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TRADE SECRET AR226-3165 DuPont-2926 Study Title H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Laboratory Project ID: DuPont-2926 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 Page 1 o f93 Company Sanitized. Does not contain TSCA CBJ H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation o f data obtained from this study. Reviewed by: Gary W. Jepson, Ph.D. Senior Research Scientist Reviewed by: V_ '/ c Judith C. Stadier, Ph.D., D.A.B.T. Director Issued by Study Director: _____C . t l A i r t j i m i A u . Carol Fiflfay, B.A. (J Staff Scientist Date Q S-ser-Zoo Date ho - f.pt'ljcfr Date -2 contain TSCA CB1 Company Sanitized. D oes not H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TABLE OF CONTENTS Page CERTIFICATION.................................... 2 LIST OF TABLES................................................................................................................................ LIST OF FIGURES.............................................................................................................................. LIST OF APPENDICES..................................................................................................................... 4 STUDY INFORMATION.............................................................. 5 STUDY PERSONNEL.................................. 7 SUMMARY................................. 8 INTRODUCTION............................................................................................................................... 9 MATERIALS AND M ETHODS............................................................................ 9 A. Test Substance and Positive Control........................................................................................9 B. Test Species................................................................................................................................9 C. Animal Husbandry.............................................................;.................................................. 10 1. Housing Environment................................................................................................................................ .. 2. Feed and Water............................................................................................................................................. 3. Identification...................................................................... 10 4. Animal Health Monitoring Program.......................................................................................................... 10 D. Quarantine and Pretest............................................................................................................11 E. Study D esign............................................................................................................................11 F. Assignment to Groups and Study Start................................................................... 11 G. Dosing Material Preparation and Administration.................................................................11 1. Test Substance..................................................................................................................................... H 2. Positive Controls............................. 12 3. Negative Controls......................................................................................................................................... H. Body W eights...........................................................................................................................12 I. Mortality and Clinical Observations......................................................................................12 J. Collection and Analysis o f Blood and Livers........................................................................ 12 K. Treatment o f Fluorine D ata...................................... 13 RESULTS AND DISCUSSION.................. ..................................................................................... A. In-Life Toxicology.................................................................................................................. 14 B. Fluorine Data.............................................. 14 1. Factors Influencing Interpretation of Analysis................................. 14 2. Positive Controls......................................................................................................................................... 5 3. Test Substance.............................................................................................................................................. C O N C L U S IO N S ............................................................................................................................... .. RECORDS AND SAMPLE STORAGE................................................................. TABLES............................................................................................................................................... 17 15 ISCA - 3 - feed. Db'aS n Compaq San H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 F IG U R E S.............................................................................................. ............................................. 23 APPENDICES................................................... ...............................................................................28 LIST OF TABLES Page 1. MEAN BODY WEIGHTS.......................................................................................................................................18 2. MEAN BODY WEIGHT GAINS........................................................................................................................... 20 3. MEAN BLOOD FLUORINE LEVELS.................................................................................................................. 21 4. MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE................................................22 LIST OF FIGURES Page 1. MEAN BODY WEIGHTS.......................................................................................................................................24 2. MICROMOLAR EQUIVALENTS IN RAT BLOOD............................................................... ............................ 25 3. MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS............................27 LIST OF APPENDICES Page A. INDIVIDUAL BODY WEIGHTS...........................................................................................................................29 B. INDIVIDUAL CLINICAL OBSERVATIONS....................................................................................................... 71 C. INDIVIDUAL FLUORINE LEVELS........................................... 84 -4- not contain t SOA CB1 Company Sanitized. Does H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION TEST SUBSTANCE: Substance Tested: Synonvms/Codes: H-24002 Haskell Number: 24002 Composition: Known Impurities: POSITIVE CONTROL: Substance Tested: Potassium perfluoroalkyl sulfonate Synonvms/Codes : H-24019 DuPont-2926 Haskell Number: 24019 - 5 - C otnpany Sanitszsd. Docs rit contain TSC CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION (Continued) POSITIVE CONTROL: DuPont-2926 Perfluorooctanoate, ammonium salt PFOA Ammonium perfluorooctanoate Haskell Number: 24020 Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.SA. Study Initiated/Completed: April 30,1999 / (see report cover page) In-Life Initiated/Completed: July 11,1999 / October 12,1999 t.nnfi nOfLtlSV-Q*rstain TSCACB1 H-24002: 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-2926 -7 - H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 SUMMARY The objective o f this study was to evaluate the potential for H-24002, when administered by gavage, to.be absorbed and to accumulate in a mammalian system. Six groups o f 5 male Crl:CD(SD)IGS BR rats each were given 75 mg/kg/day o f H-24002. 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 o f each rat from the 5-dose group. On selected days (5 ,1 0 ,1 3 ,2 4 , 52, 94) 5 rats per group were euthanized and the blood and livers were collected. Body weights and clinical signs were recorded on each day o f 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-24002. No deaths occurred during the study. No clinical signs associated with the test substance were observed in rats given H-24002. Rats dosed with H-24019 exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining o f various parts o f 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 o f the rats dosed with the test substance, H-24002, were comparable to the deionized water and com oil negative controls and greater than the H-24020 positive controls. Comparison o f 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 o f body weight gain, it appears that the mean body weights and mean body weight gains o f the rats dosed with the test substance, H-24002, are comparable to the com oil/acetone negative controls and greater than th H-24019 positive controls. A steady-state for fluorine levels in whole blood may not have been achieved during 10 consecutive days o f dosing with 75 mg/kg H-24002. 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 o f the test substance, H-24002, was 7031.0 compared to AUCINF/D values o f 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 o f the test substance, H-24002, to male rats for 10 consecutive days resulted in low absorption and retention o f fluorine in the blood. Doseadjusted areas under the curve (AUCINF/D) for positive controls, H-24019 and H-24020, were approximately 8lx and lOx the AUCINF/D for the test substance. - 8 - nol contain liCACDl Compan Sanitized. oes H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 INTRODUCTION The objective o f this study was to define the potential o f H-24002 to be absorbed and to bioaccumulate in a mammalian system, as indicated by analytical determination o f 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 o f 75 mg/kg/day was chosen based on available toxicity data and the results o f a rangefinding study. In the initial rangefinding study, 5 rats were dosed with the test substance for 4 consecutive days at a dosage of 700 mg/kg. The study was terminated because the rats experienced an overall mean body weight loss o f 21 grams. In a second rangefinding study, 5 rats were dosed with the test substance for 5 consecutive days at a dosage o f 100 mg/kg. The rats experienced an overall mean body weight gain o f 6 grams. Based on the results o f this rangefinding study, the dosage of 75 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 o f selected liver samples will be presented in a supplemental report. MATERIALS AND METHODS A. Test Substance and Positive Control The test substance, H-24002, was supplied by the sponsor as an amber brown 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 o f the study. No evidence o f 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 o f extensive experience with this strain and its suitability with respect to longevity, hardiness, sensitivity, and low incidence o f spontaneous diseases. - 9 - Sanitized. Does not contain TSCA Company H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats C. Animal Husbandry DuPont-2926 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 o f 50 10%. 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 o f 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 o f the study: Water samples are analyzed for total bacterial counts, and the presence o f 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 o f 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 o f the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. -10Company Sanitized. D oes not contain TSCA CB1 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 o f disease or injury. The rats were observed daily for mortality and signs o f illness, injury, or abnormal behavior. On the bases o f acceptable body weight gains and freedom from clinically apparent signs o f 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-24002 Vehicle Not applicable Com oil: acetone Com oil Deionized Water Dosage (mg/kg) 0 0 0 10 20 75 Number o f 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 o f adequate body weight gain, freedom from any clinical signs of disease or injury, and a body weight within 20% o f 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 o f the animal number was marked or tattooed on the tail o f each rat. The rats were between 7 and 9 weeks o f 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-24002 was administered as mg test substance received per kg weight o f each animal. The liquid test substance received was diluted with deionized water so an accurate amount could be administered at the selected dose level. The amount o f dosing mixture (mL) each rat received -11 - H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 was based on the body weight collected on each day o f dosing and the dosing mixture concentration (7.5 mg liquid test substance/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 was used as the vehicle for H-24019. It was necessary to dissolve H-24020 in acetone before suspending it in com oil. The ratio o f acetone to com oil was 20:80. The amount each rat received was based on the body weight collected on each day o f 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 oihacetone (80:20) were chosen as negative controls because they were the vehicles for the positive controls. Each negative control rat received 1 mL o f 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 o f dosing and 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 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 o f blood was collected into EDTA tubes from the orbital sinus o f 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- Compaq 'not contain 'isuA C H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 Group I I n m IV V VI Dosing Days Tissue Collected Sampling Time 1-5 Blood Test day 1 (2 hours post dosing) 1-5 Blood and Liver Test day 5 at sacrifice (2 hours post dosing) 1-10 Blood and Liver Test day 10 (2 hours post dosing) 1-10 Blood and Liver Test day 13 1-10 Blood and Liver Test day 24 1-10 Blood and Liver Test day 52 1-10 Blood and Liver 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 o f 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 o f 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 o f fluorine biopersistence. K. Treatment of Fluorine Data Noncompartmental analysis was conducted on blood fluorine data derived from rats dosed with H-24002 using WinNonlin Version 3.0 software (Pharsight Corp, Mountain View, CA). WinNonlin software provided a means o f 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 o f dosing extrapolated to infinity. The maximum observed concentration was Cmax (concentration). The points included in determination o f the terminal half-life were selected manually and given in units o f 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 o f variability and limited sensitivity o f the analytical method, the background was set at 0.2 ppm fluorine. Since 0.2 ppm was the fluoride concentration limit o f 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 no* r-nniainTSCACBl - 1 3 - Gompany Sanitize0- u" 3 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 fluorine were used as received (ppm F) from Jackson Laboratory. Fluoride ion was converted to micromolar (/xM) equivalents o f active component for further comparisons. The data and descriptions o f 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 1 rat dosed with the test substance, H-24002. Rats dosed with H-24019 exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining o f various parts o f 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 o f the rats dosed with the test substance, H-24002, were comparable to the deionized water and com oil negative controls and greater than the H-24020 positive controls. Comparison o f 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-24002 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 o f rapid body weight gain. Older animals are expected to gain weight at a slower rate than younger animals. Accounting for the age difference at study start and the expected rate o f body weight gain, it appears that the mean body weights and mean body weight gains o f the rats dosed with the test substance, H-24002, 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 o f considerations o f 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 o f the terminal half-life. A more complete list o f considerations is shown in Appendix C. Company Sanitized. Doso noi contain TSCA CBi H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats 2. Positive Controls DuPont-2926 The positive controls were H-24019 and H-24020. The H-24019 normalized xM 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 o f 40.5 days. The H-24019 AI was 59.0 and the BI was 58382.2. The H-24020 normalized juM equivalents in rat blood peaked after 5 days o f 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 o f 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 o f 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-24002 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-24002 was 39.60 2.62 ppm (Mean SD) with a terminal half-life o f 15.7 days. Blood was sampled at seven time points throughout the study, with only four o f 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-24002 AI was 23.1 and the BI was 916.0. The total internal exposure resulting from a normalized dose was described by AUCINF/D and was the basis for comparison between H-24002 and positive controls. The AUCINF/D for the fluorine component o f H-24002 was 7031.0 as compared to AUCINF/D values o f 566,479.1 and 70,789.6 for H-24019 and h-24020, respectively. The data, calculations and equations are shown in Appendix C. CONCLUSIONS Rats dosed for 10 consecutive days with 75 mg/kg H-24002 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 o f this study, administration of H-24002 to male rats for 10 consecutive days resulted in low absorption and retention o f fluorine in the blood. Dose-adjusted areas under the curve (AUCINF/D) for positive controls, H-24019 and H-24020, were approximately 8lx and lOx the AUCINF/D for the test substance. -15- Company Sanitized. Does not contain f SCA CBt H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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. -16- ^ Company Sanitized. Does not contain TSCA CBl H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TABLES - 17- Com pany Sanitised. Does not contain TSCA CBi H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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-24002 234.6 239.3 248.4 256.1 264.8 271.2 274.2 288.6 294.3 301.9 322.1 _ 364.7 371.9 - 416.0 - 444.9 - _ 473.7 - 499.5 532.7 - - 506.6 - 525.9 - - _ _ - 18- Com pany Sanitized. Does not contain TSCA 8I H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 - Indicates the animal was not weighed. Positive Controls Test Substance H-24019 563.4 570.7 - - - 585.3 597.9 H-24020_____ H-24002 - 562.3 - 499.2 - - 527.8 538.7 - - 578.1 586.4 - 593.9 -19- H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TABLE 2 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 Oil:Acetone 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-24002 30.2 67.3 20.2 70.0 230.8 292.0 -20Company Sanitized. Does not contain TSCA CSi H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TABLE 3 MEAN BLOOD FLUORINE LEVELS Negative Controls Positive Controls Test Substance Deionized Com Oil: Test Water Com Oil Acetone H-24019 H-24020 H-24002 Days (ppm) (ppm) (ppm) ____ (PPm)......... (ppm) (ppm) 1 <0.2 <0.2 <0.2 2.1 (0.9) 62.6 (3.2) 1.9 (0.4) 5 <0.2 <0.2 <0.2 48.8 (17.6) 71.7 (6.2) 6.0 (0.4) 10 <0.2 <0.2 0.3a (0.1)b 61.7 (2.8) 54.2 (7.8) 7.3 (0.5) 13 <0.2 0.2a (0.1) 0.6C(0.6) 64.5 (7.6) 26.6 (11.4) 3.1 (0.2) 24 0.2e <0.2 0.2d 42.2 (2.8) 10.5 (3.0) 1.8 (0.2) 51/52 <0.2 0.3a (0.1) <0.2 26.9 (2.6) 0.9 (0.2) 0.6 (0.1) 94 0.9C 0.3a (0.1) <0.2 13.2 (2.1) 0.2C (0.1) 0.3 (0.0) a Mean of 4 of the 5 values. One of the values was below the level of detection (LOD). b Standard deviation is in parentheses. c Mean of 3 of the 5 values. Two o f the values were below the LOD. d One value. Four of the values were below the LOD. e Mean of 2 of the 5 values. Three of the values were below the LOD. -21 Sanitized. Done not contain TSC CBI Company H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TABLE 4 MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE Test Days 1 5 10 13 24 52 94 Positive Controls H-24019 H-24020 jttM F Equivalents M 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-24002 M F Equivalents 9.35 (2.0) 32.26 (2.4) 39.60 (2.6) 16.13 (1.3) 8.90 (0.9) 2.00 (0.6) 0.45 (0.3) - 2 2 - ompany Sanitized. Does not contain TSGA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 FIGURES 1 -23- _m,,,,.5 QCSS not contain TSCA CBF H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats 400 n J FIGURE 1 MEAN BODY WEIGHTS (g) DuPont-2926 Company Sanitized. Does not contain TSCA CBt --^ --Negative C ontrol (D eionized W ater) --S --Negative C ontrol (Corn Oil) ..N egative C ontrol (Corn O ihA cetone) ~-x-..Positive C ontrol H-24019 --ac- Positive C ontrol H-24020 ----Test Substance H-24002 50 - 0 0 2 4 6 8 10 12 Test Days -24- H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD A. Normalized Rat Blood H-24019 fiM Equivalents Resulting from a 10-Day O rai G avage MeanfiMEquivalents MeanfiMEquivalents Micromolar (/iM) 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 o r m a l i z e d R a t Bl ood H -2 4020 jiM E q u i v a l e n t s R e s u l t i n g f r o m a 1 0 - Da y O r a l G avage Micromolar (/iM) 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. - 2 5 - not contain TSCACBt Sandized. Does Company H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 C. Normalized Rat Blood H-24002 jxM Equivalents Resulting from a 10-Day Oral Gavage Micromolar QiM) equivalents of H-24002 (test substance) in rat blood resulting from a 10-day oral gavage exposure. Values are means and error bars are standard deviation. - 2 6 - SawJB*-0 0 ** ComP8" * fSGA CBl H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 FIGURE 3 MICROMQLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS .'v- ,U- 1-24002 and Positive C ontrol N o-m alized Biood A U C IN F/D in Rats Resulting G rai Gavage -27- Company Sanitized. Does not contain TSCA CBt H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 APPENDICES - 28 - Company Sanitized. Does not contain s6%,k GW H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 APPENDIX A Individual Body Weights - 29- ,t contain TSCACB1 Company S="ifeed-0085 "0' H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats INDIVIDUAL BODY WEIGHTS ABBREVIATIONS: EXPLANATORY NOTES SD - sacrificed by design DuPont-2926 -30- _ Company Sanitized. Does not contain TSCA CB1 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632649 632650 632651 632652 632653 DAY 1 208.8 223.3 238.6 243.4 210.5 DAY 2 208.2 231.1 243.1 240.0 210.5 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 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 DuPont-2926 -31 - cntaUrTSOACB Sanitized. Doss no Company H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats 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 DAY 9 282.8 295.4 286.5 317.0 274.3 - 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-2926 -32Company Sanitized. Does not contain TSCA CBl H-24002: 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 8 254.1 279.4 291.8 297.0 272.0 Day 9 261.5 286.1 302.4 302.4 276.4 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-2926 -33- Company Sanitized. Does not contain TSCA CBf H-24002: 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 _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-2926 a Rats not weighed. Company Sanitized. Does not contain TSC Cffl H-24002: 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 Day 9 TEST DAYS Day 10 Day 13 234.3 271.0 268.0 319.4 268.9 232.6 271.0 273.6 328.4 276.4 . 239.6 280.9 276.0 334.8 285.2 __a _a __a _a _a Day 18 278.1 328.3 308.4 389.8 335.6 Day 24 Day 25 __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 test day 52 DuPont-2926 a Rats not weighed. -35- Sanitized. Does not contali TQOA CB1 Comparty H-24002: 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 9 261.7 285.7 294.1 289.0 278.3 ' 266.0 291.6 300.3 298.0 286.3 TEST DAYS Day 10 Day 13 Day 18 276.7 296.7 309.8 302.7 291.4 _a __a __a _a __a 336.2 352.9 368.3 356.9 351.4 Day 24 _a _a _a _a __a Day 25 380.4 389.6 411.3 397.5 387.6 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-2926 a Rats not weighed. -36- Company Sanitized. Does nTggntin TSGA CB H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER Day 74 Day 81 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE 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-2926 a Rats not weighed. -37- TSOTCBi. Company Sanitized. Boos not contain H-24002: 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 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-2926 TOW ,,lr.in,TSPfe.9 BI -38- Sanitized. Does Company H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 J CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II 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 flliipp' DuPont-2926 Company Sanitized. Does not contain TSC CB H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 627796 627806 627807 627809 627816 DAY 1 239.8 227.3 221.5 234.2 235.0 DAY 2 249.7 234.2 225.9 240.4 238.6 ) CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 253.6 239.4 237.1 252.5 250.0 252.5 242.9 244.1 260.3 258.9 267.7 258.5 254.9 272.8 265.1 277.2 270.4 257.7 277.9 274.5 289.8 275.2 260.3 282.6 278.6 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-2926 Company Sanitised. Does not contain TSCA c m H-24002: 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-2926 a Rats not weighed. -41 - Does not contain TSCACB Company Sanitized. H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 627792 627798 627813 627814 627815 ANIMAL NUMBER 627792 627798 627813 627814 627815 DAY 1 235.8 241.1 214.8 217.5 230.1 DAY 2 240.8 253.4 219.2 220.5 242.2 DAY 8 282.4 294:3 258.7 248.0 289.2 DAY 9 286.4 296.3 259.2 250.7 293.4 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OP MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 244.3 257.6 220.5 223.7 243.8 247.9 266.1 233.2 225.2 255.7 252.5 272.9 239.8 233.8 265.0 264.4 281.9 243.2 236.7 270.0 268.1 286.2 246.8 240.6 274.1 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 295.2 315.7 267.9 257.3 303.3 _a --a _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 test day- 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-2926 a Rats not weighed. -42- Company Sanitized. Does not contain TSCA CBl H-24002: 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 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 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-2926 a Rats not weighed. fSCACB' - 4 3 - TW H-24002: 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 SD test SD test SD test SD test DuPont-2926 -44- Company Sanitized. Doss not contain TSCA CB H-24002: 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-2926 - 4 5 - Company Sanitised. Does yrortontaln ISC A H-24002: 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-2926 F dWW*ont"lnT$CACB1 - 4 6 - Gompany. Saniti***, H-24002: 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-2926 -47- act contain TSCACBl Company Sanitized. Ooes H-24002: 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 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 test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2926 _ _ . . !.n T 0 0 A CRl - 4 8 - Company San'rtte , Doss H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OILACETONE (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 test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-2926 a Rats not weighed. Company Sanitized. Does not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_________________________________________ CORN OIL:ACETONE (NEGATIVE CONTROL) ANIMAL NUMBER DAY 1 DAY 2 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 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-2926 a Rats not weighed. -50- Gompany Sanitized, Does not contain TSCA l if t H-24002: Biopersistence Screening 10-Dose ()ral 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-2926 -51 - Company Sanitized. Does not contain TSCA CB H-24002: 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 GROUSE 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 test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-2926 -52- Company Sanitized. D es not contain TSCA CE i H-24002: 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 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 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-2926 - 53- .Doesnoicontam iowAODI Company Santtteed H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OP 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-2926 -54- Company Sanitized. Does not contain TSCA CBI H-24002: 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 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 ANIMAL NUMBER 332.5 352.-5 315.8 292.6 280.7 337.9 360.1 316.7 302.2 285.2 DAY 34 DAY 52 336.1 357.0 319.3 305.8 289.3 299.6 364.3 325.8 312.0 295.8 TEST DAYS 336.0 396.4 349.2 338.6 309.7 _a --a --a __a _a 380.3 423.3 375.2 368.8 330.4 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-2926 a Rats not weighed. - 55 Company Sanitized. Does not contain ISO A CSi H-24002: 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-2926 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 _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. -56- Cotnpany Sanitized. Doss not contain TSCA CBi H-24002: 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-2926 -57- Company SanltizocL Does nel contain TSCCBt H-24002: 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-2926 -58- Company Sanitized. Docs not contain TSCA CSI H-24002: 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 DnPont-2926 -59- Company Sanitised. Does not contain TSCA CBI H-24002; 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 226.6 240.7 235.6 231.5 211.6 232.9 247.4 244.3 237.9 218.2 241.4 257.1 253.6 252.6 222.5 250.9 262.5 260.1 261.4 230.4 254.2 266.7 267.7 262.3 230.6 262.1 259.2 277.3273.8 240.6 265.4 262.6 279.8 277.5 244.1 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 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 test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2926 a Rats not weighed. -60- 'Companj S a n i t i Does not contain TSCA CB| H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF HALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627757 627760 627765 627772 627781 ANIMAL NUMBER 627757 627760 62 7765 627772 627781 ANIMAL NUMBER 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 269.1 262.6 271.5 300.9 258.1 276.7 280.3 282.4 307.5 266.8 279.7 287.3 288.1 317.0 271.2 __a _a _a _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 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-2926 a Rats not weighed. - 61Company Sanitized. Does not contain TSCA CB? H-24002: 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 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-2926 a Rats not weighed. -62- Company Sanitized. Does not contain TSCA CBi H-24002: 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-2926 -63- Company Sanitized. Does not contain TSCA CBl H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 628192 628195 628207 628211 628212 227.2 245.6 238.0 220.1 252.0 224.9 250.7 241.3 224.3 . 250.9 236.5 261.4 253.4 233.4 267.8 244.2 265.9 261.0 239.6 271.0 251.3 279.5 269.9 250.9 281.1 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 DuPont-2926 - 6 4 - .Company Sanitized. Does not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628187 628188 628199 628209 628217 240.1 258.1 253.4 229.5 218.0 246.4 261.5 255.3 238.2 224.4 258.3 269.2 263.6 247.6 234.1 266.1 279.0 274.6 253.9 239.2 277.4 292.3 273.6 259.5 250.6 284.5 299.3 284.1 268.7 256.5 287.8 302.6 289.4 272.5 260.1 ANIMAL NUMBER 628187 628188 628199 628209 628217 DAY 8 306:5 313.4 302.3 285.3 270.7 DAY 9 TEST DAYS DAY 10 311.2 320.9 306.6 291.2 272.5 314.4 328.1 315.3 299.3 283.4 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-2926 -65- C om pany Sanitized. D o ss no! contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628190 628202 628204 628206 628214 230.1 220.2 255.6 236.8 239.6 235.0 223.8 257.2 238.8 243.7 241.3 233.7 267.7 244.6 249.8 249.5 238.7 277.4 254.3 254.2 256.2 250.6 283.8 261.5 262.0 269.3 252.2 293.9 267.4 265.1 273.0 255.3 296.4 269.6 268.1 ANIMAL NUMBER 628190 628202 628204 628206 628214 DAY 8 281:5 280.4 318.2 284.9 275.8 DAY 9 TEST DAYS DAY 10 DAY 13 287.1 283.9 325.6 290.0 276.7 291.3 294.7 330.8 296.5 285.4 314.2 318.6 361.0 320.0 296.9 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD tst day 13 DuPont-2926 -66- DeTnt'contain TSCA CM Company Sanitized. H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628197 628198 628201 628203 628216 229.5 238.3 216.6 234.0 223.9 233.5 239.0 226.1 239.2 224.9 240.7 247.1 233.5 251.0 231.9 249.5 259.0 239.7 263.7 238.1 258.3 266.0 246.5 271.4 245.3 258.5 277.7 250.5 275.6 246.2 260.9 281.1 254.3 278.1 249.6 ANIMAL NUMBER 628197 628198 628201 628203 628216 DAY 8 273 :9 287.8 266.5 297.6 263.6 DAY 9 277.0 298.0 269.2 300.9 267.2 TEST DAYS DAY 10 DAY 13 283.0 302.7 277.5 311.3 271.2 _a _a _a __a _a DAY 20 328.0 352.9 337.0 390.2 323.5 DAY 24 345.6 378.8 362.8 423.4 348.9 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2926 a Rats not weighed. - 67- 'Companx Sanitlzsd, oas not contain TSC CBf H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 628191 628196 628208 628210 628215 DAY 1 222.1 233.7 253.7 238.8 224.3 DAY 2 225.8 239.7 258.5 244.2 234.3 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 233.3 246.0 264.8 254.6 242.5 241.8 260.5 270.8 263.4 249.0 249.6 266.8 279.9 274.5 259.2 253.6 275.0 288.8 280.8 266.7 257.3 276.9 291.5 283.1 269.4 ANIMAL NUMBER 628191 628196 628208 628210 628215 DAY 8 275:0 299.9 300.2 298.8 283.3 DAY 9 283.5 309.9 304.5 306.8 293.4 TEST DAYS DAY 10 DAY 13 291.6 316.6 316.2 314.5 301.1 _a _a __a _a DAY 20 352.6 403.0 394.1 389.4 367.0 DAY 24 __a _a _a _a ^a DAY 27 396.6 451.0 437.6 435.2 404.9 ANIMAL NUMBER 628191 628196 628208 628210 628215 DAY 33 425.3 479.0 462.2 470.0 435.2 DAY 41 457.1 509.5 490.1 501.1 469.6 TEST DAYS DAY 47 DAY 51 482.5 539.6 516.9 523.5 493.2 498.3 565.9 543.3 542.0 514.0 SD test day- 51 SD test day 51 SD test day 51 SD test day 51 SD test day 51 a Rats not weighed. C om pany Sanitized. B o s s not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24002 {TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628194 628200 628213 628218 628219 221.3 222.5 250.9 236.4 228.5 229.5 229.3 259.9 245.1 232.1 236.4 238.4 271.6 256.0 241.0 242.5 243.8 280.0 264.6 248.7 253.2 251.1 289.9 274.9 256.0 262.2 258.5 297.8 280.9 266.7 266.1 260.4 300.2 283.4 268.7 ANIMAL NUMBER 628194 628200 628213 628218 628219 DAY 8 282 .'5 271.3 315.4 303.1 278.0 DAY 9 287.6 281.8 322.8 304.7 285.4 TEST DAYS DAY 10 DAY 13 292.9 289.6 332.0 313.8 295.3 -a -a -a DAY 20 363.1 348.2 401.1 374.7 346.0 DAY 24 _a _a _a __a DAY 27 403.5 385.3 441.5 415.4 388.6 ANIMAL NUMBER 628194 628200 628213 628218 628219 DAY 33 DAY 41 TEST DAYS DAY 47 DAY 51 DAY 54 DAY 60 434.1 416.8 458.6 446.7 420.8 460.6 444.6 478.3 472.1 454.1 487.0 465.1 501.6 506.8 478.9 -a 501.0 469.5 525.5 535.6 501.2 522.8 488.3 539.5 552.1 526.8 a Rats not weighed. - 69- DuPont-2926 10t contain SG A CB< H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 76 DAY 82 H-24002 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 88 DAY 94 628194 628200 628213 628218 628219 556.5 521.9 584.2 586.6 562.4 567.5 534.2 597.3 610.6 581.1 567.8 547.2 605.2 625.4 586.4 578.2 556.4 609.7 633.8 591.2 SD test day- 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-2926 - 70- Company Sanitized. Does not contain TSCA CSi H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 APPENDIX B Individual Clinical Observations -71 Company Sanlilzad. Does not contain TSC CB1 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number____________________ 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 - 72- Company Sanftizei.. not Olilain T6CA CBi H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal GROUP IV Number__________________ 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 - 73- * - Qf-inlti TSC CB! H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number____________________ 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 - 74- Company Sanitized. D oes net contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal GROUP IV 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 GROUP V Animal Number____________________ Observation_______________________ Test Day 627792 627798 627813 627814 627815 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 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 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number.____________________Observation________________________ Test Day 625361 625363 625364 625380 625383 No abnormalities detected No abnormalities detected No abnormalities detected No abnormali ties 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 - 76- Company Sanitized. Does not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 - 77- g j g npany Sanitized. Does not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 TM ' C mP!my S " * * not contain TSCA C8) H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 H O'1! h-4 M 1 Test Day 1-6, 9-76, 77-94 7-8 76 7, 8, 9, 10, 13, 20, 27 7-8 8 8 8 9-10 1-94 1-6, 8-94 7 - 79- Com pany Sanitised. D o e s not contain TSCA CBl. H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-2926 . Animal Number 627756 627767 627771 627773 627777 GROUP I ________________ Observation______________ _________Test Day 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 -80- f t * * * Sanitized. Doe, notcontam ,^ - C B I H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-2926 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 ) Animal Number 627762 627769 627775 627778 627783 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected Wet perineum No abnormalities detected Wet perineum No abnormalities detected 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 1-52 1-52 1, 3-52 2 1, 3-52 2 1-52 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 -81 - no! contain TSCA CBl H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 H-24002 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number 628192 628195 628207 628211 628212 GROUP I Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-5 1-5 1-5 1-5 1-5 Animal Number 628187 628188 628199 628209 628217 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 628190 628202 628204 628206 628214 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 Com pany Sanitized. D oes not contain TSCA CS H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 H-24002 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number 628197 628198 628201 628203 628216 GROUP IV Observation No abnormalities detected No abnormalities detected No abnormalities detected Alopecia right front paw No abnormalities detected No abnormalities detected Test Day 1-24 1-24 1-10 20, 24 1-24 1-24 Animal GROUP V Number______ ______________Observation______ _____________ 628191 628196 628208 628210 628215 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-51 1-51 1-51 1-51 1-51 Animal Number 628194 628200 628213 628218 628219 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 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 APPENDIX C Individual Fluorine Levels - 84- Company Sanitized. Does not contain TSCACBl H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 Terms: Active % Active Mol Wt Active Formulation Dose % F in Active Mol Wt F TERMS AND CALCULATIONS Fluorine containing compound The % of formulation that is made up o f fluorine containing components The molecular weight o f the fluorine containing components (g/mole) The mg o f formulation given per kg o f animal body weight The % fluorine in the fluorine containing components o f the formulation (weight basis) The molecular weight o f fluorine g/mol Compound Calculations: Dose Active (mg/kg) The mg o f fluorine containing compound administered per kg of animal body weight. = (% active/100) x Formulation Dose Dose Active (mmole/kg) The mmole o f 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 o f animal body weight = (% F in active/100) x Dose Active [mg/kg] Dose F (mmol/kg) The mmole o f fluorine administered per kg o f animal body weight = Dose F [mg/kg] / Mol Wt F [mg/mmol] Molar Ratio (Active/F) The moles o f fluorine containing compound per mole o f fluorine = Dose Active [mmol/kg] / Dose F [mmol/kg] Formulation Dose Normalization Factor The formulation dose that would be required to administer the amount o f active needed to achieve the normalized dose = (Normalized dose o f Active [mmol/kg] / Dose Active [mmol/kg]) x Formulation Dose - 85- Company Sanilized. Dobs not contain TSCA CBj H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 TERMS AND CALCULATIONS Individual Animal Measurement: 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 o f the actual active dose. This assumes linearity between administered dose and blood fluorine levels, but is needed because different doses o f active were used in the study. = ( 0.1 [mmol/kg] / Active dose [mmol/kg]) x (ppm F in blood minus background) /molar equivalents o f active in blood The /molar [/mol/L] concentration o f 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]) x molar ratio active/F [mmol active/mmol F] x 1000 /mol/mmol -86- Company Sanitized. D o es not contain TSCA CBf H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2926 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 o f 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 o f the active (Fluorine containing components) in the formulation - Molecular weight is the molecular weight o f the active component in the formulation H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H- 24019 DuPont-2926 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 625323 625336 625343 625349 5 5 5 5 5 51.7 38.0 38.7 78.5 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 /molar 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 -88- Company Sanitized, D oes not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat Number Test ppm F Day in Sample Blood Group III 625321 625327 625342 625345 625348 13 13 13 13 13 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-2926 /molar 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 - 89- Company Sanitized. Does not contain TSCA CBI H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ________________ DuPont-2926 Data for H- 24020 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 limolar Equivalents of Active in Blood 27.69 16.83 34.72 29.61 22.37 94.20 57.25 118.12 100.72 76.09 159.96 141.86 137.60 169.97 152.08 544.20 482.61 468.12 578.26 517.39 119.49 108.20 116.30 92.44 138.24 406.52 368.12 395.65 314.49 470.29 i -90- , n r.t$ TSt: a cb i Company Saniiizea " H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat Number Test ppm F Day in Sample Blood Group III 627758 627764 627787 627763 627788 13 13 13 13 13 43.5 20.7 13.2 30.8 24.9 Group IV 627759 627779 627770 627761 627786 24 24 24 24 24 9.2 14.9 11.6 9.9 6.7 Group V 627757 627781 627760 627765 627772 52 52 52 52 52 0.9 0.6 1.0 0.9 0.8 Group VI 627778 627783 627762 627775 627769 94 94 94 94 94 0.3 <0.2 0.2 0.2 <0.2 ppm F in Blood Minus Bkg 0.2 ppm 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 * * = Below LOD (Level of Detection) ppm F in Blood Normalized to 0.1 mmoles/kg Dose 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 * DuPont-2926 /molar 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 * -91 Company Sanitized. Does not contain TSCA CB1 H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H-24002 DuPont-2926 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 570 75 47 % F in Active: Mol Wt. F (g/mol): 51 19 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 35.25 0.062 121.3 Dose F (mmol/kg): 0.946 Molar Ratio (Active/F): 0.065 Dose F (mg/kg): 17.9775 Rat Number Test Day Sample ppm F in Blood Group I 628207 628195 628212 628211 628192 1 1 1 1 1 2.0 1.6 1.9 2.4 1.5 Group I 628207 628195 628212 628211 628192 5 5 5 5 5 6.1 6.1 6.0 6.5 5.3 Group II 628209 628187 628199 628188 628217 10 10 10 10 10 7.1 8.1 7.4 6.9 7.1 ppm F in Blood Minus Bkg 0.2 ppm 1.8 1.4 1.7 2.2 1.3 5.9 5.9 5.8 6.3 5.1 6.9 7.9 7.2 6.7 6.9 ppm F in Blood Normalized to 0.1 mmoles/kg Dose /molar Equivalents of Active in Blood 2.91 10.01 2.26 7.79 2.75 9.46 3.56 12.24 2.10 7.23 9.54 9.54 9.38 10.19 8.25 32.82 32.82 32.26 35.04 28.37 11.16 12.77 11.64 10.83 11.16 38.38 43.94 40.05 37.27 38.38 - 9 2 - Company SanUtee^. Does not contain 1SGA CBf H-24002: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Rat Number Test Day Sample ppm F in Blood Group III 628202 628190 628206 628214 628204 13 13 13 13 13 3.3 2.8 3.3 3.2 2.9 Group IV 628201 628216 628197 628198 628203 24 24 24 24 24 1.8 1.6 2.0 1.9 1.7 Group V 628208 628191 628215 628196 628210 52 52 52 52 52 0.7 0.4 0.6 0.6 0.5 Group VI 628218 628213 628194 628200 628219 94 94 94 94 94 0.2 0.3 0.3 0.3 0.3 ppm F in Blood Minus Bkg 0.2 ppm 3.1 2.6 3.1 3.0 2.7 1.6 1.4 1.8 1.7 1.5 0.5 0.2 0.4 0.4 0.3 0.0 0.1 0.1 0.1 0.1 ppm F in Blood Normalized to 0.1 mmoles/kg Dose molar Equivalents of Active in Blood 5.01 17.24 4.20 14.46 5.01 17.24 4.85 16.69 4.37 15.02 2.59 8.90 2.26 7.79 2.91 10.01 2.75 9.46 2.43 8.34 0.81 2.78 0.32 1.11 0.65 2.23 0.65 2.23 0.49 1.67 0.00 0.00 0.16 0.56 0.16 0.56 0.16 0.56 0.16 0.56 Company Sanitizad. Does not contain TSCA CBS
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CUNY - The Graduate CenterColumbia University Mailman School of Public Health - Sociomedical Sciences