds 15.4 20.8 22.2 20.9 22.5 22.6 20.5 23.5 19.7 23.6 21.2 2.41 10 GROUP: 2-F 14901 14902 14903 14904 14905 14906 14907 14908 14909 14910 MEAN SD N 7.4 7.1 6.7 7.0 7.6 8.3 7.4 7.0 6.9 6.9 7.2 0.47 10 13.7 14.3 13.8 13.2 12.5 13.2 13.4 13.2 13.7 13.7 13.5 0.49 10 20.1 38.8 17.9 23.5 20.7 24.6 23.2 24.1 23.3 26.6 24.3 5.68 10 NRBC COUNT Lymphocyte THSN/CU HM Segmented THSN/CU HH Bands THSN/CU M M Monocytes THSN/CU HR 0 8.4 0.9 0.0 0.2 0 7.0 2.3 0.0 0.2 0 19.4 1.3 0.0 0.0 0 8.2 1.2 0.0 0.2 0 13.9 1.8 0.0 0.2 0 10.7 1.5 0.0 0.3 0 10.6 2.4 0.0 0.0 0 8.2 1.2 0.0 0.2 0 9.1 0.5 0.0 0.2 0 7.7 1 .s 0.0 0.1 0 10.3 1.5 0.0 0.2 0.0 3.76 0.59 0.00 0.10 10 10 10 10 10 0 7.5 0.8 0.0 0.0 0 9.2 0.9 0.0 0.0 1 9.3 2.3 0.0 0.1 0 13.0 1.9 0.0 0.3 0 6.1 1 .o 0.0 0.1 0 11.7 1.2 0.0 0.4 0 12.2 2.5 0.0 0.6 0 9.8 2.1 0.0 0.0 0 11.4 1.3 0.0 0.1 0 5.6 I .6 0.0 0.3 0 9.6 1.6 0.0 0.2 0.3 2.56 0.61 0.00 0.20 10 10 10 10 10 Page 260 ARGUS 418-026 ~~~~~~~ ~~__~_ STUDY ID: ARGUS #41a-026 STUDY NO: 060-062 SEX: FEMALE _______________________________________I----------------_----_-------_----__________ Animal ID MPV CU MICRONS PT seconds APT1 seconds NRBC COUNT Lymphocyte THSN/CU flM Segmented THSN/CU MM Bands THSN/CU M M Monocytes THSN/CU M M ----_________-____-_______I_____________----_------------------------_------- GROUP: 3-F 14911 7.2 14912 7.2 14913 6.9 14914 7.3 14915 7.9 14916 8.0 14917 6.5 14918 7.3 14919 7.0 14920 6.9 13.5 13.3 13.2 13.8 13.2 12.4 13.0 12.6 13.2 13.2 19.8 29.1 22.2 27.0 24.5 25.3 20.0 25.7 27.2 20.9 0 5.1 1.9 0.0 0.2 0 10.6 0.7 0.0 0.0 0 10.6 1.2 0.0 0.1 0 7.5 I.7 0.0 0.0 0 18.7 0.6 0.0 0.0 1 12.8 2.0 0.0 0.6 0 7.9 3.4 0.0 0.1 0 8.4 5.5 0.0 0.3 0 7.4 2.1 0.0 0.3 0 7.1 1.4 0.0 0.0 MEAN SD N 7.2 0.45 10 13.1 0.40 10 24.2 3.27 10 0 9.6 2.1 0.0 0.2 0.3 3.87 1.45 0.00 0.20 10 10 10 10 10 GROUP: 4-F 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 MEAN SD N 7.2 7.4 6.7 7.2 6.7 7.4 7.9 7.9 6.2 7.1 7.2 0.53 10 13.5 13.6 13.5 - 13.4 13.5 13.4 13.3 13.2 13.1 13.4 0.16 9 24.1 33.4 30.1 - 29.2 20.7 22.6 19.7 18.6 22.3 24.5 5.17 9 0 5.4 0.7 0.0 0.1 0 7.9 1.3 0.0 0.1 0 10.4 1.o 0.0 0.4 0 17.9 1.o 0.0 0.4 0 9.5 0.8 0.0 0.2 0 10.5 2.3 0.0 0.0 0 15.7 0.7 0.0 0.0 0 14.0 1.1 0.0 0.3 0 15.5 1.2 0.0 0.2 0 13.9 1.4 0.0 0.5 0 12.1 1.2 0.0 0.2 0.0 3.94 0.47 0.00 0.18 10 10 10 10 10 LABCAT HE4.43 Page 261 10-APR-2002 ARGUS 418-026 STUDY ID: ARGUS #41&026 STUDY NO: 060-062 _________________I____I_---------------------------------------------__-__-___ Animal ID Eosinophil THSN/CU MM Basophils THSN/CU MM Abnormal L THSN/CU MM Other THSN/CU MM _________I___-___----------------------------I_---------_____----_____________I____I_- GROUP: 1-M 14851 0.9 0.0 0.0 0.0 14852 0.2 0.0 0.0 0.0 14853 0.5 0.0 0.0 0.0 14854 0.0 0.0 0.0 0.0 14855 0.2 0.0 0.0 0.0 14856 0.0 0.0 0.0 0.0 14857 0.0 0.0 0.0 0.0 14858 0.2 0.0 0.2 0.0 14859 0.1 0.0 0.0 0.0 14860 0.0 0.0 0.0 0.0 ~ S E X : MALE MAN SD N 0.2 0.29 10 0.0 0.00 10 0.0 0.06 10 0.0 0.00 10 ...................................................................................... GROUP: 2-M 14861 0.3 0.0 0.0 0.0 14862 0.2 0.0 0.0 0.0 14863 0.0 0.0 0.0 0.0 14864 0.3 0.0 0.0 0.0 14865 0.1 0.0 0.0 0.0 14866 0.5 0.0 0.2 0.0 14867 0.0 0.0 0.0 0.0 14868 0.5 0.0 0.0 0.0 14869 0.0 0.0 0.0 0.0 14870 0.1 0.0 0.0 0.0 MEAN SD N 0.2 0.19 10 0.0 0.00 10 0.0 0.06 10 0.0 0.00 10 Page 262 -ARGUS 4 18-026 Animal I D Eosinophil MSN/CU MM Basophils THSN/CU M M Abnormal L THSN/CU M M Other THSN/CU M M GROUP: 3-M 14871 0.0 0.0 0.0 0.0 14872 0.0 0.0 0.0 0.0 14873 0.2 0.0 0.0 0.0 14874 0.1 0.0 0.1 0.0 14875 0.1 0.0 0.0 0.0 14876 0.1 0.0 0.0 0.0 14877 0.6 0.0 0.2 0.0 14870 0.1 0.0 0.1 0.0 14879 0.0 0.0 0.0 0.0 14880 0.1 0.0 0.0 0.0 MEAN 0.1 0.0 0.0 0.0 SD 0.18 0.00 0.07 0.00 N 10 10 10 10 -_-__I___---I-_------------- GROUP: 4-M 14881 0.1 0.0 0.0 0.0 14882 0.3 0.0 0.0 0.0 14883 0.4 0.0 0.0 0.0 14884 0.1 0.0 0.1 0.0 14885 0.0 0.0 0.0 0.0 14886 0.0 0.0 0.0 0.0 14887 0.2 0.0 0.0 0.0 14888 0.0 0.0 0.0 0.0 14889 14890 0.-0- 0.-0- 0.-0- --0 . 0 MEAN 0.1 0.0 0.0 0.0 SD 0.15 0.00 0.03 0.00 N 9. 9 9 9 (--I - Data Unavailable LABCAT HE4.43 -------------- 10-APR-2002 Page 263 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 ~ ~ ~ _ _ _ _ _ ~~~~~~ Animal I D Eosinophil THSN/CU M M Basophils THSN/CU N M Abnormal L THSN/CU M M Orher THSN/CU M M -__---_-_____-__-________l_________l___--------_-~--____------------_--------_-- GROUP: I - F 14891 0.3 14892 0.2 14893 0.6 14894 0.1 14895 0.3 148% 0.1 14897 0.3 I41398 0.1 14899 0.3 14900 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 MEAN SD N 0.3 0.1s 10 0.0 0.00 10 0.0 0.08 10 0.0 0.00 10 GROUP: 2-F 14901 14902 14903 14904 14905 I4906 14907 14908 14909 14910 MEAN SD N 0.2 0.0 0.2 0.3 0.0 0.1 0.s 0.2 0.0 0.1 0.2 0.16 10 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00 10 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00 10 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00 10 SEX: FEMALE Page 264 ARGUS 418-026 STUDY ID: ARGUS #41a-o26 STUDY NO: 060-062 SEX: FENALE GROUP: 3-F 14911 0.1 14912 0.4 14913 0.1 14914 0.1 14915 0.6 14916 0.2 14917 0.2 14918 0.3 14919 0.1 14920 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 MEAN SD N 0.2 0.17 10 0.0 0.00 10 0.0 0.03 10 0.0 0.00 10 __----_______I GROUP: 4-F 14921 0.2 0.0 0.0 0.0 14922 0.2 0.0 0.0 0.0 14923 0.2 0.1 0.0 0.0 14924 0.0 0.0 0.0 0.0 14925 0.0 0.0 0.0 0.0 14926 0.0 0.0 0.0 0.0 14927 0.0 0.0 0.0 0.0 14928 0.0 0.0 0.0 0.0 14929 0.2 0.0 0.0 0.0 14930 0.0 0.0 0.0 0.0 NEAN SD N 0.1 0.10 10 0.0 0.03 10 0.0 0.00 10 0.0 0.00 10 Page 265 ARGUS 41 8-026 Group: I - M MEAN SD N Group: 2-tl MEAN SD N Group: 3-M MEAN SO N Group: 4-fl MEAN SD N 17.0 3.66 10 7.76 0.469 10 15.4 3.50 10 7.62 '0.443 10 14.7 2.31 10 7.55 0.282 10 15.2 2.80 9 7.1% 0.481 9 16.4 0.96 10 16.0 0.41 10 15.6* 0.48 10 15.5* 0.78 9 44.2 2.32 10 57.0 1.25 10 42.7 1.44 10 56.2 2.12 10 41.W 1.50 10 55.6 1.38 10 4O.W 2.24 9 57.0 2.08 9 21.2 0.53 10 21.1 1.18 10 20.7 0.51 10 21.6 1.01 9 37.2 0.50 10 1235 241.3 10 37.5 1.11 10 1160 175.6 10 37.2 0.69 10 1134 149.4 10 37.8 0.96 9 1202 165.0 9 7.7 0.35 10 8.0 0.65 10 8.0 0.64 10 7.6 0.51 9 *-Significant Difference from Control P < .Os LABCAT HE4.43 *-Significant Difference from Control P < .01 ~ __ 10-APE2002 Page 266 ARGUS 418-026 Group: 1-M MEAN SD N Group: 2-M MEAN SD N Group: 3-M MEAN SD N Group: 4-M MEAN SD N 13.7 0.41 10 14.2 0.45 10 14.1 0.68 10 14.2 0.80 9 24.7 2.80 10 25.7 3.a4 10 25.6 2.94 10 25.5 4.43 9 0 13.6 2.7 0.0 0.5 0.2 0.0 0.0 3.93 1.48 0.00 0.23 0.29 0.00 10 10 10 10 10 10 10 0 12.6 2.2 0.0 0.4 0.2 0.0 0.3 3.66 0.90 0.06 0.26 0.19 0.w 10 10 10 10 10 10 10 0 12.2 1.9 0.0 0.5 0.1 0.0 0.0 2.34 0.57 0.00 0.20 0.18 0.00 10 10 10 10 10 10 10 0 13.0 1.6 0.0 0.5 0.1 0.0 0.7 2.62 0.48 0.00 0.26 0.15 0.00 9 9 9 9 9 9 9 Page 267 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 ~ ARGUS 418-026 SEX: MALE Group: 2-M MEAN SD N Group: 3-M MEAN SD N Group: 4-H HEAN SD N 0.0 0.06 10 0.0 0.00 10 0.0 0.07 10 0.0 0.00 10 0.0 0.03 9 0.0 0.00 9 Page 268 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 ANALYSIS OF VARIANCE FOLLOWED B Y DUNNETT'S PROCEDURE SEX: FEMALE TEST(s) : UNITS: UBC RBC THSN/CU MM M I L L / C U MM HGB GRAMS/DL HCT MCV MCH Z CU MICRONS P I C 0 GRAMS MCHC PLT MPV % THSN/CU MH CU MICRONS Group: I-F MEAN SD N 12.2 3.95 10 7.17 0.315 10 15.9 0.61 10 43.3 1.85 10 60.5 1-08 10 22.2 0.64 10 36.7 0.69 10 1119 88.2 10 7.4 0. L1 10 G r o u p : 2-F MEAN SD N 11.5 3.10 10 6.95 0.226 10 15 .a 0.57 10 42.1 1.56 10 60.6 1.47 10 22.7 0.65 10 37.4* 0.54 10 1157 195.8 10 7.2 0.47 10 G r o u p : 3-F MEAN SD N 12.1 3.77 10 7.16 0.309 10 15.6 0.69 10 42.7 2.14 10 59.5 1.50 10 21.8 0.61 10 36.7 0.51 10 1181 181.6 10 7.2 0.45 10 G r o u p : 4-F MEAN SD N 13.5 3.94 10 6.95 0.297 10 15.3 0.B2 10 41.2 1.71 10 59.2 1.21 10 22.0 0.75 10 37.1 0.70 10 1126 283.3 10 7.2 0.53 10 LABCAT HE4.43 Page 269 10-APR-2002 ARGUS 418-026 Group: I - F MEAN SD N Group: 2-F MEAN SD N Group: 3-F MEAN SD N Group: 4-F MEAN SD N 13.3 0.29 10 21.2 2.41 10 13.5 0.49 10 24.3 ,5.68 10 13.1 0.40 10 24.2 3.27 10 13.4 0.16 9 24.5 5.17 9 0 10.3 1.5 0.0 0.2 0.3 0.0 0.0 3.76 0.59 0.00 0.10 0.15 0.00 10 10 10 10 10 10 10 0 9.6 1.6 0.0 0.2 0.2 0.0 0.3 2.56 0.61 0.00 0.20 0.16 0.00 10 10 10 10 10 10 10 0 9.6 2.1 . 0.0 0.2 0.2 0.0 0.3 3.87 1.45 0.00 0.20 0.17 0.00 10 10 10 10 10 10 10 0 12.1 1.2 0.0 0.2 0.1 0.0 0.0 3.94 0.47 0.00 0.18 0.10 0.03 10 10 10 10 10 10 10 Page 270 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 ARGUS 4 18-026 SEX: FEMALE Group: 2-F MEAN SD N Group: 3-F MEAN SD N Group: 4-F MEAN SD N 0.0 0.00 10 0.0 0.00 10 0.0 0.03 10 0.0 0.00 10 0.0 0.00 10 0.0 0.00 10 Page 271 ARGUS 418-026 14851 14852 14853 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other Wac Nucleated Red Cells Lymphocytes Segmented Neutrophi1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other Wac Nucleated R e d Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other uac 0 90 20.2 3 0.7 0 0.0 3 0.7 4 0.9 0 0.0 0 0.0 0 0.0 22.4 0 69 10.6 2s 3.9 0 0.0 5 0.8 1 0.2 0 0.0 0 0.0 0 0.0 15.4 0 90 21.2 7 1.6 0 0.0 1 0.2 2 0.5 0 0.0 0 0.0 0 0.0 23.5 Page 272 ARGUS 418-026 14854 14855 14856 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other Wac Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other UBC 0 a4 11.8 15 2.1 0 0.0 1 0.1 0 0.0 0 0.0 0 0.0 0 0.0 14.0 0 85 13.2 11 1.7 0 0.0 3 0.5 1 0.2 0 0.0 0 0.0 0 0.0 15.5 0 74 13.2 23 4.1 0 0.0 3 0.5 0 0.0 0 0.0 0 0.0 0 0.0 17.9 Page 273 ARGUS 418-026 14857 14859 Nucleated R e d Cells Lymphocytes Segmented Neutrophi 1s Bands Ronocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red C e l l s Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red C e l l s Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other UBC 0 67 12.5 30 5.6 0 0.0 3 0.6 0 0.0 0 0.0 0 0.0 0 0.0 18.7 0 75 12.2 19 3.1 0 0.0 4 0.6 1 0.2 0 0.0 1 0.2 0 0.0 16.2 0 77 9.5 19 2.4 0 0.0 3 0.4 1 0.1 0 0.0 0 0.0 0 0.0 12.4 Page 274 ARGUS 418-026 Lymphocytes Segmented N e u t r o p h i l s Bands Ronocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other WBC a2 11.4 12 1.7 0 0.0 6 0.8 0 0.0 0 0.0 0 0.0 0 0.0 13.9 Page 275 ARGUS 418-026 14861 I 4862 14863 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 84 1 4 . 5 11 1.9 0 0.0 3 0.5 2 0.3 0 0.0 0 0.0 0 0.0 17.3 0 82 13.2 13 2.1 0 0.0 4 0.6 1 0.2 0 0.0 0 0.0 0 0.0 16.1 0 87 11.9 10 1.4 0 0.0 3 0.4 0 0.0 0 0.0 0 0.0 0 0.0 13.7 Page 276 ARGUS 418-026 14864 14865 14866 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 85 13.7 10 1.6 1 0.2 2 0.3 2 0.3 0 0.0 0 0.0 0 0.0 16.1 0 67 9.6 31 4.4 0 0.0 1 0.1 1 0.1 0 0.0 0 0.0 0 0.0 14.3 0 81 13.9 10 1.7 0 0.0 5 0.9 3 0.5 0 0.0 1 0.2 0 0.0 17.1 Page 277 ARGUS 418-026 Animal I D TERMINAL ------ CNT-A-B-S---- -- ---_____--________ ___----l____l_l- 14867 Nucleated Red Cells Lymphocytes Segmented Neutrophi1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 80 11.5 18 2.6 0 0.0 2 0.3 0 0.0 0 0.0 0 0.0 0 0.0 14.4 7 4868 Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 1 81 10.6 11 1.4 0 0.0 4 0.5 4 0.5 0 0.0 0 0.0 0 0.0 13.1 14869 Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Is Basophi 1s Abnormal Lymphocytes Other UBC 0 89 20.4 11 2.5 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 22.9 Page 278 ARGUS 418-026 Page 279 ARGUS 418-026 14872 14873 Nucleated Red C e l l s Lymphocytes Segmented Neutrophi 1s Bands Honocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d CelLs Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other UBC 0 91 13.4 6 0.9 0 0.0 3 0.4 0 0.0 0 0.0 0 0.0 0 0.0 14.7 0 89 15.0 7 1.2 0 0.0 3 0.5 1 0.2 0 0.0 0 0.0 0 0.0 16.9 Page 280 10-APR-2002 ARGUS 418-026 --- Study Report f o r Hematology --------- -----__----___-_------------------ ____-I_ -- _ -I__ _ -- _- WHITE DIFFERENTIAL DATA 14875 14876 Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi I s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 83 11.0 14 1.9 0 0.0 2 0.3 1 0.1 0 0.0 0 0.0 0 0.0 13.3 0 76 9.0 21 2.5 0 0.0 2 0.2 1 0.1 0 0.0 0 0.0 0 0.0 11.8 Page 281 ARGUS 418-026 14877 14878 14879 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other WBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UEC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other WBC 0 83 16.3 12 2.4 0 0.0 1 0.2 3 0.6 0 0.0 1 0.2 0 0.0 19.6 0 79 11.8 15 2.2 0 0.0 4 0.6 1 0.1 0 0.0 1 0.1 0 0.0 14.9 0 84 13.2 11 1.7 0 0.0 5 0.8 0 0.0 0 0.0 0 0.0 0 0.0 15.7 Page 282 ARGUS 418-026 Page 283 ARGUS 418-026 14881 14882 14883 Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other, WBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophi1s Bands Monocytes Eosinophi I s Basophi 1s Abnormal Lymphocytes Other WBC 0 74 9.8 17 2.3 0 0.0 a 1 .I 1 0.1 0 0.0 0 0.0 0 0.0 13.3 0 84 14.5 11 1.9 0 0.0 3 0.5 2 0.3 0 0.0 0 0.0 0 0.0 17.3 0 86 17.8 10 2.1 0 0.0 2 0.4 2 0.4 0 0.0 0 0.0 0 0.0 20.7 Page 284 ARGUS 418-026 14884 14885 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UEC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocy t es Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleared Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other WBC 0 a5 10.0 10 1.2 0 0.0 3 0.4 1 0.1 0 0.0 1 0.1 0 0.0 11.8 0 89 14.1 9 1.4 0 0.0 2 0.3 0 0.0 0 0.0 0 0.0 0 0.0 15.8 0 88 12.4 9 1.3 0 0.0 3 0.4 0 0.0 0 0.0 0 0.0 0 0.0 14.1 Page 285 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 _______------_----_____--------------- Animal ID GROUP: 4-H 14887 I 4aaa I 4889 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Honocytes Eosinophi I s Basophi 1s Abnormal Lymphocytes Other uac Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other uac Nucleated R e d Cells Lymphocytes Segmented Neutrophi I s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UB c SEX: MALE ----_--------_----___ TERH INAL CNT ABS 2 a4 13.4 13 2.1 0 0.0 2 0.3 1 0.2 0 0.0 0 0.0 0 0.0 15.9 0 87 10.4 9 1.1 0 0.0 4 0.5 0 0.0 0 0.0 0 0.0 0 0.0 11.9 0 92 14.4 7 1.1 0 0.0 I 0.2 0 0.0 0 0.0 0 0.0 0 0.0 15.6 LAECAT HE4.43 Page 286 IPAPR-2002 ARGUS 4 18-026 Animal ID 14890 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other uac TERMINAL CNT ABS Page 287 ARGUS 4 18-026 14892 14893 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other WBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other UBC 0 72 7.0 24 2.3 0 0.0 2 0.2 2 0.2 0 0.0 0 0.0 0 0.0 9.7 0 90 19.4 6 1.3 0 0.0 0 0.0 3 0.6 0 0.0 1 0.2 0 0.0 21.5 Page 288 ARGUS 418-026 STUDY ID: ARGUS #41&026 STUDY NO: 060-062 Animal I D GROUP: I-F 14894 14895 14896 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other Wac Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other Wac TERMINAL CNT ABS 0 85 8.2 12 1.2 0 0.0 2 0.2 1 0.1 0 0.0 0 0.0 0 0.0 9.6 0 85 13.9 11 1.8 0 0.0 1 0.2 2 0.3 0 0.0 1 0.2 0 0.0 16.3 0 85 10.7 12 1.5 0 0.0 2 0.3 I 0.1 0 0.0 0 0.0 0 0.0 12.6 SEX: FEMALE Page 289 ARGUS 4 18-026 14897 14898 14899 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes osinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 80 10.6 18 2.4 0 0.0 0 0.0 2 0.3 0 0.0 0 0.0 0 0.0 13.2 0 a5 8.2 12 1.2 0 0.0 2 0.2 1 0.1 0 0.0 0 0.0 0 0.0 9.7 0 90 9.1 5 0.5 0 0.0 2 0.2 3 0.3 0 0.0 0 0.0 0 0.0 10.1 Page 290 ARGUS 4 18-026 Page 291 ARGUS 418-026 14901 14902 14903 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophi I s Basophi 1s Abnormal Lymphocytes Other WBC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UEC Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other UBC 0 89 7.5 9 0.8 0 0.0 0 0.0 2 0.2 0 0.0 0 0.0 0 0.0 8.4 0 91 9.2 9 0.9 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 10.1 1 78 9.3 19 2.3 0 0.0 1 0.1 2 0.2 0 0.0 0 0.0 0 0.0 11.9 Page 292 ARGUS 4 18-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 GROUP: 2-F 14904 I 45405 14906 Nucleated Red Cells Lymphocytes Segmented Neutrophiis Bands Monocytes Eosinophi I s Basophi I s Abnormal Lymphocytes Other WBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands tlonocyt es Eosinophi 1s Basophi 1s Abnomal Lymphocytes Other UBC 0 84 13.0 12 1.9 0 0.0 2 0.3 2 0.3 0 0.0 0 0.0 0 0.0 15.5 0 85 6.1 14 1.0 0 0.0 1 0.1 0 0.0 0 0.0 0 0.0 0 0.0 7.2 0 87 11.7 9 1.2 0 0.0 3 0.4 1 0.1 0 0.0 0 0.0 0 0.0 13.5 SEX: FEMALE Page 293 ARGUS 418-026 14907 14908 14909 Nucleated Red C e l l s Lymphocytes Segmented Neutrophils Bands Monocytes Eosi nophiLs Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red C e l l s Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 77 12.2 16 2.5 0 0.0 4 0.6 3 0.5 0 0.0 0 0.0 0 0.0 15.8 0 81 9.8 17 2.1 0 0.0 0 0.0 2 0.2 0 0.0 0 0.0 0 0.0 12.1 0 89 11.4 10 1.3 0 0.0 1 0.1 0 0.0 0 0.0 0 0.0 0 0.0 12.8 Page 294 ARGUS 418-026 Page 295 ARGUS 4 18-026 Animal ID 14911 14912 14913 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other WBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocyte t Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC TERMINAL CNT ABS 0 70 5.1 26 1.9 0 0.0 3 0.2 1 0.1 0 0.0 0 0.0 0 0.0 7.3 0 91 10.6 6 0.7 0 0.0 0 0.0 3 0.4 0 0.0 0 0.0 0 0.0 11.7 0 a7 10.6 10 1.2 0 0.0 1 0.1 1 0.1 0 0.0 1 0.1 0 0.0 12.2 LABCAT HE4.43 -- - - - I - - - - - - - 10-APR-2002 Page 296 ARGUS 418-026 14914 14915 I4916 Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Easophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eos i nophiLs Easophi 1s Abnormal Lymphocytes Other UBC 0 81 7.5 18 1.7 0 0.0 0 0.0 1 0.1 0 0.0 0 0.0 0 0.0 9.3 0 94 18.7 3 0.6 0 0.0 0 0.0 3 0.6 0 0.0 0 0.0 0 0.0 19.9 1 82 12.8 13 2.0 0 0.0 4 0.6 1 0.2 0 0.0 0 0.0 0 0.0 15.6 Page 297 ARGUS 418-026 I 491a 14919 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi Ls Basophi 1s Abnormal Lymphocytes Other WBC 0 58 8.4 38 5.5 0 0.0 2 0.3 2 0.3 0 0.0 0 0.0 0 0.0 14.5 0 75 7.4 21 2.1 0 0.0 3 0.3 1 0.1 0 0.0 0 0.0 0 0.0 9.9 Page 298 ARGUS 4 18-026 Page 299 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 Study Report f o r Hematology GROUP: 4-F ARGUS 418-026 SEX: FEMALE 14921 14922 14923 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Easophi 1s Abnormal Lymphocytes Other UEC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophils Basophi 1s Abnormal Lymphocytes 0tt;er UEC Nucleated R e d Cells Lymphocytes Segmented Neutrophils Bands Ronocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 85 5.4 11 0.7 0 0.0 1 0.1 3 0.2 0 0.0 0 0.0 0 0.0 6.L 0 83 7.9 14 1.3 0 0.0 1 0.1 2 0.2 0 0.0 0 0.0 0 0.0 9.5. 0 86 10.4 8 1 .o 0 0.0 3 0.4 2 0.2 1 0.1 0 0.0 0 0.0 12.1 Page 300 ARGUS 418-026 14924 14925 14926 Nucleated Red Cells Lymphocytes Segmented Neutrophi 1s Bands Ronocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Nonocytes osinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d Cells Lymphocyres Segmented Neutrophils Bands Nonocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 93 17.9 5 1 .o 0 0.0 2 0.4 0 0.0 0 0.0 0 0.0 0 0.0 19.2 0 90 9.5 8 0.8 0 0.0 2 0.2 0 0.0 0 0.0 0 0.0 0 0.0 10.5 0 82 10.5 18 2.3 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 12.8 Page 301 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 GROUP: 4-F 14927 I 4928 14929 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d C e l l s Lymphocytes Segmented Neutrophils Bands Nonocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC Nucleated R e d C e l l s Lymphocytes Segmented Neutrophils Bands Nonocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes Other UBC 0 96 15.7 4 0.7 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 16.4 0 91 14.0 7 1.I 0 0.0 2 0.3 0 0.0 0 0.0 0 0.0 0 0.0 15.4 0 91 15.5 7 1.2 0 0.0 1 0.2 1 0.2 0 0.0 0 0.0 0 0.0 17.0 SEX: FEMALE Page 302 ARGUS 418-026 Animal I D 14930 Nucleated Red Cells Lymphocytes Segmented Neutrophils Bands Monocytes Eosinophi 1s Basophi 1s Abnormal Lymphocytes other UBC TERMINAL CNT A85 0 88 13.9 9 1.4 0 0.0 3 0.5 0 0.0 0 0.0 0 0.0 0 0.0 15.8 Page 303 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 06C-062 -~- Animal I D TP ALE GLU g/dL g/dL mg/dL ___-----_---_-___-_-________I___________------------------T_------------_------- GROUP: I - M 14851 7.0 4.4 143 14852 6.6 4.1 165 14853 7.1 4.2 203 14854 6.4 3.9 142 14855 6.2 4.0 170 14856 6.9 4.1 224 14857 6.3 3.9 139 14858 6.3 4.3 141 14859 6.3 4.1 168 14860 6.5 3.9 1U MEAN SD N 6.6 0.33 10 4.1 0.17 10 164 29.2 10 GROUP: 2-H 14861 14862 14863 14864 14865 14866 14867 14868 16869 14870 MEAN SD N 6.5 6.3 6.5 6.4 6.4 6.8 6.6 6.5 6.5 6.8 6.5 0.16 10 4.1 3.9 4.2 3.9 3.9 4.4 4.2 4.2 3.8 4.1 4.1 0.19 10 168 139 164 165 141 140 160 156 176 160 157 12.8 10 CHOL ng/dL 49 49 62 45 47 52 85 49 39 60 54 12.9 10 39 52 70 71 43 60 58 25 58 38 51 14.9 10 I-BIL mg/dL 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.03 10 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.00 10 BUN w/dL 17 14 14 13 15 17 15 13 15 14 15 1.4 10 CREAT mg/dL 0.3 0.3 0.3 0.2 0.2 0.3 0.3 0.3 0.3 0.2 0.3 0.05 10 16 0.3 15 0.2 14 0.2 14 0.2 12 0.2 14 0.2 12 0.3 14 0.2 16 0.3 12 0.2 14 0.2 1.5 0.05 10 10 SEX: PlALE ALT U/L 42 37 39 34 39 55 U 42 46 44 42 5.8 10 48 46 52 35 31 52 43 46 43 51 45 7.1 10 LABCAT CC4.43 Page 304 ~ 10-APR-2002 ARGUS 418-026 ____ -__-_-- _---_---____________ __ Study Report __ for Clinical Chemistry -----___-_-___-I_---------__-_ INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD : TERMINAL STUDY ID: ARGUS #418-026 STUDY NO: 060-062 _____ Animal ID TP ALB GLU CHOL T-BIL g/dL g/dL mg/dL mg/dL mg/dL _______---____~---I-----------------I_-----_-----______I_____________--_------- GROUP: 3-M 14871 6.3 3.9 160 14872 6.7 4.0 204 14873 6.1 4.0 184 14874 6.6 4.1 192 14875 6.4 4.1 1 72 14876 6.3 4.0 142 14877 6.6 4.2 147 14878 6.5 4.0 161 14879 6.3 3.8 139 14880 6.3 4.0 165 43 0.1 48 0.1 42 0.1 49 0.1 56 0.1 57 0.1 39 0.1 28 0.1 45 0.1 43 0.1 BUN WldL 16 17 14 14 13 12 15 11 14 18 CREAT mg/dL 0.3 0.3 0.2 0.3 0.3 0.2 0.3 0.3 0.3 0.4 SEX: MALE ALT U/L 38 46 38 32 37 40 45 40 42 47 MEAN SD N 6.4 4.0 167 45 0.1 14 0.3 41 0.19 0.11 21.6 8.4 0.00 2.2 0.06 4.6 10 10 10 10 10 10 10 10 GROUP: 4-M 14881 6.7 4.4 162 40 0.1 16 0.3 51 14882 6.4 4.0 148 39 0.1 15 0.2 40 14883 7.2 4.2 181 69 0.1 15 0.3 34 14884 6.4 4.1 149 64 0.1 14 0.2 51 14885 6.5 3.9 161 48 0.1 1s 0.3 45 14886 6.9 3.9 171 63 0.1 18 0.3 29 14887 6.3 3.9 182 70 0.1 13 0.2 47 14888 5.4 3.5 157 31 0.1 16 0.3 so 14889 14890 6.-3- 4-.-2 183 56 0.1 -- 15 0.3 -4-3 MEAN SD N 6.5 4.0 166 53 0.1 15 0.3 43 0.50 0.26 13.8 14.4 0.00 1.4 0.05 7.8 9 9 9 9 9 9 9 9 LABCAT CC4.43 Page 305 10-APR-2002 ARGUS 418-026 GROUP: I - F 14891 7.3 5.1 140 59 0.1 15 14892 7.4 4.8 161 99 0.1 15 14893 7.9 5.5 I 78 a2 0.1 17 14894 7.0 4.7 180 77 0.1 14 14895 6.6 4.5 155 70 0.1 14 I 4896 7.3 4.8 137 70 0.1 16 14897 6.9 4.3 156 87 0.1 17 14898 7.7 3.4 173 a0 0.1 14 14899 6.8 4.6 142 66 0.1 17 14900 7.2 4.9 i 38 67 0.1 20 MEAN SD N 7.2 4.9 156 76 0.1 16 0.40 0.38 16.7 11 .a 0.00 1.9 10 10 10 10 10 10 _---__--_I__--------_______I_________c__--- GROUP: 2-F 1 4901 7.0 4.5 156 62 0.1 16 14902 7.8 5.4 141 64 0.1 16 14903 6.9 4.7 145 66 0.1 16 14904 7.1 4.5 185 ao 0.1 la 14905 7.4 4.9 180 72 0.2 la 14906 7.8 5.1 194 59 0.1 15 14907 6.9 4.7 151 69 0.1 15 14908 7.0 4.8 171 59 0.1 14 14909 7.1 4.8 128 70 0.1 13 1491 0 7.3 4.5 149 91 0.1 16 MEAN SO N 7.2 4.8 160 69 0.1 16 0.34 0.29 21.4 10.0 0.03 1.6 10 10 10 10 10 '10 0.4 0.4 0.4 0.4 0.3 0.4 0.3 0.3 0.3 0.4 0.4 0.05 10 0.4 0.4 0.4 0.3 0.4 0.4 0.4 0.4 0.3 0.4 0.4 0.04 10 65 sa 35 42 54 42 38 36 2a 3a 44 11.6 10 47 63 23 77 104 54 45 66 39 33 55 23.6 10 Page 306 ARGUS 418-026 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 Animal I D TP ALB GLU CHOL T-BIL BUN g/dL g/dL mg/dL V/dL mg/dL W/dL _____---_-______-_________-I--___I_------------------------------------------~------- GROUP: 3-F 1491 1 6.9 4.7 132 56 0.1 16 14912 6.4 4.3 124 49 0.1 18 1491 3 7.1 4.5 176 65 0.1 14 1491 4 6.9 4.7 146 73 0.2 14 1491 5 7.0 5.1 139 86 0.1 17 1 4916 7.7 5.1 201 97 0.1 16 14917 6.6 4.1 144 69 0.1 16 14918 7.2 4.7 208 52 0.1 12 1491 9 7.6 4.8 191 100 0.1 16 14920 7.2 4.6 165 90 0.1 14 MEAN SD N 7.1 4.7 163 74 0.1 15 0.40 0.31 30.1 18.7 0.03 1.8 IO 10 10 10 10 10 CREAT mg/dL 0.4 0.3 0.3 0.3 0.4 0.3 0.3 0.3 0.4 0.3 0.3 0.05 10 SEX: FEMALE ALT U/L 46 32 U 28 41 67 130 34 39 28 49 30.7 10 GROUP: 4-F 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 REAN SD N 7.0 6.9 6.--4 6.8 6.7 7.0 6.5 6.5 6.9 6.7 0.23 9 4.9 4.6 4.3 -- 4.6 4.3 4.1 4.3 4.4 4.4 4.4 0.23 9 156 158 140 - 142 165 179 173 166 166 161 13.1 9 54 61 -55 64 102 57 65 91 63 68 16.8 9 0.1 0.2 0.1 - 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.03 9 18 0.4 65 14 0.4 37 20 0.4 28 _- -_ - 19 0.3 33 11 0.3 48 16 0.4 64 17 0.3 37 1s 0.4 45 13 0.3 35 16 0.4 u 2.9 0.05 13.3 9 9 9 (-1 - Data U n a v a i l a b l e LABCAT CC4.43 Page 307 10-APR-2002 S t u d y Report for Clinical Chemistry INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD: TERMINAL STUDY I D : ARGUS #418-026 STUDY NO: 060-062 Animal I D GROUP: 1-M 14851 14852 14853 14854 14855 14856 14857 14858 14859 14860 MEAN SD N AST "/L ~~ 80 76 79 74 78 94 99 80 106 76 84 11.2 10 ALP U/L 100 98 88 81 77 77 123 108 102 85 94 15.0 10 CA mg/dL 11.5 11.3 11.2 11.3 11.2 12.3 10.9 11.4 11.1 11.4 11.4 0.37 10 PHOS mg/dL 9.2 8.3 8.7 8.8 8.3 8.8 8.5 9.1 8.5 10.6 8.9 0.68 10 TRIG mg/dL 90 56 129 37 54 25 41 87 40 39 60 32.3 10 NA mmol/L 149 147 148 149 147 150 148 150 147 146 148 1.4 10 ARGUS 418-026 K mmol/L 5.3 4.9 4.4 5.1 5.2 5.1 5.2 4.8 5.3 6.7 5.2 0.59 10 SEX: MALE CL mmol/L 95 96 96 100 98 98 98 101 99 100 98 2.0 10 GROUP: 2-M 14861 105 14862 101 14863 92 14864 71 14865 74 14866 87 14867 91 14868 95 14869 87 14870 98 97 11.1 9.2 79 10.8 8.2 91 11.4 8.4 74 11.4 9.0 77 11.o 8.5 82 11.6 8.5 98 10.8 8.1 111 11.3 10.1 94 11.1 8.8 101 11.4 7.9 31 148 5.5 100 45 149 4.5 101 48 148 5.0 99 81 148 5.6 99 36 147 5.8 99 89 149 5.4 101 66 149 4.8 99 71 149 5.6 98 37 168 6.2 102 76 149 4.7 100 MEAN so N 90 90 11.2 8.7 58 148 5.3 100 10.9 12.0 0.27 0.64 21 .o 0.7 0.54 1.2 10 10 10 10 10 10 10 10 Page 308 ARGUS 418-026 ---------- Study Report f o r Clinical Chemistry ____-______c__----------- --------__--___________ ______ INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD: TERMINAL ___-___-___--__---_-______________c_____----------------- STUDY ID: ARGUS U418-026 __ST_U_DY__NO_: _0_60---0_62__----__------------------------------------------_- Animal ID AST ALP CA PWS TRIG NA U/L U/L ------ -_----___------- W/dL -W--/-d-L__--__-W--J--d_L--------m-m--o-l-/L- GROUP: 3-R 14871 84 83 10.6 7.6 39 148 14872 95 101 11.3 8.9 68 148 14873 91 102 10.9 9.7 57 151 14874 80 77 11.2 8.0 41 148 14875 81 105 11.3 8.1 35 148 14876 14877 14878 91 89 10.7 7.2 83 83 11.o 8.7 104 110 11.1 8.2 41 148 56 148 63 151 14879 14880 a3 98 10.8 8.6 as 111 11.1 7.9 59 149 43 149 K mmol/L 5.1 5.1 4.9 4.6 5.6 5.0 5.2 5.3 5.5 5.0 SEX: MALE CL mmoi/L 100 100 100 98 102 100 97 100 100 101 MEAN SD N 88 96 11.o 8.3 50 149 5.1 100 7.5 12.1 0.24 0.71 11.6 1.2 0.29 1.4 10 10 10 10 10 10 10 10 GROUP: 4-R 14881 114 113 11.3 8.3 36 150 5.0 101 14882 82 122 10.8 8.2 40 148 5.6 100 14883 76 90 11.4 9.1 79 148 5.0 99 14884 14885 14886 92 121 11.2 8.6 104 104 11.o 8.2 75 114 11.o 7.1 37 149 5.4 101 55 148 5.3 98 44 150 4.4 99 14887 95 86 11 .l 8.5 53 150 4.8 101 14888 92 103 10.4 8.3 40 149 5.3 103 14889 14890 93 113 11.4 -8.8 40 150 5.5 103 flEAN SD N 91 107 11.1 8.3 47 149 5.1 101 12.7 12.7 0.32 0.55 13.7 0.9 0.38 1.7 9 9 9 9 9 9 9 9 LABCAT CC4.43 Page 309 10-APR-2002 Study Report for Clinical Chemistry ARGUS 418-026 GROUP: 1-F 14891 112 14892 108 14893 69 14894 71 14895 100 14896 83 14897 83 14898 72 14899 75 14900 80 36 11.7 6.0 41 11.2 5.7 36 12.8 8.7 33 11.7 7.4 51 11.5 8.7 47 12.1 9.6 55 11.5 8.4 56 12.6 9.2 43 11.8 9.1 44 11.8 8.9 44 144 6.9 102 44 145 5.0 98 33 145 6.5 96 42 147 5.8 102 45 146 6.6 102 29 146 7.5 102 36 146 5.5 103 28 149 6.4 102 37 148 6.7 103 23 147 5.6 104 MEAN SD N as 44 11.9 8.2 36 146 6.3 101 15.8 8.0 0.50 1.35 7.7 1.5 0.76 2.5 10 10 10 10 10 10 10 10 GROUP: 2-F 14901 107 52 11.2 6.9 25 147 5.5 101 14902 w 76 11.5 10.6 32 748 6.6 102 I 4903 61 41 11.2 8.6 41 146 6.7 102 14904 100 43 12.2 8.9 43 146 5.9 103 14905 154 35 11.7 6.7 % 145 4.8 98 14906 79 28 12.3 8.6 47 145 5.7 96 14907 74 34 11.7 8.6 45 146 6.1 102 14908 111 46 11.5 6.5 38 146 5.3 103 14909 a5 49 11 .a 8.2 &2 146 6.5 102 14910 83 51 11.2 6.1 45 147 6.3 102 MEAN SD N 95 46 11.6 8.0 45 146 5.9 101 25.8 13.3 0.39 1.39 19.0 0.9 0.62 2.3 10 10 10 10 10 10 10 10 LAECAT CC4.43 Page 3 10 10-APR-2002 ARGUS 418-026 Study Report for Clinical Chemistry INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD : TERMINAL ____- --__ ~-~~ ~ ~~ ~~ STUDY DI : ARGUS t~41a-026 SEX: FEMALE STUDY NO: 060-062 _________c___________________I__________-----------------__--_-------- A n i m a l ID AST ALP U/L U/L ____cI_-__-I---_--------------------------------I-----------_----__________ CA ng/dL PHOS W/dL TRIG mg/dL NA mmol/L K mmol/L CL mmol/L GROUP: 3-F 1491 1 70 14912 72 14913 88 1491 4 62 1491 5 aa 14916 86 14917 237 14918 as 14919 85 14920 70 36 11 .o 5.6 36 11.1 9.1 56 ii.a 8.7 31 11.2 7.5 56 12.0 9.3 44 12.8 8.6 42 11.7 8.4 71 11.8 8.3 39 11.6 6.9 43 11.4 6.9 34 146 5.7 103 34 148 6.3 106 27 144 6.2 101 55 146 5.8 102 52 147 7.5 99 48 145 5.9 99 43 146 6.9 102 32 147 5.9 101 44 145 5 .a 100 44 147 5.6 104 MEAN SD N 94 45 11.6 7.9 41 146 6.2 102 5 1 .o 12.1 0.53 1 .I7 9.2 I .2 0.60 2.2 10 10 10 10 10 10 10 10 GROUP: 4-F 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 MEAN SD N 124 76 a2 78 104 129 95 87 85 96 19.6 9 60 52 65 46 47 61 48 1 oc 49 59 18.2 9 11.5 11.2 11.4 11.5 11.4 11.2 11.3 11.5 11.7 11.4 0.16 9 8.7 7.7 9.0 9.6 8.6 7.3 8.1 7.3 8.9 8.4 0.80 9 37 42 62 27 40 33 63 46 26 42 13.5 9 143 7.7 145 5.8 1 47 5.6 146 5.9 146 6.3 145 6.0 146 6.4 146 6.0 145 5.7 145 6.2 1 .I 0.63 9 9 103 101 102 101 103 104 102 101 1 03 102 1 .I 9 (-1 - Data Unavailable LABCAT CC4.43 Page 3 11 1SAPR-2002 STUDY I D : ARGUS #418-026 STUDY NO: 060-062 Study Report for Clinical Chemistry INDIVIDUAL ANIMAL REPORT BY GROUP PERIOD: TERMINAL Animal I D GROUP: 1-b 14851 14852 14853 14854 14855 14856 14857 14858 14859 14860 MEAN SD N GLOB 9/dL 2.6 2.5 2.9 2.5 2.2 2.8 2.4 2.0 2.2 2.6 2.5 0.28 10 A/G none 1.7 1.6 1.4 1.6 1.8 1.5 1.6 2.2 1.9 1.5 1.7 0.23 10 ARGUS 418-026 SEX: MALE MEAN SD N 2.5 0.14 10 1.7 0.14 10 LABCAT CC4.43 Page 312 IO-APR-ZOO2 ARGUS 418-026 MEAN SD N 2.4 0.16 10 1.7 0.13 10 MEAN SD N 2.4 0.37 9 1.7 0.23 9 LAECAT CC4.43 Page 313 10-APR-MOZ STUDY I D : ARGUS #418-026 STUDY NO: 060-062 ARGUS 418-026 SEX: FEMALE MEAN SD N 2.4 0.17 10 GROUP: 2-F I 4901 I 4902 14903 14904 I 490s 14906 I 4907 I 4908 14909 1491 0 MAN SD N 2.5 2.4 2.2 2.6 2.5 2.7 2.2 2.2 2.3 2.8 2.4 0.22 10 2.1 0.21 10 I .8 2.3 2.1 1.7 2.0 1.9 2.1 2.2 2.1 1.6 2.0 0.23 10 Page 3 14 ARGUS 418-026 MEAN SD N 2.4 0.2~ 10 GROUP: 4-F 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 MEAN SD N 2.1 2.3 2.1 - 2.2 2.4 2.9 2.2 2.1 2.5 2.3 0.26 9 2.0 0.31 10 2.3 2.0 -2.0 2.1 1.8 1.4 2.0 2.1 1.8 1.9 0.26 9 (--I - Data Unavailable LABCAT CC4.43 Page 3 15 10-APR-2002 ARGUS 418-026 Group: 2-R REAN SD N Group: 3-R REAN SD N Group: 4-R MEAN SD N 6.5 0.16 10 4.1 ' 0.19 10 157 12.8 10 51 14.9 10 6.4 4.0 167 45 0.19 0.11 21.6 8.4 10 10 10 10 6.5 0.50 9 4.0 0.26 9 166 13.8 9 53 14.4 9 0.1 0.00 10 0.1 0.00 10 0.1 0.00 9 14 0.2 1.5 0.05 IO 10 14 0.3 2.2 0.06 10 10 15 0.3 1.4 0.05 9 9 45 90 7.1 10.9 10 10 41 aa 4.6 7.5 10 70 43 91 7.8 12.7 9 9 Page 3 16 ARGUS 4 18-026 Group: 1-M MEAN SD N Group: 2-M MEAN SD N Group: 3-M MEAN SD N Group: 4-M MEAN SD N 94 15.0 10 90 12.0 10 96 12.1 10 107 12.7 9 11.4 0.37 10 11.2 0.27 10 11.o 0.24 10 11.1 0.32 9 8.9 0.68 10 8.7 0.64 10 8.3 0.71 10 8.3 0.55 9 60 32.3 10 58 21 .o 10 50 11.6 10 47 13.7 9 148 5.2 1.4 0.59 10 10 148 5.3 0.7 0.54 10 10 149 5.1 1.2 0.29 10 10 149 5.1 0.9 0.38 9 9 98 2.0 10 100 1.2 10 100 1.L 10 101* 1.7 9 2.5 0.28 10 2.5 0.14 10 2.4 0.16 10 2.4 0.37 9 1.7 0.23 10 1.7 0.14 10 1.7 0.13 10 1.7 0.23 9 LABCAT CC4.43 Page 317 10-APR-M02 ~ ~~~ Study Report for Clinical Chemistry ARGUS 4 18-026 STUDY ID: ARGUS #418-026 STUDY NO: 060-062 ANALYSIS OF VARIANCE FOLLOUED BY DUNNETT'S PROCEDURE TEST(s): UNITS: ALP CA PHOS TRIG NA K CL U/L mg/dL mg/dL W/dL nrmOl/L mml/L mml/L Group: 1-F MEAN SD N 44 11.9 8.2 36 146 6.3 101 8.0 0.50 1.35 7.7 1.5 0.76 2.5 10 10 10 10 10 10 10 Group: 2-F MEAN 4 6 . 11.6 8.0 45 146 5.9 101 SD 13.3 0.39 1.39 19.0 0.9 0.62 2.3 N 10 10 10 10 10 10 10 Group: 3-F MEAN so 45 11- 6 7.9 41 146 6.2 102 12.1 0.53 1. I 7 9.2 1.2 0.60 2.2 N 10 10 10 10 IO 10 10 Group: 4-F MEAN 59 11.4 8.4 42 145 6.2 102 SD 18.2 0.16 0.80 13.5 1.1 0.63 1.1 N 9 9 9 9 9 9 9 SEX: FEMALE GLOB g/dL A/G none 2.4 0.17 10 2.1 0.21 10 2.4 0.22 10 2.0 0.23 10 2.4 0.28 10 2.0 0.31 10 2.3 0.26 9 1.9 0.26 9 Page 318 ARGUS 418-026 Group: 1-F MEAN SD N Group: 2-F MEAN SD N Group: 3-F MEAN SD N Group: 4-F MEAN SD N 7.2 0.40 10 7.2 0.34 10 7.1 0.40 10 6.7* 0.23 9 4.9 0.38 10 4.8 0.29 10 4.7 0.31 10 4.4* 0.23 9 156 16.7 10 160 21.4 10 163 30.1 10 161 13.1 9 76 11.8 10 69 10.0 10 74 18.7 10 68 16.8 9 0.1 0.00 10 0.1 0.03 10 0.1 0.03 10 0.1 0.03 9 16 0.4 1.9 0.05 10 10 16 0.4 1.6 0.04 10 10 15 0.3 1.8 0.05 10 10 16 0.4 2.9 0.05 9 9 44 11.6 10 55 23.6 10 49 30.7 10 44 13.3 9 85 15.8 10 95 25.8 10 94 51 .o 10 96 19.6 9 LABCAT CC4.43 Page 3 19 10-APR-2002 ARGUS 418-026 QUALITY ASSURANCE STATEMENT Study Number: 418-026 Redfield Study Number: 060-062 This study has been inspected and audited by the Quality Assurance Unit (QAU) as required by the Good LaboratoryPractice (GLP) regulations promulgatedby the U.S.Food and DrugAdministration or U.S. EnvironmentalProtectionAgency or other international regulations, as required. The following is a record of the dates that auditslinspectionswere performed and reported by the QAU. I DATEOF I AUDllhNSPECTlON 4toato2 ~ TYPEOF AUDITANSPECTION Clinical Pathology I I DATESREPORTETDO STUDY DIRECTOARND MANAGEMENT 4/08/02 APPROVED '. n BY: -0 Jih Pohell, B.S. Assurance Auditor Redfield Laboratories 5 ( r Date q I ~ Page 320 ARGUS 418-026 APPENDIX K HISTOPATHOLOGY REPORT Page 321 ARGUS 418-026 RESEARCH PATHOLOGY SERVICES, INC. 438 East Butler Avenue, New Britain, PA 18901 Phone: 215-345-7070 Fax: 215-3454326 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT SUBMITTED TO: Raymond G. York, Ph.D. , D.A.B.T Argus Research 905 Sheehy Drive, Building A Horsham, PA 19044 SUBMITTED BY: fl.Ray Brown, D.V.M., Ph.b. Veterinary Pathologist February 25,2003 Page 322 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT TABLE OF CONTENTS REPORT Paqe Method ....................................................................................................................... 1 Results ....................................................................................................................... 3 Summary .................................................................................................................... 6 Quality Assurance Unit Statement ............................................................................. 8 TABLES I. Incidence and Degree of Severity of Histomorphologic Observations .................. 9 APPENDICES I. Histomorphologic Observations ............................................................... 1-1 to 1-17 Key to Histomorphologic Observations............................................................... 1-1 Tables 1.1 . Histomorphologic Observations .Group I Male Rats ............................... 1-2 12. . Histomorphologic Observations .Group I1Male Rats .............................. 1-5 13. . Histomorphologic Observations .Group Ill Male Rats ............................. 1-6 14. . Histomorphologic Observations .Group IV Male Rats............................. 1-7 1.5 . Histomorphologic Observations .Group I Female Rats......................... 1-10 16. . Histomorphologic Observations .Group II Female Rats........................ 1-13 17. . Histomorphologic Observations .Group Ill Female Rats....................... 1-14 18. . Histomorphologic Observations .Group IV Female Rats ...................... 1-15 I1. Individual Animal Gross and Histomorphology Data.............................. 11-1to 11-81 Page 323 ~ ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT METHOD: Microscopic examination was made of the specified tissues from 40 male and 40 female Crl:CD@(SD)IGSBR VAF/Plus' rats equally divided into four groups used in a 90-day oral (gavage) repeated dose toxicity study of potassium perfluorobutane sulfonate (PFBS). The dosage group identification and treatment of the groups of rats are listed below. Group I I1 Ill Number of Rats/Sex 10 10 10 10 Dosage (mg/kg/day1 0 (Vehicle) 60 200 600 Concentration (mg/mL) 0 6 20 60 Dosage Volume (mUkg) 10 10 10 10 The rats were administered the test substance and/or vehicle by gavage, once daily, for up to 90 days. Dosages were adjusted for the most recently recorded body weight and given at approximately the same time each day. The rats were sacrificed on the day following the last administration of the test substance. The in-life portion of the study, necropsies, and recording of the gross obser- vations at necropsy were performed by the staff of Argus Research. At necropsy, the specified tissues were collected and placed in 10% neutral buffered formalin with the exception of the testes. The testes were fixed in Bouin's solution for 48-96 hours before being transferred to and retained in 10% neutral buffered formalin. The preserved tissues were then submitted to Research Pathology Services, Inc. for tissue processing, microscopic slide preparation and histopathologic evaluation. The tissues specified for microscopic evaluation from the male and female rats of Groups I and IV included: adrenal glands, aorta, bone marrow (sternum), brain, epididymides, esophagus, eyes (with optic nerve), femur, heart, colon, cecum, Research Pathology Services, Inc. -1 Page 324 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT rectum, duodenum, jejunum, ileum, kidneys, larynx, liver, lung, mandibular and mesenteric lymph nodes, mammary gland (females only), nasal cavity/turbinates, ovaries, pancreas, Peyer's patch, pharynx/nasopharynx, pituitary, prostate, salivary gland (mandibular), sciatic nerve, seminal vesicles, skeletal muscle, skin, spinal cord (cervical, midthoracic and lumbar), spleen, stomach, testes, thymus, thyroid, parathyroid, trachea, urinary bladder, uterus, vagina, and other tissues with gross changes. In addition, microscopic examination was made of sections of the kidneys, stomach, nasal cavity/turbinates, pharynxhasopharynx and other tissues with gross changes from the male and female rats of Groups II and Ill. Representative sections of these tissues were routinely processed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin for microscopic examination. Upon completion of the project, all raw data (remaining wet tissue, parafin blocks, microscopic slides and histology records) will be returned to Argus Research for archiving. Research Pathology Services, Inc. -2 Page 325 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT RESULTS: The type, incidence and degree of severity of the histomorphologic observations in the male and female rats of all dosage groups are summarized in Table 1. The individual microscopic findings are presented in tabular form in Appendix I (Tables 1-1to 1-8). A key to the individual microscopic observations precedes Table 1-1. The gross observations, detailed descriptions of the microscopic findings and a correlation of these findings with the gross observations, are presented in Appendix II. No microscopic changes directly related to treatment were observed in any of the tissues specified for examination from the male and female rats given 60 or 200 mg/kg/day of PFBS, orally, for 90 days. Compound-related microscopic changes were observed in the kidneys and stomach of the male and female rats of the 600 mg/kg/day dosage group. The primary treatment-related change in the kidneys consisted of an increased incidence of male and female rats of the high dosage group with hyperplasia of the epithelial cells of the medullary and papillary tubules and ducts in the inner medullary region (Table 1). These tubules had a dark tinctorial appearance with increased amounts of small interstitial cells with prominent dark nuclei. Other treatment-related changes included a lower incidence of focal papillary edema and a single incidence of papillary necrosis in both kidneys of one high dosage group male rat. Hyperplasia of the medullary and papillary tubules was observed in one control male rat and, therefore, the single incidences of this change in the male and female rats of Group Ill were considered to have been incidental and comparable to the control. The treatment-related effect in the stomach consisted of an increased incidence of male and female rats of the high dosage group (Group IV) with necrosis of individual squamous epithelial cells in the limiting ridge of the forestomach (Table 1). This change was characterized by individual squamous epithelial cells with dark pyknotic nuclei surrounded by a clear cytoplasmic halo. This change was seen at a Research Pathology Services, Inc. -3 Page 326 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) iN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT very low incidence in the rats of the other dosage groups, including a control female rat, but the increased incidence of this change, along with minimal or mild thickening of the mucosa of the limiting ridge due to hyperplasia and hyperkeratosis, was considered to be treatment-related in the high dosage group rats. Microscopic examination of the nasal cavity and nasal turbinates revealed a few equivocal microscopic changes that occurred at low and sporadic incidences in rats of Groups Ill and IV. These changes occurred primarily in the posterior nasal cavitylturbinates and involved the olfactory mucosa. These histomorphologic changes included single or low incidences of multifocal necrosis or atrophy of the olfactory mucosa, focal acutelsubacute or chronic inflammation, adhesions of the turbinate to either an adjacent turbinate or to the lateral nasal wall, focal hyperostosis of turbinate bone and/or foci of olfactory epithelial hyperplasia (Table 1). Foci of inflammation may occur spontaneously in the nasal cavity of rats, but in several of the above-mentioned lesions, the inflammation was associated with these other changes. The lesions in the nasal cavitylturbinates are of uncertain significance and origin mainly because although they occurred only in Groups Ill and IV, they occurred at very low and sporadic incidences and were focal or multifocal in distribution. The nasal cavitylturbinates of most rats of all groups were histologically not remarkable. The varied and focal histomorphologic characteristics of these lesions in the nasal cavitylturbinates are not typical or consistent with a systemic toxic effect. Although the mechanism is unknown, many of these lesions are more suggestive of a local irritating effect on the nasal mucosal membranes. One other Group Ill male rat had areas of chronic inflammation and squamous metaplasia of the respiratory epithelium which was associated with marked tooth dysplasia and an abscess. There were a few other miscellaneous microscopic changes observed in the various organs and tissues that generally occurred at single, low or similar frequencies among the groups. These changes were typical of those that occur spontane- ~ Research Pathology Services, Inc. -4 Page 327 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT ously and their type, incidence or severity was not influenced by compound administration. These changes also are listed and summarized in the attached histomorphology tables. Research Pathology Services, Inc. -5 Page 328 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT SUMMARY: Microscopic examination was made of the specified tissues from 40 male and 40 female rats of an oral (gavage) repeated dose 90-day toxicity study of potassium perfluorobutane sulfonate (PFBS), Three.groups of 10 male and 10 female rats in each group were given 60, 200, or 600 mg/kg/day of the test substance orally for 90 days. Also, an additional group of ten male and ten female rats was given the vehicle alone and served as a control group. No microscopic changes directly related to treatment were observed in any of the male and female rats given 60 or 200 mg/kg/day of PFBS for 90 days. Treatment-related microscopic changes were observed in the kidneys and stomach of male and female rats of the 600 mg/kg/day dosage group. The treatment-related change in the kidneys consisted primarily of an increased incidence of hyperplasia of the tubular and ductular epithelium in the inner medulla and papilla. Other treatment-associated changes that occurred at lower or single incidences in the kidneys of rats of this group were foci of papillary edema and papillary necrosis, respectively. The treatment-related effect in the stomach consisted of an increased incidence of male and female rats of the 600 mg/kg/day dosage group with necrosis of individual squamous epithelial cells in the limiting ridge of the forestomach. In some of these rats, the limiting ridge also appeared to have been thickened due to hyperplasia and hyperkeratosis of this squamous mucosa. Microscopic changes of an equivocal and uncertain nature were observed in the nasal cavity/turbinates at very low and sporadic incidences in male and female rats of the 200 and 600 mg/kg/day dosage groups. These changes were quite varied and occurred in the posterior (olfactory mucosa) region and included multifocal necrosis or atrophy of the olfactory mucosa, foci of adhesions of the olfactory mucosa between turbinates and between the turbinates and the lateral nasal cavity wall, foci of inflammation, focal hyperostosis of the turbinate bone and/or foci of Research Pathology Services, Inc. -6 Page 329 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT olfactory epithelial hyperplasia. These changes are not typical spontaneously occurring lesions in the nasal cavitylturbinates of rats, nor are they typical of the effects of systemic toxicity on the nasal mucosa. The origin and significant of these very low and sporadic changes in only rats of the mid and high dosage groups is uncertain. The nasal cavity and turbinates of most rats of all groups were histologically normal. A few other microscopic changes were observed in the various organs and tissues which were typical of those that occur spontaneously in young laboratory rats. Their type, incidence or severity was not affected by compound administration. Research Pathology Services, Inc. -7 Page 330 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT QUALITY ASSURANCE UNIT STATEMENT All aspects of the tissue processing, microscopic slide preparation, histopathologic evaluation and report preparation for the study listed above have been performed according to the Standard Operating Procedures of Research Pathology Services, Inc. and were audited in accordance with the procedures established by the Quality Assurance Unit of Research Pathology Services, Inc. in compliance with the Good Laboratory Practice regulations specified in the protocol. Quality Assurance Unit study-based inspections were performed as shown below. There were no deviations from the protocol, Standard Operating Procedures and/or appropriate Good Laboratory Practice regulations noted during the conduct of the study. The summary report of QA inspections is included in the final report submitted to the Study Director on February 25, 2003. Dates of Inspection Study Phase Dates Reportedto Manaqement 03/28/02 04/01/02 04/08/02 04/09/02 04/10/02 04112/02 06/06/02 05/08/02 0 3 18/02 0611 0102 0612 1/02 06/24/02 06/27/02 06/28/02 02/25/03 Master Schedule Pre-initiation Trimming Embedding Microtomy Staining Organization & Review Histopathology Data Entry Data Verification Data Processing Report Preparation Pre-submissionAudit Draft report Final report 03/31/02 04/30/02 04/30/02 04/30/02 04/30/02 04/30/02 06/06/02 0513 1/02 05/31/02 06/28/02 06/28/02 06/28/02 06/28/02 06/28/02 02/25/03 ALL, 4LL.d 9- L5 2. Karen W. Harkins, BS Quality Assurance Unit oa - 2 s - c 3 Date Research Pathology Services, Inc. -8 Page 331 ARGUS 418-026 ORAL (GAVAGE) REPEATEO DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 Incidence and Oegree o f S e v e r i t y o f H i s t o m r p h o l o g i c Observations Dose Group: Sex : Number o f Animal s/GrouD: I I 1 111 I V M M M M 10 10 10 10 I I1 FF 10 10 111 I V FF 10 10 NO. NORMAL -vacuolation, cortex minimal moderate AORTA: NO. EXAMINED NO. NORMAL 10 0 0 10 7009 1000 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 0000 10 0 0 10 10 0 0 10 NO. NORMAL -degeneration, articular cartilage. focal mild 10 0 0 10 100 0 9 BONE MARROW (STERNUM): NO. EXAMINED NO. NORMAL 10 0 0 10 60010 -necrosis, minimal mild moderate intersternal cartilage, focal BRAIN: NO. EXAMINED NO. NORMAL 1000 1000 10 0 0 10 70010 -di latation, minimal mild moderate ventricular CECUM: NO. EXAMINED NO. NORMAL -in f l annat ion, chroni c , mucosa mild moderate [31 lo1 101 101 1000 1000 1000 10 0 0 10 100 0 9 [OI r01 [Ol [ll 0001 0000 -parasi te(s) COLON : NO. EXAMINED NO. NORMAL 0 0 0 0 10 0 0 10 100 0 9 -parasite( s) 0001 DUODENUM: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 [ 1 = Total incidence o f specified lesion, a l l grades. Page 332 10 0 0 10 10 0 0 10 10 0 0 10 100 0 8 0000 0000 10 0 0 10 10 0 0 10 [OI [Ol [OI ro1 0 0 0 0 0000 0000 10 0 0 10 9008 [Ol [OI [OI r11 0000 0001 1001 10 0 0 10 80010 2 0 0 0 10 0 0 10 10 0 0 10 -9 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Oegree o f S e v e r i t y o f H i s t m r p h o l o g i c Observations Dose Group: Sex : Number o f Animals/Group: I I1 111 I V M M M M 10 10 10 10 I I 1 111 I V F F F F 10 10 10 10 EPIOIOYMIDES: NO. EXAMINED NO. NORMAL 10 0 0 10 7 0 0 6 - i n f i l t r a t i o n . mononuclear-cell , focal minimal [OI L-41 04 ESOPHAGUS: NO. EXAMINED NO. NORMAL EYES/OPTIC NERVE: NO. EXAMINED NO. NORMAL HEART : NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 8 0 0 6 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 -di latation, atrial moderate -inflammation, chronic, focal minimal -in f l a m a t ion, subacute minimal mild -necrosi s , mu1t if o c a l minimal - ILEUM: NO. EXAMINED NO. NORMAL JEJUNUM : NO. EXAMINED NO. NORMAL -Advanced a u t o l y s i s precludes evaluation KIDNEYS: NO. EXAMINED NO. NORMAL - a r t e r i t is , f o c a l minimal -basophil id. tubular, multifocal minimal moderate [OI r01 E01 [ll 0001 ro1 E01 101 [ll O D 0 1 121 LO1 LO1 [31 2002 0001 Dl [Ol r01 E11 1001 10 0 0 10 10 0 0 10 10 0 0 10 100 0 9 0001 10 10 10 10 4751 r11 ro1 [Ol ro1 1000 r.1 [OI [OI [31 1 0 0 2 0 0 0 1 ro1 r01 [OI [OI 0000 [Ol [OI r01 [OI d000 [OI ro1 [OI [OI 0 0 0 0 0000 ro1 [Ol ro1 [OI 0000 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 0 0 0 0 10 10 10 10 4360 ro1 ro1 [Ol [OI 0 0 0 0 r r 01 01 E01 r11 0 0 0 1 0 0 0 0 -cyst (s), medull a 0 1 0 0 0 0 0 0 - c y s t (s), papi 11a 0 0 0 0 [ ] = Total incidence o f specified lesion, a l l grades. 0001 -10 Page 333 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Degree of Severity of Histomorphologic Observations Oose Group: Sex: Number of Animals/Group: I I 1 111 IV M M M M 10 10 10 IO I I1 FF 10 10 KIDNEYS (Continued): -dilatation, pelvis mild -dilatation, tubules, papilla minimal mild -edema, papi 1 1 ary minimal -hyaline droplets, cortical tubules mild -hyperplasia, pelviclpapillary urothel ium mild -hyperplasia, tubular/ductular epithe1 i um, minimal mild moderate -infiltration, mononuclear-cell, focal minimal 0003 0001 [11 [?I 141 [OI 1240 0 0 0 0 -mineralization, multifocal minimal mild moderate -minerali zati on, pel vi s minimal 0 0 0 0 0 0 0 0 [51 [51 44 10 01 -necrosis , papi11ary moderate -nephritis. chronic, focal minimal -pyelonephritis, chronic moderate LARYNX: NO. EXAMINED NO. NORMAL 10 0 0 10 8005 10 0 80 -granuloma( s ) 0000 00 -i nflamnation, chronic, focal minimal mi Id - LIVER. NO. EXAMINED NO. NORMAL [21 [OI [Ol [SI 2004 0001 10 0 0 10 3007 [ 1 = Total incidence o f specified lesion, all grades. [21 [OI 10 10 10 0 40 Page 334 111 I V FF 10 10 0 5 0 0 121 [21 12 10 00 0 10 05 02 [OI [SI 03 02 0 10 06 -11 -~~~ ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Oegree of Severity of Histmrphologic Observations Dose Group: Sex : Number of Animals/Group: I I1 I11 I V MMMM 10 10 10 10 I I1 F F 10 10 L I V E R (Continued): -i nflamnation, chronic, focal/multi focal minimal r61 101 60 -lipidosis, tension, focal 2 0 0 2 10 -vacuolation, hepatocellular, multifocal minimal -vacuo1ati on, hepatoce.11ul ar, periportal minimal mild - LUNG: NO. EXAMINED NO. NORMAL -alveolitis, acute, focal/multifocal minimal 0 0 0 0 10 0 0 10 80010 [I1 101 r01 [Ol 1000 10 0 10 0 [OI [OI 0 0 -macrophages, a1 veol i , focal minimal [I1 [OI 101 [OI 1000 [OI [OI 00 LYMPH NODE. MANDIBULAR: NO. EXAMINED NO. NORMAL -congesti on minimal 10 0 0 10 5004 10 0 30 -hyperplasia, lymphocytic/plasmacytic minimal mild moderate 3004 0000 0 0 1 0 LYMPH NODE. MESENTERIC: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 10 0 100 -macrophages. mu1 ti focal mild 111 I V F F 10 10 [OI [41 04 00 0 10 0 10 [OI [OI 0 0 101 [OI 00 0 10 04 0 2 0 1 0 10 0 8 NO. NORMAL -hyperplasia, mu1 ti focal minimal MUSCLE, SKELETAL: NO. EXAMINEO NO. NORMAL 6 0 0 8 6008 ro1 [OI [OI [Ol 0000 10 0 0 10 10 0 0 10 [ 1 = Total incidence of specified lesion, all grades. 10 0 0 10 9 0 0 9 E11 [OI [OI [ll 1001 10 0 0 10 10 0 0 10 -12 Page 335 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUOY NUMBER: 1-7485.15 TABLE 1 (Continued) Incidence and Degree o f Severity of Histomorphologic Observations Dose Group: Sex : Number of Animals/GrouD: I I1 I11 I V M M M M 10 10 10 10 I I1 F F 10 10 Ill I V F F 10 10 NASAL CAVITY/TURBINATES: NO. EXAMINED NO. NORMAL 10 10 10 10 10 10 8 7 10 10 10 10 9 105 6 -abscess, tooth 0 0 1 0 0 0 0 0 -adhesion(s) 0 0 0 3 0 0 0 2 -atrophy, olfactory epithelium, multifocal minimal 101 r01 101 111 0 0 0 1 -deviation, nasal septum -dysplasia, tooth mild marked 0001 [OI r01 r11 LO1 0 0 0 0 00 1 0 1000 -fracture -hemorrhage moderate 0 0 0 0 r01 r01 r01 r01 0 0 0 0 0010 E01 r01 r11 r01 0010 -hyperostosis, turbinate bone minimal mild 101 r01 [OI E21 0 0 0 0 0 0 0 2 [OI [OI [OI r21 0001 0001 -hyperplasia, olfactory epithelium, focal minimal mi Id moderate -inflammation, acute/subacute, focal minimal mi Id -inflanation. chronic, focal/mul ti focal minimal mild 101 [OI r01 [21 0 0 0 0 0 0 0 1 00 0 1 r01 E01 ro1 ro1 0 0 0 0 0 0 0 0 @I [ol P I C21 0010 0012 r01 r01 r11 r11 0001 0010 0000 ro1 E01 r11 r11 0001 0 0 1 0 COI ro1 C21 [I1 0011 0 0 1 0 -metaplasia, squamous, respiratory epithelium. focal mild [OI r01 r11 r01 0 010 -necrosis, 01 factory epi the1 ium, mu1 ti focal minimal mild moderate E01 r01 E01 E21 0000 0001 0001 r01 r01 r11 E21 0011 0001 0000 NERVE, SCIATIC: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 NO. NORMAL [ 3 = Total incidence of specified lesion, all grades. 10 0 0 10 100 0 9 -13 Page 336 __ ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Degree o f S e v e r i t y o f Histomorphologic Observations Dose Group: Sex : Number o f Animals/Group: I I 1 111 I V M M M M 10 10 10 10 I 11 111 I V F F F F 10 10 10 10 OVARIES (Continued): -cyst(s), intraovarian PANCREAS : NO. EXAMINED NO. NORMAL 10 0 0 10 9 0 07 -atrophy, acinar, focal minimal r01 ro1 ro1 [ll 0 0 0 1 - c e l l u l a r a1t e r a t i on, basophi 1ic. f o c a l m i nimal [OI [Ol [OI [ll 0 0 0 1 - i n f i l t r a t i o n , mononuclear-cell, focal minimal [OI ro1 [OI C11 0001 -necrosis, individual -cell mild - p e r i t o n i t i s , subacute minimal E11 [OI [OI r01 1 0 0 0 [Ol [OI [OI E01 0 0 0 0 PARATHYROIO: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 9 -in f i 1t r a t ion, 1ymphocyti c mild PEYER'S PATCH: NO. EXAMINED NO. NORMAL -mineralization, focal minimal PHARYNX/NASOPHARY NX: NO. EXAMINED NO. NORMAL -in f l ainnati on, c h r o n i c , focal/mul t if o c a l minimal mild lo1 101 ro1 [I1 000 1 10 0 0 10 10 0 0 10 COI C01 ro1 COI 000 0 10 10 10 10 9 10 10 10 [ll [OI r01 [Ol 1 0 0 0 00 00 PITUITARY: NO. EXAMINED NO. NORMAL -cyst (s) 10 0 0 10 10 0 0 10 D O 0 0 PROSTATE: NO. EXAMINED NO. NORMAL 10 0 0 10 2005 1 = Total incidence of specified lesion, a l l grades. 0001 10 0 0 10 9 0 0 9 ro1 [OI [OI [OI 0 0 0 0 100 0 9 100 0 9 10 0 0 10 90010 10 10 10 10 9 10 8 10 r11 ro1 [21 LO1 0010 1010 10 0 0 10 100 0 9 0001 -14 Page 337 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Degree o f Severity o f Histomorphologic Observations Dose Group: Sex : Number of Animals/Group: I I 1 111 I V M M M M 10 10 10 10 I I1 F F 10 10 PROSTATE (Continued): -atrophy, focal minimal mild PI [Ol [Ol [Ol 100 0 1 000 -hyperplasia, lymphoid, focal mild -inf 1amnat ion, c hron ic , mu1t i f o c a l minimal mild -prostatitis, suppurative minimal [I1 [OI [OI 101 1 000 r71 [OI [OI [41 6 0 0 3 1 0 0 1 [OI [Ol r01 r11 0 0 0 1 RECTUM: NO. EXAMINED NO. NORMAL 10 0 0 I D 9 0 0 6 10 0 9 0 -parasi te(s) 10 04 1 0 111 I V F F 10 10 0 10 0 10 0 0 NO. NORMAL SEMINAL VESICLES: NO. EXAMINED NO. NORMAL - S K I N : NO. EXAMINED NO. NORMAL SPINAL CORD, CERVICAL: NO. EXAMINED NO. NORMAL S P I N A L CORO. LUMBAR: NO. EXAMINED NO. NORMAL SPINAL CORD, MIDTHORACIC: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 10 0 0 10 -atrophy moderate 10 0 0 10 0 0 0 0 [OI [OI r01 Dl 0 0 0 1 10 0 0 10 30 03 r01 [OI [Ol COI 0 0 0 0 1 1 = Total incidence of specified lesion, a l l grades. -15 Page 338 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1 (Continued) Incidence and Degree o f Severity of Histomorphologic Observations Dose Group: Sex : Number of Animals/Group: I I 1 111 I V M M M M 10 10 10 10 I I1 F F 10 10 SPLEEN (Continued): -pigment (hemosiderosis) minimal mi Id moderate [lo1 E01 [Ol [I01 50 0 4 40 0 4 10 0 2 20 5 0 STOMACH: NO. EXAMINEO NO. NORMAL 10 10 10 10 a76 1 9 10 87 -dilatation, mucosal glands mi niml mild E21 [I1 El [I1 112 1 10 0 0 -hyperplasia/hyperkeratosis, limiting ridge minimal mild [OI [OI [OI [51 00 04 0 0 0 1 -inflamnation, subacute, focal, forestomach minimal 101 [OI 101 I31 0000 -necrosis, individual-cell, limiting ridge minimal mild 101 121 PI [el 02 2 5 000 3 TESTES : NO. EXAMINEO NO. NORMAL 10 0 0 10 10 0 0 10 THYMUS : NO. EXAMINED NO. NORMAL -congestion, mu1 ti focal minimal mar ked 10 0 0 10 10 0 0 a [OI E01 P I E21 0 .o 0 1 00 0 1 10 0 10 0 LO1 Dl 00 00 THYROID: NO. EXAMINEO NO. NORMAL -foll icle(s) , cystic 10 0 0 10 4 0 0 3 000 2 10 0 70 00 -hypertrophy, fol1 i cular epithe1 i urn mild moderate r11 r01 ro1 r21 000 1 10 0 1 r01 [Ol 00 00 -ul timobranchial bodylcyst 500 5 30 TRACHEA: NO. EXAMINEO NO. NORMAL 10 0 0 10 6009 10 0 10 0 I11 I V F F 10 10 02 0 4 10 10 91 0 10 0 10 r01 COl 00 00 0 10 06 00 [OI r01 00 00 04 0 10 0 10 -[ 1 = Total incidence of specified lesion. all grades. -16 Page 339 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE BO-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 TABLE 1 (Continued) I cidence and Degree of Severity of Histomorphologic Observation Dose Group: Sex : Number of Animal s/Grouo: I I1 111 I V M M M M 10 10 10 10 I I1 F F 10 10 TRACHEA (Continued): -i nflatnnati on, chronic, focal minimal [41 [Ol [OI r11 4 0 0 1 r01 [Ol 0 0 URINARY BLAOOER: NO. EXAMINED NO. NORMAL 10 0 0 10 10 0 0 10 8 0 8 0 111 I V F F 10 1 0 [OI [OI 0 0 0 9 0 9 NO. NORMAL -distention, lumen minimal mild moderate VAGINA: NO. EXAMINED NO. NORMAL EAR(S) : NO. EXAMINED NO. NORMAL -chondropathy, auricular marked -i nfi 1 tration, polymorphonuclear moderate -pro1 iferation. vascular, focal moderate 0 0 0 1 0 0 0 0 [OI [OI 0 0 EO1 [OI 0 0 r r 01 01 [OI r11 0 0 0 1 10 0 0 10 6 0 0 5 r [41 01 [OI 151 1 0 0 3 0 0 0 1 3 0 0 1 10 0 0 10 10 0 0 10 0 0 1 0 0 0 0 0 r01 r11 101 0 1 0 r01 101 [OI 0 0 0 r r01 ro1 ro1 01 0 0 0 0 [ 3 = Total incidence o f specified lesion, all grades. -17 Page 340 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT APPENDIX I HISTOMORPHOLOGIC OBSERVATIONS Page 341 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT KEY TO HISTOMORPHOLOGIC OBSERVATIONS - -- * -- <>= e-> = 0 = No change (not remarkable, within normal histologic limits or indicated change not present). Tissue not available (specified tissue missing, insufficient tissue in plane of section, artifact precludes evaluation, or specified tissue not present in section). Microscopic finding(s) in tissue(s) with gross observation(s). Within normal limits [no microscopic change(s) to correlate with the gross observation(s)]. Only one of a pair of organs available for processing/evaluation. P = Indicated change or lesion present. 1 = Minimal degree or amount of indicated change or lesion. 2 = Mild degree or amount of indicated change or lesion. 3 = Moderate degree or amount of indicated change or lesion. 4 = Marked degree or amount of indicated change or lesion. ss = SD = SM = Sacrifice-Scheduled Spontaneous Death Sacrifice-Moribund 1-1 Page 342 - ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-1 Histomorphologic Observations Dose Group: Animal Number: Sex: Death TyDe: 1111111111 14851 14852 14853 14854 14855 14856 14857 14858 14859 14860 M M M M M M M M M M ss ss ss ss ss ss ss ss ss ss ADRENAL GLANDS: -vacuolation, cortex AORTA : BONE (FEMUR): BONE MARROW (STERNUM): -necrosis, intersternal cartilage, focal BRAIN: -di 1 atation, ventricular CECUM: COLON : DUODENUM: EPIDIDYMIDES: -infiltration, mononuclear-cell, focal ESOPHAGUS : EYES/OPTIC NERVE: HEART: -inflamnation, subacute -necrosis, multifocal ILEUM: JEJUNUM : KIDNEYS : -arteritis. focal -basophilia, tubular, multifocal -hyaline droplets, cortical tubules -hyperplasia, pel vic/papi 1 lary urothel i urn -hyperplasia, tubular/ductular epi the1 i um. papilla -infiltration, mononuclear-cell, focal -mineral i zation, pel vis LARYNX: - i nflamnat ion. chronic. focal LIVER: -i nflamnation, chronic, focal/mul ti focal -1 i pi dosi s , tension, focal -vacuo1 at ion, hepatocell ular, mu1 ti focal 1-2 Page 343 -ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-1 (Continued) Histomorphologic Observations Dose Group: Animal Number: Sex : Death Type: IIIIIIIIII 14851 14852 14853 14854 14855 14856 14857 14858 14859 14860 M M M M M M M M M M ss ss ss ss ss ss ss ss ss ss LIVER (Continued) : -vacuo1 a t ion, h e p a t o c e l l u l a r , p e r i p o r t a l - ,1 - - - - - LUNG : G o l i t i s , acute, focal/rnultifocal -macrophages, a l v e o l i , focal - -1-- -1- --- -- LYMPH NODE, MANDIBULAR: - h y p e r p l a s i a , 1ymphocyti c / p l asmacytic - 2 - 2 1 - 1 - 2 LYMPH NODE, MESENTERIC: MAMMARY GLAND: MUSCLE, SKELETAL: NASAL CAVITY/TUREINATES: NERVE, SCIATIC: PANCREAS : -necrosi s, i n d i v i d u a l - c e l l PARATHYROID: PEYER'S PATCH: - - - - - - - - - - - - - - - PHARYNX/NASOPHARYNX: -inflamnation, chronic, focal/mul tifocal PITUITARY: PROSTATE: -atrophy, focal -hyperplasia, lymphoid, focal -in f l amnation, c h r o n i c , mu1t i f o c a l ---1- ----- - - - - - - - - - - 2 - -2 - 1 - - - - - - - - - - - 1-111- - 2 1 1 RECTUM: -parasi te(s) SALIVARY GLAND: SEMINAL VESICLES: SKIN: SPINAL CORD, CERVICAL: SPINAL CORD, LUMBAR: SPINAL CORD, MIDTHORACIC: 1-3 Page 344 - ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-1 (Continued) Hi stomorphol ogi c Observations Dose Group: Animal Number: Sex: Death Type: I I I I I I I I I 1 14851 14852 14853 14854 14855 14856 14857 14858 14859 14860 M M M M M M M M M M ss ss ss ss ss ss ss ss ss ss SPLEEN: -pi gment ( hemos i derosi s ) 2 1 1 3 1 2 1 2 1 2 STOMACH: -di 1 atati on, mucosal glands 1- - 2 - - - - THYRO IO : -hypertrophy, follicular epithelium -ultimobranchial body/cyst TRACHEA : -infl amnati on, chronic, focal ---3- ----- P - - - - P - P P-P 1 1 - - - - 1 - - 1 1-4 Page 345 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-2 Histomorphologic Observations Dose Group: Animal Number: Sex : Death TvDe: I1 I1 I1 I1 I1 I1 I1 I1 I1 I1 14861 14862 14863 14864 14865 14866 14867 14868 14869 14870 M M M M M H M M M M ss ss ss ss ss ss ss ss ss ss KIDNEYS: -cyst(s). medulla - i n f i l t r a t i o n , mononuclear-cell , focal NASAL CAVITY/TURBINATES: PHARYNX/NASOPHARYNX: - - - - - - P - 1- -1- - - - - - - - - - - - - - - - - - - STOMACH: - d i l a t a t i o n , mucosal glands -necrosis, individual-cell, limiting ridge - -1- - - - - 1 - - 1 1-5 Page 346 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 STUDY OF IN RATS TABLE 1-3 Hi stomorphol ogi c Observations Dose Group: .Animal Number: Sex : Death T y p e : I l l 1 1 1 111 111 111 111 111 I 1 1 I l l 111 14871 14872 14873 14874 14875 14876 14877 14878 14879 14880 M M M M M M M M M M ss ss ss ss ss ss ss ss ss ss KIDNEYS : -hyperplasia, tubular/ductular epithelium, papilla - - - - - -infiltration, mononuclear-cell, focal -11-11- -1 - - NASAL CAVITY/TUREINATES: - -abscess. tooth - - - - -dysplasia, tooth - - - -inflamnati on, chronic. focal/mul ti focal - - - --P- - - - - -4- -1- - 2 - - -metap1 asi a, squamous, .respiratory epi the1 ium. focal - - - - --2- PHARYNX/NASOPHARYNX: - - - - - - STOMACH: - -di 1 atati on, mucosal glands 1 - - - -necrosis, individual-cell, limiting ridge - - 1 - 1 - 1 - - - - 1-6 Page 347 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 18- 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 TABLE 1-4 Hi stomrphologic Observations Dose Group: Animal Number: Sex : Death Tyoe: ADRENAL GLANDS: -vacuolation, cortex AORTA : IV IV IV IV IV IV IV IV IV IV 14881 14882 14883 14884 1 4 8 8 5 14886 1 4 8 8 7 14888 14889 1 4 8 9 0 M M M M M M H M H M ss ss ss ss ss ss ss ss ss so - - - - - - - BONE (FEMUR) : -degeneration, articular cartilage, focal - - - 2 - - - - - CECUM: -i nfl amnation, chronic, mucosa COLON : -parasite(s ) EPIDIDYMIDES: -infiltration, mononuclear-cell , focal -1-1- - 1 1 - ESOPHAGUS: EYES/OPTIC NERVE: - HEART: -di1 atation, atria1 -i nfla m t i on, chronic, focal -i nf1 amnati on, subacute -necrosis, multifocal ILEUM: JEJUNUM: KIDNEYS: -basophi1ia, tubular, multifocal -di latation, tubules, papi 1 1 a - -1- - - - - -edema, papi11ary -hyaline droplets, cortical tubules 11- 2 - - - - 1 - - - - - - - - - - - -hyperplasia, tubular/ductul ar epithe1 i um, papilla -necrosis I papi 1 1 ary - 1 - 1 - 1 - 2 - - - - 2- 2- 1 - 3 3 LARYNX : -i n f 1amnati on, chronic, focal - L I V E R : -inflamnation, chronic, focal/multifocal 1 - - 1 - -1- 1 - 2 - 1 - 1- - - 1 - 1-7 Page 348 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 TABLE 1-4 (Continued) Histmorphologic Observations Dose Group: Animal N u m b e r : Sex : Death T y p e : IV IV IV IV IV IV IV IV IV IV 14881 1 4 8 8 2 14883 14884 1 4 8 8 5 14886 1 4 8 8 7 1 4 8 8 8 1 4 8 8 9 1 4 8 9 0 MMMMMMMMMM SS SS SS SS SS SS SS SS SS SD L I V E R (Continued): -1 i pidosi s, tension. focal - LUNG : LYMPH NODE, MANDIBULAR: -congesti on -hyp&plasia, lymphocyticlplasmacytic LYMPH NODE, MESENTERIC.: MAMMARY GLAND: MUSCLE, SKELETAL: NASAL CAVITY/TURBINATES: -adhesion( s ) -atrophy, 01 factory epi thel i um. mu1 ti focal -deviation, nasal septum -hyperostosis, turbinate bone -hyperplasia, 01 factory epi thel i um. focal -inflamnation, chronic, focal/multi focal -necrosis, olfactory epithelium. multifocal NERVE, SCIATIC: PANCREAS : -atrophy, acinar, focal -cellular alteration, basophilic, focal -infiltration, mononuclear-cell , focal PARATHYROID: -i nfi 1tration, 1ymphocyti c PEYER'S PATCH: PHARYNX/NASOPHARYNX: PITUITARY: PROSTATE: -i nflamnation, chronic, mu1ti focal -prostatitis, suppurative RECTUM: -parasi te(s) SALIVARY GLAND: SEMINAL VESICLES: SKIN: 1-8 Page 349 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 STUDY OF I N RATS TABLE 1-4 (Continued) Histomorphologic Observations Dose Group: Animal Number: Sex : Death TvDe: S P I N A L CORD, CERVICAL: S P I N A L CORD, LUMBAR: SPINAL CDRD. MIOTHORACIC: IV IV IV IV IV IV IV IV IV IV 14881 14882 14883 14884 14885 14886 14887 14888 14889 14890 MMMMMMMMMM SS SS SS SS SS SS SS SS SS SD - - - SPLEEN: -atrophy - - p i gment (hemosi d e r o s i s) 2 STOMACH : - - d i l a t a t i o n , mucosal glands - -hyperplasia/hyperkeratosis. l i m i t i n g r i d g e -necrosis, individual-cell, limiting ridge 1 TESTES: - THYMUS : -congestion, mu1t i f o c a l THYROID : - - f o l 1ic l e ( s) , c y s t i c P -hypertrophy, f o l l i c u l a r epithelium - - u l t imobranchi a1 b o d y l c y s t TRACHEA : -in f 1amnation, c h r o n i c , f o c a l URINARY BLADDER: - EAR(S) : -in f i1t r a t i o n , polymorphonuclear -pro1 iferation. vascular, focal 1-9 Page 350 Oose G r o u p : Animal Number: Sex : Death T w e : ADRENAL GLANDS: AORTA : BONE (FEMUR) : ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-5 H i s t m r p h o l ogi c Observations ~~ ~ ~~~ ~ ~ IIIIIIIIII 14891 14892 14893 14894 14895 14896 14897 14898 14899 14900 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss - - - - - - - - - - - - - - - CECUM: -parasi te(s) COLON : -parasite( s) DUOOENUM : ESOPHAGUS : EYES/OPTIC NERVE: HEART : ILEUM: JEJUNUM : KIDNEYS : -mineral ization, mu1ti focal -nephritis, chronic, focal LARYNX: -i nflamnati on, chronic, focal LIVER: -inflamnation, chronic, focal/rnultifocal -1 ipidosis, tension, focal -vacuo1 at ion, hepatocell ul ar, peri portal - LUNG: LYMPH NODE, MANDIBULAR: -hyperplasia, lymphocytic/pl asmacyti c LYMPH NODE, MESENTERIC: MAMMARY GLAND: -hyperplasia, mu1 ti focal MUSCLE, SKELETAL: 1 1 - - - - 1 1 - - 1 - - - 1 - P - 2-- - - - - - - -111- - 1 3 1 1 - - - - - - - - - - 1-10 Page 351 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE SO-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-5 (Continued) Histomorphologic Observations Dose Group: Animal Number: Sex : Death Tvoe: 1 1 1 1 1 1 1 1 1 1 14891 14892 14893 14894 14895 14896 14897 14898 14899 14900 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss NASAL CAVITY/TURBINATES: -deviation, nasal septum -dysplasia, tooth PANCREAS: - i n f i l t r a t i o n , mononuclear-cell, focal - 1 - - - - - - - PEYER'S PATCH: -mineralization, focal PHARYNX/NASOPHARYNX: -inflamnation, chronic, focal/multifocal PITUITARY: RECTUM : -parasi te(s) - 1 - - - - 2 - - - - - - - - - S K I N : SPINAL CORD, CERVICAL: SPINAL CORD, LUMBAR: SPINAL CORD, MIDTHORACIC: - - - - - - - - SPLEEN : - p i gment ( hemosideros is ) 3 3 2 - - - 3 3 3 2 STOMACH : -necrosis, individual-cell, l i m i t i n g ridge - - - 1 - - - - - * THYROID : -ul timobranchial body/cyst URINARY BLADDER: UTERUS : - d i s t e n t i on, 1umen - 1 - 3 - - 3 3 - - 1-11 Page 352 Dose Group: Animal Number: Sex : Death Tvoe: VAGINA : ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-5 (Continued) Histomorphologic Observations I I I I I I I I I I 14891 14892 14893 14894 14895 14896 14897 14898 14899 14900 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss - - - - - - - - 1-12 Page 353 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-6 Histomorphologic Observations Dose Group: Animal Number: Sex : Death TvDe: I 1 I 1 I 1 I 1 I 1 I1 I 1 I1 I 1 I 1 14901 14902 14903 14904 14905 14906 14907 14908 14909 14910 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss KIDNEYS: - i n f i l t r a t i o n , mononuclear-cell, focal -mineral iz a t i on, mu1t if o c a l - 1 1 - - - 1 - - - - 1 - - 1 3 - - 1 1 NASAL CAVITY/TURBINATES: PHARYNX/NASOPHARYNX: - - - - - - - - - - - - - - - STOMACH: - - - - d i 1a t a t i on, mucosal g.1ands - - i n f l a m n a t i o n . subacute, f o c a l , forestomach - - -- 1 - 1 - 2 1 - 1-13 Page 354 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-7 Histomorphologic Observations Dose Group: Animal Number: Sex : Death Type: KIDNEYS : -di 1a t a t i on, p e l v i s -hyperplasia, tubular/ductular papilla -mineralization, multifocal epithelium, NASAL CAVITY/TURBINATES: -fracture -hemorrhage -hyperplasia, olfactory epithelium, focal -in f l amnati on, acute/subacute, f o c a l - i n f l amnation, chronic, focal/mul tifocal -necrosis. olfactory epithelium, multifocal PHARYNX/NASOPHARYNX: -inflamnation. chronic, focal/multifocal STOMACH : -necrosis, individual-cell, limiting ridge 111 I11 I 1 1 I 1 1 I 1 1 I11 I11 111 111 111 14911 14912 14913 14914 14915 14916 14917 14918 14919 14920 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss - - - - - - - 2 - - - 2 - - - - - 1 - - - 1- - - - - - - - - - - - - - - - P - 2 - - - - 2 - - - - - - 3- - - - ------1-2- - -1- - - - -1---2- -- - 1- - - - - - - - EAR(S1: -chondropathy, auricular 1-14 Page 355 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-8 Histomorphologic Observations Dose Group: Animal Number: Sex : Oeath Tme: AORENAL GLANDS: AORTA : BONE ( FEMUR 1 : IV IV IV IV IV IV IV IV IV IV 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss - - - - - - - - - - - - - - - - - - - BONE MARROW (STERNUM): -necrosis. intersternal cartilage, focal - - - - - -11 BRAIN: CECUM: -in f1amnat ion, c h r o n i c , mucosa -parasi te(s) COLON : DUODENUM: ESOPHAGUS: EYES/OPTIC NERVE: HEART: ILEUM: JEJUNUM : K IONEYS : -basophilia, tubular, multifocal - c y s t ( s ) , papi 11a -dilatation. tubules, papilla -edema. papillary -hyaline droplets, cortical tubules -hyperplasia. tubular/ductular epithelium, papilla - i n f i l t r a t i o n , mononuclear-cell ~ focal -mineralization, multifocal -pyelonephritis. chronic LARYNX : -granuloma(s) -inflamnat ion, c h r o n i c . f o c a l LIVER: -inflamnation, chronic, focal/multifocal - LUNG : LYMPH NODE, MANDIBULAR: -hyperplasia, lymphocytic/plasmacytic - 1- 1- - 1 - 1 - - - - - - - - - - 2 - - 1 1 2 - 1 3 - 1-15 Page 356 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUOY NUMBER: T-7485.15 TABLE 1-8 (Continued) Histomorphologic Observations Dose Group: Animal Number: Sex : Death Type: LYMPH NODE, MESENTERIC: -macrophages, mu1t i f o c a l IV IV IV IV IV IV IV IV IV IV 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss MAMMARY GLAND: - h y p e r p l a s i a . mu1t i f o c a l MUSCLE, SKELETAL: - - - - - - - - - - NASAL CAVITY/TURBINATES: - - a d h e s i o n ( s ) --P- --P- - - - - h y p e r o s t o s i s . t u r b i n a t e bone -1- --2- - - - - - h y p e r p l a s i a , o l f a c t o r y e p i t h e l i u m , f o c a l - - - - - 1 - - -in f l a m n a t i o n , acute/subacute, f o c a l --1- - - - - -in f l amnati on, c h r o n i c , focal /mu1 t i f o c a l - ---1- - - - - n e c r o s i s , o l f a c t o r y e p i t h e l i u m , m u l t i f o c a l - - 2 - - - -1 NERVE, SCIATIC: - - - - - - - - - - OVARIES : -cyst(s), intraovarian PANCREAS : - p e r i t o n i t i s , subacute PARATHYROID: PEYER'S PATCH: PHARYNX/NASOPHARYNX: PITUITARY: -cyst(s) RECTUM: SALIVARY GLAND: - S K I N : SPINAL CORD, CERVICAL: SPINAL CORD, LUMBAR: SPINAL CORO. MIDTHORACIC: SPLEEN: -pigment (hemosiderosis) ---3212333 STOMACH: - - -hyperplasia/hyperkeratosis, l i m i t i n g r i d g e 2 - - n e c r o s i s , i n d i v i d u a l - c e l l , l i m i t i n g - r i d g e 2 2 -111111 2 2 1 1 1 2 2 1-16 Page 357 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 TABLE 1-8 (Continued) Histomorphologic Observations Dose Group: Animal Number: Sex: Death TvDe: THYMUS : THYROID: -ul timobranchi al body/cyst IV IV IV IV IV IV IV IV IV IV 14921 14922 14923 14924 14925 14926 14927 14928 14929 14930 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss - - - - - - - - P- - - P P - - P UTERUS : - d i s t e n t i o n , lumen - 2 1 - - 3 - 1 1 - 1-17 Page 358 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 HISTOPATHOLOGY REPORT APPENDIX II INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS Not applicable = Microscopic evaluation/correlation not appropriate or not required by protocol. Page 359 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: KIDNEYS: LIVER: vacuo1a t i o n , c o r t e x (minimal ) hyaline droplets, cortical tubules (mild) inflamnati on, chronic, focal/mul t i focal (minimal ) in f l amnati on, c h r o n i c , mu1t i f o c a l (minimal ) pigment (hemosiderosis) (mild) d i l a t a t i o n , mucosal glands (minimal) u l timobranchi a1 b o d y l c y s t ----...in..fl.a.m..n.a.t.i.o.n....c.h.r.o.n..ic.,..f.o.c..a.l ..(.m.i.n.i.m.a.l.)...................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : AORTA BONE (FEMUR) BONE MARROW (STERNUM) BRAIN CECUM COLON DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM LARYNX LUNG LYMPH NODE. MANDIBULAR LYMPH NODE, MESENTERIC MUSCLE, SKELETAL NASAL CAVITY/TURBINATES NERVE, S C I A T I C PANCREAS PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARYNX PITUITARY RECTUM SALIVARY GLAND SEMINAL VESICLES SKIN SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC T-E-S-T-E_S _ _ _ _ _ _ _ _ _ - -. - -__T_H_Y_M__U_S___- - - - - _ _ _ _ _ _ _ _ _ _ _U_R_I N_A_R Y_ _B_LA_D_DE_R_ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - TISSUE(S) NOT AVAILABLE FOR EVALUATION: 11-1 Page 360 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED OOSE 90-DAY T O X I C I T Y POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 STUDY OF I N RATS Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LARYNX : LIVER: PROSTATE : SPLEEN: T-R-A-C-H-E-A-:--__ a r t e r i t i s , focal (minimal ) inflamnation, chronic, focal (minimal ) vacuolation, hepatocellular. periportal atrophy, focal (mild) p i gment (hemosi d e r o s i s) (mi n i mal ) inflamnation, chronic, focal (minimal ) (mi nimal ) ----- THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS AORTA BRAIN CECUM EPIDIDYMIDES ESOPHAGUS ILEUM JEJUNUM LYMPH NODE, MESENTERIC MUSCLE, SKELETAL PANCREAS PARATHYROID PITUITARY RECTUM SKIN S P I N A L CORD, CERVICAL STOMACH TESTES U. .R.I N. .A.R.Y. .B.L.A.D.D.E. R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BONE (FEMUR) COLON EYES/OPTIC NERVE LUNG NASAL CAVITY/TUREINATES PEYER'S PATCH S A L I V A R Y GLAND SPINAL CORD, LUMBAR THYMUS BONE MARROW (STERNUM) DUODENUM HEART LYMPH NODE, MANDIBULAR NERVE, SCIATIC PHARY NX/NASOPHARYNX SEMINAL VESICLES SPINAL CORD, MIDTHORACIC THYROID 11-2 Page 361 ARGUS 418-036 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N.o..t .a.p.p.l..i c.a.b.1.e................................ HISTOMORPHOLOGIC OBSERVATIONS: BONE MARROW (STERNUM) : HEART : KIDNEYS : LARYNX : LIVER: LYMPH NODE, MANDIBULAR: PROSTATE : .S.P.L.E.E.N..: ................ --------- necrosis, intersternal cartilage, focal (moderate) inflamnation, subacute (minimal) hyaline droplets, cortical tubules (mild) inflamnation, chronic, focal (minimal) vacuolation, hepatocellul ar, mu1ti focal (minimal) i nflamnation. chronic, focal/multi focal (minimal) hyperplasia, 1ymphocytic/pl asmacytic (mi1 d) hyperplasia, lymphoid, focal (mild) inf1 amnati on, chronic, mu1 ti focal (minimal ) pi gment (hemosiderosis ) (minimal ) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CECUM ESOPHAGUS LUNG NASAL CAVITY/TURBINATES PEYER'S PATCH SALIVARY GLAND S P I N A L CORD, LUMBAR THYMUS AORTA COLON EYES/OPTIC NERVE LYMPH NODE, MESENTERIC NERVE, SCIATIC PHARYNX/NASOPHARYNX SEMINAL VESICLES S P I N A L CORD, MIDTHORACIC THYROID BONE (FEMUR) DUODENUM ILEUM MAMMARY GLAND PANCREAS PITUITARY SKIN STOMACH TRACHEA BRAIN EPIDIDYMIDES JEJUNUM MUSCLE, SKELETAL PARATHYROID RECTUM SPINAL CORD, CERVICAL TESTES URINARY BLADDER 11-3 Page 362 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal G r o s s and Histomorphology Data GROSS OESERVATION(S): HISTOMORPHOLOCIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: BONE MARROW (STERNUM) : EPIDIDYMIDES: LUNG: PHARYNX/NASOPHARYNX: PROSTATE: SPLEEN: THYROID : necrosis, intersternal cartilage, focal (minimal) i nfi 1 ttation, mononuclear-cell , focal (minimal ) macrophages, alveoli, focal (minimal) i nflamnation, chronic, focal/mu1 ti focal (minimal ) i nf1 amnati on, chronic , mu1 ti foca1 (minimal ) pigment (hemosiderosis) (moderate) hypertrophy, follicular epithelium (moderate) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN CECUM COLON DUODENUM ESOPHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM KIDNEYS LARYNX LIVER LYMPH NODE, MANDIBULAR LYMPH NODE, MESENTERIC MUSCLE, SKELETAL NASAL CAVITY/TUR~INATES NERVE, SCIATIC PANCREAS PARATHYROID PEYER'S PATCH PITUITARY RECTUM SALIVARY GLAND SEMINAL VESICLES SKIN S P I N A L CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC STOMACH TESTES .---T-H-Y_M_U_S --_________--_-_-_--_T-R-A-C-H-E-A--______--------U-R--IN-A-R-Y--B-L-A-D-D-E-R--------------- 11-4 Page 363 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I I I n d i v i d u a l Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LIVER: LUNG: LYMPH NODE, MANDIBULAR: PROSTATE: i n f i l t r a t i o n , mononuclear-cell, focal (minimal) lipidosis, tension, focal in f l a m a t i o n . chronic, focal/mul t i focal (minimal ) alveolit i s , acute, focal/mul ti focal (minimal ) hyperplasia, lymphocytic/plasmacytic (mi I d ) atrophy, focal (minimal) i n f l a m n a t i o n , c h r o n i c , mu1t i f o c a l (minimal ) p i gment (hemosi deros is ) (mi n imal ) THE FOLLOWING T I S S U E I S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN EPIDIDYMIDES ILEUM MAMMARY GLAND PANCREAS PITUITARY SKIN STOMACH AORTA CECUM ESOPHAGUS JEJUNUM MUSCLE, SKELETAL PARATHYROID RECTUM SPINAL CORO, CERVICAL TESTES BONE (FEMUR) COLON EYES/OPTIC NERVE LARYNX NASAL CAV I TY/TURBI NATES PEYER'S PATCH SALIVARY GLAND SPINAL CORD, LUMBAR THYMUS BONE MARROW (STERNUM) DUODENUM HEART LYMPH NOOE. MESENTERIC NERVE, SCIATIC PHARYNX/NASOPHARYNX SEMINAL VESICLES S P I N A L CORD, MIDTHORACIC THYROI O 11-5 Page 364 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 Individual Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: BONE MARROW (STERNUM) : BRAIN: KIDNEYS : vacuolation, cortex (moderate) necrosis, intersternal cartilage, focal (mild) dilatation. ventricular (miId) basophi 1 ia, tubular, mu1 ti focal (minimal) hyperplasia, tubular/ductular epithelium. papilla (minimal) hyperplasia, 1ymphocyti c/pl asmacytic (minimal ) pi gment (hemosiderosis ) (mi1 d) dilatation, mucosal glands (mild) -----_________u l_ti_m_ob_ra_n_ch-i-a_1_b-o-d-y-l-c-y-s-t-----------------------------------.----------- THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : AORTA BONE (FEMUR) CECUM COLON DUODENUM EPIDIDYMIDES E SO PHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM LARYNX LIVER LUNG LYMPH NODE, MESENTERIC MAMMARY GLAND MUSCLE, SKELETAL NASAL CAVITY/TURBINATES NERVE, SCIATIC PANCREAS PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARYNX PITUITARY PROSTATE RECTUM SALIVARY GLAND SEMINAL VESICLES SKIN SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC T. E. .S.T.E.S. . . . . . . . . . . . . . . . . . . . . .T.H.Y.M.U.S. . . . . . . . . . . . . . . . . . . . . .T.R.A.C.H.E.A. . . . . . . . . . . . . . . . . . . . .U.R.I.N.A.R.Y. .B.L.A.D.D.E.R. . . . . . . End o f Record- 14856 11-6 Page 365 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN AORTA CECUM BONE (FEMUR) COLON ESOPHAGUS JEJUNUM EYES/OPTIC NERVE KIDNEYS HEART LARYNX LYMPH NODE, MANDIBULAR LYMPH NODE, MESENTERIC MAMMARY GLAND NASAL CAVITY/TURBINATES NERVE, SCIATIC PANCREAS PEYER'S PATCH RECTUM PHARYNX/NASOPHARYNX SALIVARY GLAND PITUITARY SEMINAL VESICLES SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC T-E_S_TE_S__------------------T-H-Y-M-U-S---------------------T-HYROID E n d o f R e c o r d - 14857 BONE MARROW (STERNUM) DUODENUM ILEUM LUNG MUSCLE, SKELETAL PARATHYROID PROSTATE SKIN STOMACH URINARY BLADDER 11-7 Page 366 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: BONE MARROW (STERNUM) : necrosis, intersternal cartilage, focal (minimal) BRAIN: dilatation. ventricular (minimal ) LIVER: lipidosis, tension, focal inflamnation, c h r o n i c . f o c a l /mu1 t i f o c a l ( m i nimal ) LYMPH NODE, MANDIBULAR: h y p e r p l a s i a , 1ymphocyt ic / p l asmacyt i c (minimal ) PROSTATE: inflamnation, c h r o n i c , mu1 t i f o c a l (mi 1d) SPLEEN: pigment (hemosiderosis) (mild) T. H. .Y.R.O.I .0.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . u. .l t.i .m.o. b. .r a. .n.c.h.i.a.l . .b.o.d.y. l.c.y.s.t. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL L I M I T S : ADRENAL GLANDS COLON AORTA OUODENUM EYES/OPTIC NERVE KIDNEYS HEART LARYNX MAMMARY GLAND MUSCLE, SKELETAL PANCREAS PARATHYROID PITUITARY RECTUM SKIN SPINAL CORD, CERVICAL STOMACH TESTES U--R-IN-A-R-Y--B-L-A-D-D_E-R-__________ End o f Record- 14858 BONE (FEMUR) EPIDIDYMIDES ILEUM LUNG NASAL CAVITY/TURBINATES PEYER'S PATCH SALIVARY GLAND SPINAL CORD, LUMBAR THYMUS CECUM E SOPHAGUS JEJUNUM LYMPH NODE. MESENTERIC ~~ NERVE, SCIATIC PHARYNX/NASOPHARYNX SEMINAL VESICLES SPINAL CORD, MIOTHORACIC TRACHEA 11-8 Page 367 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7465.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.l.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIDES: HEART : LIVER: PANCREAS : PROSTATE: RECTUM: SPLEEN: T-H--Y-R-O-ID--:-------- i n f i l t r a t i o n , mononuclear-cell, focal (minimal) necrosis, multifocal (minimil) in f l amnati on, subacute (minimal ) inflamnation, chronic, focal/multifocal (minimal) necrosi s. i n d i v i d u a l - c e l l (mi 1d ) inflamnation, chronic, multifocal (minimal) parasite(s1 pigment (hemosiderosis) (minimal ) ultimobranchial body/cyst ---- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN CECUM COLON ESOPHAGUS EYES/OPTIC NERVE I LEUM KIDNEYS LARYNX LUNG LYMPH NOOE, MESENTERIC MAMMARY GLAND MUSCLE, SKELETAL NERVE, SCIATIC PARATHYROID PEYER'S PATCH PITUITARY SALIVARY GLAND SEMINAL VESICLES SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC TESTES THYMUS TRACHEA ----------___--------------------------------------. End o f Record- 14859 BONE MARROW (STERNUM) DUODENUM JEJUNUM LYMPH NODE, MANDIBULAR NASAL CAVITY/TURBINATES PHARYNX/NASOPHARY NX SKIN STOMACH URINARY BLADDER 11-9 Page 368 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 I n d i v i d u a l Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: BRAIN: K IONEYS : LYMPH NODE, PROSTATE: SPLEEN: THYROID: TRACHEA: MANDIBULAR: vacuolation, cortex (minimal) dilatation, ventricular (moderate) h y p e r p l a s i a , p e l v i c / p a p i 11a r y u r o t h e l ium (mi 1d) mineral ization, pel vi s (minimal ) h y p e r p l a s i a , lymphocyti c / p l asmacyti c (mi 1d) inf 1amnat ion , c hronic , mu1t if oc a1 (mi nima1 ) pigment (hemosiderosis) (mild) ultimobranchial bodylcyst ----...............i.n..f1.a..n.a..t.i.o.n., ..c.h.r.o.n.i.c.,..f.o.c.a..l ..(m..i.n.i.m.a.l.)......... THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : AORTA BONE (FEMUR) COLON DUODENUM EYES/OPTIC NERVE HEART LARYNX LIVER MUSCLE, SKELETAL NASAL CAV ITY/TURB INATES PARATHYROID PEYER'S PATCH RECTUM S P I N A L CORD, CERVICAL T-E-S-T_E_S _-----_-_-_______ BONE MARROW (STERNUM) EPIOIOYMIDES ILEUM LUNG NERVE, SCIATIC PHARYNX/NASOPHARYNX SEMINAL VESICLES S P I N A L CORD, MIDTHORACIC URINARY BLADDER .--_------------_---------- CECUM . ESOPHAGUS JEJUNUM LYMPH NODE, PANCREAS PITUITARY SKIN STOMACH MESENTERIC 11-10 Page 369 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): 11-11 Page 370 ~~ ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K- -I D-N-E- -Y-S- - - - - - - - - - - - - - - - - - - -N-A-S-A-L- -C-A-V-I-T-Y-/ T-U-R- -B-I N-A-T-E- -S- - - -P-H-A-R-Y-N-X-/N-A-S-O-P-H-A-R-Y-N-X- - - - - - - - -S-T-O-M-A-C-H- - - - - - - - - - - - - - - - - End of Record- 14862 . 11-12 Page 371 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERVATION(S1: G..E.N.E.R.A.L.: ..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .ic.a.b.1..e............................... THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : KIDNEYS NASAL CAVITY/TURBINATES PHARYNX/NASOPHARYNX STOMACH -------------------------------------*----------------------------------------------------------------- E n d o f R e c o r d - 14863 . 11-13 Page 372 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Hi stomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: in f i 1t r a t i o n , m n o n u c l e a r - c e l l , f o c a l (minimal ) S.T.O..M.A.C.H.: ....................................d.i.l.a.t.a.t.i o..n.,..m..u.c.o.s.a.l .g..la.n.d..s..(.m.i.n.i.m.a.l.)....................... 11-14 Page 373 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: .S.TO..M.A.C.H.:....................................n..e.c.r.o.s.i.s.,..i .n.d.i.v.i.d.u.a..l -.c.e..l l.,..l.i.m..i.t .i .n.g..r.id..g.e..(.m..i n..i m..a.l .) ...... THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : K- -I D-N-E- -Y-S- - - - - _ - - - - - - - - - - - - -N-A- S- -A-L -C-A- -V-I T-Y-/-T-U-R-B-I-N-A-T-E-S- - - - P- H- -A-R-Y-N-X-/ N-A-S-O-P-H-A-R- -Y-N-X- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E n d o f R e c o r d - 14865 11-15 Page 374 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e..s.. ...............................N..o.t .a.p..p.l .i .ca..b.1.e............................... 11-16 Page 375 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i s t m o r p h o l o g y Data THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : K--I-O-N-E-Y-S-------___--____N_AS_AL__CA_V_IT_Y/_TU_R_BI_NA_T_ES___P_H-A-R-Y-N-X-/N-A-S-O-P-H-A-R-Y-N-X---------S-T-O-M-A-C-H-------------------------------- End o f Record- 14867 . 11-17 Page 376 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 STUDY OF IN RATS Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OESERVATION(S): HISTOMORPHOLOGIC OBSERVATIONlSl: G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .t .a.p.p. .l i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: -K-ID-N-E-Y-S-:-----------_-----------------------c-y-s--t -(-s-)-,-m--e-d-u-l-l a---------------------------------------------- 11-18 Page 377 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data 11-19 Page 378 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7465.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATIONS: S.T.O..M.A.C.H.:....................................n.e..c.r.o.s.i.s., ..i n..d.i.v.i.d.u.a..l -.c.e..l l.,..l.i.m..i.t .i n..g..r.i d..g.e..(.m..in.i.m..a.l)....... THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: .K.I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . N. .A.S.A.L. .C.A.V.I .T.Y./ T.U. R. .B.I N. A. .T.E.S. . . .P.H.A. R. Y. N. .X./N.A.S.O. P. H. .A.R.Y.N.X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14870 11-20 Page 379 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .i.ca..b.1.e............................... HISTOMORPHOLOGIC OBSERVATIONS: S.T.O.M..A.C.H.:...................................d..i l.a..t a..t i.o.n..,..m.u.c.o.s.a.l..g.l.a.n.d.s..(.m..in.i.m..a.l)........................ THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL LIMITS: .K.I D. N. .E.Y.S. . . . . . . . . . . . . . . . . . . . .N.A.S.A.L. .C.A.V.I .T.Y./ T.U. R. .B.I N. A. .T.E.S. . . .P.H. A. R. Y. N. .X./N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 14871 11-21 Page 380 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: K--ID_N-E-Y_S_: ______----_____________i_n_f i_l t_r a_t_i o_n_, _m_o-n-o-n-u-c-l-e-a-r---c-e-ll--,--fo--c-a-l--(-m-i-n-i-m-a--l)-------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: .N.A.S.A.L..C.A.V.I.T.Y./T.U.R..B.IN.A..T.E.S....P.H.A.R.Y.N..X./N.A.S.O.P.H.A.R..Y.N.X...' .....S.T.O.M.A.C.H........................................... End o f Record- 14872 11-22 Page 381 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphology Data I1-23 Page 382 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N.o..t .a.p.p..l i.c.a.b.1.e................................ HISTOMORPHOLOGIC OBSERVATIONS: .S.TO..M.A.C.H.:....................................n.e..c.r.o.s.i.s., ..i n..d.i.v.i.d.u.a..l -.c.e..l l.,..l.i.m..i t.i.n.g...r.i d..g.e..(.m..in.i.m..a.l)....... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: K. .ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . N. .A.S.A.L. .C.A.V.I T. Y. ./ T.U.R. B. .I N.A.T. E. S. . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14874 11-24 Page 383 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: i n f i 1t r a t i o n . mononuclear-cell , f o c a l (minimal ) NASAL CAVITY/TURBINATES: in f l a m n a t i on, c h r o n i c , f o c a l /mu1 t i f o c a l (minimal ) STOMACH: necrosis, individual-cell, l i m i t i n g ridge (minimal) ---------_------____*-_-------------------------------------------------------------------------------- 11-25 Page 384 ~~ ~ ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): H ISTOMORPHOLOGI C O B S E R V A T I O N ( S ) : G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a.p.p. .l i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: 11-26 Page 385 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 STUDY OF I N RATS Appendix I1 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l D g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .t .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .K.I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . .N. A. S. .A.L . .C.A.V.I T. .Y./ T.U. R. .B.I N. A. .T .E.S. . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . E n d o f R e c o r d - 14877 11-27 Page 386 -- ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): H ISTOMORPHOLOGIC OBSERVATION ( S) : HISTOMORPHOLOGIC OBSERVATIONS: NASAL CAVITY/TURBINATES: i n f l a m n a t i o n , c h r o n i c , f o c a l /mu1 t i f o c a l ( m i I d ) metaplasia, squamous, r e s p i r a t o r y epi the1 iurn, f o c a l (mi 1d) dysplasia, tooth (marked) ............................................a.b.s.c.e.s.s., ..to..o.t.h.............................................. THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: K. .I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N. X. . . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14878 11-23 Page 387 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : K--ID-N-E-Y--S--------------------N-A-S-A-L--C-A-V-I-T-Y-/T-U-R--B-IN-A-T-E-S-----P-H-A-R-Y-N-X-/N-A-S-O-P-H-A-R-Y-N-X----~ -----S-T-O-M-A-C-H-----------------End of Record- 14879 . 11-29 Page 388 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.: ..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p.p..l .ic.a.b..1.e............................... HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : N--A-S-A-L_C-A-V-I-T-Y_/ T_U -R-B-I N-_A T_E -S___PH_A_RY_N_X/N_A_SO_P_HA_R_YN_X _____S_TO-M--A-C-H---------------------------------------------------------- E n d o f R e c o r d - 14880 I 1-30 Page 389 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: CECUM: COLON : KIDNEYS: LARYNX : LYMPH NODE, MANDIBULAR: NASAL CAVITY/TURBINATES: PARATHYROID: RECTUM: SPLEEN: STOMACH: THYROID: i n f l a m n a t i o n , c h r o n i c , mucosa ( m i l d ) parasite(s) edema, papi 11a r y (mi nimal ) hyaline droplets, cortical tubules (mild) h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 iurn, papi 11a (minimal ) inflamnation. chronic, focal (minimal ) h y p e r p l a s i a , 1ymphocyti c / p l asmacytic (mi nimal ) necrosis, olfactory epithelium, multifocal (mild) deviation, nasal septum hyperostosis, t u r b i n a t e bone (mild) adhesion ( s ) i n f l amnati o n , c h r o n i c , f o c a l /mu1 t i f o c a l (mi 1d) in f i 1t r a t i on, 1ymphocyti c (mi 1d ) parasite(s) pigment (hemosiderosis) (mild) necrosis, individual-cell, limiting ridge (minimal) follicle(s), cystic THE FOLLOWING T I S S U E f S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN EYES/OPTIC NERVE LIVER MUSCLE. SKELETAL PHARYNX/NASOPHARYNX SEMINAL VESICLES SPINAL CORD, MIDTHORACIC U..R.I.N.A.R.Y...B.L.A.D.D.E.R......... End o f Record- 14881 AORTA DUODENUM HEART LUNG NERVE, SCIATIC PITUITARY SKIN TESTES BONE (FEMUR) EPIDIDYMIDES ILEUM LYMPH NODE, MESENTERIC PANCREAS PROSTATE S P I N A L CORD, CERVICAL THYMUS BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM MAMMARY GLAND PEYER'S PATCH SALIVARY GLAND S P I N A L CORD. LUMBAR TRACHEA 11-31 Page 390 -- ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 Individual Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): .G.E.N.E.R.A.L.: ..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p.p.l..i c.a.b.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIDES: KIDNEYS: PANCREAS: PROSTATE : RECTUM: SPLEEN: STOMACH: infiltration, mononuclear-cell, focal (minimal) edema, papi 1 1ary (minimal ) hyperplasia, tubular/ductular epithe1 i urn, papilla (minimal) cellular a1 teration, basophi1 ic, focal (minimal) i nf1annati on, chronic , mu1 ti focal (mini mal ) parasi te(s) pi gment (hemosi derosis ) (mi1d) hyperplasialhyperkeratosis, 1 imiting ridge (minimal) necrosis, individual-cell, limiting ridge (mild) congesti on, mu1 ti focal (minimal ) . . . . . . . . . . . . .u.l.t.i.m.o.b.r.a.n.c.h. i. a. l. . .b.o.d.y.l.c.y.s.t. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E [ S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM LYMPH NODE, MANDIBULAR NASAL CAV IT Y l T U R BI NATES PHARYNX/NASOPHARY NX SKIN .T.E.S.T.E.S.................. End o f R e c o r d - 1 4 8 8 2 AORTA BONE (FEMUR) BONE MARROW (STERNUM) CECUM COLON DUODENUM EYESIOPTIC NERVE HEART ILEUM LARYNX LIVER LUNG LYMPH NODE, MESENTERIC MAMMARY GLAND MUSCLE, SKELETAL NERVE, SCIATIC PARATHYROID PEYER'S PATCH PITUITARY SALIVARY GLAND SEMINAL VESICLES S P I N A L CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC --T-R-A-C-H-E-A_--_--______-_-_U_R_-IN_A_RY_- _BL_AD~DE_R_ _ _ _ _ _ _ _ _ _ _ I1-32 Page 391 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 Individual Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G--E-N-E-R_AL_: _N_o_g_ro_s-s--c-h-a-n-g-e_s.___________________-N-o-t--a-p-p-l-i-c-a-b-1-e------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS : HEART: KIDNEYS: LIVER: LYMPH NODE. MANDIBULAR: NASAL CAVITY/TURBINATES : vacuolation, cortex,(minimat ) inflammation. subacute (minimal) necrosis. multifocal (minimal) di 1 atation, tubules, papi 1 1 a (minimal) hyperplasia, tubular/ductular epithel i urn, papi 1la (minimal) basophilia, tubular, multifocal (minimal) i nflammation. chronic, focal/mu1ti focal (minimal) hyperplasia, 1ymphocyticlplasmacytic (mi1 d ) adhesi on( s ) atrophy, olfactory epithelium, multifocal (minimal) hyperplasia, 01 factory epitheli urn, focal (miId) inflammation. chronic, mu1 ti focal (miId) pigment (hemosiderosis) (moderate) necrosis, individual-cell, limiting ridge (minimal) . . . . . . . . . . . . .u.l.t.i.m.o.b.r.a.n.c.h.i.a.1. . .b.o.d.y./.c.y.s.t. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : AORTA BONE (FEMUR) BONE MARROW (STERNUM) CECUM COLON DUODENUM ESOPHAGUS EYES/OPTIC NERVE ILEUM LARYNX LUNG LYMPH NODE, MESENTERIC NERVE, SCIATIC PANCREAS PARATHYROID PHARYNX/NASOPHARYNX PITUITARY RECTUM SEMINAL VESICLES SKIN S P I N A L CORD, CERVICAL SPINAL CORD. MIOTHORACIC TESTES THYMUS U. .R.I N. A. .R.Y. .B.L.A.D.D.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BRAIN EPIDIDYMIDES JEJUNUM MUSCLE, SKELETAL PEYER'S PATCH SALIVARY GLAND S P I N A L CORD, LUMBAR TRACHEA T I S S U E ( S ) NOT AVAILABLE FOR EVALUATION: 11-33 Page 392 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: BONE (FEMUR) : degeneration, articular cartilage, focal (mild) EPIDIDYMIDES: i n f i l t r a t i o n , mononuclear-cell , focal (minimal) KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (mild) basophi 1 i a , t u b u l a r , mu1t i f o c a l (minimal ) LARYNX : inflamation, chronic, focal (minimal) LYMPH NODE, MANDIBULAR: h y p e r p l a s i a , lymphocyti c / p l asmacyt ic (mi 1d) PROSTATE: prostatitis, suppurative (minimal) SPLEEN: pigment (hemosiderosis) (minimal) S-T-O-M--A-C-H_: -------___--_____________n_e_cr_os_is_,_i_n-d-i v--i d-u--a-l-- c--e-l l-.---l i-m--i-t-i -n-g--r-i d--g-e--(-m-i-n-i-m-a--l)----------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS AORTA BONE MARROW (STERNUM) BRAIN CECUM COLON DUODENUM ESOPHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM LIVER MUSCLE, SKELETAL LUNG NASAL CAV I T Y / T U R B I NATES LYMPH NODE, MESENTERIC NERVE, SCIATIC MAMMARY GLAND PANCREAS PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARYNX PITUITARY RECTUM SALIVARY GLAND SEMINAL VESICLES SKIN SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC TESTES T.H..Y.M.U.S......................T.H..Y.R.O.I.D.............. --_TR_A_CH_EA____-________UR-I-N-AR-Y--B-L-A-DDER End o f Record- 14884 11-34 Page 393 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal Gross and Hi stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): E A R ( S ) : Swollen, right. proliferation, vascular, focal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i. n. f. i. l. .t.r.a.t.i.o.n... .p.o.l.y.m.o.r.p.h.o.n. u. c. .l.e.a.r. . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: EAR(S) : KIDNEYS : LARYNX : LIVER: PANCREAS : PROSTATE: SPLEEN: STOMACH: THYROID : T..R.A.C.H.E.A.:.......................... ---- pro1 i feration. vascular, focal (moderate) i nfi 1tration. polymorphonuclear (moderate) edema. papillary (minimal) inflamnation, chronic, focal (minimal) lipidosis, tension, focal i nflamnation, chronic, focal/mu1tifocal (min i mal ) atrophy, acinar, focal (minimal) inflamnation, chronic, mu1 ti focal (minimal) pigment (hemosiderosis) (mild) hyperplasia/hyperkeratosis, 1imiting ridge (minimal) necrosis, individual-cell, limiting ridge (mild) ul timobranchial body/cyst i nf1 amnat i on, chronic , focal (minimal ) THE FOLLOWING T I S S U E I S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN EPIDIDYMIDES ILEUM LYMPH NODE, MESENTERIC NERVE, SCIATIC PITUITARY SKIN T.E..S.T.E.S................. End of Record- 14885 AORTA CECUM ESOPHAGUS JEJUNUM MAMMARY GLAND PARATHYROID RECTUM S P I N A L CORD, CERVICAL THYMUS BONE (FEMUR) COLON EYES/OPTIC NERVE LUNG MUSCLE, SKELETAL PEYER'S PATCH BONE MARROW (STERNUM) DUODENUM HEART LYMPH NODE, MANDIBULAR NASAL CAVITY/TURBINATES PHARYNX/NASOPHARY NX SEMINAL VESICLES S P I N A L CORD, MIDTHORACIC 11-35 Page 394 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: LYMPH NODE, RECTUM: SPLEEN : STOMACH: MANDIBULAR: THY R O I D: hyperplasia, lymphocytic/plasmacytic (mi I d ) parasi te(s) pigment (hemosiderosis) (mi 1d ) hyperplasia/hyperkeratosis. 1i m i t i n g ridge (minimal ) necrosis, individual-cell, l i m i t i n g ridge (minimal) ultimobranchial bodylcyst -----.....h.y.p.e.r.t.r.o.p.h.y.,..f.o..l l.i.c.u..l .a.r..e.p.i.t.h.e.l.iu..m...(.m.i.l.d.)........... ______- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN EP IO1 DYMI DES CECUM ESOPHAGUS COLON EYES/OPTIC NERVE ILEUM JEJUNUM KIDNEYS LIVER LUNG LYMPH NODE, MESENTERIC MUSCLE, SKELETAL NASAL C A V I TY/TURB INATES NERVE, S C I A T I C PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARYNX PROSTATE SALIVARY GLAND SEMINAL VESICLES SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC T-H_Y-M_US_ _ _ _ - - _ _ _ - - - _ _ _T_R_AC_HE_A_ _ _ _ _ _ _ _ _ _ _ _. - -_U_ _R_-I-N-_-A- _-R_ _Y__ _-B_-L_-A_ _-D_-D- --E--R- --- -- - BONE MARROW (STERNUM) DUODENUM HEART LARYNX MAMMARY GLAND PANCREAS PITUITARY SKIN TESTES COMMENTS : NASAL CAVITY/TURBINATES The head was r e c e i v e d damaged as a result o f necropsy/dissection a r t i f a c t . There were no lesions observed and the nasal c a v i t y / t u r b i n a t e s w i l l be considered t o be ----........w.i.t.h.i.n..n.o.r.m.a.l..l.i .m.i.t.s.......................................... 11-36 Page 395 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIDES: infiltration, mononuclear-cell, focal (minimal) KIDNEYS: hyperplasia, tubular/ductul ar epithe1 i um, papi 1 1 a (mi1 d) LARYNX : inflamnation. chronic, focal (mild) LYMPH NODE, MANDIBULAR: hyperplasia, lymphocytic/plasmacytic (mild) PROSTATE: inflamnation, chronic, mu1 ti focal (minimal) RECTUM : parasite(s ) SPLEEN: pigment (hemosiderosis) (minimal) S.T.O.M..A.C.H.: ...................................d..i.l.a.t.a.t.i.o.n.,..m.u.c.o.s.a.l..g.l.a.n.d.s..(.m.i.n.i.m.a..l.)....................... THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN AORTA C_FC-L_IM_ ESOPHAGUS EYES/OPTIC NERVE JEJUNUM LIVER MUSCLE, SKELETAL NASAL CAVITY/TURBINATES PARATHYROID PEYER'S PATCH SALIVARY GLAND SEMINAL VESICLES S P I N A L CORD, LUMBAR S P I N A L CORD, MIDTHORACIC T. .H.Y.R.O.I.D. . . . . . . . . . . . . . . . . . . . . T. R. .A.C.H.E.A. . . . . . . . . . . . . . . . . BONE (FEMUR) BONE MARROW (STERNUM) COLON DUODENUM HEART ILEUM LUNG LYMPH NODE, MESENTERIC NERVE, SCIATIC PANCREAS PHARYNX/NASOPHARYNX PITUITARY SKIN SPINAL CORD, CERVICAL TESTES THYMUS URINARY BLADDER .---___-----_____-__------------------------------ 11-37 Page 396 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e..s.. ...............................N.o..t .a.p..p.l .ic.a.b.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIDES: HEART : KIDNEYS : NASAL CAVITY/TURBINATES : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) inflarnnation, subacute (mi I d ) hyperplasia, t u b u l a r / d u c t u l a r epi t h e l iurn, papi 1l a (mi i d ) adhesion(s ) inflarnnation. chronic, focal/mul t i f o c a l (mi I d ) necrosis, 01 f a c t o r y epi t h e l ium. mu1t i f o c a l (moderate) hyperostosis, t u r b i n a t e bone (mi I d ) hyperplasia, 01 f a c t o r y e p i t h e l i u m . f o c a l (moderate) pigment ( hemosi deros is ) (mi nimal ) hyperplasia/hyperkeratosi s . 1i m i t i ng r i d g e (minimal ) necrosis, individual-cell, l i m i t i n g ridge (minimal) ...h.y.p.e.r.t.ro..p.h.y.,..f.o.l.l.i .c.u.l.a.r..e..p.i.th..e.li.u.m...(.m.o..d.e.ra..te.).......... ---- THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BRAIN CECUM ESOPHAGUS LARYNX EYES/OPTIC NERVE LIVER LYMPH NODE, MESENTERIC MAMMARY GLAND PANCREAS PARATHYROID PITUITARY PROSTATE SEMINAL VESICLES SKIN S P I N A L CORD, MIDTHORACIC TESTES U- _R I N_A_R Y- -B-L_A D_D_E R_ _ - - _ _ _ - _ _ _ _ _ _ _ End of Record- 14888 BONE (FEMUR) COLON ILEUM LUNG MUSCLE, SKELETAL PEYER'S PATCH RECTUM SPINAL CORD, CERVICAL THYMUS ----- BONE MARROW (STERNUM) DUODENUM JEJUNUM LYMPH NODE, MANDIBULAR NERVE, SCIATIC PHARYNX/NASOPHARYNX SALIVARY GLAND SPINAL CORD, LUMBAR TRACHEA .- 11-38 Page 397 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l Animal G r o s s and Hi stomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: HEART: KIDNEYS : LARYNX : LIVER: LYMPH NODE, MANDIBULAR: PANCREAS : SPLEEN: STOMACH: inflamnation, chronic, focal (minimal) hyperplasia, t u b u l a r / d u c t u l a r epi the1 ium, papi I l a inflamnation, c h r o n i c , f o c a l (minimal ) lipidosis, tension, focal in f l amnati on, c h r o n i c , f o c a l /mu1 t i f o c a l (minimal ) congestion (minimal) hyperpl a s i a , lymphocyti c / p l asmacyti c (mi nimal ) in f i 1t r a t i on, mononuclear-cel 1 , f o c a l (mi nimal ) pigment (hemosiderosis) (minimal ) hyperplasia/hyperkeratosis, 1imiting ridge (mild) necrosis, individual-cell, limiting ridge (mild) (minimal ) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN EPIDIDYMIDES JEJUNUM MUSCLE, SKELETAL PEYER'S PATCH RECTUM SPINAL CORD, CERVICAL T.H..Y.M.U.S................. End o f Record- 14889 AORTA CECUM ESOPHAGUS LUNG NASAL CAVITY/TURBINATES PHARYNX/NASOPHARYNX SALIVARY GLAND S P I N A L CORD, LUMBAR THYROID BONE (FEMUR) COLON EYES/DPTIC NERVE LYMPH NODE, MESENTERIC NERVE, SCIATIC P ITU1TARY SEMINAL VESICLES S P I N A L CORD, MIDTHORACIC TRACHEA BONE MARROW (STERNUM) DUODENUM ILEUM MAMMARY GLAND PARATHYROID PROSTATE SKIN TESTES ..U.R.I.N.A.R.Y...B.L.A.D.D..E.R..... 11-39 Page 398 -- ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7465.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): GASTROINTESTINAL TRACT: Stomach- cardiac region, No microscopic change t o c o r r e l a t e , STOMACH w a l l s t h i n ; stomach and i n t e s t i n e s - distended No microscopic change t o c o r r e l a t e , DUODENUM with gas. Advanced a u t o l y s i s precludes evaluation, JEJUNUM No microscopic change t o c o r r e l a t e . ILEUM No microscopic change t o c o r r e l a t e , COLON No microscopic change t o c o r r e l a t e , CECUM No microscopic change t o c o r r e l a t e . RECTUM No microscopic change t o c o r r e l a t e , PEYER'S PATCH SPLEEN: Small . atrophy p i gment (hemosid e ros is ) T.H.Y.M..U.S.:..R.e.d................................................c.o.n.g.e.s.t.i.o.n.,..m..u.l .t i.f.o.c.a.l........................ H I STOMORPHOLOGIC OBSERVATIONS: CECUM: COLON : DUODENUM: HEART : ILEUM : JEJUNUM: KIDNEYS: PEYER'S PATCH: RECTUM: SPLEEN : STOMACH: THYMUS: THYROID: No microscopic change t o c o r r e l a t e No microscopic change t o c o r r e l a t e No microscopic change t o c o r r e l a t e d i l a t a t i o n , a t r i a l (moderate) inflamnation. subacute (minimal ) No microscopic change t o c o r r e l a t e Advanced a u t o l y s i s precludes e v a l u a t i o n necrosi s , papi 11ary (moderate) basophilia, tubular, multifocal (moderate) hyperplasia, tubular/ductular epi the1 ium, p a p i l l a (moderate) No microscopic change t o c o r r e l a t e No microscopic change t o c o r r e l a t e atrophy (moderate) pigment (hemosiderosis) (moderate) No microscopic change t o c o r r e l a t e congestion, m u l t i f o c a l (marked) u l t imobranchi a1 b o d y l c y s t ---- . . . . . . . . . .f.o.l.1.i.c. .l e. .(.s.) .,. .c.y.s.t.i.c. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL L I M I T S : AORENAL GLANDS BRAIN EPIDIDYMIDES LARYNX LYMPH NODE, MESENTERIC NERVE, SCIATIC AORTA CECUM ESOPHAGUS LIVER MAMMARY GLAND PANCREAS PHARY NX/NASOPHARYNX PITUITARY -S-A-LI-V_AR_Y_G-L-A_ND_ _ _ - - _ _.-_--S__E-_M--_I-N_A__L__-V-_E_S_I_C_L_E-S________ CONTINUED- 14890 BONE (FEMUR) COLON EYESIOPTIC NERVE LUNG MUSCLE, SKELETAL PARATHYROID PROS TAT E SKIN BONE MARROW (STERNUM) DUODENUM ILEUH LYMPH NODE, MANDIBULAR NASAL CAVITY/TURBINATES PEYER'S PATCH RECTUM SPINAL CORD, CERVICAL ---_--_--_--__------_r___________ 11-40 Page 399 _ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphology Data THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: 11-41 Page 400 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: CECUM: parasite(s) KIDNEYS : mineral iz a t i o n , mu1t i f o c a l (minimal ) LIVER: vacuolation, hepatocellular, periportal (mild) inflammation. chronic, focal/rnul tifocal (minim1) SPLEEN: p i gment ( hemosideros is) (moderate) T-H-Y-R_O-I -D-: - _ _ _._. _. ._. . . . . . . . . . . . . . . . . . . . . . . . .u.t.t.i m. .o.b. r.a.n. .c.h.i a. l. . b. .o.d.y.l.c.y.s.t. . . . . . . . . . . . . . . . . . . . . . . . --- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BRAIN COLON EYES/OPTIC NERVE HEART LARYNX LUNG MAMMARY GLAND MUSCLE, SKELETAL OVARIES PANCREAS PHARYNX/NASOPHARYNX P ITUITARY SKIN SPINAL CORD, CERVICAL STOMACH THYMUS .U.T.E.R.U.S.......................V.A.G.I.N.A................. End o f Record- 14891 BONE (FEMUR) DUODENUM ILEUM LYMPH NODE. MANDIBULAR NASAL CAVITYITURBINATES PARATHYROID RECTUM SPINAL CORD, LUMBAR TRACHEA BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM LYMPH NODE. MESENTERIC NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC URINARY BLADDER 11-42 Page 401 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l Animal G r o s s and Histomorphology Data GROSS OBSERVATION(S) : H ISTOMORPHOLOGI C OBSERVATION( S ) : G..E.N.E.R.A.L.: ..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N.o.t..a.p.p.l.i.c.a.b.1.e................................ HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LARYNX: LIVER: LYMPH NODE, MANDIBULAR: PANCREAS : PEYER'S PATCH: PHARYNX/NASOPHARYNX: SPLEEN : THYROID : U..T.E.R.U.S.:........................ mineral i z a t ion, mu1t i focal (minimal ) inflamnation, chronic, focal (mi I d ) inflamnat ion, chronic, focal/mul t ifocal (minimal ) hyperplasia, 1ymphocyt ic/pl asmacyt ic (minimal ) i n f i 1t r a t i o n , mononuclear-cell , focal (minimal ) mineral iz a t i on, focal (minimal ) in f1a m t ion, chroni c , focal /mu1 t i focal (mi 1d ) pigment (hemosiderosis) (moderate) u l t i m b r a n c h ia1 body/cyst d i s t e n t i o n , lumen (minimal ) ------ THE FOLLOWING T I S S U E f S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM MUSCLE, SKELETAL PARATHYROID SKIN STOMACH V.A..G.I.N.A................... End o f Record- 14892 AORTA CECUM EYES/OPTIC NERVE LUNG NASAL CAVITY/TURBINATES PITUITARY S P I N A L CORD, CERVICAL THYMUS BONE (FEMUR) COLON HEART LYMPH NODE, MESENTERIC NERVE, SCIATIC RECTUM S P I N A L CORD, LUMBAR TRACHEA BONE MARROW (STERNUM) DUODENUM ILEUM MAMMARY GLAND OVARIES SALIVARY GLAND S P I N A L CORD, MIDTHORACIC URINARY BLADOER 11-43 Page 402 __ ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix 11 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t.a..p.p.l .i.ca.b.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : mineral iz a t i on, mu1t i f o c a l (minimal ) LYMPH NODE, MANDIBULAR: hyperpl a s i a, 1ymphocyt ic / p l asmacyt ic (mi nimal ) NASAL CAVITY/TURBINATES: dysplasia, t o o t h (mi I d ) deviation, nasal septum S. .P.LE. .E.N.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.i.g.m.e.n.t. .(.h.e.m. .o.s.i.d.e.r.o.s.i s. ). . .(m. .i .1.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS AORTA BRAIN ESOPHAGUS CECUM EYES/OPTIC NERVE JEJUNUM LARYNX LYMPH NODE, MESENTERIC MAMMARY GLAND OVARIES PANCREAS PHARYNX/NASOPHARY NX P ITU1TARY SKIN SPINAL CORD, CERVICAL STOMACH THYMUS -U-R-IN-A-R-Y--B_LA_DD_E_R ___________ End o f Record- 14893 BONE (FEMUR) COLON HEART LIVER MUSCLE, SKELETAL PARATHYROID RECTUM SPINAL CORD, LUMBAR THYROID BONE MARROW (STERNUM) DUODENUM ILEUM LUNG NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC TRACHEA 11-44 Page 403 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 Individual Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: LIVER: inflamnation. chronic, focal/mul t i focal (minirnal ) LYMPH NODE. MANDIBULAR: hyperplasia. lymphocyti c/plasmacyti c (minimal ) STOMACH: necrosis, individual-cell, limiting ridge (minimal) TAIL: degeneration, cystic, intervertebral disk THYROID: ul timobranchial body/cyst U-T-E-R_U_S :_---------___------------____--di--s_te_nt_i-o-n-,--1-u-m-e-n--(-m-o-d-e-r-a-t-e-)-------------------------------------- THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM LYMPH NODE, MESENTERIC NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND S P I N A L CORD. MIDTHORACIC VAG INA AORTA CECUM EYES/OPTIC NERVE KIDNEYS MAMMARY GLAND OVARIES PHARY NX/NASOPHARYNX SKIN SPLEEN BONE (FEMUR) COLON HEART LARYNX MUSCLE, SKELETAL PANCREAS P ITUITARY SPINAL CORD, CERVICAL THYMUS BONE MARROW (STERNUM) DUODENUM ILEUM LUNG NASAL CAVITY/TURBINATES RPEACRTAUTMH Y R O I D S P I N A L CORD, LUMBAR TRACHEA T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: 11-45 Page 404 ARGUS 418-026 ORAL (GAVAGE) REPEATED OOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e..s.. ...............................N..o.t .a.p..p.l .i c.a..b.1.e............................... HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: mineralization, multifocal (mild) L..IV.E.R..: ......................................i.n.f.l.a.m..n.a.ti.o.n.,..c.h..ro..n.ic.., ..f o.c.a..l /.m..u.l .t.i.f.o.c.a.l..(.m..i n.i.m..a.l .) ......... THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BONE (FEMUR) BONE MARROW (STERNUM) BRAIN CECUM COLON DUODENUM ESOPHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM LARYNX LUNG LYMPH NODE. MANDIBULAR LYMPH NODE, MESENTERIC MAMMARY GLAND MUSCLE, SKELETAL NASAL CAVITY/TURBINATES NERVE, SCIATIC OVARIES PANCREAS PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARY NX PITUITARY RECTUM SALIVARY GLAND SKIN S P I N A L CORD, CERVICAL SPINAL CORD. LUMBAR SPINAL CORD, MIDTHORACIC SPLEEN STOMACH THYMUS THYROID TRACHEA URINARY BLADDER UTERUS V. A. G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 14895 11-46 Page 405 ARGUS 4 18-036 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: -LA-R--Y-N-X-:--__-______--------------------i-n-f-l-a-m--n-a-ti-o-n-,--c-h-r-o-n--ic-,--f-o-c-a--l --( m--i -n-i m--a-l -)--------------------------- THE FOLLOWING T I S S U E ( ~ ~WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN CECUM COLON ESOPHAGUS EYES/OPTIC NERVE HEART JEJUNUM KIDNEYS LIVER LYMPH NODE, MANDIBULAR LYMPH NODE, MESENTERIC MAMMARY GLAND NASAL CAVITY/TURBI NATES NERVE, SCIATIC OVARIES PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARY NX RECTUM SALIVARY GLAND SKIN S P I N A L CORD, LUMBAR S P I N A L CORD, MIDTHORACIC SPLEEN THYMUS THYROID TRACHEA U..T.E.R.U.S................. ---V-A-G-I_NA________-____-------- E n d o f R e c o r d - 14896 BONE MARROW (STERNUM) DUODENUM ILEUM LUNG MUSCLE, SKELETAL PANCREAS PITUITARY SPINAL CORD, CERVICAL STOMACH URINARY BLADDER 11-47 Page 406 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and H i stomorphology Data COLON : KIDNEYS : LIVER: LYMPH NODE, RECTUM: SPLEEN: UTERUS : MANDIBULAR: parasit e ( s ) nephritis, chronic, focal (minimal) inf 1amnat ion, chron ic , f o c a l /mu1 t i f o c a l (mi n imal ) h y p e r p l a s i a , 1ymphocytic/pl asmacyti c (minimal ) parasite(s) p i gment (hemosideros is ) (moderate) d i s t e n t i o n , lumen (moderate) THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN CECUM DUODENUM EYES/OPTIC NERVE HEART ILEYM LARYNX LUNG LYMPH NODE, MESENTERIC MUSCLE, SKELETAL NASAL CAVITY/TURBINATES NERVE, S C I A T I C PANCREAS P ITU1TARY PARATHYROID SALIVARY GLAND PEYER'S PATCH SKIN SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC STOMACH T.H. .Y.R.O.ID. . . . . . . . . . . . . . . . . . . . . .TR. .A.C.H.E.A. . . . . . . . . . . . . . . . . . . . .U.R.I.N.A.R.Y. .B.L.A.D.D.E.R. . . . . . . End o f Record- 14897 BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM MAMMARY GLAND OVARIES PHARYNX/NASOPHARYNX SPINAL CORD, CERVICAL THYMUS VAGINA .-_____--___________-------- 11-48 Page 407 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 Individual Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION (S : G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .ic.a.b.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: parasi t e ( s ) mineral iz a t i o n , mu1t i f o c a l (minimal ) hyperplasia, lymphocyti c/pl asmacytic h y p e r p l a s i a , mu1t i f o c a l (minimal ) pigment (hemosiderosis) (moderate) d i s t e n t i o n , lumen (moderate) (moderate) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN EYES/OPTIC NERVE LARYNX MUSCLE, SKELETAL PANCREAS PITUITARY SPINAL CORD, CERVICAL THYMUS VAG I NA AORTA CECUM HEART LIVER NASAL CAVITY/TURBINATES PARATHYROID RECTUM SPINAL CORD, LUMBAR THYROID BONE (FEMUR) DUODENUM ILEUM LUNG NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC TRACHEA BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM LYMPH NODE, MESENTERIC OVARIES PHARYNX/NASOPHARYNX SKIN STOMACH URINARY BLADDER End o f Record- 14898 11-49 Page 408 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a HISTOMORPHOLOGIC OBSERVATIONS: LIVER: lipidosis, tension, focal inflamnation, chronic, f o c a l / m u l tifocal ( m i n i m a l ) LYMPH NODE, MANDIBULAR: hyperplasia, lymphocytic/pl asmcytic ( m i n i m a l ) .S.P.L.E.E.N.:.....................................p.i.g.m.e.n..t .(.h.e.m..o.s.i.d.e.r.o.s.i.s.) ..(m..o.d.e.r.a.t.e.)......................... THE FOLLOWING T I S S U E f S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM LYMPH NODE, MESENTERIC NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC TRACHEA AORTA CECUM EYES/OPTIC NERVE KIDNEYS MAMMARY GLAND OVARIES PHARYNX/NASOPHARY NX SKIN STOMACH URINARY BLADDER BONE (FEMUR) COLON HEART LARYNX MUSCLE, SKELETAL PANCREAS PITUITARY S P I N A L CORD, CERVICAL THYMUS UTERUS BONE MARROW (STERNUM) DUOOENUM ILEUM LUNG NASAL CAVITY/TURE INATES PARATHYROID RECTUM SPINAL CORD, LUMBAR THYROID VAGINA 11-50 Page 409 ARGUS 4 18-036 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i stomorphology D a t a G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a.p.p. .l i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: LYMPH NODE, MANDIBULAR: hyperplasia, lymphocytic/plasmacytic (minimal) S..P.L.E.E.N.: ....................................p..i g.m..e.n.t..( .h.e.m.o.s.i.d.e.r.o.s.i.s.)..(.m.i.I.d.).............................. THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BRAIN CECUM ESOPHAGUS EYES/OPTIC NERVE JEJUNUM KIDNEYS LUNG LYMPH NODE, MESENTERIC NASAL CAVITY/TURBI NATES NERVE, SCIATIC PARATHYROID PEYER'S PATCH RECTUM SALIVARY GLAND S P I N A L CORD, LUMBAR S P I N A L CORD, MIDTHORACIC T-R_A_CH_EA- _ _ _ _ _ _ _ _ _ _ _U-T-ER-U_S_ _ _ _ BONE (FEMUR) COLON HEART LARYNX MAMMARY GLAND OVAR IES PHARYNX/NASOPHARYNX SKIN THYMUS VAG I NA ---- BONE MARROW (STERNUM) DUODENUM ILEUM LIVER MUSCLE, SKELETAL PANCREAS PITUITARY SPINAL CORD, CERVICAL THYROID T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: STOMACH U. .R.I N. .A.R.Y. .B.L.A.D.D.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d of R e c o r d - 14900 11-51 Page 410 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data THE FOLLOWING TISSUEIS) WERE W I T H I N NORMAL LIMITS: K. .I D.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . .N.A.S.A.L. .C.A.V.I .T .Y./ T.U.R. .B.I N.A. T. E. .S. . . .P.H. A. R. .Y.N.X./N.A.S.O. P. H. .A.R.Y.N.X. . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . End o f Record- 14901 . 11-52 Page 411 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : in f i 1t r a t i o n . mononuclear-cell , f o c a l (minimal ) ............................................m.i.n.e.r.a.l.i.z.a.t.i.o.n.,..m..u1.t..i.fo.c..a.l ..(.m.i.n.im..a.l.)....................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : 11-53 Page 412 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data HISTOMORPHOLOGIC OBSERVATIONS: K--ID-N-E-Y--S-:-----------------------------------i-n-f-i-l -t r-a--t -i o--n-,--m-o--n-o-n-u-c-l-e-a-r---c-e-ll-,--f-o-c-a-l--(-m--in-i-m--a-l)-------------- THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: -N-A-S-A-L--C-A-V-IT-Y-/-T-U-R-B-I-N-A-T-E-S-----P-H-A-R-Y-N-X-/-N-A-S-O-P-H-A-R-Y-N-X--------S-T-O-M-A-C-H-------------------------------------------- End o f Record- 14903 11-54 Page 413 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No gross changes. Not applicable -------------------____________^________--------------------------------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: K. .I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . .N.A.S.A.L. .C.A.V. I.T.Y./.T.U.R.B.I.N.A.T.E.S. . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . End o f Record- 14904 . 11-55 Page 414 ARGUS 41S-026 ORAL (GAVAGE) REPEATEO DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No gross changes. Not appl icab1e -----------------__-_________^__________--------------------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: K..ID.N.E..Y.S.:....................................m..in.e..ra..li.z.a.t.i.o.n....m.u.1.t..i f.o.c..a.l ..(.m.i.n.im..a.l.)....................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: 11-56 Page 415 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 Individual Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : mineralization. multifocal (moderate) .S.TO. .M.A.C.H.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i.l.a.t.a.t.i.o.n.,. .m.u.c.o.s.a.l. .g.l.a.n.d.s. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : N. .A.S.A.L. .C.A.V.I .T .Y./ T.U. R. .B.I N.A. T. E. .S. . . .P.H.A.R. Y. N. X. /.N.A.S.O.P.H.A.R. Y. N. .X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . COMMENTS : NASAL CAVITY/TURBINATES Due to dissection artifact induced during necropsy, the mast posterior section o f the nasal cavity is not available, but . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.l.l. . o. t. h. .e.r. .a.r.e.a.s. .a.r.e. .w.i.t.h.i.n. . n.o.r.m.a.l. . .h.i.s.t.o.l.o.g.i.c. .l.i.m. i. t. s. ... . . . . End o f Record- 14906 11-57 Page 416 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data ANIMAL NUMBER: 14907 DOSE GROUP: I1 SEX: F DEATH TYPE: Sacrifice-Scheduled ....................................................................................................... GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): .G.E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .i.ca..b.1.e............................... HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) STOMACH: d i l a t a t i o n , mucosal glands (minimal) -----------------------.-------------------------------------------------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : N. .A.S.A.L. .C.A.V.I.T.Y./T.U. .R.B.I.N.A. T.E.S. . . . .P.H.A.R.Y.N.X./N. A. S. O. .P.H.A.R.Y.N. X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14907 11-58 Page 417 ARGUS 41S-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 1ndi.vidual Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC O B S E R V A T I O N S : STOMACH: d i l a t a t i o n , mucosal glands (mild) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n.f.l.a.m. .n.a.t.i o. .n., . .s.u.b.a.c.u.t.e.,. .f.o.c.a. l.,. .f.o.r.e.s.t o. .m.a.c.h. . .( m. .i.n.i .m.a. l.). . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : K--ID-N-E-Y-S---------------------N-A-S-A-L--C-A-V-I-T-Y-/T-U-R--E-IN-A-T-E-S-----P-H-A-R-Y-N-X-/-N-A-S-O-P-H-A-R-Y-N-X-------------------------------- End o f Record- 14908 11-59 Page 418 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: K..ID.N.E..Y.S.:...................................m..i.n.e.r.a.l.i.z.a.t.i.o.n.,..m.u.1.t.i.f.o.c.a.l..(.m..i n.i.m.a.l.)........................ THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .N.A.S.A.L. .C.A.V.I .T .Y./ T.U. R. .B.I N.A. T. E. .S. . . .P.H.A. R. Y. N. .X./N.A.S.O.P.H. A. R. .Y.N.X. . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 14909 11-60 Page 419 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i stomorphology D a t a HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E f S ) WERE W I T H I N NORMAL L I M I T S : .N.A.S.A.L. .C.A.V.I.T.Y./ T.U. R. .B.I.N.A.T.E.S. . . .P.H.A.R.Y.N. X. /.N.A.S.O.P.H.A.R.Y. .N.X. . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 14910 11-61 Page 420 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphology Data H I STOMORPHOLOGIC OBSERVATIONS : 11-62 Page 421 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOCOGIC OBSERVATION(S1: G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .ic.a.b.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : mineralization, multifocal (mild) PHARYNX/NASOPHARYNX: inflamnation, chronic, focal/mul ti focal (minimal ) S-T-O-M--A-C-H-: -----------------------------------n-e-c-r-o-s-i-s-,--i-n-d-i-v-i-d-u-a--l --c-e--l l-,--l-i-m-i-t-i-n-g--r-i-d-g-e--(-m--in--im--a-l)---------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : NASAL CAVITY/TURB INATES 11-63 Page 422 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: NASAL CAVITY/TURBINATES: necrosis, olfactory epithelium, multifocal (minimal) ............................................in.f.l.a.m..n.a.t.io.n.., ..a.c.u.t.e./s.u..b.a.c.u.t.e., ..f.o.c.a.l..(.m..i I.d..)................. THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: K. .ID.N. E. Y. .S. . . . . . . . . . . . . . . . . . . .P.H.A.R. Y. N. X. /.N.A.S.O.P.H.A.R. Y. N. .X. . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14913 11-64 Page 423 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i stomorphology D a t a THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K. .I D.N. E. .Y.S. . . . . . . . . . . . . . . . . . . .N.A. S. A. .L .C. A. .V.I T.Y./.T.U.R.B.I.N.A.T.E.S. . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . S.T.O.M. .A.C.H. . . . . . . . . . . . . . . . End of Record- 14914 . 11-65 Page 424 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .i c.a..b.l.e............................... HISTOMORPHOLOGIC OBSERVATIONS: .K.ID.N..E.Y.S.:...................................m..i.n.e.r.a.l.i z..a.t.i o..n.,..m.u.1.t.i.f.o.c.a.l..(.m..in.i.m..a.l .) ....................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: N. .A.S.A.L. .C.A.V.I T. Y. ./ T.U.R. B. I.N.A.T.E.S. . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14915 11-66 Page 425 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: .P.H.A.R.Y.N.X./N.A.S.O..P.H.A.R.Y.N.X.: .......................i.n..f .l a.m..n.a.t.io.n.,..c.h..ro..n.ic.., ..fo..c.a.l ./m.u.1..t.i.f.o.c.a.l..(.m.i.1.d.).............. THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: K. .I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . .N.A.S.A.L. .C.A.V. I.T.Y./.T.U.R.B.I.N.A.T.E.S. . . . .S.T.O.M.A.C.H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14916 11-67 Page 426 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l Gross and H i stomcrphology D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: HISTOMORPHOLOGIC OBSERVATION(S): 11-66 Page 427 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i stomorphology Data GROSS OBSERVATION(S): H ISTOMORPHOLOGIC OBSERVATIONI S ) : HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 i um. papi 1l a (minimal ) NASAL CAVITY/TURBINATES: hemorrhage (moderate) ............................................f r.a..c.t.u.r.e.................................................... THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: 11-69 Page 428 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 Individual Animal Gross and H i stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a.p..p.l .ic.a.b..1.e............................... HISTOMORPHOLOGIC OBSERVATIONS: NASAL CAVITY/TURBINATES: inflammation, chronic, focal/multi focal (mild) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: COMMENTS: NASAL CAVITY/TURB I NATES The t i s s u e was r e c e i v e d damaged and t h e r e i s a r t i f a t present ............................................i .n..th..e..s.e.c.t.i.o.n.s..o.n..S.l.i.d.e.s..X.1.6..a.n.d..6.1..7.. ..................... End o f Record- 14919 11-70 Page 429 ARGUS 3 18-026 ORAL (GAVAGE) REPEATED OOSE 90-DAY T O X I C I T Y STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUOY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: K..ID.N..E.Y.S.:....................................d.i.1.a.t.a.t.i .o.n.,..p.e.l.v.i.s..(.m.i.1.d.)................................... THE FOLLOWING T I S S U E ( S j WERE W I T H I N NORMAL L I M I T S : N. .A.S.A.L. .C.A.V.I T. .Y ./ T.U.R. B. .I N.A. T. E. .S . . . .P.H.A.R.Y.N.X./.N.A.S.O.P.H.A.R.Y.N.X. . . . . . . . S.T.O.M. A. C. H. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 14920 11-71 Page 430 - ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I1 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATIONS: CECUM: KIDNEYS : LYMPH NODE, MANDIBULAR:. STOMACH : .T.H.Y.R.O..ID..: ................. parasite(s) m i n e r a l ization, mu1ti focal ( m i n i m a l ) hyperplasia, l y m p h o c y t i d p l a s m a c y t i c ( m i l d ) necrosis, individual-cell, l i m i t i n g ridge ( m i l d ) u l t im o b r a n chia1 bodylcyst THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BRAIN COLON EYES/OPTIC NERVE HEART LARYNX LIVER MAMMARY GLAND MUSCLE, SKELETAL OVARIES PANCREAS PHARYNX/NASOPHARYNX PITUITARY SKIN S P I N A L CORD, CERVICAL SPLEEN THYMUS U. .T.E.R.U.S. . . . . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 14921 BONE (FEMUR) DUODENUM ILEUM LUNG NASAL CAVITY/TURBINATES PARATHYROID RECTUM S P I N A L CORD, LUMBAR TRACHEA BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM LYMPH NODE, MESENTERIC NERVE. SCIATIC PEYER'S PATCH SALIVARY GLAND S P I N A L CORO, MIDTHORACIC URINARY BLADDER 11-72 Page 43 1 ARGUS 3 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: pyelonephritis, chronic (moderate) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 ium, papi 1l a (minimal ) in f l amnati on, c h r o n i c , f o c a l /mu1 t i f o c a l (minimal ) hyperplasia/hyperkeratosis, l i m i t i n g ridge (mild) necrosis, individual-cell, limiting ridge (mild) ----.......d.i.s.t.e.n.t.i o..n.,..l.u.m.e.n..(.m..i.l d..)................................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM LYMPH NODE, MESENTERIC NERVE, SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC TRACHEA AORTA CECUM EYES/OPTIC NERVE LARYNX MAMMARY GLAND OVARIES PHARYNX/NASOPHARYNX SKIN SPLEEN URINARY BLADDER BONE (FEMUR) COLON HEART LUNG MUSCLE, SKELETAL PANCREAS PITUITARY SPINAL CORD, CERVICAL THYMUS VAG I NA BONE MARROW (STERNUM) DUOOENUM ILEUM LYMPH NODE. MANDIBULAR NASAL CAVITYITURBI NATES PARATHYROID RECTUM SPINAL CORD, LUMBAR THYROID COMMENTS : MAMMARY GLAND NASAL CAVITY/TURBINATES Mamnarv t i s s u e i s o' resent i n t h e connective t i s s u e around t h e s a l iv a r y g l and. The head was r e c e i v e d w i t h e x t e n s i v e d i s s e c t i o n / n e c r o p s y a r t i f a c t . Representative s e c t i o n s were taken and no l e s i o n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .w. .e.re. . .o.b.s.e.r.v.e.d... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14922 11-73 Page 432 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: pyelonephritis, chronic (moderate) NASAL CAVITY/TURBINATES: inflammation, acute/subacute, focal (minimal ) necrosis, olfactory epithelium, multifocal (mild) hyperostosis, t u r b i n a t e bone (minimal ) adhesion ( s ) U..TE.R..U.S.:....................................d..i .s.te..n.t.i.o.n., ..1.u.m.e.n..(.m.i.n.i.m.a.l.)......................... THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS AORTA BRAIN CECUM ESOPHAGUS JEJUNUM EYES/OPTIC NERVE LARYNX LYMPH NODE, MANDIBULAR LYMPH NODE, MESENTERIC NERVE, SCIATIC OVARIES PEYER'S PATCH PHARY NX/NASOPHARYNX SALIVARY GLAND SKIN SPINAL CORD, MIDTHORACIC SPLEEN T. H. .Y.R.O.I.D. . . . . . . . . . . . . . . . . . . . . T.R. A. C. .H.E.A. . . . . . . . . . . . . . . . End o f Record- 14923 BONE (FEMUR) BONE MARROW (STERNUM) COLON DUODENUM HEART ILEUM LIVER LUNG MAMMARY GLAND MUSCLE, SKELETAL PANCREAS PARATHYROID PITUITARY RECTUM SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR STOMACH THYMUS URINARY BLADDER VAGINA .--------------------------------------------------- 11-74 Page 433 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal G r o s s and Histomorphology Data HISTOMORPHOLOGIC OBSERVATIONS: K IONEYS : cyst(s), papilla edema, papillary (minimal) hyperplasia, tubular/ductular epithe1 i um. papi 1 la (miId) basophilia, tubular, multifocal (minimal) infiltration, mononuclear-cell, focal (minimal) LIVER: i nflamati on, chronic, focal/mu1ti focal (minimal) LYMPH NODE, MANDIBULAR: hyperplasia, lymphocyti c/pl asmacytic (minimal) OVARIES : cyst(s), intraovarian SPLEEN: pigment (hemosiderosis) (moderate) S.T.O.M..A.C.H.: ....................................n.e..c.r.o.s.i.s.,..i.n.d.i.v.i.d.u.a.l..-.c.e.l.l.,.l.i..m.i.t.i.n.g..r.i.d.g.e..(.m.i.l.d..)......... THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM MAMMARY GLAND PANCREAS PITUITARY SPINAL CORD, CERVICAL THYROID AORTA CECUM EYES/OPTIC NERVE LARYNX MUSCLE, SKELETAL PARATHYROID RECTUM S P I N A L CORD, LUMBAR TRACHEA BONE (FEMUR) COLON HEART LUNG NASAL CAVITY/TURBINATES PEYER'S PATCH SALIVARY GLAND SPINAL CORD, MIDTHORACIC UTERUS BONE MARROW (STERNUM) DUODENUM ILEUM LYMPH NODE, MESENTERIC NERVE, SCIATIC PHARYNX/NASOPHARYNX SKIN THYMUS VAG INA .- T I S S U E ( S ) NOT AVAILABLE FOR EVALUATION: U. .R.I N. A. .R.Y. .B.L.A.D.D.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 14924 11-75 Page 434 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 5 Appendix I1 I n d i v i d u a l Animal G r o s s and H i stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: CECUM: KIDNEYS : LARYNX : LYMPH NODE, PITUITARY: SPLEEN : STOMACH: MANDIBULAR: in f l annat ion, chron ic , mucosa (moderate) i n f i l t r a t i o n . mononuclear-cell , focal (minimal) granul oma( s ) in f l amnati on, c h r o n i c , f o c a l (minimal ) hyperplasia, lymphocyti c / p l asmacyti c (mi nimal ) cyst( s 1 pigment (hemosiderosis) (mild) hyperpl asi alhyperkeratosi s , 1i m i ti ng r i d g e (mi nimal ) necrosis, individual-cell, limiting ridge (mild) THE FOLLOWING TISSUE($,) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS AORTA BRA1N COLON EYES/OPTIC NERVE HEART LIVER LUNG MUSCLE, SKELETAL NASAL CAVITY/TURBINATES PANCREAS PARATHYROID RECTUM SALIVARY GLAND SPINAL CORD, LUMBAR S P I N A L CORD, MIDTHORACIC T-R-A-C-H-E-A- - - _ _ _ _ _ _ _ _ _ _U _R I N- A_R-Y_B_L A D D E R End o f Record- 1 4 9 2 5 BONE (FEMUR) DUODENUM ILEUM LYMPH NODE, MESENTERIC NERVE, S C I A T I C PEYER'S PATCH SKIN THYMUS UTERUS BONE MARROW (STERNUM) ESOPHAGUS JEJUNUM MAMMARY GLAND OVARIES PHARYNX/NASOPHARYNX SPINAL CORD, CERVICAL THYROID _V_AG_IN_A_ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - 11-76 Page 435 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 Appendix I 1 Individual Animal G r o s s and H i stomorphology Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.l.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: LARYNX : LYMPH NODE, MANDIBULAR: MAMMARY GLAND: NASAL CAVITY/TURBINATES: SPLEEN: STOMACH: THYROID: U--T-E-R-U-S-:---_-------_-________-_-_--_-_ dilatation, tubules, papilla (mild) hyperplasia, tubular/ductular epi the1 i um, papi 1 la (mi 1 d) inflamnation, chronic, focal (mild) hyperplasi a, 1ymphocyti c/plasmacytic (mi1 d) hyperplasia, mu1 ti focal (minimal) inflamnation, chronic, focal/multifocal (minimal) pigment (hemosiderosis) (minimal) hyperplas i a/hyperkeratosi s , 1 imi ti ng r i dge (minimal ) necrosis, individual-cell, limiting ridge (minimal) ul timobranchia1 body/cyst distention, lumen (moderate) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM MUSCLE, SKELETAL PARATHYROID RECTUM AORTA CECUM EYES/OPTIC NERVE LIVER NERVE. SCIATIC PEYER'S PATCH SALIVARY GLAND SPINAL CORD, LUMBAR S P I N A L CORD, MIDTHORACIC U..R.I.N.A.R..Y..B.L.A.D..D.E.R.... VAGI NA .----_----------_--_----------- End of Record- 1 4 9 2 6 BONE (FEMUR) COLON HEART LUNG OVARIES PHARYNX/NASOPHARY NX SKIN THYMUS BONE MARROW (STERNUM) DUODENUM ILEUM LYMPH NODE, MESENTERIC PANCREAS PITUITARY S P I N A L CORD, CERVICAL TRACHEA 11-77 Page 436 ARGUS 418-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 6 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 5 Appendix 11 Individual Animal G r o s s and H i stomorphol ogy Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G..E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t.a.p.p.l..i .c.ab.1..e............................... HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LARYNX: LIVER: LYMPH NODE, PANCREAS : SPLEEN: STOMACH: MESENTERIC: THYROID: hyaline droplets, cortical tubules (mild) hyperplasia, tubular/ductular epithelium. papilla (mild) inflamnation, chronic, focal (minimal) inflanation, chronic, focal /mu1 ti focal (minimal ) macrophages, mu1 ti focal (miId) peritonitis, subacute (minimal ) pi gment (hemosiderosi s) (mi1 d) hyperpl asi a/hyperkeratosi s , 1 imi ti ng ridge (minimal ) necrosis, individual-cell, limiting ridge (minimal) ul timobranchi a1 bodylcyst THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS BRAIN ES0PHAGUS JEJUNUM MUSCLE, SKELETAL PARATHYROID RECTUM SPINAL CORD, LUMBAR .U.R.I.N.A.R..Y..B.L.A.D..D.E.R.... AORTA CECUM EYES/OPTIC NERVE LUNG NASAL CAVITY/TURBI NATES PEYER'S PATCH SALIVARY GLAND S P I N A L CORD, MIDTHORACIC UTERUS BONE (FEMUR) COLON HEART LYMPH NODE, MANDIBULAR NERVE, SCIATIC PHARYNX/NASOPHARYNX SKIN THYMUS VAGI NA BONE MARROW (STERNUM) DUO0ENUM ILEUM MAMMARY GLAND OVARIES PITUITARY SPINAL CORD, CERVICAL TRACHEA COMMENTS : NASAL CAVITY/TURBINATES PHARYNX/NASOPHARYNX The head was received damaged and there i s only minimal turbinate material present, but the sections that could be obtained were within normal limits. Portions of the pharynxlnasopharynx are present on S1 ide X 1 7 . 11-76 Page 437 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATION(S): H I STOMORPHOLOGIC OBSERVATION ( S I : G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a.p.p. .l i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LARYNX : LYMPH NODE, MANDIBULAR: LYMPH NODE, MESENTERIC: NASAL CAVITY/TURBINATES : SPLEEN: STOMACH : edema, papi 1l a r y (minimal ) hyperplasia, tubular/ductular epithelium, papilla (mild) inflamnation, chronic, focal (minimal ) hyperplasia, lymphocytic/plasmacytic (minimal ) macrophages, m u l t i f o c a l (mild) hyperostosis, t u r b i n a t e bone ( m i l d ) adhesion( s) pigment (hemosiderosis) (moderate) hyperplasia/hyperkeratosis. 1i m i t i n g r i d g e (minimal ) necrosis, individual-cell, l i m i t i n g ridge (minimal) ---_____d_i_st_e_nt_io_n_, _1u_m_en__(m_i n_im_a_l_) __________________------------------------ THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS BRAIN ESOPHAGUS JEJUNUM MUSCLE, SKELETAL PARATHYROID RECTUM SPINAL CORD, LUMBAR T..R.A.C.H.E.A.............. End o f Record- 14928 AORTA BONE (FEMUR) CECUM COLON EYES/OPTIC NERVE HEART LIVER LUNG NERVE, SCIATIC OVARIES PEYER'S PATCH PHARYNX/NASDPHARYNX SALIVARY GLAND SKIN SPINAL CORD, MIDTHORACIC THYMUS -----U-R-I_NA_R_Y _BL-A_DD_E_R--___---.-.V-.A.-G.-I.-N.-A..-............ BONE MARROW (STERNUM) DUODENUM ILEUM MAMMARY GLAND PANCREAS PITUITARY SPINAL CORD, CERVICAL THYROID 11-79 Page 438 ARGUS 4 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I 1 I n d i v i d u a l Animal Gross and Histomorphology Data GROSS OBSERVATIONfS) : HISTOMORPHOLOGIC OBSERVATION (SI : G--E-N-E-R-A-L-: --N-o--g-r-o-s-s--c-h-a-n-g-e-s-.-------------------------------N-o-t--a-p-p-l-i-c-a-b-1-e--------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: BONE MARROW (STERNUM): KIDNEYS: LIVER: LYMPH NODE. MANDIBULAR: necrosis, intersternal cartilage. focal (minimal) hyperplasia, tubular/ductular epithelium, papilla (mild) inflamnation, chronic, focal/mul t ifocal (minimal ) hyperplasia, lymphocytic/plasmacytic (moderate) pigment (hemosiderosis) (moderate) hyperpl a s i a/hyperkeratosi s , 1i m i t ing r i d g e (mi nimal ) necrosis, individual-cell, limiting ridge (mild) d i s t e n t i o n , lumen (minimal ) THE FOLLOWING TISSUEfS) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS CECUM EYES/OPTIC NERVE LARYNX MUSCLE, SKELETAL PANCREAS PI TU I TARY SPINAL CORD, CERVICAL THYROID AORTA BONE (FEMUR) BRAIN COLON OUOOENUM ESOPHAGUS HEART ILEUM JEJUNUM LUNG LYMPH NODE, MESENTERIC MAMMARY GLAND NASAL CAVITY/TURBINATES NERVE, S C I A T I C OVARIES PARATHYROID PEYER'S PATCH PHARYNX/NASOPHARY NX RECTUM SALIVARY GLAND SKIN SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC THYMUS .T-R-A_C_HE-A- - _ _ _ _ _ _ - - _ _ _ _.- .-.U-.-R.-I.N.A.R..Y..B.L.A.D.D.E..R........ VAG I NA ._______-_____________ 11-80 Page 439 ARGUS 3 18-026 ORAL (GAVAGE) REPEATED DOSE 90-DAY T O X I C I T Y STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-026 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I1 I n d i v i d u a l Animal Gross and H i s t m r p h o l o g y Data GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G. .E.N.E.R.A.L.:. .N.o. .g.ro. .s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC O B S E R V A T I O N S : BONE MARROW (STERNUM) : KIDNEYS : LARYNX: NASAL CAVITY/TURBINATES : SPLEEN: STOMACH : necrosis, intersternal cartilage, focal (minimal) m i n e r a l i z a t i o n , mu1t i f o c a l (minimal ) edema, papi 11a r y (mi nimal ) granuloma(s) inflamnation, chronic, focal (mild) necrosis, olfactory epithelium, multifocal (minimal) hyperplasia, olfactory epithelium, focal (minimal) pigment (hemosiderosis) (moderate) hyperplasia/hyperkeratosi s, 1i m i ti ng r i d g e (minimal ) necrosis, individual-cell, limiting ridge (mild) ----___u_l t_im_o_br_a_nc_h_ia_l _b_od_y_/c_ys_t ______________________---------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS AORTA BONE (FEMUR) BRAIN CECUM COLON DUODENUM ESOPHAGUS EYES/OPTIC NERVE HEART ILEUM JEJUNUM LIVER LUNG LYMPH NODE, MANDIBULAR LYMPH NODE, MESENTERIC MAMMARY GLAND PANCREAS RECTUM MUSCLE. SKELETAL PEYER'S PATCH SALIVARY GLAND NERVE, SCIATIC PHARYNXINASOPHARYNX SKIN OVARIES PITUITARY SPINAL CORD, CERVICAL SPINAL CORD, LUMBAR SPINAL CORD, MIDTHORACIC THYMUS TRACHEA ---_________________ URINARY BLADDER UTERUS .------------------------------- _V_AG_IN_A_ _ _ _ _ _ _ _ _ - _ _ _ _ - - - - - - .- 11-61 Page 4-40 ARGUS 4 18-026 APPENDIX L QUALITY ASSURANCE STATEMENT Page 441 905 Stuehy Drive, I%&. A Horshorn, PA I9044 Tekphone: (215) 4438710 Tdefax: (2 I S ) U3-8587 ARGUS 4 18-026 -xd ARGUS RESEARCH Chades River Loboroton'es Discovery and Development Services QUALITY ASSURANCE STATEMENT Argus Protocol: 4 18-026 Sponsor's Study Number: T-7485.15 Study Director: Raymond G. York, Ph.D., DABT The protocol, critical phases, raw data and final report were inspected by the Quality Assurance Unit (QAU), to assure conformance with: U.S. Environmental Protection Agency Health Effects Test Guidelines; 90-Day Oral Toxicity in Rodents. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3 100, August 1998. U.S. Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act/Toxic Substances Control Act (F-SCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160Part 792. The undersigned indicate that the report is an accurate representation of the raw data. Data provided by the Sponsor or a subcontractor were not audited by the Argus Research Quality Assurance Unit. Page 442 ARGUS 418-026 The QAU inspection and report audit dates are listed below: Inspection Phase Inspection Date(s) Protocol 05 DEC 01 T N S Administration 19 DEC 01 T N S Preparation 01 FEB 02 Ophthalmological Examinations 15 MAR 02 Blood Collections 19 MAR 02 Necropsy 19 MAR 02 Functional Observational Battery- Raw Data Check 12 JUN 02 Motor Activity- Raw Data Check 12 JUN 02 In-Life Data . 05-07 JUN 02 Formulations Data 07 JUN 02 Necropsy Data 08 JUN 02 Report Tables 09-1 1 JUN 02 Report Text 11 JAN02 21 MAR02 10 JUN 02 11 JUN02 Date(s) Findings Submitted to Study Director 05 DEC 01 19 DEC 01 01 FEB 02 21 MAR 02 19 MAR 02 19 MAR 02 12 JUN 02 12 JUN 02 07 JUN 02 07 JUN 02 08 JUN 02 11 J U N 0 2 11 JAN02 21 MAR 02 10 JUN 02 11 JUN 02 Date(s) Findings Submitted to Management 05 DEC 01 19 DEC 01 01 FEB 02 21 MAR 02 19 MAR 02 19 MAR 02 12 JUN 02 12 JUN 02 07 JUN 02 07 JUN 02 08 JUN 02 11 JUN02 11 JAN02 21 MAR02 10 JUN 02 11 JUN02 Matthew J. Vaneman, B.S. Date Manager of Regulatory Compliance Maureen O'Brien, B.S. Date Quality Assurance Associate and Principal Auditor Page 443 - Study Title MAY 0 6 2004 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PnSS) JN RATS SPONSOR'S STUDY NUMBER: T-7485.15 Data Requirement U.S. Environmental Protection Agency Health Effects Test Guidelines; 90-Day Oral Toxicity in Rodents. Office of Prevention, Pesticides and Toxic Substances (OPPTS)870.3100,August 199&, U.S.Environmental Protection Agency. Toxic I Substances Control Act (TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Bart 160, July 2000. Study Director Raymond G. York, Ph.D., DABT Study Completed On . 5 May 2004 (Report Amendment 1) Subcontracting Facilities Southern Research Institute 2000 Ninth Avenue South Birmingham, Alabama 35255-5537 Redfield Laboratories 100East Boone Street P.O.Box 308 Redfield, Arkansas 72132 Performing Laboratory Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044 Laboratory Project ID Argus Research, Protocol Number: 418-026 Page 1 of 5 ARGUS 418-026 Confidentiality Page This is a blank page to be inserted by the Sponsor. ARGUS 418-026 MAY 0 6 2004 GOOD LABORATORY PRACTICE STATEMENT This study was conducted according to U.S.Environmental Protection Agency (EPA TSCA) "Good Laboratory Practice Standards; Final Rule" (40 CFR Part 792). Any areas of noncompliance are documented in the study record. No deviations existed that affected the validity of the study. . Submitter: c Date - 3M . Study Director: A' Study Director Page 3 I ARGUS 418-026 Confidentiality Page This is a blank page to be inserted by the Sponsor. Page 4 ARGUS 418-026 905 h h y Drin, Mg. A . H m h a r n , PA 19014 Tekpbonq (2 IS) 443-8 7I O Tefefbx: (2 IS) f43-8587 . ' ARGUS RESEARCH Charles River Loboruton`es Discovery and Development Services REPORT AMENDMENT 1 5 MAY 2004 PROTOCOL 418-026 SPONSORS STUDY NUMBER: T-7485.15 ORAL (GAVAGE) REPEATED DOSE 90-DAY TOXICITY STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS)INRATS FINAL REPORT 1. Section,3.3 (page 28 of the report): The title of Section 3.3 reads, "Absolute (g/day) and Relative (g/kg/day) Feed Consumption Values", rather than "Maternal Absolute (g/day) and Relative `(g/kg/day)Feed Consumption Values. This change did not affect the results of the study. Assoxate Director o-rch and Senior Manager, Regulatory Compliance 5 Original page 28 - amended on May 5, 2004 ARGUS 418-026 3.2. Body Weights and Body Weight Changes (Figures 1 and 2; Summaries - Tables 3 through 6; Individual Data - Tables 27 and 28) 3.2.1. Male Rats Body weights and body weight gains for the male rats in all four dosage groups were comparable throughout the dosage period. Body weight gains were significantly reduced (p10.01) on DSs 15 to 22 in the 60 and 200 mg/kg/day dosage groups but were not considered treatment-related because: 1) they were not dosage dependent; and 2) they occurred only once. 3.2.2. Female Rats Body weights and body weight gains for the female rats in all four dosage groups were comparable throughout the dosage period. Body weight gain was significantly increased (p10.01) on DSs 43 to 50 in the 60 mg/kg/day dosage group but was not considered treatment-related because: 1) it was not dosage dependent; and 2) it occurred only once. - - 3.3. Maternal Absolute (g/day) and Relative (g/kg/day) Feed Consumption Values (Summaries Tables 7 through 10; Individual Data Tables 29 and 30) Absolute (g/day) and relative (g/kg/day) feed consumption values for the male and female rats were comparable among the four dosage groups and did not significantly differ. - 3.4. Motor Activity and Functional Observational Battery (Figures 3 through 6; Summaries Tables 11 and 12; Individual Data - Tables 31 through 34) There were no statistically significant or biologically important differences for the male and female rats among the four dosage groups in the measures of motor activity on DS 86. There were no statistically significant or biologically important differences among the four dosage groups in the measures of the functional observational battery (FOB). There were no alterations in home cage behavior, autonomic functions (lacrimation, salivation, palpebral closure, prominence of the eye, pupillary reaction to light, piloerection, respiration, defecation and urination), sensorimotor functions [responses to visual, auditory, tactile and painful stimuli (reactivity and sensitivity)], excitability (reactions to handling and behavior in the open field), gait and sensorimotor coordination (gait pattern in the open field, seventy of gait abnormalities, air righting reaction and landing foot splay) and forelimb and hindlimb grip strength and abnormal clinical observations including but not limited to: convulsions, tremors, unusual behavior, hypotonia or Page 28