Document baowg539rg510nxwezmrZx6kZ

AR226-3166 ____________________ ____________________________ DuPont-4182 TRADE SECRET Study Title H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Laboratory Project ID: DuPont-4182 Author: Carol Finlay, B.A. Study Completed on: September 5,2000 Performing Laboratory: 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 Work Request Number: Service Code Number: ompany Sanitized. Does not contain TSCA CBf-- Page 1 o f 93 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 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 5 **^0 . Date Reviewed by: v / I Judith C. Stadler, Ph.D., D.A.B.T. / Director S -SE P-20C Date Issued by Study Director: d L A & C HCkJL&u, Carol Finla/B.A. <J Staff Scientist 6 6 - eflL - t m Date1 Company Sanitized. Does not contain TSCA CB1 -2 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE OF CONTENTS Page LfiK I I f I tA 1 .....................__.................___ .......__... LIST O F TA B LES................................................................... LIST O F FIG U R E S________________________________ LIST O F A PPE N D IC E S____________________________ ............................................. d STUDY IN FO R M A TIO N ..................................... ............... STUDY PER SO N N FJ................................................ ...... SUM M ARY............................................................................... IN TRO D U CTIO N ............ .................. .................................... M ATERIALS AND M ETH O D S.......................................... A. Test Substance and Positive Control........................... B. Test Species................................................................... C. Animal H usbandry........................................................ 1. Housing Environment................................................... 2. Feed and Water............................................................ 3. Identification............................................................... 4. Animal Health Monitoring Program................................ D. Quarantine and P retest.................................................. E. Study D esign.................................................................. F. Assignment to Groups and Study S tart....................... G. Dosing M aterial Preparation and A dm inistration...... 1. Test Substance............................................................. 2. Positive Controls.......................................................... 3. Negative Controls......................................................... H. Body W eights................................................................. I. M ortality and Clinical O bservations............................ J. Collection and Analysis of Blood and L ivers............. K. Treatment of Fluorine D ata....................................... . RESULTS AND D ISC U SSIO N ............................................. A. In-Life Toxicology........................................................ B. Fluorine D a ta .............................................. ................... 1. Factors Influencing Interpretation of Analysis.................. 2. Positive Controls.......................................................... 3. Test Substance.............................................................. ..........................................................1S RECORDS AND SA M PLE ST O R A G E.............................. ......................................................... 16 Company Sanitized. Does not contain TSCA CB1 -3 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Stndy in Rats ____________________ DuPont-4182 F IG U R E S.................................................................................. .....................................................23 APPENDICES--......-- ...............................__ ....__ ..................__............................................28 LIST OF TABLES Page 1. MEAN BODY W EIGHTS.............................................................................................................................................. .. 2. MEAN BODY WEIGHT G A IN S.................................................................................................................................. 20 3. MEAN BLOOD FLUORINE LEVELS........................................................................................................................ 21 4. MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE...................................................22 LIST OF FIGURES Page 1. FIGURE 1 MEAN BODY WEIGHTS..........................................................................................................................24 2. FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD............................................................................ 25 3. FIGURE 3 MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS...........27 LIST OF APPENDICES Page A. INDIVIDUAL BODY W EIGHTS................................................................................................................................. 29 B. INDIVIDUAL CLINICAL OBSERVATIONS.............................................................................................................71 C. INDIVIDUAL FLUORINE LEVELS.............................................................................................................. 84 upany Sanitized. Does net contain TSCA CBI -4 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats J STUDY INFORMATION TEST SUBSTANCE: . 1Substance li 'ili il Svnonvms/Codes: Hr24159 Haskell Number? 24159 Composition DuPont-4182 Known Impurities:^ POSITIVE CONTROL: Substance Tested: Potassium perfluoroalkyl sulfonate Svnonvms/Codes: H-24019 Haskell Number: 24019 Company Sanitized. Does not contain TSCA CB -5 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION (Continued) DuPont-4182 Substance Tested: Octanoic acid, pentadecafluoro-, ammonium salt Svnonvms/Codes: H-24020 Perfluorooctanoate, ammonium salt PFOA Ammonium perfluorooctanoate Haskell Number: 24020 Known Impurities:; Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: April 30,1999 / (see report cover page) In-LifeInitiated/Completed: July 11,1999/O ctober 12, 1999 Company Sanitized. Does not contain TSCA CB1 -6 - H-24159: 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-4182 Company Sanitized. Does net contain TSCA CBS -7 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 SUMMARY The objective of this study was to evaluate the potential for H-24159, 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 given 35 mg/kg/day of H-24159. The test substance was administered to one group of 5 rats for 5 consecutive days and to 5 groups for 10 days. Approximately 2 hours after the first dose, blood was collected from the orbital sinus of each rat from the 5-dose group. On selected days (5 ,1 0 ,1 3 ,2 4 ,5 2 , 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, 3 negative controls, deionized water, 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-24159. No deaths occurred during the study. No clinical signs associated with the test substance were observed in rats given H-24159. 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. The com oil and com oil/acetone negative control rats exhibited no clinical signs during the study. The mean body weights and mean body weight gains of the rats dosed with the test substance, H-24159, were comparable to the deionized water and com oil negative controls and greater than the H-24020 positive controls. Comparison of body weights between the rats dosed with the test substance and the com oil/acetone negative control and H-24019 positive control rats was complicated by the fact that there was a difference in age on test day 1 between the rats. Accounting for the age difference at study start and the expected rate of body weight gain, it appears that the mean body weights and mean body weight gains of the rats dosed with the test substance, H-24159, are comparable to the com oil/acetone negative controls and greater than the H-24019 positive controls. A steady-state for fluorine levels in whole blood may not have been achieved during 10 consecutive days of dosing with 35 mg/kg H-24159. An area under the curve (estimated to infinity) was calculated and normalized for fluorine content for the test substance and each positive control. The AUCINF/D for the fluorine component of the test substance, H-24159, was 28,933.0 compared to AUCINF/D values of 566,479.1 and 70,789.6 for the positive controls, H-24019 and H-24020, respectively. Under the conditions o f this study, administration of the test substance, H-24159, to male rats for 10 consecutive days resulted in moderate absorption and retention of fluorine in the blood. Dose-adjusted areas under the curve (AUCINF/D) for positive controls, H-24019 and H-24020, were approximately 20x and 2x the AUCINF/D for the test substance. Company Sanitized. Does not contain TSCA CB1 -8 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 INTRODUCTION The objective of this study was to define the potential of H-24159 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 2 positive controls that were materials previously shown to bioaccumulate in mammals. The dosage of 35 mg/kg/day was chosen based on available toxicity data and the results of a rangefinding study. In the initial rangefinding study, 5 rats were dosed with the test substance for 5 consecutive days at a dosage of 25 mg/kg. The rats experienced an overall mean body weight gain of 21 grams. A second rangefinding study was then conducted to determine if rats could tolerate a higher dosage. Five rats were dosed with the test substance for 5 consecutive days at a dosage of 35 mg/kg. The rats experienced an overall mean body weight gain of 17 grama. A control group had an overall mean body weight gain of 25 grams. Based on the results of this rangefinding study, the dosage of 35 mg/kg/day for the test substance was chosen for the study. 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-24159, was supplied by the sponsor as J ^ M M M M f T h e positive controls, H-24019 and H-24020, were supplied by the s p o n s o r ^ t S m m j B ^ e t e s t substance and positive controls appeared to be stable under the CradRIdl^^nH e 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. . Company Sanitized. Does not contain TSCA CBI ~9~- "" " H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 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 o f 23 1C and a relative humidity of 50 10%. 2. Feed and Water Tap water was provided ad libitum. All rats were fed PM3 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. Company Sanitized. Does not contain TSCA cm -10- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats D. Quarantine and Pretest DuPont-4182 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 designee. E. Study Design Substance Negative Controls Deionized Water Com oil Com oil:acetone Positive Controls H-24019 H-24020 Test Substance H-24159 Vehicle Not applicable Com oil: acetone Com oil Deionized water Dosage (mg/kg) 0 0 0 10 20 35 Number of Animals 30 30 30 30 30 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 M aterial Preparation and Administration 1. Test Substance H-24159 was administered as mg test substance received per kg weight of each animal. The slurry received was diluted with deionized water so an accurate amount could be administered at the selected dose level. The amount of dosing mixture (mL) each rat received was based on the Company Sanitized. Does not contain TSCA CBI -11 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 body weight collected on each day of dosing and the mixture concentration (3.5 mg slurry/mL water). The rats were dosed at a volume o f 1 mL/100 g of body weight. The dosing mixture was stirred on a magnetic stir plate throughout the dosing procedure to maintain homogeneity. 2. Positive Controls The solid positive control compounds were suspended as emulsions in their respective vehicles. Com oil wets used as the vehicle for H-24019. It was necessary to dissolve H-24020 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 Deionized water was chosen as a negative control because it was the vehicle for the test substance. 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 deionized water, 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 W eights All rats were weighed on each day of dosing then weekly or every other week during the recovery period. I. M ortality 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 was individually handled and examined for abnormal behavior and appearance. J. Collection and Analysis o f 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: Company Sanitized. Does not contain TSCA CBl - 12- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 Group I I n m 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 liv e r 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 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 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 personnel for evaluation of fluorine biopersistence. K. Treatment o f Fluorine Data Noncompartmental analysis was conducted on blood fluorine data derived from rats dosed with H-24159 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 (Ti/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, 1/(1-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 less than 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 from analysis o f total blood fluorine were used as received (ppm F) from Jackson Laboratory. Fluoride ion was converted to Company Sanitized. Does not-contain TSCA CBl -13- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 micromolar (jjlM) 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 1-2, Figure 1, Appendices A-B) No deaths occurred during the study. Alopecia, considered unrelated to test substance administration, was observed in 3 rats dosed with the test substance, H-24159. 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 in rats dosed with deionized water and the positive controls, H-24019 and H-24020. The com oil and com oil/acetone negative control rats exhibited no clinical signs during the study. The mean body weights and mean body weight gains of the rats dosed with the test substance, H-24159, were comparable to the deionized water and com oil negative controls and greater than the H-24020 positive controls. Comparison of body weights between the rats dosed with the test substance and the com oil/acetone negative control and H-24019 positive control rats was complicated by the fact that there was a difference in age on test day 1 between the rats. This difference resulted in differences in mean body weights on test day 1. The H-24159 rats were younger and lighter in weight than the com oil/acetone negative control and H-24019 positive control rats. Younger animals experience a period of rapid body weight gain. Older an im als are expected to gain weight at a slower rate than younger animals. Accounting for the age difference at study start and the expected rate of body weight gain, it appears that the mean body weights and mean body weight gains of the rats dosed with the test substance, H-24159, are comparable to the com oil/acetone negative controls and greater than the H-24019 positive controls. B. Fluorine Data (Tables 3-4, Figures 2-3, 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. Company Sanitized. Does not containTSCA CBI - 14- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 2. Positive Controls The positive controls were H-24019 and H-24020. The H-24019 normalized piM 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 /xM 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-24159 normalized jlM equivalents in rat blood continued to rise throughout the dosing period and may not have reached steady-state (Figure 2C). The Cmax for H-24159 was 203.85 27.09 ppm (Mean SD) with a terminal half-life of 29.1 days. 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 H-24159 AI was 42.5 and the BI was 8667.5. The total internal exposure resulting from a normalized dose was described by AUCINF/D and was the basis for comparison between H-24159 and positive controls. The AUCINF/D for the fluorine component of H-24159 was 28,933.0 as compared to AUCINF/D values of 566,479.1 and 70,789.6 for H-24019and H-24020, respectively. The data, calculations and equations are shown in Appendix C. CONCLUSIONS Rats dosed for 10 consecutive days with 35 mg/kg H-24159 exhibited no mortality or test substance-related clinical signs of toxicity and had mean body weights and mean body weight gains that were comparable to the negative controls. A steady-state for fluorine in the blood may not have been achieved during the 10-day dosing period. Under the conditions of this study, administration of H-24159 to male rats for 10 consecutive days resulted in moderate absorption and retention of fluorine in the blood. Dose-adjusted areas under the curve (AUCINF/D) for positive controls, H-24019 and H-24020, were approximately 20x and 2x the AUCINF/D for the test substance. Company Samt?ed. Does no! contain TSCA -15- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 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. Company Sanitized. Does no! contain TSCA CB -16- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLES Company Sanitized. Does not contain TSCCB? - 17- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE 1 MEAN BODY WEIGHTS (g) Test Days 1 2 3 4 5 6 7 8 9 10 13 18 20 24 25 27. 32 33 34 39 41 46 47 51 52 53 54 55 60 61 62 67 68 74 Negative Controls Deionized Com Oil: Water Com Oil Acetone 226.8 229.8 297.6 232.8 234.1 299.6 240.3 241.4 309.4 249.0 250.4 314.3 259.1 259.3 321.5 268.3 266.8 326.0 277.1 271.2 334.9 283.6 281.9 339.2 290.2 285.2 345.2 298.3 295.9 351.7 313.6 321.1 350.7 352.6 - - - 350.5 369.8 419.4 378.3 401.0 378.7 - - - 400.7 - - - - 449.5 - 463.5 - - 407.8 - 434.5 - 454.9 - 411.4 - - - 469.7 511.0 - 464.7 - - 527.6 - - - 528.0 - - 487.0 - 505.1 - - 547.7 - 558.0 - - 515.4 - - - _ Positive Controls Test Substance 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 - - - - - 438.1 - - - - - 523.4 - - _ 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 - 465.6 - 452.3 465.8 _ - 470.9 _ H-24159 233.7 237.9 249.4 256.6 263.7 272.1 275.0 290.4 296.1 303.0 323.0 _ _ 402.6 _ 400.1 _ 424.4 _ 451.9 473.3 488.3 _ _ 491.9 _ 510.7 - 524.9 _ _ Comoaw Sanitised. Does ont enw*nTSOA C81 - 18- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE 1 (Continued) MEAN BODY WEIGHTS (g) Test Days 76 80 81 82 88 90 94 Negative Controls Deionized Com Oil: Water Com Oil Acetone - - 539.0 - 573.0 - - - 589.5 - 584.6 - - 556.2 566.9 - - 562.2 567.8 Positive Controls Test Substance H-24019 563.4 570.7 - - - 585.3 597.9 H-24020_____ H-24159 - 547.6 - 499.2 .- - 527.8 538.7 - - 560.9 570.5 - 576.4 - Indicates the animal was not weighed. Company Sanitized. Does no! contain TSCA CB! H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE2 MEAN BODY WEIGHT GAINS (g) Test Days 1-5 1-10 10-13 10-24 10-51/52 10-94 Negative Controls Deionized Com Water Com Oil OilrAcetone 32.3 29.5 23.9 71.5 66.1 54.1 15.3 25.2 - 1.0 121.1 82.4 49.3 171.4 168.8 175.9 286.3 271.0 216.1 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-24159 30.0 69.3 20.0 99.6 185.3 273.4 Company Sanitized. Does not contain TSCA CB -20- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE 3 MEAN BLOOD FLUORINE LEVELS Test Days 1 5 10 13 24 52 94 Negative Controls Deionized Com Oil: Water Com Oil Acetone (ppm) (ppm) (ppm) <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 0.3a (0.1)b <0.2 0.2a (0.1) 0.6C(0.6) 0.2e <0.2 0.2d <0.2 0.3a (0.1) <0.2 0.9C 0.3a (0.1) <0.2 Positive Controls 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) Test Substance H-24159 (ppm) 2.2 (0.6) 7.1 (3.0) 11.6 (1.5) 2.5 (0.8) 1.5 (0.4) 0.9 (0.1) 0.4 (0.1) a Mean o f 4 o f the 5 values. One o f the values was below the level o f detection (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 die LOD. e Mean o f 2 o f the 5 values. Three o f the values were below the LOD. Company Sanitized. Does not contain TSCA CBI -21 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TABLE 4 MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE Test Days 1 5 10 13 24 52 94 Positive Controls H-24019 H-24020 liM F Equivalents liM F Equivalents 28.92 (13.3)a 89.28 (23.4) 747.69 (271.5) 518.12 (44.9) 945.85 (43.5) 391.01 (56.8) 989.85 (116.9) 191.45 (82.7) 645.54 (42.9) 74.35 (22.1) 411.38 (40.6) 4.64 (1.1) 195.38 (32.5) 0.24 (0.4) a Standard deviation is in parentheses. Test Substance H-24159 xM F Equivalents 35.11 (10.4) 124.32 (53.0) 203.85 (27.1) 41.91 (14.4) 22.57 (7.6) 12.18 (1.5) 4.30 (1.6) Company Sanitized. Does not contain TSCA CBf 2 2- - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 FIGURES Company Sanitfeed. Doss not contain TSCA CB[ 2 3- - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats 4 0 0 ~| 350 - 300 - W> 160 2 5 0 13 200 w 1 5 0 - 100 - 50 - 00 2 FIGURE 1 MEAN BODY WEIGHTS (g) DuPont-4182 "O...Negative Control (Deionized Water) --B --Negative Control (Corn Oil) A ..Negative Control (Corn Oil:Acetone) X Positive Control H-24019 --5K-- Positive Control H-24020 ---- Test Substance H-24159 4 6 8 10 12 Test Days Company Sanitized. oes nof contain TSCACBf -24- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD A . N orm alized R at Blood H -24019 p M E quivalents Resulting from a 10-Day O rai Gavage Micromolar (jiM) equivalents o f 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 at B lood H -2 4 0 2 0 ft M E q u iv a le n ts R esu ltin g from a 10-D ay ` O rai G avage Micromolar (iM) equivalents o f H-24020 (positive control) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. Company Sanitized. Does not contalnTSCA CB -25- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 C. N orm alized R at Blood H -24159 /tM E quivalents R esulting from a 10-Day Oral Gavage Micromolar (/iM ) equivalents o f H-24159 (test substance) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. Company Sanitized. Does not contain TSCA CB! -26- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 FIGURE 3 MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS P^lntjtfve'Control N o r m a lisp Ilfe M o ^ 'A U C lN F /D in Ra t s R e s u l t i n g from a 10-Day Oial Gavage S IS . B S ", I LU Company Saniffeed. Does not contain TSCA CBf -27- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 APPENDICES Company Sanitized. Does not contain TSCA CBI -28- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 APPENDIX A Individual Body W eights Company Sanitized. Does not continTSC CB 2 9- - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES ABBREVIATIONS: SD - sacrificed by design DuPont-4182 Company Sanitized. Does not containTSCA CBI 3 0- - _/ ' H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats___________________________________ DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I ANIMAL NUMBER DAY 1 DAY 2 TEST DAYS DAY 3 DAY 4 DAY 5 632649 632650 632651 632652 632653 208.8 223.3 238.6 243.4 210.5 208.2 231.1 243.1 240.0 210.5 219.8 239.3 253.6 253.0 217.6 225.1 243.7 260.8 257.3 223.0 240.4 261.7 276.7 272.4 236.0 SD test day 5 SD test day 5 SD test day 5 SD test day'5 SD test day 5 IS P ' DuPont-4182 Company Sanitized. Does not contain TSCA CB! -31- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632654 632655 632656 632657 632658 DAY 1 210.1 234.4 236.4 251.5 220.8 DAY 2 217.0 238.1 243.5 255.0 227.5 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 227.9 248.1 250.2 265.0 235.1 236.0 258.7 258.0 277.0 240.8 248.5 265.7 261.9 292.0 249.3 259.9 278.0 272.2 297.3 256.7 270.6 289.3 280.3 308.0 264.1 ANIMAL NUMBER 632654 632655 632656 632657 632658 DAY 8 282.8 295.4 286.5 317.0 274.3 DAY 9 286.6 307.1 286.1 324.3 278.2 TEST DAYS DAY 10 303.1 315.8 294.5 329.6 286.0 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 Company Sanitized. Does no! contain TSC CBI -32- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632659 632660 632661 632662 632663 Day 1 199.9 232.6 238.1 248.1 219.4 Day 2 208.0 238.9 243.1 255.5 227.9 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 211.0 240.7 247.4 261.5 229.9 220.9 251.8 258.1 269.7 241.7 231.0 260.8 265.7 279.8 249.9 238.9 268.0 273.5 286.2 257.7 247.8 275.7 285.0 292.8 265.2 ANIMAL NUMBER 632659 632660 632661 632662 632663 Day 8 Day 9 254.1 279.4 291.8 297.0 272.0 . 261.5 286.1 302.4 302.4 276.4 TEST DAYS Day 10 Day 13 270.0 296.3 304.5 309.2 285.1 293.1 309.1 334.9 331.1 299.9 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 Com pany Sanitized. D oes not contain TSCA CB1 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632664 632665 632666 632667 632668 Day 1 208.2 228.3 245.8 254.3 218.7 Day 2 213.9 236.6 251.0 262.3 226.8 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS ( g ) OF MALE RATS GROUP IV TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 219.9 244.9 263.4 272.0 238.5 226.1 252.4 273.8 285.6 249.3 236.6 264.0 282.8 293.6 260.3 242.9 274.3 297.4 300.6 270.1 252.6 282.1 310.0 315.2 282.0 ANIMAL NUMBER 632664 632665 632666 632667 632668 Day 8 256.0 288.0 314.6 319.9 291.6 Day 9 262.8 297.9 326.9 330.0 301.7 TEST DAYS . Day 10 Day 13 Day 18 Day 24 273.2 306.5 334.0 342.1 314.7 _a _a _a _a 318.2 367.1 398.1 414.4 385.7 349.0 408.5 441.8 460.4 437.5 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCA CBf H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632669 632670 632671 632672 632673 Day 1 194.4 224.5 226.8 256.3 217.3 Day 2 197.8 228.6 230.9 267.1 224.8 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP V TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 202.5 237.4 237.2 272.4 230.8 209.5 246.7 243.5 281.3 241.3 215.1 251.9 249.0 295.1 248.2 221.4 259.9 256.9 304.6 258.6 228.1 268.8 262.0 ' 315.4 265.7 ANIMAL NUMBER 632669 632670 632671 632672 632673 Day 8 234.3 271.0 268.0 319.4 268.9 Day 9 232.6 271.0 273.6 328.4 276.4 TEST DAYS Day 10 Day 13 Day 18 Day 24 Day 25 239.6 280.9 276.0 334.8 285.2 _a _a __a _a 278.1 328.3 308.4 389.8 335.6 _ a 301.2 _ a 361.5 _ a 346.2 __a 441.1 _a 370.8 ANIMAL NUMBER 632669 632670 632671 632672 632673 Day 32 Day 39 TEST DAYS Day 46 Day 52 322.8 389.9 378.5 377.5 400.9 355.5 415.7 421.9 517.0 433.8 366.6 434.9 434.6 542.7 457.3 392.4 449.1 456.4 566.6 484.2 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD tsst day 52 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCACSf H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 1 197.0 228.8 238.3 238.1 211.3 Day 2 205.1 239.3 243.2 240.7 227.6 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 214.1 243.1 252.0 248.2 233.9 221.7 255.3 259.8 255.9 244.4 232.7 264.9 270.3 261.7 253.6 242.0 271.8 280.9 276.0 262.6 250.9 278.0 289.4 282.0 266.0 ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 8 Day 9 261.7 - 266.0 285.7 291.6 294.1 300.3 289.0 298.0 278.3 286.3 TEST DAYS Day 10 Day 13 Day 18 Day 24 Day 25 276.7 296.7 309.8 302.7 291.4 __a _a __a __a --a 336.2 352.9 368.3 356.9 351.4 __a 380.4 __a 389.6 411.3 _a 397.5 -- a 387.6 ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 32 Day 39 TEST DAYS Day 46 Day 52 Day 53 Day 60 Day 67 419.5 433.4 441.0 423.9 419.3 465.7 482.3 484.3 458.8 460.1 471.8 485.0 502.4 472.8 467.2 508.2 536.0 530.2 492.8 487.8 529.6 540.7 552.8 514.7 502.0 545.8 584.8 565.0 525.1 518.0 566.2 592.2 571.8 536.4 523.5 DuPont-4182 a Rats not weighed. Com pany Sanitized. D oes not contain TSCA CBT H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER Day 74 Day 81 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF HALE RATS GROUP VI TEST DAYS Day 88 Day 94 632674 632675 632676 632677 632678 581.9 612.8 587.0 544.2 539.3 __a 583.5 548.9 SD test day 94 _a 645.4 652.9 SD test day 94 __a 605.1 603.2 SD test day 94 _a 562.0 569.4 SD test day 94 __a 551.6 548.5 SD test day 94 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCACBt H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF HALE RATS GROUP I TEST DAYS 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 test day 5 SD test day 5 SD test.day 5 SD test day 5 SD test day 5 DuPont-4182 Company Sanitized. D oes not contain TSCA CBV -38- H-24159: 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 test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 Company Sanitized. Does not contain TSCACB H-24159: 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 627796 627806 627807 627809 627816 285.9 282-. 8 270.7 297.9 291.8 290.1 285.8 274.7 300.2 296.4 300.0 302.8 280.7 311.9 305.7 322.7 320.3 305.2 336.2 330.2 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 C om pany Sanitized. Does not contain TSCACEK H-24159: 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 test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCA CBf H-24159: 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 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 test day- 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSDA DR! -42- H-24159: 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 VI 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 -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-4182 a Rats not weighed. C om pany Sanitized. Does not contain TSCA CB1  H-24159: 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 VI 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 test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-4182 Company Sanitized. Does not contain TSCA CBI H-24159: 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 TEST DAYS 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 test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 DuPont-4182 Com pany Sanitized. D oes not contain TSCA CB1 H-24159: 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 II 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 test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 Company Sanitized. Does not contain TSCA CB1 H-24159: 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 III 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 test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 Company Sanitized. Does not contain TSCA CM H-24159: 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 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 625354 625365 625371 625376 625381 DAY 8 336-. 2 370.5 340.3 331.5 321.6 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 337.0 379.3 345.9 339.0 329.1 348.8 381.2 351.2 345.2 331.6 355.8 407.1 372.6 363.2 341.2 377.7 438.2 413.0 399.7 358.2 396.1 459.6 447.3 432.9 381.8 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-4182 C om pany Sanitized. D oes not contain TSCA CB1 H-24159: 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 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 27 334.7 346.2 354.3 348.8 344.6 341.3 353.6 363.4 355.1 350.8 361.9 372.9 381.7 373.1 371.5 396.7 410.0 419.8 395.1 401.3 __a 431.3 __a 440.9 _ a 465.9 _ a 432.1 _a 447.2 ANIMAL NUMBER 625356 625359 625360 625372 625374 DAY 34 DAY 52 TEST DAYS 466.2 467.7 484.1 454.7 466.8 533.7 530.3 555.4 506.2 512.3 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCA CBV -49- H-24159: 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 VI 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 27 625353 625369 625373 625375 625377 344.7 307-.3 340.6 324.7 325.0 352.7 311.9 348.2 336.0 333.7 358.1 317.2 352.6 336.9 340.7 371.7 331.1 371.5 350.1 353.5 399.1 347.6 402.3 387.9 376.3 _a __a __a _a _a 427.7 374.9 444.6 432.3 405.2 ANIMAL NUMBER DAY 34 DAY 52 TEST DAYS DAY 76 DAY 90 DAY 94 625353 625369 625373 625375 625377 453.3 388.2 477.1 455.6 419.1 __a --a _a _a _a 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 test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-4182 a Rats not weighed. -50- Company Sanitized. Doss not contain TSC A CBS H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS 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 test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 DuPont-4182 -smpany Sanitized. Does not contain TSCA CBf -51 - H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II 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 test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 Company Sanitized. Does "o{ contain TSCA CBI -52- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III 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 test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 Com pany Sanitized. Does not contain T5CACB1 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (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 test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 ! DuPont-4182 Company Sanifead Dona no, conWn TSCA m -54- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF HALE 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 27 625324 625329 625333 625334 625344 332.5 352.5 315.8 292.6 280.7 337.9 360.1 316.7 302.2 285.2 336.1 357.0 319.3 305.8 289.3 299.6 364.3 325.8 312.0 295.8 336.0 396.4 349.2 338.6 309.7 __a --a _a _a 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 test day- 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-4182 a Rats not weighed. Company Sanitized. Does no! contain TSCA CBi H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DuPont-4182 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 27 625326 625335 625346 625347 625351 311.5 294 =2 292.9 330.5 351.1 308.9 285.3 290.8 330.1 357.8 297.5 274.0 288.4 333.0 350.5 274.2 266.3 296.9 355.7 380.0 335.4 340.1 352.5 402.1 413.7 _a _a _a --a _a 390.7 393.8 388.2 436.2 452.4 ANIMAL NUMBER DAY 34 DAY 52 TEST DAYS DAY 62 DAY 76 DAY 80 DAY 90 DAY 94 625326 625335 625346 625347 625351 427.5 427.0 407.4 466.4 483.3 --a _a _a _a 497.5 506.0 485.8 568.6 559.0 540.0 538.6 523.7 617.8 596.8 547.9 547.7 532.8 618.1 607.2 565.2 562.1 542.4 632.6 624.0 577.5 579.5 556.9 638.9 636.8 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 a Rats not weighed. -m pany Sanitized. D oes no? contain TSC CB1 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS 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 test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 DuPont-4182 'm p a n y Sanitized. Does do?contain TSCA CBS H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II 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 test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 ,,mpany Sanitized. Does r o t contain TSCA CBtf H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS <g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627758 627763 627764 627787 627788 235.1 212.1 230.0 235.1 219.4 240.3 218.3 235.0 241.0 222.3 248.6 226.5 246.1 250.1 232.2 255.8 234.3 251.3 257.2 239.6 261.2 230.8 254.8 258.6 247.6 272.0 235.5 261.7 237.6 256.7 276.1 238.0 264.7 240.3 257.9 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 test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 Company Sanitized. Doss not contain TSCACW H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 627759 627761 627770 627779 627786 277.8 240-.1 291.4 289.0 251.3 284.9 257.4 301.3 293.4 255.8 288.0 266.9 306.4 301.0 257.0 -a 348.0 335.7 355.8 374.4 304.4 380.1 359.4 379.8 406.2 326.1 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-4182 a Rats not weighed. C om pany Sanitized. D oes not contain TSCA CB1 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627757 627760 627765 627772 627781 269.1 262.6 271.5 300.9 258.1 276.7 280.3 282.4 307.5 266.8 279.7 287.3 288.1 317.0 271.2 -a -a -a 324.3 348.6 349.8 375.5 315.1 343.0 379.9 382.7 404.0 338.8 372.3 419.4 400.9 446.9 372.0 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 test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-4182 a Rats not weighed. C om pany Sanitized. D oes nf contain TSCA CBf H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627762 627769 627775 627778 627783 ANIMAL NUMBER 285.9 302-.0 286.6 244.8 256.6 DAY 41 299.1 309.6 296.0 250.8 259.2 DAY 47 301.5 312.5 304.5 255.1 264.3 -a -a TEST DAYS DAY 52 DAY 55 356.5 386.6 353.3 294.0 311.3 DAY 61 381.5 414.4 377.4 320.0 340.9 DAY 68 419.6 456.5 413.9 347.1 380.0 627762 627769 627775 627778 627783 438.7 479.7 433.2 356.8 409.6 439.9 474.6 451.1 373.5 426.9 --a _a _a _a __a 453.5 512.2 460.8 386.0 449.0 473.0 511.4 477.4 393.3 473.8 471.6 531.4 478.6 398.3 474.8 DuPont-4182 a Rats not weighed. C om pany Sanitized. D oes not contain TSCA CBS H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 81 DAY 90 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI 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 test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-4182 Company Sanitized. Does not contain TSCA CBI -63- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 628162 628173 628176 628183 628186 241.7 234.4 222.7 262.7 208.4 238.0 237.2 225.0 264.0 206.4 249.0 251.4 240.7 278.3 215.6 255.1 265.1 242.9 281.1 226.8 271.8 269.1 254.2 298.4 231.5 SD test day 5 SD test day 5 SD test.day 5 SD test day 5 SD test day 5 DuPont-4182 Company Ssnfhzed. Dnss w ( cnnMin tra CBf -64- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF HALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628159 628165 628168 628172 628177 230.5 223.0 245.5 223.6 242.8 234.9 224.8 247.9 227.2 251.3 248.6 237.1 264.1 237.8 262.1 254.6 245.1 270.0 243.6 267.9 256.7 254.3 277.4 248.1 280.0 267.8 265.7 287.3 258.6 283.8 269.4 268.4 290.2 261.0 285.2 ANIMAL NUMBER 628159 628165 628168 628172 628177 DAY 8 286% 7 282.2 300.9 272.9 306.9 DAY 9 TEST DAYS DAY 10 290.9 291.9 307.0 273.8 314.1 299.3 300.1 313.0 281.8 322.5 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-4182 Company Sanitized. D oes not contain T S C A C B I H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628154 628158 628171 628175 628185 247.8 227.4 229.9 236.0 217.8 246.1 232.0 234.7 242.3 222.8 259.2 243.9 250.1 253.3 229.3 264.4 249.0 254.0 259.3 234.6 274.0 261.2 261.0 262.8 239.9 280.1 271.9 271.6 275.7 249.0 282.5 273.5 275.1 277.8 252.6 ANIMAL NUMBER 628154 628158 628171 628175 628185 DAY 8 3or. 3 285.9 280.7 287.6 262.2 DAY 9 TEST DAYS DAY 10 DAY 13 311.4 292.5 292.1 299.4 268.0 316.3 299.2 296.0 303.6 274.7 338.9 332.7 320.6 326.5 296.1 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-4182 Company S anfec. b, , ,, lc0,, (ain TSCACa H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628155 628164 628166 628170 628184 232.1 239.2 225.2 240.0 244.5 234.5 247.4 227.1 241.3 246.0 248.7 253.4 242.5 261.5 256.1 252.1 261.4 248.3 265.1 265.0 261.9 260.6 255.6 271.4 270.3 268.3 271.6 265.4 280.7 280.3 270.6 274.7 268.3 283.4 284.5 ANIMAL NUMBER 628155 628164 628166 628170 628184 DAY 8 293-. 9 288.7 284.4 302.0 294.7 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 24 302.5 289.5 287.6 304.9 304.2 312.6 300.1 297.2 313.7 308.9 _a --a __a __a 412.0 386.4 417.1 421.1 376.2 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-4182 a Rats not weighed. Com pany Sanitized. Does not contain TSCA CBI H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628156 628157 628160 628180 628181 224.3 255.4 230.4 245.1 233.8 234.7 260.7 238.5 252.3 240.1 242.0 269.9 251.2 263.6 249.3 252.2 284.3 259.7 272.7 258.0 258.1 292.5 265.9 275.4 263.3 264.3 298.0 273.7 283.3 266.2 267.9 301.4 276.9 285.9 269.0 ANIMAL NUMBER 628156 628157 628160 628180 628181 DAY 8 274-. 1 323.3 293.8 307.3 285.1 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 24 DAY 27 DAY 33 283.9 328.1 299.2 312.6 291.4 287.3 333.0 307.6 316.1 297.8 -a -a _a 387.2 416.8 __a 434.9 463.1 _a 393.6 416.4 __a 403.0 434.1 __a 395.6 410.0 ANIMAL NUMBER 628156 628157 628160 628180 628181 DAY 41 DAY 47 TEST DAYS DAY 51 439.4 494.0 446.7 465.3 431.3 459.5 516.7 460.7 493.8 442.5 475.5 532.7 474.3 508.1 450.8 SD test day 51 SD test day 51 SD test day 51 SD test day 51 SD test day 51 DuPont-4182 a Rats not weighed. Company Sanitized. Doss no! contain TSCACB J H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_________________________________________ H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI ANIMAL NUMBER DAY 1 DAY 2 TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628161 628167 628174 628178 628179 222.9 221.3 240.5 225.3 236.6 231.1 229.5 249.8 230.3 238.9 239.2 237.5 258.6 239.6 248.4 244.2 247.5 266.1 249.7 256.8 250.4 255.0 275.7 249.3 264.3 260.1 262.5 281.3 261.4 273.6 263.8 265.7 284.2 264.9 277.1 ANIMAL NUMBER 628161 628167 628174 628178 628179 DAY 8 274:7 285.6 307.3 284.6 292.6 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 24 DAY 27 DAY 33 272.8 293.2 306.6 286.4 299.0 283.4 306.4 313.3 291.3 299.3 -a -a _a 364.5 388.9 __a 434.5 470.0 --a 395.0 409.5 __a 386.1 397.8 _a 406.8 437.4 ANIMAL NUMBER 628161 628167 628174 628178 628179 DAY 41 DAY 47 TEST DAYS DAY 51 DAY 54 DAY 60 DAY 67 DAY 76 411.0 500.3 440.0 422.1 469.0 428.3 533.7 462.3 446.9 488.1 _a _a --a --a _a 439.2 555.5 487.1 464.3 513.2 458.6 580.8 496.4 475.7 542.2 475.4 593.4 509.8 488.4 557.6 489.5 611.9 543.2 503.8 589.6 DuPont-4182 a Rats not weighed. Company Sanitized. Does not contain TSCA CBi -69- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24159 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI ANIMAL NUMBER DAY 82 TEST DAYS DAY 88 DAY 94 628161 628167 628174 628178 628179 498.3 625.5 549.7 520.9 609.9 500.8 633.6 565.5 533.0 619.5 503.0 635.7 571.7 541.9 629.8 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-4182 Company Sanitized. Doss not contain TSCA CBI -70- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 APPENDIX B Individual Clinical Observations Company Sanitized. Does not contain TSCA CB1 -71- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP I Observation Test Day 632649 632650 632651 632652 632653 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 632654 632655 632656 632657 632658 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 632659 632660 632661 632662 632663 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBI -72- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP IV Observation Test Day 632664 632665 632666 632667 632668 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 632669 632670 632671 632672 632673 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 632674 632675 632676 632677 632678 GROUP VI Observation No abnormalities detected Hair Loss, Forelimb, Bilateral No abnormalities detected Hair Loss, Forepaw, Bilateral No abnormalities detected No abnormalities detected Hair Loss, Forepaw, Bilateral No abnormalities detected Test Day 1-88 94 1-81 88-94 1-94 1-53 60-94 1-94 Company Sanitized. Does not contain TSC CB1 -73- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP I Observation Test Day 627789 627801 627805 627810 627818 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 627793 627797 627799 627800 627808 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 627796 627806 627807 627809 627816 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBI -74- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV Animal Number____________________ Observation________________________Test Day 627791 627794 627804 627812 627817 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 627792 627798 627813 627814 627815 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 627795 627811 627819 627820 627821 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-94 1-94 1-94 1-94 1-94 Company Sanitized. Does not pontain TSCA CBI -75- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number . GROUP I Observation Test Day 625361 625363 625364 625380 625383 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal . Number 625355 625362 625367 625368 625378 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 625357 625358 625370 625384 625385 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBI -76- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV Animal Number____________________ Observation________________________Test Day 625354 625365 625371 625376 625381 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 625356 625359 625360 625372 625374 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 625353 625369 625373 625375 625377 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-94 1-94 1-94 1-94 1-94 Company Sanitized. Does not contain TSCA CB1 -77- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 H-24019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP I Observation Test Day 625322 625323 625336 625343 625349 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 625320 625330 625332 625341 625350 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Diarrhea No abnormalities detected Test Day 1-10 1-10 1-10 1-4, 6-10 5 1-10 Animal Number 625321 625327 625342 625345 625348 GROUP III Observation No abnormalities detected Diarrhea No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-4, 6-13 5 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBS -78- H-24159: Biopersistence Screening 10-Dose Orai Gavage Study in Rats DuPont-4182 H-24019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP IV Observation________________________ Test Day 625325 625328 625338 625340 625352 No abnormalities detected No abnormalities detected No abnormalities detected Salivation No abnormalities detected No abnormalities detected 1-24 1-24 1-6, 8-24 7 1-24 1-24 Animal Number 625324 625329 625333 625334 625344 GROUP V Observation No abnormalities detected No abnormalities detected Salivation No abnormalities detected Salivation No abnormalities detected No abnormalities detected Test Day 1-52 1-6, 8-52 7 1-6, 8-52 7 1-52 1-52 Animal Number 625326 625335 625346 625347 625351 GROUP VI Observation 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 Test 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 Company Sanitized. Does not contain TSCA CB1 -79- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-4182 GROUP I Animal ' Number____________________ Observation________________________ Test Day 627756 627767 627771 627773 627777 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 627768 627774 627776 627782 627785 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 . 1-10 Animal Number 627758 627763 627764 627787 627788 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Wet perineum No abnormalities detected Diarrhea Test Day 1-13 1-13 1-13 1-5, 7-13 6 1-8, 10-13 9 Company Sanitized. Does not contain TSCA CB! -80 H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-4182 Animal ' Number 627759 627761 627770 627779 627786 GROUP IV Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-24 1-24 1-24 1-24 1-24 Animal Number 627757 627760 627765 627772 627781 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected Wet perineum No abnormalities detected Wet perineum No abnormalities detected Test Day 1-52 1-52 1, 3-52 2 1, 3-52 2 1-52 Animal Number 627762 627769 627775 627778 627783 GROUP VI Observation No abnormalities detected Diarrhea No abnormalities detected No abnormalities detected Alopecia perineum No abnormalities detected Alopecia both front paws Alopecia right front leg Test Day 1-8, 10-94 9 1-94 1-94 81, 90, 94 1-23, 94 24, 34, 41, 47, 55, 61, 74, 81, 90 Company Sanitized. Doss not contain TSCA CBI H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 H-24159 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number____________________ Observation________________________ Test Day 628162 628173 628176 628183 628186 No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 628159 628165 628168 628172 628177 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 628154 628158 628171 628175 628185 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Alopecia both front paws Alopecia both front legs No abnormalities detected Test Day 1-13 1-13 1-13 1-7, 10-13 8-9 8-9 1-13 Company Sanitized. Does not contain TSCA CBI -82- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 H-24159 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP IV __________________ Observation________________________Test Day 628155 628164 628166 628170 628184 No abnormalities detected No abnormalities detected No abnormalities detected No abnormali ties detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 628156 628157 628160 628180 628181 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected Alopecia both front paws Alopecia both front legs No abnormalities detected No abnormalities detected Test Day 1-51 1-51 1-7, 11-19 8 8-10, 20-51 1-51 1-51 Animal Number 628161 628167 628174 628178 628179 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Alopecia both front legs No abnormalities detected Test Day 1-94 1-94 1-94 1-66, 68-94 67 1-94 Company Sanitized. Does not contain TSCACB1 -83- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 APPENDIX C Individual Fluorine Levels Company Sanitized. Does not contain TSCA CB1 -84- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 Terms: Active % Active Mol W t Active Formulation Dose % F in Active Mol Wt F TERMS AND CALCULATIONS Fluorine containing compound The % of formulation that is made up of fluorine containing components The molecular weight of the fluorine containing components (g/mole) The mg of formulation given per kg of animal body weight The % fluorine in the fluorine containing components of the formulation (weight basis) The molecular weight of fluorine g/mol Compound Calculations: Dose Active (mg/kg) The mg of fluorine containing compound administered per kg of animal body weight. = (% active/100) x 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) x 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]) x Formulation Dose Company Sanitized. Does not contain TSCA CB1 -85- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 TERMS AND CALCULATIONS Individual Animal M easurement: ppm F in blood The ppm fluoride measured in blood 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 normalized to 0.1 mmol/kg Dose The ppm fluoride minus background that would be expected if the active dose was 0.1 mmol/kg instead of the actual active dose. This 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]) x (ppm F in blood minus background) jttmolar equivalents of active in blood The /[molar [/amol/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 W t F [mg/mmol]) x molar ratio active/F [mmol active/mmol F] x 1000 /amol/mmol Company Sanitized. Does notcontain TSCA CBt H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-4182 FACTORS INFLUENCING INTERPRETATION OF KINETIC ANALYSIS 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 Company Sanitized. Does not contain TSCACBl -87- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H -24019 DuPont-4182 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 497 10 100 % F in Active: Mol Wt. F (g/mol): 65 19 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 10 0.020 49.7 Dose F (mmol/kg): 0.342 Molar Ratio (Active/F): 0.059 Dose F (mg/kg): 6.5 Rat Number Test ppm F Day in Sample Blood Group I 625322 625323 625336 625343 625349 1 1 1 1 1 1.0 1.3 2.6 2.6 2.9 Group I 625322 5 51.7 625323 5 38.0 625336 5 38.7 625343 5 78.5 625349 5 37.1 Group II 625320 625330 625332 625341 625350 10 10 10 10 10 65.6 61.1 60.5 63.1 58.1 ppm F in Blood Minus Bkg 0.2 ppm 0.8 1.1 2.4 2.4 2.7 51.5 37.8 38.5 78.3 36.9 65.4 60.9 60.3 62.9 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 /imolar 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 Company Sanitized. Doss not contain TSCA CB -88- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats__________________________________________________________ DuPont-4182 Rat Number 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 fimolar Equivalents of Active in Blood Group 111 625321 625327 625342 625345 625348 13 13 13 13 13 77.2 61.5 64.6 57.0 62.4 77.0 61.3 64.4 56.8 62.2 382.69 304.66 320.07 282.30 309.13 1184.62 943.08 990.77 873.85 956.92 Group IV 625325 625328 625338 625340 625352 24 24 24 24 24 40.3 46.3 43.2 39.1 41.9 40.1 46.1 43.0 38.9 41.7 199.30 229.12 213.71 193.33 207.25 616.92 709.23 661.54 598.46 641.54 Group V 625324 625329 625333 625334 625344 52 52 52 52 52 24.7 29.8 27.3 29.1 23.8 24.5 29.6 27.1 28.9 23.6 121.77 147.11 134.69 143.63 117.29 376.92 455.38 416.92 444.62 363.08 Group VI 625326 625335 625346 625347 625351 94 94 94 94 94 12.4 16.4 13.1 11.0 11.6 12.2 16.2 12.9 10.8 11.4 60.63 80.51 64.11 53.68 56.66 187.69 249.23 198.46 166.15 175.38 Company Sanitized. Does not contain TSCA CB1 -89- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H -24020 DuPont-4182 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 426 20 100 %F in Active: Mol Wt. F (g/mol): 69 19 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 20 0.047 42.6 Dose F (mmol/kg): 0.726 Molar Ratio (Active/F): 0.065 Dose F (mg/kg): 13.8 Rat Number Test ppm F Day in Sample Blood Group I 627773 627771 627767 627756 627777 1 1 1 1 1 13.2 8.1 16.5 14.1 10.7 Group I 627773 627771 627767 627756 627777 5 5 5 5 5 75.3 66.8 64.8 80.0 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 g molar 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 TSCA CB1 -90- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats__________________________________ Rat Number 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 Group III 627758 627764 627787 627763 627788 13 13 13 13 13 43.5 20.7 13.2 30.8 24.9 43.3 20.5 13.0 30.6 24.7 92.23 43.67 27.69 65.18 52.61 Group IV 627759 627779 627770 627761 627786 24 24 24 24 24 9.2 14.9 11.6 9.9 6.7 9.0 14.7 11.4 9.7 6.5 19.17 31.31 24.28 20.66 13.85 Group V 627757 627781 627760 627765 627772 52 52 52 52 52 0.9 0.6 1.0 0.9 0.8 0.7 0.4 0.8 0.7 0.6 1.49 0.85 1.70 1.49 1.28 Group VI 627778 627783 627762 627775 627769 94 94 94 94 94 0.3 <0.2 0.2 0.2 <0.2 0.1 * 0.0 0.0 * 0.21 * 0.00 0.00 * DuPont-4182 unolar Equivalents of Active in Blood 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 * * = Below LOD (Level o f Detection) i Company Sanitized. Does not contain TSCA CB1 -91- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H-24159 DuPont-4182 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): %Active (F Containing) in Formulation: 450 35 29 % F in Active: Mol Wt. F (g/mol): Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: Dose F (mmol/kg): Molar Ratio (Active/F): Dose F (mg/kg): Rat Number Test ppm F Day in Sample Blood Group I 628183 628186 628176 628173 628162 1 1 1 1 1 3.1 1.7 2.3 2.0 1.7 Group I 628183 628186 628176 628173 628162 5 5 5 5 5 9.0 10.8 3.4 5.1 7.4 Group II 628177 628168 628165 628172 628159 10 10 10 10 10 9.7 11.3 10.8 12.5 13.6 ppm F in Blood Minus Bkg 0.2 ppm 2.9 1.5 2.1 1.8 . 1.5 8.8 10.6 3.2 4.9 7.2 9.5 11.1 10.6 12.3 . 13.4 ppm F in Blood Normalized to 0.1 mmoles/kg Dose limolar Equivalents of Active in Blood 12.86 6.65 9.31 7.98 6.65 51.95 26.87 37.62 32.24 26.87 39.01 47.00 14.19 21.72 31.92 157.64 189.88 57.32 87.77 128.97 42.12 49.21 47.00 54.53 59.41 170.17 198.84 189.88 220.33 240.04 Company Sanitized. Does not contain TSCA CBS -92- H-24159: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat Number Test ppm F Day in Sample Blood Group III 628175 628171 628154 628185 628158 13 13 13 13 13 2.1 2.1 3.5 1.7 3.3 Group IV 628155 628170 628184 628164 628166 24 24 24 24 24 1.0 1.4 2.1 1.2 1.6 Group V 628156 628160 628181 628180 628157 52 52 52 52 52 0.9 0.8 1.0 0.9 0.8 Group VI 628178 628167 628161 628179 628174 94 94 94 94 94 0.5 0.5 0.4 0.3 0.5 ppm F in Blood Minus Bkg 0.2 ppm 1.9 1.9 3.3 1.5 3.1 0.8 1.2 1.9 1.0 1.4 0.7 0.6 0.8 0.7 0.6 0.3 0.3 0.2 0.1 0.3 ppm F in Blood Normalized to 0.1 mmoles/kg Dose 8.42 8.42 14.63 6.65 13.74 3.55 5.32 8.42 4.43 6.21 3.10 2.66 3.55 3.10 2.66 1.33 1.33 0.89 0.44 1.33 DuPont-4182 limolar Equivalents of Active in Blood 34.03 34.03 59.11 26.87 55.53 14.33 21.50 34.03 17.91 25.08 12.54 10.75 14.33 12.54 10.75 5.37 5.37 3.58 1.79 5.37 Company S a n f e A Does ,,,,coniain TSCA ^ -93-