Document zo93XRakYkG7G1dGYqw7kw2D3

9 457 TRADE SECRET M 2 - 3A 7r DuPont-8685 Study Title H-24678: Two-Week Inhalation Toxicity Study in Male Rats Laboratory Project ID: DuPont-8685 Author: David P. Kelly, B.S. Study Completed on: April 2,2003 Performing Laboratory: E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number:B M B H Service Code Number:[ Company Sanitized. Does not contain TSCA c s f Page 1 of 154 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards except for the item documented below. The item listed does not impact the validity of the study. The test substance is commercially available and was characterized by the supplier prior to the initiation of this study. An analysis was provided. Although the characterization was not performed under Good Laboratory Practice Standards, based on our knowledge of the performing laboratory and its experience with analyzing this chemical, we have no reason to doubt the validity of the analysis. Applicant / Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Director J-M -M 3 Date Applicant ! Sponsor:_______________________________________ _________ DuPont Representative Date ;C.onipaiy Sanitized. Does not contain TSCA CEjl -2- H-24678: Two-Week Inhalation Toxicity Study in Male Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24678 Dates of Inspections: Protocol: August 2,2002 Conduct: August 5,8,13, 2002 Records, Reports: March 3-7,11,2003 Dates Findings Reported to: Study Director: March 20,2003 Management: March 26, 2003 DuPont-8685 -A m . - 2 0 o3 Dm:e -ompany Sanitized. Doss not cuman ioum v, H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Cllnica] Pathology Evaluation Reported by: Nancy $t. Everds, D.V.M. Diplomate A.C.VJP. Principal Research Clinical Pathologist and Manager Date Anatomic Pathology Evaluation Reported by; A natom ic Pathology Evaluation Peer Review by: Vladimir 6apkifirh.D. Research Chemist John F. Hansen, D.V.mMX./Ph^ Diplomate A.C.V.P. Principal Research Pathologist Diplomate A.C.V.P. Senior Research Pathologist Z~~ ftfir - Z o d J , Date l ' Date z -m L -2ao3 Date Date Company Sanitized. Does not contain TSCA CBt -4 - C'"*''- H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT........................... 2 QUALITY ASSURANCE STATEMENT..................................... 3 CERTIFICATION............................................................................. 4 LIST OF TABLES............................................................................. 7 LIST OF FIGURES.............................................................................................................................. 8 LIST OF APPENDICES......................................................................................................................8 STUDY INFORMATION....................................................................................................................9 STUDY PERSONNEL........................................................................................................................ 10 S U M M A R Y .......................................................................................... 11 INTRODUCTION................................................................................ 13 STUDY DESIGN.............................................................................................. 13 MATERIALS AND M ETHODS...................... 14 A. Test Substance...........................................................................................................................14 B. Animals....... ................................................................................. 14 C. Animal Husbandry.................................................................................................................... 14 1. Temporary Animal Identification and Quarantine...................................................................................... 14 2. Housing..........................................................................................................................................................14 3. Animal Room Environment.......................................................................................................................... 14 4. Animal Selection and Permanent Identification.......................................................................................... 15 5. Feed and Water.............................................................................................................................................. 15 6. Health Monitoring Program..........................................................................................................................15' D. Inhalation Exposure System..................................................................................................... 16 1. Atmosphere Generation................................................................................................................ 2. Chamber Construction and Design...............................................................................................................16 3. Exposure M ode............................................................................................................................................. 16 E. Characterization of Chamber Atmosphere............................... 16 1. Test Substance Sampling and Analysis........................................................................................................ 16 2. Particle Size Determination...........................................................................................................................17 3. Environmental Monitoring........................................................................................................................... 17 F. Body Weights and Clinical Observations............................................................................... 17 G. Blood Fluorine A nalysis...........................................................................................................17 H. Clinical Pathology Evaluation................................................................................................. 18 1. Hematology.................................................................................................................................................... 18 2. Clinical Chemistry........ ................................................................................................................................ 19 3. Urinalysis.........................................................................................................................................................19 4. Recovery..........................................................................................................................................................19 I. Anatomic Pathology Evaluation.............................................................................................. 19 J. Statistical Analyses................................................................................................................... 21 16 Company Sanitized. Does not co<naui *aw wul H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE OF CONTENTS (Continued) Page RESULTS AND DISCU SSIO N ......................................................................... 22 In-Life A nim al M easurem ents.......................................................................................................... 22 A. Chamber Atmosphere Concentrations of H-24678 and Chamber Environmental Conditions..................................................................................................................................22 B. Body Weights and Clinical Observations.............................................................................. 22 Blood Fluorine A nalysis..................................................................... 23 A. Blood Fluorine Analysis......................................................................................................... 23 Clinical Pathology E valuation.................... 23 A. Hematology............................................................................................................................... 23 B. Clinical Chemistry.................................................................................................................... 23 C. Urine Volume............................................................................................................................ 24 D. Plasma and Urine Fluoride......................... 24 E. Conclusions............................................................................................................................... 24 Anatomic Pathology E valuation....................................................................................................... 24 A. Mortality.....................................................................................................................................24 B. Organ W eights................................ 24 C. Gross Observations.................................................................... 24 D. Microscopic Findings................................................................................................................25 E. Conclusions......................................................................................... 25 C O NCLUSIO N S..................................................................................................................................26 RECORDS AND SAM PLE ST O R A G E ......................................................................................... 27 R EFER EN C ES....................................................................................... 27 T A B L E S ................................................................................................... 29 FIG U R ES...............................................................................................................................................74 A PPEN D IC ES...................................................................................................................................... 78 -6- Company Sanitized. Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 LIST OF TABLES Page 1. CHAMBER CONCENTRATIONS OF H-24678................................................................................................... 33 2. PARTICLE SIZE DISTRIBUTION OF H-24678....................................................................................................33 3. CHAMBER ENVIRONMENTAL CONDITIONS.................................................................................................. 34 4. MEAN BODY WEIGHTS OF MALE RATS.......................................................................................................... 35 5. MEAN BODY WEIGHT GAINS OF MALE RATS...............................................................................................37 6. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS........................................ ............................... 39 7. SUMMARY OF BLOOD FLUORINE ANALYSIS................................................................................................ 40 8. SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS........................................................................ 41 9. SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS.................................. 44 10. SUMMARY OF URINALYSIS VALUES FOR MALE RATS..............................................................................47 11. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE....................... 48 12. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE....................... 51 13. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE.................................... 54 14. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE.................................... 59 15. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE..................................................................................................................................................64 16. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE..................................................................................................................................................72 -7- Company Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 LIST OF FIGURES Page 1. SCHEMATIC OF EXPOSURE SYSTEM............................................................................................................... 75 2. MEAN BODY WEIGHTS OF MALE RATS............ ............................................................................................. 76 3. MEAN BLOOD FLUORINE OF MALE RATS...................................................................................................... 77 LIST OF APPENDICES Page A. DAILY CHAMBER CONCENTRATIONS.............................................................................................................79 B. DAILY CHAMBER ENVIRONMENTAL CONDITIONS.....................................................................................82 C. INDIVIDUAL BODY W EIGHTS.............................................................................................................................87 D. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS.................................................93 E. INDIVIDUAL ANIMAL BLOOD FLUORINE........................................................................................................98 F. INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA............................................................................... 101 G. INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS................................................................... 128 H. INDIVIDUAL ANIMAL PATHOLOGY DATA....................................................................................................133 . .Company Sanitized. Dpes not contain TSCA cm H-24678: Two-Week Inhalation Toxicity Study in Male Rats STUDY INFORMATION Substance Tested: Synonyms/Codes: H-246? Haskell Number: 24678 Composition DuPont-8685 Physical Characteristics#! Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. f Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Complcted: August 2, 2002 / (see report cover page) In-Life Initiated/Completed: August 5,2002 / August 29, 2002 -9- Companjr Sanitized. Does not contain TSCA CB H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 STUDY PERSONNEL Study Director: David P. Kelly, B.S. Management: Arthur J. O'Neill, B.S. Primary Technician: William E. Ellis, Jr. Clinical Pathologist: Nancy E. Everds, D. V.M. Management: Steven R. Frame, D.V.M., Ph.D. Blood Fluorine Analysis: Vladimir Capka, Ph.D. Management: S. Mark Kennedy, Ph.D. Anatomic Pathologist: John F. Hansen, D.V.M., Ph.D. Management: Steven R. Frame, D.V.M., Ph.D. Peer Review Anatomic Pathologist: G. Tracy Makovec, D.V.M., Ph.D. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M. -10- Somparsy Sanitized, Does noi comam i aw* oesj H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 SUMMARY Four groups of 15 male rats each were exposed to concentrations of H-24678 aerosol targeted to 0.2, 2, or 20 mg/m3 (actual mean concentrations were 0.22,1.9, and 20 mg/m3). The mass median aerodynamic equivalent diameter of the aerosols ranged from 0.90 to 2.1 urn. All rats were exposed nose-only for 6 hours per day for a total of 9 exposures over a two-week period. A similarly comprised control group of 15 male rats was simultaneously exposed to air only. The first 10 rats per group were designated for standard toxicity testing. The remaining 5 rats were designated for blood fluoride analysis sampling. On the day of the last exposure, collection of an overnight urine specimen was initiated for each standard toxicity rat. On the day following the last exposure, blood samples were collected for clinical analyses from each standard toxicity rat, and 5 rats per group were sacrificed for anatomic pathology examination. All remaining rats were allowed to recover for a 15-day period. At the end of the recovery period, blood and urine samples were collected for clinical analyses from each standard toxicity rat, and all surviving rats were sacrificed. Only the standard toxicity rats were given an anatomic pathology examination. No deleterious effects were observed in clinical observations during the exposure or recovery periods, and body weights were similar in test and control rats. Clinical pathology evaluations, including fluoride measurements, showed no effects in urine, hematology, or blood chemistry parameters as a result of exposure to H-24678. Small amounts of fluorine (approximately 2 ppm), slightly above background, were detected in the blood of rats in the 20 mg/m3 group on test days 0, 3, and 9 (compared to test day 9 control data) indicating the presence of the test compound or its metabolites. No above-background fluorine was detected in rats exposed at this concentration after the 2-week recovery period (test day 24) compared to the test day 24 control group. No fluorine was detected above background levels in the 0.2 and the 2 mg/m3groups on test day 9 (the last day of the exposure period). Weight analysis of the major organs showed no effects attributable to the test substance. Histological findings were confined to the respiratory tract. There were no adverse effects in any other evaluated organs. Compound-related microscopic observations were present in the lungs and larynx of test day 10 sacrifice rats at concentrations of 2 and 20 mg/m3. Inflammation in the lungs, characterized by mixed inflammatory cells within scattered alveolar lumina was observed at 2 mg/m3in 1 of 5 rats and at 20 mg/m3in 3 of 5 rats. In addition, minimal to mild squamous metaplasia of the mucosa lining the ventral floor of the larynx was observed at 2 mg/m3 in 4 of 5 rats and at 20 mg/m3in 5 of 5 rats. There were no compound-related microscopic lesions observed in test day 24 sacrifice rats, indicating the reversibility of compound-related lesions in the lung and larynx. The no-observed-effect level (NOEL) for this study is defined as the highest concentration at which no toxicologically important effects attributable to the test substance were detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States -11 - Company Sanitized. Does not contain TSca cttf H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 Environmental Protection Agency (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994). Based on the above findings in the respiratory tract of rats exposed to H-24678 for 2 weeks, the NOEL for repeated inhalation exposure was 0.2 mg/m3. Company Sanitized. Boas not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 INTRODUCTION The purpose of this 2-week inhalation study was to investigate the effects of repeated inhalation exposure in rats to airborne concentrations of H-24678 aerosol. Inhalation is an expected route of human exposure. The data will be used to provide information for safe handling of the test substance. In a previous study at this laboratory with the same compound, the 4-hour approximate lethal concentration (ALC) in nose-only exposed rats was 57 mg/m3; no rats died after exposure to 23 mg/m3.(1) Immediately prior to the present study, a rangefinding experiment was conducted in groups of rats exposed nose-only for approximately 5 Vi-to-6 hours/day for 6 days, within an 8-day period, to a mean concentration of approximately 18 mg/m3 of the test compound. No significant clinical signs of toxicity were observed. Following a 3-day period without exposure, the same rats were exposed for 5 hours to a mean concentration of approximately 44 mg/m3 followed by a final 4 hour and 20 minute exposure to a mean concentration of 69 mg/m3of H-24678. Five of 6 rats died within 2 days of the last exposure. Clinical signs of toxicity observed immediately following the last exposure included: red nasal discharge, irregular respiration, and lethargy. The day following the last exposure lung noise and severe weight loss were also observed. Based on the above information, exposure concentrations of 0.2, 2, and 20 mg/m3were chosen for the 2-week inhalation study described in this report. STUDY DESIGN Four groups of 15 male rats each were exposed to concentrations of H-24678 targeted to 0, 0.2, 2, or 20 mg/m3. All rats were exposed nose-only for 6 hours per day for a total of 9 exposures. The first 10 rats per group were designated for standard toxicity testing. Immediately following the last exposure, collection of an overnight urine specimen was initiated for each rat. On the day following the last exposure, blood samples were collected for clinical analyses from each standard toxicity rat, and 5 rats per group were sacrificed for anatomic pathology examination. All remaining rats were allowed to recover for a 15-day period. At the end of the recovery period, standard toxicity rats were fasted overnight, blood and urine samples were collected for clinical analyses from each rat, and all surviving standard toxicity rats were sacrificed for anatomic pathology examination. The remaining 5 rats per group were designated for total fluorine analysis sampling. Blood for total fluorine analysis was collected from each rat during the exposure phase on test days 0, 3, and 9, and during the recovery period on test days 14 and 24. Selected blood samples were subsequently analyzed for fluorine, and the remaining samples were saved for possible future analysis. At the end of the recovery period, all rats were sacrificed without further examination. All rats were weighed and individually observed for clinical signs of toxicity throughout the exposure period. Group clinical signs were observed during each exposure. In addition, the - 13- .Company Sanitized. Does not cutitaui H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 alerting response to an auditory stimulus was checked before and during each exposure. After each exposure, rats were checked for the alerting response to an auditory stimulus prior to removal from restrainers and were observed for clinical signs immediately after they were returned to their cages. Surviving rats were weighed and individually observed for clinical signs of toxicity throughout the recovery period. MATERIALS AND METHODS A. Test Substance The test substance, H-24678, was supplied by the sponsor Purity was iThe test substance was expected to be stable throughout the exposure phase of the study; no evidence of instability was observed. B. Animals A total of 63 male Crl:CD(SD)IGS BR rats was received from Charles River Laboratories, Inc., Raleigh, North Carolina. The rats were approximately 6 weeks old on the day of arrival. Rats have historically been used in safety evaluation studies for inhalation toxicity testing. The Crl:CD(SD)IGS BR rat was selected based on consistently acceptable health status and on extensive experience with the strain at Haskell Laboratory'. C. Animal Husbandry 1. Temporary Animal Identification and Quarantine Upon arrival, each rat was assigned a temporary, 1- to 2-digit identification number. Rats were quarantined for 7 days prior to test initiation. During the quarantine period rats were weighed and observed 3 times for clinical signs of disease. 2. Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 3. Animal Room Environment Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted to be within a temperature range of 23 1C and a relative humidity range of 50 10%. Excursions outside of these ranges were of insufficient magnitude and/or duration to have adversely affected the validity of the study. - 14- Company Sanitized, Does not contain TSCA H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 4. Animal Selection and Permanent Identification Prior to the end of the quarantine period, rats were assigned to 4 groups of 15 male rats each. Rats were divided into groups with the aid of a computerized, stratified, randomization program, so that mean body weights for each group were similar. Rats were approximately 8 weeks old and weighed between 231 and 276 grams at the start of the exposures. Upon grouping, each rat was assigned a unique 6-digit animal number. Following grouping, a 3-digit identification number was tattooed onto the tail of each rat. Rats that were not assigned to a test group were sacrificed by carbon dioxide asphyxiation and discarded without anatomic pathology evaluation. 5. Feed and Water Except during exposure, tap water was available ad libitum. PM3 Nutrition International, LLC Certified Rodent LabDiet 5002 was available ad libitum except during exposure and fasting periods prior to necropsy. 6. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore, and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. - 15Company Sanitized. Does not contain TSCA CM H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 D. Inhalation Exposure System (Figure 1) 1. Atmosphere Generation Chamber atmospheres were generated by nebulization of the test substance in air with a Spraying Systems Nebulizer. The test substance was metered into the nebulizer with a Harvard Apparatus model 22 Syringe Infusion Pump. Filtered, high-pressure air, metered into the nebulizer by a Brooks model 5878 Mass How Controllers, atomized the test substance and carried the resulting atmosphere through a cyclone, through a glass flow-splitter, and into the exposure chamber. The flow splitter diverted aerosol to the hood exhaust to reduce the amount of test material reaching the exposure chamber. Dilution air, metered into the chamber by a Brooks model 5878 Mass Flow Controller, helped to evenly distribute the test substance throughout the exposure chamber. The infusion pump and mass flow controllers were controlled and monitored by the Camile Inhalation Toxicology Automated Data System (CITADS). Fine control of the chamber concentration was accomplished by varying the test substance feed rate to the nebulizer. Test atmospheres were exhausted through an MSA filter cartridge prior to discharge into the fume hood. 2. Chamber Construction and Design All exposure chambers were constructed of stainless steel and glass (NYU style) with a nominal internal volume of 150 L. A polycarbonate baffle at the chamber inlet promoted uniform chamber distribution of the test atmosphere. 3. Exposure Mode During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethylmethacrylate faceplate which was attached to the exposure chamber so that the nose of each animal protruded into the exposure chamber. Before the start of the exposure phase, animals were placed in restrainers on 2 separate days for approximately 15 minutes each day to acclimate the animals to the restrainers. E. Characterization of Chamber Atmosphere 1. Test Substance Sampling and Analysis The atmospheric concentration of H-24678 was determined by gravimetric analysis at approximately 60-minute intervals during each exposure. The control chamber was sampled once during the study. Known volumes of chamber atmosphere were drawn from the breathing zone of the animals through a 25 mm filter cassette that contained a pre-weighed Gelman glass fiber (Type A/E) filter. The filters were weighed on a Cahn model C-30 or C-31 Microbalance. The filter weights were automatically transferred to CITADS, which calculated the chamber concentrations based on the difference in pre- and post-sampling filter weights divided by the -16- .Compan^ Sanitized. Does not contain TSCA CSI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 volume of chamber atmosphere sampled. Gravimetric sample start- and stop-times for each sample were controlled and recorded by CITADS. 2. Particle Size Determination Samples to determine the aerosol particle size distribution (mass median aerodynamic diameter and geometric standard deviation) were taken once per week in the 2 and 20 mg/m3 chambers with a Sierra Series 210 Cyclone Preseparator/Cascade Impactor and Sierra Series 110 Constant Flow Air Sampler.(2) On the last exposure day of the study, the aerosol particle size in all 3 chambers was measured in duplicate with a QCM Impactor.<3) The QCM uses piezo-crystal sensors and allows measurement of a small mass of aerosol. The QCM sensitivity was needed to measure the particle size in the 0.2 mg/m3test chamber. 3. Environmental Monitoring Chamber airflows were set at the beginning of each exposure to achieve at least 12 air changes per hour and were monitored continually with a calibrated Brooks model 5878 Mass Flow Controller. Chamber temperature was targeted at 23 2C and was measured with an Omega type J Thermocouple Thermometer. Chamber relative humidity was targeted at 50 10% and was measured with Jumo model PT100 wet-bulb/dry-bulb resistance temperature detectors. Airflow, temperature, and relative humidity were monitored continually with the CITADS and recorded at 15-minute intervals during each exposure. On 3 occasions, the relative humidity was not measured in one or more chambers over periods of 15 minutes to approximately 2 hours due to sensor problems. Based on the overall stability of the relative humidity measurements over the duration of the study, the inability to measure humidity over these 3 periods was considered not to have an effect on the study outcome. Chamber oxygen concentration was targeted to be at least 19%. Chamber oxygen concentration was measured with a Biosystems model 3100R Oxygen Analyzer and was recorded 3 times during each exposure. F. Body Weights and Clinical Observations During the exposure phase of the study, all rats were weighed on exposure days and individually observed for clinical signs of toxicity before and after each exposure. Group clinical observations were made during exposures. In addition, rats were checked for an alerting response to an auditory stimulus prior to each exposure, approximately every 2 hours during each exposure, and after each exposure. During the recovery period, all remaining rats were weighed and individually observed twice per week. G. Blood Fluorine Analysis Blood for total fluorine analyses was collected (0.5 to i mL) from 5 rats per group on the afternoons of test days 0, 3 and 9. Blood was also taken during the recovery period on test days 14 and 24. The blood samples were frozen for total fluorine analysis as needed. Whole blood was analyzed for fluorine in rats exposed to 20 mg/m3of H-24678 and sampled immediately after exposure on test days 0, 3, and 9, and after a 15-day recovery period (test -17- Company Sanitized. Does notcontainTSCACB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 day 24). Whole blood from the remaining groups was analyzed on test day 9, the last day of exposure. Unanalyzed samples were stored for possible future fluorine analysis. The total fluorine content of the blood samples was determined using a Wickbold torch combustion method followed by analysis with a fluoride ion selective electrode.(4> The liquid whole blood was decomposed or volatilized in the presence of wet oxygen and swept through an oxy-hydrogen flame in a closed quartz apparatus. The combustion products were collected in an aqueous absorbing solution and analyzed using a fluoride ion selective electrode. H. Clinical Pathology Evaluation A clinical pathology evaluation was conducted on all rats designated for standard toxicity testing approximately 10 days after initiation of the study. The day before collection of samples for the clinical pathology evaluation, the animals were placed in metabolism cages. These animals were fasted overnight (approximately 16 hours) and urine was collected from each animal. Blood samples for hematology and clinical chemistry measurements were collected from the orbital sinus of each animal while the animal was under light carbon dioxide anesthesia. Blood samples for fluoride analysis were collected at sacrifice from the abdominal vena cava of each animal while the animal was under carbon dioxide anesthesia. Additional blood collected from the vena cava was placed in a serum tube, processed to serum, and frozen at -80C. Serum was discarded without analysis because further tests were not required to support experimental findings. Bone marrow smears were prepared at sacrifice from all surviving animals. Bone marrow smears were stained with Wright's stain and coverslipped, but analysis was not necessary to support experimental findings. 1. Hematology Blood samples were evaluated for quality by visual examination prior to analysis. Complete blood counts, including reticulocytes, were determined on a Bayer Advia 120 hematology analyzer or determined from microscopic evaluation of the blood smear. Wright-stained blood smears from all animals were examined microscopically for confirmation of automated results and evaluation of cellular morphology. Blood smears, stained with new methylene blue, were prepared from each animal undergoing a hematology evaluation but were not needed for examination. The following hematology parameters were determined: red blood cell count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count platelet count white blood cell count differential white blood cell count microscopic blood smear examination -18- Sompany Sanitized. Does .not contain s g a cl ft*'**'-: H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 2. Clinical Chemistry Serum clinical chemistry parameters were determined on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer. Plasma fluorides were determined using a phi 12 pH meter and a fluoride-selective electrode. The following clinical chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase sorbitol dehydrogenase alkaline phosphatase total bilirubin urea nitrogen creatinine cholesterol triglycerides glucose total protein albumin globulin calcium inorganic phosphorus sodium potassium chloride fluoridea 3. Urinalysis Urine volume was measured. Urine fluorides were determined using a phi 12 pH meter and a fluoride-selective electrode. The following urinalysis parameters were determined: volume fluorideb 4. Recovery Clinical pathology evaluation including hematology, clinical chemistry, and plasma and urine fluoride were performed at the end of the recovery period (test day 24) according to the methods detailed above. I. Anatomic Pathology Evaluation Male rats were exposed to the test substance for 2 weeks (total of 9 exposures for 6 hours/exposures). Ten animals per group were exposed to the following: air only (Control Group I) and to H-24678 at 0.2 mg/m3 (Low Exposure Group HI), 2 mg/m3 (Intermediate Exposure Group V), and 20 mg/m3 (High Exposure Group VII). Five animals per group were sacrificed and necropsied following the last exposure (test day 10 sacrifice). Another 5 animals a Fluoride determination was analyzed on EDTA plasma. * Fluoride determination was analyzed from urine with EDTA added. -19Company Sanitized, Does not contain iSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 per group were allowed to recover and were sacrificed and necropsied on the 15th day of recovery (test day 24 sacrifice). Rats were euthanatized by carbon dioxide anesthesia and exsanguination. Gross examinations were performed on all rats. The following tissues were collected from the standard toxicity study rats. Digestive Svstem liver esophagus stomach duodenum jejunum ileum cecum colon rectum pancreas Urinarv Svstem kidneys urinary bladder Resoiratorv Svstem lungs trachea nose (4 cross sections) pharynx/larynx Cardiovascular Svstem heart Hematopoietic Svstem spleen thymus mesenteric lymph node bone marrow3 Endocrine Svstem thyroid gland parathyroid glands adrenal glands Nervous Svstem brain (3 cross sections) spinal cord (3 cross sections) peripheral nerve (sciatic) Musculoskeletal Svstem sternum Reproductive Svstem testes epididymides prostate seminal vesicles Miscellaneous eyes (including optic nerve) gross observations a Bone marrow was collected with the sternum. The liver, kidneys, lungs, brain, and testes were weighed at necropsy, and organ weight/final body weight and organ weight/brain weight ratios were calculated. Final body weights determined just prior to necropsy were used in the assessment of organ weight changes. Gross lesions which were diagnosed at necropsy and for which microscopic examination was not appropriate (e.g., fluid accumulation, ruffled fur, missing anatomic parts) were generally not collected. Gross lesions for which a microscopic diagnosis would not be additive (e.g., osteoarthritis, pododermatitis, chronic dermatitis of the tail, urinary calculi, and deformity of the teeth, toe, tail, or pinna) were saved but were generally not processed for microscopic evaluation. Testes, epididymides, and eyes were fixed in Bouin's solution. All other tissues were fixed in 10% neutral buffered formalin. Processed tissues were embedded in paraffin, cut at a nominal thickness of 5 micrometers, stained with hematoxylin and eosin (H&E), and examined microscopically. Company Sanitized. Poes nos contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 All collected tissues from the test day 10 sacrifice rats in the control and high exposure groups were processed and received a full histopathological examination. Liver, kidneys, lungs, pharynx/larynx, testes and nose from the test day 10 sacrifice rats in the low and intermediate exposure groups (DI and V) and from the test day 24 sacrifice standard toxicity rats in the control and high exposure groups (I and VH) were processed and examined microscopically. The key to the pathology lesion grading system used in this study can be found within the pathology tables and appendices. J. Statistical Analyses Significance was judged at p < 0.05. Parameter Exposure Concentration Data Environmental Data Blood Fluorine Analysis Body Weight Body Weight Gain Organ Weight Incidence of Clinical Observations Clinical Pathologyd Preliminary Test None None Test for lack of trend Levene's test for homogeneity and Shapiro-Wilk testa0) for normality5 None Levene's test for homogeneity and Shapiro-Wilk test(10) for normality5 Method of Statistical Analysis If preliminary test is not If preliminary test is significant significant Descriptive statistics (e.g., mean, standard deviation) Student's T-test Sequential application of the Jonckheere-Terpstra trend test Preliminary tests for pairwise comparison ORa One-way analysis of variance followed with Dunnett's test<u) Kruskal-Wallis test(l2) followed with Dunn's test(13) Cochran-Armitage test for trend(5,c One-way analysis of variance followed with Dunnett's testiU) Kruskal-Wallis test(12) followed with Dunn's testTM a Pairwise comparisons and associated preliminary tests were only conducted if the test for lack of trend was significant. b If the Shapiro-Wilk test was not significant but Levene's test was significant, a robust version of Dunnett's test was used. If the Shapiro-Wilk test was significant, Kruskal-Wallis test was followed by Dunn's test, c If the incidence was not significant, but a significant lack of fit occurred, then Fisher's Exact test(12) with a Bonferroni correction was used. d When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1,0.05 was used for any calculations performed with that bilirubin data. Company Sanitized. Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 RESULTS AND DISCUSSION In-Life Animal Measurements A. Chamber Atmosphere Concentrations of H-24678 and Chamber Environmental Conditions (Tables 1-3, Appendices A-B) The mean chamber concentrations of H-24678 and chamber environmental conditions during the exposures are located in Tables 1 and 2, respectively. The mean, analytically determined, aerosol concentrations for the 9 exposures were 0.22, 1.9 and 20 mg/m3for target concentrations of 0.2, 2, and 20 mg/m3, respectively. Targeted concentrations are used throughout this report. No aerosol was detected in the control chamber. The mass median aerodynamic equivalent diameter of the H-24678 aerosol measured in the test atmospheres ranged from 0.90 to 2.1 jum. The chamber oxygen concentrations were 21% in all chambers. The daily mean relative humidities for the chambers ranged from 36 to 67%, and the daily mean temperatures ranged from 19 to 25C. Although in some cases the relative humidity and temperature measurements were slightly out of range, these deviations were minor and were not expected to affect the study outcome. B. Body Weights and Clinical Observations (Tables 4-6, Figure 2, Appendices C-D) The mean body weights of male and female rats exposed to H-24678 were not statistically different from those of the control rats during the overall course of the study. There was a slightly depressed weight gain on test day 7 in the 20 mg/m3 group but the group body weights were not statistically different from those of the controls. Nasal and ocular discharges were observed in many rats, including controls, immediately after exposure. This is a frequent observation in inhalation studies where rats are exposed in restrainers, and is not considered to be deleterious. During the study there were no notable clinical observations that may have been related to the test treatment. Company Sanitized. Does not eotaaai tjjjfeACBj H-24678: Two-Week Inhalation Toxicity Study in Male Rats Blood Fluorine Analysis DuPont-8685 A. Blood Fluorine Analysis (Table 7, Appendix E) Small amounts of fluorine (approximately 2 ppm), slightly above background (approximately 1.3 ppm in controls at test day 9), were detected in the blood of rats in the 20 mg/m3 group on test days 0, 3, and 9 (compared to test day 9 control data) indicating the presence of the test compound or its metabolites. No above-background fluorine was detected in rats exposed at this concentration after the 2-week recovery period (test day 24) compared to the test day 24 control group. No fluorine was detected above background levels in the 0.2 and the 2 mg/m3groups on test day 9 (the last day of the exposure period). Clinical Pathology Evaluation A. Hematology (Table 8, Appendix F) There were no treatment-related or statistically significant changes in hematologic parameters in rats exposed to H-24678. B. Clinical Chemistry (Table 9, Appendix F) There were no adverse changes in clinical chemistry parameters in male rats exposed to H-24678. The following statistically significant and/or treatment-related change in mean clinical chemistry parameters were considered to be non-adverse or not related to exposure to the test compound: Urea nitrogen was minimally decreased in males exposed to 20 mg/m3after 10 days of treatment, and at the end of the recovery period (test days 10 and 24). At both time-points, urea nitrogen concentrations in males exposed to 20 mg/m3were generally within the range of those in other groups, and similar to historical control values. There were no alterations in other related clinical pathology parameters (urine volume, creatinine, phosphorus), and no alterations in renal histopathology. Therefore, this change was unlikely to be related to treatment. Regardless, minimally decreased urea nitrogen has no toxicologic significance, and thus was considered non-adverse. Albumin was minimally increased in males exposed to 0.2 mg/m3on test day 10. There was no dose-relationship to the response, so this change was considered to be unrelated to treatment. -23'Sompanjr Sanitized, Does not contain TSCACBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats C. Urine Volume (Table 10, Appendix F) There were no treatment-related changes in urine volume. DuPont-8685 D. Plasma and Urine Fluoride Exposure to H-24678 did not result in changes in plasma or urine fluoride. E. Conclusions In conclusion, exposure of male rats to 20 mg/m3H-24678 did not result in adverse changes in clinical pathology parameters. Therefore, under the conditions of this study and for the clinical pathology parameters measured, the no-adverse-effect level for male rats was 20 mg/m3 H-24678, the highest exposure in this study. Anatomic Pathology Evaluation A. Mortality (Tables 15-16) There were no compound-related deaths in this study. B. Organ Weights (Tables 11-12, Appendix G) There were no compound-related organ weight effects at either sacrifice in animals exposed to H-24678. There were no statistically significant organ weight changes at the test day 10 sacrifice. Higher mean absolute liver weight than control in high exposure group rats from the test day 24 sacrifice was attributed to higher final body weight in that group. C. Gross Observations (Tables 13-14, Appendix H) There were no compound-related gross observations in this study. Discoloration of the lung was observed in 1 high exposure rat from the test day 24 sacrifice. This observation was not considered to be compound-related because there was no corresponding microscopic lesion in this rat. Other gross observations occurred in low incidences and were randomly distributed across control and treatment groups. - 2 4 - Cpmpany Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 CONCLUSIONS Four groups of 15 male rats each were exposed to concentrations of H-24678 aerosol targeted to 0.2, 2, or 20 mg/m3 (actual mean concentrations were 0.22,1.9, and 20 mg/m3). The mass median aerodynamic equivalent diameter of the aerosols ranged from 0.90 to 2.1 /im. All rats were exposed nose-only for 6 hours per day for a total of 9 exposures over a 2-week period. A similarly comprised control group of 15 male rats was simultaneously exposed to air only. No deleterious effects were observed in clinical observations during the exposure or recovery periods, and body weights were similar in test and control rats. Clinical pathology evaluations, including fluoride measurements, showed no effects in urine, hematology, or blood chemistry parameters as a result of exposure to H-24678. Small amounts of fluorine (approximately 2 ppm), slightly above background, were detected in the blood of rats in the 20 mg/m3group on test days 0, 3, and 9 (compared to test day 9 control data) indicating the presence of the test compound or its metabolites. No above-background fluorine was detected in rats exposed at this concentration after the 2-week recovery period (test day 24) compared to the test day 24 control group. No fluorine was detected above background levels in the 0.2 and the 2 mg/m3groups on test day 9 (the last day of the exposure period). Weight analysis of the major organs showed no effects attributable to the test substance. Histological findings were confined to the respiratory tract. There were no adverse effects in any other evaluated organs. Compound-related microscopic observations were present in the lungs and larynx of test day 10 sacrifice rats at concentrations of 2 and 20 mg/m3. Inflammation in the lungs, characterized by mixed inflammatory cells within scattered alveolar lumina was observed at 2 mg/m3in 1 of 5 rats and at 20 mg/m3 in 3 of 5 rats. In addition, minimal to mild squamous metaplasia of the mucosa lining the ventral floor of the larynx was observed at 2 mg/m3 in 4 of 5 rats and at 20 mg/m3 in 5 of 5 rats. There were no compound-related microscopic lesions observed in test day 24 sacrifice rats, indicating the reversibility of compound-related lesions in the lung and larynx. The no-observed-effect level (NOEL) for this study is defined as the highest concentration at which no toxicologically important effects attributable to the test substance were detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994). Based on the above findings in the respiratory tract of rats exposed to H-24678 for 2 weeks, the NOEL for repeated inhalation exposure was 0.2 mg/m3. Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 RECORDS AND SAMPLE STORAGE A sample of the test substance was collected for archive purposes and retained at Haskell Laboratory, Newark, Delaware. Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware (formerly known as the E.I. du Pont de Nemours and Company Records Management Center). REFERENCES 1. DuPont Haskell Laboratory (2002). H-24678: Inhalation Approximate Lethal Concentration (ALC) in Rats. Unpublished 2. Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual: Series 210 Ambient Cascade Impactors and Cyclone Preseparators. 3. QCM Cascade Impactor, California Measurements, Inc. Sierra Madre, California. 4. Wickbold, R. (1954). Angew. Chem. 66, 173-174 5. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 54-56, 246-248, and 349-352. The Iowa State University Press, Iowa. 6. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 7. Selwyn, M.R. (1995). The use of trend tests to determine a no-observable-effect level in animal safety studies. Journal o f the American College o f Toxicology 14(2), 158-168. 8. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41, 133-145. 9. Levene, H. (1960). Robust test for equality of variances. Contributions to Probability and Statistics (J. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. 10. Shapiro, S.S. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. 11. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50, 1096-1121. 12. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. -27- gpmpany .Sanitized. Doss not contain TSCA Qal H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 13. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 14. Fisher, R.A. (1985). Statistical Methods fo r Research Workers, 13th edition. Haffner, New York. company .Saiiiteed, 1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLES Company Sanitized-goes not contain TSCA C8l H-24678: Two-Week Inhalation Toxicity Study in Male Rats TABLES ABBREVIATIONS: EXPLANATORY NOTES Chamber Concentrations of H-24678 Chamber Environmental Conditions S.E.M. - standard error of the mean mg/m3 - milligrams per cubic meter n - number of samples Summary of Hematology Values RBC - red blood cell count HGB - hemoglobin HCT - hematocrit MCV - mean corpuscular volume MCH - mean corpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW - red cell distribution width ARET - absolute reticulocyte count PLT - platelet count WBC - white blood cell count ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell DuPont-8685 Company Sanitized. Does n g^ o^ a|n 'ibUA urfi H-24678: Two-Week Inhalation Toxicity Study in Male Rats TABLES EXPLANATORY NOTES (Continued) ABBREVIATIONS (Continued): Summary of Serum and Plasma Chemistry Values AST - aspartate aminotransferase ALT - alanine aminotransferase SDH - sorbitol dehydrogenase ALKP - alkaline phosphatase BILI - total bilirubin BUN - urea nitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose TP - total protein ALB - albumin GLOB - globulin CALC - calcium IPHS - inorganic phosphorous NA - sodium K - potassium CL - chloride PFLU - plasma fluoride Summary of Urinalysis Values VOL - volume UFLU - urine fluoride DuPont-8685 Compaq Sanitized. Does not contain TSCA CBl /''"'N H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLES NOTES: EXPLANATORY NOTES (Continued) Chamber Concentrations of H-24678 Particle Size Distribution of H-24678 Chamber Environmental Conditions Values are reported to 2 significant figures. Means and standard errors of the mean were calculated prior to rounding values. Summary of Hematology Values Summary of Serum and Plasma Chemistry Values Summary of Urinalysis Values When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. - 32 - .Company Sanitized. H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 1 CHAMBER CONCENTRATIONS OF H-24678 DESIGN CONCENTRATION (mg/m3) 0 0.2 2 20 MEASURED CONCENTRATION3 ______________________ (mg/m3)____________ MEAN 0 S.E.M. b RANGE 0 0.22 0.011 0.15 - 0.26 1.9 0.13 1.2-2.6 20 0.38 18-22 n 1 9 9 9 a Values represent the mean, standard error of the mean (S.E.M.), and range of the daily mean values obtained from n exposures. b Value not calculable from sample size. TABLE 2 PARTICLE SIZE DISTRIBUTION OF H-24678 DESIGN MASS MEDIAN GEOMETRIC % PARTICLES CONCENTRATION EXPOSURE AERODYNAMIC STANDARD BY MASS (mg/m3) NUMBER DIAMETER Gum) DEVIATION <1 /um <3 /um <10 /um 0.2 9a 2.1 2.1 16 68 NDC 2 4b 1.4 2.1 34 85 100 8b 0.90 1.7 58 98 100 9a 1.0 1.7 50 98 ND 20 3b 0.90 1.9 52 93 100 7b 1.3 1.6 32 96 100 9a 1.1 2.2 48 92 ND a Mean of 2 samples determined with QCM Impactor. b Single sample determined with Sierra Impactor. c ND = not determined. -33- Company Sanitized. Does not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 3 CHAMBER ENVIRONMENTAL CONDITIONS DESIGN RELATIVE CONCENTRATION TEMPERATURE HUMIDITY AIRFLOW (mg/m3)a (C) (%) (L/min) n 0 21-24 36-67 35 9 0.2 20-24 51-59 65 9 2 20-25 50-56 65 9 20 19-24 37-50 50 9 a Values represent the range of the daily mean values obtained from n exposures. i/*'***'\ -34- .Coftipany Sanitized. Does not contain fSCA wa H-24678: Two-Week Inhalation Toxicity Study in Male Rats ___________ _____ _______ DuPont-8685 DAYS ON TEST EXPOSURE 0 1 2 3 4 6 7 8 9 10a TABLE 4 MEAN BODY WEIGHTS OF MALE RATS Group I Omg/m3 MEAN BODY WEIGHTS (g) Group in Group V 0.2 mg/m3 2 mg/m3 255.1 10.3(15) 253.2 11.8(15) 257.0 11.6(15) 260.4 12.5(15) 261.3 12.9(15) 267.4 22.1(15) 270.5 17.0(15) 275.4 17.1(15) 276.6 21.3(15) 258.5 24.7(15) 255.1 11.6(15) 252.0 10.6(15) 257.6 12.4(15) 259.8 14.1(15) 264.0 14.7(15) 272.9 16.3(15) 275.5 17.0(15) 279.9 18.2(15) 280.2 20.3(15) 258.4 23.6(15) 254.6 9.9(15) 254.1 10.1(15) 259.0 10.5(15) 262.0 10.7(15) 264.3 10.9(15) 274.5 12.3(15) 277.5 13.4(15) 281.5 13.0(15) 282.6 13.8(15) 265.0 20.7(15) Group VII 20 mg/m3 256.4 11.9(15) 255.0 12.0(15) 256.7 12.5(15) 259.3 13.1(15) 261.6 12.8(15) 271.3 14.8(15) 273.4 15.6(15) 274.3 15.6(15) 276.1 17.2(15) 257.5 16.7(15) -35Cgrnipapx Sapitizejd. D_oesno^cooMn TSCA 08! H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 DAYS ON TEST RECOVERY 14 17 21 24 TABLE 4 (Continued) MEAN BODY WEIGHTS OF MALE RATS Group I 0 mg/m3 MEAN BODY WEIGHTS (g) Group HI Group V 0.2 mg/m3 2 mg/m3 297.1 22.5(10) 315.0 25.5(10) 338.4 25.5(10) 344.1 41.7(10) 298.2 23.6(10) 311.0 30.9(10) 334.6 31.4(10) 338.8 41.1(10) 305.3 18.4(10) 323.3 17.8(10) 343.2 20. 1( 10) 347.6 33.1(10) Group VH 20 mg/m3 296.8 19.5(10) 318.1 19.7(10) 339.4 22.2( 10) 343.1 22.2( 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. a Weight losses due to fasting of rats prior to clinical pathology evaluation. -36Rompany Sanitized. Does not contain TSGCBt H-24678: Two-Week Inhalation Toxicity Study in Male Rats__________________________________ DuPont-8685 TABLE 5 MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group I 0 mg/m3 MEAN BODY WEIGHT GAINS (g) Group HI Group V 0.2 mg/m3 2 mg/m3 Group VH 20 mg/m3 EXPOSURE 0-1 -1.8 4.4(15) -3.1 3.5(15) -0.5 4.4(15) -1.4 3.2(15) 1 - 2 3.7 5.6 4.9 1.7 3.1(15) 3.6(15) 3.6(15) 2.2(15) 2 - 3 3.4 2.2 3.0 2.6 2.1(15) 4.4(15) 3.0(15) 3.2(15) 3 - 4 1.0 4.2 2.3 2.3 4.8(15) 4.4(15) 2.5(15) 4.3(15) 4 - 6 6.0 8.9 10.2 9.7 12.5(15) 3.5(15) 4.9(15) 3.9(15) 6 - 7 3.2 2.7 3.1 2.1 8.2(15) 2.3(15) 3.4(15) 3.3(15) 7 - 8 4.9 4.4 4.0 0.9# 3.6(15) 2.5(15) 2.5(15) 2.1(15) 8 - 9 1.2 0.2 1.0 1.8 5.6(15) 4.6(15) 2.3(15) 3.5(15) 9 - 10a -18.0 13.7(15) -21.8 11.7(15) -17.6 13.1(15) -18.6 13.2(15) /^fm\ -37 - gmpanx Sanitized. Does not contain TSCA Ctt Z0***-, 1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 5 (Continued) MEAN BODY WEIGHT GAINS OF MALE RATS ________________ MEAN BODY WEIGHT GAINS (g)_____________ Group I Group III Group V Group VII DAYS ON TEST 0 mg/m3________0.2 mg/m3________2 mg/m3________ 20 mg/m3 RECOVERY 10-14 35.1 7.3(10) 35.8 11.2(10) 35.2 8.4(10) 33.7 15.1(10) 14 - 17 17.9 4.3(10) 12.8 11.5(10) 18.0 3.5(10) 21.3 6.2(10) 17-21 23.4 2.6(10) 23.6 6.0(10) 19.9 4.3(10) 21.3 6.2(10) 21-24 5.7 18.7(10) 4.2 15.6(10) 4.4 15.5(10) 3.7 16.8(10) OVERALL 0-10 3.4 17.0(15) 3.3 16.2(15) 10.4 14.5(15) 1.1 9.5(15) 10-24 82.0 16.0(10) 76.3 18.7(10) 77.4 14.1(10) 80.0 12.3(10) 0-24 87.4 34.8(10) 82.1 34.5(10) 91.2 28.2(10) 84.6 18.2(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra trend test, a Weight losses due to fasting of rats prior to clinical pathology evaluation. -38gompany Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 6 SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS ANIMAL COUNT: Group I 0 mg/m3 15 Group IB 0.2 mg/m3 15 Group V 2 mg/m3 15 Discharge Incidence Mean onset (Days) 0 (0%) 1 (7%) 17 0 (0%) Hair Loss Incidence Mean onset (Days) 1 (7%) 6 0 (0%) 1 (7%) 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. A dash indicates a clinical observation was not observed, therefore, there is no mean onset day. There were no statistically significant differences from control at p < 0.05. Group VH 20 mg/m3 15 0 (0%) 2 (13%) 16 Company Sanitized. Does not contain TSC CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 7 SUMMARY OF BLOOD FLUORINE ANALYSIS DAYS ON TEST 0 Group I 0 mg/m3 a BLOOD FLUORINE (ppm) Group HI Group V 0.2 mg/m3 2 mg/m3 aa 3 aaa 9 1.3 1.4 1.4 0.04(5) 0.22(5) 0.15(5) 24 1.6 0.23(5) a a Group VH 20 mg/m3 1.6* 0.05(5) 2.1* 0.32(5) 2.0* 0.11(5) 1.5 0.13(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from test day 9 control at p = 0.05 by Student's T-test. a Samples not evaluated for this timepoint. -40- Company Sanitized. Does not contain TSCA C8I /***"\ H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE8 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group in 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 RBC (x l0 6/jtiL) DAY 10 DAY 24 HGB (g/dL) DAY 10 DAY 24 HCT (%) DAY 10 DAY 24 MCV (fl) DAY 10 DAY 24 MCH(pg) DAY 10 DAY 24 MCHC (g/dL) DAY 10 DAY 24 RDW (%) DAY 10 DAY 24 6.98 0.27(10) 7.38 0.19(5) 14.8 0.4(10) 15.3 0.3(5) 44.3 1.3(10) 45.1 0.6(5) 63.6 2.0(10) 61.0 1.0(5) 21.3 0.5(10) 20.7 0.6(5) 33.5 0.4(10) 33.9 0.7(5) 12.2 0.4(10) 12.0 0.2(5) 7.16 0.24(10) 7.32 0.17(5) 15.1 0.4(10) 15.3 0.3(5) 45.3 1.2(10) 44.7 0.6(5) 63.3 2.1(10) 61.1 1.2(5) 21.2 0.7(10) 20.9 0.5(5) 33.4 0.3(10) 34.2 0.7(5) 12.4 0.5(10) 11.9 0.3(5) 7.30 0.31(10) 7.47 0.28(4) 15.1 0.5(10) 15.0 0.5(4) 45.6 1.9(10) 44.4 1.8(4) 62.5 1.2(10) 59.4 1.4(4) 20.8 0.5(10) 20.1 0.4(4) 33.2 0.3(10) 34.0 0.4(4) 12.4 0.6(10) 11.8 0.6(4) 7.18 0.50(10) 7.42 0.33(5) 15.0 0.7(10) 14.8 0.2(5) 45.0 2.4(10) 43.9 1.2(5) 62.8 2.2(10) 59.3 2.9(5) 21.0 0.8(10) 20.0 1.1(5) 33.4 0.6(10) 33.7 0.9(5) 12.5 0.4(10) 12.2 0.4(5) -41 - gpmpan Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 8 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group in 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 ARET (xlOYjuL) DAY 10 DAY 24 PLT (x l0 3//zL) DAY 10 DAY 24 WBC (xlOV/FL) DAY 10 DAY 24 ANEU (xl03//xL) DAY 10 DAY 24 ALYM (xl03/juL) DAY 10 DAY 24 AMON (x l0 3//xL) DAY 10 DAY 24 AEOS (xl03//xL) DAY 10 DAY 24 180.5 36.9(10) 234.3 28.9(5) 1162 173(10) 1122 188(3) 14.89 2.35(10) 10.72 1.44(5) 2.02 0.83(10) 1.92 0.46(5) 12.28 1.62(10) 8.34 1.25(5) 0.27 0.15(10) 0.25 0.11(5) 0.11 0.05(10) 0.10 0.11(5) 210.0 48.3(10) 228.3 33.8(5) 1183 207(10) 1189 206(2) 13.87 4.14(10) 10.48 3.32(5) 1.50 0.45(10) 1.67 0.55(5) 11.75 4.05(10) 8.40 2.64(5) 0.32 0.16(10) 0.21 0.14(5) 0.09 0.05(10) 0.10 0.05(5) 207.8 19.9(10) 213.4 19.4(4) 1335 93(10) 1368 58(4) 13.47 2.34(10) 10.03 1.58(4) 1.64 0.40(10) 1.57 0.51(4) 11.23 2.24(10) 8.09 1.17(4) 0.30 0.13(10) 0.14 0.03(4) 0.13 0.05(10) 0.09 0.03(4) 198.0 46.5(10) 234.8 26.7(5) 1217 224(9) 1319 96(4) 13.51 3.07(10) 10.18 3.48(5) 1.79 0.38(10) 1.88 0.42(5) 11.02 2.82(10) 7.83 2.96(5) 0.30 0.12(10) 0.22 0.08(5) 0.21 0.19(10) 0.10 0.05(5) -42Rompanx Sanitized. Does not contain TSGA CB1 ./"K H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 8 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group HI 0.2 mg/m3 Group V 2 mg/m3 Group VU 20 mg/m3 ABAS (xlOVpiL) DAY 10 DAY 24 ALUC (x l0 3//xL) DAY 10 DAY 24 0.12 0.07(10) 0.05 0.04(5) 0.09 0.05(10) 0.06 0.05(5) 0.11 0.04(10) 0.05 0.03(5) 0.10 0.05(10) 0.05 0.02(5) 0.10 0.05(10) 0.09 0.04(4) 0.06 0.02(10) 0.06 0.03(4) 0.10 0.05(10) 0.07 0.03(5) 0.08 0.03(10) 0.07 0.05(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences from control at p < 0.05. -43 - Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 9 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I Omg/m3 Group HI 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 AST (U/L) DAY 10 DAY 24 ALT (U/L) DAY 10 DAY 24 SDH (U/L) DAY 10 DAY 24 ALKP (U/L) DAY 10 DAY 24 BILI (mg/dL) DAY 10 DAY 24 BUN (mg/dL) DAY 10 DAY 24 CREA (mg/dL) DAY 10 DAY 24 94 10(10) 100 12(5) 38 8(10) 38 3(5) 12.1 3.4(10) 12.2 4.7(5) 227 18(10) 219 30(5) 0.11 0.03(10) 0.13 0.03(5) 16 2(10) 16 2(5) 0.24 0.03(10) 0.31 0.04(5) 94 12(10) 95 17(5) 39 7(10) 40 5(5) 11.4 2.0(10) 13.1 3.8(5) 258 47(10) 213 50(5) 0.10 0.03(10) 0.09 0.03(5) 16 2(10) 14 1(5) 0.28 0.05(10) 0.29 0.05(5) 94 15(10) 87 11(5) 39 6(10) 48 23(5) 12.4 3.8(10) 12.5 2.2(5) 249 57(10) 185 31(5) 0.10 0.03(10) 0.11 0.04(5) 15 2(10) 15 1(5) 0.25 0.03(10) 0.36 0.13(5) 103 12(10) 90 7(5) 41 5(10) 39 6(5) 12.5 2.7(10) 15.0 3.8(5) 261 64(10) 219 47(5) 0.10 0.04(10) 0.12 0.05(5) 13* 2(10) 13* 1(5) 0.27 0.05(10) 0.29 0.03(5) - 44 S&inpang Sanitized, Does not contain TSCA CBt H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 9 (Continued) SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m3 Group HI 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 CHOL (mg/dL) DAY 10 DAY 24 TRIG (mg/dL) DAY 10 DAY 24 GLUC (mg/dL) DAY 10 DAY 24 TP (g/dL) DAY 10 DAY 24 ALB (g/dL) DAY 10 DAY 24 GLOB (g/dL) DAY 10 DAY 24 CALC (mg/dL) DAY 10 DAY 24 66 12(10) 58 10(5) 41 15(10) 44 17(5) 86 5(10) 91 16(5) 6.1 0.2(10) 6.5 0.2(5) 4.1 0.2(10) 4.4 0.2(5) 2.1 0.1(10) 2.1 0.1(5) 11.6 0.2(10) 11.0 0.2(5) 62 12(10) 61 6(5) 41 13(10) 53 21(5) 86 6(10) 88 12(5) 6.2 0.2(10) 6.4 0.3(5) 4.3* 0.1(10) 4.4 0.2(5) 2.0 0.1(10) 2.0 0.1(5) 11.6 0.3(10) 11.0 0.6(5) 61 11(10) 60 5(5) 44 8(10) 55 18(5) 82 7(10) 92 7(5) 6.1 0.3(10) 6.3 0.4(5) 4.2 0.1(10) 4.3 0.2(5) 2.0 0.2(10) 2.0 0.2(5) 11.7 0.4(10) 10.9 0.4(5) 57 12(10) 62 14(5) 46 13(10) 52 26(5) 85 4(10) 94 6(5) 6.1 0.2(10) 6.3 0.5(5) 4.1 0.2(10) 4.3 0.2(5) 2.0 0.1(10) 2.0 0.3(5) 11.6 0.3(10) 11.0 0.4(5) -45- Sompany Sanitized, Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 9 (Continued) SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m3 Group IH 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 IPHS (mg/dL) DAY 10 DAY 24 NA (mmol/L) DAY 10 DAY 24 K (mmol/L) DAY 10 DAY 24 CL (mmol/L) DAY 10 DAY 24 PFLU (jUg/mL) DAY 10 DAY 24 10.5 0.5(10) 10.2 0.6(5) 148.5 2.2(10) 147.3 1.3(5) 6.07 0.24(10) 5.92 0.48(5) 102.5 2.4(10) 102.4 3.4(5) 0.0 0.0(5) 0.1 0.0(4) 10.7 0.5(10) 9.2 0.2(5) 149.2 2.1(10) 147.1 1.5(5) 6.20 0.39(10) 6.13 0.46(5) 102.9 3.8(10) 105.1 2.5(5) 0.0 0.0(5) 0.1 0.0(4) 10.9 0.6(10) 9.6 0.9(5) 149.4 1.9(10) 147.2 1.2(5) 6.14 0.22(10) 6.09 0.49(5) 104.1 1.7(10) 104.2 3.0(5) 0.0 0.0(5) 0.1 0.0(5) 10.5 0.7(10) 9.7 0.8(5) 150.0 2.1(10) 148.4 1.1(5) 6.16 0.42(10) 6.02 0.25(5) 105.0 2.8(10) 104.8 1.5(5) 0.0 0.0(5) 0.1 0.0(5) 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. Compaiqr Sanitized. Does not contain ISCA GBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 10 SUMMARY OF URINALYSIS VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m3 Group m 0.2 mg/m3 Group V 2 mg/m3 Group VII 20 mg/m3 VOL (mL) DAY 10 DAY 24 UFLU (fig) DAY 10 DAY 24 7.2 3.6(10) 5.2 3.7(5) 8.3 2.2(10) 10.1 2.6(5) 7.9 6.2(10) 8.1 4.4(5) 7.9 2.4(10) 12.5 4.4(5) 9.3 3.3(10) 9.3 3.1(5) 8.1 1.2(10) 12.7 2.6(5) 9.3 10.6(10) 10.8 6.5(5) 10.5 4.8(10) 14.0 2.8(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences from control at p < 0.05. -47- S&apaniSanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 11 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE Group I 0 mg/m3 Group in 0.2 mg/m3 Group V 2 mg/m3 Group VH 20 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 8.241 1.209(5) 7.898 1.292(5) 8.145 0.515(5) 7.384 1.002(5) KIDNEYS 2.296 0.179(5) 2.315 0.445(5) 2.240 0.245(5) 2.335 0.376(5) LUNGS 1.504 0.224(5) 1.606 0.262(5) 1.554 0.138(5) 1.572 0.239(5) BRAIN 1.890 0.106(5) 1.934 0.096(5) 1.870 0.100(5) 1.912 0.036(5) TESTES 2.950 0.200(5) 2.992 0.213(5) 2.862 0.358(5) 2.742 0.403(5) FINAL BODY WEIGHT (grams) 251.440 18.258(5) 250.200 18.931(5) 254.680 14.201(5) 246.280 15.327(5) -48- jSgmpany Sanitized, Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 11 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE Group I Group HI Group V Group VH _______________________ 0 mg/m3________0.2 mg/m3________2 mg/m3________ 20 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ FINAL BODY* 100 3.269 0.339(5) 3.146 0.342(5) 3.197 0.046(5) 2.996 0.330(5) KIDNEYS/ FINAL BODY* 100 0.913 0.027(5) 0.921 0.124(5) 0.878 0.055(5) 0.947 0.134(5) LUNGS/ FINAL BODY* 100 0.600 0.092(5) 0.642 0.097(5) 0.611 0.057(5) 0.637 0.073(5) BRAIN/ FINAL BODY* 100 0.754 0.060(5) 0.776 0.062(5) 0.735 0.025(5) 0.778 0.038(5) TESTES/ FINAL BODY* 100 1.176 0.075(5) 1.198 0.071(5) 1.121 0.087(5) 1.112 0.128(5) -49- 'Oompany Sanitized. Does not contain TSGA 6BI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 11 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 10 SACRIFICE Group I Group m Group V Group VE 0 mg/m3_______0.2 mg/m3________ 2 mg/m3________ 20 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/BRAIN 435.438 54.098(5) 407.488 56.895(5) 435.622 12.933(5) 386.133 51.265(5) KIDNEYS/BRAIN 121.614 9.622(5) 119.407 20.504(5) 119.535 7.755(5) 121.908 17.942(5) LUNGS/BRAIN 79.378 8.140(5) 82.699 9.683(5) 83.078 5.215(5) 82.141 11.772(5) TESTES/BRAEN 156.562 14.659(5) 154.661 7.589(5) 152.815 14.167(5) 143.359 20.667(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences from control at p < 0.05. -50Company Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 12 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group I Group HI Group V Group VII _______________________ 0 mg/m3________0.2 mg/m3________2 mg/m3________ 20 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 9.082 0.961(4) 9.366 1.297(4) 10.376 0.404(5) 10.477# 0.975(5) KIDNEYS 2.644 0.246(4) 2.636 0.204(4) 2.761 0.219(5) 2.855 0.243(5) LUNGS 1.623 0.201(4) 1.633 0.204(4) 1.840 0.264(5) 1.695 0.131(5) BRAIN 1.991 0.027(4) 1.949 0.052(4) 1.976 0.072(5) 2.023 0.114(5) TESTES 3.244 0.177(4) 2.813* 0.150(4) 3.209 0.261(5) 3.177 0.258(5) FINAL BODY WEIGHT (grams) 310.600 13.849(4) 316.900 33.900(4) 321.560 11.341(5) 339.160# 22.606(5) -51 - Company Sanitized Does not contain TSCA CB! H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 12 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group I Group HI Group V Group VII _______________________ 0 mg/m3________0.2 mg/m3________2 mg/m3________ 20 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ FINAL BODY* 100 2.923 0.263(4) 2.952 0.201(4) 3.231 0.186(5) 3.085 0.111(5) KIDNEYS/ FINAL BODY* 100 0.851 0.065(4) 0.835 0.067(4) 0.858 0.056(5) 0.844 0.081(5) LUNGS/ FINAL BODY* 100 0.523 0.065(4) 0.517 0.055(4) 0.573 0.087(5) 0.502 0.064(5) BRAIN/ FINAL BODY* 100 0.642 0.036(4) 0.620 0.066(4) 0.616 0.044(5) 0.599 0.056(5) TESTES/ FINAL BODY* 100 1.047 0.103(4) 0.893 0.070(4) 0.997 0.064(5) 0.942 0.123(5) -52- ompany Sanitized. Does not contain TSCA CB1 /'*(**'* H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 12 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 24 SACRIFICE Group I Group HI Group V Group VH Omg/m3_______ 0.2 mg/m3_______ 2 mg/m3________20 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/BRAIN 456.224 47.919(4) 481.160 71.330(4) 525.254 19.394(5) 519.153 53.128(5) KIDNEYS/BRAIN 132.855 12.579(4) 135.373 12.688(4) 139.973 14.129(5) 141.244 10.200(5) LUNGS/BRAIN 81.485 9.862(4) 83.779 10.007(4) 92.973 11.872(5) 83.911 6.893(5) TESTES/BRAIN 162.866 6.801(4) 144.282 5.310(4) 162.765 17.763(5) 157.389 14.494(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) # Statistically significant difference from control at p < 0.05 by trend test (Jonckheere-Terpstra). * Statistically significant difference from control at p < 0.05 by parametric test (Dunnett/Tamhane-Dunnett). -53Company Sanitized. Does not contain 15C.PJ H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 13 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED DISCOLORATION, TAN, MOTTLED. KIDNEYS NO ABNORMALITY DETECTED LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED (5) (5) (5) (5) 5554 1 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 o m J a n ife e d : Does not contain TSCA CUi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 13 (Continued) . INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5 55 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 -55jPflmpany Sanitized. Does not contain TSCA CL; H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED | LESION INCIDENCE (Numeric) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) (5) (5) 55 5 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 555 5 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 -56- Company Sanitized. Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S ) WITH OPTIC NERVE NO ABNORMALITY DETECTED PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 CSRtpaHlfSanitized. Does noi confata TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS LESION INCIDENCE (Numeric) TREATMENT 0 0.2 2 20 1 mg/m3 mg/m3 mg/m3 mg/m3 1 I III V VII TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED (5) (5) (5) (5) 55 5 5 (5) (5) (5) (5) 55 5 5 (5) (5) (5) (5) 55 5 5 (5) (5) (5) (5) 5555 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 -58- j&ompany Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-8685 TABLE 14 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED LUNGS NO ABNORMALITY DETECTED DISCOLORATION, RED, SCATTERED. HEART NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 55 5 5 (5) (5) (5) (5) 5554 1 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 .Company Sanitized. Does pot contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 -60- ISdilipany Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) DuPont-8685 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 0.2 2 20 irtg/m3 mg/m3 mg/m3 mg/m3 I III V VII RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED DISCOLORATION, DARK, MOTTLED. ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 554 5 1 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 -61 - Company Sanitized. Does not contain TSCA CBf H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MATE RATS DAY 24 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 0,2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 555 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 Company Sanitized, Does not contain TSCACBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED DISCOLORATION, TAN, LEFT, TAIL, 3MM DIA.. STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED | LESION INCIDENCE (Numeric) TREATMENT o 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5545 1 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 Cempany Sanitized. Does not_eomain tSCACBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III v VII DIGESTIVE SYSTEM LIVER INFLAMMATION, SUBACUTE/CHRONIC, FOCAL. minimal mild total observations per lesion HYPERPLASIA, BILE DUCT. minimal total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal total observations per lesion PANCREAS NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED (5) (4) (5) (4) 4454 1 54 54 1 1 1 1 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -64- Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS DIGESTIVE SYSTEM DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED TREATMENT LESIO INCIDI:n c e (NtMERIC) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -65Company Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. minimal total observations per lesion HYDRONEPHROSIS, UNILATERAL. mild total observations per lesion URINARY BLADDER NO ABNORMALITY DETECTED RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion (5) (5) (5) (5) 4442 1112 1112 1 1 (5) (5) 55 (5) (5) (5) (5) 554 2 13 13 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -66- Cpmpany Sanitized. Does not contain TSCACBt H-24678: Two-Week Inhalation Toxicity Study in Male Rats > ) DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED SQUAMOUS METAPLASIA. minimal mild total observations per lesion NOSE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion (5) (5) 55 (5) (5) (5) (5) 551 41 4 45 (5) (5) (5) (5) 5445 11 11 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -67 - ^HPpany Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. minimal total observations per lesion LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED (5) (5) 33 22 22 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 6 8 - 9inpanx Sanitized. Does not contain TSCACBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED (5) (5) 55 (4) (5) 45 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified .corns! sanitized. Does not contain TSCACM H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS ] LESION INCIDENCE (NUMERIC) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII MUSCULAR AND SKELETAL SYSTEM STERNUM NO ABNORMALITY DETECTED REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED OLIGOSPERMIA/GERM CELL DEBRIS. mild total observations per lesion PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion (5) (5) 55 (5) (5) (5) (5) 5555 (5) (5) 54 1 1 (5) (5) 45 1 1 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -70Company Sanitized. Does not contain TSGACBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 10 SACRIFICE LESIONS REPRODUCTIVE SYSTEM SEMINAL VESICLES NO ABNORMALITY DETECTED SPECIAL SENSES SYSTEM EYE(S ) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. | LESION INCIDENCE (NUMERIC) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) 55 (5) (5) 55 3 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified Company Sanitized. Does not contain TSCA cat H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 16 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC, FOCAL. minimal total observations per lesion URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. minimal mild total observations per lesion CYST. minimal total observations per lesion | LESION INCIDENCE (NUMERIC) TREATMENT 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) 1 54 54 (5) (5) 33 11 1 21 11 11 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -72Company Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 TABLE 16 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 24 SACRIFICE LESIONS RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED DEGENERATION, TRIGEMINAL NERVE. mild total observations per lesion REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED TREATMENT LESION INCIDENCE (NUMERIC) 0 0.2 2 20 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) 55 (5) (5) 55 (5) (5) 44 11 11 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified JSpnpan^ Sanitized. Does not contain SCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 FIGURES Company Sanitized. Does not contain TSCA CSI H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) FIGURE 1 SCHEMATIC OF EXPOSURE SYSTEM ) DuPont-8685 syringe drive filter ompan Sanifeed- Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) FIGURE 2 MEAN BODY WEIGHTS OF MALE RATS ) DuPont-8685 -0 mg/m3 -0.2 mg/m3 -2 mg/m3 -20 mg/m3 * Weight losses due to fasting of rats prior to clinical pathology evaluation. -76- oot comai n ISCA CBI )>) H-24678: Two-Week Inhalation Toxicity Study in Male Rats_______________________________________________________________________ DuPont-8685 FIGURE 3 MEAN BLOOD FLUORINE OF MALE RATS - 0 mg/m3 -0.2 mg/m3 - 2 mg/m3 - 20 mg/m3 -77Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDICES - 78 - ------------------------ -- jPompang Sapitized Does not contain TSCA CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX A Daily Chamber Concentrations -79Cotnpany Sanitized. Does not contain TSCA CEI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DAILY CHAMBER CONCENTRATIONS ABBREVIATIONS: EXPLANATORY NOTES S.D. - standard deviation mg/m3 - milligrams per cubic meter n - number of samples FOOTNOTES: a Chamber not sampled on this day. b Value not calculable from sample size. NOTES: Values are reported to 2 significant figures. Means and standard deviations were calculated prior to rounding values. DuPont-8685 ^ m 5 w fe ? d . Does r a " a'n T8CA CB' H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 D a ily Chamber C o n c e n t r a t i o n s (mg/m3) Exposure 1 2 3 4 5 6 7 8 9 Mean a 0 a 0 mg/m3 S . D. | Range b0 n Mean 0.15 0.26 0.22 0.22 0.24 0.21 0.26 1 0.20 0.19 0.2 mg/m3 S.D. Range 0.076 0.10 0.067 0.053 0.067 0.068 0.14 0.16 0.12 0.05 - 0.26 0.11 - 0.35 0.11 - 0.27 0.14 - 0.28 0.17 - 0.31 0.13 - 0.27 0.15 - 0.51 0.04 - 0.42 0.10 - 0.40 n Mean 5 1.5 5 1.2 5 1.9 5 1.8 4 2.6 5 2.2 5 2.1 4 2.0 5 1.9 2 mg/m3 S.D. Range 0.35 0.15 0.24 0.047 0.40 0.36 0.35 0.36 0.20 1.1 - 2.1 1.1 - 1.4 1.6 - 2.3 1.7 - 1.8 2.2 - 3.3 1.8 - 2.9 1.7 - 2.5 1.6 - 2.5 1.6 - 2.1 n Mean 6 22 6 20 6 20 6 18 6 19 6 20 6 21 6 20 6 20 20 mg/m3 S.D. Range 2.9 2.3 4.2 1.0 3.3 0.99 1.6 2.0 3.5 19 - 26 16 - 23 14 - 26 17 - 19 17 - 26 18 - 21 19 - 23 18 - 23 15 - 26 n 6 6 6 6 6 6 6 6 6 -81 - Company Sanitized. Does not contain TSCA CBt H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX B Daily Chamber Environmental Conditions Company Sanjfeed. Does not contain ISC a H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 DAILY CHAMBER ENVIRONMENTAL CONDITIONS ABBREVIATIONS: EXPLANATORY NOTES n - number of observations FOOTNOTES: a Due to technical error, samples were not taken for approximately the first 2 hours of the exposure. b Due to technical error, false readings were omitted. NOTES: Values are reported to 2 significant figures. Means and standard deviations were calculated prior to rounding values. -83Company Sanitized. Does not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 D aily Chamber Environm ental C o n d itio n s - Tem perature (sC) 0 mg/m3 E x p o s u r e Mean 1 s D. Range 0 .2 mg/m 3 n Mean S D. R a n g e 2 mg/m3 n Mean 1 s - D- R ange 20 mg/m3 n Mean S. D. R ange n 1 23 0 25 23 24 24 24 0 63 23 25 24 24 0 60 23 25 24 24 0. 26 23 24 24 2 22 0 35 22 23 24 24 0 66 22 24 24 24 0. 85 22 25 24 23 0 74 21 - 24 24 3 22 0 34 21 22 24 24 0 61 22 25 24 23 0 74 22 25 24 23 0 24 23 24 4 22 0 35 21 22 24 23 0 55 22 25 24 23 0. 62 21 24 24 22 0 74 21 - 23 24 5 21 0 62 20 22 24 23 1 .7 19 25 24 23 1 .4 20 25 24 21 1 .4 19 - 23 24 6 21 1 .1 19 24 24 20 1 .1 18 21 24 20 1 .1 17 22 24 19 1 .2 16 - 21 24 7 22 1 .1 21 24 24 20 0 70 19 22 24 23 1 .4 20 25 24 21 1 .3 19 - 23 24 8 24 0 37 23 24 24 24 0 52 23 25 24 24 0 47 23 25 24 24 0 34 22 - 24 24 9 23 0 30 23 24 24 23 0 86 22 24 24 25 0 35 24 25 24 23 0 45 22 - 24 24 -84smpany Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) DuPont-8685 D a i l y Cham ber E n v i r o n m e n t a l C o n d i t i o n s - R e l a t i v e H u m i d i t y (%) 0 mg/m3 E x p o su re Mean 1S.D. Range 0.2 mg/m3 n Mean S.D. Range 2 mg/m3 n Mean 1S.D. 1 Range 20 mg/m3 n Mean S.D. Range n 1 53 0 . 7 2 52 - 55 16a 56 1 . 0 54 - 58 16a 52 3 . 9 48 - 68 24 38 1 . 3 36 - 40 16 a 2 36 3 .7 34 - 53 24 51 2 . 0 47 - 57 24 50 4 .0 47 - 66 24 37 2 .5 35 - 47 23b 3 55 8 . 9 34 - 61 24 51 2 . 0 48 - 57 24 51 2 . 6 49 - 62 24 41 1 . 9 37 - 44 20b 4 60 4 . 1 57 - 79 24 53 2 . 8 49 - 63 24 50 4 . 5 47 - 69 24 44 11 37 - 91 24 5 67 9 .0 58 - 82 24 52 3 .2 48 - 58 24 51 2 . 8 48 - 58 24 50 7 .5 44 - 77 24 6 58 1 . 9 53 - 63 24 59 2 . 8 56 - 66 24 56 2 . 1 54 - 63 24 48 6 . 8 44 - 70 24 7 54 2 . 6 50 - 58 24 59 1 .9 56 - 62 24 55 1 . 8 51 - 59 24 48 3 .3 42 - 58 24 8 54 1 . 3 52 - 58 24 54 1 . 2 52 - 57 24 54 0 .9 4 52 - 56 24 44 1 .4 42 - 46 24 9 53 1 . 5 50 - 56 24 54 1 . 6 52 - 57 24 53 1 .3 50 - 55 24 43 1 . 5 41 - 46 24 -85- Company Sanitised. Does no. contain TSC/VCB1 ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-8685 D aily Chamber E nvironm ental C o n d itio n s - A irflow (Wmin) 0 mg/m3 E x p o su re Mean S.D. Range 0 .2 mg/m1 2 mg/m3 n Mean S.D. Range n Mean | S.D. Range 20 mg/m3 n Mean S.D. Range n i 35 0 .0 1 7 35 24 65 0 .0 7 1 65 24 65 0.0 5 2 65 24 50 0 .0 2 9 50 24 2 35 0 .0 3 1 35 24 65 0 .0 3 6 65 24 62 3 .1 59 - 65 24 50 0 .0 4 6 50 24 3 35 0 .0 8 1 35 24 65 0 .0 3 3 65 24 65 0 .0 3 8 65 24 50 0 .0 4 6 50 24 4 35 0 .0 1 8 35 - 36 24 65 0 .0 6 5 65 24 65 0 .0 4 5 65 24 50 0 .2 0 50 - 51 24 5 35 0.1 2 35 24 65 0.0 4 0 65 24 65 0.040 65 24 50 0.0 3 2 50 24 6 35 0 .0 4 0 35 24 65 0 .0 4 2 65 24 65 0 .0 4 0 65 24 50 0 .0 3 4 50 24 7 35 0 .0 2 4 35 - 36 24 65 0 .0 3 9 65 24 65 0 .0 4 0 65 24 50 0 .0 3 3 50 24 8 35 0 .0 2 6 35 24 65 0 .0 2 9 65 24 65 0 .0 2 6 65 24 50 0 .0 3 0 50 24 9 35 0 .0 3 3 35 24 65 0 .0 2 4 65 24 65 0 .0 2 4 65 24 50 0 .0 2 6 50 24 -86Company SanitteitL 0 nt entln TSCA CBS /"n H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX C Individual Body Weights -87- Company Sanitized. Does not contain TSCA CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES FOOTNOTES: a Weight losses due to fasting of rats prior to clinical pathology evaluation DuPont-8685 grnmm- 8 8 sanitized. Does not contain TSCA C$1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats I n d i v id u a l Body Body W eight Body W eight Body W eight Body W eight Body W eight ggggg Day 0 Day 1 Day 2 Day 3 Day 4 M ale, I 0 mg/m3 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 662492 662493 662494 662495 662496 256.8 274.2 245.1 246.6 236.9 252.1 252.0 252.1 258.4 242.4 266.0 264.2 264.6 249.6 265.3 261.5 271.7 244.0 251.9 232.3 242.1 252.9 249.5 261.2 236.1 267.0 257.3 262.7 243.9 264.5 260.5 273.9 247.8 257.6 237.0 242.9 259.0 251.2 260.2 240.3 269.3 261.8 273.3 251.9 267.9 264.3 276.6 252.5 261.0 239.2 246.4 258.3 254.3 263.3 239.3 274.4 266.4 277.1 257.6 274.7 263.1 278.9 251.7 261.4 243.9 249.0 265.0 258.8 263.8 242.9 273.4 267.7 281.1 243.4 275.8 Body Weight g Day 10 Body Weight g Day 14 Body Weight g Day 17 Body W eight g Day 21 Body W eight g Day 24 M ale, I 0 mg/m3 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 662492 662493 662494 662495 662496 261.3 276.4 248.1 243.0 228.4 233.4 253.6 238.7 243.4 229.4 286.8 290.7 297.1 250.9 296.5 276.6 297.0 278.3 286.5 263.2 311.0 321.3 321.3 286.7 329.3 289.3 314.6 292.7 306.4 280.6 335.0 340.7 339.8 297.6 353.0 309.5 338.3 318.7 330.9 303.3 354.2 368.0 361.7 323.2 376.4 2 9 9 .4a 321. T 3 1 0 .2a 3 1 9 .3a 2 9 1 . 2a 377.2 394.2 380.6 342.6 404.4 -89- DuPont-8685 W eights Body w eight Body Weight Body W eight Body Weight 9 999 Day 6 Day 7 Day 8 Day 9 272.9 292.8 264.0 270.3 250.6 254.9 271.1 261.6 273.3 248.2 284.0 281.0 291.0 205.8 289.0 277.9 291.1 269.8 272.7 249.1 256.0 270.8 264.2 264.4 253.7 283.9 284.3 293.7 235.6 290.9 280.6 295.4 271.9 276.8 251.7 262.4 279.3 262.4 270.0 255.9 287.7 286.5 301.5 248.1 300.8 286.5 297.1 276.8 273.5 252.0 262.5 282.3 263.9 268.6 254.5 290.7 293.8 307.0 232.4 306.7 I|^5inp8hy-Sa!!!!2. Etss out contain XgCA CBt f H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 In d iv id u a l Body W eights Body W eight g Day 0 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body W eight g Day 6 Body Weight g Day 7 Body W eight g Day 8 Body Weight g Day 9 M a l e , :I I I 0 . 2 mg/m3 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 662507 662508 662509 662510 662511 259.3 276.3 232.7 252.0 239.2 247.8 255.7 247.6 254.1 252.4 264.3 261.9 264.7 247.2 270.8 251.1 275.2 233.3 250.4 236.8 248.0 252.7 247.8 253.9 247.1 260.9 258.9 252.2 245.1 266.6 255.0 282.7 238.4 250.6 243.8 248.1 264.3 251.2 258.1 248.8 266.0 268.3 259.7 251.1 278.3 255.0 286.9 240.1 257.6 243.4 249.0 267.7 246.2 251.6 250.1 266.9 271.2 269.6 258.3 283.5 259.1 293.4 242.4 263.7 249.8 248.3 276.5 252.9 263.1 255.7 266.1 279.2 265.3 256.2 287.9 267.8 302.1 246.8 275.8 261.4 254.7 289.2 252.9 270.0 265.1 277.7 287.1 277.9 265.7 298.7 268.9 304.9 252.3 276.0 262.2 256.1 295.3 251.7 274.4 265.8 282.9 292.3 279.7 269.9 300.4 274.4 311.1 254.7 278.9 270.0 258.2 301.6 252.2 277.6 272.9 283.1 299.5 282.2 275.6 306.6 274.2 313.6 257.8 284.0 266.8 256.6 304.2 250.4 279.3 260.5 286.1 298.4 287.0 271.6 311.8 Body W eight g Day 10 Body W eight g Day 14 Body W eight g Day 17 Body Weight g Day 21 Body Weight 3 Day 24 M a l e , :I I I 0 . 2 mg/m3 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 662507 662508 662509 662510 662511 248.1 279.8 228.1 252.5 242.5 227.0 266.8 231.7 247.1 236.5 277.8 297.8 279.8 267.2 292.6 271.5 322.4 259.8 292.8 278.6 307.0 320.7 304.3 292.3 332.7 252.6 342.6 270.9 311.4 297.0 321.5 337.1 315.8 310.2 350.7 287.5 371.9 287.4 329.8 319.2 343.4 359.0 341.2 326-9 379.6 2 7 8 . 3a 3 6 1 .4a 278.9a 3 1 2 .6a 314.7a 357.4 371.3 363.2 347.1 402.7 -90Company Sanitized. Does not contain TSCA GB! H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) I n d iv id u a l Body Body Weight g Day 0 Male, V 2 mg/m3 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 662522 662523 662524 662525 662526 263.7 262.0 246.4 252.0 231.3 253.9 247.6 254.5 255.6 252.8 270.2 265.1 264.9 244.7 254.3 261.2 267.0 247.6 241.7 235.1 255.2 249.6 253.7 260.1 253.6 266.6 267.2 258.8 238.8 255.2 273.6 270.7 254.8 248.3 238.5 254.1 256.6 256.3 259.0 254.3 272.2 273.5 264.7 246.5 261.6 274.2 274.1 256.6 251.4 240.5 263.9 254.8 261.0 265.0 256.2 277.2 278.2 264.3 251.4 260.9 275.6 275.2 259.2 252.7 240.1 266.1 255.3 265.6 266.3 261.5 275.3 280.4 271.0 252.0 267.5 Body Weight g Day 10 Body Weight g Day 14 Body Weight g Day 17 Body Weight g Day 21 Body W eight g Day 24 Male, v 2 mg/m3 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 662522 662523 662524 662525 662526 267.4 268.1 252.5 252.0 233.4 250.3 240.0 258.3 257.1 250.7 296.4 300.6 296.6 275.4 276.2 289.5 276.8 301.6 301.2 293.2 330.1 333.3 321.1 312.1 294.4 313.8 295.6 316.0 320.6 312.2 342.9 354.5 337.3 331.2 309.1 334.5 309.9 334.1 340.7 337.9 362.6 374.5 364.0 351.9 321.9 3 2 5 .9a 3 0 1 . 8a 323.1a 3 3 0 .3a 3 2 6 .7a 385.6 400.2 380.7 368.5 332.8 -91 - ) DuPont-8685 W eights Body W eight Body Weight Body W eight Body W eight gggg Day 6 Day 7 Day 8 Day 9 285.7 289.0 270.6 264.9 251.0 268.6 257.6 278.2 274.2 268.8 293.1 294.0 279.1 270.4 271.7 289.4 294.4 271.3 267.4 249.4 277.9 262.6 274.6 278.9 272.6 294.5 299.8 286.0 272.6 271.6 291.9 298.3 276.5 275.2 253.3 281.3 264.7 282.8 278.8 274.2 300.1 300.5 288.3 278.4 278.5 290.3 301.1 279.9 277.6 254.6 283.0 265.7 284.1 279.7 274.1 303.5 304.7 289.9 275.0 275.2 Company Sanitized. Does not contain TSCACBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-8685 I n d iv id u a l Body W eights Body Weight g Day 0 Male, VII 20 mg/m3 Body Weight g Day 1 Body Weight g Day 2 Body Weight g Day 3 Body Weight g Day 4 Body W eight g Day 6 Body Weight g Day 7 Body Weight g Day 8 Body W eight g Day 9 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 662537 662538 662539 662540 662541 267.8 275.5 233.6 247.2 237.5 259.0 258.1 255.0 258.0 251.1 265.8 262.1 269.1 244.0 262.1 266.2 275.1 233.9 244.2 239.2 265.2 259.7 252.6 254.1 250.0 264.2 261.8 263.5 237.7 257.9 268.5 275.3 235.5 242.4 241.3 268.9 263.7 254.9 259.5 248.3 264.4 266.7 263.5 238.4 258.9 268.9 278.2 235.7 250.2 240.0 274.8 270.0 260.5 257.9 252.3 270.0 265.4 262.9 240.1 262.8 272.6 278.0 239.6 256.0 246.3 275.4 277.1 265.8 261.0 255.4 260.7 270.8 266.3 237.7 261.7 277.9 289.1 246.2 262.4 252.8 290.1 295.0 273.5 271.8 267.2 270.9 274.1 277.9 246.0 275.2 276.6 289.4 248.4 269.4 248.4 294.7 299.3 281.7 272.8 272.2 272.9 275.3 278.1 248.0 274.3 279.9 288.4 250.8 273.1 246.8 297.7 299.7 281.5 274.0 272.9 274.7 271.2 278.5 250.0 275.6 281.6 292.4 251.0 271.6 247.0 295.5 303.6 291.1 275.9 272.5 276.9 273.5 286.4 246.8 276.1 Body Weight g Day 10 Body Weight g Day 14 Body W eight g Day 17 Body Weight g Day 21 Body Weight S Day 24 Male, VII 20 mg/m3 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 662537 662538 662539 662540 662541 258.8 263.9 227.3 245.7 235.7 267.3 272.1 254.8 250.8 238.6 271.9 267.9 287.3 246.3 274.0 318.4 325.9 306.7 291.5 272.0 298.0 277.9 312.5 269.1 295.8 340.1 349.5 330.9 314.3 307.9 317.6 296.1 327.1 284.0 313.2 353.4 379.4 351.3 337.1 332.5 334.2 307.4 351.7 304.1 342.5 3 4 6 .2a 371.l a 3 4 3 .2a 3 2 1 .7a 3 1 3 . 6a 358.0 324.2 367.2 318.8 366.5 Company Sanitized. Does T0CA m H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX D Individual Clinical Observations and Mortality Records -93- Itteed. Does not contain TSCA ;C0MPSX H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 Sex Group Animal MI 662482 MI 662483 MX 662484 MI 662485 MI 662486 MI 662487 MI 662488 MI 662489 MI 662490 MI 662491 MI MI MI MI MI 662492 662493 662494 662495 662496 Individual C lin ic al O bservations and M ortality Records O bservation G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, H air Loss, Forelim b, B ila te ra l H air Loss, Forepaw, B ila te r a l S acrificed by design L eft G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L e ft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v ia O rb ita l fo r C lin Path, L eft S a c rific e d by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L e ft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b servations, B led v ia O rb ita l fo r C lin P ath, Eye O b serv a tio n s, B led v ia O rb ita l fo r C lin Path, A ccidentally k ille d Left R ig h t G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design L eft R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S a c rifice d by design Left Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design B ilateral Left G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, B led v i a O r b ita l fo r C lin Path, Eye O b serv a tio n s, B led v i a O r b ita l fo r C lin Path, S acrificed by design Left R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S a c rific e d by design Days 0-4 10 6-10 6-10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 24 10 24 0-24 10 24 24 0-24 24 0-24 24 0-24 24 0-24 24 0-24 24 -94Oompanjf Sanitized, Does not contain TSCA GBf H-24678: Two-Week Inhalation Toxicity Study in Male Rats Sex Group Animal M III 662497 M III 662498 M III 662499 M III 662500 M III 662501 M III 662502 M III 662503 M III 662504 M III 662505 M III 662506 M III M III 662507 662508 M III M III M III 662509 662510 662511 In d iv id u al C lin ic a l O bservations and M o rta lity Records O bservation G e n e r a l o b s e r v a t i o n , No A b n o r m a li t y D e t e c t e d Eye O b servations, B led v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a li t y D e t e c t e d Eye O b servations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a li t y D e t e c t e d Eye O b servations, B led v ia O rb ita l fo r C lin Path, L eft S a c rifice d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv atio n s, Bled v ia O rb ita l fo r C lin Path, L eft S a c rifice d by design G e n e r a l o b s e r v a t i o n . No A b n o r m a li t y D e t e c t e d Eye O b servations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bserv atio n s, Bled v ia O rb ita l fo r C lin P ath, Eye O b servations, Bled v ia O rb ita l fo r C lin Path, A ccidentally k ille d Left Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, B led v ia O rb ita l fo r C lin Path, Eye O b serv a tio n s, B led v i a O rb ita l fo r C lin Path, S acrificed by design Left R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, B led v ia O rb ita l fo r C lin Path, Eye O b serv a tio n s, B led v ia O rb ita l f o r C lin Path, S acrificed by design L eft Right G e n e r a l o b s e r v a t i o n , No A b n o rm a lity D e t e c te d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O b servation s, B led v ia O rb ita l fo r C lin Path, S acrificed by design L eft Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, B led v ia O rb ita l fo r C lin Path, L eft Eye O bservation s, B led v ia O rb ita l fo r C lin P ath, R ight S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d D ischarge, Nose, Black S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design DuPont-8685 Days 0-10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 24 0-14,21-24 17 24 0-24 24 0-24 24 0-24 24 -95Gompany Sanitized, Does not contain TSCACBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats Sex Group Animal MV 662512 MV 662513 MV 662514 MV 662515 MV 662516 MV 662517 MV 662518 MV 662519 MV 662520 MV 662521 MV MV MV MV MV 662522 662523 662524 662525 662526 Individual C lin ic a l O bservations and M o rtality Records O bservation G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v i a O r b ita l fo r C lin Path, H air Loss, Forepaw, B ila te r a l S acrificed by design L eft G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v i a O r b ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S a c rifice d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b servations, Bled v ia O rb ita l fo r C lin Path, L eft Eye O bservations, Bled v ia O r b ita l fo r C lin Path, Right S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O r b ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design L eft Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O r b ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design Left Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v ia O r b ita l f o r C lin Path, Eye O b serv a tio n s, Bled v ia O r b ita l f o r C lin Path, S acrificed by design Left Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S a c rific e d by design DuPont-8685 Days 0-10 10 10 0-9 10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-24 10,24 24 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 10 24 24 0-24 24 0-24 24 0-24 24 0-24 24 0-24 24 -96Compan^ Sanitized, Does not contain 1SCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats Sex Group Animal M VII 662527 M VII 662528 M VII 662529 M VII 662530 M VII 662531 M VII 662532 M VII 662533 M VII 662534 M VII 662535 M VII 662536 M VII 662537 M VII 662538 M VII 662539 M VII 662540 M VII 662541 Individual C lin ic al O bservations and M o rta lity Records O b serv a tio n G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S a c rifice d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S a c rifice d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v ia O r b ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, L eft S acrificed by design G e n e r a l o b s e r v a t i o n . No A b n o r m a lity D e t e c te d Eye O b serv atio n s, Bled v i a O r b ita l fo r C lin P ath, L eft S a c rific e d by design G e n e r a l o b s e r v a t i o n . No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O r b ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S a c rific e d by design L eft R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design L eft Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O b serv a tio n s, Bled v ia O r b ita l fo r C lin Path, Eye O b serv atio n s, Bled v ia O r b ita l fo r C lin Path, H air Loss, Forepaw, B ila te r a l S a c rific e d by design L eft R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, S acrificed by design L eft Right G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d Eye O bservations, Bled v ia O rb ita l fo r C lin Path, Eye O bservations, Bled v ia O rb ita l fo r C lin Path, H air Loss, Forelimb, B ila te ra l H air Loss, Forepaw, B ila te r a l S acrificed by design L eft R ig h t G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S a c rific e d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S a c rific e d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S a c rifice d by design G e n e r a l o b s e r v a t i o n , No A b n o r m a l i t y D e t e c t e d S acrificed by design DuPont-8685 Days 0-10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-10 10 10 0-24 10 24 24 0-24 10 24 24 0-21 10 24 24 24 0-24 10 24 24 0-7 10 24 8-24 17-24 24 0-24 24 0-24 24 0-24 24 0-24 24 0-24 24 -97- Company Sanitized. Does not contain TSCA CBI ? H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX E Individual Animal Blood Fluorine -98Oompany Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL ANIMAL BLOOD FLUORINE FOOTNOTES: EXPLANATORY NOTES a Insufficient sample size for accurate analysis. DuPont-8685 - 99- Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Animal Blood F lu o rin e Blood F lu o rin e Blood F lu o rin e Blood F luorine Blood F lu o rin e ppm ppm PPm ppm Day 0 Day 3 Day 9 Day 24 M ale, Group I - 0 mg/m3 662492 662493 662494 662495 662496 1.3 1.6 1.3 1.4 1.3 1.8 1.3 1.9 1.4 1.4 Male, Group I I I - 0.2 mg/m3 662507 662508 662509 662510 662511 1 .3a 1.3 1 . 8a 1.5 1.3 Male, Group V - 2 mg/m3 662522 662523 662524 662525 662526 1.4 1.2 1.5 1.5 1.6a M ale, Group V II - 20 mg/m3 662537 1.6 1.9 2.0 1.4 662538 1.5 2.0 2.0 1.4 662539 1.5 2.2 1.9 1.6 662540 1.6 2.6 2.1 1.6 662541 1.6 1.8 1.8 1.7 DuPont-8685 /"""N - 100- Companx Sanitized, Doss not contain TSCACoi H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX F Individuai Animal Clinical Pathology Data - 101 - .Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES ABBREVIATIONS General: ADEQ CLOT DECR NSR NT OK RNV UTD < - - - - adequate sample c lo tte d decreased no sample re ce iv e d fo r te s tin g not taken or not perform ed s a m p l e c o n d i t i o n OK f o r t e s t i n g resu lt not valid unable to determine le s s than Individual Hematology Values: COND - s a m p l e c o n d i t i o n RBC - r e d b l o o d c e l l c o u n t HGB - h e m o g l o b i n HCT - h e m a t o c r i t MCV - m ea n c o r p u s c u l a r v o l u m e MCH - m ea n c o r p u s c u l a r h e m o g l o b i n MCHC - m ea n c o r p u s c u l a r h e m o g l o b i n c o n c e n t r a t i o n RDW - r e d c e l l d i s t r i b u t i o n w i d t h ARET - a b s o l u t e r e t i c u l o c y t e c o u n t PLT - p l a t e l e t c o u n t WBC - w h i t e b l o o d c e l l c o u n t ANEU - a b s o l u t e n e u t r o p h i l ( a l l f o r m s ) ALYM - a b s o l u t e l y m p h o c y t e AMON - a b s o l u t e m o n o c y t e AEOS - a b s o l u t e e o s i n o p h i l ABAS - a b s o l u t e b a s o p h i l ALUC - a b s o l u t e l a r g e u n s t a i n e d c e l l Individual NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG RX HJB - Red Blood Cell Morphology Values: - Normal - anisocytosis - m icrocytes - m acrocytes - polychromasia - hypochromasia " echinocytes - acanthocytes - Target c ells - rouleaux ~ H ow ell-Jolly body - n o t observed or n o t examined; see whole blood sample condition Individual White Blood Cell / Platelet Morphology Values: NORM - N o rm al SM - Smudge w h i t e b l o o d c e l l s TOX - t o x i c n e u t r o p h i l s DB _ D 5 h l e b o d i e s VC - v a c u o l a t e d c y t o p l a s m BC - b a s o p h i l i c c y t o p l a s m PCE - p l a t e l e t c l u m p s / e s t i m a t e GP - g i a n t p l a t e l e t s BP " b i z a r r e p l a t e l e t s n o t observed or not examined; see whole blood sample condition - 102- Company Sanitized. Does not contain TSCA CB H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS : ( C o n t i n u e d ) Individual Serum and Plasma Chemistry Values: SHEM - s e r u m h e m o l y s i s SLIP - serum lip e m ia SICT - serum i c t e r u s AST - a s p a r t a t e a m i n o t r a n s f e r a s e ALT - a l a n i n e a m i n o t r a n s f e r a s e SDH - s o r b i t o l d e h y d r o g e n a s e ALKP - a l k a l i n e p h o s p h a t a s e BILI - t o t a l b i l i r u b i n BUN - u r e a n i t r o g e n CREA - c r e a t i n i n e CHOL _ c h o l e s t e r o l TRIG _ t r i g l y c e r i d e s GLUC - g l u c o s e TP - t o t a l p r o t e i n ALB - a l b u m i n GLOB - g l o b u l i n CALC - c a l c i u m IPHS - i n o r g a n i c p h o sp h o ro u s NA - s o d i u m K - potassium CL - c h l o r i d e PHEM - p l a s m a h e m o l y s i s f r o m b l o o d s a m p l e f o r f l u o r i d e d e t e r m i n a t i o n PLIP - plasm a lip e m ia from b lo o d sam ple fo r flu o rid e d e te rm in a tio n PICT - p l a s m a i c t e r u s f r o m b l o o d s a m p l e f o r f l u o r i d e d e t e r m i n a t i o n PFLU - p l a s m a f l u o r i d e Individual Urinalysis Values: VOL - v o l u m e UFLU - u r i n e f l u o r i d e NOTES : When i n d i v i d u a l a n i m a l d a t a a r e n o t r e p o r t e d , i t may b e d u e t o o n e o f t h e f o l l o w i n g r e a s o n s o r o th er reasons, a l l of which are ex p lain ed in the study records: t h e s a m p l e w a s c l o t t e d (CLOT) t h e r e was i n s u f f i c i e n t s a m p l e f o r 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) th e sample was n o t s u ita b le fo r t e s ti n g th e animal d ied p r io r to sample c o lle c tio n n o s a m p l e was a v a i l a b l e f o r t e s t i n g (NSR) When a n i n d i v i d u a l o b s e r v a t i o n was r e c o r d e d a s b e i n g l e s s t h a n a c e r t a i n v a l u e , c a l c u l a t i o n s w e re p erfo rm e d on h a l f th e re c o rd e d v a lu e . F o r exam ple, i f b i l i r u b i n was r e p o r t e d a s < 0.1, 0.05 was used fo r any c alc u la tio n s performed w ith th a t b iliru b in data. -103- Company Sanitized. Does not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number COND RBC x 1 0 6/ mL HGB g/dL M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 OK OK OK OK OK OK OK OK OK OK 7..36 6,,82 6..59 7,.10 7,.30 7,.04 6..70 6..72 6,.94 7..22 14..8 14 .7 14 .4 15 .4 15 .4 14 .7 14 .1 14 .7 14 .8 15 .4 H HM 1 Male, Group 0 . 2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 OK OK OK OK OK OK OK OK OK OK 7,.61 7..01 7..25 7..17 7,.25 7..32 6..80 7.,24 7..08 6..86 15 .3 14 .7 15 .0 15 .2 14 .7 16 .1 14 .8 15 .0 15 .5 15 .1 HCT % 43.9 43.5 43.1 46.0 45.5 43.1 42.8 44.4 44.4 46.6 45.6 44.2 45.2 44.9 44.1 47.5 44.0 45.6 46.9 44.9 In d iv id u al Hematology MCV fL MCH pg MCHC g/dL 59.6 63.7 65.4 64.8 62.4 61.3 63.9 66.0 64.0 64.5 20.1 21.5 21.9 21.7 21.1 20.9 21.1 21.9 21.3 21.4 33.8 33.7 33.5 33.5 33.8 34.1 33.0 33.1 33.2 33.1 59.9 63.0 62.3 62.7 60.8 65.0 64.7 63.0 66.3 65.5 20.1 21.0 20.6 21.2 20.2 22.0 21.8 20.8 21.9 22.0 33.5 33.3 33.1 33.9 33.3 33.9 33.7 33.0 33.0 33.6 -104- Values RDW % ARET x1 0 3/ ^ L PLT WBC x 1 0 3/ mE x 1 0 3/ mL 12.5 12.7 12.0 12.2 11.5 12.1 12.3 13.0 11.8 12.2 218.9 219.1 178.3 211.3 185.2 149.4 183.2 155.7 101.7 202.6 1178 1538 1135 1117 989 1337 1198 1143 1046 938 17.93 17.84 17.46 13.71 15.25 13.83 14.36 15.20 10.83 12.49 12.4 13.3 11.4 12.6 12.3 12.6 12.7 12.6 11.9 12.4 204.8 209.0 183.1 256.5 239.7 154.9 305.3 139.9 195.7 211.0 1283 1436 1274 1197 1311 1033 1366 1126 717 1089 11.58 11.68 16.15 11.01 13.98 24.81 12.72 13.34 11.64 11.75 ) DuPont-8685 Company Sanitized. Does no! contain TSCA CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number COND RBC x l 0 6/ h HGB g/dL M ale, Group V - 2 mg/m3 - Day 10 662512 662513 OK OK 7.14 7.31 14.7 15.0 HOT % 44.2 45.2 In d iv id u a l Hematology Values MCV fL MCH MCHC RDW pg g / d L % ARET PLT x 103/ mL x l o V f i L WBC x l 0 3/ h 61.9 61.9 20.6 33.3 12.6 213.3 1340 12.23 DuPont-8685 - 105 - Company Sanitized Does not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NEU ALYM AMON x 103/ L X l 0 3/ML x l O 3/ h M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 3.58 2.14 3.01 1.75 2.56 1.61 1.74 1.05 0.95 1.84 13.49 14.78 13.45 11.57 12.18 11.86 12.27 13.52 9.54 10.09 0.46 0.50 0.44 0-13 0.22 0.14 0.15 0.29 0.11 0.29 Male, Group I I I - 0.2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 1.97 1.96 1.74 1.03 0.97 1.60 2.19 1.18 1.09 1.23 9.04 9.25 13.34 9.41 12.27 22.53 9.72 11.70 9.99 10.22 0.25 0.19 0.62 0.24 0.46 0.23 0.50 0.27 0.31 0.13 AEOS x 1 0 3/ / L in d iv id u a l Hematology Values ABAS ALUC x1 0 3/ mL x 1 0 3/ m 0.21 0.17 0.07 0.11 0.11 0.07 0.07 0.06 0.10 0.08 0.09 0.14 0.30 0.09 0.11 0.08 0.07 0.12 0.06 0.13 0.09 0.10 0.19 0.07 0.07 0.07 0.05 0.15 0.07 0.05 0.05 0.10 0.20 0.07 0.06 0.11 0.14 0.05 0.08 0.07 0.18 0.10 0.15 0.16 0.10 0.13 0.08 0.08 0.10 0.06 0.09 0.08 0.11 0.09 0.12 0.21 0.09 0.05 0.07 0.05 ) DuPont-8685 -106- Company Sanitized. Does not contain TSCA CBl ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NEU ALYM x 10 3/ mL X l 0 3/ h AMON x I O V mL M ale, Group V - 2 mg/m3 - Day 10 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 2.21 1.88 1.19 1.50 1.91 1.67 2.21 1.16 1.28 1.41 9.21 10.43 10.53 16.24 10.05 12.94 12.07 8.11 11.54 11.18 0.46 0.41 0.17 0.29 0.32 0.13 0.52 0.16 0.31 0.23 M ale, Group V II - 20 mg/m3 - Day 10 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 1.55 2.26 1.27 1.90 1.80 2.03 1.91 2.18 1.10 1.88 12.46 11.23 8.84 12.86 15.48 9.99 12.73 11.44 10.21 4.99 0.55 0.46 0.15 0.29 0.29 0.23 0.16 0.33 0.28 0.30 AEOS x 1 0 3/ mL 0.10 0.22 0.15 0.16 0.17 0.07 0.14 0.08 0.15 0.06 0.29 0.19 0.13 0.71 0.20 0.10 0.26 0.08 0.10 0.06 In d iv id u a l Hematology Values ABAS ALUC x 1 0 3/ L x l O 3/ h 0.16 0.04 0.07 0.17 0.11 0.12 0.15 0.05 0.07 0.07 0.10 0.05 0.08 0.08 0.06 0.05 0.07 0.03 0.06 0.06 0.19 0.09 0.09 0.17 0.13 0.07 0.10 0.07 0.06 0.04 0.09 0.10 0.06 0.10 0.10 0.07 0.11 0.07 0.04 0.03 ) DuPont-8685 -107- Cpmpaiij Sanitized. Does not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number COND RBC x 1 0 6/ mL HGB g/dL M ale, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 OK OK OK OK OK 7.58 7.48 7.13 7.24 7.49 14.9 15.5 15.1 15.4 15.4 M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 OK OK OK OK OK 7.31 7.07 7.54 7.37 7.30 15.2 15.0 15.4 15.8 15.1 M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 OK OK OK CLOT OK 7.83 7.57 7.22 NT 7.27 15.7 14.9 14.5 NT 15.0 M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 OK OK OK OK OK 7.49 7.41 6.91 7.84 7.45 14.8 14.9 15.0 14.5 14.7 HCT % 45.5 45.9 44.2 44.9 44.9 45.6 43.8 44.7 44.8 44.5 47.0 43.4 43.1 NT 44.0 45.2 45.1 42.9 42.9 43.3 In d iv id u a l Hematology MCV fL MCH pg MCHC g / d L 60.0 61.4 61.9 61.9 59.9 19.7 20.8 21.2 21.3 20.6 32.8 33.9 34.3 34.4 34.3 62.4 62.0 59.3 60.7 61.0 20.8 21.3 20.4 21.5 20.7 33.3 34.3 34.4 35.3 33.9 60.0 57.3 59.6 NT 60.5 20.0 19.7 20.1 NT 20.7 33.4 34.4 33.8 NT 34.2 60.4 60.9 62.1 54.7 58.2 19.8 20.1 21.7 18.5 19.7 32.8 32.9 35.0 33.9 33.8 -108- Values RDW % ARET PLT WBC Xl03/ML x 1 0 3/ mL x 1 0 3/ mL 12.1 12.2 12.0 11.8 12.1 228.2 264.8 226.6 193.0 259.1 RNV RNV 1321 1098 947 13.17 10.45 9.67 10.60 9.69 12.4 12.0 11.7 11.5 11.9 236.4 259.8 197.3 188.5 259.5 RNV 1335 RNV RNV 1043 16.04 10.21 9.69 7.17 9.28 11.3 12.7 11.5 NT 11.7 228.6 186.3 226.1 NT 212.4 . 1375 1421 1286 NT 1388 11.95 10.42 8.17 NT 9.59 12.0 11.7 12.3 12.1 12.8 267.8 213.7 203.6 236.0 253.1 1395 1406 1220 1253 RNV 12.18 11.54 10.73 12.39 4.06 ) DuPont-8685 Company Sanitized. Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number ANEU x l 0 3///L ALYM x 1 0 3/ L AMON xloV/iL M ale, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 2.28 1.15 1.91 2.29 1.95 10.05 9.20 7.20 8.02 7.25 0.33 0.10 0.36 0.17 0.29 M ale, Group I I I - 0 . 2 mg/m3 - Day 24 662502 662503 662504 662505 662506 2.50 1.93 1.30 1.13 1.50 12.82 7.80 8.12 5.74 7.50 0.45 0.20 0.15 0.11 0.16 M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 2.30 1.52 1.34 NT 1.12 9.25 8.46 6.48 NT 8.15 0.10 0.13 0.16 NT 0.15 Male, Group VII - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 2.23 1.98 2.16 1.85 1.18 9.28 9.06 8.02 10.08 2.70 0.31 0.21 0.30 0.19 0.11 AEOS x 1 0 3/ m L 0.28 0.00 0.08 0.04 0.09 0.14 0.12 0.04 0.14 0.05 0.10 0.10 0.11 NT 0.05 0.11 0.15 0.08 0.13 0.03 In d iv id u a l Hematology Values ABAS x 1 0 3/ m L ALUC x 103/ m 0.09 0.00 0.07 0.03 0.04 0.14 0.00 0.06 0.04 0.06 0.06 0.09 0.04 0.02 0.04 0.08 0.06 0.04 0.03 0.04 0.12 0.13 0.05 NT 0.07 0.08 0.09 0.03 NT 0.05 0.11 0.07 0.10 0.06 0.03 0.14 0.07 0.07 0.08 0.01 DuPont-8685 Company Sanitized. Dees not contain TSCA CBi ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NORM ANIS MIC M ale, Group I - 0 mg/m3 - Day 10 662482 NO 662483 NO TRACE TRACE 662484 NO 662485 NO 662486 NO 662487 NO 662488 NO 662489 NO 662490 NO 662491 NO M ale, Group I I I - 0 .2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 NO NO NO NO NO NO NO NO NO NO - - In d iv id u a l Red Blood C e ll Morphology V alues MAC POLY HYPO ECHI ACAN TARG TRACE - TRACE - - - - - TRACE - TRACE - FEW - TRACE - _ - TRACE - TRACE TRACE - - TRACE - TRACE TRACE - - TRACE - TRACE - - TRACE - TRACE _ - TRACE - _ - - - TRACE - - - - TRACE - TRACE - - - - - TRACE _ FEW - - - TRACE - - - - - TRACE - FEW TRACE - - TRACE - FEW TRACE - - FEW - TRACE TRACE - _ TRACE - - - - _ TRACE _ - - - - TRACE - - - - RX - - - - - - HJB _ - - - - - - - ) DuPont-8685 -110 - Company Sanitized. Does not contain TSCA c a l ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NORM ANIS MIC M ale, Group V - 2 mg/m3 - Day 10 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 NO NO NO NO NO NO NO NO NO NO - - - - - - - - a l e , Group V II - 20 mg/m3 - Day 10 662527 NO _ _ 662528 NO - - 662529 NO TRACE TRACE 662530 NO - - 662531 NO - - 662532 NO - - 662533 NO - - 662534 NO - - 662535 NO - - 662536 NO - - In d iv id u al Red Blood C ell Morphology Values MAC POLY HYPO ECHI ACAN TARG - TRACE - TRACE TRACE - - TRACE - FEW TRACE - - TRACE - TRACE - - - TRACE - -- - - TRACE - -- - TRACE - TRACE - TRACE - _ - - - TRACE - - - - - TRACE - - TRACE - - TRACE - - - - _ TRACE _ _ _ - TRACE -- - - TRACE - TRACE TRACE - - TRACE _ - - - - TRACE - TRACE - - - TRACE - TRACE TRACE - - TRACE - - - - - TRACE - - - - - TRACE - - - - - TRACE - TRACE TRACE - RX - - - - HJB - - - _ - ) DuPont-8685 - ill - Company Sanitized. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number NORM ANIS MIC M ale, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 NO NO NO NO NO M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 NO NO NO NO NO - M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 NO NO NO CLOT NO NT NT Male, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 NO NO NO NO NO In d iv id u a l Red Blood C ell Morphology V alues MAC POLY HYPO ECHI ACAN TARG _ TRACE _ MODERATE TRACE - - TRACE - - TRACE - - TRACE - TRACE TRACE - - TRACE - - - - TRACE FEW MODERATE _ TRACE _ FEW FEW - TRACE - - - TRACE - - - - TRACE - - - TRACE TRACE - _ TRACE _ TRACE _ _ - TRACE - - TRACE - - TRACE - - - - NT NT NT NT NT NT TRACE TRACE _ TRACE _ TRACE TRACE _ - TRACE - - TRACE - - TRACE - - - - - TRACE - TRACE TRACE - - TRACE _ FEW FEW - RX - - _ - - - - - NT - HJB - - - _ - _ - - NT _ _ DuPont-8685 Company Sanitized. Does not contain TSC* c a t H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number NORM SM TOX M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 YES YES YES YES YES YES YES YES YES YES _ - - __ - - ~ M ale, Group I I I - 0 .2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 YES YES YES YES YES YES YES YES YES YES _ - _ _ - _ In d iv id u a l White Blood C ell / P la te l e t Morphology Values DB VC BC PCE GP BP V _____ _- - - - -- -- - -- - - - --- -_ --- -_ -- - -- --- -- - - _- - --,,- _,, _____ -- -- *__ _ ____ __ ___ __ _ __ _ _ _ _ _ ___ __ _ _ _ _ DuPont-8685 Company Sanitized. Does not contain TSCA CBi ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NORM SM TOX M ale, Group V - 2 mg/m3 - Day 10 662512 YES - 662513 YES _ _ 662514 YES - - 662515 YES _ _ 662516 YES _ _ 662517 YES _ _ 662518 YES _ _ 662519 YES _ _ 662520 YES _ _ 662521 YES _ _ M ale, Group V II - 20 mg/m3 - Day 10 662527 YES _ _ 662528 YES _ _ 662529 YES _ _ 662530 YES _ _ 662531 YES _ _ 662532 NO 662533 YES _ _ 662534 YES - - 662535 YES _ _ 662536 YES - - In d iv id u a l White Blood C e ll / P la te le t Morphology Values DB VC BC PCE GP BP ___ -_ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ --___ --- _ _ _ _ _ _ _ _ _ _ _ _ _ _ YES/UTD _ _ - ) DuPont-8685 -114 - Company Sanitized- Does not contain TSCAGBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number NORM SM TOX M ale, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 NO NO YES YES YES - _ _ - M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 NO YES NO NO YES _ - - _ - - M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 YES YES YES CLOT YES _ NT - _ NT - M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 YES YES YES YES NO _ - _ - _ - In d iv id u a l White Blood C ell / P la te le t Morphology Values DB VC BC PCE GP BP _ YES/UTD - YES/UTD - - _ YES/DECR - YES/ADEQ - YES/UTD - _ NT NT NT NT NT NT - - YES/DECR ) DuPont-8685 - 115 - Sanitized. Doesnoicoawu *a . ^ H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number SHEM SLIP SICT M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 TRACE NONE TRACE NONE NONE NONE TRACE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M ale, Group I I I - 0 . 2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 NONE TRACE TRACE TRACE 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 In d iv id u a l Serum and Plasma C hem istry V alues AST ALT SDH ALKP BILI BUN U/L U/L U/L U/L mg/dL mg/dL CREA mg/dL CHOL mg/dL 107 45 1 1 .9 233 0 .1 2 16 0 .2 0 67 107 41 1 9 .9 189 0 .1 0 15 0 .2 3 68 106 54 1 6 .3 214 0 .1 6 14 0 .2 4 96 90 37 11.0 223 <0.10 14 0.24 67 80 37 10.7 231 <0.10 18 0.26 58 81 27 1 1 .1 241 0 .1 0 16 0 .2 1 59 94 38 1 0 .7 218 0 .1 2 17 0 .2 3 53 89 36 1 0 .2 256 0 .1 1 17 0 .2 7 61 87 29 7 . 9 227 0 .1 1 14 0 .2 1 70 99 36 1 1 .6 237 0 .1 3 18 0 .2 7 65 99 51 1 2 .9 330 0 .1 4 15 0 .2 5 68 114 42 9 .3 192 0 .1 2 17 0 .3 0 55 78 29 7.3 246 <0.10 16 0.20 58 108 42 1 2 .7 323 0.1 1 19 0 .3 6 41 89 30 1 3 .0 219 0 .1 2 13 0 .3 5 79 74 34 9.6 250 <0.10 16 0.27 63 103 48 1 2 . 2 252 0 . 1 0 13 0 .2 3 67 91 41 1 2 .4 224 0.1 1 15 0 .2 5 58 95 42 1 2 .7 231 0 .1 2 18 0 .3 1 79 93 33 1 1 . 4 310 0 . 1 1 15 0 . 2 8 56 DuPont-8685 Company Sanitized. Does not contain TSCACB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number SHEM SLIP SICT Male, Group V - 2 mg/m3 - Day 10 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 TRACE TRACE NONE 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 NONE M ale, Group V II - 20 mg/m3 - Day 10 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 TRACE 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 In d iv id u a l Serum and Plasma C hem istry V alues AST ALT SDH ALKP BILI BUN U/L U/L U/L U/L mg/dL mg/dL CREA mg/dL CHOL mg/dL 107 41 , 2 0 . 5 227 0 .1 2 13 0 . 2 5 45 128 46 9.4 390 <0.10 12 0.25 55 87 40 11.2 236 <0.10 13 0.21 64 96 46 1 3 .4 252 0 .1 0 15 0 .2 5 62 91 42 1 6 .8 266 0 .1 2 18 0 .2 8 84 77 29 8 .1 196 0 .1 1 14 0 .2 8 49 98 43 1 2 .8 248 0 .1 3 20 0 .2 6 60 79 30 8.5 229 <0.10 15 0.20 58 87 40 1 1 .7 268 0 .1 1 14 0 .2 1 60 91 33 1 1 .2 182 0 .1 1 16 0 .2 8 68 102 36 1 2 .0 325 0 .1 1 15 0 .3 8 58 103 42 1 4 .7 212 0 .1 1 15 0 .2 7 43 109 44 14.0 197 <0.10 14 0.29 51 126 43 1 8 .2 230 0 .1 5 9 0 .1 6 43 106 48 1 2 .3 327 0 .1 2 15 0 .2 7 54 88 39 11.2 193 <0.10 14 0.29 71 93 36 1 3 .0 261 0 .1 1 12 0 .2 8 69 88 39 8.5 224 <0.10 12 0.24 49 94 34 1 0 .9 253 0 .1 2 14 0 .2 5 76 117 47 1 0 . 5 383 0 . 1 4 13 0 . 2 7 53 ) DuPont-8685 Company Saniti^ P ge5 ?<* * * * ? TSCA H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 36 47 77 48 40 34 21 35 44 30 85 6 .1 79 6 .2 87 6 .2 76 6 .0 89 6 .0 90 5.8 91 6 .0 85 6 .2 88 6 .3 85 6 .4 M ale, Group I I I - 0 .2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 52 42 27 32 35 35 69 33 37 50 81 6 .5 84 6 .4 82 6 .1 89 6 .1 81 6 .1 84 6 .5 86 6 .3 98 6 .0 96 6.3 79 5.9 In d iv id u a l Serum and Plasma C hem istry V alues ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L PHEM 4.0 2.1 11.5 11.2 144.9 6.48 98.6 NONE 4.1 2.1 11.9 10.2 146.9 6.39 100.3 NONE 4.2 2.0 11.6 10.0 146.5 5.67 99.7 NONE 3.9 2.1 11.4 10.6 147.9 6.06 102.4 NONE 3.9 2.1 11.2 10.7 148.0 5.84 103.3 NONE 3.8 2.0 11.4 10.3 147.6 6.13 102.8 NT 4.1 1.9 11.8 10.9 150.7 6.08 103.3 NT 4.2 2.0 11.4 10.4 151.2 6.01 105.9 NT 4.0 2.3 11.6 9.8 150.7 5.93 106.1 NT 4.4 2.0 11.9 11.3 150.8 6.07 102.9 NT 4.4 2.1 11.9 11.0 145.6 6.28 93.3 NONE 4.4 2.0 11.6 10.4 146.4 5.95 101.6 NONE 4.2 1.9 11.8 11.0 147.7 6.07 102.7 NONE 4.3 1.8 11.8 11.8 148.4 6.23 102.3 NONE 4.2 1.9 11.2 10.1 151.1 6.23 106.6 NONE 4.5 2.0 12.0 11.0 149.7 5.97 105.4 NT 4.2 2.1 12.0 10.1 149.1 6.71 103.3 NT 4.2 1.8 11.5 10.7 151.6 6.10 104.9 NT 4.3 2.0 11.1 10.7 151.6 5.56 102.7 NT 4.0 1.9 11.3 10.6 150.3 6.94 105.8 NT DuPont-8685 -118 - Company Sanitized. Does not contain TSCA CEB H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL M ale, Group V - 2 mg/m3 - Day 10 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 44 45 34 55 46 35 49 40 56 38 78 5 .9 68 5 .8 72 6 .4 83 6 .0 91 6 .4 84 6 .5 87 6 .6 86 5 .9 84 5 .9 88 6 .0 Male, Group V II - 20 mg/m3 - Day 10 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 40 30 40 39 56 75 57 34 45 39 82 6 .3 84 6 .2 81 6 . 1 88 5 .7 88 6 .5 76 6 .0 84 6 .2 88 5 .8 90 6.2 85 5 .9 In d iv id u a l Serum and Plasma C hem istry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L PHEM 4.1 1.8 11.4 10.5 146.5 6.13 104.0 NONE 4.2 1.6 11.0 10.7 146.3 5.73 100.9 NONE 4.3 2.1 11.5 10.6 148.6 5.93 103.7 NONE 4.1 1.9 11.5 10.5 149.4 6.22 105.6 NONE 4.3 2.1 11.6 10.6 148.5 5.96 102.7 NONE 4.3 2.2 12.1 10.5 151.0 6.27 104.8 NT 4.4 2.2 12.1 10.2 151.7 6.32 106.9 NT 3.9 2.0 11.4 11.6 149.9 6.28 104.5 NT 4.2 1.7 11.8 11.1 150.7 6.49 105.3 NT 4.1 1.9 12.2 12.2 151.0 6.09 102.7 NT 4.3 2.0 11.9 10.0 147.9 6.11 101.4 NONE 4.1 2.1 11.5 10.1 148.0 5.78 102.6 NONE 4.2 1.9 11.6 10.0 147.6 6.28 103.0 NONE 3.8 1.9 11.2 10.5 148.5 5.31 104.5 NONE 4.3 2.2 11.4 9.9 149.2 6.20 105.0 NONE 4.0 2.0 11.6 11.6 151.0 6.55 104.6 NT 4.2 2.0 12.1 10.9 152.7 6.38 106.0 NT 4.0 1.8 11.3 9.5 150.0 5.93 105.8 NT 4.1 2.1 11.5 10.6 152.0 6.29 105.5 NT 4.1 1.8 11.6 11.4 153.3 6.80 111.8 NT DuPont-8685 -119 - not contain TSCAvdJ 0mpanSaDifeed.BoeS H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number PLIP PICT PFLU iig/mL M ale, Group I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 NONE NONE NONE NONE NONE NT NT NT NT NT NONE NONE NONE NONE NONE NT NT NT NT NT 0.1 0.0 0.0 0.0 0.0 NT NT NT NT NT M ale, Group I I I - 0 .2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 NONE NONE NONE NONE NONE NT NT NT NT NT NONE NONE NONE NONE NONE NT NT NT NT NT 0.1 0.0 0.0 0.0 0.0 NT NT NT NT NT In d iv id u a l Serum and Plasma C hem istry V alues DuPont-8685 gompan S anitized.p oes not contain TSCA CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number PLIP PICT PFLU itg/mL M ale, Group v - 2 mg/m3 - Day 10 O oo o oo 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 NONE NONE NONE NONE NONE NT NT NT NT NT NONE NONE NONE NONE NONE NT NT NT NT NT 0.1 0.0 0.0 0.0 NT NT NT NT NT M ale, Group V II - 20 mg/m3 - Day 10 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 NONE NONE NONE NONE NONE NT NT NT NT NT NONE NONE NONE NONE NONE NT NT NT NT NT 0.1 0.0 0.0 NT NT NT NT NT In d iv id u a l Serum and Plasma C hem istry Values DuPont-8685 - 121 - Company Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number SHEM SLIP SICT M ale, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 TRACE SMALL TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE In d iv id u a l Serum and Plasma C hem istry V alues AST ALT SDH ALKP B IL I BUN 17/L U/L U/L U/L mg/dL mg/dL CREA mg/dL CHOL mg/dL 82 39 . 1 4 .2 238 0 .1 7 15 0 .2 8 58 106 41 1 7 .1 191 0 .1 0 16 0 .3 8 43 96 34 1 0 .7 240 0 .1 3 19 0 .2 8 69 99 38 1 4 . 1 245 0 . 1 3 13 0 . 3 2 63 115 38 4 .8 182 0 .1 2 18 0.3 0 56 106 46 1 7 .9 229 0 .1 1 13 0 .3 6 63 69 44 1 1 .9 205 0 .1 1 14 0 .2 9 60 88 39 1 4 .3 168 0 .1 0 14 0 .2 2 54 101 35 7 .4 171 0 .1 0 15 0 .2 9 70 112 36 13.8 290 <0.10 13 0.28 56 77 34 1 4 .0 166 0 .1 2 13 0 .2 9 57 79 41 1 3 .9 211 0 .1 5 17 0 .3 6 61 87 34 8 .8 170 0 .1 1 14 0 .2 7 57 104 89 11.9 225 <0.10 15 0.58 56 87 40 1 3 .7 153 0 .1 1 15 0 .2 8 67 83 38 1 8 . 5 174 0 . 1 1 13 0 . 3 3 70 88 40 1 4 .4 240 0 .1 5 13 0 .3 0 74 99 49 1 9 .1 194 0 .1 1 13 0 .2 7 46 84 32 12.7 196 <0.10 14 0.27 74 96 35 1 0 .1 290 0 .1 7 14 0 .2 6 48 ) DuPont-8685 - 122- SfiQipsP Sanitized. Does not contain TSCA CW H-24678: Two-Week Inhalation Toxicity Study in Male Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Male, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 49 17 65 43 45 85 6 .4 90 6 .4 81 6 .6 118 6.9 80 6.3 M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 80 64 29 34 60 72 6 .9 101 6.4 88 6 .2 97 6 .4 83 6 . 3 M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 47 58 36 52 84 93 6 .5 101 6.8 95 6.3 82 5 .6 89 6 .2 M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 52 68 22 87 32 90 6 .6 98 6.8 102 6.0 88 6.5 90 5 .7 In d iv id u a l Serum and Plasma C hem istry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mraol/L CL mmol/L PHEM 4.2 2.2 11.1 9.4 146.5 6.31 98.5 NSR 4.3 2.1 10.8 10.1 148.4 5.88 99.8 NONE 4.5 2.1 11.0 10.0 145.4 5.87 102.1 NONE 4.6 2.3 11.4 10.9 147.8 5.16 105.3 NONE 4.4 1.9 10.8 10.4 148.2 6.37 106.3 NONE 4.7 2.2 11.9 9.6 147.9 6.64 102.5 NSR 4.3 2.1 11.1 9.2 145.2 6.44 102.3 NONE 4.3 1.9 10.7 9.2 147.2 6.28 105.8 NONE 4.4 2.0 10.4 9.2 146.1 5.55 107.2 NONE 4.3 2.0 11.0 9.0 149.1 5.75 107.5 NONE 4.4 2.1 11.0 8.8 146.1 5.98 101.0 NONE 4.5 2.3 11.5 8.8 148.2 5.49 103.8 NONE 4.2 2.1 10.7 10.4 145.8 6.13 104.0 NONE 3.9 1.7 10.3 10.7 147.7 6.84 109.1 NONE 4.3 1.9 11.1 9.2 148.4 6.02 103.2 NONE 4.4 2.2 10.6 9.5 147.8 6.29 102.9 NONE 4.6 2.2 11.7 9.9 149.2 5.88 105.2 NONE 4.2 1.8 10.9 10.4 146.7 5.86 104.7 NONE 4.4 2.1 10.8 8.5 149.0 5.78 104.1 NONE 4.1 1.6 10.8 10.3 149.2 6.28 106.9 NONE DuPont-8685 CompanS Sntfeed.Do8S not contain TSCACBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) Animal Number PLIP PICT PFLU wg/mL Male, Group I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 NT NONE NONE NONE NONE NT NONE NONE NONE NONE NT 0.1 0.1 0.1 0.1 M ale, Group I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 NT NONE NONE NONE NONE NT NONE NONE NONE NONE NT 0.1 0.1 0.1 0.1 M ale, Group V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.2 0.1 0.1 0.1 0.1 M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 In d iv id u a l Serum and Plasma C hem istry Values - 124- ) DuPont-8685 H-24678: Two-Week Inhalation Toxicity Study in Male Rats Anim al Number VOL mL UFLU fjg M ale, G roup I - 0 mg/m3 - Day 10 662482 662483 662484 662485 662486 662487 662488 662489 662490 662491 4 .6 1 0 .0 1 2 .6 9 .0 9 .8 9 .4 7 .4 5 .8 2 .0 1 .6 12.0 9 .6 1 0 .3 8 .4 1 0 .4 6.0 6 .7 7 .0 5 .6 6 .9 M ale, G roup I I I - 0 .2 mg/m3 - Day 10 662497 662498 662499 662500 662501 662502 662503 662504 662505 662506 3 .4 1 3 .0 6.8 6 .0 3 .0 6.2 2 3 .4 9 .0 3 .0 5.4 5 .9 1 0 .7 8.6 5 .4 5 .6 5 .9 1 2 .9 8.8 7 .5 7 .7 In d iv id u a l U rin a ly s is V alues DuPont-8685 -125 - Company Santtizegi-Di-o--es---UI----- H-24678: Two-Week Inhalation Toxicity Study in Male Rats Anim al Number VOL mL UFLU xg M ale, G roup V - 2 mg/m3 - Day 10 662512 662513 662514 662515 662516 662517 662518 662519 662520 662521 6 .4 1 3 .6 1 4 .0 8 .2 1 0 .8 6 .6 4 .8 1 3 .0 8 .8 6 .8 7 .3 9 .8 9 .5 6.6 8 .4 7 .4 7 .1 9 .4 8 .4 6 .9 M ale, G roup V II - 20 mg/m3 - Day 10 662527 662528 662529 662530 662531 662532 662533 662534 662535 662536 1.6 4 .2 6 .0 3 8 .2 3 .0 5 .0 7 .6 1 3 .0 6 .6 7 .8 7 .0 8 .4 9 .2 2 3 .2 5 .9 9 .8 1 0 .1 1 3 .1 9 .8 8 .8 In d iv id u a l U rin a ly s is V alues DuPont-8685 Company Sanitized. Does not contain TSCACBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats Anim al Number VOL mL UFLU tg M ale, G roup I - 0 mg/m3 - Day 24 662487 662488 662489 662490 662491 3.4 4 .8 2 .2 1 1 .6 4 .2 1 1 .5 9 .4 7 .7 1 4 .0 8.1 M ale, G roup I I I - 0 .2 mg/m3 - Day 24 662502 662503 662504 662505 662506 5.4 1 6 .0 6 .6 6.8 5 .8 1 0 .9 1 9 .8 8.0 1 1 .7 12.1 M ale, G roup V - 2 mg/m3 - Day 24 662517 662518 662519 662520 662521 9 .0 4.6 1 3 .4 1 0 .0 9.6 1 3 .7 8 .7 1 5 .9 1 2 .2 1 2 .9 M ale, Group V II - 20 mg/m3 - Day 24 662532 662533 662534 662535 662536 6 .8 8 .0 2 2 .4 8 .0 9 .0 1 2 .1 1 5 .5 1 8 .1 1 1 .0 1 3 .1 In d iv id u a l U rin a ly s is V alues DuPont-8685 to n p ^ X S an ifeed . Does not contain ihCh CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX G Individual Animal Final Body and Organ W eights -128- gompanx Sanlfed Does contain TSCA CB1 )> H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 I n d iv id u a l A nim al F in a l Body and O rgan W eights - Day 10 S a c r if ic e Group: I C o n c e n tr a tio n : 0 mg/m3 S e x : MALES 1 ANIMAL FBW BRAIN (Gms) (Gms) %FBW KIDNEYS (Gms) %FBW %BRAIN (Gms) LIVER %FBW %BRAIN (Gms) LUNGS %FBW %BRAIN 662482 662483 662484 662485 662486 2 6 1 .3 0 2 7 6 .4 0 2 4 8 .1 0 2 4 3 .0 0 2 2 8 .4 0 1 .8 8 3 1 .8 5 3 2 .0 4 8 1 .9 1 0 1 .7 5 6 0 .7 2 0 6 0 .6 7 0 4 0 .8 2 5 5 0 .7 8 6 0 0 .7 6 8 8 2 .4 7 7 2 .4 5 3 2 .3 1 6 2 .1 6 6 2 .0 6 6 0 .9 4 8 0 0 .8 8 7 5 0 .9 3 3 5 0 .8 9 1 4 0 .9 0 4 6 131.55 1 3 2 .3 8 1 1 3 .0 9 1 1 3 .4 0 1 1 7 .6 5 8.352 9 .4 5 0 9 .3 7 6 7 .2 0 3 6 .8 2 6 3 .1 9 6 3 3 .4 1 9 0 3.7791 2.9642 2 .9 8 8 6 4 4 3 .5 5 509.98 457.81 377.12 388.72 1 .4 5 0 1.497 1.886 1 .3 3 4 1.355 0 .5 5 4 9 0 .5 4 1 6 0 .7 6 0 2 0 .5 4 9 0 0 .5 9 3 3 77.005 80.788 92.090 69.843 77.164 Mean S.D . 2 5 1 .4 4 1 8 .2 6 1.890 0.7543 0.106 0.0601 2.296 0.9130 121.61 0.179 0.0266 9.6225 8.241 3.2694 435.44 1.209 0.3389 54.098 1.504 0.5998 79.378 0.224 0.0919 8.1399 TESTES 1 (Gms) %FBW %BRAIN | 2 .7 7 0 3 .2 9 4 2 .8 9 8 2 .8 9 5 2 .8 9 5 1 .0 6 0 1 1 .1 9 1 8 1 .1 6 8 1 1 .1 9 1 4 1 .2 6 7 5 1 4 7 .1 1 1 7 7 .7 7 1 4 1 .5 0 1 5 1 .5 7 1 6 4 .8 6 2.950 1.1758 156.56 0.200 0.0748 14.659 Group: I I I C o n c e n tr a tio n : 0 .2 mg/m3 S e x : MALES 1 ANIMAL 1 662497 662498 662499 662500 662501 FBW (Gms) 2 4 8 .1 0 2 7 9 .8 0 2 2 8 .1 0 2 5 2 .5 0 2 4 2 .5 0 BRAIN (Gms) %FBW 2 .1 0 0 1 .9 3 5 1 .8 8 2 1 .8 9 1 1 .8 6 3 0.8464 0 .6 9 1 6 0 .8 2 5 1 0 .7 4 8 9 0 .7 6 8 2 KIDNEYS (Gms) %FBW %BRAIN 2 .5 7 2 2 .9 8 0 2 .0 2 7 1 .9 9 8 1 .9 9 7 1 .0 3 6 7 1.0650 0 .8 8 8 6 0.7913 0 .8 2 3 5 1 2 2 .4 8 1 5 4 .0 1 1 0 7 .7 0 1 0 5 .6 6 1 0 7 .1 9 (Gms) LIVER %FBW %BRAIN 8 .8 1 5 9 .6 9 1 6 .8 7 8 7 .3 3 5 6 .7 7 2 3 .5 5 3 0 3 .4 6 3 5 3 .0 1 5 3 2 .9 0 5 0 2 .7 9 2 6 419.76 500.83 3 6 5 .4 6 387.89 363.50 Mean S.D . 2 5 0 .2 0 1 8 .9 3 1.934 0.7760 0.096 0.0618 2.315 0.9210 119.41 0.445 0.1240 20.504 7.898 3.1459 407.49 1.292 0.3415 56.895 (Gms) LUNGS %FBW %BRA1N 1.984 1.774 1.479 1.400 1.392 0 .7 9 9 7 0 .6 3 4 0 0 .6 4 8 4 0 .5 5 4 5 0 .5 7 4 0 94.476 9 1 .6 8 0 78.587 74.035 7 4 .7 1 8 1.606 0.6421 82.699 0.262 0.0965 9.6828 TESTES 1 (Gms) %FBW %BRAIN | 3 .2 3 7 3 .1 0 9 2 .6 6 8 3 .0 0 1 2 .9 4 4 1 .3 0 4 7 1 .1 1 1 2 1 .1 6 9 7 1 .1 8 8 5 1 .2 1 4 0 154.14 1 6 0 .6 7 1 4 1 .7 6 1 5 8 .7 0 1 5 8 .0 2 2.992 1.1976 154.66 0.213 0.0709 7.5886 FBW - F i n a l Body W e ig h t -129 - Company Sanitized. Does not contain TSCA CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats > ) DuPont-8685 In d iv id u a l Anim al F in a l Body and O rgan W eights - Day 10 S a c r if ic e Group: V C o n c e n tr a tio n : 2 mg/m3 S e x : MALES 1 ANIMAL FBW BRAIN (Gms) (Gms) %FBW KIDNEYS (Gms) %FBW %BRAIN (Gms) LIVER %FBW %BRAIN (Gms) LUNGS %FBW %BRAIN 662512 662513 662514 662515 662516 2 6 7 .4 0 2 6 8 .1 0 2 5 2 .5 0 2 5 2 .0 0 2 3 3 .4 0 1 .9 6 1 1 .8 9 9 1 .8 1 6 1 .9 4 9 1 .7 2 3 0 .7 3 3 4 0 .7 0 8 3 0 .7 1 9 2 0 .7 7 3 4 0 .7 3 8 2 2 .4 1 9 2 .4 4 1 2 .1 4 4 2 .3 4 1 1 .8 5 4 0 .9 0 4 6 0 .9 1 0 5 0 .8 4 9 1 0 .9 2 9 0 0 .7 9 4 3 1 2 3 .3 6 1 2 8 .5 4 1 1 8 .0 6 1 2 0 .1 1 1 0 7 .6 0 8.707 3.2562 444.01 8.558 3.1921 450.66 7.910 3.1327 435.57 8.125 3.2242 416.88 7.426 3.1817 430.99 1 .5 8 0 1 .4 6 3 1 .5 5 6 1 .7 6 6 1 .4 0 4 0 .5 9 0 9 0 .5 4 5 7 0 .6 1 6 2 0 .7 0 0 8 0.6015 80.571 77.041 85.683 90.611 81.486 Mean S.D . 2 5 4 .6 8 1 4 .2 0 1.870 0.7345 0 .100 0.0247 2.240 0.8775 119.53 0.245 0.0552 7.7554 8.145 3.1974 435.62 0.515 0.0465 12.933 1.554 0.6110 83.078 0.138 0.0567 5.2152 TESTES 1 (Gms) %FBW %BRAIN | 3 .2 8 9 3 .1 9 9 2 .5 7 6 2 .7 2 0 2 .5 2 4 1 .2 3 0 0 1 .1 9 3 2 1 .0 2 0 2 1 .0 7 9 4 1 .0 8 1 4 1 6 7 .7 2 1 6 8 .4 6 1 4 1 .8 5 1 3 9 .5 6 1 4 6 .4 9 2.862 1.1208 152.82 0.358 0.0874 14.167 Group: V II C o n c e n t r a t i o n : 20 mg/m3 S e x : MALES 1 ANIMAL 1 662527 662528 662529 662530 662531 FBW (Gms) 2 5 8 .8 0 2 6 3 .9 0 2 2 7 .3 0 2 4 5 .7 0 2 3 5 .7 0 BRAIN (Gms) %FBW 1 .9 4 9 1 .9 1 6 1 .8 6 3 1 .9 4 3 1 .8 9 1 0 .7 5 3 1 0 .7 2 6 0 0 .8 1 9 6 0.7908 0 .8 0 2 3 KIDNEYS (Gms) %FBW %BRAIN 2 .2 9 6 2 .4 7 3 1 .9 7 5 2 .9 0 2 2 .0 2 9 0 .8 8 7 2 0 .9 3 7 1 0 .8 6 8 9 1.1811 0.8608 1 1 7 .8 0 1 2 9 .0 7 1 0 6 .0 1 1 4 9 .3 6 1 0 7 .3 0 (Gms) LIVER %FBW %BRAIN 8 .4 9 0 8 .1 9 9 7 .1 3 7 5 .9 7 0 7 .1 2 5 3 .2 8 0 5 3 .1 0 6 9 3 .1 3 9 9 2 .4 2 9 8 3 .0 2 2 9 4 3 5 .6 1 4 2 7 .9 2 383.09 307.26 376.78 Mean S.D . 2 4 6 .2 8 1 5 .3 3 1.912 0.7784 0.036 0.0381 2.335 0.9470 121.91 0.376 0.1342 17.942 7.384 2.9960 386.13 1.002 0.3299 51.265 (Gms) LUNGS %FBW %BRAIN 1 .6 8 4 1 .8 2 7 1.501 1 .6 5 1 1 .1 9 9 0 .6 5 0 7 0 .6 9 2 3 0 .6 6 0 4 0.6720 0 .5 0 8 7 86.403 95.355 80.569 84.972 6 3 .4 0 6 1.572 0.6368 82.141 0.239 0.0733 11.772 TESTES 1 (Gms) %FBW %BRAIN | 3 .1 0 2 3 .1 6 4 2 .5 7 3 2 .1 8 5 2 .6 8 4 1 .1 9 8 6 1 .1 9 8 9 1 .1 3 2 0 0 .8 8 9 3 1 .1 3 8 7 1 5 9 .1 6 1 6 5 .1 4 1 3 8 .1 1 1 1 2 .4 5 1 4 1 .9 4 2 .742 1.1115 143.36 0.403 0.1282 20.667 FBW - F i n a l Body W e ig h t -130- Company Sanitized. Doss not coofasn TSC CBI ) H-24678: Two-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-8685 I n d iv id u a l Anim al F in a l Body and O rgan W eights - Day 24 S a c r if ic e Group: I C o n c e n tr a tio n : 0 mg/m3 S e x : MALES 1 ANIMAL 1 662488 662489 662490 662491 FBW (Gms) 3 2 1 .7 0 3 1 0 .2 0 3 1 9 .3 0 2 9 1 .2 0 BRAIN (Gms) %FBW 1.988 0.6180 1.959 0.6315 1.992 0.6239 2.024 0.6951 KIDNEYS (Gms) %FBW %BRAIN 2.556 0.7945 128.57 2.540 0.8188 129.66 3.009 0.9424 151.05 2.472 0.8489 122.13 (Gms) LIVER %FBW %BRAIN 8.899 2.7662 447.64 ' 8.357 2.6941 426.60 10.485 3.2837 526.36 8.588 2.9492 424.31 (Gms) LUNGS %FBW %BRAIN 1.463 0.4548 73.592 1.504 0.4848 76.774 1.908 0.5976 95.783 1.615 0.5546 79.792 Mean S.D . 3 1 0 .6 0 1 3 .8 5 1.991 0.6421 0.027 0.0357 2 .644 0.8512 132.85 0.246 0.0647 12.579 9.082 2.9233 456.22 0.961 0.2632 47.919 1.623 0.5229 81.485 0.201 0.0650 9.8624 TESTES 1 (Gms) %FBW %BRAIN | 3.193 0.9925 160.61 3.089 0.9958 157.68 3.193 1.0000 160.29 3.499 1.2016 172.88 3.244 1.0475 162.87 0.177 0.1028 6.8010 Group: I I I C o n c e n tr a tio n : 3.2 mg/m3 S e x : MALES 1 ANIMAL 1 662503 662504 662505 662506 FBW (Gms) 3 6 1 .4 0 278.90 3 1 2 .6 0 3 1 4 .7 0 BRAIN (Gms) %FBW 1.968 0.5445 1.957 0.7017 1.876 0.6001 1.996 0.6343 KIDNEYS (Gms) %FBW %BRAIN 2.693 0.7452 136.84 2.348 0.8419 119.98 2.831 0.9056 150.91 2.670 0.8484 133.77 (Gms) LIVER %FBW %BRAIN 10.908 3.0183 554.27 8.104 2.9057 414.10 9.945 3.1814 530.12 8.506 2.7029 426.15 Mean S.D . 316.90 3 3 .9 0 1.949 0.6202 0.052 0.0657 2.636 0.8353 135.37 0.204 0.0666 12.688 9.366 2.9521 481.16 1.297 0.2010 71.330 (Gms) LUNGS %FBW %BRAIN 1.918 0.5307 97.459 1.641 0.5884 83.853 1.500 0.4798 79.957 1.474 0.4684 73.848 1.633 0.5168 83.779 0.204 0.0549 10.007 TESTES 1 (Gms) %FBW %BRAIN | 2 .9 8 2 2 .7 2 9 2 .6 5 2 2 .8 9 0 0 .8 2 5 1 0 .9 7 8 5 0 .8 4 8 4 0 .9 1 8 3 1 5 1 .5 2 1 3 9 .4 5 1 4 1 .3 6 1 4 4 .7 9 2.813 0.8926 144.28 0.150 0.0696 5.3100 FBW - F i n a l B ody W e ig h t - 131 - Company Sanitized. Does not contain TSCACBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 I n d iv id u a l Anim al F in a l Body and O rgan W eights - Day 24 S a c r if ic e Group: V C o n c e n tr a tio n : 2 mg/m3 S e x : MALES 1 ANIMAL FBW BRAIN (Gn\s) (Gms) %FBW KIDNEYS (Gms) %FBW %BRAIN (Gms) LIVR %FBW %BRAIN (Gms) LUNGS %FBW %BRAIN 662517 662518 662519 662520 662521 3 2 5 .9 0 3 0 1 .8 0 3 2 3 .1 0 3 3 0 .3 0 3 2 6 .7 0 2 .0 1 1 2 .0 8 6 1 .9 3 6 1 .9 0 8 1 .9 4 1 0 .6 1 7 1 0 .6 9 1 2 0.5992 0 .5 7 7 7 0 .5 9 4 1 2 .787 0.8552 138.59 2.613 0.8658 125.26 2.484 0.7688 128.31 3.039 0.9201 159.28 2.881 0.8818 148.43 1 0 .7 7 6 1 0 .5 3 5 9 .7 6 8 1 0 .1 8 0 10.623 3.3065 3.4907 3.0232 3 .0 8 2 0 3.2516 5 3 5 .8 5 5 0 5 .0 3 504.55 5 3 3 .5 4 547.30 2 .1 9 3 1 .9 4 4 1 .4 7 1 1 .8 3 5 1 .7 5 6 0.6729 0 .6 4 4 1 0 .4 5 5 3 0 .5 5 5 6 0.5375 1 0 9 .0 5 93.193 7 5 .9 8 1 9 6 .1 7 4 9 0 .4 6 9 Mean S.D . 3 2 1 .5 6 1 1 .3 4 1.976 0.6158 0.072 0.0444 2.761 0.8583 139.97 0.219 0.0558 14.129 10.376 3.2308 525.25 0.404 0.1864 19.394 1.840 0.5731 92.973 0.264 0.0873 11.872 TESTES 1 (Gms) %FBW %BRAIN | 3 .1 3 1 3 .0 0 1 3 .0 3 7 3 .6 4 8 3 .2 2 6 0 .9 6 0 7 0 .9 9 4 4 0 .9 4 0 0 1 .1 0 4 5 0 .9 8 7 5 1 5 5 .6 9 1 4 3 .8 6 1 5 6 .8 7 1 9 1 .1 9 1 6 6 .2 0 3.209 0.9974 162.77 0.261 0.0637 17.763 Group: V II C o n c e n tr a tio n : 20 mg/m3 S e x : MALES 1 ANIMAL FBW BRAIN (Gms) (Gms) %FBW KIDNEYS (Gms) %FBW %BRAIN (Gms) LIVER %FBW %BRAIN 662532 662533 662534 662535 662536 3 4 6 .2 0 3 7 1 .1 0 3 4 3 .2 0 3 2 1 .7 0 3 1 3 .6 0 2 .0 2 0 2 .0 4 3 2 .0 0 9 1 .8 6 0 2 .1 8 1 0 .5 8 3 5 0 .5 5 0 5 0 .5 8 5 4 0 .5 7 8 2 0 .6 9 5 5 2 .5 6 4 3 .1 6 6 2 .8 1 6 2 .7 0 2 3 .0 2 9 0 .7 4 0 6 0 .8 5 3 1 0 .8 2 0 5 0 .8 3 9 9 0 .9 6 5 9 126.93 1 5 4 .9 7 140.17 1 4 5 .2 7 138.88 1 0 .6 7 0 1 1 .6 3 7 1 1 .1 2 4 9 .5 0 7 9 .4 4 6 3 .0 8 2 0 3 .1 3 5 8 3 .2 4 1 3 2 .9 5 5 2 3.0121 5 2 8 .2 2 5 6 9 .6 0 5 5 3 .7 1 511.13 433.10 Mean S.D . 3 3 9 .1 6 2 2 .6 1 2.023 0.5986 0.114 0.0559 2.855 0.8440 141.24 0.243 0.0809 10.200 10.477 3.0853 519.15 0.975 0.1109 53.128 (Gms) LUNGS %FBW %BRAIN 1 .5 6 1 1 .7 3 5 1 .5 6 2 1 .7 5 1 1 .8 6 4 0.4509 0.4675 0 .4 5 5 1 0 .5 4 4 3 0.5944 7 7 .2 7 7 84.924 7 7 .7 5 0 9 4 .1 4 0 8 5 .4 6 5 1.695 0.5024 83.911 0.131 0.0639 6.8926 TESTES 1 (Gms) %FBW %BRAIN | 2 .8 1 8 3 .2 4 4 3 .0 2 4 3 .3 3 0 3 .4 7 0 0 .8 1 4 0 0 .8 7 4 2 0 .8 8 1 1 1 .0 3 5 1 1 .1 0 6 5 1 3 9 .5 0 1 5 8 .7 9 1 5 0 .5 2 1 7 9 .0 3 1 5 9 .1 0 3.177 0.9422 157.39 0.258 0.1229 14.494 FBW - F i n a l B ody W e ig h t Qm pm i S a n if e g d - P o e s o c o n ta in 'IS C A v d t H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 APPENDIX H Individual Animal Pathology Data - 133 - Company Sanitised. Does not contain TSCA CB1 H-24678: Two-Week Inhalation Toxicity Study in Male Rats DuPont-8685 INDIVIDUAL ANIMAL PATHOLOGY DATA KEY TO APPENDIX LESION GRADING: H isto p a th o lo g y changes a re d e sc rib e d acco rd in g to th e ir m orphologic c h a ra c te r, d is tr ib u tio n and s e v e rity . The d is tr ib u tio n (e x te n t o f tis s u e involvem ent) i s in d ic a te d , w here a p p ro p ria te , by m o d ifiers such as fo cal, m u ltifo ca l, d iffu se , u n ila te ra l, b ila te r a l, e tc . A se v e rity sco re, i f a p p ro p ria te , is a lso assig n ed as fo llo w s: MINIMAL: MILD: MODERATE: SEVERE : The amount of change p re s e n t b a re ly exceeds th a t w hich i s c o n sid e re d to be w ith in norm al lim its . In g e n e ra l, th e le s io n i s e a s ily id e n tifie d but of lim ite d s e v e rity . The le s io n probably does no t produce any fu n c tio n a l im pairm ent. The le s io n i s prom inent b u t th e re i s s ig n if ic a n t p o te n tia l fo r in c re a s e d s e v e rity . L im ited tis s u e o r organ d y sfu n c tio n i s p o s s ib le . The d eg ree o f change i s e it h e r a s com plete a s c o n sid e re d p o s s ib le o r g re a t enough in in te n s ity o r e x te n t to expect s ig n ific a n t tis s u e o r organ d y sfu n ctio n . COMMENT : G rades m inim al th ro u g h se v e re re p re s e n t p ro g re s s iv e in v o lv e m e n t/s e v e rity alo n g a continuum w ith m inim al le s io n s b e in g th e le a s t se v e re and se v e re le s io n s b e in g th e m ost se v e re . W hile th e g ra d es r e f e r to th e m orphologic c h a r a c te r is tic s o f le s io n s , th e y a ls o in d ic a te t h e i r r e la tiv e b io lo g ic sig n ific a n c e . G ro s s o b s e r v a tio n s l i s t i n g m u lt i p le m a s se s f o r a t i s s u e a r e d i s t i n g u i s h e d w ith l e t t e r s ( i . e . , A, b, c, d, e tc .). /'" 'N H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A nim al P a th o lo g y D ata Group: I C o n c e n tr a tio n : 0 mg/m3 Sex: M ales Anim al R ef M icroscopic & M acroscopic F in d in g s 662482 T erm inal S a c rific e K i l le d on Day : 10 E x p o su re G roup : M ain Anim al i s sig n e d o ff from n e cro p sy G ross P athology : No M a c r o s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. No M i c r o s c o p i c A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662483 T erm inal S a c rific e K i l le d on Day : 10 E x p o su re G roup : M ain Anim al i s sig n e d o ff from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVI;, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, m in i m a l . PARATHYROID GLANDS : M IS SIN G . FOCAL, m ild. No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE ORGANS NOT EXAMINED: PARATHYROID GLANDS DuPont-8685 -135 - Potttpan Sanitized. Does not contain TSCA CBf H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A nim al P a th o lo g y D ata Group: I C o n c e n tr a tio n : 0 mg/m3 Sex: M ales A nim al Ref M icroscopic & M acroscopic F indings 662484 T erm inal S a c rific e K i l l e d on Day : 10 E x p o su re G roup : M ain Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b serv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . FATTY CHANGE, MEDIAN CLEFT, m in im a l. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in im a l. No M ic r o s c o p ic A b n o r m a lity O b s e rv e d : LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE{S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662485 T erm inal S a c rific e K i l le d on Day : 10 .E x p o su re G roup : M ain Anim al i s s ig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 - 136 - Company Sanitized. Does not contain TSC*-* H-24678: Two-Week Inhalation Toxicity Study in Male Rats I n d iv id u a l Anim al P a th o lo g y D ata Group: I C o n c e n tr a tio n : 0 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F indings 662486 T erm inal S a c rific e K i l l e d on Day : 10 E x p o su re G roup : M ain A nim al i s s ig n e d o f f from n e cro p sy G ross P athology : No M a c r o s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . HEART : CARDIOMYOPATHY, m in im a l. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, m in i m a l . No M i c r o s c o p i c A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662487 A ccid en tally K illed D u ra tio n o f d o s in g -d a y s : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m i l d . NOSE : DEGENERATION, TRIGEMINAL NERVE, m i l d . No M ic r o s c o p ic A b n o r m a lity O b s e rv e d : LUNGS, PHARYNX/LARYNX, TESTES DuPont-8685 - 137g&mpany Sanitized, Does not contain TSCA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: I C o n c e n tr a tio n : 0 mg/m3 Sex: M ales A nim al Ref M icro sco p ic & M acroscopic F in d in g s 662488 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery A nim al i s sig n e d o f f from n e c ro p sy G ross P athology : Mo M a c r o s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O b s e rv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662489 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 / ' " "N - 138- Company Sanitized. Does not contain TSCA CBt /****\ H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A nim al P a th o lo g y D ata Group: I C o n c e n tr a tio n : 0 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662490 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M a c ro sc o p ic A b n o rm a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . CYST, m in im a l. No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662491 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o ff from n ecro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 G m p m ij m m . Does not contain TSCACBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: I I I C o n c e n tr a tio n : 0 .2 mg/m3 Sex: M ales Anim al Ref M icro sco p ic & M acroscopic F in d in g s 662497 T erm inal S a c rific e K i l le d on Day : 10 E x p o su re G roup : M ain Anim al i s s ig n e d o f f from n ecro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b serv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662498 T erm inal S a c rific e K i l l e d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/ CHRONIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O b serv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 Oompanjr Sanitized. Does not contain ISCA CBl H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A nim al P a th o lo g y D ata Group: I I I C o n c e n tr a tio n : 0 .2 mg/m3 Sex: M ales Anim al Ref M icro sco p ic & M acroscopic F in d in g s 662499 T erm inal S a c rific e K i l le d on Day : 10 E x p o su re G roup : M ain Anim al i s sig n e d o ff from n e c ro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O b se rv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662500 T erm inal S a c rific e K ille d on Day : 10 E x p o su re G roup : Main Anim al i s sig n e d o ff from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ' ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : MISSING. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, m in im a l. No M ic ro s c o p ic A b n o rm a lity O b serv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES ORGANS NOT EXAMINED: LIVER DuPont-8685 - 141 - Company.Sanitized. Bees not contain T3CA CBI H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: I I I C o n c e n tr a tio n : 0 .2 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662501 T erm inal S a c rific e K ille d on Day : 10 E x p o su re G roup : M ain A nim al i s sig n e d o ff from n ecro p sy G ross P athology : No M a c ro sc o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/ CHRONIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O b serv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662502 A ccid en tally K illed D u ra tio n o f d o s in g -d a y s : 24 E xposure Group : R ecovery A nim al i s sig n e d o ff from n ecro p sy GrosS; P a th o lo g y : No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662503 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 .Company S anitized. D oes not contain TSCA CBS H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: I I I C o n c e n tra tio n : 0 .2 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662504 T erm inal S a c rific e K ille d on Day : 24 E xposure Group : R ecovery Anim al i s s ig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 652505 T erm inal S a c rific e K ille d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro sc o p ic A b n o rm a lity O b serv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662506 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 ' Company Sanitized. Does not contain 1SC CM H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: V C o n c e n tr a tio n : 2 mg/m3 Sex: M ales A nim al Ref M icroscopic & M acroscopic F in d in g s 662512 T erm inal S a c rific e K i l le d on Day : 10 E xposure G roup : M ain Anim al i s s ig n e d o ff from n ecro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . NOSE : INFLAMMATION, SUBACUTE/CHRONIC, m in i m a l . No M ic ro s c o p ic A b n o rm a lity O b se rv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES 662513 T erm inal S a c rific e K ille d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M a c ro sc o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m in im a l. No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, TESTES, NOSE DuPont-8685 - 144- Company Sanitized. Does not contain TSCA m H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: V C o n c e n tr a tio n : 2 mg/m3 Sex: M ales A nim al R ef M icroscopic & M acroscopic F in d in g s 662514 T erm inal S a c rific e K i l l e d on Day : 10 E xposure G roup : M ain Anim al i s s ig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/ CHRONIC, FOCAL, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m in im a l. No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : KIDNEYS, LUNGS, TESTES, NOSE 662515 T erm inal S a c rific e K i l le d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE {S ) WITH OPTIC N E RV E , PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m in im a l. No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : LUNGS, TESTES, NOSE DuPont-8685 Com paq Sanitized. Does not contain TSCA CBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: V C o n c e n tr a tio n : 2 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662516 T erm inal S a c rific e K i l l e d on Day : 10 E xposure Group : M ain Anim al i s sig n e d o f f from n e cro p sy G ross P ath o lo g y : No M a c ro s c o p ic A b n o rm a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m in im a l. PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m in i m a l . No M ic ro sc o p ic A b n o rm a lity O b serv ed : KIDNEYS, TESTES, NOSE 662517 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o ff from n e c ro p sy G ross P athology : THYMUS : DISCOLORATION, DARK, MOTTLED. No M a c ro s c o p ic A b n o r m a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662518 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M acro sco p ic A b n o rm a lity O b serv ed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 ' 146 ' J & m s a n i t i z e d . Pes 0* contain TSG C M H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: V C o n c e n tr a tio n : 2 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662519 T erm inal S a c rific e K i l l e d on Day : 24 E xposure Group : R ecovery Anim al i s s ig n e d o f f from n e cro p sy G ross P athology : EPIDIDYMIDES : DISCOLORATION, TAN, LEFT, TAIL, 3MM D I A .. No M a c ro s c o p ic A b n o rm a lity O b serv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, NOSE 662520 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n ecro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a lity O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662521 T erm inal S a c rific e K ille d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 - 147 f t o m m Sanitized. Does not contain TSCA CBI /"""N H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: V II C o n c e n tr a tio n : 20 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662527 T erm inal S a c rific e K i l l e d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : M ISSIN G . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m i l d . No M i c r o s c o p ic A b n o r m a lity O b s e r v e d : HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE ORGANS NOT EXAMINED: LIVER DuPont-8685 -148- SCAC81 Company Sanitized. Does not conta.n /"V H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: V II c o n c e n tr a tio n : 20 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662528 T erm inal S a c rific e K ille d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o f f from n e c ro p sy G ross P athology : Mo M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : HYDRONEPHROSIS, UNILATERAL, m i l d . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m i l d . EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. No M ic r o s c o p ic A b n o r m a li t y O b s e rv e d : LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 TSCACBI Company Smutted. Dons not contain H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A nim al P a th o lo g y D ata G roup: V II C o n c e n tr a tio n : 20 mg/m3 Sex: M ales Anim al Ref M i c r o s c o p ic Sc M a c r o s c o p ic F i n d i n g s 662529 T erm inal S a c rific e K i l le d on Day : 10 E xposure G roup : M ain Anim al i s s ig n e d o f f from n e cro p sy G ro s s P a t h o l o g y .- No M a c ro s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y LIVER : INFLAMMATION, SUBACUTE/ CHRONIC, FOCAL, m in i m a l . LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m in i m a l . No M ic r o s c o p ic A b n o r m a lity O b s e rv e d : KIDNEYS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE DuPont-8685 -150Gompany Sanitized. Does not contain TSCA CE, H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: V II C o n c e n tra tio n : 20 m g/m S e x : M ales Anim al Ref M icro sco p ic & M acroscopic F in d in g s 662530 T erm inal S a c rific e K i l le d on Day : 10 E xposure G roup : M ain Anim al i s sig n e d o ff from n ecro p sy G ross P athology : LIVER : DISCOLORATION, TAN, MOTTLED. No M a c ro s c o p ic A b n o rm a lity O b serv e d : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . HYPERPLASIA, BILE DUCT, m in im a l. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m in i m a l . HEART : CARDIOMYOPATHY, m in im a l. PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m i l d . EYE(S ) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, m i l d . No M i c r o s c o p i c A b n o r m a li t y O b s e rv e d : SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, NOSE DuPont-8685 -151 - Company SamfMH. Does not contain TSCA t o . ,/***N- H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: V II C o n c e n tr a tio n : 20 mg/m3 Sex: M ales Anim al Ref M icroscopic & M acroscopic F in d in g s 662531 T erm inal S a c rific e K i l l e d on Day : 10 E x p o su re G roup : M ain A nim al i s sig n e d o ff from n e c ro p sy G ross P athology : No M a c r o s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. HEART : CARDIOMYOPATHY, m in i m a l . PHARYNX/LARYNX : SQUAMOUS METAPLASIA, m i l d . EYE( S } WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. No M ic ro sc o p ic A b n o rm a lity O b serv ed : KIDNEYS, LUNGS, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE 662532 T erm inal S a c rific e K i l l e d on Day : 24 E xposure Group : R ecovery A nim al i s sig n e d o ff from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 -152- SaniUzed.Dc.es not contain TSCACBi H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata Group: V II C o n c e n tr a tio n : 20 mg/m3 Sex: M ales A nim al Ref M icroscopic & M acroscopic F indings 662533 T erm inal S a c rific e K i l le d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : LUNGS : DISCOLORATION, RED, SCATTERED. No M a c ro s c o p ic A b n o rm a lity O b se rv e d : LIVER, KIDNEYS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H isto p ath o lo g y : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e rv e d : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE 662534 T erm inal S a c rific e K ille d on Day : 24 E xposure Group : R ecovery Anim al i s sig n e d o f f from n e cro p sy G ross P athology : No M a c ro s c o p ic A b n o r m a li t y O b s e rv e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 SCACW H-24678: Two-Week Inhalation Toxicity Study in Male Rats In d iv id u a l Anim al P a th o lo g y D ata G roup: V II C o n c e n tr a tio n : 20 mg/m3 Sex: M ales Anim al Ref M icro sco p ic & M acroscopic F in d in g s 662535 T erm inal S a c rific e K i l l e d on Day : 24 E xposure Group : R ecovery A nim al i s sig n e d o f f from n e c ro p sy G ross P athology : No M a c r o s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in im a l. KIDNEYS : CYST, m in im a l. NOSE : DEGENERATION, TRIGEMINAL NERVE, m i l d . No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : LUNGS, PHARYNX/LARYNX, TESTES 662536 T erm inal S a c rific e K i l l e d on Day : 24 E xposure Group : R ecovery A nim al i s sig n e d o ff from n e c ro p sy G ross P athology : No M a c r o s c o p ic A b n o r m a li t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, m in i m a l . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, m in i m a l . No M i c r o s c o p ic A b n o r m a li t y O b s e r v e d : LUNGS, PHARYNX/LARYNX, TESTES, NOSE DuPont-8685 r\ - 154- Sanitteed. Dow not contain Company