Document oDp63b0bYjV23r476kG3Emee7

TRADE SECRET Study Title H-24QQ1: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Laboratory Project ID: DuPont-2924 AR226-3156 DuPont-2924 Author: Carol Finlay, B.A. Study Completed on: August 3,2000 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; Page 1 of 81 Company Sanitized. Does not contain TSCA CBl H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 C E R T IF IC A T IO N We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. 2. OOP Date Reviewed by: Issued by Study Director: - M qA I & ; , JudithC. Stadler.Ph.D,, D.A.B.T. Director, General Toxicology tLA bl. t i f i l a * Carol Finlay, B.A. 0 Staff Scientist 3 -& U G - 2 o > Date <? - fl L& . ' l o o t Date* -2Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLE OF CONTENTS Page CERTIFICA TIO N ---------------------------- 2 LIST O F TABLES--------------------------------------------------------------------------------------------- 4 LIST O F FIG U R ES----------------------------- 4 LIST O F A PPEN D ICES------------------------------------------------------------ 4 STUDY INFORM ATION -- STUDY PERSONNEL SUM M ARY............-- ,..7 ,...8 IN T R O D U C T IO N .............................................................................................................................9 MATERIALS AND M ETHODS. I A. Test Substance and Positive Control................. 9 B. Test Species............................................................................................................................9 C. Animal Husbandry............................................................................................................... 1. Housing Environment................................................................................................................................... 1 2. Feed and Water............................................................................................................................................. 3. Identification................................................................................................................................................. 19 4. Animal Health Monitoring Program....................... :................................................................................... D Quarantine and Pretest......................................................................................................... 11 E. Study Design. 11 F. Assignment to Groups and Study Start................................................................................11 G. Dosing M aterial Preparation and Administration...............................................................11 1. Test Substance.............................................................................................................................................. *1 2. Positive Controls........................................................................................................................................... ^ 3. Negative Controls 12 H. Body W eights....... 12 I. M ortality and Clinical Observations.................................................................................... 12 J. Collection and Analysis of Blood and liv e rs ......................................................................12 K. Treatment of Fluoride Data.............................. 12 RESULTS AND DISCUSSION. ' 14 A. In-Life Toxicology...........................................................................................:................... I4 B. Fluorine D ata........................................................................................................................ I 4 1. Factors Influencing Interpretation of Analysis..................................................................................?........14 2. Positive Controls........................................................................................................................................... ^4 3. Test Substance.................... 1^ CONCLUSIONSt ....... ......... .......................... RECORDS AND SAMPLE STORAGE ase888888888*888888*888**8* 15 TABLES...................... ................................................................ . 16 * * t * M t ( M * * M l t * * M M * * t * * * I B * -3 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats FIGU RES_______________________________________________ A P P E N D IC E S __________________________________________________ DuPont-2924 21 26 LIST OF TABLES Page 1. TABLE 1 MEAN BODY WEIGHTS........................................................................................................................17 2. TABLE 2 MEAN BODY WEIGHT GAINS.............. 18 3. TABLE 3 MEAN BLOOD FLUORINE LEVELS.............................................. ....................................................19 4. TABLE 4 MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE................................20 LIST OF FIGURES Page 1. MEAN BODY WEIGHTS......................................................................................................................................... 22 2. MICROMOLAR EQUIVALENTS IN RAT BLOOD..............................................................................................23 3. MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS..............................25 LIST OF APPENDICES A. INDIVIDUAL BODY WEIGHTS.............................................................................................................................27 B. INDIVIDUAL CLINICAL OBSERVATIONS.........................................................................................................61 C. ANALYSIS OF BLOOD FLUORIDE DATA...................... 72 - 4 - Company Sanitized. Does not contain SC CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORM ATION TEST SUBSTANCE: Svnonvms/Codes: wH-24001 *** DuPont-2924 Known Impurities: Unknown POSITIVE CONTROL: Haskell Number: 24019 -5 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Known Impurities: Unknown DoPont-2924 Haskell Number: 24020 Known Impurities: Unknown 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) Tn-Life Initiated/Completed: May 30,1999 / August 30,1999 - 6 - Sanitized. Does not contain t s c a c b s Company H-24001: 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.AM. DuPont-2924 -7 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 SUMMARY The objective of this study was to evaluate the potential for H-24001, when administered by gavage, to be absorbed and to accumulate in a mammalian system. Six groups of 5 male Crl:CD(SD)IGS BR rats each were exposed to 1000 mg/kg/day of H-24001. The test substance was administered to one group of five rats for 5 consecutive days and to 5 groups for 10 days. Approximately two hours after the first dose, blood was collected from the orbital sinus of each rat from the 5-dose group. On selected days (5,10,1 3 ,2 4 ,5 2 , 93/94) 5 rats per group were euthanized and the blood and livers were collected. Body weights and clinical signs were recorded on each day of dosing and then approximately every other week during the recovery period. Additionally, 2 negative controls, com oil and com oil/acetone (80:20), and 2 positive controls, H-24019 (10 mg/kg/day) and H-24020 (20 mg/kg/day), were tested as described for H-24001. No deaths occurred during the study. No compound-related clinical signs of toxicity were observed in the rats dosed with H-24001. Rats dosed with a positive control material, H-24019, exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining of various parts of the body during the dosing period. Rats dosed with H-24020, the other positive control substance, exhibited wet perineum and diarrhea during the dosing period. Alopecia was observed during the recovery period for rats dosed with H-24001, H-24019, and H-24020. The negative control rats exhibited no clinical signs during the study. Comparison of body weights was complicated by a difference in age on test day 1 between the rats dosed with the test substance and those dosed with the positive or negative controls. Accounting for the age difference at study start and the expected rate of body weight gain, the mean body weights and mean body weight gains of the rats dosed with H-24001 were comparable to the negative controls and equal to or greater than the positive controls. A steady-state for fluorine levels in whole blood was not achieved during 10 consecutive days of dosing with 1000 mg/kg H-24001. 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 H-24001 was 1750, compared to AUCINF/D values of 566,479.1 and 70,789.6 for H-24019 and H-24020, respectively. Under the conditions of this study, administration of H-24001 to male rats foi 10 consecutive days resulted in limited 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 320x and 40x the AUCINF/D for the test substance. -8Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 IN T R O D U C T IO N The objective of this study was to define the potential of H-24001 to be absorbed and to bioaccumulate in a mammalian system, as indicated by analytical determination of total fluorine in blood and liver. The test substance was compared to two positive controls that were materials previously shown to bioaccumulate in mammals. The daily dosage for the test substance was selected based on available toxicity data and the results of a rangefinding study. In the rangefinding study, a group of 5 male rats was dosed by oral gavage with H-24001 at a dosage of 2000 mg/kg for 5 consecutive days. A group of 5 male rats was dosed with deionized water for 5 consecutive days and served as controls. The rats dosed with H-24001 experienced an overall mean body weight gain of 13 grams. The control group had an overall mean body weight gain of 27 grams. A dosage of 1000 mg/kg was selected for the limit dosage for this project. The limit dosage of 1000 mg/kg was chosen for the main study and was expected to produce less than a 10% difference in mean body weight over 10 days when compared to controls. All blood samples were analyzed for total fluorine content. This report contains the results of those analyses. Results from analyses of selected liver samples will be presented in a supplemental report. MATERIALS AND M ETHODS A. Test Substance and Positive Control The test substance, H-24001, 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 of the study. No evidence of instability, such as a change in color or physical state, was observed. - B. Test Species ' Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. The Crl:CD(SD)IGS BR rat was selected on the basis of extensive experience with this strain and its suitability with respect to longevity, hardiness, sensitivity, and low incidence of spontaneous diseases. -9 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 C. Animal H usbandry 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%. Occasional excursions outside the accepted ranges were minor and did not affect the study. 2. Feed and W ater Tap water was provided ad libitum. All rats were fed PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 chow. The feed is guaranteed by the manufacturer to meet specified nutritional requirements and to be free of specified contaminants. 3. Identification Prior to assignment to groups, each rat was temporarily identified by cage identification. After assignment to groups, an individual identification number was marked or tattooed on the tail of each rat. The information on the cage labels included the unique 6-digit Haskell animal number assigned to each rat. 4. Animal Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to assure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence 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 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. -10- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 D. Q uarantine and Pretest Upon arrival at Haskell Laboratory, the rats were removed from shipping cartons and quarantined for 6 days. The rats were weighed 3 times during the pretest period and examined daily for any clinically apparent signs of disease or injury. The rats were observed daily for mortality and signs of illness, injury, or abnormal behavior. On the bases of acceptable body weight gains and freedom from clinically apparent signs of disease or injury, the rats were released from quarantine by the laboratory animal veterinarian or designee. E. Study Design Substance Negative Controls Com oil Com oikacetone Positive Controls H-24019 H-24020 Test Substance H-24001 Vehicle Dosage (mg/kg) Number of Animals Not applicable 0 0 30 30 Com oil: acetone Com oil 10 20 30 30 None 1000 30 F. Assignment to G roups and Study S tart 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 A dm inistration 1. Test Substance H-24001 was dosed as received. The amount of test substance each rat received was based on the body weight collected on each day of dosing and the test substance density of 1150 mg/mL. The test substance was stirred on a magnetic stir plate throughout the dosing procedure. -11Company Sanitized, does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 2. Positive Controls The solid positive control materials were suspended as emulsions in their respective vehicles. Com oil was used as the vehicle for H-24020. It was necessary to dissolve H-24019 in acetone before suspending it in com oil. The ratio of acetone to com oil was 20:80. The amount each rat received was based on the body weight collected on each day of dosing and the suspension concentration. The dose volumes did not exceed 1 mL/100 g of body weight. The dosing suspensions were stirred on a magnetic stir plate throughout the dosing procedure to maintain homogeneity. 3. Negative Controls Com oil and com oilracetone (80:20) were chosen as the negative controls because they were the vehicles for the positive controls. Each negative control rat received 1 mL of com oil or com oil:acetone. These rats were dosed in a separate room from the rats dosed with the test substance or positive controls. H. Body W eights The rats were weighed on each day of dosing and then weekly or every other week during the recovery period. I. M ortality and Clinical O bservations Cage-site examinations to detect moribund or dead rats and abnormal behavior and appearance among rats were conducted at least once daily throughout the study. At every weighing, each rat were individually handled and examined for abnormal behavior and appearance. J. Collection and Analysis of Blood and Livers Approximately 2 hours after the first dose, 1-2 mL of blood was collected into EDTA tubes from the orbital sinus of each rat from Group I. At all other selected time points, 5 rats/group were euthanized by carbon dioxide anesthesia and exsanguination and blood and livers were collected according to the following schedules: 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 -12- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 Five to 10 mL of blood was collected into EDTA tubes at sacrifice. The livers were weighed. The blood from all rats was refrigerated, and the livers were frozen. The blood was appropriately packaged and shipped refrigerated to Jackson Laboratory, Deepwater, New Jersey where it was analyzed for total fluorine. The total fluorine content of the blood samples was determined by using a Wickbold torch combustion method, followed by analysis with a fluoride ion selective electrode. The liquid blood was decomposed or volatilized in the presence of wet oxygen and swept through an oxy- hydrogen 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 Hata (ppm F in each sample) was supplied to Haskell Laboratory for evaluation of fluorine biopersistence. . K. Treatm ent of Fluoride D ata Noncompartmental analysis was conducted on blood fluorine data derived from rats dosed with H-24001 by using WinNonlin Version 3.0 software (Pharsight Corp, Mountain View, CA). WinNonlin software provided a means of computing derived pharmacokinetic parameters from data files including area under the curve (AUCINF), Cmax and terminal half-life (Ti/2). The AUCENF (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 bomparative purposes. The accumulation index (AI, l/(l-e `kt)) and bioaccumulation index (BI, Cmax x AT) were calculated and reported but not further use. H-24019 and H-24020 were used as positive controls. Dosing diluents were used as negative controls, but because of variability and limited sensitivity of the analytical method, the background was set at 0.2 ppm fluorine. Since 0.2 ppm was the fluoride concentration limit of detection, any values listed as <0.2 ppm were excluded from further treatment. The percent of fluorine and molecular weight of the test substance and positive controls were used as provided by the sponsor. The measurements resulting from analysis of total blood fluorine were used as received (ppm F) from Jackson Laboratory. Fluoride ion was converted to micromolar (/xM) equivalents of active component for further comparisons. The data and descriptions of data manipulation and presentation are provided in Appendix C. - 13- Ccmpany Sanitized. Does not contain TSCA CBf H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats RESULTS AND DISCUSSION DuPont-2924 A. In-Life Toxicology (Tables 1 and 2; Figure 1, Appendices A and B) No deaths occurred during the study. No compound-related clinical signs of toxicity were observed in the rats dosed with H-24001. Rats dosed with H-24019 exhibited diarrhea, salivation, alopecia, black ocular discharge, and staining of various parts of the body during the dosing period. Rats dosed with H-24020 ^ exhibited wet perineum and diarrhea during the dosing period. Alopecia was observed during the recovery period for rats dosed with H-24001, H-24019, and H-24020. The negative control rats exhibited no clinical signs during the study. Comparison of body weights was complicated by the fact that there was a difference in age on test day 1 between the rats dosed with the test substance and those dosed with the positive or negative controls. This difference resulted in differences in mean body weights on test day 1. The rats dosed with the test substance, H-24001, were older and heavier in weight than the com oil negative control and H-24020 positive control rats, but younger and lighter in weight than the com oil/acetone negative control and H-24019 positive control rats. Accounting for the age difference at study start and the expected rate of body weight gain, the mean body weights and mean body weight gains of the rats dosed with H-24001 was comparable to the negative controls and equal to or greater than the positive controls. B. Fluorine D ata (Tables 3 and 4; Figures 2 and 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. - 2. Positive Controls The positive controls were H-24019 and H-24020. The H-24019 normalized fiM 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 jlM. 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 - 14- Sanitized. Does not contain TSCACB! Company H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 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 for H-24019 and 70,789.6 for H-24020. 3. Test Substance The H-24001 normalized iM equivalents in rat blood continued to rise throughout the dosing period and did not reach steady-state (Figure 2C). The Cmax for H-24001 was 9.188 1.917 ppm (Mean SD) with a terminal half-life of 46.9 days. Blood was sampled at seven time points throughout the study, with only four of those 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-24001 AI was 68.1 and the BI was 625.4. The total internal exposure resulting from a normalized dose was described by AUCINF/D and was the basis for comparison between H-24001 and positive controls. The AUCINF/D for the fluorine component of H-24001 was 1750 as compared to AUCINF/D values of 566,479.1 and 70,789.6 for H-24019 and H-24020, respectively. The data, calculations and equations are shown m Appendix C. CONCLUSIONS Rats dosed for 10 consecutive days with 1000 mg/kg H-24001 exhibited no mortality or clinical signs of toxicity and had mean body weight gains that were comparable to the negative control rats. A steady state for fluorine in the blood was not achieved for H-24001 during the 10-day dosing period. Under the conditions of this study, administration of H-24001 to male rats for 10 consecutive days resulted in limited 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 ` 320x and 40x the AUCINF/D for the test substance.RECORDS AND SAM PLE 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 Sanitised. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLES - 16- Comparty Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLE 1 MEAN BODY WEIGHTS (g) Test Days 1 2 3 4 5 6 7 8 9 10 13 20 24 27 34 41 47 48 ' 52 55 61 62 68 69 75 76 80 81 89 90 93 94 Negative Controls Positive Controls Com Oil 229.8 234.1 241.4 250.4 259.3 266.8 271.2 281.9 285.2 295.9 321.1 350.5 378.3 _ 407.8 434.5 454.9 _ 464.7 487.0 505.1 515.4 Com Oil:Acetone 297.6 299.6 309.4 314.3 321.5 326.0 334.9 339.2 345.2 351.7 350.7 369.8 401.0 411.4 - - - 527.6 - - - _ 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 _ _. - - 539.0 - 563.4 570.7 - - - - 499.2 _ 556.2 566.9 - 562.2 - 567.8 - . 585.3 - 597.9 - 527.8 - 538.7 a The rats were sacrificed a day early because of a laboratory event on test day 94. - Indicates that the animal was not weighed. Test Substance H-24001 245.3 251.4 260.4 267.9 277.6 286.3 291.1 298.6 305.5 309.4 321.3 .388.5 - 416.8 " 466.4 483.2 - - 506.8 " 517.6 533.2 - - 543.5 - 570.5a - - 17- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLE2 MEAN BODY WEIGHT GAINS (g) Test Days 1-5 1-10 10-13 10-24 10-52 10-93/94 Negative Controls Com Oil 29.5 66.1 25.2 82.4 168.8 271.0 Com Oil:Acetone 23.9 54.1 - 1.0 49.3 175.9 216.1 Positive Controls H-24019 17.1 27.4 10.2 69.0 119.2 279.0 H-24020 24.9 56.4 5.2 57.0 181.7 254.8 Test Substance H-24001 32.3 64.1 11.9 79.1 173.8 261.1 - 18- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLE3 MEAN BLOOD FLUORINE LEVELS Test Days 1 5 10 13 24 52 93/94 Negative Controls C om O il ppm <0.2 <0.2 <0.2 0.2a (0.1) <0.2 0.3a (0.1) 0.3a (0.1) Com Oil:Acetone ppm <0.2 <0.2 0.3a (0.1)b 0.6C(0.6) 0.2d <0.2 <0.2 Positive Controls Test Substance H-24019 ppm 2.1 (0.9) 48.8 (17.6) 61.7 (2.8) 64.5 (7.6) 42.2 (2.8) 26.9 (2.6) 13.2 (2.1) H-24020 PPm____ 62.6 (3.2) 71.7 (6.2) 54.2 (7.8) 26.6 (11.4) 10.5 (3.0) 0.9 (0.2) 0.2C (0.1) H-24001 ppm 4.1 (0.7) 13.4e (1.5) 19.5 (4.0) 6.3 (1.0) 2.6 (0.2) 1.8 (0.2) 1.1 (0.2) a Mean of 4 of the 5 values. One of the values was below the LOD. b Standard deviation is in parentheses. c Mean of 3 of the 5 values. Two of die values were below the LOD. d One value. Four of the values were below the LOD. e Mean of 4 of 5 values. Tube of blood for one rat was missing or broken. -19Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 TABLE4 MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE Test Days 1 5 10 13 24 52 93/94 Positive Controls H-24019 jxM F Equivalents 28.92 (13.3)a 747.69 (271.5) 945.85 (43.5) 989.85 (116.9) 645.54 (42.9) 41138 (40.6) 195.38 (32.5) H-24020 fiM F Equivalents 89.28 (23.4) 518.12(44.9) 391.01 (56.8) 191.45 (82.7) 74.35 (22.1) 4.64 (1.1) 0.24 (0.4) a Standard deviation is in parentheses, b Mean o f 4 of the 5 values. No data for one rat. Test Substance H-24001 fiM F Equivalents 1.85 (0.3) 6.28b (0.7) 9.19 (1.9) 2.88 (0.5) 1.16 (0.1) 0.74 (0.1) 0.41 (0.1) -20- Company Sanitized. Does not contain TSCA CBl H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 FIGURES -21Company Sanitized. Does not contain TSC CBS H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 Mean Body Weight (g) 400 n FIGURE 1 MEAN BODY WEIGHTS (g) 350 - 300 - 250 - 200 - 150 - 100 - 50 - 0 -I--------------------r---------------------- 1---------------------- 1----------------------I--------------------- 1 0 2 4 6 8 10 Test Days -- --N egative Control (Corn O il) --a --N egative Control (Corn O il:A cetone) --A --P ositive Control H -24019 --X--P ositive Control H-24Q20 --SK--Test Substance H -24001 ____ 1 12 O -P -m r Sanite,d- no. conte,,, tsca CB, H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD A. Norm alized Rat Blood H-24019 jiM Equivalents Resulting from a 10-Day Oral Gavage Micromolar (/xM) 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. Normalized Rat Blood H-24020 pM Equivalents Resulting from a 10-Day O ral Gavage Micromolar (fiM) 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 3 - Company Sanitized. Does not contain TSC CBi H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 C. Normalized Rat Blood H-24001 pM Equivalents Resulting from a 10-Day Oral Gavage Micromolar (/M) equivalents of H-24001 (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 CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 FIGURE 3 MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS 33i a h d a n t r bi Norrfi_aIied B lo o d A U C IN F /D in R a ts R e su ltin g issia lsiiH mmm from 10-day Orai Gavage -25Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 APPENDICES - 2 6 - not contain TSCACB1 Cotnpany Sanitized.Does H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 APPENDIX A Individual Body W eights -27- Company Sanitizedf. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES ABBREVIATIONS: SD - sacrificed by design DuPont-2924 -28- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 627789 627801 627805 627810 627818 222.6 215.9 249.4 230.5 229.7 220.7 209.1 250.1 231.6 228.6 223.5 223.5 263.3 241.9 239.1 236.9 233.5 273.6 254.4 252.4 247.7 240.1 283.7 265.0 260.2 SD t e s t da y 5 SD t e s t d a y 5 SD t e s t , d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2924 -29Company Sanitized. Does not contain TSCA CBI H-2401: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627793 627797 627799 627800 627808 214.8 239.9 228.9 246.9 235.6 224.4 245.9 231.4 .252.8 241.6 232.1 257.3 242.3 265.2 250.1 243.1 267.5 246.2 279.3 262.1 249.9 280.7 258.9 283.6 270.4 257.0 288.0 261.5 295.5 284.1 262.0 290.9 266.4 300.1 287.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627793 627797 627799 627800 627808 270.6 303.9 280'. 2 312.0 303.6 274.9 305.1 284.3 315.4 305.7 283.5 324.2 294.7 331.3 321.8 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d a y 10 SD t e s t da y 10 SD t e s t da y 10 DuPont-2924 -30- fcHapany Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats _______________________________ CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS ANIMAL NUMBER DAY 1 DAY 2 GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627796 627806 627807 627809 627816 239.8 227.3 221.5 234.2 235.0 249.7 234.2 225.9 240.4 238.6 253.6 239.4 237.1 252.5 250.0 252.5 242.9 244.1 260.3 258.9 267.7 258.5 254.9 272.8 265.1 277.2 270.4 257.7 277.9 274.5 289.8 275.2 260.3 282.6 278.6 ANIMAL NUMBER 627796 627806 627807 627809 627816 DAY 8 285.9 282-. 8 270.7 297.9 291.8 DAY 9 290.1 285.8 274.7 300.2 296.4 TEST DAYS DAY 10 DAY 13 300.0 302.8 280.7 311.9 305.7 322.7 320.3 305.2 336.2 330.2 SD t e s t da y 13 SD t e s t d ay 13 SD t e s t d a y 13 SD t e s t da y 13 SD t e s t d a y 13 DuPont-2924 -31 - Company Sanitized. Does not contain TSCA CBI H -24001: B iopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 627791 627794 627804 627812 627817 ANIMAL NUMBER 627791 627794 627804 627812 627817 DAY 1 231.1 224.4 224.7 221.9 233.5 DAY 2 235.4 233.0 228.8 231.5 231.3 DAY 8 274.0 286.1 267.2 278.2 277.8 DAY 9 279.1 289.5 270.6 282.7 280.4 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 241.2 238.1 230.6 236.3 229.0 246.8 247.8 243.0 245.7 244.8 255.9 260.0 251.7 255.5 255.4 262.6 267.4 252.9 264.9 266.4 268.4 270.1 259.5 269.5 270.0 TEST DAYS DAY 10 DAY 13 285.0 295.4 278.1 294.3 294.6 __a __a _a _a _a DAY 20 334.4 377.4 345.8 356.5 368.7 DAY 24 365.6 416.7 378.1 388.4 407.3 SD t e s t d ay 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d ay 24 SD t e s t d ay 24 DuPont-2924 a Rat was not weighed. -32C raP" V * " D noi contato TSCA CBI H-24001: 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 t e s t day- 52 SD t e s t d ay 52 SD t e s t d ay 52 SD t e s t d ay 52 SD t e s t d ay 52 DuPont-2924 a Rat was not weighed. Company Sanitized. Does not contain TSCA CBI H-24001: 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 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-2924 a Rat was not weighed. -34- Company Sanitized. Does not contain TSCA CBI H-24001: 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 t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 DuPont-2924 -35- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 625361 625363 625364 625380 625383 322.6 273.7 291.1 289.4 304.7 325.0 271.4 .290.9 286.2 299.7 337.6 278.4 299.9 291.5 302.7 340.3 281.7 306.0 300.1 310.7 349.7 286.7 312.0 305.5 313.1 SD t e s t d a y 5 SD t e s t d ay 5 SD t e s t , d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2924 Sanl,iMd- " no. c o m TM ISO A CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625355 625362 625367 625368 625378 280.0 290.3 301.5 312.3 309.6 282.0 294.1 307.8 318.0 306.4 293.0 303.5 315.6 326.0 327.3 297.9 308.9 320.1 336.4 328.4 306.1 313.8 327.7 343.7 333.7 311.2 315.8 333.7 347.5 336.6 315.7 323.8 345.6 360.8 346.9 ANIMAL NUMBER ' DAY 8 DAY 9 TEST DAYS DAY 10 625355 625362 625367 625368 625378 321.7 323.. 9 349.1 364.2 350.1 320.9 332.3 352.4 380.8 354.2 333.6 332.9 363.8 386.7 365.4 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 DuPont-2924 -37- Company Sanm28d. Does not coM ainTSCACB! H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE C o n tr o l) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625357 625358 625370 625384 625385 311.9 285.7 307.9 294.2 297.6 308.8 286.3 316.7 300.0 304.6 320.3 295.5 329.5 312.0 313.0 328.4 296.4 337.9 309.3 320.4 340.5 306.0 346.9 316.3 331.9 343.3 302.7 349.8 314.1 334.0 361.1 309.2 364.1 321.4 345.4 ANIMAL NUMBER 625357 625358 625370 625384 625385 DAY 8 364.2 319.. 8 373.4 325.6 347.0 'DAY 9 370.3 321.6 374.7 331.0 349.5 TEST DAYS DAY 10 DAY 13 376.9 320.3 385.6 340.6 358.9 405.6 340.7 407.0 357.1 . 377.6 SD t e s t d a y 13 SD t e s t d ay 13 SD t e s t d ay 13 SD t e s t d a y 13 SD t e s t da y 13 DuPont-2924 Company Sanitized. Does not contain TSCA CBI H-24001: 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 t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 DuPont-2924 -39- Company Sanitized. Does noi contain TSCA CBI H-24001: 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 DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 27 625356 625359 625360 625372 625374 328.8 339.1 347.9 344.7 338.0 334.7 ,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 __a _a _a 431.3 440.9 465.9 432.1 447.2 ANIMAL NUMBER 625356 625359 625360 625372 625374 DAY 34 466.2 467.7 484.1 454.7 466.8 DAY 52 TEST' DAYS 533.7 530.3 555.4 506.2 512.3 SD t e s t day- 52 SD t e s t d ay 52 SD t e s t day 52 SD t e s t d ay 52 SD t e s t d ay 52 DuPont-2924 a Rat was not weighed. -40- Cotnpany Sanitized. Does not contain TSCA CBI H-24001: 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 2,79.9 301.3 291.0 294.8 316.8 289.7 312.7 298.0 302.9 325.0 286.9 317.0 307.0 312.0 331.7 292.8 325.4 309.6 318.0 330.1 295.3 329.0 314.2 317.4 342.5 303.8 334.6 323.5 325.0 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 8 344.7 307-. 3 340.6 324.7 325.0 DAY 9 352.7 311.9 348.2 336.0 333.7 TEST DAYS DAY 10 DAY 13 358.1 317.2 352.6 336.9 340.7 371.7 331.1 371.5 350.1 353.5 DAY 20 399.1 347.6 402.3 387.9 376.3 DAY 24 ___a _a --a DAY 27 427.7 374.9 444.6 432.3. 405.2 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 34 453.3 388.2 477.1 455.6 419.1 DAY 52 --a __a __a __a __a TEST DAYS DAY 76 DAY 90 DAY 94 544.9 483.8 628.8 567.3 470.3 562.8 505.3 661.3 589.8 492.0 565.3 514.8 673.7 588.8 496.6 SD t e s t d ay 94 SD t e s t d a y 94 SD t e s t d ay 94 SD t e s t d a y 94 SD t e s t d a y 94 DuPont-2924 a Rat was not weighed. -41- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 01 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 625322 625323 625336 625343 625349 290.3 285.0 316.5 288.2 303.6 283.7 285.5 313.5 281.9 295.9 291.5 290.2 320.1 286.8 308.2 298.9 290.9 327.1 291.0 310.1 298.0 294.0 329.0 293.7 318.1 SD t e s t d a y 5 SD t e s t d a y 5 SD t e s t , d a y 5 SD t e s t d ay 5 SD t e s t d a y 5 DuPont-2924 -42- Does not contain TSCACBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 0 1 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g ) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625320 625330 625332 625341 625350 279.3 286.7 300.0 304.9 257.1 283.0 286.1 295.9 309.0 268.5 287.7 291.1 304.1 317.5 267.3 288.4 296.5 308.8 320.0 272.2 295.9 304.0 315.0 325.1 272.6 299.4 302.3 322.4 327.5 276.3 300.6 306.7 320.7 327.4 283.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 625320 625330 625332 625341 625350 308.5 314- 0 324.1 332.4 279.8 306.3 312.6 321.8 320.3 282.5 312.1 310.1 318.3 325.6 284.3 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 DuPont-2924 -43- Company Sanitized. Does not contain TSCACBI H -24001: B iopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-2 4 01 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625321 625327 625342 625345 625348 307.0 311.4 273.7 291.2 265.5 307.8 306.6 275.5 291.7 258.6 311.4 312.5 282.3 297.3 268.0 319.6 317.8 285.8 303.3 275.2 322.. 3 318.3 290.8 306.4 280.1 328.4 319.3 294.2 310.4 285.2 335.2 327.6 326.6 316.1 290.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 625321 625327 625342 625345 625348 337.8 334.3 304.3 317.3 302.7 339.6 337.0 305.9 312.9 306.5 346.1 336.3 307.8 315.0 309.7 371.2 355.3 324.4 336.9 336.4 SD t e s t d ay 13 SD t e s t d ay 13 SD t e s t d ay 13 SD t e s t d ay 13 SD t e s t d ay 13 DuPont-2924 -44- Company Sanitized. Does not contain TSCA CBi H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 01 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625325 625328 625338 625340 625352 282.8 315.6 264.6 304.0 285.5 285.9 315.2 261.9 309.2 283.9 291.7 323.9 268.5 316.9 289.1 295.5 327.7 272.6 326.0 299.6 303.2 335.0 275.7 329.8 307.9 309.2 340.4 281.9 334.1 308.2 308.3 340.1 284.4 338.4 312.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 625325 625328 625338 625340 625352 318.6 352.0 287.4 347.0 316.9 321.9 '351.7 291.3 352.2 322.3 327.4 357.5 290.2 359.2 321.0 331.6 367.4 291.1 368.1 329.6 355.8 400.2 320.4 389.3 355.7 381.3 423.9 339.9 419.0 375.3 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 SD t e s t d a y 24 DuPont-2924 -45- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-2 4 01 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625324 625329 625333 625334 625344 303.0 318.9 292.4 274.6 262.9 298.5 316.3 .291.2 277.0 262.2 305.8 326.5 297.8 286.4 269.0 312.1 335.4 304.1 290.6 273.5 320.1 338.3 307.7 292.0 274.5 322.8 346.7 312.0 300.1 284.1 326.8 351.6 313.5 304.2 -- ANIMAL NUMBER 625324 625329 625333 625334 625344 DAY 8 332.,5 352.,5 315..8 292,.6 280 .7 DAY 9 337.9 360.1 316.7 302.2 285.2 TEST DAYS DAY 10 DAY 13 336.1 357.0 319.3 305.8 289.3 299.6 364.3 325.8 312.0 295.8 DAY 20 336.0 396.4 349.2 338.6 309.7 DAY 24 _a __a __a _a DAY 27 380.3 423.3 375.2 368.8 330.4 ANIMAL NUMBER DAY 34 DAY 52 TEST DAYS 625324 625329 625333 625334 625344 397.3 442.7 384.6 384.2 348.3 447.4 498.1 427.4 426.5 391.0 SD t e s t day- 52 SD t e s t d a y 52 SD t e s t d ay 52 SD t e s t d ay 52 SD t e s t d ay 52 DuPont-2924 a Rat was not weighed. Company Sanitized. Coos not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-2 4 01 9 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DuPont-2924 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 ANIMAL NUMBER 311.5 294.2 292.9 330.5 351.1 DAY 34 308.9 285.3 290.8 330.1 357.8 DAY 52 297.5 274.0 288.4 333.0 350.5 274.2 266.3 296.9 355.7 380.0 TEST DAYS DAY 62 DAY 76 335.4 340.1 352.5 402.1 413.7 DAY 80 _a __a __a _a DAY 90 390.7 393.8 388.2 436.2 452.4 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 t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 SD t e s t d a y 94 a Rat was not weighed. -47- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 02 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I DAY 3 DAY 4 DAY 5 627756 627767 627771 627773 627777 227.2 227.0 219.5 246.8 225.4 226.4 231.8 214.7 244.4 221.4 233.4 237.9 226.1 252.7 232.9 238.6 245.8 233.5 263.8 239.4 237.5 248.6 239.6 262.3 236.0 SD t e s t d a y 5 SD t e s t d ay 5 SD t e s t , d a y 5 SD t e s t d a y 5 SD t e s t d a y 5 DuPont-2924 -48- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 *DAY 2 H - 24 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627768 627774 627776 627782 627785 236.9 258.6 212.0 221.6 220.3 244.1 261.6 216.3 228.3 221.7 245.2 275.8 223.7 237.3 234.7 256.5 283.4 226.6 239.0 238.4 256.2 289.3 229.6 238.8 241.8 265.5 301.5 233.7 244.7 250.5 271.4 303.2 236.9 246.7 255.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627768 627774 627776 627782 627785 272.3 319.. 8 246.1 251.0 260.7 291.9 326.3 252.3 264.0 268.5 293.5 338.2 254.4 268.2 267.9 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 SD t e s t d ay 10 DuPont-2924 - 4 9 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening . 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 0 2 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I I TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627758 627763 627764 627787 627788 235.1 212.1 230.0 235.1 219.4 240.3 218.3 235.0 241.0 222.3 248.6 226.5 246.1 250.1 232.2 255.8 234.3 251.3 257.2 239.6 261.2 230.8 254.8 258.6 247.6 272.0 235.5 261.7 237.6 256.7 276.1 238.0 264.7 240.3 257.9 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 t e s t d ay 13 SD t e s t d ay 13 SD t e s t day 13 SD t e s t d ay 13 SD t e s t d ay 13 DuPont-2924 -50- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 02 0 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627759 627761 627770 627779 627786 226.6 240.7 235.6 231.5 211.6 232.9 247.4 ,244.3 237.9 218.2 241.4 257.1 253.6 252.6 222.5 250.9 262.5 260.1 261.4 230.4 254.2 266.7 267.7 262.3 230.6 262.1 259.2 277.3 273.8 240.6 265.4 262.6 279.8 277.5 244.1 ANIMAL NUMBER 627759 627761 627770 627779 627786 DAY 8 277.8 24Q.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 t e s t d ay 24 SD t e s t d ay 24 SD t e s t d ay 24 SD t e s t d ay 24 SD t e s t d ay 24 DuPont-2924 a Rat was not weighed. -51 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H - 24 0 2 0 (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 ANIMAL NUMBER 269.1 262.6 271.5 300.9 258.1 DAY 41 276.7 280.3 282.4 307.5 266.8 * DAY 47 279.7 287.3 288.1 317.0 271.2 -a -a -a TEST DAYS DAY 52 324.3 348.6 349.8 375.5 315.1 343.0 379,9 382.7 404.0 338.8 372.3 419.4 400.9 446.9 372.0 627757 627760 627765 627772 627781 402.8 437.7 422.9 478.4 389.9 419.7 448.9 444.8 494.3 408.2 436.7 456.5 455.6 513.5 421.0 SD t e s t d a y 52 SD t e s t d ay 52 SD t e s t day 52 S D ' t e s t day 52 SD t e s t d ay 52 DuPont-2924 a Rat was not weighed. Company Sanitized. Does not contain TSCA CBI H-24001: 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 ANIMAL NUMBER 227.2 231.1 224.7 213.1 216.4 DAY 8 235.0 241.1 235.7 217.4 218.2 1 DAY 9 248.7 255.9 246.8 221.3 226.6 257.3 264.2 254.7 225.5 232.0 TEST DAYS DAY 10 DAY 13 263.0 272.3 265.7 230.1 238.0 DAY 20 275.1 286.3 276.7 236.9 243.9 DAY 24 279.7 289.9 280.2 240.4 247.6 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 -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-2924 a Rat was not weighed. -53- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 81 DlAY 90 H - 24 02 0 (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 t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 SD t e s t d ay 94 DuPont-2924 -54- Oompany Sanitized. Does not contain TSCA CBI H -24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626904 626905 626915 626923 626930 DAY 1 265.0 232.8 249.6 255.6 234.7 DAY 2 265.1 241.6 249.4 261.0 239.3 H - 2 40 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I DAY 3 DAY 4 ' DAY 5 279.7 249.0 260.5 265.6 245.9 286.5 258.5 265.6 273.5 252.8 300.9 274.2 275.4 280.5 258.8 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 DuPont-2924 -55- Company Sanitized. Does not contain TSCA CBi H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626900 626909 626912 626919 626921 DAY 1 251.0 231.0 245.6 242.9 260.1 DAY 2 259.5 234.8 255.7 248.5 271.0 H - 2 40 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 270.3 244.5 262.4 260.9 284.5 276.1 252.1 274.6 267.2 292.6 288.6 262.2 281.3 278.7 303.4 294.3 270.9 293.7 288.7 307.8 302.0 278.1 298.1 291.8 316.8 ANIMAL NUMBER 626900 626909 626912 626919 626921 DAY 8 312.1 287.5 309.5 298.2 323.2 DAY 9 DAY 10 320.0 295.2 316.1 306.2 329.4 331.0 298.2 322.2 307.6 335.5 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-2924 Company Sanitized. Does not contain TSCA CBi H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626901 626907 626910 626913 626914 DAY 1 235.1 248.7 257.0 225.7 240.0 DAY 2 239.7 254.0 260.3 229.5 246.2 H - 2 40 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I I I DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 254.3 268.0 267.3 235.2 257.1 254.8 272.2 279.4 241.9 266.6 264.9 289.3 288.8 250.9 280.7 268.4 300.6 293.8 255.1 288.2 274.5 299.0 297.4 258.4 295.0 ANIMAL NUMBER 626901 626907 626910 626913 626914 DAY 8 280.5 313.1 305.8266.5 305.9 DAY 9 DAY 10 DAY 13 DAY 24 DAY 34 DAY 48 292.4 320.1 310.2 269.7 314.4 294.3 321.4 318.3 272.8 319.4 301.9 345.5 334.4 282.7 342.1 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 DuPont-2924 -57- Cooepaqr Saoitzat. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626897 626903 626916 626925 626926 DAY 1 234.4 249.3 245.1 230.2 262.7 DAY 2 238.9 253.4 256.4 239.0 265.6 H - 24 0 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 247.4 261.7 259.5 249.9 279.3 254.9 273.6 272.1 258.0 281.0 261.7 286.9 282.2 268.8 292.8 271.7 296.3 289.1 275.3 299.5 283.0 305.8 294.5 282.8 301.5 ANIMAL NUMBER 626897 626903 626916 626925 626926 DAY 8 283.4 312.4 298.7294.5 305.8 DAY 9 DAY 10 DAY 13 DAY 24 DAY 34 DAY 48 295.4 318.8 303.5 296.2 311.6 303.0 321.3 310.5 303.8 319.4 -a a __a 379.3 404.0 382.7 390.7 385.7 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2924 a Rat was not weighed. -58- Ccmpany Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626898 626902 626908 626918 626922 DAY 1 251.4 268.6 250.7 232.6 227.3 DAY 2 261.5 276.7 256.9 235.8 234.1 H - 24 0 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 266.3 286.4 266.2 243.4 240.4 274.8 290.9 276.1 249.1 249.0 283.7 301.5 285.7 252.8 253.3 294.6 307.3 294.3 263.9 261.5 296.4 310.0 298.9 261.4 265.5 ANIMAL NUMBER 626898 626902 626908 626918 626922 DAY 8 300.3 316.8 308.7265.6 271.9 DAY 9 307.7 322.1 312.6 279.8 283.2 D A Y 10 310.2 322.4 319.0 276.3 279.4 D A Y 13 __a a _a __a DAY 24 _a a _a _a a DAY 34 406.6 436.3 452.4 369.6 381.9 DA Y 48 450.2 486.3 503.5 418.5 422.4 ANIMAL NUMBER 626898 626902 626908 626918 626922 DAY 52 DAY 62 DAY 69 DAY 75 DAY 83 DAY 89 DAY 93 467.6 500.1 523.4 433.2 433.6 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 DuPont-2924 a Rat was not weighed. - 5 9 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 626906 626911 626920 626924 626927 DAY 1 260.8 229.5 239.0 244.4 257.1 DAY 2 262.7 238.1 246.9 255.0 265.9 H - 24 0 0 1 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 274.7 246.2 250.9 260.8 274.5 282.9 248.5 260.5 271.6 280.3 290.4 257.9 267.4 280.6 283.5 305.6 271.7 280.3 289.5 295.2 311.8 271.4 282.5 296.8 303.3 ANIMAL NUMBER 626906 626911 626920 626924 626927 DAY 8 313.9 280.6 292.9303.4 313.1 DAY 9 323.5 286.3 298.4 310.8 312.7 DAY 10 326.6 286.6 295.4 322.6 318.4 DAY 13 a _a __a _a DAY 24 _a __a _a _a --a DAY 34 484.4 381.7 397.8 433.9 422.9 DAY 48 550.4 429.9 448.8 478.6 475.5 ANIMAL NUMBER 626906 626911 626920 626924 626927 DAY 52 DAY 62 DAY 69 DAY 75 DAY 83 DAY 89 DAY 93 572.8 439.6 467.9 494.7 499.2 597.0 446.3 471.0 503.8 516.1 613.8 455.2 484.7 516.8 - 627.4 475.8 493.1 527.5 542.4 645.0 479.0 501.8 531.4 560.1 659.1 500.1 521.5 540.6 578.9 674.6 506.9 527.1 549.5 594.5 SD test day 93 SD test day 93 SD test day 93 SD test day 93 SD test day 93 DuPont-2924 a Rat was not weighed. Company Sa,,ltfeei Does no( tsca H -24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 APPENDIX B Individual Clinical O bservations Company Sanitized. Does not contain TSCA CBt H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number 627789 627801 627805 627810 627818 GROUP I ________ O b s e r v a tio n _______ _____________________ T e s t Day No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-5 1-5 1-5 1-5 1-5 A n im al Number 627793 627797 627799 627800 627808 GROUP I I O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day . 1-10 1-10 1-10 1-10 1-10 A n im al Number 627796 627806 627807 627809 627816 GROUP I I I O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d T e st Day 1-13 1-13 1-13 1-13 1-13 -62 Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening DuPont-2924 Anim al Number 627791 627794 627804 627812 627817 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-24 1-24 1-24 1-24 1-24 Anim al Number 627792 627798 627813 627814 627815 GROUP V O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-52 1-52 1-52 1-52 1-52 A n im al Number 627795 627811 627819 627820 627821 GROUP VI O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d T e st Day 1-94 1-94 1-94 1-94 1-94 - 63Company Sanitized. Does not contain TSCACBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number. 625361 625363 625364 625380 625383 GROUP I _____________ O b s e r v a tio n ___________________________ T e s t Day No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-5 1-5 1-5 1-5 1-5 Anim al Number 625355 625362 625367 625368 625378 GROUP I I O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-10 1-10 1-10 1-10 1-10 Anim al Number 625357 625358 625370 625384 625385 GROUP I I I O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-13 1-13 1-13 1-13 1-13 - 64- Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats D uP on t-2924 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A n im al Number 625354 625365 625371 625376 625381 GROUP IV O b s e r v a tio n ____________________________ T e s t Day No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d 1-24 1-24 1-24 1-24 1-24 A nim al Number 625356 625359 625360 625372 625374 GROUP V ______O b s e r v a tio n ____________________________ T e s t Day No a b n o r m a lit ie s d e t e c t e d NO a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-52 1-52 1-52 1-52 1-52 A nim al Number 625353 625369 625373 625375 625377 GROUP VI ______ O b s e r v a tio n No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-94 1-94 1-94 1-94 1-94 Company Sanitized. Does not contain TSC CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 H -24019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A nim al Number. 625322 625323 625336 625343 625349 GROUP I Observation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1-5 1-5 1-5 1-5 1-5 A nim al Number 625320 625330 625332 625341 625350 GROUP I I O bservation ____________ ___________ T e s t Day No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d D iarrhea No a b n o r m a lit ie s d e t e c t e d 1-10 1-10 1-10 1 -4 , 6-10 5 1-10 A nim al Number 625321 625327 625342 625345 625348 GROUP I I I O bservation No a b n o r m a lit ie s d e t e c t e d D iarrhea No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T e st Day 1 -4 , 6-13 5 1-13 1-13 1-13 1-13 -66Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening D u P on t-2924 A nim al Number 625325 625328 625338 625340 625352 H -2 4019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV O bservation No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d S alivation No a b n o r m a litie s d e te c te d No a b n o r m a litie s d e t e c t e d T e st Day 1-24 1-24 1 -6 , 8-24 7 1-24 1-24 A n im al Number 625324 625329 625333 625334 625344 GROUP V O bservation No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d S alivation No a b n o r m a lit ie s d e t e c t e d S alivation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-52 1-6, 8-52 7 1 -6 , 8-52 7 1-52 1-52 A nim al Number 625326 625335 625346 625347 625351 GROUP VI O bservation No a b n o r m a litie s d e t e c t e d S alivation A lop ecia both fron t le g s A lo p e c ia abdomen No a b n o r m a lit ie s d e t e c t e d S alivation B lack ocu lar d isch arge Y e llo w -sta in e d perineum R ed-stained chin B row n-stained chin No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d S alivation T est 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 - 6 7 - Company Sanitized. Does not contain TSCA CBJ H -24001: Biopersistence Screening 10-D ose Oral Gavage Study in Rats D u P on t-2924 H -2 4 020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number 627756 627767 627771 627773 627777 GROUP I O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-5 1-5 1-5 1-5 1-5 Number 627768 627774 627776 627782 627785 GROUP I I _______________ Observation ______________________ Test:. No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d 1-10 1-10 1-10 1-10 1-10 A n im al Number 627758 627763 627764 627787 627788 GROUP I I I O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a litie s d e t e c t e d Wet perin eu m No a b n o r m a l i t i e s d e t e c t e d D iarrhea T est Day 1-13 1-13 1-13 1-5, 7- 6 1 -8 , 10- 9 - 6 8 - Company Sanitized. Does not contain TSCA CB! H -24001: Biopersistence Screening 10-D ose Oral Gavage Study in Rats D u P on t-2924 H -2 4020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number 627759 627761 627770 627779 627786 GROUP IV O bservation No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a litie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-24 1-24 1-24 1-24 1-24 A n im al Number 627757 627760 627765 627772 627781 GROUP V O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d Wet perineum No a b n o r m a l i t i e s d e t e c t e d Wet perineum No a b n o r m a lit ie s d e t e c t e d T est Day 1-52 1-52 1, 3-52 2 1, 3-52 2 1-52 A nim al Number 627762 627769 627775 627778 627783 GROUP VI O bservation No a b n o r m a lit ie s d e t e c t e d D iarrhea No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d A lo p ecia perineum No a b n o r m a lit ie s d e t e c t e d A lop ecia both fro n t paws A lop ecia r ig h t fro n t le g T est Day 1-8, 10-94 9 1-94 1-94 81, 90, 94 1 -2 3 , 94 24, 34, 41, 47, 55, 61, 74, 81, 90 - 6 9 - Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats D u P on t-2924 H -24001 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS A n im al Number GROUP I O b s e r v a tio n ____________________________ T e s t Day 626904 626905 626915 626923 626930 No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-5 1-5 1-5 1-5 1-5 A nim al Number 626900 626909 626912 626919 626921 GROUP I I O b s e r v a t i o n __________________ T e s t Day No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-10 1-10 1-10 1-10 1-10 A nim al Number 626901 626907 626910 626913 626914 GROUP I I I O bservation No a b n o r m a lit ie s d e t e c t e d No a b n o r m a li t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d T est Day 1-13 1-13 1-13 1-13 1-13 -70Company Sanitized. Does not contain TSCA CB1 H -24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 H -2 4 0 0 1 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Anim al Number - GROUP IV O b s e r v a t io n ________________________ T e st Day 626897 626903 626916 626925 626926 No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d No a b n o r m a lit ie s d e t e c t e d 1-24 1-24 1-24 1-24 1-24 Anim al Number 626898 626902 626908 626918 626922 GROUP V O bservation No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d T e st Day 1-52 1-52 1-52 1-52 1-52 Anim al Number 626906 626911 626920 626924 626927 GROUP VI ________ O b s e r v a t io n No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d A lo p ecia perineum A lop ecia both fr o n t paws A lopecia both fro n t le g s No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d No a b n o r m a l i t i e s d e t e c t e d A lop ecia underbody A lop ecia ch est A lop ecia r ig h t sid e Test Day 1-93 1-48 52 62, 69, 75 89, 93 1-93 1-93 1-24 3 4 , 48, 52, 62 69, 75,83 89, 93 Company Sanitized. Does not contain TSCACBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2924 APPENDIX C Analysis of Blood Fluoride D ata -72Company Sanitized. Doss not contain TSCA CB! H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats T erm s: Active . % Active Term s and Calculations Mol W t Active Formulation Dose % F in Active Mol Wt F The molecular weight of fluorine g/mol D uP on t-2924 Compound Calculations: Dose Active (mg/kg) The mg of fluorine containing compound administered per kg of animal body weight. = (% active/100) * Formulation Dose Dose Active (mmole/kg) The mmole of fluorine containing compound administered per kg of animal body weight = dose [mg/kg] / Mol W t Active [mg/mmol] Dose F (mg/kg) The mg Fluorine administered per kg of animal body weight = (% F in active/100) * Dose Active [mg/kg] ' Dose F (mmol/kg) - The mmole of fluorine administered per kg of animal body weight = Dose F [mg/kg] / Mol W t F [mg/mmol] Molar Ratio (Active/F) The moles of fluorine containing compound per mole of fluorine = Dose Active [mmol/kg] / Dose F [mmol/kg] Formulation Dose Normalization Factor The formulation dose that would be required to administer the amount of active needed to achieve the normalized dose = (Normalized dose of Active [mmol/kg] / Dose Active [mmol/kg]) * Formulation Dose -73Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Individual Animal M easurem ent: ppm F in blood The ppm fluoride measured in blood D uP on t-2924 Individual Animal Calculations: ppm F in Blood m inus Bkg 0.2 ppm The ppm fluoride measured in plasma minus the background fluoride measured in control animal blood. In this case the value was established at 0.2 ppm. ppm F in Blood The ppm fluoride minus background that would be expected if the norm alized to 0.1 mmol/kg active dose was 0.1 mmol/kg instead of the actual active dose. This D ose assumes linearity between administered dose and blood fluorine levels, but is needed because different doses of active were used in the study. = (0.1 [mmol/kg] / Active dose [mmol/kg]) * (ppm F in blood minus background) molar equivalents o f active in blood The /molar [/mol/L] concentration of fluorine containing compound in plasma based on the ppm fluorine in plasma normalized to 0.1 mmol/kg active dose. This assumes that all plasma fluorine is derived from the fluorine-containing component in the formulation. Note: 1 ppm - 1 mg/L = (Normalized ppm [mg/L] fluorine in blood / Mol Wt F [mg/mmol]) * molar ratio active/F [mmol active/mmol F] * 1000 mol/mmol - 74Company Sanitized. Does not contain TSCA CBI H -24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Factors Influencing Interpretation of K inetic Analysis D uP on t-2924 Considerations: - The Hata 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 hejustified 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 Fluoride 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 - 7 5 - Carapaci Sasalized. Does not contain TSCAGEM H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats D ata for H- 24019 D uP on t-2924 Given: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: C alculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 497 % F in Active: 10 Mol W t. F (g/mol): 100 10 0.020 49.7 Dose F (mmol/kg): M olar Ratio (Active/F): Dose F (mg/kg): 65 19 0.342 0.059 6.5 Rat # 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 m inus Bkg 0.2 ppm ppm F in blood Norm alized to 0.1 mmoles/Kg Dose 0.8 3.98 1.1 5.47 2.4 11.93 2.4 11.93 2.7 13.42 51.5 255.96 37.8 187.87 38.5 191.35 78.3 389.15 36.9 183.39 65.4 60.9 60.3 ` 62.9 57.9 325.04 302.67 299.69 312.61 287.76 /m olar 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 IIP- -76Company Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats R at# Test ppm F Day in Sample blood Group ES 625321 625327 625342 625345 625348 13 13 13 13 13 77.2 61.5 64.6 57.0 62.4 G roup 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 m inus 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 Norm alized 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 D u P on t-2924 /m olar 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 Company Sanitized. Does not contain SCACB1 H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H- 24020 D uP on t-2924 G iven: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 426 % F in Active: 20 Mol Wt. F (g/mol): 100 20 0.047 42.6 Dose F (mmol/kg): M olar Ratio (Active/F): Dose F (mg/kg): 69 19 0.726 0.065 13.8 R at# Test ppm F Day in Sample blood Group I 627773 1 13.2 627771 1 8.1 627767 1 16.5 627756 1 14.1 627777 1 10.7 Group I 627773 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 Norm alized 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 pm olar 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 78- Contpany Sasiksd. Doss not contain TSCA CBS H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats R at # Test Day S am ple ppm F in ppm F blood in m inus Bkg blood______ 0.2 ppm 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 G roup 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 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 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 * * = B elow LOD (Level o f Detection) ppm F in blood Normalized to 0.1 mmoles/Kg Dose D u P on t-2924 /m olar equivalents of active in blood 92.23 43.67 27.69 65.18 52.61 313.77 148.55 94.20 221.74 178.99 19.17 31.31 24.28 20.66 13.85 65.22 106.52 82.61 70.29 47.10 1.49 5.07 0.85 2.90 1.70 5.80 1.49 5.07 1.28 4.35 0.21 0.72 ** 0.00 0.00 0.00 0.00 ** - 7 9 - not contain TSCACBi Cempas sanife***Does H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats D ata for H-24001 D uP on t-2924 G iven: Mol Wt. Active (g/mole): Formulation Dose (mg/kg): % Active (F Containing) in Formulation: 60 1000 35 % F in Active: Mol Wt. F (g/mol): 60 19 Calculated Values: Dose Active (mg/kg): Dose Active (mmole/kg): Formulation Dose Normalization Factor: 350 0.583 171.4 Dose F (mmol/kg): M olar Ratio (Active/F): Dose F (mg/kg): 11.053 0.053 210 R at# Test ppm F Day in Sample blood Group I 626904 626905 626915 626923 626930 1 1 1 1 1 3.3 4.2 3.9 3.9 5.1 Group I 626904 626905 626915 626923 626930 Group II 626900 626909 626912 626919 626921 5 5 5 5 5 10 10 10 10 10 12.8 13.3 11.9 # 15.5 - 15.2 18.5 20.8 25.7 17.3 ppm F in blood m inus Bkg 0.2 ppm 3.1 4.0 3.7 3.7 4.9 12.6 13.1 11.7 # 15.3 15.0 18.3 20.6 25.5 17.1 ppm F in blood Norm alized to 0.1 mmoles/Kg Dose 0.53 0.69 0.63 0.63 0.84 2.16 2.25 2.01 # 2.62 2.57 3.14 3.53 4.37 2.93 molar equivalents of active in blood 1.48 1.90 1.76 1.76 2.33 6.00 6.24 5.57 # 7.29 * 7.14 8.71 9.81 12.14 8.14 - 8 0 - Cosnpany Sanitized. Does not contain TSCA CBI H-24001: Biopersistence Screening 10-Dose Oral Gavage Study in Rats R at# Test ppm F Day in Sample blood Group III 626901 626907 626910 626913 626914 13 13 13 13 13 7.7 5.5 6.8 5.7 5.6 G roup IY 626897 626903 626916 626925 626926 24 24 24 24 24 2.4 2.8 2.7 2.5 2.8 Group V 626898 626902 626908 626918 626922 52 52 52 52 52 1.8 2.0 1.4 1.7 1.9 Group VI 626906 626911 626920 626924 626927 94 94 94 94 94 0.8 1.0 1.2 1.2 1.1 ppm F in blood minus Bkg 0.2 ppm 7.5 5.3 6.6 5.5 5.4 2.2 2.6 2.5 2.3 2.6 1.6 1.8 1.2 1.5 1.7 0.6 0.8 1.0 1.0 0.9 # = Tube o f blood for this rat was m issing or broken. ppm F in blood Normalized to 0.1 mmoles/Kg Dose 1.29 0.91 1.13 0.94 0.93 0.38 0.45 0.43 0.39 0.45 0.27 0.31 0.21 0.26 0.29 0.10 0.14 0.17 0.17 0.15 DuPont-2924 /m olar equivalents of active in blood 3.57 2.52 3.14 2.62 2.57 1.05 1.24 1.19 1.10 1.24 0.76 0.86 0.57 0.71 0.81 0.29 0.38 0.48 0.48 0.43 -81 - Company linTSCACBI