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AR226-3155 TRADESECRET Study Title H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Laboratory Project ID: DuPont-2923 DuPont-2923 Author: Carol Finlay, B.A. Study Completed on: July 27,2000 P e r f o r m in g L a b o r a t o r y : E.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 W ork Request Num ber: S er vic e C o d e N u m ber : a Page 1 of 80 Sanitized. Does not contain TSCA CBl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Reviewed by: Gary W. Jepson, Ph.D. Senior Research Scientist LI T u . L .OOP Date Reviewed by: d j j c L C. J Z olcU , fudith C. Stadler, Ph.D., D.A.B.T. Director. General Toxicoloev o?7 -T iiL -2000 Date Issued by Study Director: -2 Company Saintizea. joes not contain S C A CBS H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLE OF CONTENTS Page CERTIFICATION........................................................................................................................... 2 LIST OF TABLES...................................................................................................... 4 LIST OF FIGURES.........................................................................................................................4 LIST OF APPENDICES............................................................... ............................................... 4 STUDY INFORMATION........................................................................................................ 5 STUDY PERSONNEL................................................................................................. 7 SUMMARY............................................................................................................. *..................... 8 INTRODUCTION............................................................................................................................ 9 MATERIALS AND METHODS................................................................................................... 9 A. Test Substance and Positive Control..................................................................................... ^ B. Test Species........................................................................................................................ .. C. Animal Husbandry............................................................................................................... in 1. Housing Environment............................................................................................................`............................ 1f) 2. Feed and Water...................................................................................................................................................... jq 3. Identification......................................................................................................................................................... 4. Animal Health Monitoring Program.................................................................................................................. D. Quarantine and Pretest........................................................................................................ E. Study Design........................................................................................................................ F. Assignment to Groups and Study Start............................................................................... 1j G. Dosing Material Preparation and Administration..............................................................." 1. Test Substance.........................................................................................................................................................^2 2. Positive Controls................................................................................................................................................... ^ 3. Negative Controls................................................................................................................................................ H. Body Weights....................................................................................................................... I. Mortality and Clinical Observations................................................................................... J. Collection and Analysis of Blood and Livers.................................................................... K. Treatment of Fluoride Data................................................................................................. RESULTS AND DISCUSSION....................................................................................................*4 A. In-Life Toxicology............................................................................................................... 14 B. Fluorine D ata........................................................................................................................u 1. Factors Influencing Interpretation o f A nalysis................................................................................................ f 2. Positive Controls..................................................................................................................................................... ^^ 3. Test Substance...................................................................................................................................................... CONCLUSIONS............................................................................................................................ 15 RECORDS AND SAMPLE STORAGE........................................................................... 15 TABLES........................... ....................................................................... ................................*......16 Company Sanitized. D oss not contain TSCA CBl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats FIGURES....... APPENDICES DuPont-2923 LIST OF TABLES Page 1. MEAN BODY W EIGHTS................................................................................................................................................ 17 2. MEAN BODY WEIGHT G A IN S.................................................................................................................................... 18 3. MEAN BLOOD FLUORINE LEVELS........................................................................................................................... 19 4. MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE.................................................... 20 LIST OF FIGURES Page 1. MEAN BODY W EIGHTS.................................................................................................................................................22 2. MICROMOLAR EQUIVALENTS IN RAT BLOOD................................................................................................... 23 LIST OF APPENDICES Page A. INDIVIDUAL BODY WEIGHTS.................................................................................................................................. -26 B. INDIVIDUAL CLINICAL OBSERVATIONS............................................................................................................. 60 C. ANALYSIS OF BLOOD FLUORIDE D A T A ................................................................................................................71 -4 Company Sanitised. Does not contain T SCA CBl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION TEST SUBSTANCE Substance Testej: Svnonvms/Codesj Haskell Number: 23961 Composition Known Impuritiel: DuPont-2923 Haskell Number: 24019 -5 Compesny Sanitized. Does not contain 3 C A CBl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Known Impurities: Unknown DuPont-2923 Haskell Number: 24020 Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Tnitiated/Completed: April 30, 1999 / (see report cover page) Tn-Life Initiated/Comoleted: May 30, 1999 / August 30, 1999 - 6Company Sanitized. Does not contain TSCA CBf ComppttHj} oaiiiM&isC. uO iiwi Cwiiiiciui OBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY PERSONNEL ' Study Director: Carol Finlay, B.A. Management: Judith C. Stadler, Ph.D., D.A.B.T. Primary Technician: Richard P. Mathena Blood Fluorine Data Analysis: Gary W. Jepson, Ph.D. Management: Matthew S. Bogdanffy, Ph.D., D.A.B.T. Toxicology Report Preparation: Wanda F. Dinbokowitz Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-2923 -7 Company Sanitized. Does not contain T SC A CB( H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 SUMMARY The objective of this study was to evaluate the potential for H-23961, when administered by gavage, to be absorbed and to accumulate in a mammalian system. Six groups of 5 male Crl:CD (SD)IGS BR rats each were exposed to 1000 mg/kg/day of H-23961. The test substance was administered to one group of five rats for 5 consecutive days and to 5 groups for 10 days. Approximately two hours after the first dose, blood was collected from the orbital sinus of each rat from the 5-dose group. On selected days (5,10,13, 24, 52,93/94) 5 rats per group were euthanized and the blood and livers were collected. Body weights and clinical signs were recorded on each day of dosing and then approximately every other week during the recovery period. Additionally, 2 negative controls, com oil and com oil/acetone (80:20), and 2 positive controls, H-24019 (10 mg/kg/day) and H-24020 (20 mg/kg/day), were tested as described for H-23961. No compound-related clinical signs of toxicity were observed in the rats dosed with H-23961. Rats dosed with a positive control material, H-24019, exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining of various parts of the body during the dosing period. Rats dosed with H-24020, the other positive control substance, exhibited wet perineum and diarrhea during the dosing period. Alopecia was observed during the recovery period for rats dosed with H-24019 and H-24020. The negative control rats exhibited no clinical signs during the study. Comparison of body weights was complicated by a difference in age on test day 1 between the rats dosed with the test substance and those dosed with the positive or negative controls. Accounting for the age difference at study start and the expected rate of body weight gain, the mean body weights and mean body weight gains of the rats dosed with H-23961 were comparable to the negative controls and equal to or greater than the positive controls. The H-23961 normalized iM equivalents in the rat blood were highly variable and near the limit of detection. Due to the variability of the data and the small sample size, no terminal half-life, AI, BI, or AUCINF could be determined. However, the H-23961 Cmax was very low (1.5 ppm) when compared to the H-24019 (990 ppm) and H-24020 (518 ppm) positive control values.Under the conditions of this study, administration of H-23961 to male rats for 10 consecutive days resulted in minimal absorption and retention of fluorine in the blood. >niiifceu* H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 INTRODUCTION The objective of this study was to define the potential of H-23961 to be absorbed and to bioaccumulate in a mammalian system, as indicated by analytical determination of total fluorine in blood and liver. The test substance was compared to two positive controls that were materials previously shown to bioaccumulate in mammals. The daily dosage for the test substance was selected based on available toxicity data and on the results of a rangefinding study. In the rangefinding study, a group of 5 male rats was dosed by oral gavage with H-23961 at a dosage of 2000 mg/kg for 5 consecutive days. A.group of 5 male rats was dosed with deionized water for 5 consecutive days and served as controls. The rats dosed with H-23961 experienced an overall mean body weight gain of 24 grams. The control group had an overall mean body weight gain of 27 grams. A dosage of 1000 mg/kg was selected for the limit dosage for this project. The limit dosage of 1000 mg/kg was chosen for the main study and was expected to produce less than a 10% difference in mean body weight over 10 days when compared to controls. All blood samples were analyzed for total fluorine content. This report contains the results of those analyses. Results from analyses of selected liver samples will be presented in a supplemental report. MATERIALS AND METHODS A. Test Substance and Positive Control The test substance, H-23961, was supplied by the sponsor as an opaque tan liquid. The positive controls, H-24019 and H-24020, were supplied by the sponsor as white solids. The test substance and positive controls appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color or physical state, was observed. B. Test Species ' Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. The Crl:CD(SD)IGS BR rat was selected on the basis of extensive experience with this strain and its suitability with respect to longevity, hardiness, sensitivity, and low incidence of spontaneous diseases. -9 Company Sanitized. Does not contain TSCA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 C. Animal Husbandry 1. Housing Environment Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. Animal rooms were maintained on an approximate 12-hour light/dark cycle (fluorescent light) and at a temperature of 23 1C and a relative humidity of 50 10%. Occasional excursions outside the accepted ranges were minor and did not affect the study. 2. Feed and Water Tap water was provided ad libitum. All rats were fed PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 chow. The feed is guaranteed by the manufacturer to meet specified nutritional requirements and to be free of specified contaminants. 3. Identification Prior to assignment to groups, each rat was temporarily identified by cage identification. After assignment to groups, an individual identification number was marked or tattooed on the tail of each rat. The information on the cage labels included the unique 6-digit Haskell animal number assigned to each rat. 4. Animal Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to assure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants,'including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. - 10Company Sanitized. Does not contain T SCA CBf H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 D. Quarantine and Pretest Upon arrival at Haskell Laboratory, the rats were removed from shipping cartons and quarantined for 6 days. The rats were weighed 3 times during the pretest period and examined daily for any clinically apparent signs of disease or injury. The rats were observed daily for mortality and signs of illness, injury, or abnormal behavior. On the bases of acceptable body weight gains and freedom from clinically apparent signs of disease or injury, the rats were released from quarantine by the laboratory animal veterinarian or designee. E. Study Design Substance Negative Controls Com oil Com oikacetone Positive Controls H-24019 H-24020 Test Substance H-23961 Vehicle Dosage (mg/kg) Number of Animals Not applicable 0 0 30 30 Com oil: acetone Com oil 10 20 30 30 None 1000 30 F. Assignment to Groups and Study Start After the quarantine period, the rats were selected on the bases of adequate body weight gain, freedom from any clinical signs of disease or injury, and a body weight within 20% of the mean. The selected rats were divided by computerized, stratified randomization into 6 groups of 5 rats, so that there were no statistically significant differences among group body weight means. After assignment to groups, each rat was housed individually. The last 3 digits of the animal number was marked or tattooed on the tail of each rat. The rats were between 7 and 9 weeks of age at the time of dosing. Dosing began on test day 1. Rats that were not assigned to the study were released for other laboratory purposes, or were sacrificed by carbon dioxide asphyxiation and discarded without pathological evaluation. G. Dosing Material Preparation and Administration 1. Test Substance H-23961 was dosed as received. The amount of test substance each rat received was based on the body weight collected on each day of dosing and the test substance density of 1050 mg/mL. The test substance was stirred on a magnetic stir plate throughout the dosing procedure. -11 - Company Sanitized. Does not contain TSCA CBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 2. Positive Controls The solid positive control materials were suspended as emulsions in their respective vehicles. Com oil was used as the vehicle for H-24020. It was necessary to dissolve H-24019 in acetone before suspending it in com oil. The ratio of acetone to com oil was 20:80. The amount each rat received was based on the body weight collected on each day of dosing and the suspension concentration. The dose volumes did not exceed 1 mL/100 g of body weight. The dosing suspensions were stirred on a magnetic stir plate throughout the dosing procedure to maintain homogeneity. 3. Negative Controls Com oil and com oil:acetone (80:20) were chosen as the negative controls because they were the vehicles for the positive controls. Each negative control rat received 1 mL of com oil or com oihacetone. These rats were dosed in a separate room from the rats dosed with the test substance or positive controls. H. Body Weights All rats were weighed on each day of dosing. The positive and negative control rats were weighed weekly or every other week during the recovery period. The rats dosed with H-23961 were weighed 3 weeks after the beginning of the recovery period and then weekly or every other week thereafter. I. Mortality and Clinical Observations Cage-site examinations to detect moribund or dead rats and abnormal behavior and appearance among rats were conducted at least once daily throughout the study. At every weighing, each rat were individually handled and examined for abnormal behavior and appearance. J. Collection and Analysis of Blood and Livers Approximately 2 hours after the first dose, 1-2 mL of blood was collected into EDTA tubes from the orbital sinus of each rat from Group I. At all other selected time points, 5 rats/group were ^ euthanized by carbon dioxide anesthesia and exsanguination and blood and livers were collected according to the following schedules: - 12- Company Sanitized. Does not contain TSCA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 Group I I n in IV V VI Dosing Days 1-5 1-5 1-10 1-10 1-10 1-10 1-10 Tissue Collected Blood Blood and Liver Blood and Liver Blood and Liver Blood and Liver Blood and Liver Blood and Liver _________Sampling Time___________ Test day 1 (2 hours post dosing) Test day 5 at sacrifice (2 hours post dosing) Test day 10 (2 hours post dosing) Test day 13 Test day 24 Test day 52 Test day 93/94 Five to 10 mL of blood was collected into EDTA tubes at sacrifice. The livers were weighed. The blood from all rats was refrigerated, and the livers were frozen. The blood was appropriately packaged and shipped refrigerated to Jackson Laboratory, Deepwater, New Jersey where it was analyzed for total fluorine. The total fluorine content of the blood samples was determined by using a Wickbold torch combustion method, followed by analysis with a fluoride ion selective electrode. The liquid blood was decomposed or volatilized in the presence of wet oxygen and swept through an oxyhydrogen flame in a closed quartz apparatus. The combustion products were collected in an aqueous absorbing solution and analyzed using a fluoride ion selective electrode. The analytical data (ppm F in each sample) was supplied to Haskell Laboratory for evaluation of fluorine biopersistence. K. Treatment of Fluoride Data Noncompartmental analysis was conducted on blood fluorine data derived from rats dosed with H-23961 by using WinNonlin Version 3.0 software (Pharsight Corp, Mountain View, CA). WinNonlin software provided a means of computing derived pharmacokinetic parameters from data files including area under the curve (AUCINF), Cmax and terminal half-life (T1/2). The AUCINF (concentration x time) represents the area under the blood concentration curve from the time of dosing extrapolated to infinity. The maximum observed concentration was Cmax (concentration). The points included in determination of the terminal half-life were selected manually and given in units of time. Since the dosages and fluorine content for each positive control and the test material varied, all doses were normalized to 0.1 mmole/kg for comparative purposes. The accumulation index (AI, l/(l-e kt)) and bioaccumulation index (BI, Cmax x AI) were calculated and reported but not further used. . H-24019 and H-24020 were used as positive controls. Dosing diluents were used as negative controls, but because of variability and limited sensitivity of the analytical method, the background was set at 0.2 ppm fluorine. Since 0.2 ppm was the fluoride concentration limit of detection, any values listed as <0.2 ppm were excluded from further treatment. The percent of fluorine and molecular weight of the test substance and positive controls were used as provided by the sponsor. The measurements resulting form analysis of total blood fluorine were used as received (ppm F) from Jackson Laboratory. Fluoride ion was converted to - 13- Company Sanitised. Does not contain T SCA CBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 micromolar (/xM) equivalents of active component for further comparisons. The data and descriptions of data manipulation and presentation are provided in Appendix C. RESULTS AND DISCUSSION A. In-Life Toxicology (Tables 1 and 2; Figure 1, Appendices A and B) No deaths occurred during the study. No compound-related clinical signs of toxicity were observed in the rats dosed with H-23961. One rat exhibited alopecia of the leg during the dosing period. This clinical sign is not considered to be test substance-related since it was only seen in one animal. Another rat dosed with H-23961 exhibited staining around the eye and broken or chipped teeth on test day 34. These clinical signs were probably caused by the rat's teeth becoming caught on the cage. Rats dosed with H-24019 exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining of various parts of the body during the dosing period. Rats dosed with H-24020 exhibited wet perineum and diarrhea during the dosing period. Alopecia was observed during.the recovery period for rats dosed with H-23961, H-24019 and H-24020. The negative control rats exhibited no clinical signs during the study. Comparison of body weights was complicated by the fact that there was a difference in age on test day 1 between the rats dosed with the test substance and those dosed with the positive or negative controls. This difference resulted in differences in mean body weights on test day 1. The rats dosed with the test substance, H-23961, were older and heavier in weight than the com oil negative control and H-24020 positive control rats, but younger and lighter in weight than the com oil/acetone negative control and H-24019 positive control rats. Accounting for the age difference at study start and the expected rate of body weight gain, the mean body weights and mean body weight gains of the rats dosed with H-23961 was comparable to the negative controls and equal to or greater than the positive controls. B. Fluorine Data (Tables 3 and 4; Figure 2; Appendix C). 1. Factors Influencing Interpretation of Analysis The data used in the kinetic analysis were derived from a limited screen, and therefore several caveats and considerations are important. A couple of considerations of particular importance are (1) a single dose was used and kinetics may or may not be linear, (2) the kinetics apply only to blood, (3) steady-state may not have been achieved, and (4) the sample size is low and may impact calculation of the terminal half-life. A more complete list of considerations is shown in Appendix C. - 14Company Sanitized. Does not contain TSC A CBS H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 2. Positive Controls The positive controls were H-24019 and H-24020. The H-24019 normalized juM equivalents in rat blood continued to rise throughout the dosing period and may not have reached steady-state (Figure 2A). The Cmax for H-24019 was 989.85 116.90 ppm (Mean SD) with a terminal half-life of 40.5 days. The H-24019 AI was 59.0 and the BI was 58382.2. The H-24020 normalized fiM equivalents in rat blood peaked after 5 days of dosing and then decreased throughout the dosing period (Figure 2B). The Cmax for H-24020 was 518.12 44.89 ppm (Mean SD) with a terminal half-life of 8.3 days. The H-24020 AI was 12.5 and the BI was 6497.5. For each of the positive controls, blood was sampled at seven time points throughout the study, with only four of them occurring post-dose. The small sample size and analytical variability should be taken into account when using the derived terminal half-life for comparative, purposes. The total internal exposure resulting from a normalized dose was described by AUCINF/D and was the basis for comparison between positive controls and the test material. The AUCINF/D for the fluorine component was 566,479.1 and 70,789.6 for H-24019 and H-24020, respectively. 3. Test Substance The H-23961 normalized pM equivalents in rat blood were highly variable and near the limit of detection (Figure 2C). The Cmax for H-23961 was 1.464 0.787 ppm (Mean SD). Due to the variability of the data and the small sample size, no terminal half-life, AI, BI, or AUCINF could be determined. However, the H-23961 Cmax of 1.464 0.787 ppm was very low when compared to the H-24020 and H-24019 positive control values of 518 44 ppm and 990 117 ppm, respectively. The data, calculations and equations are shown in Appendix C. CONCLUSIONS Rats dosed for 10 consecutive days with 1000 mg/kg H-23961 exhibited no mortality or clinical signs of toxicity and had mean body weight gains that were comparable to the negative control rats. Due to the variability of the blood fluoride data and the small sample size, no terminal half life, AI, BI, or AUCINF could be determined. However, the H-23961 Cmax was very low (1.5 ppm) when compared to the H-24019 (990 ppm) and H-24020 (518 ppm) positive control values. Under the condition of this study, administration of H-23961 to male rats for 10 consecutive days resulted in minimal absorption and retention of fluorine in the blood. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. - 15- Company Sanitized. Does not contain I S C A 051 H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLES - 16Company Sanitized. Does not contain TSCA CBS H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLE 1 MEAN BODY WEIGHTS Test Days 1 2 3 4 5 6 7 8 9 10 13 20 24 27 34 41 47 48 52 55 61 62 68 69 75 76 80 81 83 89 90 93 94 Negative Controls Com Oil 229.8 234.1 241.4 250.4 259.3 266.8 271.2 281.9 285.2 295.9 321.1 350.5 378.3 Com OilrAcetone 297.6 299.6 309.4 314.3 321.5 326.0 334.9 339.2 345.2 351.7 350.7 369.8 401.0 - 407.8 434.5 454.9 411.4 - - 464.7 487.0 505.1 _ 515.4 _ _ _ _ . 527.6 - - - - - 539.0 - - 556.2 566.9 562.2 567.8 Positive Controls H-24019 291.5 291.5 298.3 304.1 308.6 312.7 317.5 317.3 318.4 318.9 329.1 359.7 387.9 393.9 416.9 - H-24020 227.5 232.4 242.0 248.9 252.4 259.8 263.3 269.8 278.5 283.9 289.1 311.3 340.9 402.9 425.0 438.2 438.1 - 523.4 - 563.4 570.7 - 465.6 452.3 465.8 470.9 499.2 585.3 597.9 527.8 538.7 Test Substance H-23961 241.0 247.3 255.9 262.1 270.2 277.9 283.8 290.9 297.6 304.3 336.7 381.7 - 415.8 " 473.4 482.8 495.7 513.2 529.4 " 541.0 551.5 561.7a a The rats were sacrificed a day early because of a laboratory event on test day 94. - Indicates that the animal was not weighed. - 17- Company Sanitized. Does not contain TSCA C SI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLE 2 MEAN BODY WEIGHT GAINS Test Days 1-5 1-10 10-13 10-24 10-52 10-93/94 Nftpative Controls Com Oil 29.5 66.1 25.2 82.4 168.8 271.0 Com Oil:Acetone 23.9 54.1 - 1.0 49.3 175.9 216.1 Positive Controls H-24019 17.1 27.4 10.2 69.0 119.2 279.0 H-24020 24.9 56.4 5.2 57.0 181.7 254.8 Test Substance H-23961 29.2 63.3 32.4 77.4 178.5 257.4 18Company Sanitized. Does noi contain TSCA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLE3 MEAN BLOOD FLUORINE LEVELS Test Days 1 5 10 13 24 52 94 Negative Controls Com Oil ppm <0.2 <0.2 <0.2 0.2a (0.1) <0.2 0.3a (0.1) 0.3a (0.1) Com Oil'.Acetone ppm <0.2 <0.2 0.3a (0.1)b 0.6 (0.6) 0.2d <0.2 <0.2 Positive Controls Test Substance H-24019 ppm 2.1 (0.9) 48.8 (17.6) 61.7 (2.8) 64.5 (7.6) 42.2 (2.8) 26.9 (2.6) 13.2 (2.1) H-24020 ppm 62.6 (3.2) 71.7 (6.2) 54.2 (7.8) 26.6 (11.4) 10.5 (3.0) 0.9 (0.2) 0.2C (0.1) H-23961 PPm____ 1.8 (0.9) 0.7 (0.1) 1.5 (0.4) 0.5 (0.2) 0.3 (0.1) 0.3 (0)e 0.5 (0.1) a Mean o f 4 of the 5 values. One o f the values was below the LOD. b Standard deviation is in parentheses. c Mean o f 3 o f the 5 values. Two o f the values were below the LOD. d One value. Four o f the values were below the LOD. e Mean o f 2 o f the 5 values. Three o f the values were below the LOD. - 19Company Sanitized. Does not contain TSC A CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 TABLE4 MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE Test Days Positive Controls Test Substance H-24019 H-24020 H-23961 UM F Equivalents ]U.MF Equivalents juM F Equivalents 1 5 10 13 24 52 93/94 28.92 (13.3)a 747.69 (271.5) 945.85 (43.5) 989.85 (116.9) 645.54 (42.9) 411.38 (40.6) 195.38 (32.5) 89.28 (23.4) 518.12(44.9) 391.01 (56.8) 191.45 (82.7) 74.35 (22.1) 4.64 (1.1) 0.24 (0.4) 1.46 (0.79) 0.47 (0.08) 1.16 (0.32) 0.24b (0.14) 0.07 (0.08) 0.09 (0.00) 0.25 (0.08) a Standard deviation is in parentheses. b Mean o f 3 o f the 5 values. Two o f the values were below the LOD. c Mean o f 2 o f the 5 values. Three o f the values were below the LOD. -20- Company Sanitized. Does not contain T SC A CBl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 FIGURES -21 - Company Sanitized. Does not contain TSCA CBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 FIGURE 1 MEAN BODY WEIGHTS Mean Body Weights (g) 400 -, 350 - 300 - 250 200 150 - 100 - --e -- N egative C ontrol (Corn O il) --a --N egative Control (Corn O il:A cetone) --A--P ositive C ontrol H -24019 --x --P ositive C ontrol H -2 4 0 2 0 ..X - - T est Substance H -23961 50 - 0 4-------------- ,--------------- ,--------------- ,--------------- ,-------------- ,--------------- 1 0 2 4 6 8 10 12 TestDays - 22- Company Sanitized. Does not contain TSCA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD A. N o r m a l i z e d R a t Blood H-24019 iM E q u i v a l e n t s R e su ltin g from a 10-Day O r a l G avage Micromolar (/M) equivalents of H-24019 (positive control) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. B. N orm alized R a t Blood H-24020 (iM E quivalents Resulting from a 10-Day O ralGavage Micromolar (pM) equivalents of H-24020 (positive control) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. -23 - H-23961: B iopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 C. N o r m a l i z e d R a t B l o o d H - 2 3 9 6 1 iM E qui v a i e n ts R esu lting from a 1 0 -D a y O ral Gavage Micromolar (fiM) equivalents of H-23961 (test substance) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. -24- Company Sanitized. Does not contain TSC C S I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 APPENDICES -25- Company Sanitized. Does not contain TSCA CEI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 APPENDIX A Individual Body Weights -26- Company Sanitized. Does not contain T SC A CB! H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES ABBREVIATIONS: SD - sacrificed by design DuPont-2923 -27- Ccmpany Sanitizsd. D oss not contain i Sc. CB! H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats * ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 627789 627801 627805 627810 627818 222.6 215.9 249.4 230.5 229.7 220.7 209.1 250.1 231.6 228.6 223.5 223.5 263.3 241.9 239.1 236.9 233.5 273.6 254.4 252.4 247.7 240.1 283.7 265.0 260.2 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2923 - 28- c mpany sanitize* Does no} contain rsc&0i H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 . DAY 7 627793 627797 627799 627800 627808 214.8 239.9 228.9 246.9 235.6 224.4 245.9 231.4 252.8 241.6 232.1 257.3 242.3 265.2 250.1 243.1 267.5 246.2 279.3 262.1 249.9 280.7 258.9 283.6 270.4 257.0 288.0 261.5 295.5 284.1 262.0 290.9 266.4 300.1 287.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627793 627797 627799 627800 627808 270.6 303.9 280.2 312.0 303.6 274.9 305.1 284.3 315.4 305.7 283.5 324.2 294.7 331.3 321.8 SD t e s t SD t e s t SD t e s t SD t e s t SD t e s t dayday day day day 10 10 10 10 10 DuPont-2923 Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627796 627806 627807 627809 627816 239.8 227.3 221.5 234.2 235.0 249.7 234.2 225.9 240.4 238.6 253.6 239.4 237.1 252.5 250.0 252.5 242.9 244.1 260.3 258.9 267.7 258.5 254.9 272.8 265.1 277.2 270.4 257.7 277.9 274.5 289.8 275.2 260.3 282.6 278.6 ANIMAL NUMBER 627796 627806 627807 627809 627816 DAY 8 285.9 282.8 270.7 297.9 291.8 DAY 9 TEST DAYS DAY 10 DAY 13 290.1 285.8 274.7 300.2 296.4 300.0 302.8 280.7 311.9 305.7 322.7 320.3 305.2 336.2 330.2 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 DuPont-2923 -30- Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627791 627794 627804 627812 627817 231.1 224.4 224.7 221.9 233.5 235.4 233.0 228.8 231.5 231.3 241.2 238.1 230.6 236.3 229.0 246.8 247.8 243.0 245.7 244.8 255.9 260.0 251.7 255.5 255.4 262.6 267.4 252.9 264.9 266.4 268.4 270.1 259.5 269.5 270.0 ANIMAL NUMBER DAY 8 *DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 627791 627794 627804 627812 627817 274.0 286.1 267.2 278.2 277.8 279.1 289.5 270.6 282.7 280.4 285.0 295.4 278.1 294.3 294.6 -a -a -a -a -a 334.4 377.4 345.8 356.5 368.7 365.6 416.7 378.1 388.4 407.3 SD t e s t SD t e s t SD t e s t SD t e s t SD t e s t day 24 day 24 day 24 day 24 day 24 DuPont-2923 a Rat was not weighed. -31- Company Sanitized. Does not contain T SC A C B I Jm H -23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627792 627798 627813 627814 627815 235.8 241.1 214.8 217.5 230.1 240.8 253.4 219.2 220.5 242.2 244.3 257.6 220.5 223.7 243.8 247.9 266.1 233.2 225.2 255.7 252.5 272.9 239.8 233.8 265.0 264.4 281.9 243.2 236.7 270.0 268.1 286.2 246.8 240.6 274.1 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627792 627798 627813 627814 627815 282.4 294.3 258.7 248.0 289.2 286.4 296.3 259.2 250.7 293.4 295.2 315.7 267.9 257.3 303.3 -a -a 360.0 380.2 323.6 299.3 368.3 389.2 403.5 342.3 319.4 396.5 426.1 443.1 367.9 343.7 434.9 ANIMAL NUMBER DAY 41 DAY 47 TEST DAYS DAY 52 627792 627798 627813 627814 627815 456.5 470.7 395.0 358.7 462.6 482.3 '496.9 407.2 372.7 487.3 496.8 517.3 416.8 386.9 505.9 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 DuPont-2923 a Rat was not weighed. - 32- Ccmpany Sanitised. Does not contain TSCA CBI H-23961: Biopersistence Screening' 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627795 627811 627819 627820 627821 218.0 228.6 248.8 225.5 227.5 219.5 226.3 255.3 228.9 233.2 225.3 236.7 264.9 239.2 240.7 234.3 246.1 274.4 247.9 246.1 239.4 251.5 280.4 255.6 251.2 246.2 259.6 288.0 261.3 259.8 250.1 263.6 290.3 265.3 263.9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627795 627811 627819 627820 627821 261.4 273.0 304.5 281.3 272.6 265.0 .276.7 308.0 282.9 275.3 270.7 285.6 324.3 292.4 281.8 -a -a 308.0 337.8 399.7 367.2 330.1 329.8 360.6 431.2 393.0 352.9 362.0 396.4 472.5 445.5 385.6 ANIMAL NUMBER DAY 41 DAY 47 TEST DAYS DAY 52 DAY 55 DAY 61 DAY 68 627795 627811 627819 627820 627821 384.2 422.0 505.9 478.0 411.8 398.0 439.3 534.9 504.1 426.1 --a _a _a _a _a 411.1 455.4 551.7 '529.7 439.1 435.7 463.0 574.4 547.1 459.0 440.7 473.6 588.6 558.6 463.3 DuPont-2923 a Rat was not weighed. -33- Company Sanitized, Does noi contain TSCA CB1 H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 90 DAY 94 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS 627795 627811 627819 627820 627821 474.6 503.6 638.1 608.6 509.0 485.0 511.6 653.1 618.0 521.5 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 DuPont-2923 - 34- Company Sanitized. Does not contain T SC A C B l H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 625361 625363 625364 625380 625383 322.6 273.7 291.1 289.4 304.7 325.0 271.4 290.9 286.2 299.7 337.6 278.4 299.9 291.5 302.7 340.3 281.7 306.0 300.1 310.7 349.7 286.7 312.0 305.5 313.1 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2923 - 35- Casapany Sanitized. Does nof contain T S C A C B i H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL-.ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS <g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625355 625362 625367 625368 625378 280..0 290,.3 301..5 312..3 309 .6 282 .0 294..1 307..8 318 .0 306 .4 293..0 303,.5 315 .6 326 .0 327 .3 297..9 308..9 320,.1 336,.4 328 .4 306,.1 313,.8 327 .7 343 .7 333 .7 311,.2 315..8 333,.7 347 .5 336 .6 315..7 323..8 345..6 360,.8 346 .9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 625355 625362 625367 625368 625378 321.7 323.9 349.1 364.2 350.1 320.9 332.3 352.4 380.8 354.2 333.6 332.9 363.8 386.7 365.4 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 DuPont-2923 -36Compairgr SanFfczeiL Stoesnof contain TSCA CBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 . DAY 2 CORN OIL:ACETONE (NEGATIVE C o n t r o l) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625357 625358 625370 625384 625385 311.9 285.7 307.9 294.2 297.6 308.8 286.3 316.7 300.0 304.6 320.3 295.5 329.5 312.0 313.0 328.4 296.4 337.9 309.3 320.4 340.5 306.0 346.9 316.3 331.9 343.3 302.7 349.8 314.1 334.0 361.1 309.2 364.1 321.4 345.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 625357 625358 625370 625384 625385 364.2 319.8 373.4 325.6 347.0 370.3 321.6 374.7 331.0 349.5 376.9 320.3 385.6 340.6 358.9 405.6 340.7 407.0 357.1 377.6 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d ay 13 SD t e s t d a y 13 SD t e s t d a y 13 DuPont-2923 - 37- eompany Sanitized, D o e s * , , ^ T SC a CJ H -23961: B iopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL :ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 . DAY 7 625354 625365 625371 625376 625381 303.0 327.7 294.5 289.7 297.8 304.1 328.7 299.0 289.9 297.5 310.5 337.9 313.4 302.2 301.7 312.2 343.6 318.3 304.9 305.6 319.3 357.7 321.8 313.2 314.4 324.7 357.2 329.6 317.0 314.4 331.2 364.3 338.5 322.8 321.0 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 2 4 625354 625365 625371 625376 625381 336.2 370.5 340.3 331.5 321.6 ,337.0 379.3 345.9 339.0 329.1 348.8 381.2 351.2 345.2 331.6 355.8 407.1 372.6 363.2 341.2 377.7 438.2 413.0 399.7 358.2 396.1 459.6 447.3 432.9 381.8 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 DuPont-2923 - 38- Company Sanitized. Does not contain T SC A C E I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625356 625359 625360 625372 625374 291.7 297.9 296.8 294.8 295.9 291.2 >303.3 300.7 298.8 302.2 304.5 314.0 308.5 310.6 312.1 307.0 315.0 312.7 317.4 321.7 316.9 323.5 319.1 324.0 323.4 319.8 323.5 332.2 329.0 328.3 323.9 333.9 339.5 335.6 337.2 ANIMAL NUMBER 625356 625359 625360 625372 625374 DAY 8 328.8 339.1 347.9 344.7 338.0 DAY 9 334.7 346.2 354.3 348.8 344.6 TEST DAYS DAY 10 DAY 13 341.3 353.6 363.4 355.1 350.8 361.9 372.9 381.7 373.1 371.5 DAY 20 396.7 410.0 419.8 395.1 401.3 DAY 24 __a __a __a __a --a DAY 27 431.3 440.9 465.9 432.1 447.2 ANIMAL NUMBER 625356 625359 625360 625372 625374 DAY 34 466.2 467.7 484.1 454.7 466.8 DAY 52 TEST DAYS 533.7 530.3 555.4 506.2 512.3 SD t e s t SD t e s t SD t e s t SD t e s t SD t e s t day 52 day 52 day 52 day 52 day 52 DuPont-2923 a Rat was not weighed. Company Sanitized Does not contain T SC A C B I asgajisr H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625353 625369 625373 625375 625377 305.9 281.7 294.6 289.1 293.9 307.3 279.9 301.3 291.0 294.8 316.8 289.7 312.7 298.0 302.9 325.0 286.9 317.0 307.0 312.0 331.7 292.8 325.4 309.6 318.0 330.1 295.3 329.0 314.2 317.4 342.5 303.8 334.6 323.5 325.0 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 8 344.7 307.3 340.6 324.7 325.0 DAY 9 352.7 311.9 348.2 336.0 333.7 TEST DAYS DAY 10 DAY 13 358.1 317.2 352.6 336.9 340.7 371.7 331.1 371.5 350.1 353.5 DAY 20 399.1 347.6 402.3 387.9 376.3 DAY 24 __a _a _a _a _a DAY 27 427.7 374.9 444.6 432.3 405.2 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 34 453.3 388.2 477.1 455.6 419.1 DAY 52 _a __a _a __a _a TEST DAYS DAY 76 DAY 90 DAY 94 544.9 483.8 628.8 567.3 470.3 562.8 505.3 661.3 589.8 492.0 565.3 514.8 673.7 588.8 496.6 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 DuPont-2923 a Rat was not weighed. -40- contain TSCA CB| H -23961: B iopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 625322 625323 625336 625343 625349 290.3 285.0 316.5 288.2 303.6 283.7 285.5 313.5 281.9 295.9 291.5 290.2 320.1 286.8 308.2 298.9 290.9 327.1 291.0 310.1 298.0 294.0 329.0 293.7 318.1 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2923 -41- Company Sanitized. Does not contain T SC A C BI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H -2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 . DAY 7 625320 625330 625332 625341 625350 279.3 286.7 300.0 304.9 257.1 283.0 286.1 295.9 309.0 268.5 287.7 291.1 304.1 317.5 267.3 288.4 296.5 308.8 320.0 272.2 295.9 304.0 315.0 325.1 272.6 299.4 302.3 322.4 327.5 276.3 300.6 306.7 320.7 327.4 283.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 625320 625330 625332 625341 625350 308.5 314.0 324.1 332.4 279.8 306.3 312.6 321.8 320.3 282.5 312.1 310.1 318.3 325.6 284.3 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d ay 10 DuPont-2923 TSCA o bi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625321 625327 625342 625345 625348 307.0 311.4 273.7 291.2 265.5 307.8 306.6 275.5 291.7 258.6 311.4 312.5 282.3 297.3 268.0 319.6 317.8 285.8 303.3 275.2 322.3 318.3 290.8 306.4 280.1 328.4 319.3 294.2 310.4 285.2 335.2 327.6 326.6 316.1 290.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 625321 625327 625342 625345 625348 337.8 334.3 304.3 317.3 302.7 339.6 337.0 305.9 312.9 306.5 346.1 336.3 307.8 315.0 309.7 371.2 355.3 324.4 336.9 336.4 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 DuPont-2923 -43- Gompany Sanitized. D oe s not contain T SC A C BI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 . DAY 7 625325 625328 625338 625340 625352 282.8 315.6 264.6 304.0 285.5 *285.9 315.2 261.9 309.2 283.9 291.7 323.9 268.5 316.9 289.1 295.5 327.7 272.6 326.0 299.6 303.2 335.0 275.7 329.8 307.9 309.2 340.4 281.9 334.1 308.2 308.3 340.1 284.4 338.4 312.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 625325 625328 625338 625340 625352 318.6 352.0 287.4 347.0 316.9 321.9 351.7 291.3 352.2 322.3 327.4 357.5 290.2 359.2 321.0 331.6 367.4 291.1 368.1 329.6 355.8 400.2 320.4 389.3 355.7 381.3 423.9 339.9 419.0 375.3 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 DuPont-2923 -44- Company Sanitised. U se s m l eontain T8 CA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625324 625329 625333 625334 625344 303.0 318.9 292.4 274.6 262.9 298.5 316.3 291.2 277.0 262.2 305.8 326.5 297.8 286.4 269.0 312.1 335.4 304.1 290.6 273.5 320.1 338.3 307.7 292.0 274.5 322.8 346.7 312.0 300.1 284.1 326.8 351.6 313.5 304.2 - ANIMAL NUMBER 625324 625329 625333 625334 625344 DAY 8 332.5 352.5 315.8 292.6 280.7 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 337.9 360.1 316.7 302.2 285.2 336.1 357.0 319.3 305.8 289.3 299.6 364.3 325.8 312.0 295.8 336.0 396.4 349.2 338.6 309.7 DAY 24 _a _a _a _a DAY 27 380.3 423.3 375.2 368.8 330.4 ANIMAL NUMBER DAY 34 DAY 52 TEST DAYS 625324 625329 625333 625334 625344 397.3 442.7 384.6 384.2 348.3 447.4 498.1 427.4 426.5 391.0 SD t e s t SD t e s t SD t e s t SD t e s t SD t e s t day- 52 day 52 day 52 day 52 day 52 DuPont-2923 a Rat was not weighed. - 45Csb^ ss'SaniSz& D oes not contain TSCA CBI H-2396I: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H -2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DuPont-2923 625326 625335 625346 625347 625351 313.2 301.0 290.2 266.0 310.6 317.1 303.6 293.4 275.6 310.9 325.5 302.3 300.2 287.7 321.1 330.9 310.4 309.5 300.0 329.6 336.2 315.1 313.5 308.5 338.2 336.0 299.6 318.6 316.6 341.6 293.6 326.0 326.9 340.7 ANIMAL NUMBER 625326 625335 625346 625347 625351 DAY 8 311.5 294.2 292.9 330.5 351.1 DAY 9 308.9 285.3 290.8 330.1 357.8 TEST DAYS DAY 10 DAY 13 297.5 274.0 288.4 333.0 350.5 274.2 266.3 296.9 355.7 380.0 DAY 20 335.4 340.1 352.5 402.1 413.7 DAY 24 __a _a _a _a _a DAY 27 390.7 393.8 388.2 436.2 452.4 ANIMAL NUMBER 625326 625335 625346 625347 625351 DAY 34 427.5 427.0 407.4 466.4 483.3 DAY 52 __a _a _a __a _a TEST DAYS DAY 62 DAY 76 497.5 506.0 485.8 568.6 559.0 540.0 538.6 523.7 617.8 596.8 DAY 80 547.9 547.7 532.8 618.1 607.2 DAY 90 565.2 562.1 542.4 632.6 624.0 DAY 94 577.5 579.5 556.9 638.9 636.8 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 a Rat was not weighed. s o o t contain TSCA C B l Does not contain TSoa H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 627756 627767 627771 627773 627777 227.2 227.0 219.5 246.8 225.4 226.4 231.8 214.7 244.4 221.4 233.4 237.9 226.1 252.7 232.9 238.6 245.8 233.5 263.8 239.4 237.5 248.6 239.6 262.3 236.0 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2923 -47- Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H -2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627768 627774 627776 627782 627785 236.9 258.6 212.0 221.6 220.3 244.1 261.6 216.3 228.3 221.7 245.2 275.8 223.7 237.3 234.7 256.5 283.4 226.6 239.0 238.4 256.2 289.3 229.6 238.8 241.8 265.5 301.5 233.7 244.7 250.5 271.4 303.2 236.9 246.7 255.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627768 627774 627776 627782 627785 272.3 319.8 246.1 251.0 260.7 291.9 326.3 252.3 264.0 268.5 293.5 338.2 254.4 268.2 267.9 SD t e s t d ay 10 SD t e s t d a y 10 SD t e s t d ay 10 SD t e s t day 10 SD t e s t d ay 10 DuPont-2923 -48- Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627758 627763 627764 627787 627788 235 .1 212..1 230 .0 235 .1 219 .4 ' 2 4 0 . .3 218,.3 235 .0 241 .0 222 .3 248..6 226 .5 246 .1 250 .1 232 .2 255..8 234,.3 251 .3 257 .2 239 .6 261..2 230,.8 254..8 258 .6 247 . 6 272..0 235,.5 261..7 237 .6 256 .7 276..1 238,.0 264,.7 240 .3 257 .9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 627758 627763 627764 627787 627788 280.6 255.2 275.8 221.7 274.1 283.6 261.2 281.9 235.7 276.9 295.8 272.5 288.0 234.7 284.8 308.7 285.8 306.7 234.9 309.4 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 DuPont-2923 . 49. Company Sanitized. Does not contain T SC A C Bi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627759 627761 627770 627779 627786 226.6 240.7 235.6 231.5 211.6 232.9 247.4 244.3 237.9 218.2 241.4 257.1 253.6 252.6 222.5 250.9 262.5 260.1 261.4 230.4 254.2 266.7 267.7 262.3 230.6 262.1 259.2 277.3 273.8 240.6 265.4 262.6 279.8 277.5 244.1 ANIMAL NUMBER 627759 627761 627770 627779 627786 DAY 8 277.8 240.1 291.4 289.0 251.3 DAY 9 284.9 257.4 301.3 293.4 '255.8 TEST DAYS DAY 10 DAY 13 288.0 266.9 306.4 301.0 257.0 _a _a _a _a _a DAY 20 348.0 335.7 355.8 374.4 304.4 DAY 24 380.1 359.4 379.8 406.2 326.1 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 DuPont-2923 a Rat was not weighed. -50- Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 627757 627760 627765 627772 627781 221.2 226.2 228.3 245.2 219.0 225.4 232.0 235.3 256.4 226.3 236.3 244.4 247.1 266.2 236.5 241.1 251.7 251.6 277.0 242.9 247.9 260.2 256.4 276.9 247.2 252.2 254.5 261.1 285.0 251.6 254.4 258.3 264.7 291.0 256.1 ANIMAL NUMBER 627757 627760 627765 627772 627781 DAY 8 269,,1 262 .6 271..5 300 .9 258 .1 DAY 9 2 7 6 .7 2 8 0 .3 2 8 2 .4 3 0 7 .5 2 6 6 .8 TEST DAYS DAY 10 DAY 13 2 7 9 .7 2 8 7 .3 2 8 8 .1 3 1 7 .0 2 7 1 .2 _a _a a _a _a DAY 20 324.3 348.6 349.8 375.5 315.1 DAY 24 343.0 379.9 382.7 404.0 338.8 DAY 34 372.3 419.4 400.9 446.9 372.0 ANIMAL NUMBER DAY 41 DAY 47 TEST DAYS DAY 52 627757 627760 627765 627772 627781 402.8 437.7 422.9 478.4 389.9 419.7 448.9 .444.8 494.3 408.2 436.7 456.5 455.6 513.5 421.0 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 DuPont-2923 a Rat was not weighed. 51 ' Gwtipany Sanitized. Does not contain TSCAc a l H -23961: B iopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627762 627769 627775 627778 627783 227.2 231.1 224.7 213.1 216.4 235.0 241.1 235.7 217.4 218.2 248.7 255.9 246.8 221.3 226.6 257.3 264.2 254.7 225.5 232.0 263.0 272.3 265.7 230.1 238.0 275.1 286.3 276.7 236.9 243.9 279.7 289.9 280.2 240.4 247.6 ANIMAL NUMBER 627762 627769 627775 627778 627783 ANIMAL NUMBER 627762 627769 627775 627778 627783 DAY 8 285.9 302.0 286.6 244.8 256.6 DAY 4 1 438.7 479.7 433.2 356.8 409.6 DAY 9 TEST DAYS DAY 10 DAY 13 299.1 309.6 296.0 250.8 259.2 DAY 47 301.5 312.5 304.5 255.1 264.3 _a a _a _a _a TEST DAYS DAY 52 DAY 55 439.9 a 453.5 474.6 a 512.2 451.1 a 460.8 373.5 a 386.0 426.9 a 449.0 DAY 20 356.5 386.6 353.3 294.0 311.3 DAY 61 473.0 511.4 477.4 393.3 473.8 DAY 24 381.5 414.4 377.4 320.0 340.9 DAY 68 471.6 531.4 478.6 398.3 474.8 DAY 34 419.6 456.5 413.9 347.1 380.0 DuPont-2923 a Rat was not weighed. -52- Company Sanitised. Does not contain T SC CBi H-2396I: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 81 DAY 90 H - 2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I TEST DAYS DAY 94 627762 627769 627775 627778 627783 500.3 566.2 510.4 410.1 508.8 523.3 603.2 537.5 .436.5 538.5 528.6 609.6 552.8 445.3 557.2 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 DuPont-2923 Company s,,, i,feM . Does ^^ H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 I 626876 626877 626885 626889 626890 236.4 253.3 223.3 247.2 248.0 237.8 260.2 225.7 249.1 246.3 247.5 272.2 234.2 258.1 254.9 255.2 272.3 236.9 262.2 259.9 262.6 278.2 245.9 268.9 268.9 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2923 Company Sanitized. Does not contain T SC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626871 626872 626875 626882 626888 DAY 1 250.6 251.6 247.3 249.0 224.8 DAY 2 259.4 261.0 256.2 257.0 226.4 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I DAY 3 266.3 268.3 265.6 265.6 233.6 DAY 4 275.2 277.2 270.9 272.8 238.3 DAY 5 285.2 280.3 283.0 285.1 243.4 DAY 6 288.8 289.9 291.2 297.1 247.5 . DAY 7 295.9 294.2 298.2 301.4 249.5 ANIMAL NUMBER 626871 626872 626875 626882 626888 DAY 8 297.5 300.5 301.3 309.6 258.2 DAY 9 DAY 10 305.2 309.9 310.5 314.4 260.7 309.0 318.1 315.1 325.1 264.8 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 SD t e s t d a y 10 DuPont-2923 -55- Company Sanitized. Does not contain T S C A C B i H-23961: B opersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626868 626879 626886 626887 626891 DAY 1 255.0 231.4 237.1 246.2 249.7 DAY 2 265.4 242.2 243.2 253.0 256.2 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I I DAY 3 279.9 248.9 251.5 260.0 265.1 DAY 4 288.0 255.2 259.4 268.7 275.8 DAY 5 300.4 260.8 265.1 275.0 283.8 DAY 6 308.8 267.3 270.0 283.1 294.9 . DAY 7 311.6 271.7 280.8 288.3 300.8 ANIMAL NUMBER 626868 626879 626886 626887 626891 DAY 8 323.0 280.4 290.9 295.6 310.3 DAY 9 328.3 290.1 296.3 302.5 321.8 DAY 10 338.0 297.8 302.1 307.9 318.8 DAY 13 366.9 320.6 319.9 329.9 346.3 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 SD t e s t d a y 13 DuPont-2923 -56- Company Sanitized. Does not contain T SC A C B l H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626864 626865 626873 626894 626895 DAY 1 248.7 232.9 248.9 225.8 233.9 DAY 2 256.1 241.4 261.8 231.4 238.9 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP IV DAY 3 260.7 245.9 268.2 244.3 247.3 DAY 4 268.3 255.4 280.1 250.0 249.5 DAY 5 271.4 263.4 290.1 258.8 262.0 DAY 6 277.8 266.2 300.1 263.9 262.7 DAY 7 280.8 270.8 303.8 268.9 271.2 ANIMAL NUMBER 626864 626865 626873 626894 626895 DAY 8 289.1 276.8 311.4 274.7 278.2 DAY 9 294.9 280.5 318.1 ,282.6 280.3 DAY 10 300.8 283.8 328.4 292.7 287.6 DAY 13 _a _a __a _a --a DAY 24 390.7 351.8 424.7 380.8 360.6 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 2 4 SD t e s t d a y 2 4 DuPont-2923 "Rat was not weighed. -57- Company Sanitized.Does not contain TSCACBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626867 626880 626881 626884 626892 DAY 1 249.0 228.9 233.4 243.5 236.6 DAY 2 257.1 235.7 238.4 251.1 243.0 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V DAY 3 263.1 239.6 247.1 261.0 255.8 DAY 4 270.8 244.2 253.7 269.7 262.9 DAY 5 274.2 255.5 264.6 275.0 273.5 DAY 6 281.2 261.5 278.0 283.9 281.5 . DAY 7 286.9 269.3 284.1 290.1 292.3 ANIMAL NUMBER 626867 626880 626881 626884 626892 DAY 8 294.1 275.5 293.6 300.5 299.8 DAY 9 299.6 284.5 300.5 305.4 309.1 DAY 10 308.7 290.3 307.7 316.0 318.0 DAY 13 _a _a _a _a __a DAY 2 4 _a _a _a __a _a DAY 34 407.1 399.1 444.6 429.0 440.9 DAY 48 455.1 454.0 517.9 489.7 498.8 ANIMAL NUMBER V 626867 626880 626881 626884 626892 DAY 52 DAY 62 DAY 69 DAY 75 DAY 83 DAY 89 DAY 93 478.7 470.8 533.9 507.8 518.8 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d a y 52 SD t e s t d ay 52 SD t e s t d a y 52 DuPont-2923 "Rat was not weighed. -58- Company Sanif!ze{j, Does nol contain TSCA C Bl H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626866 626869 626874 626893 626896 DAY 1 240.1 255.2 223.8 246.3 233.2 DAY 2 242.5 259.0 232.2 253.8 237.5 H - 2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V I DAY 3 251.9 266.5 244.0 259.2 250.7 DAY 4 252.2 270.4 249.9 260.5 258.0 DAY 5 257.2 279.6 260.4 267.6 265.3 DAY 6 266.0 286.7 269.0 271.9 258.7 . DAY 7 270.6 290.8 277.3 273.8 270.7 DuPont-2923 ANIMAL NUMBER VI 626866 626869 626874 626893 626896 DAY 8 275.9 295.6 282.6 278.4 279.0 DAY 9 277.3 302.8 290.0 283.1 290.9 DAY 10 284.4 304.8 295.0 287.9 _a DAY 13 __a _a _a ^a _a DAY 24 _a _a __a _a _a DAY 34 398.4 400.1 444.4 389.5 405.1 DAY 48 461.3 446.4 519.5 441.7 449.6 ANIMAL NUMBER VI 626866 626869 626874 626893 626896 DAY 52 469.9 458.2 535.2 454.7 466.1 DAY 62 485.6 475.8 568.4 471.8 476.8 DAY 69 500.9 481.0 593.8 488.3 502.0 DAY 75 514.9 493.2 616.5 501.5 521.1 DAY 83 541.3 496.4 625.3 519.1 523.1 DAY 89 555.6 505.8 640.4 527.8 527.8 DAY 93 565.5 507.0 654.5 539.5 541.8 SD t e s t day- 93 SD t e s t d a y 93 SD t e s t d a y 93 SD t e s t d a y 93 SD t e s t d a y 93 a Rat was not weighed. Company Sanitized. Does not contain TSC A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 APPENDIX B Individual Clinical Observations -60Company Sanitized. Does not contain T S C A C B I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 ' CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS . A nim al Number GROUP I . __________O b s e r v a t i o n ___________________________ T e s t D ay 627789 627801 627805 627810 627818 No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-5 1-5 1-5 1-5 1-5 A nim al Number 627793 627797 627799 627800 627808 GROUP I I O b servation _______________________ T e s t D ay No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d 1-10 1-10 1-10 1-10 1-10 A nim al Number 627796 627806 627807 627809 627816 GROUP I I I O b servation _____________________ T e s t D ay No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d 1-13 1-13 1-13 1-13 1-13 -61 Company Sanitized. Does not contain T SC A C BI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 627791 627794 627804 627812 627817 '_______ GROUP IV . m ^,, O b s e r v a t i o n _____________ _________________ T e s t D ay No a b n o r m a l i t i e s No a b n o r m a l i t i e s No a b n o r m a l i t i e s No a b n o r m a litie s No a b n o r m a l it i e s d etected d etected d etected d etected d etected 1-24 1-24 1-24 1-24 1-24 A nim al Number 627792 627798 627813 627814 627815 GROUP V O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d No a b n o r m a litie s d e te c t e d No a b n o r m a l it i e s d e t e c t e d T est- Day 1-52 1-52 1-52 1-52 1-52 A nim al Number 627795 627811 627819 627820 627821 GROUP V I O b servation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d T est Day 1-94 1-94 1-94 1-94 1-94 - 62- Company S an itised . Does not contain TSC A C B i H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 625361 625363 625364 625380 625383 GROUP I O b servation No a b n o r m a litie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d T e st Day 1-5 1-5 1-5 1-5 1-5 A nim al Number 625355 625362 625367 625368 625378 GROUP I I O b s e r v a t i o n __________________________ T e s t D ay No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d 1-10 1-10 1-10 1-10 1-10 A nim al Number 625357 625358 625370 625384 625385 GROUP I I I ' ______ O b s e r v a t io n _______________________________ T e s t D ay No a b n o r m a l i t i e s No a b n o r m a l i t i e s No a b n o r m a l i t i e s No a b n o r m a l i t i e s No a b n o r m a l i t i e s d etected d etected d etected d etected d etected 1-13 1-13 1-13 1-13 1-13 -63 Company S a n teed . Does not contain TSCA CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats CORN OIL-.ACETONE (NEGATIVE CONTROL) DuPont-2923 INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 625354 625365 625371 625376 625381 GROUP IV O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d T est Day 1-24 1-24 1-24 1-24 1-24 A nim al Number 625356 625359 625360 625372 625374 GROUP V O b s e r v a t io n _______________________________T e s t D ay No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d 1-52 1-52 1-52 1-52 1-52 Anim al Number 625353 625369 625373 625375 625377 GROUP V I ___________________O b s e r v a t io n No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d T e st Day 1-94 1-94 1-94 1-94 1-94 Company S an itized . Does not contain T SC A CBi H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 H -2 4 0 1 9 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS . Animal Number 625322 625323 625336 625343 625349 GROUP I _____________ Observation m __ ___________ _________ Test Day No a b n o r m a l it i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-5 1-5 1-5 1-5 1-5 A nim al Number 625320 625330 625332 625341 625350 GROUP I I O b servation No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e te c te d D iarrh ea No a b n o r m a litie s d e t e c t e d T e st Day 1-10 1-10 1-10 1 -4 , 6-10 5 1-10 A nim al Number 625321 625327 625342 625345 625348 GROUP I I I O b servation No a b n o r m a lit ie s d e t e c t e d D iarrh ea No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d T e st Day 1 -4 , 6-13 5 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain T3CA CB1 H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H -2 4 0 1 9 (POSITIVE CONTROL) DuPont-2923 INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 625325 625328 625338 625340 625352 GROUP IV O b servation No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e te c t e d S a liv a tio n No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-24 1-24 1 -6 , 8-24 7 1-24 1-24 Anim al Number 625324 625329 625333 625334 625344 GROUP V O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d S a liv a tio n No a b n o r m a litie s d e t e c t e d S a liv a tio n No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-52 1 -6 , 8-52 7 1 -6 , 8-52 7 1-52 1-52 A nim al Number 625326 625335 625346 625347 625351 GROUP V I O b servation No abnormalities detected Salivation Alopecia both front legs Alopecia abdomen No abnormalities detected Salivation Black ocular discharge Yellow-stained perineum Red-stained chin Brown-stained chin No abnormalities detected No abnormalities detected Salivation T e st Day 1 -6 , 9-76, 77-94 7-8 76 7, 8, 9, 10, 13, 20, 27 1 -6 , 11-94 7-8 8 8 8 9-10 1-94 1 -6 , 8-94 7 - 66Compsny Sanitized. Does not contain T SC CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 H -2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number 627756 627767 627771 627773 627777 GROUP I O b servation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-5 1-5 1-5 1-5 1-5 Anim al Number 627768 627774 627776 627782 627785 GROUP I I O b servation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d T e st Day 1-10 1-10 1-10 1-10 1-10 A nim al Number 627758 627763 627764 627787 627788 GROUP I I I O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d No a b n o r m a l it i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d Wet p erin eu m No a b n o r m a lit ie s d e t e c t e d D iarrh ea T e s t .Day 1-13 1-13 1-13 1 -5 , 7-13 6 1 -8 , 10-13 9 -67Company Sanitized. Does not contain T SC A CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 H -2 4 0 2 0 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 627759 627761 627770 627779 627786 GROUP IV O b servation No a b n o r m a litie s No a b n o r m a litie s No a b n o r m a litie s No a b n o r m a litie s No a b n o r m a litie s d etected d etected d etected d etected d etected T e st Day 1-24 1-24 1-24 1-24 1-24 Anim al Number 627757 627760 627765 627772 627781 GROUP V O b servation No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d Wet p erin eu m No a b n o r m a litie s d e t e c t e d Wet p erin eu m No a b n o r m a lit ie s d e t e c t e d T e st Day 1-52 1-52 1, 3-52 2 1, 3-52 2 1-52 A nim al Number 627762 627769 627775 627778 627783 GROUP V I O b servation No a b n o r m a lit ie s d e t e c t e d D iarrh ea No a b n o r m a litie s d e te c t e d No a b n o r m a litie s d e te c t e d A lo p e c ia perineum No a b n o r m a lit ie s d e t e c t e d A lo p ecia b oth fr o n t paws A lo p ecia r ig h t fro n t le g <J\ i O H( CO 1 i--1 T e st Day .9 1-94 1-94 81, 90, 94 1 -2 3 , 94 24, 34, 41, 47, 55, 61, 7 4 , 81, 90 Company Sanitized. Does not contain T SC A CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 H -2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 626876 626877 626885 626889 626890 GROUP I O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 0-5 0-5 0-5 0-5 0-5 A nim al Number 626871 626872 626875 626882 626888 GROUP I I O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d A lop ecia l e f t fro n t le g No a b n o r m a lit ie s d e t e c t e d T e st Day 0-10 0-10 0-10 1-10 0-10 A nim al Number 626868 626879 626886 626887 626891 GROUP I I I O b servation No a b n o r m a lit ie s No a b n o r m a litie s No a b n o r m a lit ie s No a b n o r m a lit ie s No a b n o r m a lit ie s d etected d etected d etected d etected d etected T est Day 0-13 0-13 0-13 0-13 0-13 - 69Company Sanitized. Does not contain T SC A CBI H-23961: Biopersistence Screening 1Q-Dose Oral Gavage Study in Rats . DuPont-2923 H -2 3 9 6 1 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number 626864 626865 626873 626894 626895 GROUP IV O b servation No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e te c te d No a b n o r m a litie s d e t e c t e d T e st Day 0-24 0-24 0-24 0-24 0-24 A nim al Number 626867 626880 626881 626884 626892 GROUP V O b servation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d T est Day 0-52 0-52 U-b2 0-52 0-52 A nim al Number 626866 626869 626874 626893 626896 GROUP V I O b servation No a b n o r m a lit ie s d e t e c t e d A lop ecia both fro n t le g s No a b n o r m a litie s d e t e c t e d S ta in p erio cu la r both b la ck T eeth broken or ch ip p ed No a b n o r m a litie s d e t e c t e d T e st Day 0-93 52, 62, 69 0-93 34 34 0-93 - 70- Company Sanitised. Does net contain T SC A C5I H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 APPENDIX C Analysis of Blood Fluoride Data -71 Company Sanitized. Does not contain TS C A CBI H -23961: Bpersistence Screening 10-Dose Oral Gavage Study in Rats Terms: Active % Active __ ' Terms and Calculations Mol Wt Active Formulation Dose % F in Active Mol Wt F DuPont-2923 Compound Calculations: Dose Active (mg/kg) The mg of fluorine containing compound administered per kg of animal body weight. = (% active/100) * Formulation Dose Dose Active (mmole/kg) The mmole of fluorine containing compound administered per kg of animal body weight = dose [mg/kg] / Mol Wt Active [mg/mmol] Dose F (mg/kg) The mg Fluorine administered per kg of animal body weight = (% F in active/100) * Dose Active [mg/kg] Dose F (mmol/kg) The mmole of fluorine administered per kg of animal body weight = Dose F [mg/kg] / Mol Wt F [mg/mmol] Molar Ratio (Active/F) The moles of fluorine containing compound per mole of fluorine = Dose Active [mmol/kg] / Dose F [mmol/kg] Formulation Dose Normalization Factor The formulation dose that would be required to administer the amount of active needed to achieve the normalized dose = (Normalized dose of Active [mmol/kg] / Dose Active [mmol/kg]) * Formulation Dose -72- Company Sanitized. Does not contain T SG A CBS H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Individual Animal Measurement: ppm F in blood The ppm fluoride measured in blood DuPont-2923 Individual Animal Calculations: ppm F in Blood minus Bkg 0.2 ppm The ppm fluoride measured in plasma minus the background fluoride measured in control animal blood. In this case the value was established at 0.2 ppm. ppm F in Blood The ppm fluoride minus background that would be expected if the normalized to 0.1 mmol/kg active dose was 0.1 mmol/kg instead of the actual active dose. This Dose assumes linearity between administered dose and blood fluorine levels, but is needed because different doses of active were used in the study. = (0.1 [mmol/kg] / Active dose [mmol/kg]) * (ppm F in blood minus background) /molar equivalents of active in blood The /molar [/mol/L] concentration of fluorine containing compound in plasma based on the ppm fluorine in plasma normalized to 0.1 mmol/kg active dose. This assumes that all plasma fluorine is derived from the-fluorine-containing component in the formulation. Note: 1 ppm - 1 mg/L = (Normalized ppm [mg/L] fluorine in blood / Mol Wt F [mg/mmol]) * molar ratio active/F [mmol active/mmol F] * 1000 /mol/mmol - 7 3 - Company Sanitized. Does not contain T SC A CBi H -23961: B iopersistence Screening 10-Dose Oral Gavage Study in Rats Factors Influencing Interpretation of Kinetic Analysis DuPont-2923 Considerations: - The data used for kinetic analysis was from a limited screen and extrapolation should be done cautiously. - Sample size is low - Analytical data used without validation - Steady-state not reached - Terminal phase may not be reached - Some compounds are mixtures of fluorinated compounds - Different active and formulation doses were used - Different vehicles were used to deliver formulations - The kinetics apply only to plasma, not to specific tissues or the whole body - Each compound may have very different potency for producing toxicity Assumptions: (May or may not bejustified in all cases) - Plasma fluorine concentrations are linear with respect to dose - Analytical method is appropriate for all types of compounds - Elimination kinetics can be determined based on total fluorine rather than on concentrations of individual components - Background plasma Fluorine is 0.2 ppm - % F data is the % Fluorine of the active (Fluorine containing component(s) in the formulation - Molecular weight is the molecular weight of the active component in the formulation -74Compmsg SaniSizssL Does not contain TSCACEJ2 H -23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H -24019 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 497 % F in Active: 10 Mol Wt. F (g/mol): 100 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 10 0.020 49.7 Dose F (mmol/kg): Molar Ratio (Active/F): Dose F (mg/kg): DuPont-2923 65 19 0.342 0.059 6.5 Rat# Test ppm F Day in Sample blood ppm Fin blood minus Bkg 0.2 ppm Group I 625322 625323 625336 625343 625349 1 1 1 1 1 1.0 1.3 2.6 2.6 2.9 0.8 1.1 2.4 2.4 2.7 Group I 625322 625323 625336 625343 625349 5 5 5 5 5 51.7 38.0 38.7 78.5 37.1 51.5 37.8 38.5 78.3 36.9 Group II 625320 625330 625332 625341 625350 10 10 10 10 10 65.6 ' 65.4 61.1 60.9 60.5 60.3 63.1 62.9 58.1 57.9 ppm F in blood Normalized to 0.1 mmoles/kg Dose 3.98 5.47 11.93 11.93 13.42 255.96 187.87 191.35 389.15 183.39 325.04 302.67 299.69 312.61 287.76 umolar equivalents of active in blood 12.31 16.92 36.92 36.92 41.54 792.31 581.54 592.31 1204.62 567.69 1006.15 ' 936.92 927.69 967.69 890.77 -75Company Sanitized. Does not contain T SCA CBS H -23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat# Group III 625321 625327 625342 625345 625348 Test Day Sample 13 13 13 13 13 ppm F in blood 77.2 61.5 64.6 57.0 62.4 Group IV 625325 625328 625338 625340 625352 24 24 24 24 24 40.3 46.3 43.2 39.1 41.9 Group V 625324 625329 625333 625334 625344 52 52 52 52 52 24.7 29.8 27.3 29.1 23.8 Group VI 625326 625335 625346 625347 625351 94 94 94 94 94 12.4 16.4 13.1 11.0 11.6 ppm F in blood minus Bkg 0.2 ppm 77.0 61.3 64.4 56.8 62.2 40.1 46.1 43.0 38.9 41.7 24.5 29.6 27.1 28.9 23.6 12.2 16.2 12.9 10.8 11.4 ppm F in blood Normalized to 0.1 mmoles/kg Dose 382.69 304.66 320.07 282.30 309.13 199.30 229.12 213.71 193.33 207.25 121.77 147.11 134.69 143.63 117.29 60.63 80.51 64.11 53.68 56.66 DuPont-2923 umolar equivalents of active in blood 1184.62 943.08 990.77 873.85 956.92 616.92 709.23 661.54 598.46 641.54 376.92 455.38 416.92 444.62 363.08 187.69 249.23 198.46 166.15 175.38 -76- Company Sanitized. Does not contain T SCA CBS H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 Data for H- 24020 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 426 % F in Active: 20 Mol Wt. F (g/mol): 100 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 20 0.047 42.6 Dose F (mmol/kg): Molar Ratio (Active/F): Dose F (mg/kg): 69 19 0.726 0.065 13.8 R at# Test ppm F Day in Sample blood Group I 627773 1 13.2 627771 1 8.1 627767 1 16.5 627756 1 14.1 627777 1 10.7 Group I 627773 5 75.3 627771 5 66.8 627767 5 64.8 627756 5 80.0 627777 5 71.6 Group II 627768 627774 627776 627782 627785 10 10 10 10 10 56.3 51.0 54.8 43.6 65.1 ppm F in blood minus Bkg 0.2 ppm 13.0 7.9 16.3 13.9 10.5 75.1 66.6 64.6 79.8 71.4 56.1 50.8 54.6 43.4 64.9 ppm F in blood Normalized to 0.1 mmoles/kg Dose 27.69 16.83 34.72 29.61 22.37 159.96 141.86 137.60 169.97 152.08 119.49 108.20 116.30 92.44 138.24 umolar equivalents of active in blood 94.20 57.25 118.12 100.72 76.09 544.20 482.61 468.12 578.26 517.39 406.52 368.12 395.65 314.49 470.29 Company Sanitized. Does not contain T SC A CBI H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat # Test ppm F Day in Sample blood ppm F in blood minus Bkg 0.2 ppm ppm F in blood Normalized to 0.1 mmoles/kg Dose umolar equivalents of active in blood Group III 627758 627764 627787 627763 627788 Group IV 627759 627779 627770 627761 627786 Group V 627757 627781 627760 627765 627772 Group VI 627778 627783 627762 627775 627769 13 13 13 13 13 24 24 24 24 24 52 52 52 52 52 94 94 94 94 94 43.5 20.7 13.2 30.8 24.9 9.2 14.9 11.6 9.9 6.7 0.9 0.6 1.0 0.9 0.8 0.3 <0.2 0.2 0.2 <0.2 * = Below LOD (Level of Detection) 43.3 20.5 13.0 30.6 24.7 9.0 14.7 11.4 9.7 6.5 0.7 0.4 0.8 0.7 0.6 0.1 * 0.0 0.0 * 92.23 43.67 27.69 65.18 52.61 19.17 31.31 24.28 20.66 13.85 1.49 0,85 1.70 1.49 1.28 0.21 * 0.00 0.00 * 313.77 148.55 94.20 221.74 178.99 65.22 106.52 82.61 70.29 47.10 5.07 2.90 5.80 5.07 4.35 0.72 * 0.00 0.00 * -78Company Sanitized. Does not contain T SC A CBJ H-23961: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2923 Data for H- 23961 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 27500 1000 28 % F in Active: Mol Wt. F (g/mol): Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 280 0.010 9821.4 Dose F (mmol/kg): Molar Ratio (Active/F): Dose F (mg/kg): 40 19 5.895 0.002 112 Rat# Test ppm F Day in Sample blood Group I 626876 626877 626885 626889 626890 1 1 1 1 1 3.4 1.6 1.4 1.3 1.5 Group I 626876 626877 626885 626889 - 626890 5 5 5 5 5 0.8 0.7 0.6 0.7 0.8 Group II 626871 626872 626875 626882 626888 10 10 10 10 10 1.2 1.1 1.8 1.5 1.9 ppm F in blood minus Bkg 0.2 ppm 3.2 1.4 1.2 1.1 1.3 0.6 0.5 0.4 0.5 0.6 1.0 0.9 1.6 1.3 1.7 ppm F in blood Normalized to 0.1 mmoles/kg Dose 31.43 13.75 11.79 10.80 12.77 5.89 4.91 3.93 4.91 . 5.89 9.82 8.84 15.71 12.77 16.70 umolar equivalents of active in blood 2.86 1.25 1.07 0.98 1.16 0.54 0.45 0.36 0.45 0.54 0.89 0.80 1.43 1.16 1.52 -79- Company Sanitized. Does not contain TSCA C B I H-23961: Biopersistence Screening Rat# Test ppm F Day in Sample blood ppm F in blood minus Bkg 0.2 ppm ppm F in blood Normalized to 0.1 mmoles/kg Dose DuPont-2923 umolar equivalents of active in blood Group III 626868 626879 626886 626887 626891 Group IV 626864 626865 626873 626894 626895 Group V 626867 626880 626881 626884 626892 Group VI 626866 626869 626874 626893 626896 13 13 13 13 13 24 24 24 24 24 52 52 52 52 52 93 93 93 93 93 0.5 0.6 <0.2 0.3 <0.2 0.2 0.3 0.4 0.2 0.3 0.3 <0.2 <0.2 <0.2 0.3 0.6 0.4 0.5 0.4 0.5 * = Below LOD (Level o f Detection) 0.3 0.4 * 0.1 * 0.0 0.1 0.2 0.0 0.1 0.1 * * * 0.1 0.4 0.2 0.3 0.2 0.3 2.95 0.27 3.93 0.36 ** 0.98 0.09 ** 0.00 0.00 0.98 0.09 1.96 0.18 0.00 0.00 0.98 0.09 0.98 0.09 ** * ** 0.98 0.09 3.93 0.36 1.96 0.18 2.95 0.27 1.96 0.18 2.95 0.27 -80- Company Sanitized. Does not contain T SC A CB!