Document wDyroQ0RqK9abjGRyJK6DZ856

Revision Number 1 DuPont-14162 TRADE SECRET A R 286- Study Title APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice 3T g Author: Carol Finlay, B.A. Original Completed on: August 1,2005 Revision 1 Completed on: January 12, 2006 P e r f o r m in g L a b o r a t o r y : E.I. du Pont de Nemours and Company HaskellSMLaboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 U.S.A. L a b o r a t o r y P r o j e c t ID: DuPont-14162 W o r k R e q u e s t N u m b e r : 15073 S e r v ic e C o d e N u m b e r : 1025 (Rats) and 879 (Mice) Page 1 of 405 APFO (Linear/Brnched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR 792) Good Laboratory Practice Standards, which are compatible with current OECD Good Laboratory Practices, except for the items documented below. The items listed do not impact the validity of the study. 1. Linear and Branched APFO were characterized prior to the initiation of this study. Although the characterization was not performed under Good Laboratory Practice Standards, the accuracy of the data is considered sufficient for the purposes of this study. 2. Linear/branched APFO is commercially available and was characterized prior to the initiation of this study. A certificate of analysis was provided. Although the characterization was not performed under Good Laboratory Practice Standards, based on our monitoring, we have no reason to doubt the validity of the analysis. Study Director: Senior Staff Toxicologist Haskell Laboratory for Health and Environmental Sciences -2- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice________ ' : - ' ', -,________ _____________DuPont-14162 QUALITY ASSURANCE DOCUMENTATION Report Number: Work Request Number: Study Code Number: DuPont-14162 15073 1025 (Rats) and 879 (Mice) The conduct of these studies has been subjected to periodic Quality Assurance inspections. The dates of inspection are indicated below. Phase Audited Conduct: Report/Records: Audit Dates Date Reported to Date Reported to Study Director Management 4 Mar 2004 25 Mar 2004 4 Mar 2004 25 Mar 2004 4 Mar 2004 25 Mar 2004 28-31 Mar 2005 4-5 Apr 2005 6-7 Apr 2005 6-8, 11-12 Apr 2005 6 May 2005 15,17, 18,19 Jul 2005 1 Apr 2005 5 Apr 2005 7 Apr 2005 13 Apr 2005 6 May 2005 19 Jul 2005 12 Apr 2005 11 Apr 2005 7 Apr 2005 6 May 2005 9 May 2005 29 Jul 2005 Reported by: Annet L. Reigel Quality Assurance Auditor l-A \/(r- ZOOS' Date -3- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Analytical Evaluations by: Principal Research Scientist and Manager ^2 Date Clinical Pathology Evaluation by: Nancy E. Everds, D.V.M. Diplomate A.C.V.P. Principal Research Scientist Biochemical Measurements by: ?r f l John C. O'Connor, M.S. Senior Research Toxicologist and Group Manager l-A ova- ^405 Approved by: Scott E. Loveless, Ph.D. Research Manager and Director Issued by Study Director: Carol Finlay, B., Senior Staff Toxicologist Date 1- 0Lu.fi - f Date) -4- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT.......................................... 2 QUALITY ASSURANCE DOCUMENTATION............................................................................3 CERTIFICATION............................................................................................................................ 4 LIST OF TABLES - RATS..............................................................................................................6 LIST OF TABLES - MICE............................................................... 7 LIST OF FIGURES - RATS.................... 8 LIST OF FIGURES - MICE........................ 8 LIST OF APPENDICES - RATS.....................................................................................................8 LIST OF APPENDICES - M ICE.....................................................................................................8 DATES................................................... 9 RECORDS AND SAMPLE STORAGE.................... 9 MANUSCRIPT FOR PUBLICATION.......................................................................................... 10 ABSTRACT.............................................................................................................................. 11 INTRODUCTION...................................................................... 12 MATERIALS AND METHODS.............................................................................................. 13 RESULTS................................................................................................................................. 17 DISCUSSION........................................................................................................................... 22 ACKNOWLEDGMENTS........................................................................................................25 REFERENCES......................................................................................................................... 26 FIGURES......................................................... 29 TABLES................................................................................................................................... 34 RAT TABLES................................................................................................................................ 41 RAT FIGURES............................................................................................................................... 82 RAT APPENDICES....................................................................................................................... 86 MOUSE TABLES........................................................................................................................ 229 MOUSE FIGURES....................................................................................................................... 272 MOUSE APPENDICES................................................................................................. 276 -5- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 LIST OF TABLES - RATS Page Table 1 Homogeneity/Concentration Verification and Stability Analysis for Rat Study.................. 43 Table 2 Recovery of H-24921, H-26313, H-26225 Added to Dosing Vehicle for Rat Study................................44 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Rat Study..................................................................................................................................................... 45 Table 4 Summary of Dosing Suspension Analyses for Rat Study..........................................................................47 Table 5 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear/Branched)............................................48 Table 6 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear)............................................................ 50 Table 7 Mean Body Weights (g) of Male Rats Dosed with APFO (Branched)....................................................... 52 Table 8 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear/Branched)...................................54 Table 9 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear)...................................................56 Table 10 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Branched)..............................................58 Table 11 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Linear/Branched).................60 Table 12 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Linear).................................61 Table 13 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Branched)............................62 Table 14 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Linear/Branched)...............................63 Table 15 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Linear)................................................... 64 Table 16 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Branched).......................................... 65 Table 17 Summary of Clinical Observations for Male Rats Dosed with APFO (Linear/Branched)........................66 Table 18 Summary of Clinical Observations for Male Rats Dosed with APFO (Linear)........................................67 Table 19 Summary of Clinical Observations for Male Rats Dosed with APFO (Branched)...................................68 Table 20 Percent Survival of Male R ats........................................................................................................... 70 Table 21 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Linear/Branched)............... 71 Table 22 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Linear)................................72 Table 23 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Branched)...........................73 Table 24 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Linear/Branched)...................74 Table 25 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Linear)....................................75 Table 26 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Branched)...............................76 Table 27 Incidences of Gross Observations in Male Rats Dosed with APFO (Linear/Branched)...........................77 Table 28 Incidences of Gross Observations in Male Rats Dosed with APFO (Linear)...........................................78 Table 29 Incidences of Gross Observations in Male Rats Dosed with APFO (Branched)......................... 79 Table 30 Summary of Peroxisomal Beta-Oxidation Activity in Male Rats............................................................. 80 Table 31 Summary of % Relative Liver Weights in Male Rats......................... 81 -6- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice __________ Revision Number 1 DuPont-14162 LIST OF TABLES - MICE Page Table 1 Homogeneity/Concentration Verification and Stability Analysis for Mouse Study................................231 Table 2 Recovery of Fl-24921, H-26313, H-26225 Added to Dosing Vehicle for Mouse Study........................ 232 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Mouse Study...............................................................................................................................................233 Table 4 Summary of Dosing Suspension Analysis for Mouse Study................................................................... 235 Table 5 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear/Branched)..........................................236 Table 6 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear).......................................................... 238 Table 7 Mean Body Weights (g) of Male Mice Dosed with APFO (Branched).....................................................240 Table 8 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear/Branched).................................242 Table 9 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear).................................................244 Table 10 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Branched)............................................246 Table 11 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Linear/Branched).............. 248 Table 12 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Linear)...............................249 Table 13 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Branched)......................... 250 Table 14 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Linear/Branched).................................251 Table 15 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Linear).................................................252 Table 16 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Branched)............................................253 Table 17 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear/Branched)..................... 254 Table 18 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear)......................................256 Table 19 Summary of Clinical Observations for Male Mice Dosed with APFO (Branched).................................258 Table 20 Percent Survival of Male M ice................................................................................................................. 260 Table 21 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Linear/Branched).............261 Table 22 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Linear)............................. 262 Table 23 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Branched)........................ 263 Table 24 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Linear/Branched)................264 Table 25 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Linear)................................ 265 Table 26 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Branched)............................ 266 Table 27 Incidences of Gross Observations in Male Mice Dosed with APFO (Linear/Branched)........................ 267 Table 28 Incidences of Gross Observations in Male Mice Dosed with APFO (Linear).........................................268 Table 29 Incidences of Gross Observations in Male Mice Dosed with APFO (Branched)................................... 269 Table 30 Summary of Peroxisomal Beta-Oxidation Activity in Male Mice...........................................................270 Table 31 Summary of % Relative Liver Weights in Male Mice............................................................................. 271 -7- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Figure 1 Figure 2 Figure 3 LIST OF FIGURES - RATS Page Mean Body Weights of Male Rats Dosed with APFO (Linear/Branched)..............................................83 Mean Body Weights of Male Rats Dosed with APFO (Linear).............................................................. 84 Mean Body Weights of Male Rats Dosed with APFO (Branched).........................................................85 Figure 1 Figure 2 Figure 3 LIST OF FIGURES - MICE Page Mean Body Weights of Male Mice Dosed with APFO (Linear/Branched)...........................................273 Mean Body Weights of Male Mice Dosed with APFO (Linear)...........................................................274 Mean Body Weights of Male Mice Dosed with APFO (Branched)......................................................275 Appendix A Appendix B Appendix C Appendix D Appendix E Appendix F Appendix G Appendix H LIST OF APPENDICES - RATS Page Individual PFOA Serum Concentrations for Rats............................................................................ 87 Individual Body Weights for Rats............................... 98 Individual Food Consumption for Rats...........................................................................................112 Individual Clinical Observations and Mortality Records for R ats................................................. 120 Individual Animal Clinical Pathology Data for Rats.......................................................................137 Individual Animal Body and Organ Weights for R ats................................................................... 166 Individual Animal Gross Observations for R ats.............................................................................177 Individual Rat Beta-Oxidation Data......................................................... 215 Appendix A Appendix B Appendix C Appendix D Appendix E Appendix F Appendix G Appendix H Appendix I LIST OF APPENDICES - MICE Page Individual PFOA Serum Concentrations for Mice........................................................................ 277 Individual Body Weights for Mice..................................................................................................285 Individual Food Consumption for Mice..........................................................................................299 Individual Clinical Observations and Mortality Records for M ice................................................ 307 Individual Animal Clinical Pathology Data for M ice................................................................... .327 Individual Animal Final Body and Organ Weights for Mice......................................................... 335 Individual Animal Gross Observations for M ice........................................................................... 346 Individual Mouse Beta-Oxidation Data...........................................................................................388 Revision 1 ....................................................................................................................................... 402 -8- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice__________________________________________DuPont-14162 Rat Study Initiation Date: Rat Study Completion Date: Mouse Study Initiation Date: Mouse Study Completion Date: DATES January 22, 2004 See report cover page February 25, 2004 See report cover page RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, the protocols, amendments, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. -9- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 MANUSCRIPT FOR PUBLICATION - 10- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 COMPARATIVE RESPONSES OF RATS AND MICE EXPOSED TO LINEAR/BRANCHED, LINEAR, OR BRANCHED AMMONIUM PERFLUOROOCTANOATE (APFO) Scott E. Loveless,*'1 Carol Finlay,* Nancy E. Everds,* Steven R. Frame,* Peter J. Gillies,# John C. O'Connor,* and Gerald L. Kennedy* * DuPont Haskell Laboratory for Health and Environment Sciences, Newark, DE, 19714 # DuPont Nutrition and Health, Newark, DE, 19714 ABSTRACT Ammonium perfluorooctanoate (APFO), as formerly used in the production of commercial products, was a mixture of linear and branched isomers in a ratio of approximately 80:20 (linear/branched). The extensive toxicologic database for APFO has been developed essentially using this mixture of isomers. The current production of APFO uses a synthetic process that produces only the linear isomer. The present study was undertaken to compare the biologic activity of linear/branched APFO with that of linear APFO. In addition, a form of APFO consisting of only branched molecules was also evaluated. Rats and mice were given doses by oral gavage ranging from 0.3 to 30 mg/kg of either the linear/branched, linear, or branched APFO for 14 days. Clinical signs, body weights, food consumption, selected hematology and serum lipid parameters, liver and kidney weights, hepatic peroxisomal P-oxidation, and serum PFOA concentrations were evaluated for each of the three test materials in each of the two rodent species. Clinical signs were generally unremarkable in rats and mice dosed with linear/branched, linear, or branched APFO. Mean body weights were 19, 19, and 5% lower than that of controls in rats dosed with 30 mg/kg of linear/branched, linear, and branched APFO, respectively. Similar changes were present in mice (means were 21, 18, and 3% lower than that of controls, respectively). Ex vivo hemolysis was seen in rats but not mice. In rats, total cholesterol, HDL, and non-HDL cholesterol decreases were produced by all 3 materials. Triglycerides were decreased to a similar extent with the linear form producing a response at a lower dose. In mice, all 3 forms reduced both total and HDL cholesterol similarly but, unlike in the rat, triglycerides were increased at low doses, but similar to control or decreased at the highest dose. Liver weight increases were seen in both species with all three forms. Increased hepatic p-oxidation activity was seen in both species but was least pronounced in rats given the branched material. In mice, all doses produced increased hepatic beta-oxidation activity with little difference noted either by material form tested or dose. In rats, serum PFOA levels were approximately 50 ppm at the LOEL of 1 mg/kg for linear/branched and branched material, and 20 ppm at the LOEL of 0.3 mg/kg for the linear material (LOELs based primarily upon lipid parameters). In mice, serum PFOA levels were similar for all 3 materials. At the LOEL (0.3 mg/kg, based upon liver weight), serum PFOA levels were 10-14 ppm. In both rats and mice, the overall responses to the linear/branched and the linear forms of PFOA were similar, but the branched form appears to be less potent. Based on these results, the toxicological database developed primarily from testing linear/branched APFO is applicable to linear APFO. Key Words: APFO, PFOA !To whom correspondence should be addressed at DuPont Haskell Laboratory, P.O. Box 50, Elkton Rd, Newark, DE 19714-0050. Email: scott.e.loveless@usa.dupont.com - 11- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INTRODUCTION Ammonium perfluorooctanoate (APFO; FC-143, Cg, C7Fi5COO'NH4+, CAS Registry No. 3825-26-1) is a surfactant used as a processing aid in the production of fluoropolymers. Perfluorooctanoate (PFOA; C7F15COO'), the dissociation product of APFO, is not metabolized (Vanden Heuvel et al., 1991) and has been identified in blood samples from exposed workers and the general population (Taves et al., 1976; Hansen et al., 2001; Olsen et al., 2003). A large database of experimental studies on the potential health hazards of PFOA is available, as are recent toxicology reviews (USEPA, 2002; Kennedy et al., 2004). In addition to toxicology studies in laboratory animals, the potential association of APFO exposure with health effects in fluorochemical production workers has been studied since 1976 through medical monitoring and epidemiological investigations (Ubel et al., 1980; Olsen et al., 1998, 2000). Clinical laboratory evaluations including liver tests and hormone concentrations (e.g., estradiol, testosterone, and cholecystokinin) have been normal (Olsen et al., 1998,2000). A form of APFO containing both linear and branched components (generally in a ratio of 70-80% linear, 20-30% branched; denoted as linear/branched) has been used in studies to evaluate many biological endpoints. Numerous repeated-dose studies have been conducted with linear/branched APFO in a variety of species (mice, rats, and monkeys), and these have been reviewed recently (Butenhoff et al., 2002; Kennedy et al., 2004; USEPA, 2002). Together, these studies demonstrate that liver is the primary target organ for APFO toxicity. The hepatic changes include increased liver weights due to hepatocellular hypertrophy and proliferation of smooth endoplasmic reticulum and peroxisomes in rodents. Other effects observed in rodents include body weight decreases, increased kidney weights (without histological correlates), and hypolipidemia (decreased triglycerides and cholesterol) in mice (Xie et al., 2003). Studies evaluating genotoxicity, reproductive toxicity, effects on the developing organism, and carcinogenicity have also used this material (reviewed in Kennedy et al., 2004). The purpose of the current study was to determine if there are substantial differences in the toxicity profile in rats and mice, based on selected endpoints, among the 3 forms of APFO (linear/branched, linear, and branched). The test materials studied were linear/branched APFO (78:22), linear APFO, and branched APFO (58:42 blend of the 2 most prevalent branched forms in linear/branched APFO). Doses for rats and mice were chosen ranging from those expected to be at or near no-observed effect levels to those expected to produce clear effects. This study focused specifically on evaluation of body weights, serum lipid profiles, liver and kidney weights, and hepatic beta-oxidation. - 12- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 Test Materials MATERIALS AND METHODS Linear/branched APFO was provided by 3M Company, Specialty Materials Manufacturing Division (St. Paul, MN). This test material was 77.6% linear. Mole percents of branched content were as follows: 12.6% internal monomethyl (non-alpha); 9% isopropyl; 0.2% tert-butyl; 0.1% gem-dimethyl; and 0.1% alpha monomethyl. The certificate of analysis indicated 2.01% lesser-homolog (C4-C7) impurities. Homolog distribution was as follows: C4, 0.01%; Cs,.0.03%; C6,0.43%; C7, 0.57%; C8, 97.99%; C<>, 0.16%. The sample also included 0.09% monohydro APFO, 0.72% monounsaturated APFO, and 0.3% undefined material that was possibly substituted perfluorocyclo species (0.2% cyclopentyl and 0.1% cyclohexyl). This test material, a white solid, was 97.99% pure. Linear and branched APFO were provided by DuPont (Wilmington, DE). Linear APFO was a white to slightly opaque liquid in a 20% aqueous solution. Branched APFO was a white solid. It was prepared by combining 58.3% Ammonium 2,2,3,4,4,5,5,6,6,7,7,7-pentadecafluoro-3-(trifluoromethyl)heptanoate (internal mono methyl-non alpha) (referred to as Branch A) with 41.7% Ammonium 2,2,3,3,4,4,5,5,6,7,7,7-pentadecafluoro-6(trifluoromethyl)heptanoate (isopropyl) (referred to as Branch B) The Branch A material was a mixture of 3- and 4-methyl in a ratio of 92:8. Animals and Husbandry The research described in this study was conducted in a laboratory accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International and the investigators complied with the regulations and standards of the Animal Welfare Act and adhered to the principles of the Guide for the Care and Use of Laboratory Animals. Male Crl:CD(SD)IGS BR rats and Crl:CD-l(ICR)BR mice were obtained from Charles River Laboratories, Inc. (Raleigh, North Carolina). All rats and mice were housed individually in stainless steel, wire-mesh cages suspended above cage boards. Animal rooms were targeted at a temperature of 22-24C and a relative humidity of 40-60%, and were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle. Throughout the test period, LLC Certified Rodent LabDiet 5002 (PMI Nutrition International, Inc., St. Louis, MO) and tap water were available ad libitum. Prior to testing, rats and mice were evaluated by clinical observations and body weight determinations during a 4-day quarantine period to assure freedom from potential confounding variables. Experimental Design At approximately 8 weeks of age, rats and mice were selected for the study on the basis of adequate body weight gain and freedom from clinical signs of disease or injury. The animals were randomized into 6 groups of 10 male animals so that there were no statistically significant differences among group body weight means. Each animal was assigned an identification number which was recorded on a card (rats) or label (mice) and affixed to the cage. The - 13- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 animals were tattooed with the identification number. Each test group was administered one of the test materials at daily doses of either 0, 0.3,1, 3, 10, or 30 mg/kg. Studies with each test material were run as separate experiments, each with its own control group. The dose of the test material administered to the animals was adjusted for the percentage of active material (APFO) such that the dose of APFO was the same. The study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practices Standards. Control of bias was minimized by using a concurrent control group for each test material, starting each sub-study within one or two days of each other, having identical study designs, and having day-to-day activities performed by a small pool of personnel. Interanimal variation was minimized by using animals in good health, the same age, of appropriate body weight range, and by randomly assigning animals to groups. Test Material Administration All test materials were prepared in NANOpure water for dosing. The rats and mice were dosed by intragastric intubation for 14 consecutive days at a volume of 10 mL/kg of body weight. Control rats and mice received NANOpure water only. The animals were dosed at approximately the same time each day. Individual dose volumes were calculated using the body weight obtained prior to dosing. Analysis of Dosing Preparations Samples of dosing preparations for linear/branched, linear, and branched APFO at concentrations of 0, 0.03, 0.10, and 3.0 mg/mL were analyzed for uniformity of mixing/concentration verification and stability. Concentrations of compound were measured by high performance liquid chromatography tandem mass spectrometry LLC-MS/MS. In Vivo Parameters Body weights for all rats and mice were recorded daily. Observations for clinical signs of toxicity and mortality were conducted at least twice daily throughout the study. Food consumption was measured twice weekly during the study. Body weight gains were calculated from day 0 to day 13. In addition for mice, body weight gain was normalized for differences in liver weights using the following formula: (final body weight - liver weight) - (body weight day 0 - mean weight of group A control livers) Collection, processing, and analysis of blood and tissues Blood samples for clinical pathology and serum PFOA measurements were collected approximately 24 hours after the last dose of APFO. The order of blood collection and euthanasia was stratified across dose groups for each test material; animals dosed with a given test article were sacrificed on the same day. After final body weights were determined, animals were anesthetized by C 02anesthesia, and blood was collected from the orbital sinus of each rat and mouse, and from the abdominal vena cava of each rat. Animals were euthanized by exsanguination while under anesthesia. Livers and kidneys were removed and weighed and relative (to body weight) organ weights were calculated. - 14- APFO (Linear/Branched), APFO (Linear), and APFO (Branched) 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Clinical Pathology Evaluation On the first day of necropsy for rats dosed with linear/branched APFO, a dose-related increase in the incidence of hemolysis was noted in the orbital sinus blood samples. In order to further evaluate this finding of hemolysis, blood smears were prepared from additional blood collected from the abdominal vena cava from all remaining rats (half of the animals treated with linear/branched APFO, and all the animals treated with either linear APFO or branched APFO). Wright-Giemsa-stained blood smears were examined microscopically for evaluation of red blood cell morphology. Sera from orbital sinus samples were used for the determination of lipid parameters in the mouse, and for concentrations of test material in the mouse and rat (stored frozen at -80C until analyzed). Sera from abdominal vena cava samples were used for the determination of lipid parameters in the rat; vena cava samples were less hemolyzed than orbital sinus samples, so they were used to minimize potential interference by hemoglobin with clinical chemistry assays. Serum lipid parameters [cholesterol, F1DL cholesterol, non-HDL cholesterol (calculated), and triglycerides] were determined on an Olympus AU640 clinical chemistry analyzer (Melville, NY). H epatic Peroxisom al (1-oxidation Evaluation At necropsy, a section of liver was removed from 10 animals/group and hepatic peroxisomes were prepared for [3-oxidation analysis, a measure of peroxisome proliferation. A portion of the liver was homogenized (1 g tissue to 4 mL buffer for rats or 8 mL buffer for mice) in buffer containing 50 mM Tris-HCl, 50 mM Trizma-base, 0.25 M sucrose, and 5.4 mM EDTA, pH 7.4. The homogenates were centrifuged at 15,000 x g for 15 min at 4C to remove cellular debris. The resulting supernatants were removed and centrifuged at 15,000 x g for 15 min at 4C; these pellets contained the peroxisomal fractions. The peroxisomal pellets were resuspended in homogenization buffer and stored at -80C until analyzed. Peroxisomal suspensions were diluted to a protein concentration of approximately 0.25 mg/mL (rats) or 0.5 mg/mL (mice) for analysis. Peroxisomal P-oxidation activity was determined using [^Cjpalmitoyl CoA as the substrate (Lazarow, 1981). Protein content of the peroxisomes was determined before and after analysis by the Biorad method (Bradford, 1976). Final rate calculations were made using the post-assay protein concentrations. Analytical Procedures Concentrations of branched and linear PFOA were measured in rat and mouse blood serum samples using a modified version of the method described in Flaherty (2005). Briefly, acetonitrile was added to an aliquot of blood serum to precipitate protein and extract PFOA isomers. A stable isotope internal standard (dual 13C-PFOA) was added to each sample to facilitate quantification. The sample was then analyzed by reversed-phase liquid chromatography with mass spectrometric detection. HPLC conditions were adjusted so that isomers in the branched APFO (Branch A and Branch B) were partially resolved from each other and from linear PFOA. This adjustment - 15- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 also permitted partial resolution of the components of the mixed linear/branched test material. In all cases, the resolution was adequate to permit individual quantification of linear PFOA, Branch A, and Branch B isomers. The mass spectrometer used was equipped with an electrospray interface operating in the negative ion mode and a triple quadrupole (LC/MS/MS). The parent-to-daughter ion transition representing M - C 0 2was monitored for all analytes and the internal standard. The limit of quantification of the analytical method was 5 ppb. For linear/branched APFO, the serum concentrations of linear and branched APFO were added to determine the total PFOA concentration and the ratio of branched to linear was calculated. For branched APFO, serum was analyzed separately for the 2 branched isomers and added to determine total serum PFOA concentration. The ratio of branched materials (A to B) was calculated. Statistical Analysis For each form of APFO preliminary tests were conducted for homogeneity of variance (Levene, 1960) and normality (Shapiro-Wilk, 1965). If data were normally distributed and had homogeneity of variances, a one-way analysis of variance (Snedecor, 1967) was conducted, followed by Dunnett's test (1964). For data that did not show homogeneity of variances, a robust version of Dunnett's test (1980) was used. Non-normally distributed data was analyzed by non-parametric procedures (Kruskal-Wallis test (1952) followed by Dunn's test (1964)). Significance was judged at p < 0.05. To compare the three forms of APFO at each dose a two-factor full factorial ANOVA with dose and formulation was used as a preliminary analysis of each response. The Shapiro-Wilk (Shapiro and Wilk, 1965) and Levene tests (Levene, 1960) were used to assess normality and variance homogeneity, respectively, for each response separately. Where appropriate, a normalizing, variance stabilizing transformation of the response was used, usually a logarithm or square-root transform. The error term used when comparing dose groups from different compounds included both the pooled within-group variance and the between-experiments variance. The three controls were used to estimate the between-experiments variance. REML estimates (Searle et al., 1992) of these variance components were obtained using SAS 9.2 Proc Mixed. Differences between formulations at each dose level and dose effects within each formulation were then obtained from contrasts within the 2-factor ANOVA. In addition to the comparisons discussed above, regression analyses were also performed to distinguish whether there were statistical differences among the 3 APFO test materials for each endpoint. These analyses were done using both administered dose vs each endpoint as well as individual serum concentrations vs. each endpoint in order to smooth the dose response. Each endpoint was modeled, using a polynomial of degree 1, 2, or 3 with separate intercepts, slopes, and curvatures. Backward elimination methods were used to determine which terms were retained in the final model. If adjustments to the j-th order term, j= l, 2, 3, for different test substances were retained on this basis, then the overall j-th order term was likewise retained whether or not it was significant - see Pack (1993); USEPA (1995); See and Baylor (1998); Kalliomaa et al., (1998); and Slob (2002). - 16- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice__________ ______________________________ DuPont-14162 RESULTS Rats Clinical Signs/Mortality All rats dosed with the 3 APFO test materials were free of clinical signs of toxicity and survived until the end of the study. Body Weights and Body Weight Gains Statistically significant reductions in mean body weights were observed in rats dosed with 30 mg/kg linear/branched or linear APFO. The changes were associated with statistically significant lower body weight gains in rats dosed with >10 mg/kg of linear/branched APFO (Table 1). Mean body weights of rats dosed with 30 mg/kg linear/branched or linear APFO were 73 and 69% of control at mid-study (test day 7),, respectively, and 81% of control for both at the end of study (test day 13). Mean body weights of rats dosed with 10 mg/kg of linear/branched APFO were 89% of control only on test day 13. Overall body weight gains (test days 0-13) were 55 and 22% of control, respectively, in rats dosed with 10 or 30 mg/kg linear/branched APFO, and 74 and 15% of control, respectively, in rats dosed with 10 or 30 mg/kg linear APFO. In rats dosed with 3 mg/kg linear APFO or 30 mg/kg branched APFO, there were slight, albeit statistically significant, decreases in mean body weight gain (74-76% of controls) that did not result in statistically significant decreases in mean body weights. Overall, the magnitudes of the decreases in mean body weight gain in rats dosed with linear/branched APFO and linear APFO were similar, while the magnitude of effect in rats dosed with branched APFO was less pronounced. Food Consumption/Food Efficiency Mean food consumption and food efficiency (test day 0-13; data not shown) in rats given 30 mg/kg of either linear/branched or linear were similarly reduced (food consumption was 73% and 78% of control, and food efficiency was 24% and 18% of control, respectively, for linear/branched and linear APFO). With the branched material, both food consumption and food efficiency were approximately 90% of control (not statistically significant). Analysis of Dosing Preparations The results of analysis indicate that branched/linear, linear, and branched APFO were at the targeted concentrations, adequately mixed, and stable in the vehicle. No test material was detected in the control (0 mg/mL) samples. H em atology Numerous serum samples from all treatment groups were hemolyzed, and hemolysis increased with increasing dose (data not shown). Hemolysis in control samples was never greater than trace. In a given rat, hemolysis was more severe in serum samples from the orbital sinus compared to those from the vena cava. Hemolysis greater than -17- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 respective control values was observed in vena cava samples from rats dosed with the linear/branched and linear APFO at doses >3 mg/kg, and with the branched APFO at doses of 10 and 30 mg/kg. Hemolysis greater than respective control values was observed in orbital sinus samples from rats dosed with linear/branched APFO at >0.3 mg/kg, with linear APFO at doses >1 mg/kg, and with branched APFO at doses >3 mg/kg. To investigate the cause of hemolysis, red blood cell morphology was evaluated on all available peripheral blood smears to determine whether or not the hemolysis occurred in vivo (prior to blood collection) or only in vitro (during blood collection or processing). There were no treatment-related changes in polychromasia, suggesting that hemolysis occurred only during blood collection, not in vivo. Treatment-related increases in acanthocytes were observed on the peripheral blood smears of rats dosed with linear/branched and linear APFO at doses >3 mg/kg, and with the branched APFO at 10 and 30 mg/kg. Treatmentrelated increases in poikilocytes or schistocytes were observed in rats dosed with linear/branched and branched APFO only at the 30 mg/kg dose, and in rats dosed with linear APFO at doses >3 mg/kg. Although for each chemical form there appeared to be a dose-response, acanthocytes, poikilocytes, and schistocytes were never present in high numbers, even at the highest doses. Clinical Chemistry Total serum cholesterol concentrations were decreased in rats dosed with >0.3 mg/kg linear APFO, and in rats dosed with >1 mg/kg linear/branched APFO or branched APFO (Table 2). Serum cholesterol concentrations were less affected at doses of 30 mg/kg than at 3 or 10 mg/kg for each of the 3 test materials. For linear/branched APFO, total cholesterol concentrations were lowest in rats dosed with 3 mg/kg (45% of control). However, for linear and branched APFO, total cholesterol concentrations were similar at doses of 3 and 10 mg/kg (56-60% of control and 56-59% of control, respectively). HDL cholesterol concentrations were significantly decreased at doses >3 mg/kg by each of the 3 test materials. Like total cholesterol, the lowest HDL cholesterol concentrations occurred at doses of 3 or 10 mg/kg for each of the test materials. HDL cholesterol concentrations as a percent of control for these two doses were 52-57% (linear/branched), 58% (linear), and 65-70% (branched). Changes at doses of 30 mg/kg were less prominent than at lower doses for each of the test materials. Non-HDL cholesterol concentrations were decreased at doses >1 mg/kg by each of the 3 test materials. In addition, non-HDL cholesterol concentrations were statistically significantly decreased at doses of 1 mg/kg for linear/branched APFO, and at 0.3 and 1 mg/kg for linear APFO. Like total and HDL cholesterol, the lowest non-HDL cholesterol concentrations occurred at doses of 3 or 10 mg/kg for each of the test materials. Non-HDL cholesterol concentrations as a percent of control for these two doses were 40-60% (linear/branched, excluding an outlier), 52-64% (linear), and 50% (branched). Non-HDL cholesterol changes at doses of 30 mg/kg were less prominent or were not present. -18- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice , Revision Number 1 DuPont-14162 Serum triglyceride concentrations were decreased in rats dosed with >0.3 mg/kg linear APFO, and in rats dosed with >1 mg/kg linear/branched APFO or branched APFO (Table 2 and Figure 1). Unlike cholesterol, the dose-response for triglyceride concentration for each of the test materials was flat at doses >3 mg/kg. At doses >3 mg/kg, triglyceride concentrations ranged from 51-67% of control for linear/branched APFO, 72-79% of control for linear APFO, and 53-62% of control for branched APFO. Organ Weights Absolute liver weights were significantly increased in rats dosed with >1 mg/kg branched APFO or >3 mg/kg linear/branched APFO or linear APFO (Table 3). Liver weights relative to body weights were increased in a dosedependent manner in all groups dosed with the test materials (Table 3 and Figure 2), with the highest relative liver weights at 30 mg/kg (means were 199,183, and 188% of control for linear/branched, linear, and branched APFO, respectively). A few instances of statistically significant alterations in absolute or relative kidney weights were observed with all 3 test materials. Overall, the magnitudes of the alterations were small and were not considered treatment-related. Hepatic Peroxisomal p-Oxidation In rats, each of the three APFO test materials caused statistically significant increases in hepatic P-oxidation activity (Table 4 and Figure 3). Rats dosed with linear/branched or linear APFO had a dose-dependent increase in hepatic p-oxidation activity that was statistically significant at dosages of >1 mg/kg, with the greatest increases at 30 mg/kg (465 and 567% of control, respectively). Hepatic p-oxidation was significantly increased in rats dosed with >3 mg/kg branched APFO, with the greatest increase at 30 mg/kg (289% of control). Overall, the linear/branched and linear APFO increased hepatic P-oxidation activity to similar magnitudes, while the branched APFO was less potent. Serum PFOA Concentrations Small amounts (<1 pg/ml) of PFOA were detected in sera control rats (Table 5). Overall, serum PFOA concentrations increased proportionally with dose. For example, at doses of 0.3, 1, and 3 mg/kg APFO, serum levels of PFOA were approximately 20, 60, and 100 pg/ml, respectively, for all 3 test materials. However, for branched APFO, the slope of the dose response diminished at the three higher doses compared to linear/branched APFO and linear APFO (Figure 4). For linear/branched APFO, the ratio of linear to branched APFO administered was 3.5. The ratio of linear to branched PFOA in serum increased as the dose increased (from 5.1 at 0.3 mg/kg to 11 at 30 mg/kg). With branched APFO, the ratio of Branch A to Branch B administered was 1.4:1. With increasing dose, the ratio of Branch A to Branch B in serum increased (1.3:1 at 0.3 mg/kg to 2.8:1 at 30 mg/kg). Regression Analysis When analyzed by administered dose, there were no statistically significant differences detected between endpoints measured for rats dosed with linear APFO and linear/branched APFO. For most endpoints, especially at higher - 19- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 doses, the branched form of APFO was statistically different from the linear or linear/branched forms. In general, this regression analysis confirmed the findings of the ANOVA tests concerning the effects of branched APFO on the nutritional endpoints of body weight, body weight gain, and food efficiency. When analyzed by PFOA serum concentrations, however, there were no differences observed for nutritional endpoints among the three forms of APFO. In contrast, for a given serum concentration of PFOA, relative liver weights were higher and relative kidney weights were lower in rats dosed with branched APFO compared to the other two test materials. M ice Clinical Signs/Mortality No adverse clinical signs of toxicity were observed in mice dosed with either linear/branched APFO or branched APFO. The incidence of enophthalmos (3/10) and lethargy (2/10) was significantly increased in mice dosed with 30 mg/kg linear APFO. No clinical signs were seen in mice given 10 mg/kg linear APFO or less. One mouse dosed with 30 mg/kg linear APFO died during the study; the cause of death was not determined. Body Weights and Body Weight Gains Mean body weights were significantly lower compared to controls following 7 and 13 days of dosing with 30 mg/kg of linear/branched APFO (84 and 79% of control) or linear APFO (84 and 82% of control) at both days (Table 1). Overall mean body weight gains were also lower for these two groups. Mean body weights of control mice increased 1 to 2 grams over the course of the study (test days 0-13); however, mean body weights of groups dosed with >10 mg/kg linear/branched APFO or linear APFO decreased between 1 and 6 grams. Treatment-related increases in liver weights (Table 3) decreased the apparent magnitude of body weight effects. At necropsy body weight excluding liver weights of mice dosed with 30 mg/kg were 67% of control for linear/branched APFO, 75% of control for linear APFO, and 83% of control for branched APFO (data not shown). Therefore, all 3 groups dosed with 30 mg/kg APFO had significant body weight loss. Mean body weight gains of mice, when adjusted for increased liver weights, were between -1.3 and 0.3 g for control mice and mice dosed with <3 mg/kg, respectively. However, body weight gains adjusted for increased liver weights were substantially lower for mice dosed with >10 mg/kg of linear/branched and linear (-5.7 to -9.5 g), or dosed with 30 mg/kg of branched (-5.1 g). Other changes in mean body weights or body weight gain were observed but were considered to be unrelated to treatment. Overall, the effects on mean body weight and body weight gain were of similar magnitude in mice dosed with linear/branched APFO and linear APFO. Mean body weights and mean body weight gains were generally less affected in mice dosed with branched APFO, even when adjusted for liver weight increases. Food Consumption/Food Efficiency Mean food consumption (test day 0-13; data not shown) was decreased, compared to controls, in mice dosed with linear/branched or linear APFO only at 30 mg/kg (85% and 91% of control, respectively). Over the same time -20- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_________________________________________ DuPont-14162 period in the 30 mg/kg groups, mean food efficiency (g body weight gain/g food consumed) was negative only in the linear/branched form of APFO (data not shown). Food consumption and food efficiency were less affected in mice dosed with branched APFO (food consumption was 95% of control). Analysis of Dosing Preparations The results of analysis indicate that branched/linear, linear, and branched APFO were at the targeted concentrations, adequately mixed, and stable in the vehicle. No test material was detected in the conlrol (0 mg/mL) samples. Clinical Chemistry Serum total and HDL cholesterol concentrations were decreased (variable statistical significance) in mice dosed with >3 mg/kg for each of the test materials (Table 2). The dose-response for both parameters was flat at doses >3 mg/kg for each of the three test materials. Concentrations in these groups were 61-82% of control for total cholesterol and 51-71% of control for HDL cholesterol. In addition, HDL cholesterol concentrations in mice dosed with 1 mg/kg of each of the test materials were minimally lower than controls (82-84% of control group means for the three APFO test materials). There were no treatment-related changes in mean non-HDL cholesterol concentrations in mice. However, mice treated with each of the test materials tended to have wider ranges (both increased and decreased) of non-HDL cholesterol concentrations compared to control mice. Serum triglyceride concentrations were statistically significantly increased in mice dosed with 0.3,1, 3, or 10 mg/kg of linear/branched APFO (Table 2 and Figure 1); mean triglyceride concentration was highest at 10 mg/kg (161% of control). In addition, a few mice dosed with linear APFO or branched APFO at doses >1 mg/kg had increased triglyceride concentrations, resulting in increases in mean triglyceride concentrations ranging from 111-149% of control. Triglyceride concentrations of mice dosed with 30 mg/kg were either similar to controls (branched - 95% of control group mean) or somewhat less than controls (linear/branched and linear - 86% and 83% of control group mean, respectively). Organ Weights As in rats, absolute and relative liver weights were increased in mice dosed with each of the test materials (Table 3 and Figure 2). Absolute liver weights were significantly increased in mice dosed with >3 mg/kg of each of the three test materials; maximum mean absolute liver weights occurred at doses of 10 or 30 mg/kg. Relative liver weights were increased (variable statistical significance) in a dose-related manner in mice dosed with >0.3 mg/kg of each of the three test materials. Maximum relative liver weights occurred at doses of 30 mg/kg for each test material; means were 356, 325, and 409% of control means for linear/branched, linear, and branched, respectively. -21 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 A few instances of statistically significant decreases in absolute or relative kidney weights were observed with linear and linear/branched APFO. Overall, the magnitudes of the alterations were small when normalized for body weight, did not show a dose-dependent effect, and thus were considered to be unrelated to treatment with the test materials. Hepatic Peroxisomal P-Oxidation Similar to the effects observed in rats, each of the three forms of APFO caused statistically significant increases in hepatic P-oxidation activity in mice (Table 4). Statistically significant increases in hepatic p-oxidation were observed at doses of >0.3 mg/kg for linear/branched and linear APFO and >1 mg/kg for branched APFO. The magnitude of the increases was not proportional to the dose administered as the greatest increase was seen at a dose of 1 or 3 mg/kg rather than at 30 mg/kg. Linear/branched and linear APFO caused similar increases in hepatic p-oxidation at 1 and 3 mg/kg (263-273% and 280-287% of control, respectively, for the two test materials), while branched APFO caused the greatest increase at 3 mg/kg (245% of control). Overall, increases in hepatic p-oxidation were of similar magnitude for each of the three APFO test materials. Serum PFOA Concentration In the mouse, PFOA serum concentrations increased with increasing dose (Table 5 and Figure 4). The serum concentrations at a given dose of each test material appeared similar, and, like the rat, concentrations of PFOA in mice dosed with linear APFO were higher than those of mice dosed with the other two test materials following exposure to 10 or 30 mg/kg. In mice dosed with linear/branched APFO, the ratio of linear to branched PFOA in the serum increased from 4.1 at a dose of 0.3 mg/kg to 9.9 at a dose of 30 mg/kg. With branched APFO, the ratio of Branch A to Branch B increased from 1.4 at a dose of 0.3 mg/kg to 5 at a dose of 30 mg/kg. Regression Analysis Regression analysis results for mice did not differ when analyzed by administered dose or serum PFOA concentration. The regression analysis confirmed the results of pair-wise statistical tests. DISCUSSION The purpose of the current study was to determine if there are substantial differences in the toxicity profile, based on selected endpoints, among the three isomeric forms of APFO (linear/branched, linear, and branched). For completeness, both rats and mice were utilized, and a wide range of doses was employed. Because linear/branched APFO is 78% linear APFO, we hypothesized that the toxicity profile of linear/branched and linear APFO would be similar. To determine the contribution of branched APFO to the toxicity of linear/branched APFO, we synthesized a form of APFO that was 100% branched. Body weight and nutritional parameters, organ weights, and hepatic P-oxidation results in this study were consistent with those of previous studies conducted with linear/branched APFO (reviewed in Kennedy et al., 2004). Branched APFO had the least effect on body weight, body weight gain, and food consumption for both rats and mice - 22- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Ratsand Mice Revision Number 1 DuPont-14162 compared to both the linear/branched and linear forms. In the rat, however, these differences were not significant when effects were compared using serum concentrations, rather than administered dose. Internal dose, defined as serum PFOA concentrations, increased with administered APFO dose for each test material. In rats given equivalent doses, branched APFO resulted in lower serum PFOA concentrations compared to the other two test materials. Possible explanations for this finding might include time of blood collection, absorption differences, or differences in urinary excretion between the branched forms and the other two forms of APFO. Differences in renal excretion of organic anions may be driven by differential affinity for organic anion transporters among the different forms of APFO, which may contribute to the lower relative serum concentrations at higher doses (Kudo and Kawashima, 2003). The ratio of linear/branched APFO administered daily to rats and mice was approximately 4:1 (80/20%). Following 14 daily doses of 0.3 mg/kg in rats, the serum ratio of linear to branched was 5:1 and this ratio became greater with dose (6.2, 6.9, 8.5, and 11:1 with doses of 1, 3, 10, and 30 mg/kg, respectively). In mice, the same trend was observed with the starting ratio of 3.8-4.4 seen in mice treated with either 0.3, 1, or 3 mg/kg and higher ratios observed with the 2 highest doses (6.6 at 10 mg/kg, 9.9 at 30 mg/kg). The reason for the changing isomer pattern is unknown. Tissue storage of APFO (either linear/branched or linear) is minimal and no particular tissue storage site appears to exist (Johnson, 1984; Kemper, 2003). However, in rats exposed orally to linear/branched APFO, the amount of branched isomer in serum decreases after cessation of dosing (DuPont, unpublished observations). Therefore, this changing isomer pattern most likely reflects altered absorption or preferential clearance of branched APFO. The branched material tested contained internal mono-methyl non-alpha branching (Branch A) and isopropyl branching (Branch B) in a ratio of 1.4:1 (58.3% Branch A :41.7% Branch B). In serum samples collected after 14 doses, the percentage of mono-methyl branching rose with escalating dose, to 2.8:1 in rats and 5.0:1 in mice receiving 30 mg/kg. Again, the reason for this shift is unknown but is most likely a reflection of changes in absorption and/or clearance of the specific isomers. The activity of hepatic p-oxidation paralleled serum PFOA concentrations in rats. The increase in activity seen with the branched material was lower than that for the other 2 materials. A 2 to 3 fold increase was seen at 30 mg/kg, the same relative increase as produced by 1 to 3 mg/kg of either the linear/branched or the linear forms. In mice, P-oxidation increases similarly for all 3 materials with a relatively flat dose response as the dose increased from 0.3 to 30 mg/kg. The actual numerical levels of P oxidation were greater in the groups receiving either 1 or 3, not 30 mg/kg. Liver weights in both species increased proportionately to dose suggesting that the liver weight increases are not due solely to peroxisomal proliferation. Given that APFO exhibits PPAR-a activity (Intrasuksri et al., 1998; Maloney and Waxman, 1999), it was expected that it would lower serum cholesterol and triglycerides levels in rats. Haughom and Spydevold (1992) reported decreases in total cholesterol (50-70% of controls) and triglycerides (60% of controls) after dietary administration of - 23- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 0.02% APFO (estimated dose of 10 mg/kg). These results are consistent with the current study. Although the dose response in our study varied among the 3 test materials, serum cholesterol concentrations in rats were decreased in the dose range (1 to 10 mg/kg) consistent with that used by Haughom and Spydevold, but were generally less affected at the highest dose (30 mg/kg). In mice, Xie et al. (2003) reported a decrease in serum cholesterol (80% of controls) in C57BL/6 mice after 7 days of dietary administration of 0.02% APFO (estimated dose of 30 mg/kg). In our study, cholesterol was decreased in mice at doses greater than 3 mg/kg, and thus the effects on cholesterol were consistent with those of Xie et al. In the same experiment, Xie also reported a decrease in serum triglycerides (estimated at 60% of controls). In our study, triglyceride concentrations in mice increased with increasing dose (up to 61% at 10 mg/kg of linear/branched), but were similar to controls or slightly decreased at 30 mg/kg. Therefore, at a similar high dose of 30 mg/kg, triglyceride concentrations were similar between the two studies. The more definitive decrease in triglyceride concentrations reported by Xie et al. may be due to effects of the route of administration (dietary), differing mouse strains, or differing durations of exposure. Serum lipid perturbations observed in rodents at high doses (30 mg/kg) of linear/branched APFO have not been observed in monkeys. Cynomolgus monkeys dosed with up to 30/20 mg/kg by gavage for up to 6 months showed no treatment-related alterations in serum lipids (Butenhoff et al., 2002). Cynomolgus monkeys are similar to humans with respect to cholesterol and triglyceride metabolism, and have been used as animal models in the development of hypolipidemic pharmacologic agents. The increase in serum triglycerides in mice at lower concentrations of APFO occurred despite increased hepatic P-oxidation. This finding suggests that in mice, but not in rats or primates, perturbations in lipid metabolism beyond those associated with PPAR-a meditated events underlie this observation. Other investigators have also noted that effects of APFO on hepatic lipid content are different from those of clofibrate, a well-characterized peroxisome proliferating agent (Kawashima et al., 1995). Although dosing with fibrates generally decreases serum cholesterol and triglyceride concentrations in rats and mice, other peroxisomal proliferators have no lipid-lowering effects (Kawashima et al., 1995). Dose-related ex vivo hemolysis in rats (but not mice) was detected in serum samples collected from the orbital sinus and vena cava. This effect was considered to be an ex vivo effect because the extensive database on APFO-exposed rats contains no indication of red cell effects despite rigorous investigation of clinical and anatomic pathology endpoints. Sensitive indicators of in vivo hemolysis (including, but not limited to, increased splenic weights, increased extramedullary hematopoiesis, increased splenic pigment, decreased red cell mass, increased reticulocytes, increased mean cell volume, and decreased mean cell hemoglobin concentration) have never been affected in any previous toxicity study conducted with APFO. Therefore, hemolysis observed in serum from rats most likely resulted from a test-material related increase in fragility of red cells ex vivo during blood collection and/or processing. - 24- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_________________________________________ DuPont-14162 Acanthocytes were observed on some blood smears of rats on this study. Acanthocytes are red blood cells with irregular projections, thought to arise as a result of asymmetry between the lipid bilayer hemileaflets of red blood cells (Bull, 2000). They have been associated with altered lipid content of the red cell lipid bilayer, because lipid content of mammalian erythrocytes is reflective of plasma lipid concentrations. Other shape changes (poikilocytes or schistocytes) were observed occasionally on some blood smears of rats on this study. Both of these shape changes were only present in trace amounts and did not appear to have any effect on red cell survival. The morphologic changes were similar with each test material. These morphologic changes, as well as ex vivo hemolysis, were likely due to alterations in plasma lipids. A wide variety of endpoints were examined in rats and mice using a range of doses from 0.3 to 30 mg/kg. For each endpoint the lowest dose tested producing an effect (LOEL) was determined for each of the 3 materials (Table 6). In rats, the LOEL was 1 mg/kg for linear/branched and branched, and 0.3 mg/kg for linear, based on reductions in total cholesterol and triglycerides. In mice, the LOEL was 0.3 mg/kg for all materials, based on liver weight changes and hepatic P-oxidation (and on increases in triglycerides with the linear/branched material). These LOEL doses correspond to serum PFOA levels of approximately 20-50 pg/mL (ppm) in rats and approximately 10-15 pg/mL in mice. In conclusion, the toxicity profile of linear/branched APFO and linear APFO was similar for the endpoints measured in rats and mice. The observations in this experiment were similar to those seen in other rodent studies. Internal dose, as determined by serum PFOA concentrations, increased with dose for each APFO test material. In rats, branched APFO resulted in considerably lower serum PFOA concentrations compared to the other two test materials. These lower serum PFOA concentrations also correlated with lower hepatic P-oxidation levels. At the highest dose, the ratio of linear to branched forms in serum was twice that of the administered test material, and the ratio of the internal monomethyl isomer to the isopropyl more than doubled. In rats and mice, serum cholesterol generally decreased with increasing doses of test material. In rats, serum triglyceride concentrations decreased with increasing doses of test material. However, in mice, triglyceride concentrations increased up to doses of 10 mg/kg, then decreased at 30 mg/kg. In both rats and mice, the overall responses to the linear/branched and the linear forms of PFOA were similar, but the branched form appears to be less potent. Based on these results, the toxicological database developed primarily from testing linear/branched APFO is applicable to linear APFO. ACKNOWLEDGMENTS The authors would like to thank Dr. John W. Green for his statistical analysis of the data and Charlene Smith and Diana Ritchie for their expert technical assistance. - 25- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 REFERENCES Bradford, M.M. (1976). ARapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem. 72, 248-254. Bull, B.S. (2000). Morphology of the erythron. In Williams' Hematology (E. Beutler, M.A. Lichtman, B.S. Collier, T.J. Kipps, and U. Seligsohn, Eds) 6thed., Chapter 22, McCraw-Hill Publishers, NY, NY. Butenhoff, J., Costa, G., Elcombe, C., Farrar, D., Hansen, K., Iwai, H., Jung, R., Kennedy, G., Lieder, P., Olsen, G., Thomford, P. (2002): Toxicity of ammonium perfluorooctanoate (APFO) in male Cynomolgus monkeys after oral dosing for six months. Toxicol. Sci. 69, 244-257. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6 ,241-252. Dunnett, C.W. (1964). New tables for multiple comparisons with a control. Biometrics 20,482-491. Dunnett, C.W. (1980). Pairwise multiple comparisons in the unequal variance case. J. Amer. Statist. Assoc. 75, 796-800. Flaherty, J. M., et al. (2005). Quantitative determination of perfluorooctanoic acid (PFOA) in serum and plasma by liquid chromatography tandem mass spectrometry. J. Chromatogr. B., manuscript submitted. Hansen, K.J., Clemen, L.A., Ellefson, M.E., Johnson, H.O. (2001). Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ. Sci. Technol. 35, 766-770. Haughom B. and Spydevold O. The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. Biochim Biophys Acta. 1992 Sep 22; 1128(l):65-72. Intrasuksri, U., Rangwala, S.M., O'Brien, M., Noonan, D.J., and Feller, D. (1998). Mechanisms of peroxisome proliferation by perfluorooctanioic acid and endogenous fatty acids. Gen. Pharmacol. 31:187-197. Johnson, J.D., Gibson, S.J., and Ober, R.E. (1984). Cholestyramine-enhanced fecal eliminationof carbon-14 in rats after administration of ammonium [14-C]perfluorooctanoate or potassium [14C] perfluorooctanesulfonate. Fund. Applied Tox. 4(6):972-976. Kalliomaa, K., Haag-Groenlund, M., Victorin, K. (1998). A new model function for continuous data sets in health risk assessment of chemicals using the benchmark dose concept. Regul. Toxicol. Pharmacol. 27,98-107. - 26- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice __________ Revision Number 1 DuPont-14162 Kawashima, Yoichi; Kobayashi, Hiromi; Miura, Hiroaki; Kozuka, Hiroshi. (1995). Characterization of hepatic responses of rat to administration of perfluorooctanoic and perfluorodecanoic acids at low levels. Toxicology 99(3), 169-78. Kemper, R.A. (2003). Perfluorooctonanoic acid: Toxicokinetics in the rat. USEPA Administrative Record 226-1499. Kennedy, G.L., Butenhoff, J.L., Olsen, G.W., O'Connor, J.C., Seacat, A.M., Perkins, R.G., Biegel, L.B., Murphy, S.R. (2004). The toxicology of perfluorooctanoate. Crit. Rev. Toxicol 34:351-384. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. Kudo, N. and Kawashima, Y. (2003). Toxicity and toxicokinetics of perfluoorooctanoic acid in humans and animals. J. Tox. Sci. 28,49-57. Lazarow, P.B. (1981). Assay of Peroxisomal Beta-Oxidation of Fatty Acids. Methods in Enzymology 72, 315-319. Levene, H. (1960). Robust test for equality of variances. In Contributions to Probability and Statistics (J. Olkin, Ed.), pp 278-292. Stanford University Press, Palo Alto. Maloney, E.K. and Waxman, E.J. (1999) trans-Activation of PPAR-a and PPAR-yby structurally diverse environmental chemicals. Toxicol. Applied Pharmacol. 161:209-218. Olsen, G.W., Gilliland, F.D., Burlew, M.M., Burris, J.M., Mandel, J.S., Mandel, H. (1998). An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J. Occup. Environ. Med. 40, 614-620. Olsen, G.W., Burris, J.M., Burlew, M.M., Mandel, J.H. (2000). Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem. Toxicol. 23, 603-620. Pack, S. (1993). A review of statistical data analysis and experimental design in OECD aquatic toxicology test guidelines. Shell Research Ltd., Sittingbourne Research Centre, Sittingbourne, Kent, ME9 8AG, U.K. Searle, S. R., Casella, G., McCulloch, C.E. (1992). Variance Components, Wiley, New York. See, K.and Baylor, A. J. (1998). Added risk and inverse estimation for count responses in reproductive aquatic toxicology studies, Biometrics 54, 67-73. APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Shapiro, S.S. and Wilk, M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. Slob, Wout (2002). Dose-Response Modeling of Continuous Endpoints, Toxicol. Sci. 66,298-312. Snedecor, G.W. and Cochran, W.G. (1967). In Statistical Methods, 6thedition, pp 246-248 and 349-352. The Iowa State University Press, Iowa. Taves, D., Guy, W., Brey, W. (1976). Organic fluorocarbons in human plasma: prevalence and characterization. In: Biochemistry Involving Carbon-Fluorine Bonds (R. Filler, Ed.), pp. 117-134. American Chemical Society, Washington, DC. Ubel, F.A., Sorenson, S.D., Roach, D.E. (1980). Health status of plant workers exposed to fluorochemicals--a preliminary report. Am. Ind. Hyg. Assoc. J. 41, 584-589. USEPA. (2002). Revised draft. Hazard assessment of perfluorooctanoic acid and its salts. USEPA Public Docket AR-226. Vanden Heuvel, J., Kuslikis, B., Van Rafelghem, M. (1991). Tissue distribution, metabolism, and elimination of perfluorooctanoic acid in male and female rats. Biochem. Toxicol. 6, 83-92. Xie, Y., Yang, Q., Nelson, B.D., and DePierre, J.W. (2003). The relationship between liver peroxisome proliferation and adipose tissue atrophy induced by peroxisome proliferator exposure and withdrawal in mice. Biochem. Pharmacol. 66: 749-756. - 28- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 FIGURES - 29- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Manuscript Figure 1 Rat and Mouse Serum Triglyceride Concentrations 260 240 ... B-- Linear/ B ran ch ed -R at -- - Linear-R at 220 - - B ran ch ed -R at A Linear/ Branched-M ouse 200 1) E, 180 - A - Linear-M ouse - "A - B ranched-M ouse c o '(M0 160 '* c*-< 140 <ocou a 120 o ,, ** * 9 0 ^ ^ ^ . c 1 " " * -. -....... ..... ....... i ~ ! * X --i ^ i' m a a a *m -- : 0) 100 : . * # ak & * * H S ^L * " 1 -- ---------p r T -- - -- - -- ^----- ------- --------- v -- s\ **\ i \\ z o> 80 O) u 60 I- K IB m " m * m 40 m m *,--1819 m i I __ j 6____________________ -- r - - - -- --- --------------------------------------- -------------------------- i 20 0 10 100 Dose (mg/kg) - 30- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Manuscript Figure 2 Rat and Mouse Liver Weight/Body Weight Revision Number 1 DuPont-14162 -31 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Manuscript Figure 3 Rat Hepatic p-Oxidation Concentrations Revision Number 1 DuPont- 4 162 - 32- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Manuscript Figure 4 Rat and Mouse Serum PFOA Concentrations 300 250 200 3o> co2 150 n o 100 O o <ou. 0. Dose (mg/kg) 10 Revision Number 1 DuPont-14162 100 - 33- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 TABLES -34- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Manuscript Table 1 Mean Body Weights and Body Weight Gains in Rats and Mice Treated with Various Forms of APFO Rats Dose (mg/kg) 0 Test M aterial Linear/Branched Linear Branched Day 0 268 13a 285 12 285 11 Day 7 321 21 331 14 328 20 0.3 Linear/Branched 268 9 315 9 Linear 282 11 324 14 Branched 284 16 328 25 1 Linear/Branched 270 10 322 11 Linear 280 15 321 23 Branched 289 11 338 24 3 Linear/Branched 272 11 326 20 Linear 280 11 317 14 Branched 285 7 322 14 10 Linear/Branched 268 14 296 27 Linear 281 14 310 17 Branched 282 9 321 15 30 Linear/Branched 268 12 233 37* Linear 281 14 230 38* Branched 284 13 314 14 * Statistically significant difference from control (p<0.05). a Mean standard deviation. Day 13 354 25 363 13 357 25 346 13 353 20 359 33 351 15 349 32 367 31 356 29 339 16 348 19 315 35 339 18 348 15 287 13* 293 22* 339 19 Weight Gain Day 0-13 86 14 78 9 72 16 78 9 70 15 75 19 81 13 69 21 78 22 84 21 59 14* 64 14 47 26* 58 17 67 10 19 16* 12 18* 55 7* Day 0 31 2 31 1 32 2 31 2 31 2 31 1 32 1 32 1 32 1 32 2 32 2 32 1 32 1 31 1 32 2 31 1 31 1 32 2 Revision Number 1 DuPont-14162 M ice Day 7 32 2 31 2 32 2 32 2 32 2 33 2 32 3 34 1 33 2 33 3 32 3 34 1 32 1 32 2 34 2 27 2* 26 2* 32 2 Day 13 33 2 33 1 33 2 33 2 33 2 34 2 34 3 34 1 34 2 34 3 34 4 35 1* 29 2* 30 3 35 2* 26 2* 27 2* 32 2 Weight Gain Day 0-13 2 1 1 1 1 1 11 1 1 2 1 12 2 1 2 1 2 1 23 3 1* -2 3* -1 3 3 2* -6 1* -4 3* 0 1 - 35- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Manuscript Table 2 Summary of Clinical Chemistry Values in Rats and Mice Treated with Various Forms of APFO Dose (mg/kg) 0 Test Material Linear/Branched Linear Branched Cholesterol (mg/dL) 51 14a 45 10 46 8 0.3 Linear/Branched 49 13 Linear 33 10* Branched 42 6 1 Linear/Branched 33 10 Linear 29 11* Branched 36 9* 3 Linear/Branched 23 7* Linear 25 4* Branched 27 8* Rats HDL Non-HDL (mg/dL) (mg/dL) 21 4 30 11 19 4 25 6 20 3 26 5 Triglycerides (mg/dL) 61 22 53 11 45 18 21 4 16 3 19 2 28 9 17 7* 23 5 51 12 42 10* 45 14 16 3 15 4 17 4 17 7* 14 7* 18 6 40 15* 36 7* 40 15 11 3* 11 2* 14 2* 12 5* 13 3* 13 6* 41 13 38 9* 28 6 Cholesterol (mg/dL) 145 21 150 25 146 22 Mice HDL (mg/dL) Non-HDL (mg/dL) 97 12 Al 10 95 16 56 11 94 13 52 10 Triglycerides (mg/dL) 99 14 103 31 134 22 137 24 147 38 125 26 90 12 90 19 77 10 47 14 57 20 48 20 136 20* 125 35 118 28b 138 33 139 20 127 39 81 14 78 10 79 18 57 21 61 13 48 22 145 27* 137 22 161 44 97 23* 97 24* 96 26* 55 11* 51 7* 62 13* 42 15 46 20 34 13* 140 31* 137 38 149 48 10 Linear/Branched 36 22* Linear 27 7* Branched 26 10* 12 4* 11 7* 13 4* 24 19 16 5* 13 6* 31 8* 42 12 25 8* 114 44 116 32 120 43 69 27* 64 15* 67 21* 45 17 52 19 54 23 159 38* 135 50 200 57 30 Linear/Branched 41 6 Linear 41 15 Branched 34 8* 14 2* 15 5 16 3* 26 4 26 10 19 5 36 +1* 41 9* 24 3* 88 32* 101 33* 113 17 49 17* 56 19* 67 12* 39 16 45 15 46 7 85 30 86 16 127 30 * Statistically significant difference from control (p<0.05). a Mean standard deviation, b Excludes one animal considered to be an outlier. - 36- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Manuscript Table 3 Liver and Kidney Weights and Liver and Kidney to Body Weight Ratios in Rats and Mice Treated with Various Forms of APFO Dose (mg/kg) 0 Test M aterial Linear/Branched Linear Branched Liver Wt (g) 11.18 1.78* 12.09 0.96 11.05 1.43 Rats Liver/Body Wt (g/100g) 3.43 0.40 3.63 0.35 3.38 0.29 Kidney Wt (g) 2.84 0.25 2.89 0.27 2.63 0.29 Kidney/Body Wt (g/100g) 0.88 0.05 0.87 0.06 0.80 0.06 0.3 Linear/Branched 11.57 0.99 3.63 0.23 2.76 0.21 0.86 0.05 Linear 12.54 1.09 3.86 0.14 2.72 0.59 0.83 0.15 Branched 11.73 1.52 3.58 0.27 2.72 0.34 0.83 0.07 1 Linear/Branched 12.72 1.00 3.94 0.20* 2.91 0.31 0.90 0.07 Linear 13.41 2.16 4.13 0.33* 2.83 0.17 0.88 0.08 Branched 13.14 1.75* 3.91 0.33* 2.79 0.31 0.83 0.06 3 Linear/Branched 17.92 2.33* 5.42 0.39* 3.14 0.23* 0.96 0.06* Linear 15.42 1.20* 4.94 0.23* 2.88 0.29 0.92 0.07 Branched 14.02 1.24* 4.41 0.37* 2.70 0.25 0.85 0.06 10 Linear/Branched 16.29 1.72* 5.67 0.52* 2.62 0.27 0.91 0.06 Linear 18.81 1.85* 6.03 0.41* 2.94 0.23 0.94 0.06 Branched 18.55 2.81* 5.77 0.75* 2.84 0.27 0.88 0.07* 30 Linear/Branched 17.67 1.54* 6.82 0.56* 2.49 0.19* 0.96 0.08* Linear 17.41 1.59* 6.64 0.51* 2.42 0.19* 0.92 0.07 Branched 19.82 2.62* 6.37 0.70* 2.72 0.21 0.88 0.05* * Statistically significant difference from control (p<0.05). a Mean standard deviation. Liver Wt (g) 1.64 0.11 1.70 0.12 1.62 0.14 M ice Liver/Body W t(g/100g) 5.14 0.27 5.52 0.24 5.14 0.31 Kidney Wt (g) 0.50 0.04 0.56 0.05 0.52 0.04 Kidney/Body W t(g/100g) 1.57 0.16 1.84 0.16 1.64 0.16 1.92 0.14 2.00 0.11 1.95 0.19 6.12 0.25 6.45 0.23* 6.12 0.34* 0.54 0.07 0.53 0.03 0.55 0.04 1.73 0.18 1.71 0.09 1.72 0.15 2.55 0.15 7.92 0.49 2.73 0.14* 8.33 0.31* 2.53 0.26 7.85 0.85* 0.54 0.06 0.56 0.08 0.55 0.05 1.66 0.15 1.72 0.19 1.69 0.12 3.47 0.35* 10.72 0.63* 3.70 0.49* 11.37 1.06* 4.03 0.32* 11.94 0.83* 0.54 0.07 0.57 0.09 0.53 0.06 1.66 0.15 1.74 0.18 1.58 0.18 4.61 0.42* 16.27 1.05* 4.83 0.71* 17.18 1.13* 5.90 0.63* 17.71 1.81* 0.45 0.04 0.46 0.08* 0.54 0.04 1.60 0.08 1.63 0.17* 1.63 0.10 4.56 0.58* 18.28 1.57* 4.64 0.51* 17.96 1.06* 6.51 0.65* 21.01 1.40* 0.40 0.05* 0.44 0.06* 0.48 0.05 1.60 0.14 1.70 0.17 1.57 0.11 - 37- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Manuscript Table 4 Summary of Hepatic p-Oxidation Activity in Rats and Mice Treated with Various Forms of APFO Dose (rng/kg) 0 Test Material Linear/Branched Linear Branched Rats Beta-Oxidation Activity (nmol/min/mg protein) 18.2 3.8a 15.7 3.6 13.0 3.3 Mice Beta-Oxidation Activity (nmol/min/mg protein) 17.9 5.7 17.3 4.1 18.2 4.3 0.3 Linear/Branched Linear Branched 18.0 3.7 16.0 3.1 12.9 3.8 34.4 7.4* 42.0 10.8* 24.2 3.7 1 Linear/Branched 27.0 4.3* Linear 29.8 5.6* Branched 15.4 3.1 48.8 8.9* 49.6 11.4* 36.9 10.2* 3 Linear/Branched 57.6 10.0* Linear 67.5 14.3* Branched 17.4 3.5* 10 Linear/Branched 82.2 18.1* Linear 74.8 10.1* Branched 28.7 8.0* 47.1 7.1* 48.5 10.0* 44.5 8.5* 31.6 7.4* 37.2 9.0* 42.5 4.4* 30 Linear/Branched 84.7 16.3* Linear 89.0+13.6* Branched 37.6 12.2* * Statistically significant difference from control (p<0.05). a Mean standard deviation. 30.7 8.2* 31.9 + 4.5* 35.4 9.7* Revision Number 1 DuPont-14162 - 38- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Manuscript Table 5 Serum PFOA Concentrations in Rats and Mice Treated with Various Forms of APFO Dose (mg/kg) 0 Mean SD Test Substance (pg/ml) Linear/Branched 0.37 0.14 Linear 0.39 0.51 Branched 0.11 0.24a Rats Linear/ Branched Ratio* Branch A/ Branch B Ratio** Mean SD (pg/ml) 0.04 0.02 0.07 0.06 0.02 0.03 Mice Linear/ Branched Ratio* Branch A/ Branch B Ratio** 0.3 Linear/Branched 19 2.5 Linear 20 3.2 Branched 16 3.2 5.1 1.1 - - -- 1.3 0.16 1 Linear/Branched 51 10 6.2 1.4 -- Linear 65 11 - - Branched 48 12 - 1.7 0.35 10 1.4 13 2.4 14 3.5 27 5.0 32 5.2 34 10 4.1 0.50 - 3.8 0.49 - -- 1.4 0.29 -2.1 0.38 3 Linear/Branched 106 10 6.9 0.85 -- Linear 137 18 - - Branched 73 25 - 2.0 0.26 10 Linear/Branched 183 46 8.5 0.68 -- Linear 206 65 - - Branched 92 20 -- 2.0 0.37 66 8.6 69 10 82 10 190 29 225 68 172 29 4.4 0.48 - 6.6 1.1 - 3.0 0.36 -- 3.4 0.52 30 Linear/Branched 208 51 Linear 223 77 Branched 124 33 * Ratio of material administered was 3.5 ** Ratio of material administered was 1.4 11 3.5 - -- 2.8 0.38 241 28 259 34 244 50 9.9 0.84 - -- 5.0 1.1 a Five of the 10 serum samples labeled as controls could not conclusively be linked to the appropriate animals and were therefore excluded from the calculation of the mean. - 39- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Manuscript Table 6 Summary of Effects in Rodents Dosed with APFO Low Observed Effect Level (mg/kg) Endpoint Rats LOEL (mg/kg) Mice LOEL (mg/kg) Survival Clinical Signs Body Weight Food Consumption Hemolysis - Vena Cava Red Cell Morphology Relative Liver Weight p-Oxidation Total Cholesterol Non-HDL Cholesterol HDL Cholesterol Triglycerides3 L/B L B L/B L B >30 >30 >30 >30 30 >30 >30 >30 >30 >30 30 >30 10 3 30 10 10 >30 10 3 >30 30 30 >30 3 3 10 NE NE NE 3 3 10 NE NE NE 1 1 1 0.3 0.3 0.3 1 1 3 0.3 0.3 0.3 1 0.3 1 3 3 3 13 1 >30 >30 >30 33 3333 1 0.3 1 0.3 1 1 Overall LOEL 1 0.3 1 0.3 0.3 0.3 Serum PFOA at LOEL (pg/ml) 51 20b 48 10 13 14 L/B = linear/branched APFO L = linear APFO B = branched APFO NE = not evaluated a decreased in rats; increased in mice b serum PFOA at 1 mg/kg was 65 pg/ml Revision Number 1 DuPont-14162 -40- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 RAT TABLES -41 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice RAT TABLES EXPLANATORY NOTES H-24921 APFO (Linear/Branched) STUDY DESIGN Groups H-26313 H-26225 APFO (Linear) APFO (Branched) IA IIIA VA VIIA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Revision Number 1 DuPont-14162 Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day Summary of Clinical Chemistry Values CHOL - cholesterol TRIG - triglycerides HDL - high-density lipoprotein cholesterol nonHDL - non-high-density lipoprotein cholesterol NOTES: Summary of Clinical Chemistry Values Groups with identical values may vary in statistical significance, because tabulated statistics are rounded to fewer decimal places than the values used for statistical determination. - 42- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 1 Homogeneity/Concentration Verification and Stability Analysis for Rat Study Sample Sample Day H-24921 15-Mar-2004 Nominal mg/mL Measureda mg/mL 0 NDC 0.03 0.029, 0.029 0.10 0.098,0.095 3.0 2.84, 2.69 Mean C.V. Stability15 % Nominal (%) % Nominal -- ---- 96.7 0 96.7 97.0 2 91.0 92.2 4 87.3d H-26313 16-Mar-2004 H-26225 17-Mar-2004 0 NDC 0.03 0.030,0.029 0.10 0.090, 0.102 3.0 2.75, 2.94 0 NDC 0.03 0.029, 0.031 0.10 0.112,0.105 3.0 2.72, 2.91 --- -- -- 96.7 2 100.0 96.0 8 97.0 95.0 5 97.0 -- ---- 100.0 4 103.3 109.0 5 104.0 94.0 5 103.0 a Mean results for the analysis of the duplicate samples, b Samples held 5 hours at room temperature, c Denotes none detected. d Reported results based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. -43- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 2 Recovery of H-24921, H-26313, H-26225 Added to Dosing Vehicle for Rat Study Sample Type Re c o v e r y (A) Recovery Recovery mg/mL Nominal Measured 0.030 0.033 0.030 0.032 0.030 0.30 M ean Percent Nominal 110.0 106.7 100.0 105.6 5.1, C.V. 5% Re c o v e r y Rec o v er y(B) Recovery 0.10 0.103 103.0 0.10 0.097 97.0 0.10 0.100 100.0 M ean 100.0 3.0, C.V.0.03% Recovery Rec o v er y (B) Rec o v e r y (C) 3.00 2.69 89.7 3.00 2.72 90.7 3.00 2.94 98.0 M ean 92.8 4.5, C .V .5 % (A)Processed with H-24921 samples from dosing prepared on March 15, 2004. (B) Processed with H-26313 samples from dosing prepared on March 16, 2004. (C) Processed with H-26225 samples from dosing prepared on March 17, 2004. - 44- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Rat Study Test Substance Sample Date H-24921 (3/15/04) Control Nominal mg/mL Measured 0.00 n d (a ) Percent Nominal -- #1 #2 #1 #2 #1 #2 5 Hour(c ) 0.03 0.03 0.10 0.10 3.00 3.00 0.03 0.10 3.00 0.029 0.029 Mean<&: 0.029 0.00 C.V. 0% 0.098 0.095 M ean(B).- 0.097 0.002 C.V. 2% 2.84 2.69 M ea n ^h 2.770.10 C.V. 4% 0.029 0.091 2.62(D) 96.7 96.7 (96.7%) 98.0 95.0 (97.0%) 94.7 89.7 (92.2%) 96.7 91.0 87.3 H-26313 (3/16/04) Control #1 #2 #1 #2 #1 #2 5 HOUr(C) 0.00 0.03 0.03 0.10 0.10 3.00 3.00 0.03 0.10 3.00 n d (a ) 0.030 0.029 Mean&l- 0.029 0.001 C.V. 2% 0.090 0.102 M e a n ^ h 0.096 0.008 C.V. 8% 2.75 2.94 Mean(); 2.85 0.13 C.V.5% 0.030 0.097 2.91 -- 100.0 96.7 (96.7%) 90.0 102.0 (96.0%) 91.7 98.0 (95.0%) 100.0 97.0 97.0 - 45- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Rat Study (Continued) Test Substance __________________ mg/mL__________________ Percent Sample Date____________ Nominal______________ Measured_______________ Nominal H-26225 (3/17/04) Control 0.00 n d (a ) -- #1 #2 #1 #2 #1 #2 5 Hour(c ) 0.03 0.03 0.10 0.10 3.00 3.00 0.03 0.10 3.00 0.029 0.031 MeantB). 0.0300.001 C.V. 4% 0.112 0.105 M e a n ^ h 0.109 _0.005 C.V. 5% 2.72 2.91 M e a n ^ h 2.82 + 0.13 C.V. 5% 0.031 0.104 3.09 96.7 103.3 (100.0%) 112.0 105.0 (109.0%) 90.7 97.0 (94.0%) 103.3 104.0 103.0 (A) Denotes none detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples. (C) Stability samples held 5 hours a room temperature. (D) Reported result based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. - 46- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 4 Summary of Dosing Suspension Analyses for Rat Study Sample Type Concentration H-24921 (3/15/2004) #1 #2 Average Measured Cone*5 Average Percent Nominal*5 Standard Deviation*5 Coefficient of Variation*5 Stability 5-hour Room Temperature Concentration H-26313 (3/16/2004) #1 #2 Average Measured Cone*5 Average Percent Nominal*5 Standard Deviation*5 Coefficient of Variation*5 Stability 5-hour Room Temperature Concentration H-26225 (3/17/2004) #1 #2 Average Measured Cone*5 Average Percent Nominal*5 Standard Deviation*5 Coefficient of Variation*5 Concentrations and Stability of H-24921, H-26313, H-26225 (mg/mL) Nominal: 0.03 0.10 3.00 0.029 (96.7)a 0.029 (96.7) 0.029 (96.7) 0.00 0% 0.029 (96.7) 0.098 (98.0) 0.095 (95.0) 0.097 (97.0) 0.002 2% 0.091 (91.0) 2.84 (94.7) 2.69 (89.7) 2.77 (92.2) 0.10 4% 2.62c (87.3) 0.030 (100.0) 0.029 (96.7) 0.029 (96.7) 0.001 2% 0.030 (100.0) 0.029 (96.7) 0.031 (103.3) 0.030 (100.0) 0.001 4% 0.090 (90.0) 0.102 (102.0) 0.096 (96.0) 0.008 8% 0.097 (97.0) 0.112 (112.0) 0.105 (105.0) 0.109 (109.0) 0.005 5% 2.75 (91.7) 2.94 (98.0) 2.85 (95.0) 0.13 5% 2.91 (97.0) 2.72 (90.7) 2.91 (97.0) 2.82 (94.0) 0.13 5% Stability 5-hour Room Temperature 0.031 0.104 3.09 (103.3) (104.0) (103.0) a Numbers in parentheses are the respective percent of nominal values. b The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples. c Reported result based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. - 47- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group : Dosage(mg/kg) DAYO DAY1 DAY2 DAY 3 DAY 4 DAY 5 DAY6 DAY7 DAY 8 DAY9 DAY10 DAY11 DAY12 Table 5 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear/Branched) IA 0 268.2 13.3(10) 275.6 13.5(10) 283.7 15.0(10) 291.8 14.6(10) 299.5 16.9(10) 306.1 17.1(10) 314.5 17.9(10) 320.7 21.0(10) 328.0 19.8(10) 334.1 19.7(10) 338.9 20.7(10) 345.9 22.6(10) 349.0 22.0(10) IIIA 0.3 267.9 9.1(10) 271.4 8.6(10) 279.0 8.1(10) 287.2 7.9(10) 295.0 8.4(10) 300.2 9.3(10) 308.8 9.1(10) 315.4 9.4(10) 319.8 9.3(10) 327.9 10.8(10) 332.3 10.9(10) 337.3 11.2(10) 341.2 11.9(10) VA 1 270.0 10.4(10) 275.2 10.4(10) 283.5 10.5(10) 292.2 11.8(10) 299.5 10.5(10) 304.8 10.4(10) 315.3 1 1 . 3 (10) 321.5 10.6(10) 326.9 11.1(10) 333.2 11.3(10) 338.9 11.4(10) 344.4 14.2(10) 347.1 15.9(10) VI IA 3 271.9 10.5(10) 275.7 12.0(10) 286.3 13.5(10) 294.0 14.2(10) 301.7 14.6(10) 308.3 16.4(10) 316.6 18.8(10) 325.7 20.1(10) 331.9 21.9(10) 338.9 23.4(10) 343.9 23.6(10) 350.7 24.8(10) 351.7 26.1(10) IXA 10 268.0 13.8(10) 271.7 14.9(10) 279.0 15.1(10) 283.6 17.2(10) 284.5 17.0(10) 289.5 20.1(10) 294.1 23.7(10) 295.9 26.5(10) 300.1 30.7(10) 304.1 34.0(10) 305.8 37.1(10) 307.5 41.5(10) 310.4 37.0(10) Revision Number 1 DuPont-14162 XIA 30 268.0 12.0(10) 266.7 11.1(10) 261.70 12.3(10) 249.0* 13.7(10) 233.40 14.5(10) 227.6* 21.7(10) 226.5* 32.1(10) 233.2* 36.7(10) 248.2* 28.5(10) 258.7* 24.0(10) 266.2* 20.2(10) 277.2* 16.8(10) 282.0* 13.2(10) - 48- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY13 DAY14 Table 5 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear/Branched) (Continued) XA 0 353.8 25.0(10) 324.9 21.5(10) IIIA 0.3 345.6 12.6(10) 319.0 11.8(10) VA 1 350.8 15.3(10) 322.8 15.8(10) VIIA 3 355.9 28.6(10) 329.8 25.7(10) IXA 10 314.7 35.0(10) 288.7 33.3(10) XIA 30 286.7* 13.0(10) 258.9* 10.5(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. -49- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group: Dosage(mg/kg) DAYO DAY1 DAY2 DAY 3 DAY4 DAY 5 DAY 6 DAY7 DAY 8 DAY 9 DAY10 DAY11 DAY12 Table 6 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear) IB 0 284.6 12.3(10) 290.3 12.0(10) 297.1 11.5(10) 306.0 13.4(10) 311.6 13.7(10) 315.6 13.6(10) 327.8 14.3(10) 331.3 14.2(10) 341.0 12.9(10) 343.7 13.5(10) 350.0 13.9(10) 353.0 14.7(10) 356.4 13.8(10) IIIB 0.3 282.2 11.1(10) 286.2 11.3(10) 293.5 11.6(10) 299.9 12.0(10) 305.7 13.5(10) 312.8 13.5(10) 320.4 14.2(10) 323.9 14.4(10) 331.4 15.3(10) 333.4 16.9(10) 341.1 17.5(10) 341.7 18.8(10) 346.8 19.7(10) VB 1 279.7 14.6(10) 283.7 14.8(10) 291.1 14.9(10) 296.4 16.5(10) 301.5 19.-4(10) 308.3 21.0(10) 317.1 22.8(10) 321.0 22.9(10) 327.3 24.3(10) 332.2 30.5(10) 336.9 28.6(10) 338.8 30.5(10) 342.1 32.4(10) VIIB 3 279.7 11.4(10) 284.2 11.1(10) 289.9 11.2(10) 294.9 11.7(10) 300.6 12.2(10) 305.2 13.1(10) 312.4 14.1(10) 317.1 13.6(10) 320.7 13.3(10) 325.9 14.6(10) 329.5 15.1(10) 331.2 17.3(10) 334.2 15.0(10) IXB 10 281.1 13.9(10) 284.7 14.9(10) 292.3 14.8(10) 299.2 14.9(10) 302.9 14.4(10) 305.8 12.1(10) 308.4 14.0(10) 310.0 17.2(10) 318.5 22.7(10) 323.9 1 8 . 5 (10) 327.9 18.0(10) 329.2 17.3(10) 333.8 17.6(10) XIB 30 281.0 13.5(10) 280.2 13.1(10) 270.5* 15.1(10) 255.4* 16.7(10) 240.0* 16.9(10) 230.6* 25.0(10) 228.1* 31.9(10) 229.6* 38.0(10) 244.6* 36.2(10) 255.2* 32.2(10) 266.4* 29.1(10) 276.8* 26.2(10) 284.5* 2 4 . 4 (10) -50- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group: Dosage(mg/kg) DAY13 DAY 14 Table 6 Mean Body Weights (g) of Male Rats Dosed with APFO (Linear) (Continued) IB 0 362.8 13.1(10) 333.5 12.1(10) IIIB 0.3 352.7 20.0(10) 324.8 19.2(10) VB 1 348.9 32.5(10) 323.4 30.5(10) VI IB 3 339.0 16.1(10) 311.6 14.5(10) IXB 10 339.4 18.4(10) 311.9 16.7(10) XIB 30 292.5* 21.7(10) 262.7* 22.4(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. -51 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice______ ______ Revision Number 1 DuPont-14162 Group: Dosage(mg/kg) DAYO DAY1 DAY2 DAY3 DAY4 DAY 5 DAY 6 DAY7 DAY 8 DAY 9 DAY10 DAYll DAY 12 Table 7 Mean Body Weights (g) of Male Rats Dosed with APFO (Branched) IC 0 284.9 11.2(10) 288.5 12.6(10) 293.8 13.0(10) 301.4 14.6(10) 309.9 15.6(10) 317.7 17.3(10) 323.5 17.6(10) 328.0 19.9(10) 330.7 19.0(10) 339.0 20.5(10) 339.9 22.1(10) 344.6 23.0(10) 351.7 23.4(10) me 0.3 284.0 16.3(10) 289.8 17.0(10) 295.4 19.0(10) 302.3 21.1(10) 308.6 23.2(10) 316.5 22.1(10) 322.4 24.8(10) 327.9 25.4(10) 335.4 27.9(10) 340.2 29.7(10) 341.7 30.9(10) 347.5 30.8(10) 352.4 32.0(10) VC 1 289.2 11.3(10) 293.3 10.8(10) 299.9 14.2(10) 308.0 15.2(10) 315.4 17.4(10) 326.2 19.7(10) 331.1 21.3(10) 337.6 23.8(10) 343.5 23.2(10) 347.7 24.3(10) 350.0 25.4(10) 355.6 29.2(10) 360.5 27.6(10) VI IC 3 284.6 7.4(10) 287.5 8.5(10) 293.4 10.4(10) 298.6 11.0(10) 306.1 12.0(10) 312.9 12.8(10) 316.8 13.7(10) 322.4 14.3(10) 325.3 15.9(10) 332.8 16.3(10) 334.3 16.3(10) 336.1 16.2(10) 341.8 17.8(10) IXC 10 281.9 8.5(10) 287.3 8.5(10) 290.6 11.2(10) 295.0 10.9(10) 301.3 12.6(10) 309.7 12.0(10) 314.3 12.0(10) 320.6 14.6(10) 323.7 11.9(10) 332.0 13.8(10) 333.4 13.2(10) 337.0 12.8(10) 342.8 14.5(10) XIC 30 284.1 13.1(10) 281.1 1 2 . 2 (10) 280.6 1 3 . 3 (10) 284.5 1 5 . 9 (10) 293.5 1 3 . 3 (10) 305.5 13.5(10) 310.7 13.6(10) 314.3 14.0(10) 315.7 17.2(10) 322.8 17.9(10) 321.9 15.6(10) 327.4 1 5 . 7 (10) 335.4 17.8(10) - 52- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY13 DAY14 Table 7 Mean Body Weights (g) of Male Rats Dosed with APFO (Branched) (Continued) IC 0 357.1 24.7(10) 326.8 23.1(10) me 0.3 359.0 32.8(10) 327.6 28.8(10) VC 1 367.4 30.7(10) 335.8 27.6(10) VI IC 3 348.2 18.6(10) 318.3 16.6(10) IXC 10 348.5 15.1(10) 320.8 14.5(10) XIC 30 339.0 18.7(10) 310.8 15.3(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences from control at p < 0.05. -53- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAYO -DAY1 DAY1 -DAY2 DAY2 -DAY 3 DAY 3 -DAY 4 DAY 4 -DAY 5 DAY 5 -DAY6 DAY 6 -DAY7 DAY7 -DAY 8 DAY 8 -DAY 9 DAY 9 -DAY10 DAY10 -DAY11 DAY 11 -DAY12 DAY12 -DAY13 Table 8 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear/Branched) IA 0 7.4 2.5(10) 8.1 2.7(10) 8.1 3.0(10) 7.7 3.9(10) 6.6 4.8(10) 8.4 3.0(10) 6.2 4.6(10) 7.3 3.6(10) 6.0 2.1(10) 4.8 4.4(10) 7.1 3.0(10) 3.1 1.7(10) 4.8 4.0(10) IIIA 0.3 3.5* 3.9(10) 7.6 2.2(10) 8.2 2.2(10) 7.8 1.9(10) 5.1 2.5(10) 8.6 2.1(10) 6.7 1.2(10) 4.4 2.4(10) 8.0 2.1(10) 4.5 2.4(10) 5.0 3.8(10) 3.9 3.0(10) 4.4 2.6(10) VA 1 5.2 2.6(10) 8.3 2.7(10) 8.7 3.4(10) 7.3 2.6(10) 5.3 2.7(10) 10.5 1.2(10) 6.2 2.2(10) 5.4 2.6(10) 6.3 2.7(10) 5.6 2.4(10) 5.5 3.4(10) 2.6 2.8(10) 3.8 2.3(10) VI IA 3 3.8 3.1(10) 10.6 2.5(10) 7.7 1.5(10) 7.7 2.2(10) 6.6 3.5(10) 8.4 2.6(10) 9.1 3.4(10) 6.2 4.8(10) 7.1 2.4(10) 5.0 2.5(10) 6.8 2.7(10) 1.0 3.2(10) 4.1 4.3(10) IXA 10 3.7 2.3(10) 7.3 2.4(10) 4.6 3.7(10) 0.8 5.2(10) 5.0 5.9(10) 4.6 6.8(10) 1.7 4.9(10) 4.2 8.8(10) 4.0 7.0(10) 1.7 4.9(10) 1.7 5.0(10) 2.9 6.9(10) 4.3 7.3(10) XIA 30 -1.3* 4.7(10) -5.0* 4.7(10) -12.70 7.9(10) -15.60 5.5(10) -5.8 12.6(10) -1.0 13.3(10) 6.7 13.1(10) 15.0 9.3(10) 10.5 7.2(10) 7.5 5.'5 ( 1 0 ) 11.0* 5.0(10) 4.8 5.8(10) 4.7 5.6(10) -54- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and M ice___________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY13 -DAY14 Table 8 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear/Branched) (Continued) IA 0 -28.9 5.0(10) IIIA 0.3 -26.6 2.9(10) VA 1 -28.0 2.8(10) VI IA 3 -26.1 3.7(10) IXA 10 -26.0 4.4(10) XIA 30 -27.8 6.1(10) DAYO -DAY13 DAY0 -DAY14 85.6 14.1(10) 56.8 11.4(10) 77.7 9.1(10) 51.1 8.9(10) 80.8 13.3(10) 52.8 13.5(10) 84.0 21.3(10) 57.9 18.9(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 46.6* 26.4(10) 20.7* 26.0(10) 18.6* 15.7(10) -9.2* 16.1(10) -55- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAYO -DAY1 DAY1 -DAY2 DAY2 -DAY 3 DAY3 -DAY4 DAY4 -DAY5 DAY5 -DAY 6 DAY 6 -DAY7 DAY7 -DAY8 DAY 8 -DAY9 DAY9 -DAY10 DAY10 -DAY11 DAY 11 -DAY12 DAY12 -DAY13 Table 9 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear) IB 0 5.7 2.2(10) 6.8 2.0(10) 8.9 2.9(10) 5.6 1.4(10) 4.0 5.7(10) 12.2 5.1(10) 3.5 3.8(10) 9.7 2.2(10) 2.8 1.8(10) 6.3 2.2(10) 3.0 2.8(10) 3.5 2.9(10) 6.4 1.9(10) IIIB 0.3 3.9 3.1(10) 7.4 2.6(10) 6.4 2.4(10) 5.8 2.4(10) 7.0 1.5(10) 7.6 2.5(10) 3.5 3.1(10) 7.5 6.7(10) 2.0 9.5(10) 7.7 1.9(10) 0.6 3.9(10) 5.1 3.0(10) 5.9 1.9(10) VB 1 4.0 2.6(10) 7.4 2.3(10) 5.3 2.6(10) 5.1 3.8(10) 6.8 3.1(10) 8.8 2.8(10) 3.9 2.5(10) 6.3 3.5(10) 4.8 9.9(10) 4.8 7.0(10) 1.9 3.1(10) 3.3 2.9(10) 6.8 2.0(10) VI IB 3 4.5 3.1(10) 5.8 2.8(10) 5.0* 2.2(10) 5.7 2.5(10) 4.5 2.7(10) 7.3 3.6(10) 4.7 2.3(10) 3.60 1.9(10) 5.2 2.6(10) 3.6 1.4(10) 1.7 3.6(10) 3.0 3.0(10) 4.8 3.8(10) IXB 10 3.7 2.6(10) 7.6 1.3(10) 6.9 2.9(10) 3.7 5.5(10) 2.9 4.8(10) 2.5 6.7(10) 1.6 ` 6.7(10) 8.5 9.3(10) 5.4 6.5(10) 4.0 2.0(10) 1.3 2.9(10) 4.6 2.6(10) 5.6 2.4(10) XIB 30 -0.8 5.3(10) -9.70 8.1(10) -15.1* 4.8(10) -15.40 4.3(10) -9.40 11.2(10) -2.5* 12.4(10) 1.5 14.2(10) 14.9 6.5(10) 10.60 6.0(10) 11.2 6.4(10) 10.3* 5.6(10) 7.8* 5.3(10) 8.0 4.5(10) - 56- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) D A Y 13 -DAY14 Table 9 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Linear) (Continued) IB 0 -29.3 4.5(10) IIIB 0.3 -27.9 3.2(10) VB 1 -25.6 4.4(10) VIIB 3 -27.5 4.0(10) IXB 10 -27.6 2.9(10) XIB 30 -29.8 5.0(10) DAY0 -DAY13 DAY0 -DAY14 78.2 9.2(10) 48.9 7.2(10) 70.5 15.4(10) 42.5 14.3(10) 69.3 21.2(10) 43.7 19.0(10) 59.4* 14.0(10) 31.9 12.1(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 58.4 17.0(10) 30.8 16.8(10) 11.6* 17.7(10) -18.2* 18.3(10) - 57- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group : Dosage(mg/kg) DAYO -DAY1 DAY1 -DAY2 DAY2 -DAY 3 DAY3 -DAY4 DAY4 -DAY 5 DAY 5 -DAY6 DAY6 -DAY7 DAY7 -DAY 8 DAY 8 -DAY 9 DAY 9 -DAY10 D AY 10 -DAY11 DAY11 -DAY12 D AY 12 -DAY13 Table 10 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Branched) IC 0 3.6 3.7(10) 5.4 2.5(10) 7.5 3.1(10) 8.6 2.5(10) 7.7 3.3(10) 5.8 2.1(10) 4.5 3.6(10) 2.7 2.3(10) 8.3 2.8(10) 0.9 2.6(10) 4.7 2.5(10) 7.1 1 . 5 (10) 5.3 2.7(10) me 0.3 5.9 2.8(10) 5.6 3.5(10) 6.9 3.3(10) 6.3 4.6(10) 7.9 2.0(10) 5.9 3.8(10) 5.5 2.7(10) 7.4* 3.3(10) 4.9 3.1(10) 1.5 4.7(10) 5.8 3.0(10) 5.0 3.2(10) 6.6 3.6(10) VC 1 4.1 4.0(10) 6.7 4.2(10) 8.1 2.2(10) 7.4 4.3(10) 10.8 3.6(10) 5.0 2.9(10) 6.4 2.9(10) 6.0 3.0(10) 4.2* 2.7(10) 2.3 3.5(10) 5.6 4.3(10) 4.8 3.7(10) 7.0 3.9(10) VIIC 3 2.9 2.4(10) 5.9 2.5(10) 5.2 2.5(10) 7.5 3.0(10) 6.9 3.6(10) 3.9 3.2(10) 5.6 3.0(10) 2.9 3.5(10) 7.5 3.6(10) 1.6 4.6(10) 1.8 5.8(10) 5.7 3.0(10) 6.4 2.7(10) IXC 10 5.4 2.7(10) 3.3 3.9(10) 4.4 2.4(10) 6.2 3.6(10) 8.4 3.1(10) 4.7 1.6(10) 6.3 2.9(10) 3.1 4.1(10) 8.3 3.6(10) 1.5 2.9(10) 3.6 3.1(10) 5.8 2.8(10) 5.7 1.7(10) Revision Number 1 DuPont-14162 XIC 30 -3.0* 3.3(10) -0.5 7.0(10) 3.8 7.5(10) 9.0 5.3(10) 12.1* 3.8(10) 5.2 2.3(10) 3.6 4.1(10) 1.3 5.7(10) 7.1 3.5(10) -0.9 4.5(10) 5.5 3.8(10) 7.9 3.5(10) 3.6 2.6(10) - 58- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY13 -DAY14 Table 10 Mean Body Weight Gains (g) of Male Rats Dosed with APFO (Branched) (Continued) IC 0 -30.3 3.8(10) me 0.3 -31.4 5.5(10) VC 1 -31.6 4.7(10) VI IC 3 -29.9 5 . 6 (10) IXC 10 -27.6 2.6(10) XIC 30 -28.2 4.2(10) DAY0 -DAY13 DAY0 -DAY14 72.2 15.8(10) 41.9 15.0(10) 75.0 19.1(10) 43.6 15.3(10) 78.2 21.8(10) 46.6 19.0(10) 63.6 14.1(10) 33.7 13.2(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 66.6 9.7(10) 38.9 8.6(10) 5 4 . 9@ 7.4(10) 26.7 4.6(10) - 59- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : Dosage (mg/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 11 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Linear/Branched) IA 0 25.2 1.7(10) 26.4 2.9(10) 27.1 2.1(10) 26.1 2.2(10) IIIA 0.3 25.2 2.0(10) 25.8 1.1(10) 26.6 1.1(10) 25.5 1.7(10) VA 1 25.3 1.3(10) 26.7 1.3(10) 29.4 7.5(10) 26.3 2.1(10) V I IA 3 25.7 2.3(10) 26.8 2.9(10) 30.1 3.9(10) 26.8 3.2(10) IXA 10 23.6 2.3(10) 2 1 . 0@ 2.7(10) 24.3 7.6(10) 21.8* 2.5(10) XIA 30 17.1* 2.2(10) 1 0 . 7@ 8.0(10) 25.4 4.1(10) 26.5 4.0(10) DAY0-DAY13 26.2 2.1(10) 25.8 1.1(10) 26.9 2.6(10) 27.3 2.8(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 22.6* 3.0(10) 19.2* 2.2(10) -60- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 12 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Linear) IB 0 26.3 1.9(10) 25.7 1.7(10) 27.1 2.1(10) 25.8 2.3(10) IIIB 0.3 25.7 2.2(10) 25.5 2.0(10) 26.1 2.0(10) 25.8 2.1(10) VB 1 26.3 3.0(10) 27.6 4 . 7 (10) 26.7 3.8(10) 26.4 3.9(10) VIIB 3 23.7 1.3(10) 23.5 2.0(10) 24.6 2.5(10) 23.1 2.2(10) IXB 10 25.8 2.6(10) 22.8 4.4(10) 27.9 4.2(10) 26.0 1.9(10) XIB 30 14.8* 3.2(10) 13.3* 7.8(10) 27.0 3.1(10) 29.2 2.3(10) DAY0-DAY13 26.2 1.8(10) 25.7 1.9(10) 26.8 3.4(10) 23.7* 1.8(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. 25.4 2.0(10) 20.5* 3.0(10) -61 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : D o s a g e (itig/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 13 Mean Daily Food Consumption (g/day) by Male Rats Dosed with APFO (Branched) IC 0 25.8 2.8(9) 27.0 4.0(10) 27.1 4.8(10) 27.3 3.9(10) me .0.3 27.0 3.4(10) 24.1 4.3(10) 26.2 3.5(10) 26.3 2.5(10) VC 1 26.9 2.7(10) 27.1 3.6(10) 26.4 3.3(10) 27.2 3.8(10) VI IC 3 25.9 2.1(10) 24.7 2.6(10) 25.2 2.4(10) 26.2 5.1(10) IXC 10 26.2 3.3(10) 23.6 2.2(10) 26.4 1.1(10) 25.8 1.8(10) XIC 30 22.1 5.9(10) 2 3 . 4@ 1.2(10) 2 2 . 8@ 1.9(10) 24.6 2.0(10) DAY0-DAY13 26.2 3.1(9) 25.8 2.6(10) 26.9 3 . 2 (10) 25.4 2.1(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. 25.4 1.8(10) 23.3 1.6(10) - 62- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice ____ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 14 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Linear/Branched) (g Body Weight Gain/g Food Consumed) IA 0 0.311 0.053(10) 0.272 0.062(10) 0.224 0.063(10) 0.188 0.058(10) IIIA 0.3 0.257 0.072(10) 0.273 0.032(10) 0.212 0.041(10) 0.173 0.033(10) VA 1 0.292 0.069(10) 0.274 0.038(10) 0.202 0.045(10) 0.149 0.061(10) VI IA 3 0.285 0.047(10) 0.293 0.050(10) 0.203 0.057(10) 0.145 0.055(10) IXA 10 0.219 0.054(10) 0.136 0.144(10) -0.172 1.186(10) 0.136 0.193(10) XIA 30 -0.3900 0.285(10) -3.791 5.879(10) 0.435 0.286(10) 0.242 0.133(10) DAY0-DAY13 0.251 0.028(10) 0.235 0.022(10) 0.236 0.032(10) 0.238 0.034(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 0.157* 0.080(10) 0.059* 0.051(10) - 63- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 15 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Linear) (g Body Weight Gain/g Food Consumed) IB 0 0.271 0.053(10) 0.246 0.026(10) 0.231 0.039(10) 0.163 0.056(10) II IB 0.3 0.229 0.067(10) 0.233 0.038(10) 0.218 0.060(10) 0.148 0.047(10) VB 1 0.213 0.046(10) 0.221 0.056(10) 0.193 0.064(10) 0.146 0.058(10) VIIB 3 0.214 0.066(10) 0.236 0.050(10) 0.168 0.037(10) 0.135 0.052(10) IXB 10 0.237 0.066(10) 0.099 0.195(10) 0.213 0.064(10) 0.147 0.053(10) DAY0-DAY13 0.230 0.019(10) 0.209 0.035(10) 0.195 0.041(10) 0.192 0.037(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. 0.177* 0.049(10) Revision Number 1 DuPont-14162 XIB 30 -0.6600 0.486(10) -3.5930 9.644(10) 0.463 0.175(10) 0.298* 0.107(10) 0.041* 0.063(10) - 64- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group : Dosage(mg/kg) DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 16 Mean Daily Food Efficiency of Male Rats Dosed with APFO (Branched) (g Body Weight Gain/g Food Consumed) IC 0 0.198 0.063(9) 0.245 0.040(10) 0.147 0.040(10) 0.209 0.023(10) me 0.3 0.228 0.069(10) 0.276 0.096(10) 0.170 0.065(10) 0.217 0.035(10) VC 1 0.231 0.043(10) 0.268 0.065(10) 0.156 0.053(10) 0.210 0.039(10) VI IC 3 0.180 0.072(10) 0.240 0.055(10) 0.155 0.060(10) 0.177 0.084(10) IXC 10 0.168 0.054(10) 0.268 0.044(10) 0.163 0.050(10) 0.192 0.046(10) DAY0-DAY13 0.204 0.027(9) 0.223 0.044(10) 0.221 0.030(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. 0.192 0.040(10) 0.202 0.023(10) Revision Number 1 DuPont-14162 XIC 30 -0.0150 0.223(10) 0.317 0.081(10) 0.109 0.061(10) 0.228 0 . 0 5 4 (10) 0.182 0.022(10) - 65- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Table 17 Summary of Clinical Observations for Male Rats Dosed with APFO (Linear/Branched) Treatment Group Dose (mg/kg) Animal Count Hair Loss Forelimb Right Incidence M e a n onset (Days) Forelimb Left Incidence M e a n o nset (Days) TOTALS Incidence M e a n o n s e t (Days) IA IIIA VA VIIA IXA XIA 0 0.3 1 3 10 30 10 10 10 10 10 10 0 0 0 0 0 1 ( 10%) 10 0 0 1 ( 10% ) 0 00 2 0( 0% ) 0%) 1 ( 10%) 2 0( 0% ) 10 %) 10% ) 10 Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the test days each observation was first recorded for that group. There were no statistically significant differences from control at p < 0.05. Revision Number 1 DuPont-14162 - 66- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_______ Treatment Group Dose (mg/kg) Animal Count H a ir L oss F o rep a w L eft Incidence M e a n onset (Days) Forepaw Bilateral Incidence M e a n onset (Days) Forelimb Left Incidence M e a n onset (Days) Forelimb Bilateral Incidence M e a n onset (Days) TOTALS Incidence M e a n onset (Days) Table 18 Summary of Clinical Observations for Male Rats Dosed with APFO (Linear) IB IIIB VB VIIB IXB XIB 0 0.3 1 3 10 30 10 10 10 10 10 10 0 0 0 1 ( 10%) 0 0 10 2 ( 20%) 9 0 1 ( 10%) 0 0 0 9 0 0 0 1 ( 10% ) 0 0 10 1 ( 10%) 0 0 1 ( 10% ) 0 0 0 0 2 ( 20%) 6 0 ( 0% ) 1 ( 10% ) 5 1 ( 10% ) 10 0 ( 0%) 0 ( 0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the test days each observation was first recorded for that group. There were no statistically significant differences from control at p < 0.05. Revision Number 1 DuPont-14162 - 67- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Table 19 Summary of Clinical Observations for Male Rats Dosed with APFO (Branched) Treatment Group Dose (mg/kg) Animal Count Hair Loss Forepaw Right Incidence M e a n o n s e t (Days) Forepaw Bilateral Incidence M e a n onset (Days) Forelimb Left Incidence M e a n o nset (Days) Forelimb Bilateral Incidence M e a n o n s e t (Days) TOTALS Incidence M e a n onset (Days) IC me VC VIIC IXC XIC 0 0.3 1 3 10 30 10 10 10 10 10 10 0 0 0 1 ( 10%) 0 0 9 0 0 0 0 1 ( 10%) 0 12 1 ( 10%) 0 0 0 0 0 12 1 ( 10%) 12 1 ( 10%) 12 0(0%) 0(0%) 1 ( 10%) 9 1 ( 10%) 12 0 ( 0%) Revision Number 1 DuPont-14162 - 68- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 19 Summary of Clinical Observations for Male Rats Dosed with APFO (Branched) (Continued) Treatment Group Dose (mg/kg) Animal Count W ound Superficial Shoulder Left Incidence M e a n onset (Days) IC me VC VIIC IXC XIC 0 0.3 1 3 10 30 10 10 10 10 10 10 0(0%) 0(0%) 1 ( 10%) 12 0(0%) 0(0%) 0 ( 0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the test days each observation was first recorded for that group. There were no statistically significant differences from control at p < 0.05. -69- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 20 Percent Survival of Male Rats Group I Group III Group V Group VII Group IX Group XI DAYS ON TEST_______0 mg/kg______ 0.3 mg/kg_____ 1 mg/kg______3 mg/kg_____ 10 mg/kg 30 mg/kg APFO (Linear/Branched) - A 0 100 100 100 100 100 100 7 100 100 100 100 100 100 14 100 100 100 100 100 100 Number at study start Sacrificed by design Alive on test day 14 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 APFO (Linear) - B 0 7 14 Number at study start Sacrificed by design Alive on test day 14 100 100 100 10 10 10 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 APFO (Branched) - C 0 7 14 Number at study start Sacrificed by design Alive on test day 14 100 100 100 10 10 10 100 100 100 100 100 100 100 100 100 100 100 100 10 10 10 10 10 10 10 10 10 10 10 10 Percent Survival = (Number of Rats Alive/Number of Rats at Risk)*100 There were no statistically significant decreases in survival at p < 0.05 by Cochran-Armitage trend test. 100 100 100 10 10 10 -70- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 21 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Linear/Branched) Group IA Group IIIA Group VA Group VIIA Group IXA Group XIA 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL) DAY 14 non-HDL (mg/dL) DAY 14 51 14(10) 61 22(10) 21 4(10) 30 11(10) 49 13(10) 51 12(10) 21 4(10) 28 9(10) 33 10(10) 40 @ 15(10) 16 3(10) 17@ 7(10) 23 @ 7(10) 41 13(10) 11@ 3(10) 12@ 5(10) 36@ 22(10) 31@ 5(10) 12@ 4(10) 24 19(10) 41 6(10) 36@ 7(10) 14@ 2(10) 26 4(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. -71- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 22 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Linear) Group IB Group IIIB Group VB Group VIIB Group IXB Group XIB 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL) DAY 14 non-HDL (mg/dL) DAY 14 45 10(10) 53 11(10) 19 4(10) 25 6(10) 33* 10(10) 42* 10(10) 16 3(10) 17* 7(10) 29* 11(10) 36* 7(10) 15 4(10) 14* 7(10) 25* 4(10) 38* 9(10) 11* 2(10) 13* 3(10) 27* 7(10) 42 12(10) 11* 2(10) 16* 5(10) 41 15(10) 41* 9(10) 15 5(10) 26 10(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. - 72- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 23 Summary of Clinical Chemistry Values for Male Rats Dosed with APFO (Branched) Group IC Group IIIC Group VC Group VIIC Group IXC Group XIC 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL) DAY 14 non-HDL (mg/dL) DAY 14 46 8(10) 45 18(10) 20 3(10) 26 5(10) 42 6(10) 45 14(10) 19 2(10) 23 5(10) 36* 9(10) 40 15(10) 17 4(10) 18 6(10) 27* 8(10) 28 6(10) 14* 2(10) 13@ 6(10) 26* 10(10) 25 @ 8(10) 13* 4(10) 13@ 6(10) 34* 8(10) 24 @ 3(10) 16* 3(10) 19 5(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 73- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 24 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Linear/Branched) Mean Final Body and Absolute (g) and Relative Organ Weights (% of body weight) Group : Dosage(mg/kg) IA IIIA VA 0 0.3 1 Test LIVER 11.183 1.778(10) 11.573 0.988(10) 12.720 1.001(10) KIDNEYS 2.844 0.247(10) 2.757 0.208(10) 2.909 0.311(10) FINAL BODY WEIGHT 324.9 21.5(10) 319.0 11.8(10) 322.8 15.8(10) LIVER/FINAL BODY * 100 3.431 0.401(10) 3.625 0.229(10) 3.938* 0.198(10) KIDNEYS/FINAL BODY * 100 0.875 0.047(10) 0.864 0.048(10) 0.900 0.070(10) VI IA 3 17.925* 2.329(10) 3.144* 0.233(10) 329.8 25.7(10) 5.424* 0.390(10) 0.955* 0.060(10) IXA 10 16.291* 1.724(10) 2.618 0.266(10) 288.7* 33.3(10) 5.672* 0.515(10) 0.910 0.060(10) XIA 30 17.666* 1.535(9) 2.494* 0.189(9) 258.9* 10.5(10) 6.819* 0.562(9) 0.963* 0.081(9) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. - 74- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 25 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Linear) Mean Final Body and Absolute (g) and Relative Organ Weights (% of body weight) Group : Dosage(mg/kg) IB IIIB VB 0 0.3 1 Test LIVER 12.089 0.958(10) 12.539 1.090(10) 13.410 2.165(10) KIDNEYS 2.889 0.266(10) 2.723 0.586(10) 2.830 0.174(10) FINAL BODY WEIGHT 333.5 12.1(10) 324.8 19.2(10) 323.4 30.5(10) LIVER/FINAL BODY * 100 3.631 0.347(10) 3.855 0.139(10) 4.129* 0.332(10) KIDNEYS/FINAL BODY * 100 0.866 0.062(10) 0.834 0.151(10) 0.880 0.079(10) VI IB 3 15.417* 1 . 2 0 1 (10) 2.881 0.294(10) 311.6 14.5(10) 4.944* 0.228(10) 0.924 0.070(10) IXB 10 18.813* 1.853(10) 2.937 0.233(10) 311.9 16.7(10) 6.028* 0.407(10) 0.942 0.059(10) XXB 30 17.414* 1.586(10) 2.4190 0.189(10) 262.7* 22.4(10) 6.642* 0.507(10) 0.923 0.071(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 75- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 26 Mean Final Body and Organ Weights for Male Rats Dosed with APFO (Branched) Mean Final Body and Absolute (g) and Relative Organ Weights (% of body weight) Group : Dosage(mg/kg) IC m e 0 0.3 VC 1 Test LIVER KIDNEYS FINAL BODY WEIGHT LIVER/FINAL BODY * 100 KIDNEYS/FINAL BODY * 100 11.049 1.429(10) 2.632 0.289(10) 326.8 23.1(10) 3.375 0.288(10) 0.804 0.056(10) 11.733 1.516(10) 2.715 0.340(10) 327.6 28.8(10) 3.577 0.267(10) 0.828 0.067(10) 13.139* 1.753(10) 2.793 0.309(10) 335.8 27.6(10) 3.906* 0.330(10) 0.831 0.060(10) VIIC 3 14.024* 1.236(10) 2.703 0.253(10) 318.3 16.6(10) 4.412* 0.374(10) 0.849 0.061(10) IXC 10 18.553* 2.809(10) 2.835 0.272(10) 320.8 14.5(10) 5.771* 0.745(10) 0.883* 0.066(10) XIC 30 19.816* 2.623(10) 2.721 0.208(10) 310.8 1 5 . 3 (10) 6.366* 0.704(10) 0.875* 0.052(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. - 76- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 27 Incidences of Gross Observations in Male Rats Dosed with APFO (Linear/Branched) 1 1 | LESIONS 1 I1 j LIVER j NO ABNORMALITY DETECTED j DISCOLORATION j KIDNEYS I1 | NO ABNORMALITY DETECTED | TREATMENT | per day LESION INCIDENCE (Numeric) 1 ----- 1 Males 1 11 1 o | 0.3 | 1 1 3 1 10 j 30 | I mg/kg| mg/kgj mg/kg| mg/kg| mg/kgj mg/kgj 1 IA 1 IIIA j VA j VI IA | IXA j XIA j 1 11 | (10) 1 10 11 1 1 (10) 1 10 (10) 1 10 11 1 | (10) 1 10 | (10) 1 10 | | (10) | 1 | 10 | (10) | 10 ! 1 1 (10) 1 10 1 1 (10) 1 1 |9 1 ! I 1 (10) I 10 1 1 (10) j 1 |9 I1 | 1 j (10) 1 1 j 10 | 1 1 | 1 1 j i 1 1 Figure in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 77- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 28 Incidences of Gross Observations in Male Rats Dosed with APFO (Linear) LESIONS 1 LESION INCIDENCE (Numeric) 1! Males | TREATMENT j per day 1 o 1 0.3 1 1 1 mg/kg| mg/kg| mg/kg 1 IB j IIIB j VB 1 3 1 10 1 30 1 mg/kgj mg/kg| mg/kgj VIIB j IXB j XIB 1 1 LIVER NO ABNORMALITY DETECTED DISCOLORATION KIDNEYS NO ABNORMALITY DETECTED 1 1 (10) 1 1 1 10 1 1 1 1 (10) I 1 1 10 1 (10) 1 10 j 1 (10) 1 10 j (10) 1 10 j 1 (10) 1 10 (10) 10 GO) 10 (10) 19 11 1 1 (10) I1 1 10 1 j (10) I 1 1 10 1 1 (10) I 1 1 10 1 1 1 1 1 Figure in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 78- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 29 Incidences of Gross Observations in Male Rats Dosed with APFO (Branched) LESIONS LIVER NO ABNORMALITY DETECTED DISCOLORATION KIDNEYS NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Males 1 TREATMENT 1 per day 1 1 1 o 1 0.3 1 1 1 3 1 10 1 30 1 mg/kg| mg/kgj mg/kg| mg/kgj mg/kg j mg/kg 1 i c 1 IIIC 1 VC j VI IC j IXC 1 XIC !! 1 1 GO) I 1 1 10 ! 1 1 (10) 1 10 1 1 (10) 1 1 1 10 ! 1 1 (10) 1 10 1 1 (10) 1 10 ! 1 1 (10) 1 10 1 1 GO) 1 1 1 10 1 1 1 (10) 11 1 10 1 J (10) 1 j 10 1 1 1 j (10) 1 1 10 j (10) 19 11 1 (10) 1 10 Figure in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 79- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 30 Summary of Peroxisomal Beta-Oxidation Activity in Male Rats Group I III V VII IX XI Hepatic Peroxisomal Beta-Oxidation Activity ______________________ (nmol/min/mg protein)_________ Dosage APFO (mg/kg/day)____ (Linear/Branched)_______APFO (Linear)_______ APFO (Branched) 0 18.2 3.8a 15.7 3.6 13.0 3.3 0.3 18.0 3.7 16.0 3.1 12.9 3.8 1 27.0 4.3* 29.8 5.6* 15.4 3.1 3 57.6 10.0* 67.5 14.3* 17.4 3.5* 10 82.2 18.1* 74.8 10.1* 28.7 8.0* 30 84.7 16.3* 89.0 13.6* 37.6 12.2* a Mean standard deviation. The n = 10 for each group. * Statistically significant difference from control (p < 0.05) by Dunnett's test. - 80- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 31 Summary of % Relative Liver Weights in Male Rats Group I III V VII IX XI Dosage (mg/kg/day) 0 0.3 1 3 10 30 Relative Liver Weights to Full Body Weights (%) APFO (Linear/Branched) 3.4 0.4a 3.6 0.2 3.9 0.2* 5.4 0.4* APFO (Linear) 3.6 0.3 3.9 0.1 4.1 0.3* 4.9 0.2* APFO (Branched) 3.4 0.3 3.6 0.3 3.9 0.3* 4.4 0.4* 5.7 0.5* 6.0 0.4* 5.8 0.7* 6.8 0.6b* 6.6 0.5* 6.4 0.7* a Mean standard deviation. The n = 10 for each group, b The n = 9. * Statistically significant difference from control (p < 0.05) Dunnett's test. -81- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 RAT FIGURES -82- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Figure 1 Mean Body Weights of Male Rats Dosed with APFO (Linear/Branched) Revision Number 1 DuPont-14162 -- --IA 0 mg/kg -- IIIA0.3 mg/kg &- VA 1 mg/kg - X - VIIA 3 mg/kg --X--IXA 10 mg/kg -- --XIA 30 mg/kg - 83- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Figure 2 Mean Body Weights of Male Rats Dosed with APFO (Linear) Revision Number 1 DuPont-14162 IB 0 mg/kg IIIB 0.3 mg/kg VB 1 mg/kg VIIB 3 mg/kg -- I XB 10 mg/kg XIB 30 mg/kg - 84- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Figure 3 Mean Body Weights of Male Rats Dosed with APFO (Branched) Revision Number 1 DuPont-14162 IC 0 mg/kg IIIC 0.3 mg/kg VC 1 mg/kg --K -V IIC 3 mg/kg )K--IXC 10 mg/kg -- XI C 30 mg/kg - 85- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 RAT APPENDICES -86- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice ___________ Revision Number 1 DuPont-14162 Appendix A Individual PFOA Serum Concentrations for Rats -87- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL PFOA SERUM CONCENTRATIONS FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Groups may also be identified by the group number only (I, III, etc.) with the test substance described in the title (APFO (Linear/Branched), APFO (Linear), or APFO (Branched). Abbreviations mg/kg = mg/kg/day L = Linear B = Branched Avg = Average s dev = standard deviation N/A = Not applicable Note H-26225 is comprised of two components, H-26203 and H-26204. -88- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and M ic e __________ ________________ Individual PFOA Serum Concentrations for Rats Revision Number 1 DuPont-14162 Dose Group Level IA Omg/kg ID 101 102 103 104 105 106 107 108 109 110 Avg. pg/mL Linear 0.249 0.153 0.187 0.262 0.218 0.102 0.101 0.086 0.234 0.083 0.168 pg/mL Branched 0.405 0.229 0.260 0.257 0.265 0.121 0.155 0.087 0.196 0.084 0.206 s dev L+B 0.654 0.382 0.447 0.520 0.483 0.223 0.256 0.173 0.430 0.167 0.373 0.138 L/B 0.62 0.67 0.72 1.02 0.82 0.84 0.65 0.99 1.19 0.98 0.85 0.18 niA 0.3 mg/kg 301 19.1 4.4 23.7 4.38 302 13.8 2.8 16.7 4.84 303 17.0 4.2 21.2 4.09 304 14.9 3.5 18.5 4.35 305 17.0 4.2 21.4 4.13 306 15.3 2.8 18.2 5.43 307 15.9 3.3 19.2 4.88 308 16.9 3.2 20.1 5.21 309 15.5 2.7 18.2 5.76 310 13.5 1.7 15.2 7.89 Avg. 16.0 3.3 19.2 5.10 s dev 2.5 1.13 - 89- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual PFOA Seram Concentrations for Rats Revision Number 1 DuPont-14162 Group VA Dose Level 1.0 mg/kg ED 501 502 503 504 505 506 507 508 509 510 Avg. Pg/mL pg/mL Linear Branched 45.6 9.8 43.3 7.3 44.6 8.0 38.5 6.3 61.3 12.8 46.5 8.3 43.4 6.5 33.8 5.7 45.2 6.2 32.8 3.4 43.5 7.4 s dev L+B 55.4 50.6 52.6 44.8 74.1 54.9 49.9 39.5 51.4 36.2 50.9 10.3 L/B 4.64 5.91 5.56 6.07 4.77 5.59 6.70 5.93 7.23 9.61 6.20 1.43 VILA 3.0 mg/kg 701 702 703 704 705 706 707 708 709 710 Avg. 92.3 92.3 83.4 80.3 86.3 104.9 100.1 106.2 89.3 90.3 92.5 14.0 14.4 13.4 13.3 12.5 16.9 12.7 16.6 12.2 10.4 13.6 s dev 106.2 106.7 96.8 93.6 98.8 121.8 112.8 122.8 101.5 100.7 106.2 10.1 6.61 6.43 6.23 6.03 6.90 6.19 7.89 6.38 7.32 8.68 6.86 0.85 -90- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice ____________________ Revision Number 1 DuPont-14162 Individual PFOA Serum Concentrations for Rats Dose Group Level IXA 10 mg/kg ID 901 902 903 904 905 906 907 908 909 910 Avg. pg/mL Linear 121 161 206 94 147 163 188 223 142 194 164 pg/mL Branched 15.1 18.2 25.5 11.0 17.0 16.3 22.6 29.9 16.6 24.5 20 s dev L+B 135.7 178.9 231.8 105.1 164.0 178.8 210.8 252.6 158.1 219.0 183 45.5 L/B 8.01 8.85 8.10 8.59 8.66 10.00 8.35 7.46 8.52 7.95 8.45 0.68 XIA 30 mg/kg 1101 133 1102 229 1103 193 1104 135 1105 182 1106 198 1107 124 1108 227 1109 232 1110 247 Avg. 190 13 27 19 14 18 19 6 22 18 23 18 s dev 146.3 256.7 211.9 148.8 199.3 217.2 129.6 249.9 250.0 269.3 208 50.9 9.85 8.43 10.09 9.70 10.24 10.30 20.89 10.15 12.94 10.88 11.35 3.54 Test substance H24921 L/B ratio = 0.78/0.22 = 3.55 ng/mL values corrected for standard composition and converted to pg/mL by multiplying linear values by 0.00078 and branched values by 0.00022. APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual PFOA Serum Concentrations for Rats Dose Group Level IB 0 mg/kg ID 101 102 103 104 105 106 107 108 109 110 Avg. s dev (ig/mL Linear 0.236 0.199 0.192 0.275 0.230 0.303 0.191 0.181 0.260 1.846 0.391 0.513 IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 Avg. s dev 24.0 21.9 23.2 20.9 20.9 19.9 14.8 15.5 22.6 17.6 20.1 3.2 Revision Number 1 DuPont-14162 -92- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual PFOA Serum Concentrations for Rats Group VB Dose Level______ ID 1.0mg/kg 501 502 503 504 505 506 507 508 509 510 Avg. s dev pg/mL Linear 73.0 86.9 65.7 52.0 71.6 49.9 57.4 71.2 64.5 56.4 64.9 11.3 VIIB 3.0 mg/kg 701 702 703 704 705 706 707 708 709 710 Avg. sdev 124 108 131 164 132 125 153 162 133 136 137 18 Revision Number 1 DuPont-14162 -93- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual PFOA Serum Concentrations for Rats Group IXB Dose Level 10 mg/kg ID 901 902 903 904 905 906 907 908 909 910 Avg. s dev pg/mL Linear 115 254 230 337 225 192 171 238 129 170 206 65 XEB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Avg. s dev 291 206 185 244 363 88 165 290 205 190 223 77 Revision Number 1 DuPont-14162 -94- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual PFOA Seram Concentrations for Rats Dose Group Level IC Omg/kg ID 101 102 103 104 105 106 107 108 109 110 Avg. H26203 Pg/mL pg/mL + H26203 H26204 H26204 *** *** *** *$* *** 0.00 0.00 0.00 0.11 0.43 0.54 0.00 0.00 0.00 0.02 0 0.02 0.00 0.00 0.00 0.11 s dev 0.24 H26204/ H26203 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A m e 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 Avg. 5.6 6.5 12.1 6.1 8.1 14.3 8.3 10.4 18.7 6.6 9.8 16.4 9.4 13.2 22.6 6.8 8.2 15.0 6.5 5.8 12.3 7.7 10.3 18.0 6.2 8.0 14.1 7.6 8.7 16.3 7.1 8.9 16.0 s dev 3.19 1.17 1.32 1.27 1.49 1.40 1.20 0.91 1.34 1.29 1.15 1.25 0.16 * Five of the 10 serum samples labeled as controls could not conclusively be linked to the appropriate animals and were therefore excluded from the calculation of the mean. -95- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual PFOA Serum Concentrations for Rats Dose Group Level VC 1.0 mg/kg ID 501 502 503 504 505 506 507 508 509 510 Avg. pg/mL H26203 16.3 21.7 18.5 17.0 19.4 20.9 18.6 11.5 16.7 13.6 17.4 H26203 pg/mL + H26204 H26204 31.4 47.6 46.2 67.9 41.6 60.1 31.2 48.2 38.5 58.0 26.0 46.9 29.4 48.0 15.2 26.7 25.2 41.9 19.9 33.5 30.5 47.9 s dev 12.22 H26204/ H26203 1.93 2.14 2.25 1.84 1.98 1.25 1.58 1.33 1.51 1.46 1.73 0.35 VIIC 3.0 mg/kg 701 39.8 79.6 119.4 702 25.8 59.1 84.9 703 22.2 44.3 66.5 704 29.8 64.2 94.0 705 24.0 55.9 79.9 706 18.0 29.9 47.9 707 12.2 26.2 38.4 708 31.7 53.8 85.4 709 20.7 40.8 61.5 710 18.5 29.8 48.3 Avg. 24.3 48.4 72.6 s dev 24.84 2.00 2.29 2.00 2.16 2.33 1.66 2.14 1.70 1.98 1.61 1.99 0.26 -96- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual PFOA Seram Concentrations for Rats Group IXC Dose Level 10 mg/kg ID 901 902 903 904 905 906 907 908 909 910 Avg. pg/mL H26203 34 37 21 30 29 25 30 31 36 32 30 Pg/mL H26204 72 65 26 48 60 59 58 75 76 76 61 s dev H26203 + H26204 105 102 46 78 89 83 87 106 112 108 92 20 H26204/ H26203 2.14 1.77 1.23 1.61 2.07 2.37 1.93 2.39 2.12 2.35 2.00 0.37 XIC 30 mg/kg 1101 39 93 131 1102 40 116 155 1103 29 104 133 1104 47 139 186 1105 18 53 71 1106 38 105 143 1107 29 83 112 1108 27 78 105 1109 27 63 90 1110 34 83 116 Avg. 33 92 124 s dev 33 2.41 2.92 3.62 2.99 2.96 2.75 2.86 2.87 2.31 2.44 2.81 0.38 Test substance H26225 ratio = 58% H26204/42% H26203 = 1.38 -97- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix B Individual Body Weights for Rats - 98- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 INDIVIDUAL BODY WEIGHTS FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) Dosage (mg/kg) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC IIIC VC VIIC IXC XIC 0 (Control) 0.3 1 3 10 30 Groups may also be identified by the group number only (I, III, etc.) with the test substance described in the title (APFO (Linear/Branched), APFO (Linear), or APFO (Branched). Abbreviations mg/kg = mg/kg/day - 99- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Study: 15073 1025 Individual Body Weights for Rats Print Date: 16-Apr-2004 Print Time: 12:30:54 Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 Male, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 259.8 295.8 249.4 269.2 259.8 257.7 267.1 268.5 282.7 271.8 265.5 300.8 254.5 279.2 265.1 270.0 274.2 275.4 292.7 278.3 275.3 309.8 261.2 286.3 271.1 272.8 282.0 286.1 305.1 287.2 286.5 315.1 271.1 297.2 278.9 279.7 287.8 297.4 314.8 289.4 295.2 326.5 279.0 299.8 286.5 286.1 294.4 301.2 331.0 295.1 . 301.2 329.7 283.4 314.2 284.3 294.3 302.4 313.5 334.0 303.9 310.7 339.8 291.9 315.5 292.9 303.7 310.4 320.5 347.4 312.2 315.2 348.6 295.1 318.7 295.5 301.6 318.7 332.7 357.5 323.8 325.6 357.5 305.1 329.2 303.9 312.2 324.4 335.2 362.7 324.6 Male, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 258.6 284.2 253.8 270.4 264.7 268.9 271.6 276.3 259.1 271.2 268.0 290.3 262.5 269.2 266.9 268.6 277.6 275.5 260.4 275.1 278.2 294.7 269.7 277.8 276.6 275.2 286.9 284.6 267.2 278.8 288.7 301.6 277.6 288.6 286.0 279.7 294.3 290.1 275.5 289.9 292.4 311.9 285.2 294.7 295.7 287.1 303.0 298.6 284.5 297.0 295.9 318.3 290.1 302.4 295.2 291.0 310.8 303.2 290.8 303.8 308.4 326.4 297.4 306.8 304.2 299.7 319.9 311.3 301.6 311.8 315.0 334.5 305.0 312.8 309.1 306.4 325.2 318.7 307.0 320.3 319.7 335.5 310.5 317.8 310.0 310.5 328.4 325.7 311.6 328.7 Male, V A 1 mg/kg 501 502 503 504 505 506 507 508 509 510 260.8 284.6 255.9 275.1 265.8 267.6 278.4 281.3 275.1 255.7 267.3 290.5 259.2 276.7 270.8 274.7 280.5 290.6 277.9 263.8 272.7 300.0 269.6 285.3 278.4 277.2 290.1 298.9 286.9 276.1 283.4 305.0 275.1 292.2 282.3 284.5 302.2 312.0 298.9 286.8 290.6 312.9 287.6 301.5 289.4 292.2 307.1 315.4 306.7 291.6 297.5 313.5 292.9 307.3 289.6 299.2 313.3 321.2 313.3 300.1 306.5 325.5 302.3 317.8 298.4 309.3 325.4 331.4 324.7 311.7 315.3 330.6 312.3 320.7 303.8 316.8 329.4 338.0 331.7 316.6 326.5 335.8 315.9 323.9 307.4 321.8 331.9 346.1 336.4 323.3 - 100- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Individual Body Weights for Rats Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weight g D a y 14 Male, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 331.7 360.3 311.0 334.1 307.4 321.6 330.7 340.2 370.9 332.7 324.6 365.9 315.8 340.8 310.5 329.1 337.5 348.3 376.0 340.0 333.7 378.8 319.0 348.2 314.7 337.0 345.4 351.9 385.2 345.2 335.9 380.2 323.4 349.9 318.0 338.4 349.2 356.2 386.8 351.9 337.4 391.7 323.4 357.9 318.1 344.8 354.1 365.3 392.2 353.0 310.7 354.4 294.1 327.7 293.8 322.3 328.5 331.6 357.7 328.5 Male, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 327.0 346.4 315.6 326.7 318.1 316.2 339.6 331.4 319.4 338.1 Male, VA 1 mg/kg 331.6 349.2 321.2 328.0 319.6 322.3 346.0 340.3 324.6 340.5 342.5 354.1 322.0 335.2 322.9 333.5 347.3 343.5 325.5 346.5 344.5 358.9 325.7 339.0 324.5 331.6 351.1 348.3 334.6 353.5 347.4 364.7 332.6 341.4 329.5 334.4 360.5 349.1 337.4 359.2 323.8 335.5 303.7 312.9 301.7 312.8 330.1 323.3 313.8 332.5 501 502 503 504 505 506 507 508 509 510 330.1 337.0 326.0 330.9 311.9 327.6 341.2 352.9 344.6 330.2 336.0 344.8 330.8 340.7 315.4 . 334.7 342.4 358.0 349.6 336.4 345.6 350.6 332.8 345.8 315.7 336.4 351.6 366.9 357.9 340.9 351.4 351.6 333.1 347.1 316.0 334.9 353.9 372.2 362.9 347.4 354.4 353.5 338.1 352.2 317.9 343.6 358.7 372.7 366.4 350.5 327.0 324.5 306.9 321.0 292.5 318.0 327.6 349.4 339.6 321.3 -101 - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Study: 15073 1025 In d iv id u a l B ody W eig h ts f o r R a ts Print Date: 16-Apr-2004 Print Time: 12:30:54 Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 Male, VI IA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 264.6 292.1 261.8 287.2 264.2 269.7 269.0 277.4 270.7 262.1 264.7 295.3 264.2 296.8 265.1 270.2 274.6 280.8 276.2 269.1 273.4 306.6 274.3 312.8 278.6 278.6 283.7 290.9 286.7 277.4 280.7 313.8 279.9 321.8 286.4 286.3 292.6 298.2 297.4 283.1 290.3 321.8 288.6 332.7 295.7 292.2 300.6 302.3 302.1 290.6 . 296.5 327.4 296.2 345.9 301.3 302.3 302.3 306.5 311.3 293.0 304.2 338.1 303.0 360.4 306.2 309.3 310.5 314.2 319.2 301.1 312.4 345.2 311.0 374.6 314.2 321.4 324.9 318.5 325.3 309.5 317.0 362.6 319.0 380.5 321.1 320.1 330.6 320.6 330.0 317.1 Male, IXA 10 mg/kg 901 902 903 904 905 906 907 908 909 910 266.8 294.8 245.8 271.7 253.0 270.2 274.1 278.3 268.5 256.9 271.6 298.5 244.7 277.9 257.5 275.6 279.7 279.4 273.3 258.7 279.2 308.7 256.3 283.9 261.9 280.1 285.5 288.9 280.3 265.2 284.4 312.5 254.7 291.5 264.3 288.2 296.6 291.8 286.3 266.1 286.4 313.6 255.8 296.8 267.1 280.1 296.4 284.2 294.7 269.6 284.7 325.9 256.4 302.8 272.5 295.5 302.5 292.2 294.9 267.5 290.9 336.0 256.2 310.1 280.0 285.6 316.8 296.0 302.7 266.9 294.2 339.1 252.7 312.6 280.5 277.3 326.8 300.5 304.7 270.2 295.3 344.7 256.4 322.4 285.4 259.0 336.7 303.5 318.7 278.9 Male, X I A 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 263.7 288.5 257.3 281.0 251.4 263.6 263.3 280.6 271.9 259.0 266.7 290.8 255.6 272.0 251.3 263.0 258.7 272.7 271.2 264.9 267.0 290.2 251.6 266.1 251.4 253.6 248.1 266.4 258.7 263.4 250.6 276.1 244.3 241.4 241.3 243.5 232.4 254.7 238.0 267.5 232.8 251.3 230.5 226.0 231.0 222.9 214.9 239.8 221.5 262.9 218.6 236.9 243.2 212.4 247.3 206.9 201.3 229.2 209.9 269.9 204.9 222.5 257.2 200.6 257.8 201.8 191.7 247.9 198.5 282.4 193.7 215.0 269.4 198.1 269.4 220.1 216.8 269.9 192.3 287.5 216.7 239.0 271.2 221.1 269.7 238.2 236.0 281.9 215.1 293.4 - 102- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 I n d iv id u a l Body W eig h ts f o r R a ts Body Weight g Day 9 Body Weight 9 D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weight g D a y 14 Male, V I IA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 320.1 368.8 324.9 392.1 326.4 328.8 339.3 327.6 338.7 322.5 Male, IXA 10 mg/kg 326.6 370.7 332.6 400.2 331.3 332.5 344.2 329.0 341.6 330.2 333.4 378.6 335.5 409.1 339.0 342.5 354.1 331.8 348.5 334.6 330.9 383.8 338.6 412.0 336.9 343.8 349.3 333.4 352.3 336.1 340.9 386.5 338.1 424.8 339.5 345.4 355.0 333.4 354.6 340.3 317.0 357.1 318.9 392.3 315.6 317.9 329.2 308.3 325.5 316.0 901 902 903 904 905 906 907 908 909 910 304.1 354.0 264.3 328.2 292.9 244.6 338.2 305.6 326.2 282.9 309.3 357.5 267.5 332.7 296.0 233.0 340.1 310.4 327.4 283.8 309.1 360.9 265.4 337.7 297.8 225.9 350.3 310.0 335.1 282.8 309.7 363.9 268.6 340.6 302.3 247.0 348.4 305.9 333.8 283.4 311.3 367.3 265.4 342.7 302.1 270.4 350.4 311.7 341.0 284.3 285.5 333.5 241.9 318.5 278.0 241.6 323.0 281.4 317.1 266.6 Male, XI A 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 235.8 253.4 273.7 238.2 271.3 255.8 239.2 294.2 229.9 295.6 245.4 264.0 273.7 244.8 278.2 267.7 250.4 300.5 244.7 292.4 261.9 276.7 284.4 265.4 283.8 277.4 265.2 306.5 252.3 298.7 271.1 282.0 284.5 269.7 282.6 291.0 271.8 306.8 264.7 295.6 276.6 293.5 283.1 273.0 285.1 302.2 272.2 311.2 277.5 292.2 255.9 253.3 256.4 249.4 259.7 266.4 245.1 280.4 252.8 269.2 - 103- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Individual Body Wei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 278.2 267.8 288.6 286.7 292.3 269.9 277.3 287.0 310.7 287.0 283.5 277.2 296.3 294.3 297.9 276.5 280.4 291.4 316.3 289.2 293.5 283.8 304.6 300.0 302.3 285.1 286.6 294.9 322.6 297.7 304.9 293.5 317.1 309.2 312.6 289.9 294.3 299.6 334.9 304.1 311.8 298.1 326.0 313.8 316.9 295.2 299.5 304.6 339.8 310.3 Male, IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 275.2 267.6 296.3 274.6 297.3 268.6 279.6 283.2 294.5 285.4 277.5 275.4 296.5 273.7 300.8 271.7 287.2 285.7 301.4 291.6 280.3 281.6 306.3 284.2 307.7 279.6 298.5 291.9 308.0 297.2 282.6 290.9 . 310.8 291.4 317.6 286.0 306.8 296.7 312.2 304.3 283.2 295.1 320.1 296.1 322.9 292.2 314.1 304.6 317.2 311.9 Male, VB 1 mg/kg 501 502 503 504 505 506 507 508 509 510 269.1 250.0 283.1 277.4 301.1 274.9 272.4 286.2 296.9 285.7 ' 277.8 252.1 284.4 281.4 308.5 280.3 276.4 289.9 297.5 288.5 281.2 260.1 291.2 289.7 314.9 292.0 281.6 299.6 305.2 295.5 284.2 263.4 300.4 297.3 322.7 297.0 282.6 303.3 312.0 301.5 285.5 260.6 304.0 304.1 331.5 306.5 290.1 309.3 318.9 304.6 -104- Revision Number 1 DuPont-14162 .ghts for Rats Print Date: 16-Apr-2004 Print Time: 12:30:54 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 304.5 303.8 322.5 322.2 317.5 298.8 309.7 311.4 346.6 318.8 322.0 314.1 344.0 333.2 335.1 310.4 315.4 318.6 354.5 330.7 . 332.3 317.8 345.9 333.4 339.6 310.0 321.4 325.3 358.5 328.3 340.4 327.1 355.1 344.3 347.9 325.4 330.4 334.7 366.4 338.0 291.5 300.0 326.5 302.2 330.9 300.8 319.7 311.2 323.6 321.4 293.9 307.9 332.3 310.5 337.4 309.3 331.0 321.3 329.9 330.1 295.4 316.0 339.7 317.1 337.8 310.1 332.6 321.0 334.7 334.4 299.9 321.3 345.4 325.7 345.2 319.0 327.7 343.8 342.9 342.7 291.7 264.6 312.0 311.2 339.2 318.0 291.2 313.2 326.6 315.0 297.0 270.8 317.0 319.3 351.9 330.3 301.5 321.7 338.3 322.9 300.9 275.6 324.2 325.8 355.0 334.2 299.7 327.4 340.3 326.8 306.2 280.9 329.1 328.7 368.1 343.4 308.8 328.2 347.6 332.2 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Individual Body Weights for Rats Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weig g D a y 14 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 344.5 331.9 359.2 347.4 351.8 324.6 332.2 335.4 368.3 341.9 Male, IIIB 0.3 mg/kg 348.0 337.0 369.2 354.0 358.5 333.6 339.7 340.1 374.9 345.0 351.1 338.5 375.5 359.2 359.2 334.9 342.4 339.5 376.2 353.1 350.7 345.8 380.2 364.7 360.7 340.0 343.5 345.5 375.3 357.7 356.4 353.3 385.0 370.7 369.4 345.4 351.4 351.1 378.3 366.7 331.4 318.4 348.3 343.5 334.9 320.4 324.9 322.5 353.2 337.1 301 302 303 304 305 306 307 308 309 310 299.6 321.5 346.4 329.7 350.7 318.2 351.8 329.0 341.7 345.4 Male, VB 1 mg/kg 306.6 326.4 350.6 338.2 360.4 327.1 360.2 335.8 350.8 355.0 303.7 331.7 357.1 339.1 356.4 321.3 361.7 336.7 351.3 357.6 307.0 334.2 362.1 344.3 360.2 328.8 373.8 342.0 356.5 358.9 312.8 338.2 370.5 351.9 368.4 336.0 378.6 344.9 361.1 364.4 286.1 306.0 338.0 325.9 342.3 310.0 346.0 319.9 334.7 338.8 501 502 503 504 505 506 507 508 509 510 303.7 277.7 328.4 332.9 375.2 374.9 310.1 331.8 351.8 335.0 311.5 282.9 334.6 341.4 381.8 360.6 33.8 336.7 361.1 344.7 307.7 282.6 338.6 339.5 388.0 365.3 317.8 338.1 363.7 346.3 305.3 286.3 339.9 344.1 394.4 372.8 318.4 341.2 366.8 351.7 311.9 290.0 348.1 351.6 399.0 379.1 327.6 346.3 374.3 361.4 292.1 268.0 327.5 330.9 371.5 347.8 297.4 319.2 347.1 332.2 - 105- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice____________________________________________________________________________ DuPont-14162 Study:: 15073 1025 Individual Body Weights for Rats Print Date: 16-Apr-2004 Print Time : 12:30:54 Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weigl g Day 8 Male, VI IB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 275.8 262.8 288.9 282.8 288.9 267.6 275.8 289.1 297.1 267.8 284.4 265.5 291.3 293.2 293.8 272.6 280.6 292.5 296.4 271.3 286.0 273.3 298.9 300.0 299.0 283.0 286.3 297.9 302.3 272.5 290.8 279.7 299.6 ' 306.2 306.4 289.8 290.4 302.6 309.1 274.8 292.9 284.8 302.8 313.7 311.4 298.4 299.5 305.9 317.0 279.9 299.3 287.9 307.0 322.7 315.8 297.0 304.2 312.3 320.9 284.6 306.3 291.8 312.9 329.9 320.4 304.7 319.2 315.3 332.6 291.3 308.8 297.4 319.9 334.4 326.7 313.1 323.2 316.0 335.4 296.5 310.0 301.7 321.9 339.1 327.5 317.6 329.0 321.8 337.4 301.4 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908. 909 910 282.5 254.6 289.9 266.4 287.6 274.6 271.7 292.9 299.2 291.2 287.3 260.3 291.2 266.6 290.2 277.5 273.0 295.6 306.5 299.0 296.5 268.5 298.5 276.3 297.3 283.8 278.8 302.0 314.8 306.6 308.1 274.5 300.1 282.7 301.2 292.6 287.3 308.3 320.8 316.6 312.4 279.7 306.1 284.4 308.1 295.0 292.7 316.6 310.0 324.2 319.6 286.6 306.1 292.0 309.5 301.7 298.4 310.6 306.6 327.2 327.5 290.4 292.6 297.5 312.3 307.2 305.3 317.0 301.7 332.2 336.6 298.1 278.7 298.6 311.3 306.3 313.1 315.4 306.2 335.3 342.6 303.4 269.4 302.7 329.3 319.4 312.4 333.0 327.0 345.5 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 280.3 269.4 280.2 277.0 293.0 252.1 280.4 289.4 301.3 286.5 281.4 266.4 282.2 277.1 279.1 252.9 284.9 294.1 298.9 284.5 272.7 256.2 277.0 259.9 259.2 245.0 277.5 294.9 276.2 286.1 251.8 234.4 270.8 240.1 245.7 232.6 263.1 277.8 263.1 274.2 237.8 218.0 251.9 223.0 227.7 224.0 244.0 261.8 244.4 267.3 219.9 205.7 235.2 210.3 213.0 213.8 229.0 252.2 238.3 288.2 209.6 191.0 223.2 198.3 220.3 223.2 217.8 241.3 254.0 302.4 200.2 178.7 208.6 209.5 236.4 243.2 208.6 230.0 272.6 308.3 222.4 190.4 223.8 232.3 260.0 248.5 227.0 237.6 283.8 319.7 -106- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Individual Body Weights for Rats Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weight g D a y 14 Male, VIIB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 312.2 308.2 326.1 348.6 335.7 324.5 333.1 323.5 342.9 304.3 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908 909 910 349.6 308.6 288.6 311.0 324.3 328.9 315.8 332.2 332.7 347.1 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 242.9 200.8 238.6 243.2 266.8 257.9 245.9 246.1 288.2 321.6 318.1 311.5 329.5 354.5 337.6 326.6 337.0 326.1 347.2 307.0 351.7 310.2 296.0 315.4 328.8 329.8 320.1 337.8 336.2 352.7 246.5 218.1 254.4 258.2 283.1 261.0 256.3 264.5 298.8 323.3 317.2 311.0 327.6 358.6 336.4 329.3 345.8 325.6 353.2 307.7 352.0 310.2 302.9 317.1 329.8 332.7 317.8 334.6 339.1 355.7 253.3 240.1 268.6 264.9 285.4 268.6 269.0 279.3 308.1 330.3 319.4 319.9 331.1 358.9 338.4 334.1 344.0 329.3 354.1 313.1 361.7 314.2 309.8 320.6 333.8 337.2 321.5 341.4 339.3 358.9 273.6 249.3 273.1 277.2 292.3 269.3 275.6 285.4 313.9 335.5 325.4 320.6 336.6 372.5 340.3 338.6 347.4 334.5 354.3 320.0 366.5 321.3 314.4 323.3 342.7 344.7 325.1 344.2 344.1 367.8 275.5 264.6 282.2 288.8 296.1 281.3 287.0 291.0 320.4 338.5 299.2 297.0 305.5 336.6 312.8 308.1 322.8 310.9 330.5 292.3 337.5 296.7 288.0 300.2 309.6 318.4 298.6 315.4 316.6 337.5 247.8 226.7 257.5 252.5 266.1 257.0 258.6 261.2 296.0 303.9 - 107- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 I n d i v i d u a l B o d y Wei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 282.0 291.6 294.7 282.1 276.4 298.1 286.2 275.0 298.7 263.8 287.3 288.3 300.7 283.6 282.5 308.9 288.2 277.4 301.9 265.9 293.0 293.6 312.1 291.2 287.5 312.2 292.7 281.0 304.4 270.7 303.4 301.2 321.2 303.1 291.7 323.6 298.3 288.6 308.0 274.7 311.9 311.7 331.3 312.2 295.1 332.1 307.5 293.5 319.6 284.5 Male, IIIC 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 286.3 281.9 321.6 272.5 288.4 277.2 294.7 271.1 283.6 262.2 290.5 286.8 325.5 275.6 295.4 284.6 307.1 274.2 291.0 267.3 300.5 287.1 336.4 279.0 304.4 287.1 311.9 278.0 295.6 273.8 309.7 298.6 346.6 283.7 313.2 292.6 317.9 283.0 303.3 273.9 314.4 299.0 355.0 286.4 321.0 296.4 334.9 291.7 306.8 280.3 Male, VC 1 mg/kg 501 502 503 504 505 506 507 508 509 510 290.3 282.9 295.4 278.3 291.7 292.7 314.5 276.4 291.7 278.3 289.2 285.3 302.2 284.5 287.8 297.4 317.8 285.1 298.2 285.2 298.8 290.9 306.9 285.5 294.5 306.3 331.7 287.1 309.3 288.3 308.5 298.8 313.7 294.4 304.6 311.1 344.0 293.3 316.4 295.0 316.5 306.1 316.5 304.1 304.2 322.7 358.7 299.0 322.6 303.3 - 108- Revision Number 1 DuPont-14162 .ghts for Rats Print Date: 16-Apr-2004 Print Time: 12:30:54 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 319.3 315.2 339.9 320.6 305.4 342.8 310.6 301.0 332.9 288.8 328.2 322.9 344.4 325.3 311.2 349.5 318.5 307.2 336.2 291.2 329.9 327.8 353.9 332.1 314.2 358.2 315.7 312.9 341.7 293.4 335.8 333.7 353.6 333.9 318.3 360.0 319.7 315.3 340.9 296.0 323.3 308.0 359.1 292.8 329.1 306.3 342.6 298.6 313.9 291.6 329.6 313.9 373.2 299.6 333.3 311.2 349.4 305.5 318.4 290.2 336.4 316.8 378.0 302.7 342.7 312.8 356.5 308.8 325.9 298.8 342.0 321.8 388.6 306.8 349.6 321.5 370.2 316.6 335.0 301.4 324.5 318.6 324.1 312.9 310.5 332.6 377.3 310.9 333.2 317.0 327.9 324.5 325.4 314.7 318.7 337.3 386.7 312.6 339.2 324.4 332.3 329.2 332.0 322.8 321.8 344.7 400.4 317.9 344.5 330.0 338.4 337.5 333.3 326.4 331.9 347.7 404.8 323.3 351.9 340.0 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_______ Study: 15073 1025 I n d i v i d u a l B o d y Wei Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 345.4 341.7 360.6 342.5 326.4 372.2 322.0 322.0 353.1 304.1 Male, IIIC 0.3 mg/kg 347.4 340.4 366.7 341.0 326.2 374.1 324.4 319.1 355.8 303.6 353.6 346.8 369.9 349.5 325.6 380.5 328.1 324.9 360.3 306.6 358.8 353.4 377.1 357.9 333.9 387.4 336.7 331.0 369.5 311.4 364.1 360.7 387.9 362.6 339.9 393.6 336.9 335.5 373.4 315.9 301 302 303 304 305 306 307 308 309 310 348.1 326.1 398.8 309.8 357.2 326.0 373.0 324.9 337.1 301.4 345.8 326.4 396.6 307.9 362.9 323.9 384.7 323.5 339.2 306.4 353.2 331.7 401.4 310.9 370.4 329.3 388.0 336.5 342.7 310.7 360.7 333.8 409.9 320.8 376.9 334.4 392.4 340.3 344.9 310.2 364.0 340.7 414.5 324.9 380.7 340.5 405.4 345.8 358.2 315.1 Male, VC 1 mg/kg 501 502 503 504 505 506 507 508 509 510 342.3 346.1 340.0 329.2 334.0 351.9 412.6 327.3 351.8 342.1 347.4 344.9 339.6 329.0 342.4 353.3 417.7 329.3 357.0 339.5 350.6 350.4 342.9 335.8 346.8 355.5 434.0 329.9 364.3 346.2 354.8 358.7 352.8 338.3 348.4 357.5 434.8 337.1 365.8 356.5 364.2 362.3 355.9 343.3 354.6 366.7 450.9 344.1 372.0 360.3 - 109- .ghts for Rats Body Weight g D a y 14 339.1 325.6 353.5 334.1 311.5 362.1 308.2 302.2 340.1 291.3 331.1 313.1 378.6 298.0 352.7 306.2 361.9 316.9 326.6 290.5 329.5 3 3 3 -9 330.2 316.3 321.2 329.8 410.3 312.9 342.2 331.7 Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 I n d i v i d u a l B o d y W ei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, VIIC 3 mg/kg 701 702 703 704 705 705 707 708 709 710 290.1 281.5 286.3 275.1 282.2 289.7 283.8 286.8 297.8 272.3 296.4 287.1 287.3 274.6 285.9 291.7 287.2 292.6 299.4 272.7 304.5 295.6 290.7 276.2 292.5 298.2 296.0 298.0 306.5 275.7 310.0 298.0 293.1 278.8 302.1 302.4 304.7 302.2 312.5 282.1 314.2 305.2 298.5 282.1 308.4 316.2 312.0 310.5 321.3 292.2 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 294.3 287.5 284.9 282.3 269.7 287.4 285.4 265.7 280.9 280.9 302.4 288.8 289.7 291.2 278.7 293.8 288.7 271.3 284.1 283.8 311.4 294.6 291.1 291.0 279.0 303.0 290.8 272.5 282.5 289.8 313.7 300.2 292.0 298.4 283.2 307.0 293.1 275.9 290.7 296.0 323.9 302.7 295.2 305.8 290.2 317.6 301.0 283.2 289.6 303.3 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 277.2 281.6 304.9 277.1 271.6 286.1 298.4 279.4 299.5 264.7 268.8 283.4 302.1 274.0 267.9 283.1 292.4 278.0 294.4 266.9 273.9 284.9 305.7 258.4 273.1 279.4 294.7 282.3 284.9 268.8 274.4 286.0 305.0 257.1 276.8 271.1 303.1 288.5 303.7 278.8 286.9 289.7 315.0 276.5 285.6 285.3 311.7 295.4 306.9 281.6 - 110- Revision Number 1 DuPont-14162 .ghts f o r .R a t s Print Date: 16-Apr-2004 Print Time: 12:30:54 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 325.5 313.2 301.7 288.0 318.8 318.8 320.3 322.2 323.3 297.3 326.7 318.6 307.2 286.1 320.6 324.9 321.9 325.5 331.8 304.5 334.9 328.0 312.3 288.7 329.9 327.3 329.4 329.2 332.9 310.9 338.9 327.7 314.1 288.2 328.9 331.0 337.8 338.1 334.5 313.7 328.6 315.8 301.1 316.4 298.0 325.8 304.5 295.1 298.3 312.9 333.9 317.6 305.4 321.2 302.4 330.6 311.5 297.9 305.2 317.7 343.3 325.5 308.4 330.2 305.7 341.1 318.2 303.0 307.5 323.1 340.9 320.7 313.8 333.4 313.6 342.4 322.6 308.3 315.0 326.4 297.5 304.2 327.3 294.0 290.1 300.2 321.3 304.7 322.8 293.0 301.2 311.1 333.3 298.1 293.7 305.9 328.0 313.6 323.4 299.1 307.3 314.5 333.9 304.0 295.0 309.0 325.9 318.3 335.9 299.6 301.7 314.6 345.3 294.7 298.9 309.3 328.4 320.2 338.7 305.0 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 I n d iv id u a l Body W eig h ts f o r R a ts Body Weight 9 Day 9 Body Weight 9 D a y 10 Body Weight 9 D a y 11 Body Weight 9 D a y 12 Body Weight 9 D a y 13 Body Weight 9 D a y 14 Male, VIIC 3 mg/kg 701 702 703 704 705 706 707 708 709 710 343.1 336.4 326.7 292.9 330.7 342.3 343.1 344.4 346.2 321.7 343.6 333.8 320.0 296.0 337.2 341.3 347.8 350.5 344.2 328.8 348.9 340.9 328.3 296.5 336.8 345.9 337.1 348.8 350.7 327.0 353.8 348.4 333.7 298.7 338.7 349.8 341.4 360.5 358.5 334.5 360.1 355.3 335.7 305.5 344.4 360.8 351.0 366.4 365.5 337.1 331.3 323.6 313-8 275.5 321.6 324.4 316.1 334.4 328.5 313-5 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 357.0 331.1 320.3 341.5 318.7 350.3 324.8 316.8 323.8 335.3 353.3 337.1 321.5 342.4 318.3 350.9 326.7 316.1 328.2 339.8 361.7 339.1 326.5 340.1 323.7 351.7 333.1 320.3 332.3 341.7 371.6 340.8 330.1 348.5 327.8 359.0 342.8 324.7 336.5 346.0 379.4 349.6 334.6 353.2 332.1 363.1 346.9 329.9 343.3 352.5 349.9 324.0 307.5 321.6 302.9 333.5 323.0 301.9 319.9 324.0 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 310.6 317.2 356.0 308.4 301.1 315.1 337.3 326.1 345.3 310.9 316.9 318.4 346.4 305.6 298.5 316.5 339.1 325.5 339.7 312.4 320.4 325.0 350.6 314.9 308.3 319.1 341.9 330.9 351.3 312.0 323.4 333.1 361.7 325.0 312.7 330.0 355.1 336.6 360.0 316.0 327.5 337.8 368.8 322.4 316.3 333.9 359.3 342.0 361.7 320.0 302.2 307.6 334.7 299.7 290.9 308.0 331.7 310.4 327.0 295.7 - Ill - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:30:54 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice __________ Revision Number 1 DuPont-14162 Appendix C Individual Food Consumption for Rats - 112- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 INDIVIDUAL FOOD CONSUMPTION FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA IB TUB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day g/anm/day = grams/animal/day -113- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Individual Food Consumption for Rats Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 10 Food Cons. g/anm/day D a y 13 Male, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 25.3 26.6 22.9 25.3 25.4 24.9 23.9 25.7 29.0 23.4 26.5 27.7 23.7 30.1 23.7 24.1 24.4 26.4 32.2 25.7 26.5 29.3 27.3 28.1 24.3 25.3 26.0 26.4 31.5 26.3 25.1 28.7 23.1 25.5 23.9 26.0 25.5 25.7 30.5 27.0 Male, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 26.8 22.7 23.6 23.3 26.6 26.4 23.8 23.6 28.6 26.9 27.5 26.2 25.3 23.9 26.6 26.4 26.7 24.4 25.0 26.5 27.8 25.9 26.0 25.8 25.7 27.7 25.1 26.9 28.0 27.5 28.8 26.5 23.4 24.4 23.3 26.1 26.3 25.1 24.5 26.2 Male, VA 1 mg/kg 501 502 503 504 505 506 507 508 509 510 23.6 24.5 24.4 25.4 25.4 24.8 26.0 26.3 28.3 24.7 25.2 25.3 27.3 28.3 25.0 27.9 27.5 26.6 28.5 25.8 27.4 24.8 28.4 27.7 24.5 27.9 27.4 28.4 50.5 27.4 25.7 26.0 24.8 27.5 21.7 27.9 26.1 27.9 29.0 26.3 -114- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:06 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Male, V I IA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 23.3 28.2 23.9 30.0 24.0 23.5 26.0 26.6 27.4 24.0 25.6 28.7 25.6 33.7 24.9 26.8 27.3 26.5 25.9 22.9 Male, IXA 10 mg/kg 901 902 903 904 905 906 907 908 909 910 27.4 25.3 21.7 23.7 20.5 24.7 24.4 24.5 23.7 19.9 25.0 23.5 17.0 22.9 20.5 20.0 22.6 19.7 22.3 16.7 Male, XIA 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 17.2 21.1 14.2 16.1 17.9 14.2 15.4 17.3 17.8 19.7 3.4 1.0 17.9 1.7 18.9 14.6 11.8 16.9 1.0 19.7 Food Cons. g/anm/day D a y 10 27.2 32.5 28.9 35.1 25.3 33.0 31.1 26.5 35.5 25.4 30.4 29.7 24.8 25.3 22.8 4.2 29.2 27.9 26.3 22.5 24.2 20.4 22.1 32.3 24.4 29.2 26.0 30.8 21.9 22.8 I n d iv id u a l F ood C o n su m p tio n f o r R a ts Food Cons. g/anm/day D a y 13 26.2 29.4 24.8 34.3 24.5 25.0 29.3 25.1 25.8 23.9 23.7 24.1 18.1 25.0 21.3 19.3 23.4 20.8 24.0 18.7 29.4 26.7 22.2 29.8 19.8 32.1 27.8 25.3 29.6 22.5 - 115- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:06 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 I n d iv id u a l F ood C o n su m p tio n f o r R a ts Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 10 Food Cons. g/anm/day D a y 13 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 28.0 25.9 28.7 27.0 24.3 24.7 28.1 22.9 27.1 25.9 25.5 26.1 28.5 26.5 23.8 23.5 25.3 23.7 26.1 28.0 29.4 26.0 30.1 29.0 25.1 25.0 27.4 24.0 26.7 28.4 25.6 25.4 29.5 27.5 24.1 23.7 24.4 23.8 24.3 29.4 Male, I I I B 0.3 mg/leg 301 302 303 304 305 306 307 308 309 310 21.5 24.1 27.5 29.0 27.5 25.0 26.6 24.2 24.7 26.6 21.7 24.8 27.8 25.2 26.5 25.1 28.2 24.2 24.2 27.4 23.5 23.2 27.7 27.1 27.5 25.4 29.6 25.4 25.3 26.0 23.7 23.6 28.4 26.6 27.4 23.5 29.5 24.2 25.1 25.7 Male, VB 1 mg/kg 501 502 503 504 505 506 507 508 509 510 25.0 22.8 25.7 24.3 28.8 28.0 25.4 22.8 27.9 32.7 23.4 21.5 24.8 35.3 29.9 28.9 25.9 24.0 28.0 34.8 23.1 20.9 25.6 30.5 31.5 31.8 26.2 23.1 25.7 28.2 20.7 21.2 26.4 25.5 31.0 31.1 24.8 24.8 31.3 27.6 - 116- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:06 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________ Study: 15073 1025 Food Cons. g/amn/day Day 3 Food Cons. g/anm/day Day 7 Male, VIIB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 24.9 23.7 22.5 25.4 23.1 23.4 23.7 25.4 23.2 21.5 22.9 23.3 21.5 26.7 22.1 22.7 25.9 24.3 25.1 20.5 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908 909 910 26.3 23.1 31.6 27.2 22.2 25.8 23.7 25.3 26.5 26.6 26.0 22.0 19.9 32.5 19.9 22.5 24.3 20.7 15.9 24.3 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 16.4 15.8 16.8 11.5 9.1 11.2 16.7 19.2 13.8 17.4 26.2 0.5 13.7 20.0 8.6 10.1 10.2 5.5 17.7 20.8 Food Cons. g/anm/day D a y 10 22.5 24.2 23.1 27.7 21.8 23.7 23.9 27.1 29.2 22.6 34.6 22.1 31.4 25.4 23.7 31.4 23.8 27.1 31.4 27.6 24.9 22.6 23.1 31.7 29.3 25.6 26.2 26.9 30.9 28.9 I n d iv id u a l F ood C o n su m p tio n f o r R a ts Food Cons. g/anm/day D a y 13 22.3 23.4 21.6 27.7 19.6 22.9 24.1 24.6 24.0 20.9 27.1 24.6 29.0 23.2 24.1 26.3 24.5 26.1 28.1 26.8 29.0 28.8 28.1 34.6 28.2 27.0 30.0 27.3 31.6 27.7 - 117- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:06 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice________ ___ Study: 15073 1025 Individual Food Consumption for Rats Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day Day 10 Food Cons g/anm/day D a y 13 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 26.2 24.3 NM 27.7 22.9 30.6 23.9 23.4 29.4 23.5 . 25.6 25.7 36.2 30.1 24.1 29.5 25.0 24.5 27.0 22.6 26.3 24.3 30.0 29.9 23.2 31.0 23.1 24.1 37.2 21.7 26.3 26.6 34.4 30.6 24.3 30.8 23.8 25.4 29.3 21.'6 Male, IIIC 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 25.8 23.7 29.0 31.9 27.6 24.7 27.7 31.6 26.8 21.2 26.8 23.3 28.1 24.2 14.1 23.2 30.0 '2 4 . 0 25.4 22.0 26.1 22.0 29.9 26.0 29.4 23.8 31.8 24.5 27.5 21.2 25.9 23.2 29.0 26.9 28.8 24.5 28.8 27.6 26.8 21.6 Male, VC 1 mg/kg 501 502 503 504 505 506 507 508 509 510 26.6 24.7 25.6 24.0 26.4 27.3 33.9 27.2 26.1 27.2 27.6 26.7 23.9 23.9 24.5 27.7 35.9 24.4 28.0 28.1 25.9 28.3 23.3 23.1 25.6 24.7 34.4 24.4 26.4 27.9 24.9 28.2 25.5 24.3 25.4 25.0 36.9 25.2 26.9 29.5 Key: NM = Not Measurable - 118- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:06 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 I n d iv id u a l F ood C o n su m p tio n f o r R a ts Food Cons. g/anm/day Day 3 Food Cons. <g / a n m / d a y Day 7 Food Cons. g/anm/day D a y 10 Food Cons g/anm/day D a y 13 Male, V I IC 3 mg/kg 701 702 703 704 705 706 707 708 709 710 27.4 24.9 23.3 28.7 28.4 25.2 24.7 26.5 27.7 22.8 24.0 23.9 21.6 20.7 29.6 24.8 25.3 26.2 26.7 23.9 24.1 24.3 24.2 20.9 24.2 23.9 26.7 29.0 26.8 28.1 23.1 24.6 24.8 26.2 26.8 24.3 19.2 39.0 28.0 25.6 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 29.1 25.3 27.3 25.8 22.6 25.8 29.0 23.2 21.7 32.4 25.9 23.6 21.1 25.4 23.3 25.1 22.6 22.9 19.7 26.8 27.4 25.2 27.8 26.8 26.1 26.2 27.7 25.2 24.7 27.0 29.8 25.4 23.7 25.4 26.2 24.9 27.2 24.0 24.5 26.8 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 18.6 20.3 23.1 11.4 25.3 34.5 19.4 23.0 24.4 21.4 21.6 24.1 24.2 25.3 21.4 23.4 23.5 24.3 24.0 22.8 21.5 22.2 28.0 22.5 21.6 22.2 23.2 23.5 22.1 21.7 23.9 24.3 28.0 25.7 22.7 24.9 25.8 24.9 25.5 20.7 - 119- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 12:51:05 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix D Individual Clinical Observations and Mortality Records for Rats - 120- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA IB IIIB VB VIIB IXB XEB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 - 121- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Sex Group Animal M IA 101 M IA 102 M IA 103 M IA 104 M IA 105 M IA 106 M IA 107 M IA 108 M IA 109 M IA 110 M IIIA 301 M IIIA 302 M IIIA 303 M IIIA 304 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 122- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Individual Clinical Observations and Mortality Records for Rats Sex Group Animal Observation Days M IIIA 305 M IIIA 306 M IIIA 307 M IIIA 308 General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 M IIIA 309 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M IIIA 310 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 501 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 502 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 503 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 M VA 504 General observation, No Abnormality Detected Hair Loss, Forelimb, Left Sacrificed by design 0-1 2-14 14 M VA 505 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 506 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 507 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VA 508 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 123- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Sex Group Animal M VA 509 M VA 510 M VIIA 701 M VI IA 702 M VIIA 703 M VIIA 704 M VIIA 705 M VIIA 706 M VIIA 707 M VIIA 708 M VIIA 709 M VIIA 710 M IXA 901 M IXA 902 M IXA 903 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 - 124- Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Sex Group Animal M IXA 904 M IXA 905 M IXA 906 M IXA 907 M IXA 908 M IXA 909 M IXA 910 M XIA 1101 M XIA 1102 M XIA 1103 M XIA 1104 M XIA 1105 M XIA 1106 M XIA 1107 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 2 5 -Mar-2005 Print Time: 13:41:01 -125- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_____________________________________________________ _______________________DuPont-14162 Study: 15073 1025 Sex Group Animal M XIA 1108 M XIA 1109 M XIA 1110 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Hair Loss, Forelimb, Right Sacrificed by design 0-9 10-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 126- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_____________________ _______________________________________________________ DuPont-14162 Study: 15073 1025 Sex Group Animal M IB 101 M IB 102 M IB 103 M IB 104 M IB 105 M IB 106 M IB 107 M IB 108 M IB 109 M IB 110 M IIIB 301 M IIIB 302 M IIIB 303 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design 0-14 9-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Hair Loss, Forepaw, Bilateral Sacrificed by design 0-8 9-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 127- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice________ ____ Study: 15073 1025 Sex Group Animal Observation Individual Clinical Observations and Mortality Records for Rats Days M IIIB 304 M IIIB 305 M IIIB 306 M IIIB 307 M IIIB 308 M IIIB 309 M IIIB 310 M VB 501 M VB 502 M VB 503 M VB M VB M VB M VB 504 505 506 507 General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormali ty Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 9-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 -128- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Individual Clinical Observations and Mortality Records for Rats Sex Group Animal Observation Days M VB 508 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VB 509 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VB 510 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VIIB 701 M VIIB 702 General observation, No Abnormality Detected Sacrificed by design General observation, NO Abnormality Detected Sacrificed by design 0-14 14 0-14 14 M VIIB 703 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VIIB 704 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VIIB 705 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 M VIIB 706 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 M VIIB 707 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VIIB 708 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M VIIB 709 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 M VIIB 710 General observation, No Abnormality Detected Hair Loss, Forelimb, Left Hair Loss, Forepaw, Left Sacrificed by design 0-9 10-14 10-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 129- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Sex Group Animal M IXB 901 M IXB 902 M IXB 903 M IXB 904 M IXB 905 M IXB 906 M IXB 907 M IXB 908 M IXB 909 M IXB 910 M XIB 1101 M XIB 1102 M XIB 1103 M XIB 1104 M XIB 1105 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 -130- Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and M ice___________ Study: 15073 1025 Sex Group Animal M XIB 1106 M XIB 1107 M XIB 1108 M XIB 1109 M XIB 1110 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 131 - APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 1025 Sex Group Animal M IC 101 M IC 102 M IC 103 M IC 104 M IC 105 M IC 106 M IC 107 M IC 108 M IC 109 M IC 110 M me 301 M me 302 M me 303 M me 304 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormal ity Detected Hair Loss, Forelimb, Left Sacrificed by design 0-11 12-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 132- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ __ Study: 15073 1025 Sex Group Animal M m e 305 M m e 306 M m e 307 M m e 308 M m e 309 M m e 310 M VC 501 M VC 502 M VC 503 M VC 504 M VC 505 M VC 506 M VC 507 M VC 508 Individual Clinical Observations and Mortality Records for Rats Observation General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormali ty Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, NO Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, NO Abnormality Detected Wound, Superficial, Shoulder, Left Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-11 12-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 -133- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Sex Group Animal M VC 509 M VC 510 M VIIC 701 M VIIC 702 M VIIC 703 M VIIC 704 M VIIC 705 M VIIC 706 M VIIC 707 M VIIC 708 M VIIC 709 M VIIC 710 M IXC 901 M IXC 902 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Hair Loss, Forepaw, Right Sacrificed by design 0-8 9-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 -134- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_______ Study: 15073 1025 Sex Group Animal Observation Individual Clinical Observations and Mortality Records for Rats Days M IXC 903 M IXC 904 M IXC 905 M IXC 906 General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormali ty Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 M IXC 907 M IXC 908 M IXC 909 M IXC 910 M XIC 1101 General observation, No Abnormality Detected Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design 0-11 12-14 12-14 14 0-14 14 0-14 14 0-14 14 0-14 14 M XIC 1102 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M XIC 1103 General observation. No Abnormality Detected Sacrificed by design 0-14 14 M XIC 1104 General observation, No Abnormality Detected Sacrificed by design 0-14 14 M XIC 1105 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 135- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 1025 Sex Group Animal M XIC 1106 M XIC 1107 M XIC 1108 M XIC 1109 M XIC 1110 Individual Clinical Observations and Mortality Records for Rats Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 25-Mar-2005 Print Time: 13:41:01 - 136- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix E Individual Animal Clinical Pathology Data for Rats - 137- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA FOR RATS EXPLANATORY NOTES STUDY DESIGN APFO H-24921 (Linear/Branched) IA IIIA VA VI IA IXA XIA Groups H-26313 A PFO (Linear) IB IIIB VB VIIB IXB XIB H-26225 APFO (Branched) IC IIIC VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 A B B R E V IA T IO N S General: mg/kg Mod - mg/kg/day - moderate Individual Red Blood Cell Morphology Values: ANIS anisocytosis MIC microcytes MAC macrocytes POLY polychromasia HYPO hypochromasia ECHI echinocytes ACAN acanthocytes TARG target cells RX rouleaux HJB Howell-Jolly body OTHR other red blood cell morphology - not observed or not examined; see SCH schistocyte POIK poikilocytosis whole blood sample condition Individual Clinical Chemistry Values: S H E M - h e m o lysis from vena cava sample SL I P - lip e m i a fr o m vena cava sample SICT - icterus from vena cava sample CHOL - cholesterol TRIG - triglycerides HDL - high-density lipoprotein cholesterol nonHDL - non-high-density lipoprotein cholesterol HEM - hemolysis from orbital sinus sample LIP - lipemia from orbital sinus sample ICT - icterus from orbital sinus sample -138- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________________________ Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA FOR RATS EXPLANATORY NOTES (Continued) NOTES : During the collection of blood and tissues for H-24921 Set A animals, a decision to prepare blood smears was made. All remaining animals are included in the appendix. W h e n individual animal data are not reported, it m a y be due to one of the following reasons or other reasons, all of which are explained in the study records: the s a m p l e w a s c l o t t e d (CLOT) t h e r e w a s i n s u f f i c i e n t s a m p l e for t e s t i n g (QNS) a v a l i d r e s u l t c o u l d n o t b e o b t a i n e d (RNV) the sample was not suitable for testing the animal died prior to sample collection n o s a m p l e w a s a v a i l a b l e for t e s t i n g (NSR) n o t p e r f o r m e d (NP) - 139- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, Group IA - 0 mg/kg H-24921 - D a y 14 Animal 108 109 110 ANIS _ - MIC _ _ - MAC POLY _ - - Male, G r o u p I I I A - 0.3 m g / k g H - 2 4 9 2 1 - D a y 14 Animal ANIS MIC . MAC POLY 307 308 309 310 _ - - _ - - _ - - Male, G r o u p V A - 1 m g / k g H - 2 4 9 2 1 - D a y 14 Animal 507 508 509 510 ANIS _ - - MIC _ _ - MAC POLY _ - HYPO _ - - HYPO _ - - HYPO _ - ECHI _ - - ACAN Trace - - TARG - - ECHI - - ACAN - Trace - - TARG - ECHI - - - ACAN - Trace - TARG _ - RX HJB OTHR _-- -- RX HJB OTHR ---- -- RX HJB _- -- -- -' OTHR Revision Number 1 DuPont-14162 - 140- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Clinical Pathology Data for Rats Male, G r o u p V I I A - 3 m g / k g H - 24921 - D a y 14 Animal 707 708 709 710 ANIS _ - - NP MIC NP MAC _ NP POLY _ - NP Male, G r o u p IX A - 10 m g / k g H-24 9 2 1 - D a y 14 Animal 907 908 909 910 ANIS _ NP MIC _ _ - NP MAC NP POLY _ NP Male, Group XIA - 30 mg/kg H-24921 Animal 1106 1107 1108 1109 1110 ANIS _ ~ - Trace MIC _ - Trace - MAC D a y 14 POLY _ Trace - HYPO _ - NP HYPO _ NP HYPO _ - ECHI _ - NP ACAN _ Mod Trace NP TARG _ - _ NP ECHI _ NP ACAN Few Trace Trace NP TARG _ NP ECHI _ - ACAN Few Trace - Mod Trace TARG _ - RX _ - NP RX _ - - NP RX _ - HJB _ - NP OTHR HJB _ NP OTHR HJB _ - OTHR SCH-TRACE; POK-TRACE - 141- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice _______ ___ I n d iv id u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r R a ts Male, G r o u p IB - 0 m g / k g H - 2 6 3 1 3 - D a y 14 Animal 101 102 103 104 105 106 107 108 109 110 ANIS _ - NP - MIC _ _ - NP - - MAC - NP - - POLY _ - - - NP - - HYPO - - - NP - - Male, G r o u p I I I B - 0.3 m g / k g H-26 3 1 3 - D a y 14 Animal 301 302 303 304 305 306 307 308 309 310 ANIS _ - - NP - - MIC - NP - _ _ _ MAC NP POLY _ NP - - HYPO _ - - NP _ - - ECHI - - - - - NP - - ACAN - - - NP - Trace - TARG - -' - - - NP - - ECHI _ _ NP - - ACAN _ .Trace NP - Trace - TARG NP - ~ - RX - - - - NP - RX - - - NP - - HJB - - - - NP - - OTHR HJB - - - NP - OTHR Revision Number 1 DuPont-14162 - 142- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Clinical Pathology Data for Rats Male, G r o u p V B - 1 m g / k g H - 2 6 3 1 3 - D a y 14 Animal ANIS MIC MAC POLY HYPO 501 502 - 503 - 504 - 505 - 506 - 507 - 508 - 509 - 510 - -------------------- Male, G r o u p V I I B - 3 m g / k g H - 26313 - D a y 14 Animal ANIS 701 702 703 704 _ 705 706 - 707 - 708 - 709 - 710 MIC MAC --- POLY HYPO -- ____ ------- ---- ------- ECHI ACAN TARG Trace - Trace Trace - Trace - - : _ ECHI ACAN TARG Trace Trace Trace Trace - Trace - Trace _ RX _ : - RX - HJB OTHR _ - _ - HJB OTHR - POIK-TRACE - POIK-TRACE - 143- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 I n d iv id u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r R a ts Male, G r o u p I X B - 10 m g / k g H - 2 6 3 1 3 - D a y 14 Animal ANIS MIC MAC POLY HYPO 901----- 902 ----- 903 ----- 904 ----- 905 ----- 906 ----- 907 ----- 908 ----- 909 ----- 910 Male, G r o u p X I B - 30 m g / k g H - 2 6 3 1 3 - D a y 14 Animal 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 ANIS _ _ _ _ _ _ _ _ _ MIC _ _ _ _ _ _ _ _ _ MAC POLY ___ ___ ___ ___ ___ ___ ___ ___ ___ HYPO ECHI - _ - - _ - ACAN T race Few _ T race Few T race Few Few TARG - _ - - _ - ECHI - - - - __ - ACAN Few Few T race T race Few Few M od TARG - - : - - _ RX - _ - - _ - - RX - : __ - - H JB OTHR - _ POIK-TRACE ~ POIK-TRACE - POIK-TRACE - POIK-TRACE - POIK-TRACE - POIK-TRACE - POIK-TRACE H JB OTHR - POIK-TRACE : POIK-TRACE __ - POIK-TRACE - POIK-TRACE - 144- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Clinical Pathology Data for Rats Male, Group IC - 0 m g / k g H-26225 - Day 14 Animal 101 102 103 104 105 106 107 108 109 110 ANIS Trace - _ - MIC Trace _ - MAC _ - POLY _ - Trace - HYPO _ - ECHI _ - ACAN _ - Trace - TARG _ - - RX _ - - - HJB OTHR _ - - POIK-TRACE - Male, Group IIIC - 0.3 m g / k g H-26225 - D a y 14 Animal ANIS MIC MAC POLY HYPO ECHI ACAN TARG RX HJB OTHR 301 _ _ _ __ _ _ _ 302 - - - _ - ~- - - - 303 - - - - - - Trace - - .- 304 - - - -- - - - - 305 - - - - Trace - - - 306 - - - _ - - - _ - - 307 - - - - - - - - - - 308 - - -- - - Trace - -- 309 - - - - Few - - - 310 - - - - - - - - - - - 145- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in M ale Rats and M ice Revision Number 1 D uP on t-14162 I n d iv id u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r R a ts Male, Group VC - 1 mg/kg H-26225 - D a y 14 Animal ANIS MIC MAC POLY 501 502 503 504 505 505 507 508 509 510 -- - - - -'------------- HYPO Male, G r o u p V I C -3 m g / k g H - 2 6 2 2 5 - D a y 14 Animal ANIS MIC MAC POLY HYPO 701----- 702 ----- 703 ----- 704 ----- 705 706 707 _____ 708 709 710 --------- ECHI _ - - - - ACAN T race T race T race T race T race T race TARG _ - - - ECHI - _ ACAN T race T race T race T race T race TARG - - : - RX - - - - - RX - - : - H JB _ - - - - OTHR PO IK -T R A C E - H JB - - : - OTHR - 146- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-D ay Oral G avage Study in M ale R ats and M ice_______________ R evision Number 1 D u P on t-14162 Individual Animal Clinical Pathology Data for Rats Male, Group IXC - 10 mg/kg H-26225 Animal 901 902 903 904 905 906 907 908 909 910 ANIS _ - _ - - MIC _ - _ - _ _ - MAC D a y 14 POLY Trace - - - - - - - Male, G r o u p X I C - 30 m g / k g H - 2 6 2 2 5 - D a y 14 Animal 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 ANIS _ - MIC _ _ _ - - _ - - MAC _ POLY _ - - HYPO _ _ - - - HYPO _ - _ ECHI - - _ - ACAN - Trace Trace Trace Trace Mod Few TARG - - - _ - ECHI M od - - - - - _ - - ACAN M od T race Few T race T race T race T race Few Few TARG _ - - _ - - RX : - _ - RX _ - - _ - - HJB OTHR : POIK-TRACE - _ - H JB OTHR - - SCH-TRACE - POIK-TRACE - _ - POIK-TRACE - POIK-TRACE - 147- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, Group IA - 0 mg/kg H-24921 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 101 102 103 104 105 106 107 108 109 110 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 37 38 63 76 38 40 55 65 59 39 TRIG mg/dL 46 38 53 77 52 107 34 73 70 60 Male, G r o u p I I I A - 0.3 m g / k g H - 2 4 9 2 1 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 301 302 303 304 305 306 307 308 309 310 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 38 74 33 36 57 38 52 56 56 46 TRIG mg/dL 41 33 43 58 42 52 70 48 60 63 HDL mg/dL 18 19 25 29 19 19 20 24 24 17 nonHDL mg/dL 19 19 38 47 19 21 35 41 35 22 HDL mg/dL 15 29 16 17 25 18 22 23 23 20 nonHDL mg/dL 23 45 17 19 32 20 30 33 33 26 Revision Number 1 DuPont-14162 - 148- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p V A - 1 m g / k g H - 2 4 9 2 1 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 501 502 503 504 505 506 507 508 509 510 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 42 27 26 30 24 25 26 48 48 36 Male, Group V I I A - 3 mg/kg H-24921 - Day 14 Animal SHEM SLIP SICT CHOL mg/dL 701 702 703 704 705 706 707 708 709 710 None None Trace None Trace None None None None None None None None None None None None None None None None None None None None None None None None None 20 22 39 26 22 16 15 16 25 30 TRIG mg/dL 35 29 32 58 31 26 29 40 66 58 TRIG mg/dL 24 53 38 66 28 34 50 29 40 43 HDL mg/dL 19 15 15 16 13 13 15 19 22 16 nonHDL mg/dL 23 12 11 14 11 12 11 29 26 20 HDL mg/dL 11 13 18 13 11 8 8 7 12 12 nonHDL mg/dL 9 9 21 13 11 8 7 9 13 18 Revision Number 1 DuPont-14162 - 149- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ I n d iv id u a l A n im al C li n i c a l P a th o lo g y D a ta f o r R a ts Male, Group IXA - 10 m g / k g H-24921 D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 901 902 903 904 905 906 907 908 909 910 Trace Trace Trace Trace None Small None None None None None None None None None None None None None None None None None None None None None None None None 30 30 28 19 23 95 45 25 23 39 Male, Group XIA - 30 mg/kg H-24921 D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Small Trace Trace Trace Trace None None None Trace None None None None None None None None None None None None None None None None None None None None None 40 47 42 36 42 49 39 34 45 31 TRIG mg/dL 31 34 38 ' 21 31 33 29 26 34 33 HDL mg/dL 12 14 10 10 12 22 12 9 10 11 nonHDL mg/dL 18 16 18 9 11 73 33 16 13 28 TRIG mg/dL 24 38 33 32 37 46 35 34 33 50 HDL mg/dL 15 15 16 13 13 18 15 10 15 12 nonHDL mg/dL 25 32 26 23 29 31 24 24 30 19 Revision Number 1 DuPont-14162 - 150- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p IB - 0 m g / k g H-26 3 1 3 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 101 102 103 104 105 106 107 108 109 110 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 46 40 47 64 37 53 38 28 43 50 TRIG mg/dL 38 58 54 67 53 54 44 50 71 41 Male, G r o u p I IIB - 0.3 m g / k g H-26 3 1 3 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 301 302 303 304 305 306 307 308 309 310 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 24 22 28 29 31 42 53 24 40 33 TRIG mg/dL 28 35 55 43 39 34 37 39 51 57 HDL mg/dL 20 20 22 27 16 22 17 12 17 21 nonHDL mg/dL 26 20 25 37 21 31 21 16 26 29 HDL mg/dL 12 12 16 15 16 19 22 13 18 15 nonHDL mg/dL 12 10 12 14 15 23 31 11 22 18 Revision Number 1 DuPont-14162 -151 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ I n d iv id u a l A n im al C li n i c a l P a th o lo g y D a ta f o r R a ts Male, G r o u p V B - 1 m g / k g H - 26313 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 501 502 503 504 505 506 507 508 509 510 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 19 13 33 40 28 28 25 25 30 51 M a l e , G r o u p V I I B - 3 m g / k g H--2 6 3 1 3 - D a y 1 4 Animal SHEM SLIP SICT CHOL mg/dL 701 702 703 704 705 706 707 708 709 710 None None None None Trace None Trace None None None None None None None None None None None None None None None None None None None None None None None 23 23 17 33 25 27 25 28 20 24 TRIG mg/dL 31 32 37 29 48 42 33 29 34 49 TRIG mg/dL 30 32 33 44 31 40 30 42 33 60 HDL m g/dL 11 9 17 17 16 16 13 14 15 24 nonHDL mg/dL 8 4 16 23 12 12 12 11 15 27 HDL mg/dL 12 13 9 15 10 12 10 12 9 11 nonHDL m g/dL 11 10 8 18 15 15 15 16 11 13 Revision Number 1 DuPont-14162 - 152- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, G r o u p I XB - 10 m g / k g H - 2 6 3 1 3 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 901 902 903 904 905 906 907 908 909 910 None None None Trace None None Trace None None None None None None None None None None None None None None None None None None None None None None None 20 21 30 33 17 22 27 32 32 39 Male, Group XIB - 30 m g / k g H-26313 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 None Trace None None Trace None None Trace None None None None None None None None None None None None None None None None None None None None None None 50 51 67 57 32 39 31 39 21 24 TRIG mg/dL 34 47 39 25 27 57 50 45 38 59 TRIG mg/dL 57 35 29 43 39 43 50 43 40 30 HDL mg/dL 9 9 13 14 9 10 10 13 12 13 nonHDL mg/dL 11 12 17 19 8 12 17 19 20 26 HDL mg/dL 17 18 22 23 10 18 14 11 8 9 nonHDL mg/dL 33 33 45 34 22 21 17 28 13 15 Revision Number 1 DuPont-14162 - 153- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice I n d iv id u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r R a ts Male, Group IC - 0 mg/kg H-26225 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 101 102 103 104 105 106 107 108 109 110 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 63 51 37 37 45 45 40 52 48 41 TRIG mg/dL 43 50 66 29 35 26 40 83 46 29 Male, G r o u p III C - 0.3 m g / k g H - 2 6 2 2 5 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 301 302 303 304 305 306 307 308 309 310 None None None None None None None None None None None None None None None None None None None None . None None None None None None None None None None 34 36 49 39 44 39 51 46 32 45 TRIG mg/dL 42 43 66 23 42 23 56 43 56 57 HDL mg/dL 27 23 18 16 18 21 17 23 20 19 nonHDL mg/dL 36 28 19 21 27 24 23 29 28 22 HDL mg/dL 16 17 19 18 21 19 21 19 15 20 nonHDL mg/dL 18 19 30 21 23 20 30 27 17 25 Revision Number 1 DuPont-14162 -154- APFO (Linear/Branched), APFO (Linear), and APFO (Branched) 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, G r o u p V C - 1 m g / k g H - 2 6 2 2 5 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 501 502 503 504 505 506 507 508 509 510 None None None None None None Trace None None None None None None None None None None None None None None None None None None None None None None None 36 33 27 34 32 25 57 46 38 30 M a l e , G r o u p V I I C - 3 m g / k g H-- 2 6 2 2 5 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 701 702 703 704 705 706 707 708 709 710 None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None 31 35 25 19 24 19 42 19 24 27 TRIG mg/dL 33 35 37 34 22 40 76 49 44 31 TRIG mg/dL 17 33 25 29 21 38 30 25 35 30 HDL mg/dL 16 18 14 18 17 13 26 19 18 15 nonHDL mg/dL 20 15 13 16 15 12 31 27 20 15 HDL mg/dL 16 18 12 13 13 12 17 11 13 13 nonHDL mg/dL 15 17 13 6 11 7 25 8 11 14 Revision Number 1 DuPont-14162 - 155- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice I n d iv id u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r R a ts M a l e , G r o u p I X C - 10 m g / k g H--2 6 2 2 5 - D a y 14 Animal SHEM SLIP SICT CHOL mg/dL 901 902 903 904 905 905 907 908 909 910 None None None None Trace None Trace None None None None None None None None None None None None None None None None None None None None None None None 35 34 17 22 11 30 20 27 43 21 M a l e , G r o u p X I C - 3 0 m g / k g H-- 2 6 2 2 5 - D a y 1 4 Animal SHEM SLIP SICT CHOL mg/dL 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 None None None None Trace None Trace None None None None None None None None None None None None None None None None None None None None None None None 23 36 40 37 26 36 30 28 49 39 TRIG mg/dL 35 37 20 29 18 28 14 23 27 18 TRIG mg/dL 22 25 24 24 24 28 18 27 26 20 HDL mg/dL 18 16 10 12 8 15 10 14 18 11 nonHDL mg/dL 17 18 7 10 3 15 10 13 25 10 HDL mg/dL 13 17 18 18 13 16 13 13 22 16 nonHDL mg/dL 10 19 22 19 13 20 17 15 27 23 Revision Number 1 DuPont-14162 - 156- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, Group IA - 0 m g / k g H-24921 - D a y 14 Animal HEM LIP ICT 101 102 103 104 105 106 107 108 109 110 Trace None None None None Trace None None None None None None None None None None None None None None None None None None None None None None None None Male, G r o u p III A - 0.3 m g / k g H- 2 4 9 2 1 - D a y 14 Animal HEM LIP ICT 301 302 303 304 305 306 307 308 309 310 Trace Trace Trace Trace Trace Trace None Trace Trace None None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 157- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p V A - 1 m g / k g H- 2 4 9 2 1 - D a y 14 Animal HEM LIP ICT 501 502 503 504 505 506 507 508 509 510 Trace Trace None None Trace Trace None Trace Trace Trace None None None None None None None None None None None None None None None None None None None None M ale, G r o u p V I I A - 3 m g / k g H-24921 Animal HEM LIP ICT 701 702 703 704 705 706 707 708 709 710 Trace None Trace None Trace Trace None Trace Trace Trace None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 158- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p I X A - 10 m g / k g H - 2 4 9 2 1 - D a y 14 Animal HEM LIP ICT 901 902 903 904 905 906 907 908 909 910 Small Trace Small Moderate Trace Moderate Small Moderate Small Trace None None None None None None None None None None None None None None None None None None None None M a l e , G r o u p X X A - 3 0 m g / k g H-24921 Animal HEM LIP ICT 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Moderate Moderate Small Moderate Small Small Moderate Trace Small None None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 -159- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p IB - 0 m g / k g H - 2 6 3 1 3 - D a y 14 Animal HEM LIP ICT 101 102 103 104 105 106 107 108 109 110 None None None None None None None Trace Trace None None None None None None None None None None None None None None None None None None None None None Male, G r o u p I I I B - 0.3 m g / k g H - 2 6 3 1 3 - D a y 14 Animal HEM LIP ICT 301 302 303 304 305 306 307 308 309 310 Trace None Trace None Trace None None None None None None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 -160- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, Group V B - 1 m g / k g H-26313 - D a y 14 Animal HEM LIP ICT 501 502 503 504 505 506 507 508 509 510 Trace Trace None Trace None Trace None Trace Trace Trace None None None None None None None None None None None None None None None None None None None None M a l e , G r o u p V I I B - 3 m g / k g H--2 6 3 1 3 Animal HEM LIP ICT 701 702 703 704 705 706 707 708 709 710 Trace Trace Trace Trace Small Trace Trace Trace Trace Trace None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 161 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, Group IXB - 10 m g / k g H-26313 - Day 14 Animal HEM 901 902 903 904 905 906 907 908 909 910 Trace Trace Moderate Small Trace None Small Trace Trace None LIP None None None None None None None None None None ICT None None None None None None None None None None M a l e , G r o u p X I B - 3 0 m g / k g H--2 6 3 1 3 Animal HEM LIP ICT 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Trace Small Small Small Moderate Trace Small Small Moderate Moderate None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 162- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Clinical Pathology Data for Rats Male, G r o u p IC - 0 m g / k g H - 2 6 2 2 5 - D a y 14 Animal HEM LIP ICT 101 102 103 104 105 106 107 108 109 110 Trace None None Trace None None Trace None Trace None None None None None None None None None None None None None None None None None None None None None Male, Group m e - 0.3 mg/kg H-26225 Animal HEM LIP ICT 301 302 303 304 305 306 307 308 309 310 Trace Small Trace Trace Trace Trace None None None Trace None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 163- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, G r o u p V C - 1 m g / k g H - 2 6 2 2 5 - D a y 14 Animal HEM LIP ICT 501 502 503 504 505 506 507 508 509 510 None Trace None None Trace Trace Trace None None None None None None None None None None None None None None None None None None None None None None None M ale, G r o u p V I I C - 3 m g / k g H-26225 Animal HEM LIP ICT 701 702 703 704 705 706 707 708 709 710 Trace Small Trace Trace Trace None Small Trace Trace None None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 164- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Rats Male, G r o u p IXC - 10 m g / k g H-26225 - D a y 14 Animal HEM LIP ICT 901 902 903 904 905 906 907 908 909 910 Trace Trace Trace Small Trace Trace Small Moderate Trace None None None None None None None None None None None None None None None None None None None None None Male, Group XIC - 30 m g / k g H-26225 - D a y 14 Animal HEM LIP ICT 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Small Trace Trace Small Trace Moderate Small Small None Trace None None None None None None None None None None None None None None None None None None None None Revision Number 1 DuPont-14162 - 165- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix F Individual Animal Body and Organ Weights for Rats - 166- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day FBW = Final Body Weight Note 1025 = Rats - 167- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 A Group : IA 0 mg/kg Treatment : 0 mg/kg IA Sex :MALES | ANIMAL | F B W | | (G m s } | (Gms) KIDNEYS %FBW 1 | (Gms) LIVER %FBW | 101 |310.70 | 2.462 0.7924 | 102 |354.40 | 3.154 0.8900 | 103 294.10 j 2.629 0.8939 1 104 |327.70 j 2.795 0.8529 | 105 293.80 \ 2.613 0.8894 | 106 322.30 j 2.634 0.8173 1 107 328.50 j 2.967 0.9032 | 108 331.60 j 3.034 0.9150 1 109 |357.70 j 3.030 0.8471 | 110 328.50 | 3.118 0.9492 | M ean | S.D. i 324.93 21.471 i | 2.844 0.8750 0.247 0.0473 | 8.251 j 12.025 \ 10.247 | 11.603 j 9.985 i 10.253 j 11.246 j 13.241 | 14.506 i 10.471 1 1 | 11.183 \ 1.778 2.6556 3.3931 3.4842 3.5407 3.3986 3.1812 3.4234 3.9931 4.0554 3.1875 3.4313 0.4008 Group : IIIA 0.3 mg/kg Treatment : 0.3 mg/kg IIIA Sex :MALES | ANIMAL | FBW 1 j (Gms) (Gms) KIDNEYS %FBW | 301 j 302 i 303 j 304 | 305 \ 306 j 307 i 308 \ 309 j 310 j 1 | Mean i S.D. 323.80 335.50 303.70 312.90 301.70 312.80 330.10 323.30 313.80 332.50 1 319.01 11.810 2.691 2.977 2.521 2.745 2.340 2.797 2.810 3.067 2.822 2.796 0.8311 0.8873 0.8301 0.8773 0.7756 0.8942 0.8513 0.9487 0.8993 0.8409 2.757 0.8636 0.208 0.0481 1 |(Gms) LIVER %FBW | 10.221 3.1566 j 12.735 3.7958 j 11.189 3.6842 i 11.395 3.6417 \ 10.324 3.4219 \ 10.972 3.5077 | 11.960 \ 12.058 \ 11.534 \ 13.337 1 1 j 11.573 3.6231 3.7297 3.6756 4.0111 3.6248 | 0.988 0.2285 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 - 168- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 A G r o u p : V A 1 m g / k g T r e a t m e n t : 1 m g / k g V A S e x :M A L E S 1 ANIMAL | FBW 1 1 | (Gms) 1 (Gms) KIDNEYS %FBW 1 501 |327.00 1 2.958 0.9046 1 502 324.50 1 2.833 0.8730 1 503 306.90 1 2.846 0.9273 1 504 321.00 1 2.846 0.8866 1 505 292.50 1 2.358 0.8062 1 506 318.00 1 3.041 0.9563 1 507 327.60 1 3.028 0.9243 1 508 349.40 1 3.585 1.0260 1 509 339.60 1 2.656 0.7821 1 510 321.30 1 2.940 0.9150 1 1j 11 1 Mean 322.78 1 2.909 0.9001 1 S.D. 15.751 1 0.311 0.0701 1 |(Gms) LIVER %FBW | 12.546 \ 13.151 i 12.193 | 11.304 | 10.945 | 12.763 | 13.839 | 13.954 | 13.351 | 13.150 1 1 | 12.720 i 1.001 3.8367 4.0527 3.9730 3.5215 3.7419 4.0135 4.2244 3.9937 3.9314 4.0927 3.9381 0.1976 Group : VIIA 3 mg/kg Treatment : 3 mg/kg VIIA Sex :MALES | ANIMAL | FBW | 1 j (Gms) j(Gms) KIDNEYS %FBW | 701 |317.00 | 3.290 1.0379 i 702 357.10 \ 703 318.90 \ 704 392.30 3.250 2.929 3.514 0.9101 0.9185 0.8957 | 705 315.60 2.737 0.8672 i 706 317.90 3.341 1.0510 i 707 329.20 3.267 0.9924 i 708 308.30 1 2.981 0.9669 \ 709 325.50 3.153 0.9687 \ 710 316.00 2.977 0.9421 |1 1 11 | Mean 329.78 i 3.144 0.9550 j S.D. 25.710 0.233 0.0601 1 |(Gms) LIVER %FBW | 16.222 \ 18.230 j 17.227 i 23.449 \ 17.220 \ 17.338 i 18.886 1 16.565 j 19.258 j 14.851 5.1174 5.1050 5.4020 5.9773 5.4563 5.4539 5.7369 5.3730 5.9164 4.6997 I | 17.925 5.4238 j 2.329 0.3904 | \ | | | j j \ \ j \ 1 I | | | | \ i i j j i \ | | 1 | | FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing Study:15073 1025 A G r o u p : I X A 10 m g / k g T r e a t m e n t : 1 0 m g / k g I X A S e x :M A L E S ANIMAL 1 FBW 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 901 902 903 904 905 906 907 908 909 910 1285.50 333.50 241.90 318.50 278.00 241.60 323.00 1281.40 1317.10 1266.60 1 1 i i i i \ i \ i 2.733 2.869 2.351 2.651 2.303 2.235 3.059 2.775 2.704 2.501 0.9573 0.8603 0.9719 0.8323 0.8284 0.9251 0.9471 0.9861 0.8527 0.9381 Mean S.D. 1288.71 1 2.618 0.9099 33.255 i 0.266 0.0603 1 15.544 \ 17.737 i 14.930 i 14.680 \ 15.669 \ 14.302 i 17.183 i 16.646 i 20.082 1 16.134 5.4445 5.3184 6.1720 4.6091 5.6363 5.9197 5.3198 5.9154 6.3330 6.0518 1 1 16.291 5.6720 \ 1.724 0.5146 G r o u p : X I A 3 0 m g / k g T r e a t m e n t : 30 m g / k g X I A S e x :M A L E S ANIMAL 1 FBW 1 1 (Gms) j (Gms) KIDNEYS %FBW 1 (Gms) LIVER %FBW 1101 1255.90 1 NW 1102 253.30 2.276 0.8985 1103 256.40 2.331 0.9091 1104 249.40 2.369 0.9499 1105 259.70 2.457 0.9461 1106 266.40 2.515 0.9441 1107 245.10 2.473 1.0090 1108 280.40 1 2.511 0.8955 1109 252.80 1 2.925 1.1570 1110 269.20 2.588 0.9614 1I 1! Mean 258.86 2.494 0.9634 S.D. 10.487 0.189 0.0808 1 NW \ 18.737 j 16.320 i 15.230 [ 15.890 \ 19.311 i 17.482 \ 18.817 i 19.304 \ 17.905 7.3972 6.3651 6.1067 6.1186 7.2489 7.1326 6.7108 7.6361 6.6512 1 i 17.666 6.8186 \ 1.535 0.5622 *** Lis t i ng Complete *** NW - Not Weighed FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 B G r o u p : I B 0 m g / k g T r e a t m e n t : 0 m g / k g I B S e x :M A L E S 1 ANIMAL 1 FBW 1 (Gms) (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 101 102 103 104 105 106 107 108 109 110 Mean S.D. 1331.40 1318.40 1348.30 343.50 1334.90 1320.40 324.90 1322.50 1353.20 337.10 1 1 [333.46 112.115 1 1 1 1 2.690 2.924 3.147 3.060 2.584 2.822 2.645 2.558 3.259 3.203 0.8117 0.9183 0.9035 0.8908 0.7716 0.8808 0.8141 0.7932 0.9227 0.9502 2.889 0.8657 0.266 0.0625 1 11.345 j 12.960 1 12.234 j 12.030 \ 10.798 j 14.126 \ 11.287 i 11.493 j 12.377 i 12.239 1 1 1 12.089 j 0.958 3.4234 4.0704 3.5125 3.5022 3.2242 4.4089 3.4740 3.5637 3.5042 3.6307 3.6314 0.3468 1 j 1 1 j j j j j j j j 1 1 1 j G r o u p : I I I B 0 . 3 m g / k g T r e a t m e n t : C .3 m g / k g I I I B S e x :M A L E S 1 ANIMAL 1 FBW 1 1 j (Gms) j (Gms) KIDNEYS %FBW 1 301 1 302 1 303 1 304 1 305 1 306 1 307 ! 308 1 309 1 310 Mean 1 S.D. 12 8 6 . 1 0 306.00 338.00 325.90 1342.30 310.00 346.00 319.90 334.70 338.80 1 324.77 19.205 1 j j 1 1 j j j j j I 1 j i 2.184 1.327 2.951 2.852 3.355 2.602 3.091 2.737 3.064 3.070 0.7634 0.4337 0.8731 0.8751 0.9801 0.8394 0.8934 0.8556 0.9154 0.9061 2.723 0.8335 0.586 0.1512 1 1 (Gms) LIVER %FBW 1 10.111 j 11.811 \ 13.322 1 12.330 1 13.143 1 12.121 1 13.568 1 12.061 \ 13.246 1 13.676 3.5341 3.8598 3.9414 3.7834 3.8396 3.9100 3.9214 3.7702 3.9576 4.0366 1 \ 12.539 3.8554 i 1.090 0.1390 1 j 1 i \ j j j j j 1 j 1 1 \ FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl-400 - 171 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing Study:15073 1025 B G r o u p : V B 1 m g / k g T r e a t m e n t : 1 m g / k g V B S e x :M A L E S 1 ANIMAL 1 FBW 1 1 1 (G m s ) 1 (Gms) KIDNEYS %FBW 1 501 1 502 1 503 1 504 1 505 1 506 1 507 1 508 1 509 1 510 1 Mean 1 S.D. 1292.10 268.00 327.50 1330.90 371.50 347.80 1297.40 319.20 1347.10 332.20 [ 1 323.37 30.484 1 2.634 2.878 2.772 2.837 3.138 . 3.091 2.782 2.650 2.860 2.656 1 1 1 2.830 0.174 0.9017 1.0739 0.8464 0.8574 0.8447 0.8887 0.9354 0.8302 0.8240 0.7995 0.8802 0.0790 1 1 (Gms) LIVER %FBW 1 10.663 \ 11.023 i 12.679 \ 14.022 17.696 1 15.895 1 12.058 j 12.318 \ 14.022 1 13.728 1 1 1 13.410 j 2.165 3.6505 4.1131 3.8715 4.2375 4.7634 4.5702 4.0545 3.8590 4.0398 4.1325 4.1292 0.3318 G r o u p : V I I B 3 m g / k g T r e a t m e n t : 3 m g / k g V I I B S e x :M A L E S 1 ANIMAL 1 FBW 1 j (Gms) (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 1 701 1299.20 2.785 0.9308 1 702 297.00 1 2.970 1.0000 i 703 305.50 1 2.497 0.8173 \ 704 336.60 3.236 0.9614 1 705 312.80 2.689 0.8597 \ 706 308.10 1 3.058 0.9925 i 707 322.80 1 2.931 0.9080 1 708 310.90 1 2.861 0.9202 1 709 330.50 3.347 1.0127 i 710 292.30 2.435 0.8330 1I 11 j Mean 311.57 1 2.881 0.9236 \ S.D. 14.524 0.294 0.0698 1 14.578 \ 13.363 i 14.185 i 17.154 \ 15.044 \ 15.874 i 16.441 \ 15.870 \ 16.721 i 14.937 4.8723 4.4993 4.6432 5.0963 4.8095 5.1522 5.0932 5.1045 5.0593 5.1102 1 15.417 4.9440 \ 1.201 0.2278 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 - 172- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing Study:15073 1025 B G r o u p : I X B 1 0 m g / k g T r e a t m e n t : 1 0 m g / k g I X B S e x :M A L E S 1 ANIMAL | FBW 1 | (Gms) (Gms) KIDNEYS %FBW 1 | (Gms) LIVER %FBW 1 901 1 902 1 903 1 904 1 905 1 906 1 907 1 908 1 909 1 910 1 Mean 1 S.D. |337.50 296.70 288.00 300.20 309.60 318.40 298.60 315.40 316.60 337,50 1 1 |311.85 16.695 3.228 2.905 2.783 3.045 2.911 2.993 2.808 2.556 2.782 3.357 0.9564 0.9791 0.9663 1.0143 0.9402 0.9400 0.9404 0.8104 0.8787 0.9947 2.937 0.9421 0.233 0.0592 | 19.971 j 17.937 | 17.977 i 17.369 | 17.043 | 19.541 | 17.466 \ 20.760 j 17.408 j 22.658 1 1 j 18.813 i 1.853 5.9173 6.0455 6.2420 5.7858 5.5048 6.1372 5.8493 6.5821 5.4984 6.7135 6.0276 0.4072 G r o u p : X I B 30 m g / k g T r e a t m e n t : 30 m g / k g X I B 3ex .-MALES 1 ANIMAL | FBW 1 j (Gms) (Gms) KIDNEYS %FBW 1 1101 1 1102 1 1103 1 1104 1 1105 1 1106 1 1107 1 1108 1 1109 1 1110 Mean 1 S.D. |2 4 7 . 8 0 226.70 257.50 |252.50 266.10 257.00 |258.60 261.20 296.00 303.90 I 262.73 22.407 2.459 2.264 2.407 2.430 2.586 1.991 2.332 2.517 2.637 2.565 0.9923 0.9987 0.9348 0.9624 0.9718 0.7747 0.9018 0.9636 0.8909 0.8440 2.419 0.9235 0.189 0.0715 *** Listing Complete *** 1 |(Gms) LIVER %FBW | 16.723 j 16.351 j 17.577 i 17.379 j 18.471 | 13.903 \ 17.418 1 17.806 j 19.815 | 18.700 1 1 I 17.414 \ 1.586 6.7486 7.2126 6.8260 6.8828 6.9414 5.4097 6.7355 6.8170 6.6943 6.1533 6.6421 0.5075 FBW - Final Body Weight | | |. | | | j i \ \ | | 1 1 | | | \ | | | | j j j 1 j | 1 j j - 173- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 C G r o u p : I C 0 m g / k g T r e a t m e n t : 0 m g / k g I C S e x :M A L E S 1 ANIMAL 1 FBW 1 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 101 1 102 1 103 1 104 1 105 1 106 1 107 1 108 1 109 1 110 1 1 1 Mean 1 S.D. 13 3 9 . 1 0 325.60 353.50 334.10 1311.50 362.10 308.20 302.20 340.10 291.30 1 1 326.77 123.064 1 j i j i 1 i j i j 1 j 2.660 2.666 2.782 2.760 2.550 2.866 2.657 2.115 3.067 2.194 0.7844 0.8188 0.7870 0.8261 0.8186 0.7915 0.8621 0.6999 0.9018 0.7532 2.632 0.8043 0.289 0.0559 1 1 (Gms) LIVER %FBW 1 10.913 3.2182 j 10.659 3.2736 1 13.563 \ 13.134 \ 10.262 3.8368 3.9312 3.2944 1 11.369 3.1397 1 9.440 3.0629 \ 10.025 3.3173 \ 11.724 3.4472 j 9.399 1 i 1 11.049 3.2266 3.3748 j 1.429 0.2881 1 1 1 1 1 1 1 1 1 1 1 1 I ! 1 1 G r o u p : I I I C 0. 3 m g / k g T r e a t m e n t : 0 .3 m g / k g I I I C S e x :M A L E S 1 ANIMAL 1 FBW 1 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 301 331.10 1 2.464 0.7442 1 302 313.10 \ 2.905 0.9278 1 303 378.60 \ 3.174 0.8384 1 304 1298.00 \ 2.440 0.8188 1 305 352.70 1 3.265 0.9257 1 306 306.20 1 2.386 0.7792 1 307 361.90 1 2.836 0.7836 1 308 316.90 i 2.378 0.7504 1 309 326.60 \ 2.879 0.8815 1 310 290.50 j 2.419 0.8327 Mean 1 S.D. 1 327.56 1 2.715 0.8282 28.783 \ 0.340 0.0667 1 1 (Gms) LIVER %FBW 1 11.198 1 12.033 l 14.810 j 11.747 j 12.035 j 9.481 \ 13.248 \ 11.236 1 11.568 j 9-971 1 1 1 11.733 \ 1.516 3.3821 3.8432 3.9118 3.9419 3.4122 3.0963 3.6607 3.5456 3.5419 3.4324 3.5768 0.2672 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 - 174- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 C Group : VC 1 mg/kg Treatment : 1 mg/kg VC Sex MALES | ANIMAL | FBW | 1 | (Gms) | (Gms) KIDNEYS %FBW | 501 | 502 1 503 j 504 | 505 | 506 | 507 | 508 | 509 I 510 1 1 | Mean j S.D. |329.50 333.90 330.20 316.30 321.20 329.80 410.30 312.90 |3 4 2 . 2 0 (331.70 I I 335.80 27.561 | \ j j j j | | | | I 1 j j 2.666 2.978 2.788 2.583 2.339 2.605 3.357 2.552 2.896 3.162 0.8091 0.8919 0.8443 0.8166 0.7282 0.7899 0.8182 0.8156 0.8463 0.9533 2.793 0.8313 0.309 0.0600 1 |(Gms) LIVER %FBW | 11.549 3.5050 i 14.688 4.3989 \ 12.814 3.8807 i 12.358 3.9071 \ 12.602 3.9234 j 11.059 3.3532 \ 16.665 4.0617 j 11.399 3.6430 j 14.074 4.1128 j 14.177 1 1 j 13.139 \ 1.753 4.2740 3.9060 0.3303 | j | j | j \ j j \ j | 1 | j Group : VIIC 3 mg/kg Treatment : 3 mg/kg VIIC Sex MALES | ANIMAL |FBW | | I (Gms) I(Gms) KIDNEYS %FBW | |(Gms) LIVER %FBW 701 702 703 704 705 706 707 708 709 710 Mean S.D. |3 3 1 . 3 0 323.60 313.80 |275.50 321.60 324.40 316.10 1334.40 328.50 313.50 1 1 318.27 16.628 | j \ | \ | j j j j I 1 | \ 3.113 2.743 2.704 2.388 2.358 2.507 2.693 3.080 2.785 2.654 0.9396 0.8477 0.8617 0.8668 0.7332 0.7728 0.8519 0.9211 0.8478 0.8466 2.703 0.8489 0.253 0.0607 | 16.405 j 14.858 j 13.346 | 13.492 j 13.427 | 11.964 \ 13.271 | 14.440 j 15.160 | 13.879 I 1 | 14.024 j 1.236 4.9517 4.5915 4.2530 4.8973 4.1751 3.6880 4.1984 4.3182 4.6149 4.4271 4.4115 0.3742 FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 - 175- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073 1025 C G r o u p : I X C 10 m g / k g T r e a t m e n t : 1 0 m g / k g I X C S e x :M A L E S 1 ANIMAL 1 FBW 1 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 901 1349.90 1 3.031 0.8662 902 324.00 i 3.133 0.9670 903 307.50 j 2.596 0.8442 904 1321.60 \ 2.665 0.8287 905 302.90 i 2.787 0.9201 9 0 6 13 3 3 . 5 0 \ 3 . 0 6 8 0 . 9 1 9 9 907 1323.00 \ 2.767 0.8567 908 301.90 \ 2.323 0.7695 909 319.90 \ 2.782 0.8696 910 324.00 1 3.193 0.9855 Mean S.D. 1! 320.82 1 2.835 0.8827 14.489 0.272 0.0657 (Gms) LIVER %FBW 21.150 19.557 16.421 21.062 14.927 18.361 15.425 15.340 21.646 21.644 6.0446 6.0361 5.3402 6.5491 4.9280 5.5055 4.7755 5.0812 6.7665 6.6802 18.553 5.7707 2.809 0.7455 G r o u p : X I C 30 m g / k g T r e a t m e n t : 30 m g / k g X I C S e x :M A L E S ANIMAL 1 FBW 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 Mean S.D. 1302.20 307.60 334.70 299.70 290.90 308.00 331.70 310.40 327.00 295.70 1 1 1 1 1 1 I 1310.79 1 115.311 2.419 2.769 2.908 2.576 2.717 2.449 3.089 2.876 2.745 2.657 0.8005 0.9002 0.8688 0.8595 0.9340 0.7951 0.9313 0.9265 0.8394 0.8985 2.721 0.8754 0.208 0.0516 1 17.853 \ 22.i l l \ 22.453 \ 18.502 i 14.825 i 22.759 \ 19.202 i 19.875 \ 22.138 1 18.080 5.9077 7.3053 6.7084 6.1735 5.0963 7.3893 5.7890 6.4030 6.7700 6.1143 ! 1 19.816 6.3657 2.623 0.7045 *** Listing Complete *** FBW - Final Body Weight 1 1 1 1 1 1 1 1 1 1 1 1 1 1 - 176- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix G Individual Animal Gross Observations for Rats - 177- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL GROSS OBSERVATIONS FOR RATS EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VBA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviation mg/kg = mg/kg/day Note 1025 = Rats - 178- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice ______ Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : IA 0 mg/kg Treatment: 0 mg/kg IA Sex: Males Animal Ref 101 Macroscopic Findings Only Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy 102 No Macroscopic Abnormality Observed : LIVER, KIDNEYS Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 179- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : IA 0 mg/kg Treatment: 0 mg/kg IA Sex: Males Animal Ref Macroscopic Findings Only 106 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 107 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is sign e d off from necropsy 110 No Macroscopic Abnormality Observed : LIVER, KIDNEYS Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 180- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice ___________________ _____ DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IIIA 0.3 m g / k g Treatment: 0.3 m g / k g IIIA Sex: D a t e :2 1 - J U N - 0 4 Males Animal Ref Macroscopic Findings Only 301 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 181 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : IIIA 0.3 m g / k g Treatment: 0.3 m g / k g IIIA Sex: D a t e :2 1 - J U N - 0 4 Males Animal Ref Macroscopic Findings Only 306 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 307 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -182- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : VA 1 mg/kg Treatment: 1 mg/kg VA Sex: Males Animal Ref Macroscopic Findings Only 501 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice K i l l e d o n D a y : 14 A nimal is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 Date:21-JUN-04 - 183- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Listing Showing animal data for individual'animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : VA 1 mg/kg Treatment: 1 mg/kg VA Sex: Males Animal Ref Macroscopic Findings Only 506 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 507 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 184- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : V I IA 3 mg/kg Treatment: 3 mg/kg V I IA Sex: Males D a t e :2 l - J U N - 0 4 Animal Ref Macroscopic Findings Only 701 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 185- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) Dose Group : VIIA 3 mg/kg Treatment: 3 mg/kg VIIA animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 706 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 707 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -186- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_______ __ _______________________________ DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : I X A 10 m g / k g T r e a t m e n t : 10 m g / k g I X A animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 901 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 902 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 904 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 905 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -187- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IX A 10 m g / k g Treatment: 10 m g / k g IX A Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 905 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 907 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 908 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 909 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MIDDLE. No Macroscopic Abnormality Observed : KIDNEYS 910 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -188- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________ ________________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : X I A 30 m g / k g Treatment: 30 m g / k g X I A animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1101 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1102 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MIDDLE. No Macroscopic Abnormality Observed : KIDNEYS 1103 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1104 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1105 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 189- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_________________________________________ DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : X I A 30 m g / k g Treatment: 30 m g / k g X I A Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1106 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1107 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1108 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1109 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1110 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS *** L i s t i n g C o m p l e t e *** - 190- AFFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice _____ ; . Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : IB 0 mg/kg Treatment: 0 m g /kg IB Sex: Males Animal Ref M a c r o s c o p i c F i n d i n g s Only- 101 Terminal Sacrifice Killed on D ay : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 102 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice K i l l e d o n D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 Date: 21- JUN-04 -191- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : IB 0 mg/kg Treatment: 0 mg/kg IB Sex: Males Animal Ref Macroscopic Findings Only 106 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 107 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy 110 No Macroscopic Abnormality Observed : LIVER, KIDNEYS Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 192- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice______________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose G r o u p : IIIB 0.3 m g / k g Treatment: 0.3 m g / k g IIIB Sex: Date:21-JUN-04 Males Animal Ref Macroscopic Findings Only 301 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice K i l l e d o n D a y : 14 A n imal is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d of f from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 193- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) D o s e G r oup : IIIB 0.3 m g / k g Treatment: 0.3 m g / k g IIIB Sex: D a t e :2 1 - J U N - 0 4 Males Animal Ref Macroscopic Findings Only 306 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 307 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice K i l l e d o n D a y : 14 A n imal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 194- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : VB 1 mg/kg Treatment: 1 mg/kg VB Sex: Males Animal Ref Macroscopic Findings Only 501 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d o f f from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 195- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : VB 1 mg/kg Treatment: 1 mg/kg VB Sex: Males Animal Ref Macroscopic Findings Only 506 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 507 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 - 196- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 . 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : VIIB 3 mg/kg Treatment: 3 mg/kg VIIB animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 701 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 197- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose Group : VIIB 3 m g /kg Treatment: 3 mg/kg VIXB Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 706 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 707 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice K i l l e d o n D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : . LIVER, KIDNEYS APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXB 10 m g / k g Treatment: 10 m g / k g IXB animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 901 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 902 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 904 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 905 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 199- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXB 10 m g / k g Treatment: 10 m g / k g IXB Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 905 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 907 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 908 Terminal Sacrifice K i l l e d o n D a y : 14 A n imal is s i g n e d off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 909 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 910 Terminal Sacrifice K i l l e d on D a y : 14 A n imal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 200- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) D o s e Gro u p : X I B 30 m g / k g Treatment: 30 m g / k g X I B animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1101 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1102 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1103 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1104 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g ne d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1105 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -201 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_________________________________________ DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 B (* A P P R O V E D P R O T O C O L *) Dose G r o u p : X I B 30 m g / k g Treatment: 30 m g / k g X IB animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1106 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1107 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1108 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1109 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1110 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS *** L i s t i n g Compl e t e *** - 202- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : IC 0 m g /kg Treatment: 0 m g / k g IC Sex: Males Animal Ref M a c r o s c o p i c F i n d i n g s Only- 101 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 102 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 -203- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : IC 0 mg/kg Treatment: 0 m g /kg IC Sex: Males Animal Ref Macroscopic Findings Only 106 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 107 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy 110 No Macroscopic Abnormality Observed : LIVER, KIDNEYS Terminal Sacrifice K i l l e d on D a y : 14 A nimal is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 -204- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : IIIC 0.3 m g /kg Treatment: 0.3 mg/kg IIIC Sex: D a t e :2 l - J U N - 0 4 Males Animal Ref Macroscopic Findings Only 301 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -205- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : IIIC 0.3 m g / k g Treatment: 0.3 m g / k g IIIC Sex: D a t e :2 l - J U N - 0 4 Males Animal Ref Macroscopic Findings Only 306 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 307 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -206- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : VC 1 mg/kg Treatment: 1 mg/kg VC Sex: Males Animal Ref M a c r o s c o p i c F i n d i n g s Only- 501 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 Date: 21- JUN-04 -207- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : VC 1 mg/kg Treatment: 1 mg/kg VC Sex: Males Animal Ref Macroscopic Findings Only 506 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 507 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice K i l l e d on D a y : 14 A nimal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :2 1 - J U N - 0 4 -208- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice __________ _______________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : VIIC 3 mg/kg Treatment: 3 mg/kg VIIC animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 701 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -209- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) Dose Group : VIIC 3 mg/kg Treatment: 3 mg/kg VIIC animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 706 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 707 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i gned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 210- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ ______________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXC 10 m g / k g T reatment: 10 m g / k g IXC animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 901 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 902 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 904 Terminal Sacrifice K i l l e d o n D a y : 14 A nimal is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 905 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -211 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXC 10 m g / k g Treatment: 10 m g / k g IXC animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 906 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 907 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n ed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 908 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n ed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 909 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 910 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS - 212- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice_____________ ____________________________DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : XIC 30 m g / k g Treatment: 30 m g / k g X IC animals Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1101 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1102 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1103 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1104 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1105 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -213- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 1 0 2 5 C (* A P P R O V E D P R O T O C O L *) D o s e Gro u p : X IC 30 m g / k g Treatment: 30 m g / k g XIC Sex: Males D a t e :2 1 - J U N - 0 4 Animal Ref Macroscopic Findings Only 1106 Terminal Sacrifice K i l l e d o n D a y : 14 A n i m a l is s i g n e d off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1107 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1108 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1109 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s igned off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1110 Terminal Sacrifice K i l l e d on D a y : 14 A n i m a l is s i g n e d off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS *** Listing Comp l e t e *** -214- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix H Individual Rat Beta-Oxidation Data -215- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL RAT BETA-OXIDATION DATA EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA IB IC MB IIIC VB v c vnB VIIC IXB IXC XIB XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviation mg/kg = mg/kg/day -216- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group______ Number Beta-Oxidation Rate (nmol/min/mg protein) 101 17.09 102 16.93 103 14.95 104 14.94 105 14.80 106 17.65 107 26.05 108 23.38 109 19.60 110 16.86 301 13.86 302 16.63 303 16.25 304 17.26 305 16.30 306 16.40 307 23.65 308 20.47 309 24.58 310 14.57 501 29.38 502 28.73 503 25.82 504 18.98 505 30.82 506 30.12 507 27.36 508 31.74 509 20.56 510 26.09 - 217- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VIIA 701 702 703 704 705 706 707 708 709 710 59.93 54.79 74.45 40.52 54.04 58.77 70.55 62.69 50.56 49.92 IXA 901 902 903 904 905 906 907 908 909 910 82.72 101.91 115.55 52.42 79.18 97.52 72.55 75.17 72.86 72.37 XIA 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 93.91 102.06 97.54 64.77 100.30 71.03 68.73 65.20 80.42 103.40 -218- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice , _____________________________DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) 101 19.29 102 18.22 103 12.37 104 9.81 105 17.61 106 21.27 107 14.46 108 15.40 109 16.78 110 12.00 301 15.71 302 21.72 303 14.39 304 12.43 305 20.50 306 15.49 307 16.59 308 14.98 309 12.22 310 15.71 501 29.03 502 28.05 503 24.26 504 33.97 505 38.22 506 28.10 507 26.60 508 39.73 509 25.55 510 24.29 -219- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VIIB 701 702 703 704 705 706 707 708 709 710 56.15 48.99 58.17 47.97 88.36 81.91 73.75 70.33 66.61 82.36 IXB 901 902 903 904 905 906 907 908 909 910 XIB 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 59.47 79.42 85.31 66.29 91.07 82.03 62.62 74.45 71.19 75.80 101.30 106.79 85.94 82.90 96.87 73.28 96.05 97.16 87.73 61.90 -220- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice__________________________________________DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) 101 13.35 102 10.36 103 8.61 104 14.46 105 14.85 106 12.64 107 13.82 108 20.48 109 11.52 110 10.28 301 14.43 302 18.14 303 10.07 304 8.14 305 10.92 306 11.54 307 17.73 308 17.80 309 10.64 310 9.54 501 13.74 502 16.13 503 13.83 504 12.00 505 14.66 506 11.25 507 17.63 508 19.42 509 14.43 510 20.70 -221 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Data Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VIIC 701 702 703 704 705 706 707 708 709 710 21.69 21.80 18.34 14.05 15.09 17.25 13.08 22.29 17.23 13.59 IXC 901 902 903 904 905 906 907 908 909 910 XIC 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 26.89 34.80 30.64 43.61 18.41 18.69 27.67 20.55 34.37 31.61 32.28 59.10 27.60 44.94 21.14 50.85 37.19 46.31 26.51 29.94 -222- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________________________ Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Liver Data Animal Relative Liver to Full Group_______ Number______ Body Weight (%) 101 2.7 102 3.4 103 3.5 104 3.5 105 3.4 106 3.2 107 3.4 108 4.0 109 4.1 110 3.2 301 3.2 302 3.8 303 3.7 304 3.6 305 3.4 306 3.5 307 3.6 308 3.7 309 3.7 310 4.0 501 3.8 502 4.1 503 4.0 504 3.5 505 3.7 506 4.0 507 4.2 508 4.0 509 3.9 510 4.1 -223- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ . Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Liver Data Group Animal Number Relative Liver to Full Body Weight (%) VILA. 701 702 703 704 705 706 707 708 709 710 5.1 5.1 5.4 6.0 5.5 5.5 5.7 5.4 5.9 4.7 IXA 901 902 903 904 905 906 907 908 909 910 5.4 5.3 6.2 4.6 5.6 5.9 5.3 5.9 6.3 6.1 XIA 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 No data 7.4 6.4 6.1 6.1 7.2 7.1 6.7 7.6 6.7 -224- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Liver Data Animal Relative Liver to Full Group_______ Number______ Body Weight (%) 101 3.4 102 4.1 103 3.5 104 3.5 105 3.2 106 4.4 107 3.5 108 3.6 109 3.5 110 3.6 301 3.5 302 3.9 303 3.9 304 3.8 305 3.8 306 3.9 307 3.9 308 3.8 309 4.0 310 4.0 501 3.7 502 4.1 503 3.9 504 4.2 505 4.8 506 4.6 507 4.1 508 3.9 509 4.0 510 4.1 -225- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Liver Data Animal Relative Liver to Full Group_______ Number______ Body Weight (%) VIIB 701 702 703 704 705 706 707 708 709 710 4.9 4.5 4.6 5.1 4.8 5.2 5.1 5.1 5.1 5.1 IXB 901 902 903 904 905 906 907 908 909 910 XIB 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 5.9 6.0 6.2 5.8 5.5 6.1 5.8 6.6 5.5 6.7 6.7 7.2 6.8 6.9 6.9 5.4 6.7 6.8 6.7 6.2 -226- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice__________ _______________________________ DuPont-14162 Individual Rat Beta-Oxidation Liver Data Animal Relative Liver to Full Group_______ Number______ Body Weight (%) 101 3.2 102 3.3 103 3.8 104 3.9 105 3.3 106 3.1 107 3.1 108 3.3 109 3.4 110 3.2 301 3.4 302 3.8 303 3.9 304 3.9 305 3.4 306 3.1 307 3.7 308 3.5 309 3.5 310 3.4 501 3.5 502 4.4 503 3.9 504 3.9 505 3.9 506 3.4 507 4.1 508 3.6 509 4.1 510 4.3 -227- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Rat Beta-Oxidation Liver Data Animal Relative Liver to Full Group_______ Number______ Body Weight (%) VIIC 701 702 703 704 705 706 707 708 709 710 5.0 4.6 4.3 4.9 4.2 3.7 4.2 4.3 4.6 4.4 IXC 901 902 903 904 905 906 907 908 909 910 XIC 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 6.0 6.0 5.3 6.5 4.9 5.5 4.8 5.1 6.8 6.7 5.9 7.3 6.7 6.2 5.1 7.4 5.8 6.4 6.8 6.1 -228- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice . Revision Number 1 DuPont-14162 MOUSE TABLES -229- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice MOUSE TABLES EXPLANATORY NOTES H-24921 APFO (Linear/Branched) STUDY DESIGN Groups H-26313 H-26225 APFO (Linear) APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Revision Number 1 DuPont-14162 Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day Summary of Clinical Chemistry Values CHOL cholesterol TRIG triglycerides HDL high-density lipoprotein cholesterol nonHDL non-high-density lipoprotein cholesterol Clinical Chemistry Note Groups with identical values may vary in statistical significance, because tabulated statistics are rounded to fewer decimal places than the values used for statistical determination. -230- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 1 Homogeneity/Concentration Verification and Stability Analysis for Mouse Study Sample Sample Day H-24921 1-Mar-2004 Nominal mg/mL 0 0.03 0.10 3.0 Measureda mg/mL NDC 0.027,0.028 0.090, 0.096 2.81,2.69 Mean % Nominal -- 93.3 93.0 91.7 C.V. Stability15 (%) % Nominal ---- 2 90.0 5 92.0d 3 90.3 H-26313 2-Mar-2004 H-26225 3-Mar-2004 0 NDC 0.03 0.031,0.033 0.10 0.104e, 0.108 3.0 3.22, 3.22 0 NDC 0.03 0.031,0.032 0.10 0.101,0.111 3.0 3.34, 3.09 -- 106.7 106.0 107.3 -- 106.7 106.0 107.0 ---- 5 103.3 3 1 1 1 .0 0 100.3 ---- 0.5 100.0 7 102.0 6 104.7 a Mean results for the analysis of the duplicate samples, b Samples held 5 hours at room temperature, c Denotes none detected. d Reported results based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. e Reported results based on re-analysis of the original sample. Original analysis was higher than expected due to aliquot error and not reported. -231- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 2 Recovery of H-24921, H-26313, H-26225 Added to Dosing Vehicle for Mouse Study Sample Type Recovery" Recovery0 Recovery0 mg/mL Nominal Measured 0.030 0.031 0.030 0.032d 0.030 0.033 Mean Percent Nominal 103.3 106.7 110.0 106.7 3.4, C.V. 3% Recovery" Rec o v e r Yb Recovery0 0.10 0.108e 108.0 0.10 0.109 109.0 0.10 0.110 110.0 Mean 109.0 1.0, C.V. 1% Recovery" R ec o v er Yb Recovery0 3.00 2.75 91.7 3.00 3.17 105.6 3.00 3.08 102.7 Mean 100.0 7.3, C.V. 7% a Processed with H-24921 samples from dosing prepared on March 1,2004. b Processed with H-26313 samples from dosing prepared on March 2,2004. c Processed with H-26225 samples from dosing prepared on March 3,2004. d Reported result from reanalysis of original sample. The original analysis was higher than expected due to aliquot error and not reported. e Reported result from reanalysis of original sample. The original analysis was lower than expected due to aliquot error and not reported. -232- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Mouse Study Test Substance Sample Date H-24921 (3/1/04) Control Nominal 0.00 mg/mL Measured NDa Percent Nominal -- #1 #2 #1 #2 #1 #2 5 Hourc H-26313 (3/2/04) Control 0.03 0.03 M eati0: 0.10 0.10 M eati0: 3.00 3.00 M ean0: 0.03 0.10 3.00 0.00 0.027 0.028 0.028 0.001 C .V .2 % 0.090 0.096 0.093 0.004 C.V. 5% 2.81 2.69 2.75 0.09 C.V. 3% 0.027 0.092d 2.71 NDa 90.0 93.3 (93.3%) 90.0 96.0 (93.0%) 93.7 89.7 (91.7%) 90.0 92.0 90.3 -- #1 #2 #1 #2 #1 #2 5 Hour0 0.03 0.03 M ean0: 0.10 0.10 M eati3: 3.00 3.00 M eati0: 0.03 0.10 3.00 0.031 0.033 0.032 0.001 C.V. 5% 0.104 0.108 0.106 0.003 C.V. 3% 3.22 3.22 3.22 0.00 C.V. 0% 0.031 0.111 3.01 103.3 110.0 (106.7%) 104.0 108.0 (106.0%) 107.3 107.3 (107.3%) 103.3 111.0 100.3 -233- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 3 Concentration Verification and Stability of H-24921, H-26313, H-26225 in Dosing Solutions for Mouse Study (Continued) Test Substance Sample Date H-26225 (3/3/04) Control Nominal 0.00 mg/mL Measured NDa Percent Nominal -- #1 #2 #1 #2 #1 #2 5 Hourc 0.03 0.03 Mean*: 0.10 0.10 Mean*: 3.00 3.00 Mean*: 0.03 0.10 3.00 0.031 0.032 0.032 0.0002 C.V. 0.5% 0.101 0.111 0.106 0.007 C.V. 7% 3.34 3.09 3.21 0.182 C.V. 6% 0.030 0.102 3.14 103.3 106.7 (106.7%) 101.0 111.0 (106.0%) 111.3 103.0 (107.0%) 100.0 102.0 104.7 a Denotes none detected. b The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples. c Stability samples held 5 hours a room temperature. d Reported result based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. e Reported result based on re-analysis of the original sample. Original analysis was higher than expected due to aliquot error and not reported. -234- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________________________ Revision Number 1 DuPont-14162 Table 4 Summary of Dosing Suspension Analysis for Mouse Study Sample Type Concentration H-24921 (3/1/2004) #1 #2 Average Measured Conc.b Average Percent Nominalb Standard Deviationb Coefficient o f Variationb Stability 5-hour Room Temperature Concentration H-26313 (3/2/2004) #1 #2 Average Measured Conc.b Average Percent N om inal11 Standard Deviation11 Coefficient o f Variation11 Stabilitv 5-hour Room Temperature Concentration H-26225 (3/3/2004) #1 #2 Average Measured Conc.b Average Percent Nom inal11 Standard Deviation11 Coefficient o f Variation11 Stability 5-hour Room Temperature Concentrations and Stability of FI-24921, FI-26313, FI-26225 (mg/mL) Nominal:_______ 0.03_____________ 0.10 3.00 0.027 (90.0)a 0.028 (93.3) 0.028 (93.3) 0.001 2% 0.027 (90.0) 0.090 (90.0) 0.096 (96.0) 0.093 (93.0) 0.004 5% 0.092c (92.0) 2.81 (93.7) 2.69 (89.7) 2.75 (91.7) 0.09 3% 2.71 (90.3) 0.031 (103.3) 0.033 (110.0) 0.032 (106.7) 0.001 5% 0.031 (103.3) 0.104d (104.0) 0.108 (108.0) 0.106 (106.0) 0.003 3% 0.111 (111.0) 3.22 (107.3) 3.22 (107.3) 3.22 (107.3) 0 .0 0 0% 3.01 (100.3) 0.031 (103.3) 0.032 (106.7) 0.032 (106.7) 0.0002 0.5% 0.030 (100.0) 0.101 (101.0) 0.111 (111.0) 0.106 (106.0) 0.007 7% 0.102 (102.0) 3.34 (111.3) 3.09 (103.0) 3.21 (107.0) 0.182 6% 3.14 (104.7) a Numbers in parentheses are the respective percent of nominal values. b The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples. c Reported result based on re-analysis of the original sample. Original analysis was lower than expected due to aliquot error and not reported. d Reported result based on re-analysis of the original sample. Original analysis was higher than expected due to aliquot error and not reported. -235- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) Test DAYO DAY1 DAY2 DAY 3 DAY4 DAY5 DAY 6 DAY7 DAY 8 DAY 9 DAY10 DAY11 DAY12 Table 5 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear/Branched) IA IIIA VA VI IA IXA 0 0.3 1 3 10 31.2 2.2(10) 30.5 2.2(10) 30.5 2.1(10) 30.8 2.9(10) 31.5 1.8(9) 31.7 1.7(9) 31.9 1.9(9) 32.1 1.9(9) 32.0 1.9(9) 32.0 1.8(9) 32.6 2.0(9) 33.0 1.8(9) 32.8 2.0(9) 31.4 1.6(10) 31.0 1.7(10) 30.4 1.7(10) 31.4 1.6(10) 31.3 1.8(10) 31.3 1.8(10) 31.6 1.8(10) 31.9 1.7(10) 31.5 1.7(10) 31.0 1.8(10) 32.1 1.7(10) 32.7 1.9(10) 32.3 1.9(10) 32.1 1.4(10) 31.4 1.7(10) 31.3 1.8(10) 32.1 1.9(10) 31.9 2.6(10) 31.7 2.8(10) 32.0 3.1(10) 32.3 3.1(10) 32.4 3.1(10) 32.2 3.2(10) 32.7 2.8(10) 33.2 2.8(10) 33.1 2.7(10) 31.8 1.8(10) 31.2 1.7(10) 31.3 1.8(10) 32.1 1.9(10) 32.0 2.9(10) 31.7 3.1(10) 32.1 3.2(10) 32.7 3.0(10) 32.7 2.8(10) 32.8 2.6(10) 33.0 2.7(10) 33.5 2.4(10) 33.5 2.6(10) 31.7 1.4(10) 30.8 1.0(10) 30.9 1.1(10) 31.3 1.0(10) 32.0 1.2(10) 31.6 1.0(10) 31.6 0.7(10) 31.5 0.9(10) 31.6 1.5(10) 30.9 1.4(10) 30.7 1.8(10) 30.8 2.1(10) 30.1* 2.0(10) Revision Number 1 DuPont-14162 XIA 30 31.4 1.4(10) 30.5 1.2(10) 30.8 1.0(10) 30.6 1.4(10) 30.7 1.4(10) 2 8 . 7@ 1.5(10) 27.60 1.7(10) 27.40 1.8(10) 27.40 2.1(10) 27.10 2.1(10) 26.7 2.0(10) 26.5* 1.9(10) 25.8* 1.8(10) -236- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAY13 D A Y 14 Table 5 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear/Branched) (Continued) IA IIIA VA VIIA IXA XIA 0 0.3 1 3 10 30 33.1 2.0(9) 31.9 1.9(9) 32.6 1.8(10) 31.5 1.7(10) 33.5 2.6(10) 32.2 2.0(10) 33.7 2.7(10) 32.4 2.6(10) 29.4* 2.1(10) 28.3 1.9(10) 25.6* 1.8(10) 2 4 . 9@ 1.7(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. -237- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group: Dosage(mg/kg) Test DAYO DAY1 DAY 2 DAY 3 DAY4 DAY 5 DAY 6 DAY7 DAY 8 DAY 9 D A Y 10 DAY11 DAY12 Table 6 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear) IB IIIB VB VIIB IXB 0 0.3 1 3 10 31.3 1.4(10) 31.0 1.6(10) 30.9 1.4(10) 31.0 1.5(10) 30.4 1.7(10) 30.7 1.7(10) 31.3 2.0(10) 31.0 1.8(10) 30.8 1.2(10) 31.1 1.2(10) 31.5 1.4(10) 31.5 1.4(10) 31.8 1.3(10) 31.4 1.5(10) 30.9 1.3(10) 31.0 1.4(10) 31.8 1.5(10) 31.3 1.5(10) 31.5 1.4(10) 32.2 1.4(10) 31.9 1.5(10) 31.2 1.3(10) 31.6 1.3(10) 31.8 1.2(10) 31.8 1.4(10) 32.1 1.4(10) 31.9 1.1(10) 31.6 1.1(10) 32.0 1.1(10) 32.4 1.2(10) 32.1 1.1(10) 32.6 1.1(10) 33.3 1.0(10) 33.5 1.2(10) 32.6 1.3(10) 33.1* 1.3(10) 33.5 1.4(10) 33.5 1.2(10) 33.8 1.2(10) 31.6 1.6(10) 31.7 1.9(10) 31.8 2.1(10) 32.2 2.7(10) 31.9 2.9(10) 32.1 3.1(10) 32.9 3.4(10) 32.3 3.3(10) 32.3 3.1(10) 32.8 3.4(10) 33.0 3.6(10) 33.1 3.7(10) 33.4 3.5(10) 31.1 1.2(10) 31.2 1.4(10) 31.9 1.4(10) 32.7 1.7(10) 32.6* 1.7(10) 32.6 1.7(10) 33.0 2.0(10) 31.7 2.3(10) 31.9 2.0(10) 31.0 2.4(10) 31.0 2.6(10) 30.6 2.5(10) 30.1 2.6(10) Revision Number 1 DuPont-14162 XIB 30 31.3 1.3(10) 32.1 1.3(10) 32.4 1.4(10) 32.8 1.1(10) 30.4 1.2(10) 28.8 1.5(10) 27.7* 1.9(10) 25.7* 2.1(10) 26.0* 2.3(10) 26.0* 2.3(10) 26.7* 2.1(9) 26.1* 1-8(9) 26.3* 1.9(9) -238- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAY13 DAY14 Table 6 Mean Body Weights (g) of Male Mice Dosed with APFO (Linear) (Continued) IB IIIB VB VIIB IXB 0 0.3 1 3 10 32.6 1.4(10) 30.7 1.3(10) 32.7 1.5(10) 31.0 1.1(10) 34.2 1.1(10) 32.8* 1.1(10) 34.0 3.5(10) 32.5 3.4(10) 30.1 3.0(10) 28.0 2.8(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control p < 0.05 by Dunnett's test. XIB 30 27.2* 1.9(9) 25.8* 1.7(9) -239- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) Test DAYO DAY1 DAY2 DAY 3 DAY 4 DAY 5 DAY 6 DAY7 DAY 8 DAY 9 DAY10 DAY11 D A Y 12 Table 7 Mean Body Weights (g) of Male Mice Dosed with APFO (Branched) IC m e VC VI IC IXC 0 0.3 1 3 10 31.5 2.1(10) 31.0 1.8(10) 31.4 1.7(10) 31.3 1.6(10) 31.1 1.7(10) 31.9 1.7(10) 31.4 1.8(10) 32.1 1.7(10) 31.7 1.8(10) 31.8 2.0(10) 31.7 1.8(10) 31.9 1.8(10) 32.7 1.8(10) 31.3 1.1(10) 31.1 1.5(10) 32.0 1.6(10) 31.6 1.7(10) 31.7 1.7(10) 32.4 1.8(10) 32.2 1.9(10) 32.6 2.0(10) 32.2 1.9(10) 32.8 1.9(10) 32.6 2.0(10) 32.7 1.8(10) 33.7 2.0(10) 32.1 1.3(10) 31.3 1.3(10) 32.0 1.6(10) 31.6 1.4(10) 31.7 1.4(10) 32.3 1.5(10) 32.1 1.4(10) 32.6 1.6(10) 32.1 1.5(10) 32.5 1.6(10) 32.5 1.4(10) 32.7 1.6(10) 33.7 1.5(10) 32.1 1.3(10) 31.9 1.2(10) 32.8 1.3(10) 32.3 1.4(10) 32.4 1.2(10) 33.4 1 . 3 (10) 33.2 1.3(10) 33.9 1.2(10) 33.4 1.2(10) 34.0* 1.2(10) 33.6 1.2(10) 33.9* 1.1(10) 35.4* 1.4(10) 31.7 1.6(10) 31.0 1.9(10) 31.9 2.1(10) 31.6 2.1(10) 31.9 2.1(10) 32.8 1.9(10) 32.8 2.1(10) 33.9 2.0(10) 33.5 1.9(10) 34.0* 1.8(10) 34.0* 1.7(10) 34.0* 1.7(10) 35.3* 1.7(10) Revision Number 1 DuPont-14162 XIC 30 31.6 1.5(10) 31.3 1.5(10) 32.5 1.5(10) 32.4 1.4(10) 32.2 1.6(10) 33.0 1.7(10) 31.6 1.8(10) 32.2 1.8(10) 31.1 1.6(10) 31.9 1.3(10) 31.1 1.9(10) 31.4 1.9(10) 32.7 1.6(10) -240- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group : Dosage(mg/kg) Test DAY13 DAY14 Table 7 Mean Body Weights (g) of Male Mice Dosed with APFO (Branched) (Continued) IC m e VC VI IC IXC 0 0.3 1 3 10 32.8 2.1(10) 31.5 1.9(10) 33.8 1.8(10) 31.9 1.8(10) 33.6 1.6(10) 32.3 1.6(10) 34.9* 1.1(10) 33.7* 1.1(10) 34.9* 1.5(10) 33.3 1.3(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control p < 0.05 by Dunnett's test. Revision Number 1 DuPont-14162 XIC 30 32.0 2.0(10) 31.0 2.1(10) -241 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAYO -DAY1 DAY1 -DAY2 DAY 2 -DAY3 DAY 3 -DAY 4 DAY 4 -DAY 5 DAY 5 -DAY 6 DAY 6 -DAY7 DAY7 -DAY 8 DAY 8 -DAY 9 DAY 9 -DAY10 DAY10 -DAY11 DAY11 -DAY12 DAY12 -DAY13 DAY13 -DAY14 Table 8 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear/Branched) IA IIIA VA VI IA IXA 0 0.3 1 3 10 XIA 30 -0.6 0.3(10) -0.1 0.4(10) 0.3 1.2(10) - 0.1 0.4(9) 0.2 0.3(9) 0.2 0.6(9) 0.2 0.3(9) -0.2 0.3(9) 0.0 0.4(9) 0.6 0.4(9) 0.4 0.2(9) -0.2 0.3(9) 0.3 0.3(9) -1.2 0.6(9) -0.4 0.6(10) -0.5* 0.3(10) 0.9 0.3(10) - 0.1 0.4(10) 0.0 0.3(10) 0.3 0.2(10) 0.4 0.4(10) -0.4 0.4(10) -0.5* 0.3(10) 1.0 0.4(10) 0.6 0.3(10) -0.3 0.4(10) 0.2 0.3(10) -1.1 0.2(10) -0.7 0.6(10) - 0.1 0.3(10) 0.8 1.6(10) -0.2 1.0(10) -0.2 0.4(10) 0.3 0.4(10) 0.3 0.2(10) 0.1 0.5(10) -0.2 0.2(10) 0.5 0.5(10) 0.4 0.3(10) - 0.1 0.5(10) 0.4 0.2(10) -1.2 0.8(10) -0.7 0.5(10) 0.2 0.4(10) 0.8 0.4(10) -0.2 1.3(10) -0.3 0.6(10) 0.4 0.3(10) 0.6 0.4(10) 0.0 0.5(10) 0.1 0.5(10) 0.1 0.3(10) 0.5 0.3(10) 0.0 0.5(10) 0.1 0.3(10) -1.3 0.6(10) -0.9 0.7(10) 0.1 0.2(10) 0.4 0.5(10) 0.7@ 0.5(10) -0.4 0.6(10) - 0.0 0.7(10) - 0.0 0.6(10) 0.0 0.9(10) -0.6 0.9(10) -0.2* 0.7(10) 0.1 1.0(10) -0.7 0.7(10) -0.70 1.0(10) - 1.0 0.5(10) -0.9 0.5(10) 0.3 0.6(10) -0.2 0.7(10) 0.1 0.6(10) -2.0* 0.8(10) -1.1* 0.6(10) -0.3 0.5(10) 0.0 0.8(10) -0.3 0.7(10) -0.4* 0.4(10) -0.2 0.6(10) -0.7 0.6(10) -0.2 0.5(10) -0.7 0.3(10) -242- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAYO -DAY7 DAY7 -DAY13 DAYO -DAY13 DAYO -DAY14 Table 8 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear/Branched) (Continued) IA IIIA VA VI IA IXA XIA 0 0.3 1 3 10 30 0.5 0.7(9) 0.9 0.5(9) 1.5 0.7(9) 0.3 0.6(9) 0.6 1.0(10) 0.6 0.5(10) 1.2 1.3(10) 0.1 1.2(10) 0.2 2.8(10) 1.1 1.1(10) 1-4 2.3(10) 0.2 1.7(10) 0.8 1.7(10) 1.0 0.9(10) 1.8 1.2(10) 0.5 1.3(10) -0.2 1.5(10) -2.2* 1.6(10) -2.30 2.7(10) -3.4@ 2.5(10) -4.10 1.2(10) -1.8* 0.5(10) -5.80 1.1(10) -6.50 1.1(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. -243- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) Test DAYO -DAY1 DAY1 -DAY2 DAY2 -DAY3 DAY 3 -DAY 4 DAY 4 -DAY5 DAY 5 -DAY6 DAY 6 -DAY7 DAY7 -DAY 8 DAY 8 -DAY 9 DAY 9 -DAY10 DAY10 -DAY11 DAY11 -DAY12 DAY12 -DAY13 DAY13 -DAY14 Table 9 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear) IB IIIB VB VIIB IXB 0 0.3 1 3 10 -0.3 0.5(10) - 0.1 0.5(10) 0.1 1.3(10) -0.6 0.7(10) 0.3 0.2(10) 0.6 0.4(10) -0.3 0.6(10) -0.2 0.7(10) 0.3 0.3(10) 0.4 0.4(10) 0.0 0.4(10) 0.3 0.3(10) 0.8 0.3(10) -1.9 0.3(10) -0.5 0.4(10) 0.1 0.2(10) 0.8 0.3(10) -0.6 0.3(10) 0.2 0.2(10) 0.7 0.3(10) -0.3 0 .3 (10) -0.7 0.3(10) 0.4 0.4(10) 0.3 0.2(10) -0.0 0.3(10) 0.2 0.4(10) 0.6 0.3(10) -1.7 0.5(10) -0.3 0.3(10) 0.4 0.4(10) 0.4 0.4(10) -0.3 0.7(10) 0.5 0.4(10) 0.8 0.3(10) 0.1 0.3(10) -0.90 0.3(10) 0.5 0.2(10) 0.4 0.3(10) 0.0 0.4(10) 0.3 0.4(10) 0.4 0.5(10) -1.5 0.4(10) 0.1 0.5(10) 0.1 1.4(10) 0.4 0.8(10) -0.3 0.4(10) 0.3 0.4(10) 0.8 . 0.4(10) -0.5 0.4(10) - 0.0 0.4(10) 0.5 0.4(10) 0.2 0.4(10) 0.1 0.4(10) 0.3 0.3(10) 0.5 0.6(10) -1.4 0.6(10) 0.1 0.5(10) 0.70 0.4(10) 0.7 0.4(10) - 0.1 0.5(10) - 0.1 0.1(10) 0.4 0.6(10) -1.2 0.7(10) 0.1 0.5(10) -0.90 0.8(10) - 0.0 0.7(10) -0.3 0.7(10) -0.6* 0.9(10) 0.0 0.9(10) -2.1 0.9(10) -244- Revision Number 1 DuPont-14162 XIB 30 0.80 0.4(10) 0.3 0.3(10) 0.4 1.0(10) -2.3* 0.8(10) .-1.70 1.1(10) -1.1* 0.9(10) -2.00 1.3(10) 0.4 1.4(10) - 0.0 0.9(10) 0.3 0.6(9) -0.6 1.0(9) 0.2 0.8(9) 0.9 0.7(9) -1.4 0.8(9) APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAYO -DAY7 DAY7 -DAY13 DAYO -DAY13 DAYO -DAY14 Table 9 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Linear) (Continued) IB IIIB VB VIIB IXB XIB 0 0.3 1 3 10 30 -0.3 2.0(10) 1.6 1.0(10) 1.3 1.4(10) -0.6 1.2(10) 0.5 0.6(10) 0.8 0.4(10) 1.3 0.7(10) -0.5 0.7(10) 1.6 0.7(10) 0.8 0.4(10) 2.4 0.7(10) 0.9* 1.0(10) 0.8 2.7(10) 1.6 0.7(10) 2.4 2.8(10) 1.0 2.6(10) 0.6 1.5(10) -1.6* 1.4(10) -1.0 2.6(10) -3.1* 2.2(10) - 5 . 6@ 2.5(10) 1.1 1.4(9) - 3 . 9@ 2.6(9) -5.3* 2.5(9) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. -245- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) Test DAYO -DAY1 DAY1 -DAY2 DAY 2 -DAY3 DAY 3 -DAY 4 DAY4 -DAY 5 DAY5 -DAY 6 DAY 6 -DAY7 DAY7 -DAY8 DAY 8 -DAY9 DAY 9 -DAY10 DAY10 -DAY11 DAY11 -DAY12 DAY12 -DAY13 DAY13 -DAY14 Table 10 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Branched) IC m e VC VIIC IXC 0 0.3 1 3 10 -0.6 0.6(10) 0.4 0.3(10) - 0.1 0.5(10) -0.2 0.4(10) 0.8 0.2(10) -0.5 0.4(10) 0.7 0.4(10) -0.4 0.4(10) 0.1 0 . 4 (10) - 0.1 0.5(10) 0.2 0.2(10) 0.8 0.3(10) 0.1 0.5(10) -1.3 0.4(10) - 0.1 0.9(10) 0.8 0.4(10) -0.4 0.3(10) 0.1 0.2(10) 0.7 0.3(10) -0.2 0.4(10) 0.4 0.4(10) -0.3 0.4(10) 0.5 0.4(10) -0.2 0.4(10) 0.1 0.3(10) 0.9 0.4(10) 0.1 0.4(10) -1.9 0.5(10) -0.8 0.4(10) 0.7 0.5(10) -0.4 0.5(10) 0.1 0.3(10) 0.7 0.3(10) -0.2 0.4(10) 0.5 0.4(10) -0.5 0.4(10) 0.4 0.3(10) - 0.0 0.3(10) 0.2 0.3(10) 1.0 0.5(10) - 0.1 0.3(10) -1.3 0.4(10) -0.3 0.4(10) 0.9* 0.3(10) -0.5 0.3(10) 0.0 0.3(10) 1.0 0.5(10) -0.2 0.3(10) 0.7 0.2(10) -0.5 0.4(10) 0.6 0.4(10) -0.3 0.4(10) 0.3 0.3(10) 1.4* 0.4(10) -0.5* 0.4(10) -1.2 0.3(10) -0.7 1.6(10) 0.9* 0.4(10) -0.3 0.5(10) 0.4* 0.4(10) 0.9 0.4(10) - 0.1 0.5(10) 1.2 0.8(10) -0.5 0.8(10) 0.5 0.6(10) 0.0 0.6(10) - 0.0 0.6(10) 1.3* 0.5(10) -0.4* 0.5(10) -1.5 0.6(10) -246- Revision Number 1 DuPont-14162 XIC 30 -0.4 0.4(10) 1.3* 0.3(10) - 0.1 0.6(10) -0.2 0.8(10) 0.8 0.7(10) -1.5* 0.7(10) 0.7 0.7(10) -1.1* 0.6(10) 0.7* 0.7(10) -0.8* 0.8(10) 0.4 0.3(10) 1.3* 0.6(10) -0.7* 0.6(10) -1.1 0.8(10) APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ Revision Number 1 DuPont-14162 Group ; Dosage(mg/kg) Test DAYO -DAY7 DAY7 -DAY13 DAYO -DAY13 DAYO -DAY14 Table 10 Mean Body Weight Gains (g) of Male Mice Dosed with APFO (Branched) (Continued) IC m e VC VIIC IXC XIC 0 0.3 1 3 10 30 0.5 0.7(10) 0.8 0.7(10) 1.3 0.9(10) -0.0 0.9(10) 1.3 1.4(10) 1.2 0.7(10) 2.5 1.1(10) 0.6 1.3(10) 0.5 0.7(10) 1.0 0.5(10) 1.5 0.6(10) 0.2 0.7(10) 1.8* 0.8(10) 1.0 0.7(10) 2.8* 0.8(10) 1.6* 0.8(10) 2.2* 1.3(10) 0.9 1.4(10) 3.1* 1.7(10) 1.6* 1.2(10) 0.6 1.2(10) -0.2* 0.8(10) 0.4 1.4(10) -0.7 1.7(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control p < 0.05 by Dunnett's test. -247- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group: Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 11 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Linear/Branched) IA IIIA VA VI IA IXA XIA 0 0.3 1 3 10 30 5.3 0.8(10) 5.4 0.4(9) 5.2 0.8(9) 5.8 0.6(9) 5.4 0.4(10) 5.3 0.4(10) 5.2 0.9(10) 5.7 0.6(10) 5.5 0.5(10) 5.3 1.2(10) 5.3 0.6(10) 5.8 0.6(10) 5.6 0.3(10) 5.3 0.8(10) 5.0 0.3(10) 5.7 0.4(10) 6.2 0.9(10) 5.0 0.5(10) 6.1 1.1(10) 5.4 0.9(10) 5.4 1.1(10) 4.3@ 0.7(10) 5.2 1.1(10) 4.2* 0.6(10) DAY0-DAY7 DAY7-DAY13 DAY0-DAY13 5.4 0.3(9) 5.5 0.6(9) 5.5 0.4(9) 5.4 0.3(10) 5.5 0.7(10) 5.4 0.5(10) 5.4 0.9(10) 5.6 0.5(10) 5.5 0.7(10) 5.4 0.4(10) 5.3 0.3(10) 5.4 0.3(10) 5.5 0.5(10) 5.7 1.0(10) 5.6 0.7(10) 4.8 0.7(10) 4.7* 0.7(10) 4.7* 0.4(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. -248- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 12 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Linear) IB IIIB VB VI IB IXB 0 0.3 1 3 10 XIB 30 5.4 0.7(10) 5.4 0.9(10) 5.1 0.7(10) 5.6 0.9(10) 5.2 0.4(10) 5.5 0.6(10) 4.9 0.7(10) 5.4 0.8(10) 5.5 0.5(10) 5.6 0.4(10) 5.4 0.5(10) 6.0 1.0(10) 5.2 1.1(10) 5.5 0.9(10) 5.3 0.6(10) 5.5 0.6(10) 5.6 0.5(10) 5.4 0.5(10) 6 . 0@ 0.4(10) 5.2 1.0(10) 5.6 0.4(10) 4 . 0@ 1.4(10) 4.9 1.2(10) 4.7 0.8(9) DAY0-DAY7 DAY7-DAY13 DAY0-DAY13 5.4 0.7(10) 5.3 0.7(10) 5.4 0.6(10) 5.4 0.5(10) 5.1 0.6(10) 5.3 0.5(10) 5.6 0.3(10) 5.7 0.7(10) 5.6 0.5(10) 5.4 0.9(10) 5.4 0.6(10) 5.4 0.7(10) 5.5 0.5(10) 5.6 0.5(10) 5.5 0.5(10) 4.7 0.7(10) 5.0 0.3(9) 4.9 0.4(9) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. -249- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 13 Mean Daily Food Consumption (g/day) by Male Mice Dosed with APFO (Branched) IC m e VC VIIC IXC 0 0.3 1 3 10 5.8 0.6(10) 5.4 0.3(10) 5.8 0.6(10) 5.5 0.7(10) 5.6 0.8(10) 5.5 0.4(10) 5.8 0.5(10) 5.4 0.3(10) 5.4 0.6(10) 5.2 0.3(10) 5.5 0.4(10) 5.3 0.4(10) 5.8 0.5(10) 5.7 0.3(10) 6.1 0.4(10) 5.6 0.4(10) 5.6 1.3(10) 5.3 0.7(10) 6.3 0.5(10) 5.5 0.5(10) DAY0-DAY7 DAY7-DAY13 DAY0-DAY13 5.6 0.2(10) 5.7 0.6(10) 5.6 0 . 4 (10) 5.5 0.5(10) 5.6 0.4(10) 5.5 0.4(10) 5.3 0.4(10) 5.4 0.3(10) 5.3 0.3(10) 5.7 0.3(10) 5.9 0.2(10) 5.8 0.2(10) 5.4 0.8(10) 5.9 0.3(10) 5.6 0.5(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences at p < 0.05. XIC 30 5.7 0.6(10) 4.7 0.8(10) 5.4 0.6(10) 5.4 1.0(10) 5.2 0.6(10) 5.4 0.7(10) 5.3 0.6(10) -250- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice________ Revision Number 1 DuPont-14162 Group : Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 14 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Linear/Branched) (g Body Weight Gain/g Food Consumed) IA IIIA VA VI IA IXA 0 0.3 1 3 10 -0.038 0.107(101 0.027 0.026(9) 0.030 0.029(9) 0.027 0.013(9) -0.002 0.044(10) 0.026 0.014(10) 0.008 0.026(10) 0.030 0.022(10) -0.006 0.096(10) -0.022 0.164(10) 0.028 0.042(10) 0.043 0.042(10) 0.017 0.016(10) 0.013 0.112(10) 0.019 0.061(10) 0.040 0.013(10) -0.024 0.036(10) 0.010 0.076(10) -0.055* 0.083(10) -0.0900 0.066(10) DAY0-DAY7 DAY7-DAY13 DAY0-DAY13 0.013 0.018(9) 0.029 0.018(9) 0.021 0.010(9) 0.014 0.026(10) 0.019 0.015(10) 0.016 0.017(10) -0.011 0.122(10) 0.036 0.039(10) 0.016 0.039(10) 0.019 0.051(10) 0.031 0.029(10) 0.025 0.018(10) -0.005 0.042(10) -0.071* 0.061(10) -0.0350 0.043(10) Data arranged as:Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. XIA 30 -0.074 0.145(10) -0.1900 0.096(10) -0.047* 0.059(10) -0.0940 0.061(10) -0.1280 0.056(10) -0.065* 0.025(10) -0.0960 0.024(10) -251 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Group : Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 15 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Linear) (g Body Weight Gain/g Food Consumed) IB IIIB VB VIIB IXB 0 0.3 1 3 10 -0.029 0.119(10) -0.005 0.029(10) 0.038 0.053(10) 0.066 0.033(10) 0.026 0.021(10) 0.002 0.024(10) -0.003 0.025(10) 0.052 0.024(10) 0.030 0.018(10) 0.048 0.026(10) -0.000 0.028(10) 0.045 0.028(10) -0.004 0.244(10) -0.000 0.052(10) 0.038 0.031(10) 0.061 0.035(10) 0.0930 0 . 0 3 6 (10) -0.047 0.055(10) -0.044* 0.049(10) -0.0640 0.075(10) DAY0-DAY7 DAY7-DAY13 DAY0-DAY13 -0.016 0.068(10) 0.052 0.033(10) 0.017 0.019(10) 0.012 0.015(10) 0.027 0.014(10) 0.019 0.010(10) 0.041@ 0.018(10) 0.023 0.013(10) 0.033 0.010(10) 0.002 0.116(10) 0.050 0.021(10) 0.028 0.050(10) 0.014 0.039(10) -0.051* 0.045(10) -0.016 0.036(10) Data arranged as:Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. Revision Number 1 DuPont-14162 XIB 30 0.0870 0.055(10) -0.5360 0.368(10) 0.037 0.080(9) 0.024 0.112(9) 0.183 0.116(10) 0.037 0.047(9) 0.062 0.044(9) -252- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Group : Dosage(mg/kg) Test DAY0-DAY3 DAY3-DAY7 DAY7-DAY10 DAY10-DAY13 Table 16 Mean Daily Food Efficiency of Male Mice Dosed with APFO (Branched) (g Body Weight Gain/g Food Consumed) IC m e VC VIIC IXC 0 0.3 1 3 10 -0.016 0.043(10) 0.035 0.018(10) -0.020 0.029(10) 0.066 0.035(10) 0.013 0.060(10) 0.044 0.021(10) 0.002 0.027(10) 0.073 0.029(10) -0.032 0.028(10) 0.050 0.021(10) -0.008 0.032(10) 0.069 0.024(10) 0.011 0.039(10) 0.0700 0.018(10) -0.017 0.033(10) 0.074 0.017(10) -0.037 0.180(10) 0.1140 0.061(10) 0.005 0.050(10) 0.050 0.046(10) DAY0-DAY7 DAY7-DAYX3 DAY0-DAY13 0.013 0.017(10) 0.022 0.020(10) 0.018 0.011(10) 0.031 0.032(10) 0.037 0.024(10) 0.034 0.013(10) 0.014 0.019(10) 0.030 0.015(10) 0.022 0.009(10) 0.045* 0.018(10) 0.027 0.019(10) 0.037* 0.010(10) 0.055* 0.031(10) 0.026 0.039(10) 0.042* 0.023(10) Data arranged as:Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control p < 0.05 by Dunn's test. * Statistically significant difference from control p < 0.05 by Dunnett's test. Revision Number 1 DuPont-14162 XIC 30 0.0430 0.040(10) -0.011 0.054(10) -0.069* 0.053(10) 0.057 0.045(10) 0.015 0.034(10) -0.006 0.025(10) 0.005 0.021(10) -253- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Table 17 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear/Branched) Treatment Group: Dose Animal Count Mass Inguen Right M a s s #1 Not Ulcerated Incidence M e a n o nset (Days) Eye Observations Enophthalmus Incidence M e a n onset (Days) Discharge Eye right Incidence M e a n onset (Days) Lethargic Incidence M e a n o nset (Days) Stain Fur/Skin Incidence M e a n onset (Days) IA 0 mg/kg 10 0 0 0 0 0 IIIA 0.3 mg/kg 10 VA 1 mg/kg 10 VI IA 3 mg/kg 10 IXA 10 mg/kg 10 XIA 30 mg/kg 10 O' 0 1 ( 10%) 9 0 0 0 1 ( 10%) 0 0 1 ( 10%) 36 0 1 ( 10%) 0 0 0 4 0 0 0 0 1 ( 10%) 12 0 0 1 ( 10%) 0 0 3 Revision Number 1 DuPont-14162 -254- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 17 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear/Branched) (Continued) Treatment Group: Dose Animal Count Swollen Observations Forelimb incidence M e a n onset (Days) Abdomen Incidence Me a n onset (Days) IA 0 mg/kg 10 0 0 IIIA 0.3 mg/kg 10 VA 1 mg/kg 10 VI IA 3 mg/kg 10 IXA 10 mg/kg 10 XIA 30 mg/kg 10 0 1 ( 10%) 0 0 0 3 0 0 00 1( 13 Incidence - The number of animals for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that group. There were no statistically significant differences at p < 0.05. -255- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Treatment Group: Dose Animal Count Eye Observations Enophthalmus Incidence M e a n onset (Days) Carriage High Incidence M e a n onset (Days) Pale Incidence M e a n onset (Days) Lethargic Incidence M e a n onset (Days) Stain Fur/Skin Incidence M e a n onset (Days) Table 18 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear) IB 0 mg/kg 10 IIIB 0.3 mg/kg 10 VB 1 mg/kg 10 VIIB 3 mg/kg 10 IXB 10 mg/kg 10 XIB 30 mg/kg 10 0 0 0 0 0 3 ( 30%) 11 0 0 0 0 0 1 ( 10%) 8 0 0 0 0 0 1 ( 10%) 9 0 0 0 0 1 ( 10%) 2 ( 20%) 12 10 1 ( 10%) 0 0 1 ( 10%) 0 1 ( 10%) 6 68 Revision Number 1 DuPont-14162 -256- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 18 Summary of Clinical Observations for Male Mice Dosed with APFO (Linear) (Continued) Treatment Group: Dose Animal Count Swollen Observations Shoulder Incidence M e a n o nset (Days) Forelimb Incidence M e a n onset (Days) IB 0 mg/kg 10 0 0 IIIB 0.3 mg/kg 10 VB 1 mg/kg 10 00 00 VIIB 3 mg/kg 10 IXB 10 mg/kg 10 XIB 30 m g / k g 10 1 ( 10%) 3 0 1 ( 10%) 3 0 0 0 Incidence - The number of animals for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that group. # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra trend test. -257- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Table 19 Summary of Clinical Observations for Male Mice Dosed with APFO (Branched) Treatment Group: Dose Animal Count Mass Perineum Mas s #1 Not Ulcerated Incidence M e a n o nset (Days) Eye Observations Enophthalmus Incidence M e a n onset (Days) Hair Loss Incidence M e a n onset (Days) Stain Fur/Skin Incidence M e a n o nset (Days) IC 0 mg/kg 10 me 0.3 mg/kg 10 VC 1 mg/kg 10 VIIC 3 mg/kg 10 00 1 ( 10%) 5 0 00 00 1 ( 10%) 4 0 00 1 ( 10%) 10 0 00 IXC 10 mg/kg 10 XIC 30 mg/kg 10 00 1 ( 10%) 10 0 00 1 ( 10%) 7 0 Revision Number 1 DuPont-14162 -258- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________ Revision Number 1 DuPont-14162 Table 19 Summary of Clinical Observations for Male Mice Dosed with APFO (Branched) (Continued) Treatment Group: Dose Animal Count Swollen Observations Neck Incidence M e a n onset (Days) Face Incidence M e a n onset (Days) IC 0 mg/kg 10 0 0 me 0.3 mg/kg . 10 VC 1 mg/kg 10 00 00 VI IC 3 mg/kg 10 IXC 10 mg/kg 10 XIC 30 m g / k g 10 0 1 ( 10%) 0 . 12 0 1 ( 10%) 0 10 Incidence - The number of animals for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that group. There were no statistically significant differences at p < 0.05. -259- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 DAYS ON TEST Table 20 Percent Survival of Male Mice Group I Group III Group V Group VII Group IX Group XI 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg APFO (Linear/Branched) - A 0 100 100 100 100 100 100 7 90 100 100 100 100 100 14 90 100 100 100 100 100 Number at study start 10 10 10 10 10 10 Found dead 100 000 Sacrificed by design 9 10 10 10 10 10 Alive on test day 14 9 10 10 10 10 10 APFO (Linear) - B 0 100 100 100 100 100 100 7 100 100 100 100 100 100 14 100 100 100 100 100 90 Number at study start 10 10 10 10 10 10 Found dead 00000 1 Sacrificed by design 10 10 10 10 10 9 Alive on test day 14 10 10 10 10 10 9 APFO (Branched) - C 0 100 100 100 100 100 100 7 100 100 100 100 100 100 14 100 100 100 100 100 100 Number at study start 10 10 10 10 10 10 Found dead 000000 Sacrificed by design 10 10 10 10 10 10 Alive on test day 14 10 10 10 10 10 10 Percent Survival = (Number of Mice Alive/Number of Mice at Risk)*100 Number of Mice at Risk = Number at Study Start - Number Sacrificed by Design There were no statistically significant decreases in survival at p < 0.05 by Cochran-Armitage trend test. -260- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 21 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Linear/Branched) GroupIA Group IIIA Group VA Group VILA Group IXA Group XIA 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL)' DAY 14 nonHDL (mg/dL) DAY 14 145 21(9) 99 14(9) 97 12(9) 47 10(9) 137 24(10) 136@ 20(10) 90 12(10) 47 14(10) 138 33(10) 145 @ 27(10) 81 14(10) 57 21(10) 97 @ 23(10) 140@ 31(10) 55 @ 11(10) 42 15(10) 114 44(10) 159@ 38(10) 69 @ 27(10) 45 17(10) 88@ 32(10) 85 30(10) 49 @ 17(10) 39 16(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. -261 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 22 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Linear) Group IB Group IIIB Group VB Group VIIB Group IXB Group XTB Omg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL) DAY 14 nonHDL (mg/dL) DAY 14 150 25(10) 103 31(10) 95 16(10) 56 11(10) 147 38(10) 125 35(10) 90 19(10) 57 20(10) 139 20(10) 137 22(10) 78 10(10) 61 13(10) 97 @ 24(10) 137 38(10) 51* 7(10) 46 20(10) 116 32(10) 135 50(10) 64* 15(10) 52 19(10) 101@ 33(9) 86 16(9) 56* 19(9) 45 15(9) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. -262- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 23 Summary of Clinical Chemistry Values for Male Mice Dosed with APFO (Branched) Group IC Group IIIC Group VC Group VIIC Group IXC Group XIC 0 mg/kg 0.3 mg/kg 1 mg/kg 3 mg/kg__ 10 mg/kg 30 mg/kg CHOL (mg/dL) DAY 14 TRIG (mg/dL) DAY 14 HDL (mg/dL) DAY 14 nonHDL (mg/dL) DAY 14 146 22(10) 134 22(10) 94 13(10) 52 10(10) 125 26(10) 118 28 (9)a 77 10(10) 48 20(10) 127 39(10) 161 44(10) 79 18(10) 48 22(10) 96* 26(10) 149 48(10) 62* 13(10) 34 @ 13(10) 120 43(10) 200 57(10) 67* 21(10) 54 23(10) 113 17(10) 127 30(10) 67* 12(10) 46 7(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) a Excludes one animal considered to be an outlier. * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. -263- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Table 24 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Linear/Branched) Mean Final Body, Absolute and Relative Organ Weights (grams) Group : Dosage(mg/kg) IA IIIA 0 0.3 Test LIVER 1.639 0.113(9) 1.925 0.138(10) KIDNEYS 0.498 0.039(9) 0.544 0.069(10) FINAL BODY WEIGHT 31.9 1.9(9) 31.5 1.7(10) LIVER/ FINAL BODY * 100 5.143 0.274(9) 6.115 0.245(10) KIDNEYS/ FINAL BODY * 100 1.567 0 . 1 6 3 (9) 1.727 0.180(10) VA 1 2.547 0.150(10) 0.536 0.060(10) 32.2 2.0(10) 7.918 0.487(10) 1.662 0.146(10) VI IA 3 3.4690 0.352(10) 0.539 0.074(10) 32.4 2.6(10) 10.7160 0.632(10) 1.661 0.150(10) IXA 10 4.6090 0.421(10) 0.452 0.041(9) 28.3 1.9(10) 16.2720 1.051(10) 1.599 0.082(9) XIA 30 4.5570 0.583(10) 0.401* 0.053(10) 24.90 1.7(10) 18.2830 1.569(10) 1.605 0.137(10) Da t a a r r a nged as: Mean Standard deviation (Number of values included in calculation) * Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant Nonparametric comparison to control (Dunn's) significant -264- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 25 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Linear) Mean Final Body, Absolute and Relative Organ Weights (grams) Group: Dosage(mg/kg) IB IIIB 0 0.3 Test LIVER 1.697 0.125(10) 1.998 0.112(10) KIDNEYS 0.565 0.055(10) 0.529 0.031(10) FINAL BODY WEIGHT 30.7 1.3(10) 30.9 1.1(10) LIVER/ FINAL BODY * 100 5.517 0.243(10) 6.452* 0.233(10) KIDNEYS/ FINAL BODY * 100 1.837 0.159(10) 1.710 0.087(10) VB 1 2.7290 0.143(10) 0.563 0.076(10) 32.8* 1.1(10) 8.329* 0.307(10) 1.715 0.189(10) VIIB 3 3.6950 0.491(10) 0.566 0.087(10) 32.5 3.4(10) 11.369* 1.060(10) 1.741 0.185(10) IXB 10 4.8330 0.711(10) 0.461* 0.084(10) 28.0 2.8(10) 17.181* 1.129(10) 1.633* 0.170(10) Da t a s u m m a r ized as: Mean S t a n d a r d D e v i a t i o n (n) * Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant 0 Nonparametric comparison to control (Dunn's) significant XIB 30 4.6390 0.508(9) 0.440* 0.058(9) 25.8* 1.7(9) 17.957* 1.059(9) 1.705 0.169(9) -265- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Table 26 Mean Final Body and Organ Weights for Male Mice Dosed with APFO (Branched) Mean Final Body, Absolute and Relative Organ Weights (grams) Group : Dosage(mg/kg) IC m e 0 0.3 Test LIVER 1.620 0.138(10) 1.954 0.186(10) KIDNEYS 0.516 0.041(10) 0.549 0.045(10) FINAL BODY WEIGHT 31.5 1.9(10) 31.9 1.8(10) LIVER/ FINAL BODY * 100 5.139 0.311(10) 6.123* 0 . 3 4 4 (10) KIDNEYS/ FINAL BODY * 100 1.641 0.160(10) 1.724 0.148(10) VC 1 2.531 0.264(10) 0.547 0.048(10) 32.3 1.6(10) 7.853* 0.850(10) 1.694 0.115(10) VI IC 3 4.0270 0.317(10) 0.531 0.057(10) 33.7* 1.1(10) 11.945* 0.832(10) 1.578 0.184(10) IXC 10 5.8980 0.634(10) 0.543 0.035(10) 33.3 1.3(10) 17.708* 1.807(10) 1.631 0.101(10) XIC 30 6.5070 0.654(10) 0.485 0.054(10) 30.9 2.1(10) 21.013* 1.395(10) 1.566 0.109(10) Da t a summa r ized as: Mean S t a n d a r d D e v i a t i o n (n) * Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant @ Nonparametric comparison to control (Dunn's) significant -266- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Table 27 Incidences of Gross Observations in Male Mice Dosed with APFO (Linear/Branched) LESION INCIDENCE (Numeric) Males LESIONS 1 TREATMENT 1 1 1 0 1 0.3 m g /kg 1 mg/kg IA 1 IIIA 1 1 13 m g /kg 1 mg/kg V A j VI IA 1 10 mg /kg IXA 30 mg/kg XIA LIVER NO ABNORMALITY DETECTED DISCOLORATION KIDNEYS NO ABNORMALITY DETECTED SKIN STAIN, YELLOW, VENTRAL BODY. (10) 10 (10) 1 (10) j 1 1 10 1 1 1 (10) I 10 1 10 I (1) 1 1 1 1 (10) j (10) I 10 1 9 1 1 (10) j (10) 1 10 1 10 1 1 1 1 1 Figure in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified (10) 6 4 (10) 10 (10) 6 4 (10) 10 Revision Number 1 DuPont-14162 -267- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Table 28 Incidences of Gross Observations in Male Mice Dosed with APFO (Linear) | | | i | LESIONS 1 1 1| 1 1 | LIVER 1 | NO ABNORMALITY DETECTED | DISCOLORATION 1 1 | KIDNEYS i 1 | NO ABNORMALITY | 1 | SKIN | DETECTED | STAIN, YELLOW, VENTRAL BODY. | LESION INCIDENCE (Numeric) | -------------------------------- | _____ Males __ ____ | TREATMENT 1 Per day 1 1 0 | 0.3 | 1 m g / k g 1 mg/kg| mg/kg IB | IIIB | VB 11 3 1 10 1 30 mg/kg| mg/kg| mg/kg VIIB | IXB | XIB 11 (10) 10 1 I (10) 1 I 1 10 1 1 I (10) 1 I 1 10 1 (10) 10 1 (10) 1 1 1 10 1 1 (10) 1 1 1 10 1 11 11 11 11 (10) 9 1 (10) 10 1 1 (10) 1 1 13 |? 1 1 I (10) 1 1 1 10 1 1 1 1 1 1 1 1 (10) 1 1 13 |7 I 1 I (10) 1 1 1 10 1 1 1 (1) 1 11 1 Figure in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified Revision Number 1 DuPont-14162 -268- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Table 29 Incidences of Gross Observations in Male Mice Dosed with APFO (Branched) 1 LESION INCIDENCE (Numeric) j l 1 Males LESIONS | LIVER I | NO ABNORMALITY II D I S C O L O R A T I O N | KIDNEYS I I NO ABNORMALITY DETECTED DETECTED 1 TREATMENT 1 per day 1 1 1o 1 0.3 1 1 13 1 10 1 30 1 1 mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| 1 ic 1 IIIC j VC j VI IC j IXC j XIC j 111 1 1 1 (10) ! ! 1 10 1 1 1 (10) 1 1 10 1 1 1 (10) I ! 1 10 1 1 1 (10) 1 1 10 1 1 1 (10) 1 10 1 1 (10) 1 1 1 10 I 1 (io) I 1 10 1 1 (10) 1 1 10 1 j (10) 1 I 15 15 1 1 (10) 1 1 10 1 1 1 (10) j I 13 17 1 1 (10) 1 1 j 10 1 1 1 1 1 1 Figure in parentheses is the number of animals grossly examined for this tissue Th e absence of a number indicates the finding specified was not identified Revision Number 1 DuPont-14162 -269- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group I Table 30 Summary of Peroxisomal Beta-Oxidation Activity in Male Mice Dosage (mg/kg/day) Hepatic Peroxisomal Beta-Oxidation Activity _________ (nmol/min/mg protein)_________ APFO (Linear/Branched)a APFO (Linear)a APFO (Branched)' 0 17.9 5.7 b 17.3 4.1 18.2 4.3 III 0.3 34.4 7.4* 42.0 10.8* 24.2 3.7 V1 48.8 8.9* 49.6 11.4* 36.9 10.2* VII 3 47.1 7.1* 48.5 10.0* 44.5 8.5* IX 10 31.6 7.4* 37.2 9.0* 42.5 4.4* XI 30 30.7 8.2* 31.9 4.5b* 35.4 9.7* aMean standard deviation. The n = 10 for each group unless otherwise noted. bThe n = 9. Statistically significant difference from control (p < 0.05) by Dunnetf s test (*) -270- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Group I Table 31 Summary of % Relative Liver Weights in Male Mice Dosage (mg/kg/day) 0 Relative Liver Weights to Full Body Weights APFO (%) (Linear/Branched)3 APFO (Linear)3 APFO (Branched)3 5.1 0.3 b 5.5 0.2 5.1 0.3 III 0.3 6.1 0.2 6.510.2* 6.1 0.3* Y1 7.90.5 8.310.3* 7.9 10.9* VII 3 10.7 0.6@ 11.411.1* 11.910.8* IX 10 16.3 1.1 17.211.1* 17.711.8* XI 30 18.3 1.6 1 8 .0 1 1 .1 b* 21.011.4* aMean standard deviation. The n = 10 for each group unless otherwise noted. bThe n = 9. Statistically significant difference from control (p < 0.05) by Dunnett's test (*) or Dunn's test (@). -271 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 MOUSE FIGURES -272- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Figure 1 Mean Body Weights of Male Mice Dosed with APFO (Linear/Branched) Revision Number 1 DuPont-14162 0 mg/kg _ e _ 0.3 mg/kg --s~ 1 mg/kg - X - 3 mg/kg --X --10 mg/kg - e - 30 mg/kg -273- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Figure 2 Mean Body Weights of Male Mice Dosed with APFO (Linear) Revision Number 1 DuPont-14162 -- 0 mg/kg 0.3 mg/kg - A - 1 mg/kg X 3 mg/kg X 10 mg/kg O 30 mg/kg -274- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ Figure 3 Mean Body Weights of Male Mice Dosed with APFO (Branched) Revision Number 1 DuPont-14162 0 mg/kg -B- 0.3 mg/kg --r~ 1 mg/kg -x- 3 mg/kg -x- 10 mg/kg 30 mg/kg -275- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 MOUSE APPENDICES -276- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________ Revision Number 1 DuPont-14162 Appendix A Individual PFOA Serum Concentrations for Mice -277- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL PFOA SERUM CONCENTRATIONS FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA meIB IC MB VB VC VIIB VIIC IXB IXC XIB XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day Ctrl = Control L = Linear B = Branched Avg. = Average S dev = Standard deviation QNS = Quantity not sufficient for analysis NSR = No sample received N/A = Not Applicable Note: H-26225 is comprised of two components, H-26203 and H-26204. -278- APFO (Linear/Branched), AFFO (Linear), and AFFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice___________________________ DuPont-14162 Individual PFOA Serum Concentrations for Mice Group Dose Level IA Ctrl pg/mL pg/mL ID Linear Branched L-bB 101 NSR NSR N/A 102 0.041 0.016 0.057 103 0.029 0.010 0.039 104 0.067 0.018 0.085 105 0.040 0.012 0.052 106 0.019 0.007 0.026 107 0.013 0.000 0.013 108 0.017 0.000 0.017 109 0.013 0.009 0.022 110 0.011 0.008 0.019 Avg. 0.028 0.009 0.037 s dev 0.024 L/B N/A 2,50 3.02 3.79 3.28 2.67 * * 1.36 1.36 2.57 0.92 IDA 0.3 mg/kg 301 8.1 302 7.8 303 6.5 304 8.1 305 9.7 306 9.4 307 8.8 308 7.2 309 9.5 310 7.3 Avg. 8.2 2.4 1.8 1.6 2.3 2.8 2.0 2.1 1.7 2.0 1.7 2.0 s dev 10.5 3.37 9.6 4.35 8.1 4.20 10.4 3.55 12.6 3.42 11.4 4.62 10.9 4.21 8.8 4.33 11.5 4.83 9.0 4.31 10.3 4.12 1.4 0.50 VA 1.0 mg/kg 501 11.1 502 23.2 503 23.8 504 23.3 505 22.2 506 20.6 507 21.6 508 17.7 509 26.0 510 20.9 Avg. 21.0 Ratio not determined (divide by zero error). 3.2 5.4 6.2 6.9 5.6 7.0 5.5 4.4 5.6 5.3 5.5 s dev 14.3 3.48 28.6 4.31 30.0 3.82 30.2 3.37 27.9 3.95 27.6 2.92 27.1 3.94 22.1 4.01 31.6 4.67 26.2 3.95 26.6 3.84 5.0 0.49 -279- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual PFOA Serum Concentrations for Mice Group Dose Level VIIA 3.0 mg/kg (ig/mL p,g/mL ID Linear Branched 701 45.0 9.0 702 56.1 12.8 703 58.1 14.5 704 47.7 13.2 705 58.1 14.6 706 41.3 10.3 707 56.1 12.1 708 55.4 11.0 709 53.7 12.0 710 65.7 14.0 Avg. 53.7 12.3 s dev L+B 53.9 69.0 72.6 60.9 72.7 51.5 68.2 66.4 65.7 79.7 66.1 8.6 L/B 5.02 4.38 4.01 3.60 3.98 4.02 4.64 5.04 4.48 4.68 4.39 0.48 IXA 10 mg/kg 901 155 902 193 903 166 904 160 905 213 906 146 907 171 908 147 909 146 910 151 Avg. 165 29.6 33.5 25.8 23.5 39.6 19.7 23.7 20.6 24.4 16.9 26 s dev 184.4 226.8 192.0 183.0 252.2 165.4 194.4 167.8 170.9 167.6 190 28.5 5.23 5.77 6.44 6.80 5.38 7.38 7.21 7.15 6.00 8.94 6.63 1.12 XIA 30 mg/kg 1101 198 22.3 220.3 8.88 1102 246 26.2 271.8 9.36 1103 191 20.3 211.2 9.43 1104 233 26.9 259.9 8.67 1105 208 21.2 228.8 9.81 1106 222 21.7 244.0 10.25 1107 204 20.1 224.5 10.19 1108 193 17.6 210.4 10.98 1109 218 22.4 240.1 9.71 1110 272 24.2 296.6 11.26 Avg. 218 22 241 9.9 s dev 28.0 0.84 Note: Test substance H24921 L/B ratio = 0.78/0.22 = 3.55 ng/mL values corrected for standard composition and converted to pg/mL by multiplying linear values by 0.00078 and branched values by 0.00022 -280- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual PFOA Seram Concentrations for Mice Group IB Dose Level Ctrl ID 101 102 103 104 105 106 107 108 109 110 Avg. s dev pg/mL Linear 0.077 0.037 0.218 0.062 0.131 0.035 0.018 0.038 0.022 0.030 0.067 0.060 IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 Avg. s dev 12.4 11.5 18.1 13.3 14.3 10.9 11.7 10.4 QNS 11.2 12.6 2.4 VB 1.0 mg/kg 501 502 503 504 505 506 507 508 509 510 Avg. s dev 34.3 42.1 31.0 38.4 31.8 30.9 25.1 32.9 28.0 26.6 32.1 5.2 Revision Number 1 DuPont-14162 -281 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual PFOA Seram Concentrations for Mice Group viro Dose Level 3.0 mg/kg ID 701 702 703 704 705 706 707 708 709 710 Avg. s dev pg/mL Linear 77 63 78 66 71 61 83 50 68 72 69 10 IXB 10 mg/kg 901 197 902 132 903 134 904 235 905 372 906 233 907 216 908 233 909 266 910 231 Avg. 225 s dev 68 xro 30 mg/kg 1101 253 1102 276 1103 297 1104 218 1105 NSR 1106 298 1107 253 1108 286 1109 246 1110 203 Avg. 259 s dev 34 Revision Number 1 DuPont-14162 -282- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________________________ Revision Number 1 DuPont-14162 Individual PFOA Seram Concentrations for Mice Group IC Dose Level Ctrl H26203 pg/mL pg/mL + ID H26203 H26204 H26204 H26204/H26203 101 * * 0.079 N/A 102 * * 0.043 N/A 103 * * 0.027 N/A 104 * 0.029 N/A 105 * * 0.017 N/A 106 * * 0.000 N/A 107 * * 0.000 N/A 108 * * 0.000 N/A 109 * * 0.000 N/A 110 * * 0.000 N/A Avg. * 0.02 N/A s dev 0.03 m e 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 Avg. 6.2 6.2 7.3 5.8 5.0 6.1 5.1 4.3 6.2 5.0 5.7 9.4 10.8 14.3 8.2 7.7 7.7 6.4 5.7 6.9 4.9 8.2 s dev 15.6 17.0 21.6 14.0 12.7 13.8 11.5 10.1 13.1 9.9 13.9 3.52 1.53 1.74 1.97 1.42 1.54 1.26 1.25 1.31 1.11 0.99 1.41 0.29 VC 1.0mg/kg 501 14.4 34.9 49.4 2.42 502 12.1 28.1 40.2 2.33 503 12.4 29.8 42.2 2.40 504 11.5 24.2 35.7 2.11 505 11.4 27.0 38.4 2.38 506 11.3 26.7 38.0 2.35 507 8.3 15.3 23.5 1.84 508 9.5 14.3 23.8 1.51 509 8.8 17.2 26.0 1.94 510 7.8 10.8 18.6 1.38 Avg. 10.8 22.8 33.6 2.07 s dev 10.0 0.38 * A total branched content was determined instead of individual values. -283- APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual PFOA Serum Concentrations for Mice H26203 Dose pg/mL pg/mL + Group Level ID H26203 H26204 H26204 H26204/H26203 v n c 3.0 mg/kg 701 25.0 73.9 98.8 2.96 702 15.4 50.0 65.4 3.24 703 22.4 76.2 98.5 3.40 704 18.0 63.2 81.2 3.51 705 20.1 65.6 85.7 3.27 706 20.0 59.6 79.7 2.97 707 24.1 59.0 83.2 2.44 708 21.4 57.0 78.3 2.67 709 19.8 53.7 73.5 2.71 710 21.5 57.6 79.1 2.67 Avg. 20.8 61.6 82.3 2.99 s dev 10.3 0.36 IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 Avg. 38 41 35 36 47 38 33 40 39 46 39 145 171 136 115 184 112 107 119 114 125 133 s dev 183 212 171 151 232 150 139 160 154 170 172 29 3.87 4.14 3.87 3.19 3.90 2.96 3.27 2.94 2.91 2.73 3.38 0.52 XIC 30 mg/kg 1101 48 276 324 5.79 1102 39 213 252 5.43 1103 40 260 301 6.43 1104 33 204 236 6.21 1105 43 257 300 5.95 1106 44 170 214 3.87 1107 34 154 189 4.50 1108 42 155 197 3.66 1109 36 145 182 4.02 1110 50 194 244 3.89 Avg. 41 203 244 4.97 s dev 50 1.09 Note: Test substance H26225 ratio = 58% H26204/42% H26203 = 1.38 -284- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix B Individual Body Weights for Mice -285- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BODY WEIGHTS FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day -286- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 A i n d i v i d u a l B o d y Wei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male,, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 27.3 29.6 30.7 29.7 32.1 34.8 33.3 29.3 32.1 32.8 27.0 28.5 30.2 29.5 31.3 33.9 33.0 28.4 31.3 32.2 26.9 29.1 29.7 29.3 31.8 33.7 32.6 28.4 31.2 32.0 24.0 29.4 31.0 29.4 32.3 34.1 33.3 29.4 32.0 32.8 NM 29.2 30.4 29.4 32.6 33.8 32.8 29.7 32.5 32.8 Male,, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 28.3 30.8 30.6 30.8 33.3 33.6 31.9 31.0 30.5 33.1 28.5 29.5 30.9 29.6 32.4 33.1 31.3 30.3 30.3 33.7 27.8 29.0 30.6 29.0 32.0 33.1 30.5 29.8 29.8 32.7 29.0 30.0 32.0 29.8 32.6 34.1 31.8 30.8 30.4 33.3 29.3 29.7 32.7 29.0 32.4 34.3 31.7 30.7 30.1 33.3 Male,, V A 1 mg/kg 501 502 503 504 505 506 507 508 509 510 31.9 31.4 31.4 30.0 32.8 34.8 31.7 31.0 31.8 34.0 32.3 30.6 29.7 29.2 31.9 34.0 31.3 30.4 30.7 34.1 32.0 30.2 29.6 29.2 32.1 33.8 30.8 30.0 30.9 34.4 28.5 31.9 31.2 31.0 33.4 34.5 31.9 31.5 32.0 35.0 25.5 31.8 31.3 31.2 33.3 34.5 32.3 31.6 32.3 35.2 Key: N M = Not Measurable -287- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:40:20 :ghts for Mice Body Weight g iy 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 29.5 30.9 30.0 32.8 33.8 33.3 29.6 32.4 33.0 29.2 30.0 33.0 29.2 32.4 34.2 31.0 30.6 30.2 33.5 24.7 31.8 30.8 31.2 33.9 34.2 31.9 31.7 32.0 35.1 29.7 31.0 29.2 33.8 34.3 33.1 30.3 32.0 33.9 29.6 30.0 33.4 29.7 32.8 34.2 31.2 31.0 30.1 33.9 24.2 32.6 31.2 31.5 34.5 34.8 31.8 31.9 32.3 35.4 29.8 30.7 29.8 34.0 34.3 33.7 30.4 32.6 33.8 29.7 30.6 33.2 30.0 32.7 34.8 32.2 31.5 30.7 34.0 24,5 32.8 31.4 31.6 34.9 34.9 32.2 32.6 32.4 35.7 29.9 31.0 29.8 33.5 34.2 33.6 29.5 32.5 33.6 28.9 30.5 33.1 29.8 32.3 33.8 31.1 30.9 30.8 33.9 24.5 32.1 31.5 31.6 35.2 34.2 33.1 33.3 32.7 35.9 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 A I n d iv i d u a l B ody W e ig h ts f o r M ice Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g Day 12 Body Weight g D a y 13 B o d y Weig] g D a y 14 Male, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 30.5 31.6 29.6 33.7 34.1 33.3 29.4 32.3 33.4 30.7 31.8 29.8 34.7 35.1 34.3 30.4 32.7 33.8 31.2 32.3 30.6 35.0 35.3 34.5 31.1 32.9 34.1 31.0 31.8 30.0 35.2 35.4 34.3 30.7 32.8 33.9 31.4 32.4 30.1 35.1 35.6 34.5 30.8 33.6 34.1 30.7 30.6 30.1 33.6 34.4 33.7 29.1 31.8 33.0 Male, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 28.8 29.8 32.7 28.9 31.9 33.4 31.1 30.5 29.7 33.5 29.5 31.0 33.7 30.1 32.9 34.6 31.7 31.4 31.5 34.1 30.0 31.3 34.9 30.7 33.3 35.4 32.5 32.3 31.6 34.8 30.1 31.0 34.9 30.1 32.6 34.6 31.6 32.2 31.4 34.8 30.2 31.2 34.6 30.4 33.4 34.9 31.9 32.7 31.6 34.9 29.1 29.9 33.4 29.3 32.3 33.5 31.2 31.9 30.6 33.6 Male, V A 1 mg/kg 501 502 503 504 505 506 507 508 509 510 24.1 31.8 31.3 31.5 34.9 34.0 32.8 32.9 32.8 35.6 25.9 32.1 32.0 31.8 35.8 34.5 33.0 33.2 32.8 36.0 26.7 32.0 32.5 32.2 36.5 34.9 33.0 34.0 33.0 36.7 27.3 32.1 32.0 31.7 35.7 34.4 32.9 34.0 33.2 37.4 27.9 32.4 32.6 32.3 36.2 34.5 33.3 34.4 33.1 37.8 28.2 31.5 31.4 31.6 34.5 33.8 31.3 33.0 31.9 35.1 -288 - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:40:20 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Study: 15073 879 A Print Date: 16-Apr-2004 Print Time: 09:40:20 Individual Body Weights for Mice Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 Male, V I IA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 28.7 30.2 32.2 30.1 33.3 34.0 32.6 31.0 32.2 33.9 28.9 29.1 31.9 29.4 32.2 33.8 32.3 30.2 31.4 32.5 28.7 29.5 31.4 29.9 33.0 34.3 32.4 29.7 31.6 32.8 28.9 30.5 32.6 30.2 33.6 34.8 33.1 30.8 32.3 34.3 25.2 30.3 33.2 30.6 33.9 35.0 33.6 31.0 32.7 34.0 23.7 30.6 33.0 30.3 33.9 34.0 33.1 31.0 33.0 34.1 23.9 31.4 33.6 30.4 34.3 34.5 33.3 31.4 32.9 34.8 24.9 31.9 34.5 31.7 34.9 35.4 33.8 31.7 33.3 34.5 25.8 31.6 34.1 31.0 35.2 34.7 34.5 31.8 33.6 34.5 Male, IXA 10 mg/kg 901 902 903 904 905 906 907 908 909 910 29.0 30.5 31.2 31.4 32.6 32.9 31.1 31.4 32.9 33.9 28.7 29.9 30.9 30.2 32.0 31.4 30.9 30.5 31.0 32.0 28.6 30.0 30.8 30.5 32.3 31.7 30.7 31.0 31.1 32.2 29.4 30.9 30.3 31.0 31.9 32.1 31.2 31.3 31.4 33.0 30.1 31.6 31.8 31.1 32.2 32.5 31.7 31.4 32.5 34.6 29.9 31.0 31.3 31.4 30.9 32.7 31.3 31.4 32.6 33.2 30.7 31.1 31.8 31.4 31.1 32.8 31.1 31.3 32.9 31.4 30.9 30.9 32.8 32.0 30.6 31.7 30.7 31.5 33.4 30.9 30.6 31.0 32.8 31.9 29.7 33.8 29.6 32.6 33.1 30.5 Male, XIA 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 30.5 30.5 30.3 29.5 33.0 32.7 32.8 30.9 30.7 33.4 29.8 29.9 29.1 29.1 32.1 30.8 32.0 30.5 29.7 32.0 29.8 30.7 29.6 30.0 31.5 30.3 32.6 30.4 30.7 32.3 29.9 30.5 29.1 30.3 31.9 28.4 32.8 29.7 30.8 32.1 29.6 30.5 29.3 29.1 31.9 29.5 33.2 30.2 30.7 32.5 29.0 28.1 26.7 26.9 29.4 28.8 31.3 27.2 28.9 30.6 27.7 27.1 24.8 25.2 28.5 27.9 29.9 27.2 28.7 29.4 27,1 26.1 24.9 24.5 29.1 27.3 29.8 27.1 29.0 28.7 27.2 25.3 24.6 24.4 28.3 27.6 29.3 27.4 29.4 30.6 -289- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice____________________________________________________________________________ DuPont-14162 Study: 15073 879 A I n d iv i d u a l B ody W e ig h ts f o r M ice Body Weight g Day 9 Body Weight g Day 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weigl g D a y 14 Male, VI IA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 26.9 31.1 34.3 31.2 35.3 35.2 34.2 31.9 33.3 34.8 27.2 31.0 35.2 31.0 35.6 35.0 34.4 31.9 33.5 34.8 28.1 31.7 35.7 31.9 35.7 35.1 34.8 32.6 34.0 35.2 28.1 31.1 35.5 31.2 36.0 35.9 34.3 32.9 34.6 35.5 27.7 31.4 35.9 31.7 36.1 36.1 34.8 32.8 34.4 35.6 26.0 30.7 33.8 31.4 34.7 34.0 33.8 32.0 33.1 34.1 Male, IXA 10 mg/kg 901 902 903 904 905 906 907 908 909 910 30.8 29.9 32.0 31.6 30.2 32.2 29.7 31.1 33.2 28.6 30.6 30.5 33.1 32.0 29.3 32.4 28.5 30.6 32.5 27.8 32.1 30.0 32.8 32.3 28.4 34.0 28.0 31.2 31.2 28.0 30.9 29.6 31.6 31.1 27.3 32.5 26.9 31.9 31.0 27.7 30.6 29.5 30.2 31.1 26.7 32.3 26.6 28.8 31.1 26.9 29.1 27.8 28.9 30.3 25.8 31.0 26.8 28.0 30.0 25.6 Male, X I A 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 26.5 24.9 25.9 23.6 28.5 27.7 28.8 26.0 28.7 30.3 26.2 24.7 25.7 23.2 28.6 27.6 28.6 25.5 28.4 28.9 25.6 24.4 25.0 23.4 28.3 27.9 27.4 26.2 28.9 28.3 25.1 24.3 24.1 22.6 27.5 27.3 27.7 25.1 28.0 26.3 24.7 23.9 24.1 22.6 26.9 26.4 28.2 25.3 27.3 26.5 23.9 22.8 24.0 22.1 26.1 26.2 27.1 24.7 26.5 25.5 Print Date: 16-Apr-2004 Print Time: 09:40:20 -290- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_________ Study: 15073 879 B Individual B o d y Wei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weigl g Day 4 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 29.5 32.2 30.7 30.9 33.8 32.0 33.2 29.8 31.0 30.1 29.0 31.4 30.7 31.1 33.2 31.3 33.6 29.5 31.2 29.0 29.1 32.2 30.5 30.7 33.0 30.7 32.6 30.0 31.5 29.0 29.6 32.3 30.9 31.2 29.4 31.3 33.6 30.3 32.5 29.1 28.9 32.1 31.0 31.0 27.2 30.4 32.5 29.7 32.2 29.0 Male, IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 29.5 31.6 30.2 30.8 34.4 33.5 31.1 30.5 30.9 31.6 29.1 31.6 30.2 30.4 33.6 32.4 30.2 30.4 30.4 31.0 28.7 31.7 30.3 30.7 33.9 32.6 30.1 30.6 30.5 30.7 29.6 32.7 31.1 31.1 34.8 33.7 31.2 30.8 31.3 31.9 29.5 32.1 30.2 30.6 34.2 33.2 30.3 30.7 30.8 31.0 Male, VB 1 mg/kg 501 502 503 504 505 506 507 508 509 510 30.4 31.0 31.4 32.7 33.9 33.4 31.8 31.2 31.4 31.5 30.3 30.2 31.4 32.3 34.0 32.7 31.3 31.2 31.4 31.0 30.2 30.3 31.4 32.8 33.8 33.2 31.9 32.0 32.1 31.8 31.1 30.9 32.2 33.5 34.5 34.0 32.1 31.9 31.8 31.7 30.6 30.0 31.8 32.8 33.0 33.9 32.4 31.8 32.2 32.4 -291 - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:56:46 .ghts for Mice Body Weight g Day 5 Body W eig h t g Day 6 Body Weight g Day 7 B ody W eig h t g Day 8 29.1 32.6 31.1 31.1 27.6 30.5 32.9 30.1 32.6 29.7 29.4 33.8 31.5 31.1 27.7 31.3 33.8 31.0 33.6 30.0 28.9 32.7 31.5 31.2 28.7 30.5 33.4 30.7 33.4 29.0 29.4 31.6 31.0 31.3 29.7 30.3 32.6 30.2 32.8 29.5 29.9 32.5 30.3 31.0 33.9 33.4 30.3 31.0 31.1 31.3 30.4 33.0 30.9 31.8 34.0 34.5 30.8 31.8 31.9 32.5 30.1 32.6 30.9 31.6 34.4 34.2 30.2 31.3 31.7 31.8 29.5 32.2 30.1 30.8 33.6 32.7 29.8 31.0 30.9 30.9 31.4 30.3 32.2 33.4 34.2 33.6 33.0 32.0 32.7 32.8 32.1 31.4 32.6 34.1 34.6 34.6 33.5 33.4 33.2 33.7 32.3 31.1 33.1 34.3 34.7 35.1 33.2 33.5 33.4 33.8 31.4 29.9 31.7 33.3 34.1 34.2 32.3 32.9 32.8 33.2 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 B I n d iv i d u a l B ody W e ig h ts f o r M ice Body Weight g Day 9 Body Weight g Day 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 Body Weight g D a y 14 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 29.6 32.5 31.1 31.5 30.5 30.4 32.7 30.6 32.7 29.8 29.1 33.0 32.3 31.8 31.0 30.7 33.1 30.9 33.3 30.1 29.4 33.3 32.0 31.8 31.6 30.8 33.0 31.2 32.9 29.4 29.9 33.6 32.0 32.0 32.1 30.8 33.0 31.2 33.5 30.1 30.9 34.1 32.7 33.3 32.9 31.3 34.1 32.1 34.4 30.6 28.7 31.9 30.8 31.2 31.0 29.8 32.4 30.3 32.1 29.1 Male, IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 29.5 32.4 30.5 31.1 33.5 33.7 30.7 31.1 31.5 31.5 30.1 32.3 31.1 31.2 33.8 33.8 30.9 31.4 31.8 31.9 30.2 32.5 31.0 31.0 34.0 34.1 30.2 31.3 31.9 32.0 30.3 32.6 30.8 31.2 33.8 34.8 31.0 32.0 32.1 32.0 30.5 33.3 31.5 32.0 34.8 35.4 31.4 32.5 33.3 32.3 29.3 31.4 30.5 30.5 32.6 32.7 29.9 30.7 31.1 30.8 Male, VB 1 mg/kg 501 502 503 504 505 506 507 508 509 510 31.7 30.6 32.2 33.5 34.7 34.4 32.8 33.6 33.6 33.5 31.7 30.8 32.9 33.6 35.2 35.1 33.3 34.1 33.7 34.2 32.6 31.0 33.1 33.8 34.7 34.9 32.9 34.0 33.4 34.4 32.2 31.4 33.6 34.2 35.1 35.1 33.5 34.9 33.9 34.1 32.8 32.5 34.1 34.1 35.7 35.7 33.9 34.3 34.4 34.9 31.5 30.6 32.7 32.4 33.7 34.3 32.4 33.7 33.1 33.2 -292- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:56:46 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____ Study: 15073 879 B I n d i v i d u a l B o d y We: Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, VIIB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 29.2 30.6 30.9 33.2 31.6 34.7 31.9 31.7 30.1 31.8 29.3 30.0 31.7 34.0 31.9 35.3 32.4 31.2 29.8 31.4 29.6 31.0 32.4 34.9 31.4 35.5 28.9 32.4 30.4 31.6 30.0 31.5 33.4 36.1 31.9 36.0 27.2 33.3 31.0 31.5 29.6 31.2 33.1 35.6 32.3 36.1 26.3 32.7 30.4 31.4 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908 909 910 29.9 31.7 30.0 32.1 33.0 31.9 31.5 29.9 31.7 29.3 29.3 31.0 30.8 31.9 33.6 32.6 31.9 30.0 31.7 29.3 30.3 32.1 31.5 33.1 34.7 32.9 32.2 30.5 32.0 30.1 30.7 33.1 31.6 34.2 36.0 33.9 32.6 31.2 32.6 30.8 30.7 33.4 32.3 33.9 35.5 33.9 33.0 31.2 32.2 30.0 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 29.3 32.2 29.7 32.9 32.9 32.1 31.6 30.3 30.0 31.7 30.4 32.3 30.5 33.8 33.2 33.5 32.4 31.2 30.7 32.6 30.9 32.3 30.5 34.5 33.4 33.9 32.6 31.4 31.3 33.2 32.1 33.3 30.8 33.6 33.6 33.9 33.7 31.6 33.1 31.8 30.6 30.8 28.5 31.4 30.5 31.3 30.3 28.3 31.9 30.7 -293 - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:56:46 .ghts for Mice Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 30.1 32.0 33.0 36.0 32.5 36.7 25.7 33.1 30.5 31.7 31.0 32.3 34.2 36.9 33.6 37.6 25.7 34.2 30.7 32.6 30.1 32.5 33.6 36.7 32.9 36.9 25.5 33.2 30.1 31.8 29.9 32.0 33.7 36.6 32.7 36.5 26.3 32.9 30.3 32.2 30.7 33.2 32.2 33.9 35.6 34.0 32.8 30.9 32.3 29.9 30.3 34.5 32.1 33.7 36.9 34.0 32.9 31.7 33.3 30.1 28.0 33.3 31.9 32.2 36.5 32.5 31.1 30.9 31.7 29.3 28.9 32.9 32.5 32.2 35.9 32.7 31.6 31.5 31.1 29.2 29.3 28.7 27.7 29.5 25.9 30.4 29.4 26.8 30.8 29.3 29.2 27.0 28.4 29.0 24.1 28.7 28.4 24.7 29.1 28.5 25.5 23.6 26.7 27.9 22.0 26.8 26.0 23.7 25.6 28.9 25.9 23.4 27.7 24.8 23.2 29.3 26.2 24.4 25.8 29.7 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 B I n d iv i d u a l B ody W e ig h ts f o r M ice Body Weight g Day 9 Body Weight g Day 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 B o d y Weigl g D a y 14 Male, VIIB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 30.2 32.3 34.1 37.5 33.6 37.7 26.3 33.4 30.3 32.6 30.7 32.2 34.4 37.4 34.0 38.0 25.4 33.6 31.0 32.9 30.9 32.9 34.6 37.9 34.1 38.5 25.5 33.4 31.0 32.1 31.4 32.9 35.0 37.8 34.3 38.7 26.0 33.5 31.6 32.9 31.6 32.7 35.0 37.7 34.5 39.7 27.0 35.1 32.6 33.6 29.9 30.6 34.1 37.1 33.3 37.9 26.7 33.2 30.7 31.8 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908 909 910 27.2 33.0 30.4 32.0 35.7 32.3 29.8 30.9 29.9 28.4 27.8 32.1 30.6 31.4 36.9 32.7 29.8 30.8 29.0 28.4 27.0 32.4 31.8 30.6 35.9 31.7 29.2 30.8 29.0 28.0 26.5 31.6 29.5 30.0 35.6 31.4 28.5 31.4 27.6 28.6 25.6 32.8 31.2 29.7 36.0 31.9 28.5 30.4 27.0 28.0 23.7 30.5 28.4 27.5 33.3 30.3 25.7 28.3 27.2 25.5 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 26.2 23.4 27.8 27.0 23.2 29.6 25.7 24.0 24.3 29.1 27.3 23.5 27.4 27.8 NM 29.7 25.7 25.2 24.5 29.1 26.0 22.7 28.0 27.0 27.7 24.7 24.8 25.7 28.3 25.9 23.2 28.9 26.4 27.5 24.8 24.4 27.7 27.9 27.9 23.5 29.1 27.5 28.3 26.4 24.8 29.0 28.1 26.2 23.2 27.1 25.8 26.1 24.7 24.1 28.9 26.0 Key: N M = Not Measurable -294- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:56:46 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C I n d i v i d u a l B o d y We: Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 31.2 27.9 30.2 31.7 32.6 29.1 31.5 34.2 32.6 34.3 30.3 27.7 30.9 30.8 31.3 29.0 31.0 33.6 31.8 33.4 30.7 28.4 31.3 30.9 31.6 29.6 31.4 34.2 32.7 33.2 30.7 28.2 31.6 31.7 31.8 29.3 31.5 33.7 31.7 32.9 30.3 27.9 30.9 31.2 31.3 29.1 31.4 33.6 32.3 33.1 Male, IIIC 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 31.3 29.4 31.6 31.6 31.7 30.3 30.0 31.6 32.3 33.0 32.1 28.8 31.5 30.5 31.8 29.7 29.6 33-6 31.2 32.5 32.4 29.2 32.5 32.1 32.8 30.4 30.3 34.8 32.1 33.0 32.0 29.1 32.0 31.6 33.1 29.4 29.8 34.2 31.8 32.8 32.3 29.2 32.1 31.9 32.9 29.4 29.6 34.4 31.8 33.2 Male, VC 1 mg/kg 501 502 503 ' 504 505 506 507 508 509 510 32.8 30.5 31.1 33.3 32.2 31.5 30.9 32.8 31.1 34.8 32.3 30.1 30.2 32.8 31.1 30.5 30.6 31.9 29.8 33.6 33.4 30.5 30.2 33.7 32.3 30.7 30.6 33.1 30.6 34.4 33.0 30.0 30.3 32.5 31.8 30.6 31.1 32.3 30.1 34.3 32.9 29.8 30.1 32.5 32.2 30.9 31.8 31.9 30.2 34.3 -295- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 10:01:46 ights for Mice Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 31.1 28.8 31.9 32.0 32.1 30.0 31.8 34.5 33.1 33.6 30.6 28.3 30.8 31.3 32.0 29.0 31.6 34.0 32.6 33.6 31.4 29.0 32.3 32.0 32.6 29.8 32.2 34.1 33.4 33.9 30.6 28.6 31.3 31.6 32.2 29.4 31.7 34.7 33.1 33.5 32.9 29.9 33.2 32.3 33.9 29.7 30.4 35.3 32.3 33.6 32.7 29.5 32.4 32.3 33.2 29.5 30.2 35.3 32.1 34.3 32.8 30.0 33.0 33.3 34.1 29.8 30.3 35.9 32.2 34.2 32.8 29.8 33.1 32.3 33.3 29.9 30.1 35.8 31.6 33.7 33.2 30.7 30.9 32.7 33.1 31.1 32.2 32.9 31.0 35.4 33.4 30.7 30.4 32.9 32.3 31.3 32.2 32.2 30.7 35.1 34.2 31.0 30.9 32.8 32.9 31.6 32.4 32.9 31.4 36.3 33.2 30.2 31.0 32.4 31.9 31.8 32.2 32.5 30.5 35.6 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice__________________ __________________________________________________________ DuPont-14162 Study: 15073 879 C Individual Body Weights for Mice Body Weight g Day 9 Body Weight g D a y 10 Body Weight g D a y 11 Body Weight g D a y 12 Body Weight g D a y 13 B o d y Weig] g D a y 14 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 30.9 28.4 31.7 31.1 31.9 29.8 32.2 35.4 33.5 33.0 30.7 29.0 31.4 31.3 32.3 29.5 31.3 34.9 33.2 33.3 31.0 29.4 31.8 31.4 32.4 29.6 31.8 35.3 33.4 33.3 32.2 29.8 32.8 32.5 32.8 30.0 32.5 35.8 34.2 34.3 32.1 29.4 32.7 32.6 32.4 30.0 33.8 36.2 34.4 34.7 31.2 28.6 31.7 31.4 31.3 28.6 31.5 34.9 32.8 33.1 Male, IIIC 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 32.6 30.1 34.0 33.2 33.8 30.6 30.5 35.9 32.7 34.1 32.3 30.4 33.6 32.6 33.9 30.2 29.8 36.0 32.4 34.7 32.6 30.9 33.8 32.6 34.0 30.7 30.2 35.8 32.4 34.4 33.0 31.3 34.4 33.8 35.8 31.8 30.9 36.7 33.4 35.5 33.3 31.6 34.5 33.5 35.1 32.3 31.0 36.5 33.8 36.0 32.0 29.9 33.0 31.6 33.1 30.3 29.4 35.1 30.8 33.5 Male, V C 1 mg/kg 501 502 503 504 505 506 507 508 509 510 33.7 31.0 31.2 33.1 32.6 32.0 32.0 32.5 30.9 36.1 33.4 31.0 31.1 33.6 32.3 32.0 32.4 32.8 30.9 35.6 33.9 31.1 31.3 33.3 32.4 32.1 32.8 33.1 30.8 36.1 35.4 32.4 32.2 34.4 33.5 33.3 32.8 34.5 32.1 36.5 35.3 32.4 32.1 34.3 33.0 32.9 33.1 34.3 31.8 36.9 33.7 31.0 31.0 32.1 32.3 31.9 31.8 32.5 30.5 36.0 Print Date: 16-Apr-2004 Print Time: 10:01:46 -296- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 C I n d i v i d u a l B o d y Wei Body Weight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Male, VIIC 3 mg/kg 701 702 703 704 705 706 707 708 709 710 30.9 30.2 32.0 33.2 33.0 29.9 32.4 33.2 33.5 32.8 30.4 30.6 31.3 32.3 33.0 29.8 32.4 32.9 32.8 33.1 31.1 31.9 32.1 33.6 34.3 30.6 33.4 34.0 33.2 33.8 30.4 31.6 31.9 33.1 33.8 29.9 33.4 33.7 32.6 32.9 30.7 31.8 32.2 32.6 33.8 30.2 33.1 33.5 32.6 33.2 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 33.2 30.9 28.5 32.8 33.5 31.2 30.2 32.8 31.8 32.4 32.5 29.8 28.7 27.6 33.4 31.1 29.9 32.8 32.4 32.1 33.7 30.0 29.1 28.4 34.0 32.4 30.8 34.3 33.3 32.9 32.7 29.5 29.2 28.4 34.5 31.4 30.3 34.1 32.9 32.7 33.5 29.6 29.8 28.6 34.3 32.2 30.9 34.6 33.3 32.5 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 30.6 30.1 31.8 32.2 29.6 31.5 30.6 33.2 32.2 34.6 31.0 29.4 31.5 31.9 29.2 31.4 30.2 32.9 31.3 33.9 31.8 31.0 32.3 33.4 30.7 32.5 31.2 34.5 32.7 35.3 31.8 31.5 33.0 32.9 31.0 31.8 30.6 34.9 32.0 34.5 32.2 32.5 32.0 33.0 30.6 30.2 30.0 34.6 32.5 34.5 -297- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 10:01:46 .ghts for Mice Body Weight g Day 5 Body Weight g Day 6 Body Weight g Day 7 Body Weight g Day 8 31.9 33.0 33.2 34.7 35.3 30.9 33.6 34.0 33.6 33.9 31.8 32.6 32.5 34.2 35.2 30.9 33.8 34.2 33.8 33.3 32.6 33.2 33.4 34.9 35.9 31.7 34.9 34.6 34.1 33.8 31.6 33.4 32.8 34.1 35.2 31.4 34.0 34.4 33.8 33.0 34.'7 30.8 30.6 30.1 35.1 33.2 31.3 34.9 34.1 33.6 33.9 30.1 30.2 30.5 36.0 33.0 31.3 35.2 34.2 33.5 35.7 31.3 31.3 32.9 36.9 34.7 32.5 36.6 34.1 33.4 34.4 30.8 31.1 32.0 35.9 33.7 32.0 35.5 35.4 33.9 32.2 32.5 32.6 33.4 32.3 31.9 30.2 35.4 33.9 35.8 31.1 32.2 30.4 31.5 30.5 29.2 29.4 34.1 32.6 34.5 31.6 32.5 32.0 31.8 31.8 30.5 29.5 34.4 32.2 35.9 30.2 31.8 30.9 30.4 30.6 30.5 28.4 33.5 31.4 33.7 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice______________________________________________________________________ ______DuPont-14162 Study: 15073 879 C I n d i v i d u a l B ody W e ig h ts f o r M ice Body Weight g Day 9 Body Weight g D a y 10 Body Weight g Day 11 Body Weight g D a y 12 Body Weight g D a y 13 B o d y Weig] g D a y 14 Male, VIIC 3 mg/kg 701 702 703 704 705 706 707 708 709 710 31.8 33.8 33.7 34.9 35.4 32.0 34.1 34.7 34.6 34.5 31.2 33.2 33.5 34.8 34.9 32.2 34.2 . 34.7 33.8 33.7 32.0 33.8 33.6 35.0 35.2 32.4 34.2 35.2 34.3 33.6 33.1 34.4 35.2 36.6 37.0 33.4 35.7 36.9 35.8 35.4 32.7 34.5 35.1 35.7 35.9 33.3 35.0 36.4 35.1 35.0 31.8 32.9 34.3 34.6 34.4 32.0 34.1 35.4 33.7 33.9 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 34.5 31.3 31.9 32.2 36.8 34.9 33.5 35.5 35.5 33.8 33.8 30.9 32.0 33.7 36.6 34.5 33.5 35.9 35.4 33.8 33.7 31.3 32.5 32.2 36.6 35.1 33.2 35.7 35.4 33.9 34.1 32.3 34.4 34.4 37.7 36.4 34.4 37.0 37.0 35.2 33.8 32.0 34.3 33.8 36.8 35.6 34.2 36.7 35.6 35.7 33.4 31.0 32.3 32.8 35.6 33.6 32.3 35.0 33.6 33.5 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 31.6 31.7 31.3 32.0 32.1 31.0 29.4 33.1 31.9 34.5 30.6 31.4 29.1 31.7 31.0 30.7 27.8 33.4 30.8 34.4 31.2 31.5 29.6 32.0 31.3 30.7 28.5 34.4 30.7 34.5 32.3 33.1 31.2 33.6 32.3 31.6 31.0 34.9 31.5 35.9 32.2 32.1 30.8 32.7 31.3 30.9 29.1 34.4 30.5 36.1 31.0 31.8 29.4 32.6 30.5 28.6 27.9 32.3 30.5 34.9 Print Date: 16-Apr-2004 Print Time: 10:01:46 -298- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix C Individual Food Consumption for Mice -299- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 INDIVIDUAL FOOD CONSUMPTION FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC IIIC VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day g/anm/day = grams/animal/day -300- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 A Individual Food Consumption for Mice Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day Day 10 Food Cons g/anm/day D a y 13 Male, IA 0 mg/kg 101 102 103 104 105 106 107 108 109 110 3.2 5.1 5.1 5.1 5.4 5.8 6.1 5.9 5.5 5.5 5.1 4.8 4.9 5.6 5.3 5.6 5.6 5.9 5.6 5.1 4.7 4.5 5.4 5.6 6.0 6.6 4.4 4.7 5.3 5.3 5.4 5.9 5.6 6.1 7.0 6.4 5.3 Male, IIIA 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 5.6 5.3 5.9 5.5 5.2 5.8 5.8 4.8 5.3 5.0 5.2 5.3 5.7 4.9 4.8 6.3 5.3 5.3 5.0 5.7 4.7 4.2 6.3 5.5 4.3 5.8 5.4 4.8 4.5 6.9 5.3 5.6 6.3 5.5 5.7 6.1 4.9 5.6 5.3 7.1 Male, VA 1 mg/kg 501 502 503 504 505 506 507 508 509 510 4.2 4.9 5.8 6.0 5.2 5.7 5.5 5.6 6.0 5.6 2.1 5.6 5.5 5.7 6.2 6.1 5.3 5.5 5.6 5.9 4.2 6.1 5.8 5.0 5.9 5.4 5.0 5.3 5.0 5.6 4.8 5.4 5.9 5.6 6.3 5.7 5.4 6.1 5.6 6.9 -301 - Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:49:23 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________ Study: 15073 879 A Individual Food Consumption for Mice Food Cons. g/anm/day Day 3 F o o d <C o n s . g/anm/day Day 7 Food Cons. g/anm/day D a y 10 Food Cons g/anm/day D a y 13 Male, VIIA 3 mg/kg 701 702 703 704 705 706 707 708 709 710 5.9 5.0 5.2 6.0 5.4 5.7 5.9 5.3 5.7 5.8 3.4 6.1 5.2 5.4 6.2 5.2 5.6 5.3 5.7 5.6 5.0 4.8 4.9 5.2 5.6 4.8 5.2 4.6 4.6 5.2 4.9 5.5 5.7 5.9 6.1 6.3 5.6 5.4 5.7 5.7 Male, IXA 10 mg/kg 901 902 903 904 905 906 907 908 909 910 6.8 5.3 5.4 6.4 6.6 7.2 5.5 7.7 5.8 5.4 5.0 4.9 5.0 5.8 3.9 5.3 4.9 5.1 5.6 4.5 6.1 6.2 6.8 7.6 5.2 , 6.2 4.2 7.4 6.1 4.7 5.8 5.0 6.2 6.4 4.3 6.6 4.0 6.0 4.8 4.5 Male, X IA 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 5.1 5.8 4.6 5.1 5.2 3.1 6.7 7.1 5.7 5.7 4.9 4.5 3.1 4.2 5.2 3.7 4.5 4.8 5.0 3.8 3.2 4.7 5.0 3.8 6.3 6.7 5.1 5.2 6.1 5.6 4.7 3.4 4.2 3.9 3.7 5.0 4.0 4.3 5.2 3.6 -302- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:49:23 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Orai Gavage Study in Male Rats and Mice Study: 15073 879 B Individual Food Consumption for Mice Food Cons. g / arati/d a y Day 3 Food Cons. g / arati/d a y Day 7 Food Cons. g / arati/d a y D a y 10 Food Cons g / arati/d a y D a y 13 Male, IB 0 mg/kg 101 102 103 104 105 106 107 108 109 110 5.2 5.4 5.5 5.1 4.2 5.4 6.7 5.4 6.4 4.8 5.5 6.4 5.9 5.2 3.4 5.0 5.5 6.0 6.5 4.9 4.6 6.0 5.5 5.0 5.0 4.8 4.8 5.1 6.2 3.5 5.0 7.7 4.8 5.6 5.5 4.7 5.9 5.3 6.3 5.3 Male, IIIB 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 4.9 5.5 5.0 4.6 6.0 5.6 5.0 5.6 5.2 5.0 5.5 6.5 5.4 5.0 5.7 6.8 5.1 5.5 5.3 4.7 5.0 5.3 3.8 4.1 6.1 4.8 5.1 5.2 4.4 4.8 5.1 5.4 5.1 4.5 6.3 7.1 5.5 5.4 5.2 4.6 Male, VB 1 mg/kg 501 502 503 504 505 506 507 508 509 510 5.1 5.2 5.8 5.8 6.4 5.9 5.5 4.7 5.6 5.2 5.9 5.1 5.8 5.4 5.9 5.9 5.2 5.3 5.6 6.2 5.0 5.3 5.9 5.1 6.2 5.4 4.4 5.6 5.5 5.4 5.6 5.1 6.7 5.6 8.4 6.3 5.3 5.6 5.4 5.7 -303- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:57:23 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 B I n d i v i d u a l F o o d C o n su m p tio n f o r M ice Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons g/anm/day D a y 10 Food Cons, g/anm/day D a y 13 Male, VIIB 3 mg/kg 701 702 703 704 705 706 707 708 709 710 5.0 5.5 5.6 6.1 5.4 5.4 2.3 6.0 5.6 5.0 5.3 5.8 5.7 6.5 6.2 5.9 3.3 6.0 5.4 5.3 4.8 4.9 5.3 6.0 5.8 5.2 4.0 5.1 6.0 5.6 5.3 5.4 5.5 5.8 5.6 6.8 4.3 5.6 5.8 4.9 Male, IXB 10 mg/kg 901 902 903 904 905 906 907 908 909 910 4.6 5.7 5.5 6.0 5.9 5.8 5.3 5.9 6.4 5.0 4.4 6.0 5.6 5.6 6.0 5.4 5.3 5.3 5.6 5.2 6.0 6.3 5.7 6.5 6.5 5.9 5.6 5.3 6.4 5.5 4.1 6.1 6.4 4.3 6.8 5.3 4.3 6.0 4.3 4.8 Male, XIB 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 5.7 6.3 5.5 5.5 5.0 5.7 5.4 6.0 5.8 4.8 4.3 3.3 4.1 4.3 2.2 4.9 5.1 2.1 3.5 6.8 5.3 5.8 4.7 5.8 1.6 5.4 5.2 5.3 4.5 5.3 4.9 4.2 5.5 3.8 3.8 4.6 4.0 5.6 5.6 -304- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 09:57:23 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Individual Food Consumption for Mice Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 10 Food Cons g/anm/day D a y 13 Male, IC 0 mg/kg 101 102 103 104 105 106 107 108 109 110 5.1 5.4 7.1 6.0 5.6 6.2 6.1 5.5 5.4 5.5 5.8 5.5 5.3 5.9 5.3 5.0 5.6 5.2 5.5 5.6 5.4 5.1 7.0 5.7 6.0 5.3 6.4 5.3 5.5 5.9 5.2 4.5 6.6 6.1 5.0 4.8 6.3 5.1 5.4 6.3 Male, IIIC 0.3 mg/kg 301 302 303 304 305 306 307 308 309 310 6.2 5.7 6.0 5.3 5.1 3.9 5.3 6.8 6.2 5.2 5.6 5.2 5.7 5.5 5.9 4.8 5.0 6.2 5.5 5.4 5.4 5.5 6.2 5.8 5.8 4.7 6.5 6.4 5.7 5.6 5.2 5.3 5.1 5.2 5.8 4.9 5.3 6.0 5.7 5.5 Male, VC 1 mg/kg 501 502 503 504 505 506 507 508 509 510 5.9 5.7 4.8 6.0 5.9 4.3 5.2 5.3 5.3 5.7 5.2 5.5 4.9 5.4 5.3 4.9 5.3 4.7 5.1 5.6 5.3 5.5 5.4 5.4 5.2 5.3 5.9 4.7 6.1 5.8 5.4 5.7 4.9 5.7 4.9 5.7 4.8 5.1 4.8 5.6 -305- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 10:02:22 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Individual Food Consumption for Mice Food Cons. g/anm/day Day 3 Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 10 Food Cons g/anm/day D a y 13 Male, VIIC 3 mg/kg 701 702 703 704 705 706 707 708 709 710 5.3 6.0 5.7 5.2 6.1 5.2 6.5 6.2 5.9 5.7 . 5.6 5.9 5.6 5.4 6.0 5.6 6.2 5.3 5.8 5.2 5.4 6.5 6.1 5.6 6.2 6.5 6.7 6.2 6.0 5.7 6.0 5.5 5.7 5.6 5.9 5.9 4.9 5.7 6.0 5.1 Male, IXC 10 mg/kg 901 902 903 904 905 906 907 908 909 910 6.6 5.2 5.2 2.8 6.6 6.4 6.7 6.7 4.5 5.6 5.3 5.6 4.9 4.6 5.4 4.8 5.8 6.6 5.8 4.5 6.5 6.6 5.6 5.7 6.8 6.1 7.0 6.3 6.6 5.8 5.6 5.5 5.6 5.0 5.1 6.1 4.8 6.1 5.5 5.9 Male, XIC 30 mg/kg 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 6.4 5.6 6.6 5.5 5.2 5.0 6.2 6.3 5.3 5.2 4.4 6.0 6.4 4.0 4.9 4.2 4.1 5.0 4.4 4.3 4.7 6.3 5.6 5.3 5.2 5.2 5.6 6.1 5.8 4.5 6.0 6.6 5.7 4.7 4.5 5.7 4.1 7.3 4.9 4.9 -306- Revision Number 1 DuPont-14162 Print Date: 16-Apr-2004 Print Time: 10:02:22 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix D Individual Clinical Observations and Mortality Records for Mice -307- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB niB VB VIIB IXB XIB IC me VC vne IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 -308- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 A Sex Group Animal M IA 101 M IA 102 M IA 103 M IA 104 M IA 105 M IA 106 M IA 107 M IA 108 M IA 109 M IA 110 Individual Clinical Observations Observation General observation, No Abnormality Detected Found dead in cage. General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design Mice Days 0-4 4 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -309- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 A Sex Group Animal M IIIA 301 M IIIA 302 M IIIA 303 M IIIA 304 M IIIA 305 M IIIA 306 M IIIA 307 M IIIA 308 M IIIA 309 M IIIA 310 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -310- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 A Sex Group Animal M VA 501 M VA M VA M VA M VA M VA M VA M VA M VA M VA 502 503 504 505 506 507 508 509 510 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Discharge, Eye right. Black Swollen Observations, Forelimb, Right Sacrificed by design 0-2 3-14 4-5 3-5 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -311 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 A Sex Group Animal M VI IA 701 M VI IA 702 M VI IA 703 M VI IA 704 M VI IA 705 M VI IA 706 M VI IA 707 M VI IA 708 M VI IA 709 M VI IA 710 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormali ty Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Stain Fur/Skin, Neck, Yellow M a s s Inguen, Right, M a s s #1, N o t U l c e r a t e d , 1.0 c m M a s s Inguen, Right, M a s s #1, N o t U l c e r a t e d , 0.5 c m Sacrificed by design 0-2,6-8 3-6 10-14 9-9 14 General observation. No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -312- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice___________________________________ Study: 15073 879 A Sex Group Animal M IXA 901 M IXA 902 M IXA 903 M IXA 904 M IXA 905 M IXA 906 M IXA 907 M IXA 908 M IXA 909 M IXA 910 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -313- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 A Sex Group Animal M XIA 1101 M XIA 1102 M XIA 1103 M XIA 1104 M XIA 1105 M XIA 1106 M XIA 1107 M XIA 1108 M XIA 1109 M XIA 1110 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Bilateral Eye Observations, Enophthalmus, Right Lethargic Sacrificed by design 0-5,8-11 12-14 6-7 12-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 t~4 1 O General observation, No Abnormality Detected Sacrificed by design 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Swollen Observations,, Abdomen Sacrificed by design 0-12 13-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:00:53 -314- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 B Sex Group Animal M IB 101 M IB 102 M IB 103 M IB 104 M IB 105 M IB M IB M IB M IB M IB 106 107 108 109 110 Individual Clinical Observations Observation General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Stain Fur/Skin, Neck, Yellow Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Mice Days 0-14 14 0-14 14 0-14 14 0-14 14 0-5,8-14 6-7 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 -315- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice________ ___ study: 15073 879 B Sex Group Animal M IIIB 301 M IIIB 302 M IIIB 303 M IIIB 304 M IIIB 305 M IIIB 306 M IIIB 307 M IIIB 308 M IIIB 309 M IIIB 310 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 -316- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 B Sex Group Animal M VB 501 M VB 502 M VB 503 M VB 504 M VB 505 M VB 506 M VB 507 M VB 508 M VB 509 M VB 510 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 -317- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 B Sex Group Animal M V IIB 701 M VIIB 702 M V IIB 703 M VIIB 704 M VIIB 705 M VIIB 706 M V IIB 707 M VIIB 708 M VIIB 709 M VIIB 710 Individual Clinical Observations Observation General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Stain Fur/Skin, Dorsal Body, Yellow Swollen Observations, Forelimb, Right Swollen Observations, Shoulder, Right Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Mice Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 . 0-14 14 0-2,5 6-14 3-4 3-4 14 0-14 14 0-14 14 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 -318- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 B Sex Group Animal M IXB 901 M IXB 902 M IXB 903 M IXB 904 M IXB 905 M IXB 906 M IXB 907 M IXB 908 M IXB 909 M IXB 910 Individual Clinical Observations for Mice Observation Days General observation. No Abnormality Detected Lethargic Sacrificed by design 0-11,12-14 12 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 -319- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 B Sex Group Animal M XIB 1101 M XIB 1102 M XIB 1103 M XIB 1104 M XIB 1105 M XIB 1106 M XIB 1107 M XIB 1108 M XIB 1109 M XIB 1110 I n d iv i d u a l C l i n i c a l O b s e r v a tio n s f o r M ice Observation Days General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Bilateral Sacrificed by design 0-12,14 13 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Eye Observations, Enophthalmus, BilateralLethargic Carriage, High Pale Stain Fur/Skin, Ventral body. Yellow Found dead in cage. 0-6 7-9 8 8-9 9 8-9 10 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 , 14 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Bilateral Lethargic Sacrificed by design 0-11 12-14 12 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 19-Apr-2004 Print Time: 14:12:30 - 320- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 150731 879 C Sex Group Animal M IC 101 M IC M IC M IC M IC M IC M IC M IC M IC M IC 102 103 104 105 106 107 108 109 110 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Eye Observations, Enophthalmus, Left Sacrificed by design 0-4 5-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 2Q-Apr-2004 Print Time: 13:02:08 -321- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Sex Group Animal M me 301 M me 302 M me 303 M me 304 M me 305 M me 306 M me 307 M me 308 M me 309 M me 310 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation. No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, NO Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:02:08 -322- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Sex Group Animal M VC 501 M VC 502 M VC 503 M VC 504 M VC 505 M VC 506 M VC M VC M VC M VC 507 508 509 510 Individual Clinical Observations for Mice Observation Days 0 1 p-4 (to General observation. No Abnormality Detected Sacrificed by design 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Hair Loss, Perineum M a s s P e r i n e u m , M a s s #1, N o t U l c e r a t e d , 1.0 c m M a s s P e r i n e u m , M a s s #1, N o t U l c e r a t e d , 0.5 c m M a s s P erineum, M a s s #1, N o t U l c e r a t e d , 0.2 c m M a s s P e r i n e u m , M a s s #1, N o t U l c e r a t e d , .7cm Sacrificed by design 0-3 10-14 9 4-7,10-11 12-14 8 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:02:08 -323- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Study: 15073 879 C Sex Group Animal M VIIC 701 M VIIC 702 M VI IC 703 M VIIC 704 M VIIC 705 M VIIC 706 M VIIC 707 M VIIC 708 M VIIC 709 M VIIC 710 Individual Clinical Observations for Mice Observation Days General observation, No Abnormali ty Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:02:08 -324- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Sex Group Animal M IXC 901 M IXC 902 M IXC 903 M IXC 904 M IXC 905 M IXC 906 M IXC 907 M IXC 908 M IXC 909 M IXC 910 Individual Clinical Observations for Mice Observation Days General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Swollen Observations, Face Swollen Observations, Neck Sacrificed by design CO 1 t--1 0-9,11 10 10 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 General observation. No Abnormality Detected Sacrificed by design 0-14 14 General observation, No Abnormality Detected Stain Fur/Skin, Neck, Yellow Sacrificed by design 0-6,12-14 7-11 14 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-20Q4 Print Time: 13:02:08 -325- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Study: 15073 879 C Sex Group Animal M XIC 1101 M XIC 1102 M XIC 1103 M XIC 1104 M XIC 1105 M XIC 1106 M XIC 1107 M XIC 1108 M XIC 1109 M XIC 1110 Individual Clinical Observations Observation General observation, No Abnormali ty Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, NO Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormali ty Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Mice Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Revision Number 1 DuPont-14162 Print Date: 20-Apr-2004 Print Time: 13:02:08 -326- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix E Individual Animal Clinical Pathology Data for Mice -327- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VBA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 ABBREVIATIONS : General: mg/kg NSR NP - mg/kg/day no sample received for testing not taken or not performed Individual Clinical Chemistry Values: HEM - hemolysis LIP - lipemia ICT - icterus CHOL - cholesterol TRIG - triglycerides HDL - high-density lipoprotein cholesterol nonHDL - non-high-density lipoprotein cholesterol NOTES: When individual animal data are not reported, it may be due to one of the following reasons or other reasons, all of which are explained in the study records: the sample was clotted (CLOT) there was insufficient sample for testing (QNS) a valid result could not be obtained (RNV) the sample was not suitable for testing the animal died prior to sample collection no sample was available for testing (NSR) -328- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ I n d iv i d u a l A n im al C l i n i c a l P a th o lo g y D a ta , f o r M ice Male, Group IA Animal 101 102 103 104 105 106 107 108 109 110 Male, HEM NSR None None Trace Trace None None None None None Group LIP NP None None None None None None None None None IIIA Animal 301 302 303 304 305 306 307 308 309 310 HEM Trace None None Small Small None None None None None Male, Group LIP None None None None None None None None None None VA Animal 501 502 503 504 505 506 507 508 509 510 HEM None None Trace None Trace None None Trace None None LIP None None None None None None None None None None - 0 mg/kg H- 24921 - ICT CHOL mg/dL TRIG mg/dL NP None None None None None None None None None NP 113 134 157 137 168 151 121 143 177 NP 87 88 121 98 103 112 93 76 111 -0.3 mg/kg H -24921- ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 146 111 150 115 185 110 132 140 120 161 146 150 156 113 140 98 118 133 152 149 - 1 m g / k g H- 24921 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 98 131 149 173 93 115 136 200 160 127 119 132 143 141 115 139 142 151 151 214 Day HDL mg/dL NP 77 95 104 97 109 100 85 94 115 14 nonHDL mg/dL NP 36 39 53 40 59 51 36 49 62 Day HDL mg/dL 97 75 99 83 111 75 93 88 78 97 14 nonHDL mg/dL 49 36 51 32 74 35 39 52 42 64 Day HDL mg/dL 62 83 80 91 66 69 91 106 91 72 14 nonHDL mg/dL 36 48 69 82 27 46 45 94 69 55 Revision Number 1 DuPont-14162 -329- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ I n d iv i d u a l A n im al C l i n i c a l P a th o lo g y D a ta f o r M ice Male, Group Animal 701 702 703 704 705 706 707 708 709 710 Male, HEM None Small None Trace None None None None None Trace Group Animal 901 902 903 904 905 906 907 908 909 910 Male, HEM None None None None None None Trace None None Trace Group Animal 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 HEM None None Trace None None None None None None None VIIA LIP None None None None None None None None None None - 3 mg/ k g H- 24921 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 71 121 92 98 109 70 73 101 97 140 96 150 138 160 109 124 123 205 159 133 IXA LIP None None None None None None None None None None - 10 m g / k g H--24 9 2 1 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None Trace 90 111 73 109 171 94 122 69 96 208 148 214 164 145 149 180 227 127 116 121 XIA LIP None None None None None None None None None None - 30 m g / k g H-- 2 4 9 2 1 - ICT CHOL mg/dL TRIG mg/dL None Trace None None None None None None None Moderate 73 98 66 85 106 60 102 45 162 85 83 51 110 54 93 93 138 59 114 58 Day HDL mg/dL 47 66 60 60 70 40 44 50 47 67 14 nonHDL mg/dL 24 55 32 38 39 30 29 51 50 73 Day HDL mg/dL 52 64 46 70 108 57 76 44 49 125 14 nonHDL mg/dL 38 47 27 39 63 37 46 25 47 83 Day HDL mg/dL 44 60 37 52 64 29 56 24 82 45 14 nonHDL mg/dL 29 38 29 33 42 31 46 21 80 40 Revision Number 1 DuPont-14162 -330- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Mice Male, Group IB Animal 101 102 103 104 105 106 107 108 109 110 HEM Trace None Trace None None Trace None None None Trace Male, Group LIP None None None None None None None None None None IIIB Animal 301 302 303 304 305 306 307 308 309 310 HEM Trace None Trace None Trace None None None None None Male, Group LIP None None None None None None None None None None VB Animal 501 502 503 504 505 506 507 508 509 510 HEM None None None None Trace None None Trace None None LIP None None None None None None None None None None - 0 m g / k g H- 26313 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 159 133 197 136 134 129 173 116 150 173 96 93 151 138 91 62 71 74 108 141 -0. mg/kg H -26313- ICT CHOL mg/dL TRIG mg/dL None None None None' None None None None None None 137 118 140 103 151 163 149 151 242 115 113 121 79 135 141 125 158 130 187 64 - 1 mg/kg H- 26313 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 141 125 137 138 137 117 158 129 185 123 111 123 129 160 165 111 149 113 148 158 Day HDL mg/dL 107 90 119 87 77 83 111 71 93 107 14 nonHDL mg/dL 52 43 78 49 57 46 62 45 57 66 Day HDL mg/dL 90 78 88 64 90 91 91 87 138 79 14 nonHDL mg/dL 47 40 52 39 61 72 58 64 104 36 Day HDL mg/dL 89 68 82 69 82 72 91 68 93 68 14 nonHDL mg/dL 52 57 55 69 55 45 67 61 92 55 Revision Number 1 DuPont-14162 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Clinical Pathology Data for Mice Male, Group Animal 701 702 703 704 705 706 707 708 709 710 Male, HEM None None None None None None None None None None Group Animal 901 902 903 904 905 906 907 908 909 910 Male, HEM None None None None None None None None Trace None Group Animal 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 HEM None None None None NSR None None None None None VI IB LIP None None None None None None None None None None IXB LIP None None None None None None None None None None XIB LIP None None None None NP None None None None None - 3 mg/kg H- 26313 - ICT CHOL mg/dL TRIG mg/dL None None None None None None Trace None None None 72 113 71 96 ' 133 69 81 135 102 98 103 173 105 122 157 160 75 133 135 202 - 10 m g / k g H--26313 - ICT CHOL mg/dL TRIG mg/dL None None None None None Trace None None None None 100 148 105 57 129 135 95 98 169 122 75 235 149 62 156 144 111 119 175 128 - 30 m g / k g H--26 3 1 3 - ICT CHOL mg/dL TRIG mg/dL None Trace None Trace NP None Small Trace Trace None 100 80 162 59 NP 75 78 136 97 120 104 84 73 74 NP 70 64 106 97 101 Day HDL mg/dL 51 55 44 59 55 37 51 62 47 46 14 nonHDL mg/dL 21 58 27 37 78 32 30 73 55 52 Day HDL mg/dL 58 68 68 33 68 74 53 55 87 75 14 nonHDL mg/dL 42 80 37 24 61 61 42 43 82 47 Day HDL mg/dL 61 43 88 30 NP 39 49 75 49 66 14 nonHDL mg/dL 39 37 74 29 NP 36 29 61 48 54 -332- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Clinical Pathology Data for Mice Male, Group IC Animal 101 102 103 104 105 105 107 108 109 110 HEM None Trace None Trace Trace Trace None Trace None None Male, Group LIP None None None None None None None None None None me Animal 301 302 303 304 305 306 307 308 309 310 HEM None Trace Trace Trace Trace Trace None None Trace None Male, Group LIP Trace None None None None None None None None None VC Animal 501 502 503 504 505 506 507 508 509 510 HEM None Trace None None Trace None None None None None LIP None None None None None None None None None None - 0 mg/kg H- 26225 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 130 182 141 140 153 123 116 181 150 148 95 141 134 151 106 162 151 137 113 150 -0.30 mg/kg H-26225 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 182 118 115 104 118 97 122 144 101 148 710 131 127 94 174 117 97 112 78 129 - 1 m g / k g H- 26225 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 138 102 185 187 149 80 74 115 103 136 157 118 270 179 138 144 176 163 112 152 Day HDL mg/dL 88 120 97 91 98 81 76 110 89 92 14 nonHDL mg/dL 42 62 44 49 55 42 40 71 61 56 Day HDL mg/dL 83 78 79 65 73 67 83 89 62 92 14 nonHDL mg/dL 99 40 36 39 45 30 39 55 39 56 Day HDL mg/dL 83 74 100 104 91 52 50 75 74 85 14 nonHDL mg/dL 55 28 85 83 58 28 24 40 29 51 Revision Number 1 DuPont-14162 -333- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Clinical Pathology Data for Mice Male, Group VIIC Animal 701 702 703 704 705 706 707 708 709 710 Male, HEM None None None None None None None None None None Group LIP None None None None Trace None None None None None IXC Animal 901 902 903 904 905 906 907 908 909 910 Male, HEM None None None None None None None None None None Group LIP Trace None None None None None Trace None None None XIC Animal 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 HEM None None None None None Trace None None None None LIP None None None None None None None None None None - 3 mg/ k g H- 26225 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 119 57 126 88 90 85 77 128 68 121 159 100 228 153 232 107 138 99 146 128 - 10 m g / k g H- 2 6 2 2 5 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 125 72 79 75 114 119 105 149 153 211 258 161 141 266 249 164 230 114 256 162 - 30 m g / k g H-- 2 6 2 2 5 - ICT CHOL mg/dL TRIG mg/dL None None None None None None None None None None 132 130 96 108 85 93 123 108 121 130 145 106 117 137 113 116 75 160 117 182 Day HDL mg/dL 74 45 73 57 60 55 51 80 44 77 14 nonHDL mg/dL 45 12 53 31 . 30 30 26 48 24 44 Day HDL mg/dL 74 47 52 35 64 68 50 88 81 106 14 nonHDL mg/dL 51 25 27 40 50 51 55 61 72 105 Day HDL mg/dL 81 84 54 60 55 50 77 65 69 72 14 nonHDL mg/dL 51 46 42 48 30 43 46 43 52 58 -334- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 Appendix F Individual Animai Final Body and Organ Weights for Mice -335- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VIIA IXA XIA IB IC IIIB m e VB VC v iro VIIC IXB IXC XIB XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day FBW = Final Body Weight Note 879 = Mice APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice__________ Organ Weight Listing Study:15073/24921/879A Group : IA 0 mg/kg Treatment : 0 mg/kg IA Sex MALES 11 A N I M A L FBW I 11 (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 102 130.700 1 0.530 1.7264 103 30.600 0.535 1.7484 104 30.100 0.475 1.5781 105 33.600 0.471 1.4018 106 34.400 0.527 1.5320 107 33.700 0.475 1.4095 108 29.100 0.516 1.7732 109 31.800 0.423 1.3302 110 33.000 0.529 1.6030 t1 1I Mean 31.889 1 0.498 1.5669 S.D. \ 1.864 0.039 0.1627 1 1.721 5.6059 1 1.608 5.2549 1 1.507 5.0066 1 1.795 5.3423 1 1.709 4.9680 1 1.733 5.1424 1 1.536 5.2784 1 1.474 4.6352 1 1.669 5.0576 1 1 1.639 5.1435 1 0.113 0.2737 1 j 1 j 1 1 1 j j i j I j \ Group : IIIA 0.3 mg/kg Treatment : 0.3 mg / k g IIIA Sex :MALES ANIMAL FBW 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 301 302 303 304 305 306 307 308 309 310 Mean S.D. 29.100 29.900 33.400 29.300 32.300 33.500 31.200 31.900 30.600 33.600 31.480 1.728 1 1 1 j j 1 i i j j I 1 j 1 0.433 0.562 0.591 0.547 0.511 0.547 0.472 0.540 0.547 0.691 1.4880 1.8796 1.7695 1.8669 1.5820 1.6328 1.5128 1.6928 1.7876 2.0565 0.544 1.7269 0.069 0.1798 1 1.764 6.0619 1 1.923 6.4314 1 2.176 6.5150 i 1.777 6.0648 i 2.029 6.2817 j 1.999 5.9672 j 1.918 6.1474 j 1.826 5.7241 I 1.789 5.8464 i 2.052 6.1071 1 1 1 1.925 6.1147 j 0.138 0.2452 FEW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073/24921/879A G r o u p : V A 1 m g / k g T r e a t m e n t : 1 m g / k g V A S e x :M A L E S 1 ANIMAL 1 FBW 1 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 501 1 502 1 503 1 504 1 505 1 506 1 507 1 508 1 509 1 510 Mean 1 S.D. 128.200 131.500 131.400 31.600 34.500 33.800 31.300 33.000 31.900 (35.100 ! (32.230 j 1.980 1 1 1 1 1 j j \ \ j 1 1 1 \ 0.531 0.490 0.462 0.523 0.564 0.572 0.458 0.549 0.548 0.662 1.8830 1.5556 1.4713 1.6551 1.6348 1.6923 1.4633 1.6636 1.7179 1.8860 0.536 1.6623 0.060 0.1457 1 1 (Gms) LIVER %FBW 1 2.468 8.7518 \ 2.339 7.4254 \ 2.570 8.1847 1 2.576 8.1519 1 2.398 6.9507 j 2.764 8.1775 j 2.400 7.6677 i 2.622 7.9455 \ 2.551 7.9969 j 2.782 7.9259 1 1 2.547 7.9178 1 0.150 0.4872 G r o u p : V I I A 3 m g / k g T r e a t m e n t : 3 m g / k g V I I I A S e x :M A L E S 1 ANIMAL 1 FBW 1 (Gms) \ (Gms) KIDNEYS %FBW 1 701 26.000 1 0.392 1.5077 1 702 30.700 j 0.496 1.6156 i 703 33.800 j 0.635 1.8787 i 704 31.400 \ 0.535 1.7038 i 705 34.700 j 0.595 1.7147 \ 706 34.000 \ 0.628 1.8471 \ 707 33.800 \ 0.533 1.5769 \ 708 32.000 \ 0.525 1.6406 \ 709 33.100 \ 0.577 1.7432 1 710 34.100 j 0.472 1.3842 (Gms) LIVER %FBW 2.651 3.388 3.264 3.416 3.649 3.947 3.379 3.691 3.598 3.707 10.196 11.036 9.6568 10.879 10.516 11.609 9.9970 11.534 10.870 10.871 1 Mean \ S.D. 32.360 1 0.539 1.6613 2.585 0.074 0.1502 3.469 10.717 0.352 0.6318 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 FBW - Final Body Weight -338 - Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing Study:15073724921/879A G r o u p : I X A 10 m g / k g T r e a t m e n t : 1 0 m g / k g I X A S e x :M A L E S 1 ANIMAL 1 FBW 1 (Gms) (Gms) KIDNEYS %FBW ! 1 (Gms) LIVER %FBW 1 901 1 902 1 903 1 904 1 905 1 906 1 907 1 908 1 909 1 910 1 l 1 Mean 1 S.D. 29.100 27.800 28.900 30.300 25.800 31.000 26.800 28.000 30.000 25.600 28.330 1.865 1 1 1 1 1 1 1 1 1 1 I I 1 1 0.489 1.6804 0.450 1.6187 NW 0.493 1.6271 0.406 1.5736 0.505 1.6290 0.380 1.4179 0.452 1.6143 0.463 1.5433 0.432 1.6875 0.452 1.5991 0.041 0.0816 1 4.241 14.574 1 4.760 17.122 1 4.455 15.415 1 5.070 16.733 1 4.589 17.787 1 5.004 16.142 1 4.274 15.948 1 4.371 15.611 1 5.322 17.740 1 4.006 15.648 1 1 1 4.609 16.272 1 0.421 1.0515 G r o u p : X I A 3 0 m g / k g T r e a t m e n t : 30 m g / k g X I A S e x :M A L E S 1 ANIMAL 1 FBW 1 (Gms) 1 (Gms) KIDNEYS %FBW 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 23.900 22.800 24.000 22.100 26.100 26.200 27.100 24.700 26.500 25.500 1 1 1 1 1 1 1 1 i 1 0.334 1.3975 0.364 1.5965 0.370 1.5417 0.339 1.5339 0.450 1.7241 0.405 1.5458 0.463 1.7085 0.371 1.5020 0.429 1.6189 0.480 1.8824 Mean S.D. 24.890 0.401 1.6051 1.666 1 0.053 0.1368 *** L i s t i ng Compl e t e *** 1 1 (Gms) LIVER %FBW 1 4.283 17.921 1 4.360 19.123 1 4.148 17.283 1 3.960 17.919 1 4.867 18.648 1 4.452 16.992 1 5.955 21.974 I 4.481 18.142 i 4.951 18.683 1 4.116 16.141 1 4.557 18.283 1 0.583 1.5691 1 1 1 1 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 NW - Not Weighed FBW - Final Body Weight -339- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073/26313/879B G r o u p : I B 0 m g / k g T r e a t m e n t : 0 m g / k g I B S e x :M A L E S | ANIMAL | FBW | 1 1 (Gms) | (Gms) KIDNEYS %FBW 101 102 103 104 105 106 107 108 109 110 |28.700 31.900 30.800 |31.200 |31.000 29.800 32.400 30.300 |32.100 |2 9 . 1 0 0 | i j i | | j \ \ j 0.512 0.594 0.543 0.628 0.575 0.461 0.528 0.584 0.646 0.576 1.7840 1.8621 1.7630 2.0128 1.8548 1.5470 1.6296 1.9274 2.0125 1.9794 Mean S.D. i1 30.730 j 0.565 1.8373 \ 1.254 0.055 0.1586 1 |(Gms) LIVER %FBW | 1.458 5.0801 \ 1.783 5.5893 i 1.698 5.5130 \ 1.792 5.7436 \ 1.816 5.8581 | 1.563 5.2450 j 1.744 5.3827 i 1.641 5.4158 \ 1.852 5.7695 j 1-622 5.5739 1 1 1 1.697 5.5171 j 0.125 0.2434 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 G r o u p : I I I B 0 . 3 m g / k g T r e a t m e n t : 0 . 3 m g / k g I I I B S e x :M A L E S | ANIMAL | FBW | j (Gms) | (Gms) KIDNEYS %FBW 1 |(Gms) LIVER %FBW | 301 i 302 \ 303 \ 304 i 305 | 306 j 307 \ 308 j 309 i 310 | Mean j S.D. |29.300 31.400 30.500 30.500 |32.600 32.700 29.900 30.700 31.100 30.800 1 30.950 \ 1.071 | i \ \ j \ i ] j | 1 1 j 0.490 1.6724 0.498 1.5860 0.530 1.7377 0.522 1.7115 0.581 1.7822 0.525 1.6055 0.505 1.6890 0.544 1.7720 0.518 1.6656 0.578 1.8766 0.529 1.7098 0.031 0.0867 | 1.845 6.2969 | 1.919 6.1115 | 1.910 6.2623 | 1.978 6.4852 j 2.203 6.7577 j 2.119 6.4801 \ 1.952 6.5284 j 2.113 6.8827 i 1.955 6.2862 \ 1.981 6.4318 1 1 | 1.998 6.4523 | 0.112 0.2335 FBW - Final Body Weight -340- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing S t u d y :15073/26313/879B G r o u p : V B 1 m g / k g T r e a t m e n t : 1 m g / k g V B S e x :M A L E S 1 ANIMAL 1 FBW I (Gms) 1(Gms) KIDNEYS %FBW 1 501 1 502 1 503 1 504 1 505 1 506 1 507 1 508 1 509 1 510 1 1 Mean 1 S.D. 31.500 30.600 32.700 32.400 33.700 34.300 32.400 33.700 33.100 33.200 32.760 1.104 1 1 1 1 1 1 j 1 t 1 1 1 0.548 1.7397 0.439 1.4346 0.595 1.8196 0.542 1.6728 0.611 1.8131 0.721 2.1020 0.508 1.5679 0.508 1.5074 0.563 1.7009 0.595 1.7922 0.563 1.7150 0.076 0.1892 1 1 (Gms) LIVER %FBW 1 2 . 5 0 7 7. 9 5 8 7 j 2 . 5 9 2 8. 4 7 0 6 I 2 . 8 7 0 8. 7 7 6 8 j 2 . 6 4 8 8. 1 7 2 8 1 2 . 8 8 2 8. 5 5 1 9 j 2 . 8 0 5 8. 1 7 7 8 1 2 . 5 7 6 7. 9 5 0 6 1 2 . 7 7 6 8. 2 3 7 4 1 2 . 9 1 3 8. 8 0 0 6 j 2 . 7 2 0 8. 1 9 2 8 1 1 j 2 . 7 2 9 8. 3 2 9 0 j 0 . 1 4 3 0 .3 0 6 8 1 j 1 I 1 1 j j 1 1 j j 1 1 j j G r o u p : V I I B 3 m g / k g T r e a t m e n t : 3 m g / k g V I I B S e x :M A L E S 1 ANIMAL 1 FBW I (Gms) I (Gins) KIDNEYS %FBW 1 701 1 702 1 703 1 704 1 705 1 706 1 707 1 708 1 709 1 710 1 1 Mean I S.D. 29.900 30.600 34.100 37.100 33.300 37.900 26.700 33.200 30.700 31.800 32.530 3.362 1 j 1 1 j 1 1 j j 1 1 j 1 0.517 0.529 0.542 0.653 0.476 0.763 0.502 0.502 0.584 0.593 1.7291 1.7288 1.5894 1.7601 1.4294 2.0132 1.8801 1.5120 1.9023 1.8648 0.566 1.7409 0.087 0.1850 1 j(Gms) LIVER %FBW 1 2 . 9 4 2 9. 8 3 9 5 1 3.405 11 .127 1 3.649 10 .701 1 4.205 11 .334 j 3.969 11 .919 j 4.669 12 .319 1 3.621 13 .562 ! 3.523 10 .611 j 3.255 10 .603 j 3.712 11 .673 1 1 1 3.695 11 .369 j 0 . 4 9 1 1 .0 6 0 0 1 1 1 j 1 j 1 j 1 j j 1 1 1 I 1 FBW - Final Body Weight -341- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Organ Weight Listing Study:15073/26313/879B G r o u p : I X B 10 m g / k g T r e a t m e n t : 10 m g / k g I X B S e x :M A L E S 1 ANIMAL 1 FBW 1 1 (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 1 901 1 902 1 903 1 904 1 905 1 906 1 907 1 908 1 909 1 910 1 Mean 1 S.D. 12 3 . 7 0 0 30.500 28.400 27.500 133.300 130.300 25.700 28.300 27.200 25.500 1 j i j \ j i j 11 28.040 1 j 2.804 0.296 0.511 0.496 0.488 0.583 0.554 0.420 0.459 0.407 0.395 1.2489 1.6754 1.7465 1.7745 1.7508 1.8284 1.6342 1.6219 1.4963 1.5490 0.461 1.6326 0.084 0.1700 1 3.729 15.734 \ 5.422 17.777 \ 4.339 15.278 1 4.970 18.073 j 6.274 18.841 \ 5 . 2 1 5 1 7 .2J.1 j 4.628 18.008 \ 4.772 16.862 1 4.822 17.728 j 4.157 16.302 1 1 I 4.833 17.181 i 0.711 1.1293 G r o u p : X I B 3 0 m g / k g T r e a t m e n t : 30 m g / k g X I B S e x :M A L E S 1 ANIMAL 1 FBW 1 i (Gms) \ (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 1 1101 j 1102 \ 1103 i 1104 \ 1106 \ 1107 i 1108 1 1109 j 1110 1 Mean i S.D. 26.200 23.200 27.100 25.800 26.100 24.700 24.100 28.900 26.000 1 1 25.789 i 1.675 1 j \ j j \ j \ I 1 1 0.537 0.390 0.418 0.415 0.423 0.448 0.369 0.534 0.429 2.0496 1.6810 1.5424 1.6085 1.6207 1.8138 1.5311 1.8478 1.6500 0.440 1.7050 0.058 0.1687 1 4.953 18.905 i 4.078 17.578 \ 5.126 18.915 \ 4.590 17.791 \ 4.729 18.119 1 4.503 18.231 1 4.108 17.046 j 5.548 19.197 i 4.116 15.831 1 1 1 4.639 17.957 i 0.508 1.0594 *** Listing Complete *** FBW - Final Body Weight -342- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl-400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing S t u d y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9C G r o u p : I C 0 m g / k g T r e a t m e n t : 0 m g / k g I C S e x :M A L E S 1 ANIMAL 1 FBW | 1 1 (Gms) i (Gms) KIDNEYS %FBW 1 j (Gms) LIVER %FBW 1 101 1 102 1 103 1 104 1 105 1 106 1 107 1 108 1 109 1 110 1 Mean 1 S.D. 131.200 28.600 31.700 31.400 31.300 28.600 31.500 134.900 132.800 33.100 1 ! 31.510 1.909 | \ \ | i j | j | i 1 1 | i 0.526 1.6859 0.495 1.7308 0.524 1.6530 0.541 1.7229 0.569 1.8179 0.522 1.8252 0.424 1.3460 0.510 1.4613 0.485 1.4787 0.560 1.6918 0.516 1.6414 0.041 0.1600 1 1.660 5.3205 \ 1.483 5.1853 \ 1.740 5.4890 j 1.639 5.2197 1 1.637 5.2300 \ 1.320 4.6154 1 1.766 5.6063 1 1.769 5.0688 \ 1.603 4.8872 \ 1.578 4.7674 1 1 1 1.620 5.1390 \ 0.138 0.3112 1 \ 1 \ j j j j 1 1 1 j 1 I j \ Group : IIIC 0.3 mg/kg Treatment : 0.3 mg/kg IIIC Sex MALES 1 ANIMAL 1 FBW | 1 \ (Gms) \ (Gms) KIDNEYS %FBW 1 301 1 302 1 303 1 304 1 305 1 306 1 307 1 308 1 309 310 1 Mean 1 S.D. 132.000 29.900 33.000 131.600 133.100 30.300 29.400 35.100 30.800 33.500 I 1 131.870 i 1.812 | \ \ | | \ \ | j | 1 1 | j 0.544 1.7000 0.467 1.5619 0.545 1.6515 0.557 1.7627 0.503 1.5196 0.520 1.7162 0.597 2.0306 0.577 1.6439 0.555 1.8019 0.620 1.8507 0.549 1.7239 0.045 0.1483 1 1 (Gms) LIVER %FBW 1 2.071 6.4719 j 1.724 5.7659 \ 2.130 6.4545 j 1.803 5.7057 1 2.040 6.1631 \ 1.779 5.8713 j 1.858 6.3197 ! 2.142 6.1026 1 1.765 5.7305 1 2.226 6.6448 1 i 1.954 6.1230 \ 0.186 0.3438 1 \ 1 \ \ j j j j j j j i 1 j j FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073/26225/879C G r o u p : V C 1 m g / k g T r e a t m e n t : 1 m g / k g V C S e x :M A L E S ANIMAL 1 FBW 1 j (Gms) 1 (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 501 133.700 1 0.535 1.5875 502 31.000 j 0.590 1.9032 503 31.000 1 0.546 1.7613 504 32.100 1 0.542 1.6885 505 32.300 j 0.489 1.5139 506 131.900 i 0.509 1.5956 507 31.800 \ 0.538 1.6918 508 32.500 \ 0.564 1.7354 509 30.500 j 0.503 1.6492 510 Mean 36.000 1 32.280 j 1 1 j 0.653 1.8139 0.547 1.6940 S.D. i 1.590 1 0.048 0.1154 1 2.729 8.0979 j 2.484 8.0129 \ 2.553 8.2355 i 2.673 8.3271 i 3.042 9.4180 \ 2.707 8.4859 \ 2.296 7.2201 1 2.266 6.9723 \ 2.177 7.1377 j 2.384 6.6222 1 1 1 2.531 7.8530 i 0.264 0.8504 G r o u p : V I I C 3 m g / k g T r e a t m e n t : 3 m g / k g V I I C S e x :M A L E S 1 ANIMAL 1 FBW 1 i (Gms) j (Gms) KIDNEYS %FBW 1 1 (Gms) LIVER %FBW 1 701 \ 702 i 703 1 704 i 705 \ 706 \ 707 \ 708 \ 709 i 710 j Mean j S.D. 131.800 32.900 34.300 34.600 34.400 32.000 34.100 35.400 33.700 33.900 1 1 j j j \ j \ j j 11 33.710 1 \ 1.149 0.515 0.594 0.515 0.508 0.506 0.514 0.544 0.489 0.465 0.663 1.6195 1.8055 1.5015 1.4682 1.4709 1.6063 1.5953 1.3814 1.3798 1.9558 0.531 1.5784 0.057 0.1840 1 3.982 12.522 \ 3.620 11.003 j 4.375 12.755 \ 3,677 10.627 i 3.934 11.436 \ 3.722 11.631 1 4.569 13.399 1 4.332 12.237 \ 4.075 12.092 i 3.983 11.749 1 j 4.027 11.945 \ 0.317 0.8320 FBW - Final Body Weight Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Organ Weight Listing Study:15073/26225/879C G r o u p : I X C 1 0 m g / k g T r e a t m e n t : 1 0 m g / k g I X C S e x :M A L E S 1 ANIMAL | FBW 1 1 | (Gms) 1 (Gms) KIDNEYS %FBW 1 |(Gms) LIVER %FBW 1 901 |33.400 1 0.493 1.4760 1 902 31.000 1 0.528 1.7032 1 903 32.300 1 0.521 1.6130 1 904 32.800 1 0.517 1.5762 1 905 35.600 1 0.525 1.4747 1 906 33.600 1 0.546 1.6250 ! 907 32.300 1 0.542 1.6780 1 908 |35.000 1 0.598 1.7086 1 909 33.600 1 0.560 1.6667 1 910 33.500 1 0.600 1.7910 j 11 1 Mean 1 S.D. 133.310 1 0.543 1.6313 \ 1.331 1 0.035 0.1012 | 5.837 17.476 \ 5.024 16.206 j 5.995 18.560 \ 5.779 17.619 j 6.243 17.537 i 5.167 15.378 | 5.840 18.080 j 5.488 15.680 \ 6.370 18.958 j 7.232 21.588 1 1 | 5.898 17.708 i 0.634 1.8065 | \ | \ j | j i | j j | 1 | i G r o u p : X I C 3 0 m g / k g T r e a t m e n t : 3 0 m g / k g X I C S e x :M A L E S 1 ANIMAL | FBW 1 1 j (Gms) 1 (Gms) KIDNEYS %FBW 1 1101 1 1102 ! 1103 1104 1 1105 1 1106 1 1107 i 1108 i 1109 1 1110 I 1 Mean 1 S.D. |31.000 31.800 29.400 32.600 30.500 |28.600 27.900 !3 2 -3 0 0 30.500 |3 4 . 9 0 0 1 1 30.950 j 2.068 1 1 1 1 1 1 1 i 1 1 1 0.464 1.4968 0.504 1.5849 0.492 1.6735 0.554 1.6994 0.482 1.5803 0.457 1.5979 0.386 1.3835 0.452 1.3994 0.481 1.5770 0.582 1.6676 0.485 1.5660 0.054 0.1092 *** Listing Complete *** 1 |(Gms) LIVER %FBW | 6.693 21.590 \ 6.595 20.739 j 5.740 19.524 | 6.489 19.905 | 6.524 21.390 j 5.535 19.353 j 6.304 22.595 | 6.309 19.533 \ 6.959 22.816 j 7.918 22.688 1 I 6.507 21.013 \ 0.654 1.3945 | | | j j 1 j j i ! j .j 1 j j FBW - Final Body Weight -345- Revision Number 1 DuPont-14162 Individual Animal & Summary Stats Report PLACES 2000 vl.400 APFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix G Individual Animal Gross Observations for Mice -346- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL ANIMAL GROSS OBSERVATIONS FOR MICE EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day Note 879 = Mice -347- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : IA 0 mg/kg Treatment: 0 mg/kg IA Sex: Males Animal Ref Findings 101 Found Dead Duration of dosing-days: 4 Animal is signed off from necropsy SKIN : STAIN, YELLOW, VENTRAL BODY, WET. No Macroscopic Abnormality Observed : LIVER, KIDNEYS 102 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -348- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : IA 0 mg/kg Treatment: 0 m g / k g IA Sex: Males Animal Ref Findings 106 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 107 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 110 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 Date:19-MAY-04 -349- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : IIIA 0.3 mg/kg Treatment: 0.3 m g / k g IIIA Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 301 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from n e cropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from n e cropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 306 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -350- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A {* A P P R O V E D P R O T O C O L *) Dose Group : IIIA 0.3 mg/kg Treatment: 0.3 mg/kg IIIA Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 307 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from n e cropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -351 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice I n d i v i d u a l A n i m a l L i s t i n g Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : V A 1 m g / k g Treatment: 1 mg/kg V A Sex: Males Animal Ref Findings 501 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from n e cropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -352- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : VA 1 mg/kg Treatment: 1 mg/kg VA Sex: Males Animal Ref Findings 507 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -353- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Date:19-MAY-04 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : V I IA' 3 m g / k g T r e a t m e n t : 3 m g / k g V I I I A S e x : M a l e s Animal Ref Findings 701 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 706 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -354- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : VIIA 3 mg/kg Treatment: 3 mg/kg VIIIA animals Sex: Males Date:19-MAY-04 Animal Ref Findings 707 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice Killed on Day : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, FEW. No Macroscopic Abnormality Observed : KIDNEYS -355 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : IXA 10 mg/kg Treatment: 10 mg/kg IXA animals Sex: Males D a t e :19- M A Y - 04 Animal Ref Findings 901 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 902 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 904 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 905 Terminal Sacrifice K i l l e d on Day : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED, mild. No Macroscopic Abnormality Observed : KIDNEYS -356- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : IXA 10 mg / k g Treatment: 10 m g / k g IXA Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 906 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 907 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 908 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 909 Terminal Sacrifice K i l l e d on Day : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED, severe. No Macroscopic Abnormality Observed : KIDNEYS 910 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : D I S C O L O R A T I O N , YELLOW, M I D D L E , 3M M DIA. No Macroscopic Abnormality Observed : KIDNEYS -357- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) Dose Group : XIA 30 mg/kg Treatment: 30 m g / k g X IA animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 1101 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1102 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : D I S C OLORATION, YELLOW, FEW, < 3M M DIA. No Macroscopic Abnormality Observed : KIDNEYS 1103 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1104 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED, mild. No Macroscopic Abnormality Observed : KIDNEYS 1105 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -358- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 4 9 2 1 / 8 7 9 A (* A P P R O V E D P R O T O C O L *) D ose Group : XIA 30 mg/kg Treatment: 30 m g / k g X I A Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 1105 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1107 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1108 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED, mild. No Macroscopic Abnormality Observed : KIDNEYS 1109 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1110 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS *** Listing Complete *** -359- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : IB 0 mg/kg Treatment: 0 mg/kg IB Sex: Males Animal Ref Findings 101 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 102 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 106 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -360- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : IB 0 mg/kg Treatment: 0 mg/kg IB Sex: Males Animal Ref Findings 107 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 110 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e : 1 9 - M A Y - 04 -361 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : IIIB 0.3 mg/kg Treatment: 0.3 m g / k g IIIB Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 301 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 306 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -362- APFO (Linear/Branched), APFO (Linear), and AFFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : IIIB 0.3 mg/kg Treatment: 0.3 mg/kg IIIB Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 307 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice Killed on Day : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from nec r o p s y No Macroscopic Abnormality Observed : LIVER, KIDNEYS -363- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : VB 1 mg/kg Treatment: 1 mg / k g V B Sex: Males Animal Ref Findings 501 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 506 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -364- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : VB 1 mg/kg Treatment: 1 mg/kg VB Sex: Males Animal Ref Findings 507 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 Date:19-MAY-04 -365- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B {* A P P R O V E D P R O T O C O L *) Dose Group : VIIB 3 mg/kg Treatment: 3 mg/kg VIIB animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 701 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice K i l l e d o n D a y 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 706 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from ne c r o p s y No Macroscopic Abnormality Observed : LIVER, KIDNEYS -366- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : VIIB 3 mg/kg Treatment: 3 mg/kg VIIB animals Sex: Males Date:19-MAY-04 Animal Ref Findings 707 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -367- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXB 10 m g / k g Treatment: 10 m g / k g IXB Sex: Males Date :19-MAY-04 Animal Ref Findings 901 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED, MIDDLE LOBE. No Macroscopic Abnormality Observed : KIDNEYS 902 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 904 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 905 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -368- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : IXB 10 mg / k g Treatment: 10 m g / k g IXB animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 906 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 907 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 908 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 909 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -369- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IXB 10 m g / k g Treatment: 10 m g / k g IXB animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 910 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -370- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Gr o u p : XIB 30 mg/kg Treatment: 30 m g / k g XI B animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 1101 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1102 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1103 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1104 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -371 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : XIB 30 mg/kg Treatment: 30 m g / k g XI B animals Sex: Males Date:19-MAY-04 Animal Ref Findings 1105 Found Dead Duration of dosing-days: 10 Animal is signed off from necropsy SKIN : STAIN, YELLOW, VENTRAL BODY. No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1106 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1107 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1108 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -372- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 3 1 3 / 8 7 9 B (* A P P R O V E D P R O T O C O L *) Dose Group : XIB 30 mg / k g Treatment: 30 m g / k g XI B animals Sex: Males D a t e :1 9 - M A Y - 04 Animal Ref Findings 1109 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1110 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS *** Lis t i n g Complete *** -373- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : IC 0 mg/kg Treatment: 0 mg/kg IC Sex: Males Animal Ref Findings 101 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 102 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 103 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 104 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 105 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 106 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -374- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C {* A P P R O V E D P R O T O C O L *) Dose Group : IC 0 mg/kg Treatment: 0 mg/kg IC Sex: Males Animal Ref Findings 107 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 108 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 109 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 110 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e : 1 9 - M A Y - 04 -375- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) D o s e G r o u p : IIIC 0.3 m g / k g Treatment: 0.3 m g / k g IIIC Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 301 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 302 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 303 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 304 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 305 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 306 Terminal Sacrifice Killed on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -376- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : IIIC 0.3 mg/kg Treatment: 0.3 mg/kg IIIC Sex: D a t e :1 9 - M A Y - 0 4 Males Animal Ref Findings 307 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 308 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 309 Terminal Sacrifice K i l l e d on Day : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 310 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from n e c r o p s y No Macroscopic Abnormality Observed : LIVER, KIDNEYS -377- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : VC 1 mg/kg Treatment: 1 mg/kg VC Sex: Males Animal Ref Findings 501 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 502 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 503 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 504 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 505 Terminal Sacrifice Ki l l e d on Day : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 506 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t e :1 9 - M A Y - 0 4 -378- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : VC 1 mg/kg Treatment: 1 mg/kg VC Sex: Males Animal Ref Findings 507 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 508 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 509 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 510 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS Revision Number 1 DuPont-14162 D a t : 1 9 - M A Y - 04 -379- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : VIIC 3 mg/kg Treatment: 3 mg/kg VIIC Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 701 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 702 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 703 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 704 Terminal Sacrifice Kil l e d on Day : 14 Animal is signed off from'necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 705 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 706 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -380- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : VIIC 3 mg/kg Treatment: 3 mg/kg VIIC animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 707 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 708 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 709 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 710 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS -381 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual animals S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose G r o u p : IXC 10 m g / k g Treatment: 10 m g / k g IXC Sex: Males Date:19-MAY-04 Animal Ref Findings 901 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 902 Terminal Sacrifice Ki l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 903 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 904 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, FEW. No Macroscopic Abnormality Observed : KIDNEYS 905 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -382- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : IXC 10 mg/kg Treatment: 10 m g / k g IXC animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 906 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 907 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 908 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 909 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -383- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose G r o u p : IXC 10 m g / k g Treatment: 10 m g / k g IXC animals Sex: Males D a t e :1 9 - M A Y - 0 4 Animal Ref Findings 910 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -384- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : XIC 30 mg/kg Treatment: 30 mg/kg XIC animals Sex: Males D a t e : 1 9 -MAY-04 Animal Ref Findings 1101 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1102 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, FEW. No Macroscopic Abnormality Observed : KIDNEYS 1103 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1104 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy No Macroscopic Abnormality Observed : LIVER, KIDNEYS 1105 Terminal Sacrifice K i l l e d o n D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -385- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) Dose Group : XIC 30 mg/kg Treatment: 30 m g / k g XIC animals Sex: Males D a t e :1 9 - M A Y - 04 Animal Ref Findings 1106 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1107 Terminal Sacrifice Kil l e d on D a y : 14 Animal is signed off from, n e c r o p s y LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1108 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS 1109 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS -386- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice________ ____ Revision Number 1 DuPont-14162 Individual Animal Listing Showing animal data for individual S T U D Y : 1 5 0 7 3 / 2 6 2 2 5 / 8 7 9 C (* A P P R O V E D P R O T O C O L *) D o s e Gr o u p : XIC 30 mg/kg Treatment: 30 m g / k g XIC animals Sex: Males Date:19-MAY-04 Animal Ref Findings 1110 Terminal Sacrifice K i l l e d on D a y : 14 Animal is signed off from necropsy LIVER : DISCOLORATION, TAN, MOTTLED. No Macroscopic Abnormality Observed : KIDNEYS *** Listing Complete *** -387- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 Appendix H Individual Mouse Beta-Oxidation Data - 388- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL MOUSE BETA-OXIDATION DATA EXPLANATORY NOTES STUDY DESIGN Groups H-24921 H-26313 APFO (Linear/Branched) APFO (Linear) H-26225 APFO (Branched) IA IIIA VA VILA IXA XIA IB IIIB VB VIIB IXB XIB IC me VC VIIC IXC XIC Dosage (mg/kg) 0 (Control) 0.3 1 3 10 30 Abbreviations mg/kg = mg/kg/day AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (LINEAR/BRANCHED) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) IA 102 103 104 105 106 107 108 109 110 10.85 19.04 13.05 27.37 16.40 25.21 12.99 21.25 15.00 IIIA 301 302 303 304 305 306 307 308 309 310 29.17 26.26 21.84 36.38 39.63 41.56 44.52 40.53 34.51 29.77 VA 501 502 503 504 505 506 507 508 509 510 36.01 42.53 54.62 50.01 58.28 60.65 50.46 47.96 34.28 53.56 -390- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (LINEAR/BRANCHED) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VBA 701 702 703 704 705 706 707 708 709 710 46.41 42.99 35.97 39.28 48.21 58.01 43.32 48.10 55.76 53.41 IXA 901 902 903 904 905 906 907 908 909 910 28.79 27.58 33.48 29.15 28.00 36.66 19.74 29.69 47.64 35.77 XIA 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 21.65 20.27 35.41 31.31 24.91 28.68 25.89 38.33 46.83 33.38 -391 - AFFO (Linear/Branched), AFFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (LINEAR) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) 101 13.89 102 10.96 103 23.43 104 13.44 105 16.38 106 21.91 107 16.69 108 20.50 109 15.43 110 20.84 301 27.42 302 29.39 303 49.64 304 33.36 305 41.32 306 47.64 307 36.67 308 42.53 309 49.88 310 62.52 501 36.57 502 36.78 503 52.01 504 44.25 505 56.64 506 53.11 507 36.80 508 47.49 509 69.02 510 63.29 -392- AFFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (LINEAR) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VIIB 701 702 703 704 705 706 707 708 709 710 36.18 45.22 44.09 45.97 64.10 53.13 38.44 38.50 58.57 60.45 IXB 901 902 903 904 905 906 907 908 909 910 XIB 1101 1102 1103 1104 1106 1107 1108 1109 1110 23.13 37.93 31.61 42.59 54.84 39.08 30.96 32.25 45.77 33.79 32.59 34.53 33.85 32.73 24.13 39.67 29.76 32.96 27.22 -393- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (BRANCHED) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) 101 11.54 102 19.31 103 21.67 104 18.20 105 15.59 106 14.19 107 16.63 108 16.02 109 25.79 110 23.01 IIIC 301 302 303 304 305 306 307 308 309 310 23.43 21.83 24.14 21.80 26.22 32.93 24.79 25.84 19.95 21.35 VC 501 502 503 504 505 506 507 508 509 510 33.55 25.95 36.55 38.84 56.70 50.80 33.79 34.79 35.10 22.70 -394- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL BETA-OXIDATION DATA IN MALE MICE DOSED WITH APFO (BRANCHED) Animal Group_______ Number Beta-Oxidation Rate (nmol/min/mg protein) VIIC 701 702 703 704 705 706 707 708 709 710 31.72 42.65 35.95 40.98 55.19 54.86 48.97 35.87 45.86 53.07 IXC 901 902 903 904 905 906 907 908 909 910 41.68 47.20 44.50 39.06 46.50 43.82 39.29 35.54 38.12 48.83 XIC 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 28.59 30.44 23.43 26.33 36.80 37.56 35.04 33.41 54.60 48.30 -395- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (LINEAR/BRANCHED) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) IA 102 103 104 105 106 107 108 109 110 5.6 5.3 5.0 5.3 5.0 5.1 5.3 4.6 5.1 IIIA 301 302 303 304 305 306 307 308 309 310 6.1 6.4 6.5 6.1 6.3 6.0 6.1 5.7 5.8 6.1 VA 501 502 503 504 505 506 507 508 509 510 8.8 7.4 8.2 8.2 7.0 8.2 7.7 7.9 8.0 7.9 -396- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice _________ _______________________________ DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (LINEAR/BRANCHED) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) VIIA 701 702 703 704 705 706 707 708 709 710 10.2 11.0 9.7 10.9 10.5 11.6 10.0 11.5 10.9 10.9 IXA 901 902 903 904 905 906 907 908 909 910 14.6 17.1 15.4 16.7 17.8 16.1 15.9 15.6 17.7 15.6 XIA 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 17.9 19.1 17.3 17.9 18.6 17.0 22.0 18.1 18.7 16.1 -397- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________ Revision Number 1 DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (LINEAR) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) 101 5.1 102 5.6 103 5.5 104 5.7 105 5.9 106 5.2 107 5.4 108 5.4 109 5.8 110 5.6 301 6.3 302 6.1 303 6.3 304 6.5 305 6.8 306 6.5 307 6.5 308 6.9 309 6.3 310 6.4 501 8.0 502 8.5 503 8.8 504 8.2 505 8.6 506 8.2 507 8.0 508 8.2 509 8.8 510 8.2 -398- AFFO (Linear/Branched), APFO (Linear), and AFFO (Branched): Revision Number 1 14-Day Oral Gavage Study in Male Rats and Mice _________ -^ ...__________________________ DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (LINEAR) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) VIIB 701 702 703 704 705 706 707 708 709 710 9.8 11.1 10.7 11.3 11.9 12.3 13.6 10.6 10.6 11.7 IXB 901 902 903 904 905 906 907 908 909 910 15.7 17.8 15.3 18.1 18.8 17.2 18.0 16.9 17.7 16.3 XEB 1101 1102 1103 1104 1106 1107 1108 1109 1110 18.9 17.6 18.9 17.8 18.1 18.2 17.0 19.2 15.8 -399- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (BRANCHED) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) 101 5.3 102 5.2 103 5.5 104 5.2 105 5.2 106 4.6 107 5.6 108 5.1 109 4.9 110 4.8 301 6.5 302 5.8 303 6.5 304 5.7 305 6.2 306 5.9 307 6.3 308 6.1 309 5.7 310 6.6 501 8.1 502 8.0 503 8.2 504 8.3 505 9.4 506 8.5 507 7.2 508 7.0 509 7.1 510 6.6 -400- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice____________________________ Revision Number 1 DuPont-14162 INDIVIDUAL RELATIVE LIVER TO FULL BODY WEIGHT (FOR BETA-OXIDATION) IN MALE MICE DOSED WITH APFO (BRANCHED) Animal Relative Liver to Full Group_______ Number______ Body Weight (%) VIIC 701 702 703 704 705 706 707 708 709 710 12.5 11.0 12.8 10.6 11.4 11.6 13.4 12.2 12.1 11.7 IXC 901 902 903 904 905 906 907 908 909 910 17.5 16.2 18.6 17.6 17.5 15.4 18.1 15.7 19.0 21.6 XIC 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 21.6 20.7 19.5 19.9 21.4 19.4 22.6 19.5 22.8 22.7 -401 - APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice Revision Number 1 DuPont-14162 Appendix I Revision 1 -402- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice_____________ Revision Number 1 DuPont-14162 REVISION 1 QUALITY ASSURANCE DOCUMENTATION Report Number: Work Request Number: Study Code Number: DuPont-14162 15073 1025 (Rats) and 879 (Mice) The conduct of this study has been subjected to periodic Quality Assurance inspections. The dates of inspection are indicated below. Phase Audited Audit Dates Date Reported to Study Director Date Reported to Management Report Revision 1: 5 Jan 2006 5 Jan 2006 11 Jan 2006 7 tW 7 0 0 6 Date -403- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice REVISION 1 EXPLANATION The report was revised as follows: Page 31 Manuscript Figure 2:Error bars corrected 402 Appendix I: Revision 1 added. The following pages were revised to reflect these changes. Page 1 Title Page 8 Table of Contents Revision Number 1 DuPont-14162 -404- APFO (Linear/Branched), APFO (Linear), and APFO (Branched): 14-Day Oral Gavage Study in Male Rats and Mice REVISION 1 CERTIFICATION Revision Number 1 DuPont-14162 Study D irector: Carol fn lay, B.A. Q Senior Staff Toxicologist 2- Ik-kkr 3o D ate -405-