Document YGK2pw5doM5kK3wG2ZD86NoKN

464 DuPont-l 1414 TRADE SECRET Study Title H-25134: Four-Week Inhalation Toxicity Study in Male Rats Test Guidelines: OECD Guideline for the Testing o f Chemicals Section 4: Health Effects, Number 412 (1981) Author: Linda A. Malley, Ph.D., D.A.B.T. Study Completed on: June 25, 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 Laboratory Project ID: DuPont-11414 Company Sanitized. Does not contain TSCA CBI Page 1 o f 206 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles o f Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17 and MAFF Japan Good Laboratory Practice Standards (59 NohSan No. 3850) except for the item documented below. The item listed does not impact the validity o f the study. The sponsor characterized the test substance. Although the characterization was not performed under Good Laboratory Practice Standards, both the validity and accuracy o f the analysis was considered acceptable and therefore sufficient for the purpose o f this study. Applicant / Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Director: Linda A. Malley, Fh.D,, D.A.B.T. Senior Research Toxicologist Date Applicant / Sponsor:______________________________________ __________ DuPont Representative Date Company Sanitized. Does not contain TSCA H-25134; Four-Week Inhalation Toxicity Study in Male Rats QUALITY ASSURANCE STATEMENT DuPont-11414 Haskell Sample Number(s): 25134 Dates o f Inspections: Protocol: September 20, 2002; October 7, 2002 Conduct: October 14,15,2002; November 1, 2002 Records, Reports: February 3,6,26-28,2003; March 20,21,24, 2003; April 7, 2003; May 27-30, 2003; June 1, 2003 Dates Findings Reported to: Study Director: September 20, 2002; October 15, 2002; November 3, 2002; March 5,25, 2003; April 7, 2003; June 2, 2003 Management: October 20, 2002; November 3, 2002; March 5,2003; April 7,29, 2003; May 9, 2003; June 9,2003 MatthewT. Fremzel, BS. Quality Assurance Auditor Company Sanitized. Does not contain TSCA CBI H-25134; Four-Week Inhalation Toxicity Study in Male Rats DuPont-1414 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Clinical Pathology Evaluation Reported by: NancyE- Everds, D.V.M Diploiriate A.C.VJ*. Principal Research Clinical Pathologist and Manager Anatomic Pathology Evaluation Reported by; Anatomic Pathology Evaluation Peer Reviewed by: John F, Hansen, D.V.M., PJi Diplomate A.C.V.P. Principal Research Pathologist '7Vt*K( Steven R Frame, D.V.M^ i.D Diplomate A.C.V.P. Date Date Date Approved fay: Supervisor Z 3 f -ZccB Date Issued by Study Director: landa A. Malley, Ph.D., D.AR.T. Senior Research Toxicologist Date Company Sanitized. Does not contain TSCA CBI -4 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT..................................... 2 QUALITY ASSURANCE STATEM ENT.........................................................................................3 CERTIFICATION....................................... 4 LIST OF TABLES..................................... .............. ............................................................................7 LIST OF FIGURES........................................ 8 LIST OF APPENDICES......................... 8 STUDY INFORMATION.....................................................................................................................9 STUDY PERSONNEL............. 10 SUM M ARY........................................................................................................................................... 11 INTRODUCTION............................. 13 STUDY DESIGN.................................................................................... 13 MATERIALS AND M ETHODS............................................................ 14 A. Test Guidelines.......................................................................................................................... 14 B. Test Substance.......................................................................... 14 C. Test Species................................................ 14 D. Animal Husbandry....................................................................................................................14 1. Animal Housing.......... ..................................................................................................................................14 2. Cage and Cage Rack Changes.......................................................................................................................14 3. Environmental Conditions............................................................................................................................. 14 4. Feed and W ater................. ........................................................................................................................... 15 5. Animal Health and Environmental Monitoring Program.......................... 15 E. Pretest Period.............................................. 15 F. Assignment to Groups................................................................................................................16 G. Inhalation Exposure System................................................................ 16 1. Atmosphere Generation................................................................................................................................16 2. Chamber Construction and Design............................................................................................................... 17 3. Exposure M ode............................................................................................................................................. 17 H. Characterization o f Chamber Atmosphere.............................................................................. 17 1. Test Substance Sampling and Analysis............. ...........................................................................................17 2. Particle Size Determination........................................................................................................................... 17 3. Environmental Monitoring........................................... 17 I. Body Weights and Clinical Observations.... ,.......................... ..............................................18 J. Food Consumption and Food Efficiency.................................................................................18 K. Clinical Pathology Evaluation.................................................................................................. 18 1. Hematology and Coagulation........... .................... S anitized. .D o esn o t -contain- T 3 d i i -5 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE OF CONTENTS (Continued) Page 2. Clinical Chemistry.............. 19 3. Urinalysis......................................................................................................................................................20 4. Recovery........................................................... 20 L. Blood Fluorine A nalysis...........................................................................................................20 M. Recovery Period................................. 21 N. Anatomic Pathology Evaluation.............................................................................................. 21 O. Statistical A nalyses................................................................................................................... 23 RESULTS AND DISCUSSION.........................................................................................................24 In-Life Animal Measurements............................................................. .............................................24 A. Chamber Concentrations o f the Test Substance .....................................................................24 B. Chamber Environmental Conditions........................................................... 24 C. Body Weights and Body Weight G ains.................................................................................. 25 D. Food Consumption and Food Efficiency................................................................................ 25 E. Post-Exposure Clinical Observations and Clinical Observations at the Time o f Body Weight Determinations............................................................ 25 Clinical Pathology E valuation........................................................................................................... 26 A. Hematology and Coagulation....................................................................................................26 B. Clinical Chem istry.....................................................................................................................26 C. Urinalysis....................................................................................................................................27 D. Plasma and Urine Fluoride......................................... 27 E. Conclusions.................................................................................................................................27 Blood Fluorine A nalysis......................................................................................................................27 A. Blood Fluorine A nalysis........................................................................................................... 27 Anatomic Pathology Evaluation............................................. 28 . A. Mortality................................................................................. 28 B. Organ W eights........................................................................................................................... 28 C. Gross Observations................................................................................................................... 29 D. Microscopic Findings..................................................... 29 E. Conclusions....................... 30 C O N C L U S IO N S ....................................................................................................................... 31 RECORDS AND SAMPLE STORAGE.............. i..........................................................................31 REFERENCES.................................. 32 TABLES................................................................................................................................................. 34 FIGURES................................................................................................................................................ 84 A P P E N D I C E S ...................................................................................... 89 Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 LIST OF TABLES Page 1. CHAMBER CONCENTRATIONS OF H-25134..................................................................................................... 38 2. PARTICLE SIZE DISTRIBUTION OF H-25134.......... 38 3. CHAMBER ENVIRONMENTAL CONDITIONS................................................................................................... 39 4. MEAN BODY WEIGHTS OF MALE RATS.......................... 40 5. MEAN BODY WEIGHT GAINS OF MALE RATS................................................................................................ 42 6. MEAN DAILY FOOD CONSUMPTION BY MALE RATS...................................................................................44 7. MEAN DAILY FOOD EFFICIENCY OF MALE RATS.........................................................................................45 8. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS PRIOR TO EXPOSURE..............................46 9. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS AFTER EXPOSURE...................................47 10. SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS.......................................................................... 48 11. SUMMARY OF COAGULATION VALUES FOR MALE RATS......................................................................... 50 12. SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE R A TS.......................................................... 51 13. SUMMARY OF URINALYSIS VALUES FOR MALE RATS........................... 54 14. SUMMARY OF BLOOD FLUORINE ANALYSIS........................................................ 55 15. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE.........................56 16. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE........................ 59 17. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE..................................... 62 18. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE..................................... 68 19. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE................................................................................................................................................... 74 20. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE................................................................................................................................................... 83 Company Sanitized. Does not contain TSCA CBl H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 LIST OF FIGURES Page 1. SCHEMATIC OF EXPOSURE SYSTEM................................................................................................................ 85 2. MEAN DAILY CHAMBER CONCENTRATIONS.............................................................................................. 86 3. MEAN BODY WEIGHTS OF MALE RATS.......................................................................................................... 87 4. MEAN BLOOD FLUORINE OF MALE RATS...................................................................................................... 88 LIST OF APPENDICES Page A. DAILY CHAMBER CONCENTRATIONS.............................................................................................................. 90 B. DAILY CHAMBER ENVIRONMENTAL CONDITIONS.................................................... 93 C. INDIVIDUAL BODY WEIGHTS.............................................................................................................................. 98 D. INDIVIDUAL FOOD CONSUMPTION..................................................................................................................103 E. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS................................................ 109 F. INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA................................................................................ 126 G. INDIVIDUAL ANIMAL BLOOD FLUORINE............................................ 154 H. INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS................................................................... 157 I. INDIVIDUAL ANIMAL PATHOLOGY DATA.................................................................................................... 166 Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats STUDY INFORMATION Substance Tested: Svnonvms/Codes: DuPont-11414 Submitter's Notebook Humbert's): Haskell Number: 25134 CAS Registry Number: Composition: Known Impurities: Physical Characteristics: Dark brown solid Stability: The test substance appeared to be stable under the conditions o f the study; no evidence o f instability was observed. Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: October 4,2002 / (see report cover page) Company Sanitized. Does not contain TSCA CBI -9 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 STUDY PERSONNEL Study Director: Linda A. Malley, Ph.D., D.A.B.T. 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. Anatomic Pathologist: John F. Hansen, D.V.M., Ph.D. Management: Steven R. Frame, D.V.M., Ph.D. Peer Review Anatomic Pathologist: Steven R. Frame, D.V.M., Ph.D. Blood Fluorine Data Analysis: Vladimir Capka, Ph.D. Management: S. Mark Kennedy, Ph.D. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: Thomas W. Mayer, D.V.M., A.C.L.A.M. Company Sanitized. Does n o t contain TSCA CB| H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 SUMMARY The purpose o f this study was to assess the potential subchronic toxicity o f exposure to H-25134 in adult male rats. Young adult male Crl:CD(IGS)BR rats (15 rats/exposure concentration) were exposed to atmosphere containing 0, 5, 30, or 100 mg/m3 H-25134 for 6 horns per day, over a 4-week period for a total of 20 exposures. Body weight and food consumption were determined weekly and clinical signs o f toxicity were monitored throughout the study. Blood samples were collected on test days 0, 7, 14, 25, and 54 for analysis of fluorine concentration. Blood samples and urine samples were collected at the end o f the exposure period from 10 rats/concentration for evaluation o f clinical pathology and urinalysis parameters. After the last exposure, 10 rats/concentration underwent gross necropsy. Selected tissues were processed for histopathology and examined. Additional blood samples were collected for future analysis of perfluorooctanoic acid (PFOA) concentration. At the end o f an approximately one-month recovery period, blood samples and urine samples were collected from all surviving rats for evaluation o f selected clinical pathology and urinalysis parameters, and fluorine concentration. All surviving rats underwent gross necropsy, selected tissues were processed for histopathology, and were examined by light microscopy. Test substance-related, statistically significant decreases in body weight gain and food efficiency occurred in rats exposed to 30 or 100 mg/m3. Although slightly decreased body weight gain for rats exposed to 5 mg/m3 also appeared to be test substance-related, it was not considered to be adverse since the mean body weights were only 4.3% lower than the control value. Unscheduled mortality did not occur during the study. Incidences of clinical signs following exposure and at the time o f body weight determination were similar for all groups. Cholesterol concentration was mildly decreased in males exposed to 100 mg/m3at test day 25; these changes were considered to be potentially adverse. After 31 days o f recovery, cholesterol concentrations for all test groups were similar to control. Triglycerides were mildly decreased in males exposed to 5, 30, or 100 mg/m3. Although these changes showed a flat concentrationresponse, they were considered to be test substance-related. However, the mildly decreased concentrations were not associated with histological changes, and therefore, they were not considered to be adverse. After 31 days o f recovery, the triglyceride concentrations for all test groups were similar to the control values. Blood fluorine (but not plasma fluoride) concentration was slightly increased above background concentration in rats exposed to 30 or 100 mg/m3. Urine fluoride was also increased in rats exposed to 30 or 100 mg/m3. At the end o f the onemonth recovery period, blood fluorine concentrations and urine fluoride amounts were similar to control. There were no other treatment-related changes in clinical pathology parameters for any test group. Statistically significant changes in organ weight and relative organ weight (relative to body weight or brain weight) that were secondary to decreased body weight occurred in the heart and testes. Squamous metaplasia/hyperplasia o f the ventral laryngeal mucosa was observed in rats exposed to 5, 30, or 100 mg/m3at the sacrifice on test day 25. The lesion was minimal, focal, and not concentration-related with respect to incidence or severity. Squamous metaplasia of the -11 C o m p ly Sar't'^ed. Doss not contain TSCA CBi / " '"'N H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 ventral larynx o f rats is a common, nonspecific response to irritants and is generally considered an adaptive response. This lesion was not present in animals sacrificed after a one-month recovery. The no-observed-effect level (NOEL) for this study is defined as the highest concentration at which toxicologically important effects attributable to the test substance were not detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985), and the no-observed-adverse effect level (NOAEL) as defined by the European Union (1994). Under the conditions o f the study, the NOEL was 5 mg/m3based on decreased body weight gain at 30 mg/m3and above. The minimal morphological changes in the larynx observed at all exposure concentrations were considered to be a nonspecific, adaptive response and is o f equivocal toxicological significance. Company Sanife8d Doos not contain t$Ca cbi - 12- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 INTRODUCTION The test substance contains an organofluoride melt additive and is used as a protectant for textiles. The exposure concentrations of the test substance were selected on the basis of range finding exposures and a knowledge about the physical and chemical properties of the test substance. In a one-week range-finding study, groups o f 5 male rats were exposed to 0, 5, 30, or 100 mg/m3 H-25134 for 6 hours per day for 5 consecutive days. There were no test substance-related effects on clinical signs or body weight for any exposure concentration. The 4-hour approximate lethal concentration (ALC) was determined to be 377 mg/m3.(1) Based on these data, the exposure concentrations for the main study were selected to be 0, 5, 30, and 100 mg/m3. The objective o f this study was to evaluate the subchronic toxicity of H-25134 when administered by inhalation to male Crl:CD(SD)IGS BR rats over a 4-week period. An airexposed group o f male rats served as the negative control. The inhalation route o f exposure was chosen because it is the potential route for human exposure. STUDY DESIGN Four groups o f male rats (15 rats each) were exposed to concentrations o f H -25134 targeted to 0, 5, 30, or 100 mg/m3. The first 10 rats per group were designated for subchronic toxicity, and the remaining rats per group were designated for blood fluorine analysis and recovery. Rats were exposed nose-only for 6 hours per day for a total o f 20 exposures (excluding weekends). Throughout the exposure period, blood was collected weekly from the rats designated for blood fluorine analysis. At the end of the exposure period, blood and urine samples were collected for clinical analyses, and 10 rats per group were sacrificed for pathology examination. All remaining rats were allowed to recover for approximately a 4-week period. At the end o f the recovery period, all surviving rats were bled for blood fluorine analysis and sacrificed for pathology examination. All rats were weighed weekly during the exposure phase o f the study. At every weighing, each rat was individually handled and examined for abnormal behavior and appearance. During the daily exposures, rats were checked for viability. Immediately following each exposure, each rat was individually handled and examined for abnormal behavior and appearance. The amount of food consumed by each rat was determined weekly'during the exposure phase o f the study. Surviving rats were weighed and individually observed for clinical signs o f toxicity throughout the recovery period. - 13 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats MATERIALS AND METHODS DuPont-11414 A. Test Guidelines The study design complies with the following test guidelines: Organisation for Economic Co-Operation and Development (OECD) (1981). 412 Repeated Dose Inhalation Toxicity: 28-Day or 14-Day Study. Guidelinefo r Testing o f Chemicals. B. Test Substance The test substance, H-25134, was supplied by the sponsor as a dark brown solid. Purity was not supplied by the sponsor. The test substance was assumed to be stable throughout the exposure phase o f the study; no evidence o f instability was observed. C. Test Species A total o f 66 male Crl:CD(SD)IGS BR rats was received from Charles River Laboratories, Inc., Raleigh, North Carolina. The male rats were approximately 5 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. D. Animal Husbandry 1. Animal Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 2. Cage and Cage Rack Changes Cages and cage racks were changed at least every other week. 3. Environmental Conditions Rats were housed in one room in proximity to the inhalation chambers. Animal rooms were targeted at a temperature of 23 1C and a relative humidity o f 50 10%. Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/ dark cycle. Excursions outside of these ranges on 2 occasions were of insufficient magnitude and/or duration to have adversely affected the validity o f the study. - 14- /"n H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 4. Feed and Water Except dining exposures, PMI Nutrition International, LLC Certified Rodent LabDiet 5002 and tap water were available ad libitum. During the urine collection period, rats were fasted overnight for approximately 16 hours; water, however, was available ad libitum. 5. Animal Health and Environmental 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 o f the study: Water samples are analyzed for total bacterial counts, and the presence o f coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore, and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations 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 o f the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation o f these data did not indicate any conditions that affected the validity o f the study. E. Pretest Period Upon arrival at Haskell Laboratory, all rats were housed 1 per cage in quarantine. The rats were: quarantined for 6 days. identified temporarily by cage identification. weighed 3 times during quarantine and once prior to initiation o f exposures. observed with respect to weight gain and any gross signs o f disease or injury. The rats were released from quarantine by the laboratory animal veterinarian or designee on the basis o f body weights and clinical signs. -15- ComPany Sar}itfeerfi 0065 con,ainrscA c Bl H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 F. Assignment to Groups Rats were selected for use on study on the bases of adequate body weight gain and freedom from any clinical signs o f disease or injury. They were distributed by computerized, stratified randomization into study groups as designated in the Study Design, so that there were no statistically significant differences among group body weight means. The weight variation of selected rats did not exceed 20% o f the mean weight. The first 10 rats in each group were designated for subchronic toxicity, and the remaining rats in each group were designated for blood fluorine analysis and recovery. After assignment to groups, each rat was housed individually. Each rat was assigned a unique 6-digit Haskell animal number and an individual cage identification number. After assignment to groups, the cage identification number was tattooed on the tail of each rat. The Haskell animal number and cage identification number were both included on the cage label. At study start (test day 0), male rats were approximately 7 weeks o f age and weighed between 245 and 306 grams. On test day 0, when possible, rats with body weights that are not within 20% of the mean were removed from study and replaced with rats having body weights within that range (subject to the same selection criteria as the original rats). Rats that were not assigned to a test group or which were removed from study on test day 0, for out-of-range body weights, were released for other laboratory purposes or sacrificed by carbon dioxide asphyxiation and discarded without pathology evaluation, at the discretion of the study director. G. Inhalation Exposure System (Figure 1) 1. Atmosphere Generation Chamber atmospheres were generated by heating the test substance in a glass 250, 500, or 1000 mL, three-necked flask. The test substance was stirred constantly during heating using stir rods attached to FMI pumps. The flasks were heated to 280C using either a 500 or 1000 mL heating mantel. A measured amount o f the test substance was added to the flask prior to heating. Houseline-air was metered into the flask with a Brooks Flowmeter. The resulting particulate stream exiting the flask was split between the inhalation chamber and a collection flask that removed excess test material from the air stream. The particulate stream was further mixed with dilution air, controlled by a Brooks Mass Flow Controller, at the top o f the inhalation chamber. A stainless steel baffle was used to ensure a homogeneous distribution of the particulate stream through the chamber. Tubing between the generation flask and the chamber was heated by heat tape controlled with a Variac voltage controller. Vacuum pumps controlled the exhaust and the amount of air that was split from the generation stream to the collection flask. The heating mantel and mass flow controllers were controlled and monitored by the Camile Inhalation Toxicology Automated Data System (CITADS). Since the test material was a solid, waxy material prior to heating, the heating mantels and stirring rods were turned on prior to placing the Company Sanitized. Po* not C3r)tafn TSc>iCBf - 16- / " " ''N /***n H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 restrainers containing the rats in the chamber portholes. When the heating mantel reached the target temperature, the rats were placed in the portholes, and the daily exposure was initiated. The animals were exposed for 6 hours after being placed into the portholes. After 6 hours, the heating mantels and stirrers were turned off, and the rats were removed from the chambers. 2. Chamber Construction and Design All exposure chambers were constructed o f stainless steel and glass (NYU style) with a nominal internal volume o f 150 L. A baffle inside the chamber 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 and stainless steel faceplate which was attached to the exposure chamber so that the nose o f each animal extended into the exposure chamber. Approximately 1 week 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. H. Characterization of Chamber Atmosphere 1. Test Substance Sampling and Analysis The concentration o f H-25134 in each chamber was determined by gravimetric analysis at approximately 60-minute intervals during each exposure, except for the control chamber, which was not sampled. Known volumes of chamber atmosphere were drawn from the sampling port 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-33 Microbalance. The filter weights were automatically transferred to the CITADS, which calculated the chamber concentrations based on the difference in pre- and post-sampling filter weights divided by the volume o f chamber atmosphere sampled. Gravimetric sample start- and stop-times for each sample were also controlled and recorded by CITADS. 2. Particle Size Determination A sample to determine particle size distribution (mass median aerodynamic diameter and percent particles less than 1,3, and 10 pm diameter) was taken from each test chambers once per week with a Sierra Series 210 Cyclone Preseparator/Cascade Impactor and Sierra Series 110 Constant Flow Air Sampler.(2) 3. Environmental Monitoring Chamber airflow was set at the beginning o f each exposure to achieve at least 12 air changes per hour and was monitored continually with a calibrated Brooks model 5851E Mass Flow Controller. Chamber temperature was targeted at 22 3C and was measured with an Omega - 17- Comp*ny Sanitised. Doe? net cy ia:n H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 thermocouple. Chamber relative humidity was targeted at 50 20% and was measured with Jumo model PT100 wet-bulb/dry-bulb resistance temperature detectors. Airflow, temperature, and relative humidity were monitored continually with CHADS and recorded at 15-minute intervals during each exposure. 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 twice during each exposure. I. Body Weights and Clinical Observations All rats were weighed once a week. At every weighing, each rat was individually handled and examined for abnormal behavior and appearance. After loading the animals into the restrainers, and placing the restrainers into the chambers, rats were checked for viability prior to each exposure, 2 to 3 times during the exposure, and at the end of the exposure, prior to removing them from the chamber portholes. Each rat was individually handled and examined for abnormal behavior and appearance when it was removed from the chamber at the end o f the daily exposure period. Fur stains and hair loss associated with restraint and deposition of the test substance were not recorded for individual rats following the daily exposures. Cage-site examinations to detect moribund or dead rats and abnormal behavior and appearance among rats were conducted prior to loading the animals into the chamber on exposure days, and at least once daily on non-exposure days. J. Food Consumption and Food Efficiency The amount of food consumed by each animal over each weighing interval was determined by weighing each feeder at the beginning and end of the interval and subtracting the final weight and the amount o f spillage from the feeder during the interval from the initial weight. From these measurements, mean daily food consumption over the interval was determined. From the food consumption and body weight data, the mean daily food efficiency were calculated. Food consumption and food efficiency were not determined during the recovery phase. K. Clinical Pathology Evaluation A clinical pathology evaluation was conducted on, the first 10 rats/group approximately 25 days after initiation o f the study. The day before collection o f 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 coagulation parameters 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 - 18- Comoanv Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 vena cava was divided into 2 aliquots. One aliquot was processed to plasma for analysis of plasma fluoride. The second aliquot was processed to plasma and frozen at -20C for future analysis of PFOA). Additional blood was placed in a serum tube, processed to serum, and stored at -80C for possible future analysis. Bone marrow smears were prepared at the sacrifice from all surviving animals. Bone marrow smears were stained with W right's stain, but analysis was not necessary to support experimental findings. 1. Hematology and Coagulation 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 o f 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. Coagulation times were determined on a Sysmex CA-1000 Coagulation Analyzer. The following hematology and coagulation 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 prothrombin time activated partial thromboplastin time 2. Clinical Chemistry Serum clinical chemistry parameters were determined on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer. Plasma fluoride was 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 total protein albumin , globulin calcium inorganic phosphorus sodium potassium chloride Comp"* Saw tSCA CB* - 19- H-25134: Four-Week Inhalation Toxicity Study in Male Rats triglycerides glucose fluoridea DuPont-11414 3. Urinalysis Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, respectively. Urine constituents were semi-quantitatively measured on a Bayer Clinitek AtlasTM Automated Urine Chemistry analyzer. Urine protein was measured on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer. Urine osmolality was determined using an Advanced Osmometer 3900. Urine fluoride was determined using a phi 12 pH meter and a fluoride-selective electrode. Sediments from all urine specimens were evaluated microscopically. The following urinalysis parameters were determined: quality color clarity volume osmolality pH glucose ketone bilirubin blood urobilinogen fluorideb protein microscopic urine sediment examination 4. Recovery Near the end o f the recovery period blood and urine samples were collected from all surviving rats according to the procedures described above. The following parameters were evaluated according to the methods detailed above: cholesterol, triglycerides, total protein, albumin, globulin, and urine fluoride. L. Blood Fluorine Analysis On test days 0, 7, 14, 21, 25, and 54, blood (approximately 0.5 mL) was collected from the orbital sinus o f designated animals (5 rats/concentration), while the animals were under light carbon dioxide anesthesia, for total blood fluorine analysis. On the day o f blood collection, blood was collected from the animals approximately 1 hour after the daily exposure. The blood was collected in plastic tubes containing EDTA while on ice and stored frozen. The total fluorine content of the blood samples was determined on selected blood samples using a Wickbold torch combustion method, followed by analysis with a fluoride ion selective electrode. The liquid blood was decomposed or volatilized in the presence o f wet oxygen and swept through an 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 a Fluoride determination was analyzed on EDTA plasma, b Fluoride determination was analyzed from urine with EDTA added. Company Sanitized. Doss not contain TSCA H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 electrode. Rationale for the number of blood samples analyzed was documented in study records. M. Recovery Period At the conclusion of the 4-week exposure period, the 5 rats per concentration designated for blood fluorine analysis were allowed to recover for approximately 1 month. During the recovery period, exposures were not conducted; however, body weights were collected weekly. At every weighing, each rat was individually handled and examined for abnormal behavior and appearance. Cage-site examinations to detect moribund or dead rats and abnormal behavior and appearance among rats were conducted once daily. As described in section L. above, blood samples for blood fluorine analysis were collected at the end o f the recovery period (test day 54). N. Anatomic Pathology Evaluation Ten animals per group were sacrificed and necropsied following the last exposure (initial sacrifice animals). The other 5 animals per group were allowed to recover (recovery animals) for approximately 4 weeks and were then sacrificed and necropsied. Rats were euthanatized by carbon dioxide anesthesia and exsanguination. Gross examinations were performed on all rats. -21 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 The following tissues were collected from rats that were found dead or sacrificed by design. Digestive System liver esophagus stomach duodenum jejunum ileum cecum colon rectum salivary glands pancreas Urinarv Svstem kidneys urinary bladder Cardiovascular Svstem heart aorta Hematopoietic Svstem spleen thymus mandibular lymph node mesenteric lymph node bone marrow3 Endocrine Svstem pituitary gland thyroid gland parathyroid glands adrenal glands Musculoskeletal Svstem skeletal muscle femur/knee joint sternum Renroductive Svstem testes epididymides prostate seminal vesicles Miscellaneous skin eyes (including optic nerve) gross observationsb Resniratorv Svstem lungs trachea nose (4 cross sections) larynx pharynx Nervous Svstem brain (including cerebmm, cerebellum, medulla/pons) spinal cord (cervical, mid-thoracic, lumbar) sciatic nerve a Bone marrow was collected with the femur and sternum. b Gross observations made at necropsy for which histopathology is not appropriate (e.g., fluid, ruffled fur, and missing anatomic parts) will generally not be collected. The liver, kidneys, lungs, heart, spleen, brain, thymus, adrenal glands, testes and epididymides were weighed at necropsy, and organ weight/fmal 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. 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. All collected tissues from rats sacrificed at the end of the exposure period from control and high concentration groups were processed and received a full histopathological examination. The pharynx/larynx was identified as a target tissue by histopathology, and was processed from the low and intermediate group initial sacrifice animals and from the control and high exposure group recovery animals. H-25134; Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 The key to the pathology lesion grading system used in this study can be found within the pathology tables and appendices. O. Statistical Analyses Significance was judged at p < 0.05. Parameter Exposure Concentration Data Environmental Data Blood Fluorine Analysis Body Weight Body Weight Gain Food Consumption Food Efficiency Organ Weight Incidence of Clinical Observations Clinical Pathologyd Preliminary Test Method of Statistical Analysis If preliminary test is not If preliminary test is significant significant None Descriptive statistics (e.g., mean, standard deviation) Test for lack of trend'3' Levene's test for homogeneity'6' and Shapiro-Wilk test'7' for normalityb None Levene's test for homogeneity<6) and Shapiro-Wilk test(7) for normalityb Sequential application'4' of the Jonckheere-Terpstra trend test(5) Preliminary tests for pairwise comparison ORa One-way analysis of variance'8' followed with Dunnett's test'9' Kruskal-Wallis test'10' followed with Dunn's test"1' Cochran-Armitage test for trend'8'0 One-way analysis of variance'8' followed with Dunnett's test'9' Kruskal-Wallis test'10' followed with Dunn's test'1" a Pairwise comparisons and associated preliminary tests are only conducted if the test for lack of trend is significant. b If the Shapiro-Wilk test is not significant but Levene's test is significant, a robust version of Dunnett's test will be used. If the Shapiro-Wilk test is significant, Kruskal-Wallis test is followed by Dunn's test, c If the incidence is not significant, but a significant lack of fit occurs, then Fisher's Exact test(12) with a Bonferroni correction is used. d When an individual observation is recorded as being less than a certain value, calculations are performed on half the recorded value. For example, if bilirubin is reported as <0.1, 0.05 is used for any calculations performed with that bilirubin data. n<*con* t s c a c b i Comp0* Satfizd. 0* -23 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 RESULTS AND DISCUSSION In-Life Animal Measurements A. Chamber Concentrations of the Test Substance (Tables 1-2, Figure 2, Appendix A) The mean concentrations standard error of the mean for the gravimetric samples over the 20 exposures were 5.1 0 .1 9 , 31 0.93, and 100 2.4 mg/m3 in chambers targeted at 5, 30, and 100 mg/m3, respectively. Daily mean concentrations ranged from 74-138% o f the nominal concentration for the 5 mg/m3group. Daily mean concentrations ranged from 67-123% of the nominal concentration for the 30 mg/m3group. Daily mean concentrations ranged from 66120% of the nominal concentration for the 100 mg/m3group. Although the mean daily chamber concentrations were occasionally less than 90% o f the nominal concentrations, the mean concentrations for each week were consistent (Figure 2), and were acceptable for evaluating the toxicity at the targeted concentrations. The mass median aerodynamic diameter (MMAD) ranged from 3.0-3.8 pm for the 5 mg/m3 group, 4.7-5.2 pm for the 30 mg/m3group, and 3.9-4.5 pm for the 100 mg/m3group. The geometric standard deviation (GSD) ranged from 1.5 to 1.6 for the 5 mg/m3group, 1.7-2.0 for the 30 mg/m3group, and 1.4-3.1 for the 100 mg/m3 group. In the 5 mg/m3group, 0.2-0.4% o f the particles were less than 1 pm, 32-50% o f the particles were less than 3 pm, and 98-100% o f the particles were less than 10 pm. In the 30 mg/m3group, 0.1-0.2% o f the particles were less than 1 pm, 20-32% of the particles were less than 3 pm, and 93-100% of the particles were less than 10 pm. In the 100 mg/m3 group, <1-7% o f the particles were less than 1 pm, 10-70% o f the particles were less than 3 pm, and 99-100% o f the particles were less than 10 pm. These data indicate that the generation system provided particles that were in the respirable range for rats. Nominal concentrations of the test substance were not calculated since a portion of the air stream containing the test substance was diverted to a water scrubber. B. Chamber Environmental Conditions (Table 3, Appendix B) The overall mean chamber temperatures in the 4 exposure chambers during the 20 exposures were 21-25C. The temperature range o f the daily means for all 4 chambers was 19-25C. Although the chamber temperatures slightly exceeded the targeted range o f 22-24C, the slightly lower and higher temperatures did not adversely affect the health of the animals, based on their clinical appearance. Company Sanitized. Does not contain TSCA CBI - 24- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 The overall mean relative humidity in the 4 exposure chambers during the 20 exposures was 3765%. The humidity range of daily means for all 4 chambers was 33-74%. The slightly higher humidity values did not adversely affect the health o f the animals, based on their clinical appearance. The overall mean chamber airflow in the 4 exposure chambers during the 20 exposures was 3550 L/min. The airflow in the chamber was adequate to achieve at least 12 air changes per hour. C. Body Weights and Body Weight Gains (Tables 4-5, Figure 3, Appendix C) A non-linear decrease in body weight gain was observed males exposed to 5, 30 or 100 mg/m3, however, the mean values were only statistically significant for the 30 and 100 mg/m3 concentrations for test days 7-21 and over the interval o f test days 0-25. Mean body weight values were slightly (not statistically) lower than the control values by test day 25. The lower body weight gain was correlated with slightly lower (not statistically significant) food consumption and significantly lower food efficiency values for males exposed to 30 or 100 mg/m3. In addition, during the recovery period, the body weight gain values were similar to controls. Although a clear concentration-response relationship is not evident, when the lower body weight gain for the rats exposed to 30, and 100 mg/m3 is considered together with the food consumption, food efficiency, and the recovery of these parameters during the recovery period, the decreased body weight gain appears to be test substance-related and is considered to be adverse for rats exposed to 30 or 100 mg/m3. D. Food Consumption and Food Efficiency (Tables 6-7, Appendix D) Food consumption was slightly (not statistically significant) lower in males exposed to 30 or 100 mg/m3compared to the control value. In addition, food efficiency was significantly lower for rats exposed to 30 or 100 mg/m3during test days 14-21, and over the interval o f test days 021. These observations correlate with the lower body weight and weight gain values observed in these groups, and were considered to be test substance-related and adverse. There were no statistically significant changes in food consumption or food efficiency observed in males exposed to 5 mg/m3. E. Post-Exposure Clinical Observations and Clinical Observations at the Time of Body Weight Determinations (Tables 8-9, Appendix E) Post-exposure Observations There were no adverse or test substance-related clinical signs o f toxicity observed in any exposure group following the daily exposure periods. The incidences of discharge from the eye/nose were similar among all exposure groups and are commonly observed in rats restrained - 25 Company Sanitized. Does not contain TSCA CBI il H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 in nose-only inhalation exposure systems. Clinical signs o f hair loss due to the restrainers, and fur/skin stains associated with urination and defecation during exposure were not recorded for post-exposure observations. Clinical Observations at the Time o f Body Weight Determination There were no adverse or test substance-related clinical signs of toxicity observed in any exposure group at the time o f body weight determination. All clinical signs observed were common in this strain o f rat. Clinical Pathology Evaluation A. Hematology and Coagulation (Table 10-11, Appendix F) There were no treatment-related or statistically significant changes in hematologic parameters in rats exposed to H-25134. B. Clinical Chemistry (Table 12, Appendix F) Cholesterol concentration was mildly decreased in males exposed to 100 mg/m3 at test day 25. Mean cholesterol concentration (33 mg/dL) in this group was 69% of the control group mean (48 mg/dL). Cholesterol concentration was also minimally decreased (change in mean not statistically significant) in some males exposed to 5 or 30 mg/m3. Decreased cholesterol was considered to be potentially adverse at 100 mg/m3, due to the magnitude o f the change. After 31 days o f recovery, cholesterol concentrations o f rats previously exposed to H-25134 were similar to control group values. There were no other adverse changes in clinical chemistry parameters in male rats exposed to H-25134. 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: Triglycerides were mildly decreased in males exposed to 5, 30, or 100 mg/m3 (statistically significant only in males exposed to 5 or 30 mg/m3). Although these changes showed a flat concentration response (55, 64, and 75% o f control group mean, respectively), they were considered to be treatment-related due to the consistency o f the response. However, the changes were not considered to be adverse, because mildly decreased triglycerides concentrations are not associated with adverse effects. After 31 days o f recovery, triglyceride concentrations o f rats previously exposed to H-25134 were similar to control group values. - 26- Company Sanitized. Does not contain TS C A CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 The following statistically significant changes in clinical chemistry parameters were considered to be unrelated to exposure to the test compound because there was no concentration-response relationship. Minimally decreased inorganic phosphorus in males exposed to 30 mg/m3 Minimally increased chloride in males exposed to 5 mg/m3 C. Urinalysis (Table 13, Appendix F) There were no treatment-related changes in urine volume. D. Plasma and Urine Fluoride (Tables 12-13, Appendix F) Exposure to H-25134 caused increased mean urine fluoride in males exposed to 30 or 100 mg/m3 (statistically significant only at 100 mg/m3). Increased mean urine fluoride indicates exposure to and metabolism of a fluoride-containing molecule, and is considered to be non-adverse in isolation. After 31 days of recovery, urine fluorides were similar in all groups, including controls. E. Conclusions In conclusion, exposure o f male rats to 100 mg/m3H-25134 resulted in potentially adverse mild decreases in serum cholesterol. Treatment related but non-adverse changes included mildly decreased serum triglycerides in male rats exposed to 5, 30, or 100 mg/m3, and increased urine fluoride in males exposed to 30 or 100 mg/m3. After 31 days o f recovery, serum cholesterol, serum triglycerides, and urine fluoride of rats previously exposed to H-25134 were similar to control group values. Therefore, under the conditions o f this study and for the clinical pathology parameters measured, the no-adverse-effect level for male rats was 30 mg/m3H-25134, the highest exposure in this study. Blood Fluorine Analysis A. Blood Fluorine Analysis (Table 14, Appendix G) Blood fluorine concentration was slightly increased above background concentration in rats exposed to 30 mg/m3 on test day 25, and in rats exposed to 100 mg/m3on test days 7, 14, and 25. 2 7 - ^*npany S enitteed. D o es not co n tain TS CA Cg j H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 However, on test day 54, following approximately a one-month recovery period, blood fluorine concentrations in rats exposed to 5, 30, or 100 mg/m3were similar to the control value. The test substance contains fluorine in the chemical structure, and the increase in blood fluorine concentration is considered to be a marker o f exposure, and was not considered to be adverse. Anatomic Pathology Evaluation A. Mortality There were no test substance-related deaths in this study. B. Organ Weights (Tables 15-16, Appendix H) Absolute and relative to brain mean heart weights were significantly lower than the control in the 30 and 100 mg/m3groups at the initial sacrifice. There were no test substance-related gross or microscopic effects in the heart. This weight change was attributed to lower mean final body weights in these groups. Absolute and relative to brain mean thymus weights were significantly higher than the control in the 100 mg/m3 group, and the relative to body mean thymic weights were significantly higher than the control in all test exposure groups at the initial sacrifice. The relative (to body and to brain) and absolute mean weights o f the thymus were lower than controls in the 30 and 100 mg/m3 groups at the recovery sacrifice. There were no test substance-related gross or microscopic effects in the thymus at either time point, and there was no clear concentration relationship in the weight effect. Thus, this fluctuation of thymus weight (higher at the initial sacrifice and then lower at the recovery sacrifice) was considered to be spurious. The relative to body mean testes weights were significantly higher than the control in all test exposure groups at the initial sacrifice and were attributed to lower mean final body weights in these groups. The relative to body mean adrenal weight was significantly higher (statistically) than control in the 100 mg/m3group at the initial sacrifice. The higher mean adrenal weight was primarily due to an unusually high weight (0.112 g) in one animal (664860). Thus, higher relative to body mean adrenal weight in the 100 mg/m3males was considered to be spurious. The absolute and relative to brain, mean adrenal weights in 100 mg/m3animals and the mean relative to body, adrenal weights in the 30 and 100 mg/m3groups were significantly higher than the control at the recovery sacrifice. There were no gross or microscopic test substance effects in the adrenal gland at either sacrifice and the magnitude o f the weight differences were small. The adrenal gland, as do other organs, would be expected to increase slightly in weight as young animals grow and increase in body weight. In comparing organ weights from control animals in the initial and recovery sacrifices this is indeed the fact, except for the adrenal gland, which actually had a - 2 8 - Company sanitized. Does not contain 1S u A VBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 lower mean absolute weight in recovery controls than in the younger initial sacrifice controls (0.055g VS 0.05 lg). Thus, the statistically significant adrenal weight changes in 30 mg/m3and in 100 mg/m3recovery animals were considered to be spurious and not test substance related or biologically important. The relative to body, mean kidney weight was significantly higher in 100 mg/m3 animals at the recovery sacrifice. The magnitude of the change was extremely miniscule and there were no test substance-effects in the kidney. Thus, this weight change was considered to be spurious. There were no other significant organ weight changes at either time point. C. Gross Observations (Tables 17-18, Appendix I) Gross observations noted were sporadic across groups and were not test substance-related. D. Microscopic Findings (Tables 19-20, Appendix I) Squamous metaplasia/hyperplasia of the ventral pharyngeal mucosa was observed at all exposure concentrations of H -25134 in initial sacrifice animals and was considered test substance-related. This lesion was limited in location to a very small and specific portion o f the ventral epiglottis and was extremely minimal in its extent and severity. The specific location o f the lesion was not always present in the slides examined, which accounts for the apparent lower incidence o f this lesion in the highest exposure group. There was no apparent concentration response across exposure groups, either in incidence or severity, indicating that all exposure concentrations were above the irritant threshold for this substance. This lesion was not present in recovery animals, indicating reversibility o f the lesion. Squamous metaplasia o f the ventral laryngeal mucosa in rats is a common, nonspecific response to irritants and represents replacement of normal pseudostratified epithelium with squamous epithelium. This squamous epithelium is indistinguishable from that which normally lines other areas of larynx. Squamous metaplasia o f the larynx occurring absent more severe changes, such as keratinization or ulceration, is generally considered an adaptive response where one epithelial type is replaced by a more resistant one.(13,14,15:) In the present study, squamous metaplasia was minimal and focal, reversible, and not associated with other histological changes. Therefore, these changes can be regarded as adaptive and o f equivocal toxicological significance. Other microscopic observations noted are known to occur spontaneously in rats o f this strain and age and were not present in a concentration response fashion in either incidence or severity. - 29- Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 E. Conclusions There were no compound-related mortality, organ weight, or gross findings in rats exposed to H-25134. The NOEL for anatomic pathology was 100 mg/m3. The minimal microscopic squamous metaplasia/hyperplasia o f the pharyngeal mucosa at all exposure levels represents a common adaptive response to an irritant exposure and is of equivocal toxicological significance. Laryngeal squamous metaplasias was not present in recovery animals indicating reversibility of the lesion. Company Sanitized!. Does not contain TSCA CBI - 30- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 CONCLUSIONS Test substance-related, statistically significant decreases in body weight gain and food efficiency occurred in rats exposed to 30 or 100 mg/m3. Although slightly decreased body weight gain for rats exposed to 5 mg/m3also appeared to be test substance-related, it was not considered to be adverse since the mean body weights were only 4.3% lower than the control value. Unscheduled mortality did not occur during the study. Incidences o f clinical signs following exposure and at the time o f body weight determination were similar for all groups. Cholesterol concentration was mildly decreased in males exposed to 100 mg/m3at test day 25; these changes were considered to be potentially adverse. After 31 days of recovery, cholesterol concentrations for all test groups were similar to control. Triglycerides were mildly decreased in males exposed to 5, 30, or 100 mg/m3. Although these changes showed a flat concentrationresponse, they were considered to be test substance-related. However, the mildly decreased concentrations were not associated with histological changes, and therefore, they were not considered to be adverse. After 31 days of recovery, the triglyceride concentrations for all test groups were similar to the control values. Blood fluorine (but not plasma fluoride) concentration was slightly increased above background concentration in rats exposed to 30 or 100 mg/m3. Urine fluoride was also increased in rats exposed to 30 or 100 mg/m3. At the end o f the onemonth recovery period, blood fluorine concentrations and urine fluoride amounts were similar to control. There were no other treatment-related changes in clinical pathology parameters for any test group. Statistically significant changes in organ weight and relative organ weight (relative to body weight or brain weight) that were secondary to decreased body weight occurred in the heart and testes. Squamous metaplasia/hyperplasia o f the ventral laryngeal mucosa was observed in rats exposed to 5, 30, or 100 mg/m3at the sacrifice on test day 25. The lesion was minimal, focal, and not concentration-related with respect to incidence or severity. Squamous metaplasia of the ventral larynx of rats is a common, nonspecific response to irritants and is generally considered an adaptive response. This lesion was not present in animals sacrificed after a one-month recovery. The no-observed-effect level (NOEL) for this study is defined as the highest concentration at which toxicologically important effects attributable to the test substance were not detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985), and the no-observed-adverse effect level (NOAEL) as defined by the European Union (1994). Under the conditions o f the study, the NOEL was 5 mg/m3based on decreased body weight gain at 30 mg/m3and above. The minimal morphological changes in the larynx obsertved at all exposure concentrations were considered to be a nonspecific, adaptive response and is o f equivocal toxicological significance. -31 - D o not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 RECORDS AND SAMPLE STORAGE All data and records for analytical characterizations conducted by the sponsor will be retained by the sponsor. Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done. A sample of the test substance will be 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. REFERENCES 2. Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual: Series 210 Ambient Cascade Impactors and Cyclone Preseparators. 3. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 4. 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. 5. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41, 133-145. 6. Levene, H. (1960). Robust test for equality o f variances. Contributions to Probability and Statistics (J. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. 7. Shapiro, S.S. and Wilk., M.B. (1965). An analysis o f variance test for normality (complete samples). Biometrika 52, 591-611. 8. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 246-248 and 349-352. The Iowa State University Press, Iowa. 9. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50,1096-1121. 10. Kruskal, W.H. and Wallis, W.A. (1952). Use o f ranks in one-criterion analysis o f variance. J. Amer. Statist. Assoc. 47, 583-621. 11. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. Company Sanitized. 88 not contain TSCA CBl -32- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 12. Fisher, R.A. (1985). Statistical Methods fo r Research Workers, 13th edition. Haffner, New York. 13. Lewis, D.J. (1991). Morphological assessment o f pathological changes within the rat larynx. Toxicol. Pathol. 19(4 P tl), 352-357. 14. Burger G.T., Renne R.A., Sagartz J.W., Ayres P.H., Coggins C.R., Mosberg A.T., and Hayes A.W. (1989). Histologic changes in the respiratory tract induced by inhalation o f xenobiotics: physiologic adaptation or toxicity? Toxicol. Appl. Pharmacol. 101(3), 521-542. 15. Kilgour J.D., Foster J., Soames A., Farrar D.G., and Hext P.M. (2002). Responses in the respiratory tract of rats following exposure to sulphuric acid aerosols for 5 or 28 days. J. Appl. Toxicol. 22(6), 387-395. Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLES Company San/tfeetf. Does not contain TSCACBI -34- H-25134: Four-Week Inhalation Toxicity Study in Male Rats TABLES ABBREVIATIONS: EXPLANATORY NOTES Chamber Concentrations of H-25134 Chamber Environmental Conditions S.D. - standard deviation S.E.M. - standard error o f 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 Summary of Coagulation Values PT - prothrombin time APTT - activated partial thromboplastin time DuPont-11414 Con>Pany$a , 9 ^08$ " 0'*>ma,n TSca CBi -35- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLES EXPLANATORY NOTES (Continued) ABBREVIATIONS (Continued): Summary of Clinical 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 UOSM - urine osmolality pH - the logarithm of the reciprocal of the hydrogen ion concentration URO - urobilinogen UFLU - urine fluoride UMTP - urine protein Company sam t,**. D" "'c,,ta,,,TSC ACB, -36- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLES NOTES: EXPLANATORY NOTES (Continued) Chamber Concentrations of H-25134 Particle Size Distribution of H-25134 Chamber Environmental Conditions Values are reported to 2 significant figures. Calculations were performed prior to rounding values. Summary of Hematology Values Summary of Coagulation Values Summary of Clinical 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. Company Sam ian, uoes not contain isC A C B l -37- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 1 CHAMBER CONCENTRATIONS OF H-25134 DESIGN CONCENTRATION (mg/m3) 5 30 100 GROUP III V VII MEASURED CONCENTRATION3 ___________________ (m g/m 3)____________ MEAN S.E.M. RANGE 5.1 0.19 3.7 - 6.9 31 0.93 2 0 -3 7 100 2.4 66 - 120 n 20 20 20 a Values represent the mean, standard error of the mean (S.E.M.), and range of the daily mean values obtained from n exposures. TABLE 2 PARTICLE SIZE DISTRIBUTION OF H-25134 DESIGN MASS MEDIAN GEOMETRIC % PARTICLES CONCENTRATION EXPOSURE AERODYNAMIC STANDARD BY MASS (mg/m3) NUMBER DIAMETER (pm) DEVIATION <1 pm <3 pm <10 pm 5 4 3.7 1.6 0.2 34 99 8 3.0 1.5 0.4 50 100 13 3.8 1.6 0.2 32 100 17 3.7 1.6 0.3 33 98 30 3 4.7 1.7 0.15 20 93 6 4.7 1.7 0.2 22 93 11 5.2 1.9 >1 23 100 16 4.7 2.0 0.1 32 99 100 2 3.9 1.5 >1 26 99 7 4.0 3.1 7 70 100 12 4.4 1.4 >1 10 100 16 4.5 1.6 >1 13 99 Company Sa.moq. ooes ,,oi comam 1SCA CBI -38- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 3 CHAMBER ENVIRONMENTAL CONDITIONS DESIGN TEMPERATURE RELATIVE HUMIDITY AIRFLOW CONCENTRATION (C)a (% f (L/min)a (mg/m3) GROUP MEAN S.E.M. RANGE MEAN S.E.M. RANGE MEAN S.E.M. RANGE n 0 I 24 0.13 2 2 -2 5 58 1.7 45 -6 7 35 0.032 35 20 5 III 21 0.20 19 -2 3 65 1.6 5 2 -7 4 50 0.0087 50 20 30 V 24 0.090 2 3 -2 5 37 0.54 3 3 -4 1 50 0.011 50 20 100 VII 25 0.090 2 4 -2 5 58 0.41 5 5 -6 1 50 0.0079 50 20 a Values represent the mean, standard error of the mean (S.E.M.), and range of the daily mean values obtained from n exposures. 2 "3tP sIS) tc c cfCt c c S *fti c. & -39- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 4 MEAN BODY WEIGHTS OF MALE RATS ___________________ MEAN BODY WEIGHTS (g)________________ Group I Group III Group V Group VII DAYS ON TEST______ 0 mg/m3_________5 mg/m3________ 30 mg/m3_______ 100 mg/m3 EXPOSURE 0 275.5 13.2(15) 272.1 14.3(15) 273.4 13.9(15) 271.7 15.6(15) 7 304.7 295.8 295.8 294.9 21.3(15) 18.3(15) 18.9(15) 24.5(15) 14 333.2 320.7 314.8 318.6 26.8(15) 21.7(15) 22.8(15) 29.4(15) 21 358.2 345.3 333.6 340.7 31.4(15) 25.3(15) 27.8(15) 33.0(15) 25a 343.7 329.0 315.2 323.3 34.5(10) 26.9(10) 28.9(10) 35.6(10) Company SanilUed. Does not contain TSCA CSI -40- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 DAYS ON TEST RECOVERY 28 35 42 49 56a TABLE 4 (Continued) MEAN BODY WEIGHTS OF MALE RATS Group I 0 mg/m3 MEAN BODY WEIGHTS (g) Group III Group V 5 mg/m3 30 mg/m3 359.9 21.2(5) 397.4 30.6(5) 430.6 24.4(5) 460.4 21.4(5) 447.1 21.0(5) 346.8 15.4(5) 386.9 18.9(5) 414.4 19.1(5) 438.9 22.4(5) 422.1 21.5(5) 350.3 20.1(5) 392.9 20.7(5) 426.8 22.1(5) 456.0 27.7(5) 439.7 27.1(5) Group VII 100 mg/m3 357.0 32.7(5) 395.2 36.2(5) 429.2 40.0(5) 454.5 47.1(5) 441.6 46.0(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. a Weight losses due to fasting of rats prior to clinical pathology evaluation. cmCompany Sanitized. Does not contain t s c a H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 5 MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group I 0 mg/m3 MEAN BODY WEIGHT GAINS (g) Group III Group V 5 mg/m3 30 mg/m3 Group VII 100 mg/m3 EXPOSURE 0 -7 7 - 14 29.2 11.6(15) 28.5 7.9(15) 23.7 7.5(15) 24.9 6.3(15) 22.3 6.4(15) 19.1# 6.3(15) 23.2 11.0(15) 23.6# 7.7(15) 14-21 25.0 9.4(15) 24.6 5.7(15) 18.8# 6.9(15) 22.1# 5.5(15) 21 - 25a -18.8 6.5(10) -22.4 4.5(10) -19.4 5.4(10) -17.5 3.3(10) RECOVERY 28-35 37.6 14.8(5) 40.1 4.7(5) 42.5 6.6(5) 38.1 7.8(5) 35-42 33.1 11.0(5) 27.5 8.2(5) 33.9 5.7(5) 34.0 5.3(5) 42-49 29.9 5.3(5) 24.5 7.0(5) 29.2 7.6(5) 25.3 8.0(5) 49 - 56a -13.4 3.5(5) -16.8 3.3(5) -16.3 4.0(5) -12.9 6.1(5) Com^ s , ,, Ite6 d 0 o e contain Ts c a c -42- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 5 (Continued) MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group I 0 mg/m3 MEAN BODY WEIGHT GAINS (g) Group III Group V 5 mg/m3 30 mg/m3 Group VII 100 mg/m3 OVERALL 0-25 69.0 21.9(10) 56.4 16.7(10) 39.6# 15.8(10) 51.5# 21.1(10) 28-56 87.2 16.0(5) 75.4 11.3(5) 89.4 17.1(5) 84.5 20.1(5) 0-56 170.0 23.7(5) 151.1 14.6(5) 170.6 22.1(5) 170.2 38.3(5) 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. Company Sanitized. Does not contain TSCA CBI -43 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 6 MEAN DAILY FOOD CONSUMPTION BY MALE RATS DAYS ON TEST MEAN DAILY FOOD CONSUMED PER ANIMAL (g) Group I Group III Group V Group VII 0 mg/m3 5 mg/m3 30 mg/m3 100 mg/m3 EXPOSURE 7 24.6 2.3(15) 24.1 1.7(15) 23.8 1.9(15) 23.7 2.7(15) 14 24.3 24.1 22.6 23.3 2.6(15) 1.7(15) 1.8(15) 2.1(15) 21 24.4 24.4 22.5 23.7 2.9(15) 2.1(15) 2.0(15) 1.9(15) OVERALL 0-21 24.4 2.378(15) 24.2 1.688(15) 23.0 1.727(15) 23.6 2.052(15) Data arranged as: Mean Standard deviation (Number of values included in calculation) There were no statistically significant differences from control at p < 0.05. Company Sanitized. Does not contain TSCA CBI -44- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 7 MEAN DAILY FOOD EFFICIENCY OF MALE RATS DAYS ON TEST MEAN DAILY FOOD EFFICIENCY (g WEIGHT GAIN/g FOOD CONSUMED) Group I Group III Group V Group VII 0 mg/m3 5 mg/m3 30 mg/m3 100 mg/m3 EXPOSURE 0 -7 0.167 0.055(15) 0.139 0.038(15) 0.133 0.033(15) 0.135 0.056(15) 14 0.165 0.147 0.119# 0.143# 0.035(15) 0.033(15) 0.036(15) 0.039(15) 21 0.144 0.143 0.118# 0.132# 0.046(15) 0.025(15) 0.040(15) 0.027(15) OVERALL 0-21 0.159 0.031(15) 0.143 0.025(15) 0.123# 0.030(15) 0.138# 0.032(15) 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. ACompany Sanitized. Does not contain TSC Cflf -45 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 8 SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS PRIOR TO EXPOSURE ANIMAL COUNT: Exophthalmus Incidence Mean onset (Days) Enophthalmus Incidence Mean onset (Days) Discharge Incidence Mean onset (Days) Hair Loss Incidence Mean onset (Days) Wound Incidence Mean onset (Days) Group I 0 mg/m3 15 1 (7%) 28 1 (7%) 42 1 (7%) 35 2 (13%) 23 0 (0%) Group III 5 mg/m3 15 0 (0%) 0 (0%) 1 (7%) 28 1 (7%) 20 1 (7%) 21 Group V 30 mg/m3 15 0 (0%) 0 (0%) 1 (7%) 28 3 (20%) 22 2 (13%) 14 Group VII 100 mg/m3 15 1 (7%) 28 1 (7%) 42 1 (7%) 28 3 (20%) 23 0 (0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the test days each observation was first recorded for that group. 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. -46- Does no! contain Ts Aa CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 9 SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS AFTER EXPOSURE ANIMAL COUNT: Group I 0 mg/m3 15 Group III 5 mg/m3 15 Group V 30 mg/m3 15 Group VII 100 mg/m3 15 Discharge Incidence Mean onset (Days) 12 (80%) 9 13 (87%) 11 12 (80%) 9 12 (80%) 7 Wound Incidence Mean onset (Days) 0 (0%) 1 (7%) 8 2 (13%) 11 1 (7%) 4 Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean o f 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. Company Sanitized. Does not contain TSCA CB1 -47- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 10 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 RBC (x l0 6/pL) DAY 25 HGB (g/dL) DAY 25 HCT (%) DAY 25 MCV (fl) DAY 25 MCH (pg) DAY 25 MCHC (g/dL) DAY 25 RDW (%) DAY 25 ARET (x l0 3/pL) DAY 25 PLT (x l0 3/pL) DAY 25 WBC (xlOVpL) DAY 25 ANEU (x l0 3/pL) DAY 25 ALYM (x l0 3/pL) DAY 25 7.93 0.26(10) 15.7 0.4(10) 46.1 1.3(10) 58.1 1.4(10) 19.8 0.5(10) 34.1 0.5(10) 10.9 0.3(10) 169.5 46.6(10) 1207 136(6) 11.48 2.55(10) 1.49 0.60(10) 9.50 2.05(10) 7.85 0.28(9) 15.7 0.4(9) 45.6 1.1(9) 58.1 1.9(9) 20.0 0.6(9) 34.3 0.6(9) 10.8 0.5(9) 175.2 31.0(9) 1261 134(4) 12.08 1.55(9) 1.57 0.65(9) 10.06 1.47(9) 8.13 0.36(10) 15.8 0.5(10) 46.0 1.4(10) 56.6 1.5(10) 19.5 0.6(10) 34.4 0.5(10) 11.0 0.4(10) 134.0 35.0(10) 1100 159(5) 12.21 2.85(10) 1.20 0.47(10) 10.46 2.27(10) 7.95 0.25(10) 15.7 0.6(10) 45.9 1.7(10) 57.7 1.6(10) 19.8 0.7(10) 34.2 0.6(10) 10.7 0.3(10) 149.5 21.7(10) 1133 100(8) 12.27 2.71(10) 1.29 0.35(10) 10.51 2.66(10) -48- om -u-y Sanitized. Does re certain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 10 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 AMON (xlOVpL) DAY 25 AEOS (xlOVpL) DAY 25 ABAS (x l0 3/pL) DAY 25 ALUC (xlOVpL) DAY 25 0.25 0.11(10) 0.09 0.05(10) 0.07 0.03(10) 0.08 0.02(10) 0.21 0.08(9) 0.09 0.02(9) 0.07 0.03(9) 0.08 0.02(9) 0.22 0.12(10) 0.10 0.06(10) 0.09 0.05(10) 0.13 0.12(10) 0.22 0.13(10) 0.09 0.05(10) 0.08 0.04(10) 0.08 0.06(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. Company Sanitized. Does not contain TSCACBI -49- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 11 SUMMARY OF COAGULATION VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 PT (seconds) DAY 25 APTT (seconds) DAY 25 15.7 1.4(10) 20.9 1.5(10) 16.1 2.1(10) 20.8 1.5(10) 15.5 0.8(10) 19.9 1.7(10) 15.4 0.4(10) 19.7 1.6(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. CornpanVSanitiz Does n 'M n ,ai,, TSCitC8( -50- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 12 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 AST (U/L) DAY 25 ALT (U/L) DAY 25 SDH (U/L) DAY 25 ALKP (U/L) DAY 25 BILI (mg/dL) DAY 25 BUN (mg/dL) DAY 25 CREA (mg/dL) DAY 25 CHOL (mg/dL) DAY 25 DAY 56 TRIG (mg/dL) DAY 25 DAY 56 103 19(10) 31 5(10) 12.4 5.4(10) 197 34(10) 0.08 0.03(10) 15 1(10) 0.32 0.05(10) 48 7(10) 52 8(5) 36 11(10) 54 11(5) 100 11(10) 33 5(10) 12.7 5.0(7) 215 28(10) 0.08 0.03(10) 15 1(10) 0.31 0.07(10) 43 9(10) 52 7(5) 20* 9(10) 52 ' 23(5) 109 14(9) 36 8(9) 11.3 5.3(8) 174 31(9) 0.10 0.03(9) 15 1(10) 0.33 0.05(10) 44 9(10) 51 13(5) 23* 6(9) 61 24(5) 101 13(10) 35 7(10) 13.1 4.4(9) 213 40(10) 0.08 0.03(10) 14 2(10) 0.33 0.05(10) 33* 10(10) 51 18(5) 27 6(10) 64 24(5) Company Sanitized. Does not oes not contain TSCAC8I -51 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 12 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 GLUC (mg/dL) DAY 25 TP (g/dL) DAY 25 DAY 56 ALB (g/dL) DAY 25 DAY 56 GLOB (g/dL) DAY 25 DAY 56 CALC (mg/dL) DAY 25 IPHS (mg/dL) DAY 25 NA (mmol/L) DAY 25 K (mmol/L) DAY 25 88 8(10) 6.3 0.2(10) 6.6 0.2(5) 4.3 0.2(10) 4.2 0.1(5) 2.0 0.1(10) 2.4 0.2(5) 10.8 0.4(10) 9.6 0.9(10) 146.9 1.5(10) 5.97 0.35(10) 92 15(10) 6.1 0.3(10) 6.6 0.3(5) 4.3 0.2(10) 4.4 0.2(5) 1.8 0.1(10) 2.2 0.2(5) 10.8 0.2(10) 9.6 0.9(10) 147.4 2.1(10) 6.09 0.54(10) 92 7(10) 6.4 0.3(9) 6.3 0.1(5) 4.4 0.2(9) 4.2 0.2(5) 2.0 0.2(9) 2.2 0.1(5) 10.6 0.4(10) 8.7@ 0.7(10) 148.4 2.4(10) 5.89 0.41(9) 91 11(10) 6.2 0.4(10) 6.5 0.3(5) 4.2 0.2(10) 4.2 0.2(5) 2.0 0.2(10) 2.3 0.1(5) 10.7 0.4(10) 9.0 1.0(10) 149.2 2.6(10) 5.89 0.21(10) Company Sanitized. Does not contain TSCA CBI -52- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 12 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I Group III Group V Group VII 0 mg/m3_______ 5 mg/m3_________30 mg/m3_______ 100 mg/m3 CL (mmol/L) DAY 25 PFLU (pg/mL) DAY 25 102.0 1.6(10) 0.1 0.0(10) 104.0* 2.2(10) 0.1 0.1(10) 102.3 1.4(10) 0.1 0.0(10) 103.3 1.8(10) 0.1 0.0(9) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. -53 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 13 SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 VOL (mL) DAY 25 UOSM (mOsm) DAY 25 pH DAY 25 URO (EU/dL) DAY 25 UFLU(pg) DAY 25 DAY 56 UMTP (mg/dL) DAY 25 6.2 4.6(10) 1547 964(10) 6.7 0.5(10) 0.2 0.0(10) 13.2 3.0(7) 14.7 5.0(5) 129 72(10) 5.6 3.6(10) 1330 859(10) 6.9 0.5(10) 0.2 0.0(10) 12.8 5.1(9) 13.0 3.3(5) 102 72(10) 4.8 2.8(10) 1390 848(10) 6.6 0.5(10) 0.2 0.0(10) 18.6 5.2(8) 11.7 2.0(5) 86 62(10) 6.6 4.4(10) 1129 692(10) 6.5 0.5(10) 0.2 0.0(10) 23.9* 8.4(8) 13.9 3.5(5) 75 66(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. -54- C ^ * ny S" " " d- . contain TSCA CB, H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 14 SUMMARY OF BLOOD FLUORINE ANALYSIS DAYS ON TEST 0 7 14 Group I 0 mg/m3 1.3 0.11(5) 1.4 0.11(5) 1,0 0.19(5) BLOOD FLUORINE (ppm) Group III Group V 5 mg/m3 30 mg/m3 aa aa aa 25 1.1 1.4 2.5 0.04(5) 0.08(5) 0.24(4) 54 1.2 1.3 1.8 0.12(5) 0.22(5) 0.16(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) a Samples not evaluated for this timepoint. Group VII 100 mg/m3 1.7 0.21(5) 2.1 0.23(5) 3.1 0.71(5) 3.8 0.53(5) 1.7 0.29(5) Company Sanitized. Does - oes noi contain TSCA H-25134: Four-Week Inhalation Toxicity Study in Male Rats___________ DuPont-11414 TABLE 15 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 9.990 1.280(10) 9.607 0.787(10) 9.115 1.031(10) 9.535 1.275(10) KIDNEYS 2.921 0.408(10) 2.982 0.346(10) 2.800 0.259(10) 2.966 0.361(10) LUNGS 1.691 0.203(10) 1.673 0.198(10) 1.561 0.185(10) 1.657 0.183(10) HEART 1.373 0.214(10) 1.365 0.165(10) 1.199# 0.116(10) 1.239# 0.150(10) SPLEEN 0.583 0.130(10) 0.606 0.072(10) 0.575 0.131(10) 0.579 0.098(10) BRAIN 1.957 0.138(10) 1.977 0.085(10) 1.964 0.094(10) 1.980 0.086(10) THYMUS 0.375 0.099(10) 0.429 0.055(10) 0.402 0.082(10) 0.455# 0.065(10) ADRENAL GLANDS 0.055 0.012(10) 0.066 0.005(10) 0.060 0.015(10) 0.070 0.017(10) TESTES 3.057 0.302(10) 3.241 0.253(10) 3.252 0.352(10) 3.251 0.285(10) EPIDIDYMIDES 1.018 0.105(10) 1.077 0.195(10) 0.979 0.101(10) 1.059 0.129(10) FINAL BODY WEIGHT (grams) 343.690 34.542(10) 328.990 26.854(10) 315.200 28.945(10) 323.340 35.591(10) .-------------------- Com - 56 - C n " " ' Bees not contain TSCA CB, H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 T A B L E 15 (C ontinued) M EA N FINAL B O D Y A N D O RG AN W EIGHTS FROM M ALE RATS D A Y 25 SACRIFICE Group I Group III Group V Group VII _________________________ 0 mg/m3________ 5 mg/m3_______ 30 mg/m3______ 100 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ FINAL BODY * 100 2.906 0.230(10) 2.922 0.120(10) 2.893 0.228(10) 2.948 0.209(10) KIDNEYS/ FINAL BODY * 100 0.850 0.091(10) 0.905 0.052(10) 0.891 0.080(10) 0.917 0.040(10) LUNGS/ FINAL BODY * 100 0.492 0.040(10) 0.509 0.046(10) 0.495 0.038(10) 0.515 0.053(10) HEART/ FINAL BODY * 100 0.398 0.039(10) 0.415 0.032(10) 0.382 0.037(10) 0.384 0.035(10) SPLEEN/ FINAL BODY * 100 0.169 0.027(10) 0.184 0.014(10) 0.182 0.039(10) 0.179 0.020(10) BRAIN/ FINAL BODY * 100 0.573 0.053(10) 0.603 0.033(10) 0.627 0.049(10) 0.620 0.083(10) THYMUS/ FINAL BODY * 100 0.108 0.020(10) 0.130# 0.013(10) 0.128# 0.028(10) 0.141# 0.013(10) ADRENAL GLANDS/ FINAL BODY * 100 0.016 0.004(10) 0.020 0.002(10) 0.019 0.005(10) 0.022# 0.004(10) TESTES/ FINAL BODY * 100 0.893 0.088(10) 0.988# 0.076(10) 1.036# 0.111(10) 1.009# 0.060(10) EPIDIDYMIDES/ FINAL BODY * 100 0.299 0.041(10) 0.327 0.044(10) 0.313 0.041(10) 0.330 0.041(10) Company Sanitized. Does oes no, not contain TSCACBt -57- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 T A B L E 15 (C ontinued) M EA N FINA L B O D Y A N D O RG AN W EIGHTS FROM M ALE RATS D A Y 25 SACRIFICE Group I Group III Group V Group VII _________________________ 0 mg/m3________ 5 mg/m3_______ 30 mg/m3______ 100 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/ BRAIN * 100 510.099 51.485(10) 485.628 28.495(10) 464.261 51.808(10) 482.222 66.222(10) KIDNEYS/ BRAIN * 100 149.057 16.981(10) 150.650 14.019(10) 142.608 12.456(10) 150.138 19.996(10) LUNGS/ BRAIN * 100 86.257 6.599(10) 84.461 7.714(10) 79.368 7.616(10) 83.705 8.594(10) HEART/ BRAIN * 100 SPLEEN/ BRAIN * 100 70.019 8.664(10) 29.690 5.707(10) 68.903 6.147(10) 30.582 2.762(10) 61.056# 5.645(10) 29.226 6.493(10) 62.623# 7.408(10) 29.290 5.021(10) THYMUS/ BRAIN * 100 19.188 4.908(10) ADRENAL GLANDS/ BRAIN * 100 2.819 0.587(10) TESTES/ BRAIN * 100 156.386 13.738(10) EPIDIDYMIDES/ BRAIN * 100 52.166 5.496(10) 21.668 2.342(10) 3.313 0.234(10) 164.101 13.377(10) 54.384 8.519(10) 20.424 4.020(10) 3.029 0.733(10) 165.435 13.748(10) 49.807 4.358(10) 23.031# 3.425(10) 3.531 0.816(10) 164.535 16.688(10) 53.488 5.963(10) 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). - 58- Company Sanltteod. D o ^^ H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 16 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 12.850 0.739(5) 11.943 1.666(5) 13.727 1.443(5) 13.911 3.387(5) KIDNEYS 3.523 0.357(5) 3.423 0.190(5) 3.635 0.274(5) 3.865 0.565(5) LUNGS 1.878 0.227(5) 2.001 0.247(5) 2.150 0.292(5) 2.076 0.470(5) HEART 1.553 0.083(5) 1.618 0.221(5) 1.591 0.109(5) 1.701 0.289(5) SPLEEN 0.867 0.051(5) 0.746 0.108(5) 0.828 0.136(5) 0.859 0.239(5) BRAIN 2.028 0.138(5) 2.113 0.111(5) 2.115 0.093(5) 2.082 0.132(5) THYMUS 0.543 0.056(5) 0.454 0.110(5) 0.418# 0.024(5) 0.408# 0.053(5) ADRENAL GLANDS 0.051 0.006(5) 0.052 0.011(5) 0.064 0.004(5) 0.070# 0.009(5) TESTES 3.324 0.298(5) 3.452 0.199(5) 3.358 0.234(5) 3.235 0.200(5) EPIDIDYMIDES 1.279 0.159(5) 1.293 0.056(5) 1.379 0.090(5) 1.346 0.185(5) FINAL BODY WEIGHT (grams) 447.060 20.987(5) 422.120 21.505(5) 439.700 27.084(5) 441.560 45.978(5) Company Stnitim i. Doftjnutuumam i s H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TA BLE 16 (C ontinued) M EA N FINAL B O D Y A N D O RG AN W EIGHTS FROM M ALE RATS D A Y 56 SACRIFICE Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ FINAL BODY * 100 2.874 0.098(5) 2.826 0.325(5) 3.117 0.174(5) 3.114 0.463(5) KIDNEYS/ FINAL BODY * 100 0.787 0.055(5) 0.811 0.018(5) 0.826 0.022(5) 0.874# 0.065(5) LUNGS/ FINAL BODY * 100 0.420 0.044(5) 0.474 0.045(5) 0.489 0.058(5) 0.466 0.064(5) HEART/ FINAL BODY * 100 0.348 0.018(5) 0.383 0.041(5) 0.362 0.017(5) 0.384 0.038(5) SPLEEN/ FINAL BODY * 100 0.194 0.008(5) 0.176 0.020(5) 0.188 0.030(5) 0.192 0.037(5) BRAIN/ FINAL BODY * 100 0.455 0.042(5) 0.502 0.042(5) 0.483 0.039(5) 0.474 0.034(5) THYMUS/ FINAL BODY * 100 0.121 0.009(5) 0.107 0.024(5) 0.095# 0.006(5) 0.092# 0.007(5) ADRENAL GLANDS/ FINAL BODY* 100 0.011 0.001(5) 0.012 0.002(5) 0.015# 0.001(5) 0.016# 0.003(5) TESTES/ . FINAL BODY * 100 0.746 0.089(5) 0.818 0.028(5) 0.766 0.075(5) 0.739 0.089(5) EPIDIDYMIDES/ FINAL BODY * 100 0.287 0.036(5) 0.307 0.008(5) 0.314 0.020(5) 0.304 0.019(5) -60- Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 16 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 56 SACRIFICE Group I 0 mg/m3 Group III 5 mg/m3 Group V 30 mg/m3 Group VII 100 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/ BRAIN * 100 635.644 52.028(5) 568.638 102.669(5) 650.438 76.152(5) 663.344 130.705(5) KIDNEYS/ BRAIN * 100 174.355 20.595(5) 162.469 14.260(5) 172.253 16.007(5) 184.981 16.942(5) LUNGS/ BRAIN * 100 92.982 12.504(5) 94.718 10.315(5) 101.597 11.829(5) 99.177 18.738(5) HEART/ BRAIN * 100 76.909 7.491(5) 76.730 11.376(5) 75.287 4.756(5) 81.300 9.197(5) SPLEEN/ BRAIN * 100 43.015 5.174(5) 35.527 6.596(5) 39.076 5.767(5) 40.855 8.988(5) THYMUS/ BRAIN * 100 26.875 3.578(5) 21.354 4.424(5) 19.818# 1.880(5) 19.554# 1.374(5) ADRENAL GLANDS/ BRAIN * 100 2.505 0.225(5) 2.463 0.437(5) 3.016 0.280(5) 3.355# 0.446(5) TESTES/ BRAIN * 100 164.553 19.967(5) 163.618 10.273(5) 159.371 17.720(5) 155.735 12.248(5) EPIDIDYMIDES/ BRAIN * 100 63.089 6.557(5) 61.401 5.265(5) 65.401 6.687(5) 64.464 6.055(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). 61 - Company Sanitized. Dobs not contain T s e a ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) ') DuPont-11414 TABLE 17 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED DILATATION, RIGHT. LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SKELETAL MUSCLE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED AORTA NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 GO) 7 3 (10) 10 (10) 10 GO) 10 (10) 10 (10) 10 (10) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 GO) 10 (10) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 Figures 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 TSCA CB) -62- ) .. H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 TABLE 17 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED LESION INCIDENCE (Animal No| TREATMENT 0 5 30 100 1 mg/m3 mg/m3 mg/m3 mg/m3 1 I III V VII (10) 10 (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 (10) 10 GO) 10 GO) 10 GO) 10 (10) 10 (10) 10 GO) 10 (10) 10 GO) 10 GO) 10 GO) 10 GO) 10 (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 GO) 10 GO) 10 (10) 10 (10) 10 (10) 10 Figures 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 S a n d e d . Does not contafn TSCA CBl - 63- ), ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats____________________________________________ ) DuPont-11414 TABLE 17 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII CECUM NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 GO) 10 COLON NO ABNORMALITY DETECTED (10) GO) (10) (10) 10 10 10 10 RECTUM NO ABNORMALITY DETECTED GO) GO) (10) (10) 10 10 10 10 MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED (10) GO) (10) (10) 10 10 10 10 SALIVARY GLANDS NO ABNORMALITY DETECTED (10) (10) GO) (10) 10 10 10 10 3 QfNfl. MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED O3oa THYMUS NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified contain TSCA CBl -64- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 17 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED PITUITARY GLAND NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED | TREATMENT | 1 LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII GO) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 GO) 10 GO) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 17 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No| 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII PHARYNX/LARYNX NO ABNORMALITY DETECTED (10) GO) GO) GO) 10 10 10 10 EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED (10) (10) GO) (10) 10 10 10 10 SKIN NO ABNORMALITY DETECTED (10) (10) GO) GO) 10 10 10 10 Company Sanitized. PROSTATE NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 GO) 10 SEMINAL VESICLES NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 (10) 10 URINARY BLADDER NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 (10) 10 oo TESTES NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 GO) 10 O3W 1 oo Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified at 5' 2 o -66- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 17 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII EPIDIDYMIDES NO ABNORMALITY DETECTED DISCOLORATION, TAN, RAISED, RIGHT, 7 MM DIA.. DISCOLORATION, YELLOW, RAISED, RIGHT, 5MM DIA.. (10) 9 1 GO) 9 1 (10) 10 GO) 10 FEMUR/KNEE JOINT NO ABNORMALITY DETECTED oO a3ot STERNUM NO ABNORMALITY DETECTED < 3CO NOSE NO ABNORMALITY DETECTED (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 (10) 10 GO) 10 (10) 10 (10) 10 GO) 10 GO) 10 (10) 10 .N 2 Figures in parentheses is the number of animals grossly examined for this tissue o o The absence of a number indicates the finding specified was not identified O39 contain TSCACBf - 67- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 ompany Sanitized. O ooo O3 3oo & S' <n 2 S TABLE 18 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 15 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED DILATATION, LEFT. DILATATION, RIGHT. LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SKELETAL MUSCLE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED AORTA NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5544 1 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 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified -68- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 18 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII o # I a0C)O 8 p2 oa o ST 5' to 2 BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 69- (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 18 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII CECUM NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 COLON NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 RECTUM NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 ,p*ny Sanitized. SALIVARY GLANDS NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 THYMUS NO ABNORMALITY DETECTED oo (5) (5) (5) (5) 5555 93 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified ) .. H-25134: Four-Week Inhalation Toxicity Study in Male Rats > ) DuPont-11414 TABLE 18 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII ADRENAL GLANDS NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 SCIATIC NERVE NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 Company S a n d e d . Does not PITUITARY GLAND NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 THYROID GLAND NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 PARATHYROID GLANDS NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 TRACHEA NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 ESOPHAGUS oo NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 a> S' Figures in parentheses is the number of animals grossly examined for this tissue 3 The absence of a number indicates the finding specified was not identified 2 S -71 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 18 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I I11 V VII PHARYNX/LARYNX NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 EYE(S ) WITH OPTIC NERVE NO ABNORMALITY DETECTED RUPTURE, RIGHT. (5) (5) (5) (5) 4 554 11 SKIN NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 Comptmy Smitxwf. Ooes PROSTATE NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 SEMINAL VESICLES NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 URINARY BLADDER NO ABNORMALITY DETECTED CALCULUS\CALCULI. (5) (5) (5) (5) 5 554 1 33 Figures in parentheses is the number of animals grossly examined for this tissue .1} The absence of a number indicates the finding specified was not identified S 3 (H0 >o o 00 - 72- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 TABLE 18 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Animal No 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 N & Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified IO3 oo3 3at --(0I S a - 73- (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 (5) 5 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 19 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC, FOCAL. minimal total observations per lesion GO) 2 8 8 Company Sanitized. Does PANCREAS NO ABNORMALITY DETECTED ATROPHY, FOCAL. minimal total observations per lesion GO) 8 2 2 ESOPHAGUS NO ABNORMALITY DETECTED (10) 10 O3 STOMACH NO ABNORMALITY DETECTED 3oo DUODENUM 3ST NO ABNORMALITY DETECTED GO) 10 (10) 10 o >o Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DJ GO) 2 8 8 (10) 10 GO) 10 GO) 10 GO) 10 - 74- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESIOIg INCIDI3NCE (NIJMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII DIGESTIVE SYSTEM JEJUNUM NO ABNORMALITY DETECTED (10) 10 ILEUM NO ABNORMALITY DETECTED (10) 10 CECUM NO ABNORMALITY DETECTED (10) 10 S00 *PK]ti*ie COLON NO ABNORMALITY DETECTED (10) 10 RECTUM NO ABNORMALITY DETECTED (10) 10 SALIVARY GLANDS (10) O:I NO ABNORMALITY DETECTED 10 aul .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 -.1 HOI CV* O w - 75- (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 'Company Sanitized. Does not contain TSCA CBI TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. minimal mil-d total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal mild total observations per lesion URINARY BLADDER NO ABNORMALITY DETECTED RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED | LESION INCIDENCE (NUMERIC) TREATMENT 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII GO) (3) 6 4 1 41 12 1 13 GO) 10 GO) 10 (10) 10 (10) 9 1 1 (10) 10 (10) 10 (10) 10 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -76- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM PHARYNX/LARYNX NO ABNORMALITY DETECTED HYPERPLASIA/SQUAMOUS METAPLASIA. minimal to ta l observations per lesion GO) GO) GO) (10) 10 3 3 5 775 775 NOSE NO ABNORMALITY DETECTED GO) GO) 10 10 CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. s minimal to ta l observations per lesion GO) 9 1 1 AORTA 3 NO ABNORMALITY DETECTED GO) 10 3 2 Figure in parentheses is number of animals microscopically examined for this tissue 3 The absence of a number indicates the lesion specified was not identified GO) 9 1 1 (10) 10 - 77- ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED GO) 10 (9) 9 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 (10) 10 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 notcontain TSCACBI - 78- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESIOI1 INCIDI3NCE (NXJMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED GO) 10 PARATHYROID GLANDS NO ABNORMALITY DETECTED (8) 8 ADRENAL GLANDS NO ABNORMALITY DETECTED GO) 10 NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED GO) 10 SPINAL CORD (10) NO ABNORMALITY DETECTED 10 3O SCIATIC NERVE (10) 8 NO ABNORMALITY DETECTED 3 10 n 3 Figure in parentheses is number of animals microscopically examined for this tissue 3 The absence of a number indicates the lesion specified was not identified o00 (10) 10 (8) 8 GO) 10 (10) 10 (10) 10 (10) 10 - 79- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, minimal total observations per lesion DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES. minimal total observations per lesion UNILATERAL. GO) 10 (10) 10 (10) 10 (10) 10 GO) 10 GO) 10 GO) 10 GO) 8 1 1 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 <? TS C A C B ! - 80- ). ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats______________ ) DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS REPRODUCTIVE SYSTEM EPIDIDYMIDES NO ABNORMALITY DETECTED SPERMATOCELE. mild moderate total observations per lesion OLIGOSPERMIA/GERM CELL DEBRIS. minimal total observations per lesion PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion SEMINAL VESICLES NO ABNORMALITY DETECTED TREATMENT LESION INCIDENCE (NUMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (10) 9 1 1 (1) 1 1 (10) 9 1 1 (10) 10 GO) 9 1 1 GO) 8 2 2 GO) 10 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 CBI -81 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 19 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 5 30 100 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED SPECIAL SENSES SYSTEM EYE(S ) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. (10) 10 (10) 10 ( 10) 10 ( 10) 10 2 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 CBI - 82- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 TABLE 20 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 56 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 5 30 100 mg/m3 mg/m3 mg/m3 III V VII RESPIRATORY SYSTEM PHARYNX/LARYNX NO ABNORMALITY DETECTED (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 s Oi o SH Company Sanitized. Does not contain TSCA CBI - 83- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 FIGURES CampanySanHIged. Doesnotcon<ain tsca cbi -84- Doe notcontain SCACBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats FIGURE 1 SCHEMATIC OF EXPOSURE SYSTEM dilution houseline air pump and stirrer * generation houseline air heated flask exposure chamber collection flask -85- restrainers to exhaust DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) FIGURE 2 MEAN DAILY CHAMBER CONCENTRATIONS DuPont-11414 ---- 5 mg/m3 -- -- 30 mg/m3 --A-- 100 mg/m3 -86- H-25134: Four-Week Inhalation Toxicity Study in Male Rats FIGURE 3 MEAN BODY WEIGHTS OF MALE RATS DuPont-11414 /luaduioQ > q Days on Test 2 * Weight losses due to fasting of rats prior to clinical pathology evaluation. - 87- -0 mg/m3 - 5 mg/m3 - 30 mg/m' -100 mg/m3 H-25134: Four-Week Inhalation Toxicity Study in Male Rats FIGURE 4 MEAN BLOOD FLUORINE OF MALE RATS DuPont-11414 AueduioO <a3/>. Na 23.` -u>t o>o m Days on Test - 88- -O -- 0 mg/m3 5 mg/m3 -S -- 30 mg/m3 -A -- 100 mg/m3 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDICES not contain TSCA CBl Company Son*'- " - 89- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX A Daily Chamber Concentrations Company Sanitized. Does not contain TSCA CBf H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 DAILY CHAMBER CONCENTRATIONS ABBREVIATIONS: EXPLANATORY NOTES S.D. - standard deviation mg/m3 - milligrams per cubic meter n - number of samples FOOTNOTES: a Weekly means, standard errors of the mean, ranges, and n are calculated from daily means for the chamber during the specified week. NOTES: Values are reported to 2 significant figures. Calculations were performed prior to rounding values. Company Sanitized. Does no! contain TSCA CB! -91 - / # |5IKa^s^ H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 D a ily Cham ber C o n c e n tra tio n s (mg/m3 ) 5 mg/m3 E xposure Mean S.D . Range 1 5.4 0.55 4.6 6.2 2 5.0 2.3 1.1 - 8.0 3 4.2 2.0 1.6 - 6.8 4 5.7 1.9 3.6 - 8.9 5 3 .7 2.3 0.43 6.9 Week l a 4 .8 0.38 3 .7 - 5.7 6 6.6 2.3 3.3 - 8.9 7 6.9 1.7 4.2 - 9.1 8 4.0 1.9 2.0 - 7.5 9 4.7 2 .6 2.3 8.3 10 4 .2 2 .8 1.2 - 8 .5 30 mg/m3 n Mean | S.D . | Range 100 mg/m3 n Mean S.D . Range 6 25 6 20 6 34 6 36 7 26 14 8 .8 50 8 66 40 28 150 13 4 .4 - 43 6 100 16 17 17 10 - 62 63 6 7 100 99 71 24 43 31 81 _ 250 150 42 - 180 10 11 40 7 97 42 36 - 150 5 28 3 .0 20 - 36 5 93 7 .0 66 - 100 6 37 12 21 53 6 96 35 77 _ 170 6 28 10 13 - 40 6 90 51 24 - 160 6 30 7 .8 20 - 41 6 95 25 68 - 140 6 31 10 18 - 47 6 94 37 48 - 140 6 32 11 21 49 6 120 33 62 - 160 n 9 9 7 8 7 5 7 8 6 6 7 Week 2 5 .3 0 .6 2 4 .0 - 6 .9 5 32 1 .4 28 - 37 5 98 4 .5 90 - 120 5 11 12 5 .8 4 .7 1 .8 3 .3 3 .2 0 .7 5 _ _ 7 .8 9 .1 6 6 31 29 5 .2 20 _ 35 6 120 7 .4 22 - 43 6 110 51 29 17 62 _ - 180 140 8 6 13 5 .5 1 .6 3 .2 - 8 .0 6 32 6 .5 25 - 41 6 100 34 56 - 160 7 14 4 .7 2 .6 . 1 .9 - 8 .4 6 32 8 .8 22 - 48 6 110 34 60 - 170 7 15 5 .4 1 .8 3 .2 7 .8 6 34 8 .2 25 - 46 6 100 16 88 - 130 6 Week 3 5 .2 0 .2 1 4 .7 - 5 .8 5 32 0 .9 29 - 34 5 110 2 .1 100 - 120 5 16 4 .7 1 .1 3 .5 _ 6 .8 6 32 11 21 49 6 110 13 89 _ 120 6 17 18 19 5 .4 4 .7 5 .8 1 .1 3 .6 - 6.6 6 34 1 .6 1 .8 2 .6 4 .0 - 7 .1 8.4 6 6 25 31 5 .3 25 - 40 6 99 38 2 .5 22 - 28 6 110 7 .4 4 .7 22 - 34 6 110 22 53 98 _ 160 120 7 6 88 - 150 7 20 4 .6 1 .7 2 .8 - 6 .6 6 30 3 .9 26 - 38 6 93 15 79 - 120 6 Week 4 5 .0 0 .2 3 4 .6 - 5 .8 5 30 1 .4 25 - 34 5 100 3 .0 93 - 110 5 Company Sanftteed. Does no( eonlaJn 7SCA CBI - 92- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX B Daily Chamber Environmental Conditions Company Sanitized. Does not contain TSCA CB1 - 93- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 DAILY CHAMBER ENVIRONMENTAL CONDITIONS ABBREVIATIONS: EXPLANATORY NOTES n - number of observations FOOTNOTES: Weekly means, standard errors o f the mean, ranges, and n are calculated from daily means for the chamber during the specified week. NOTES: Values are reported to 2 significant figures. Calculations were performed prior to rounding values. Company Sanitized. Does no! contain TSCA CBI ). H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) ) DuPont-11414 oo na3 >3< ato 3 a(N0 o 08) O3 o3 s? 3 3 2 a D a ily Cham ber E n v iro n m e n ta l C o n d itio n s - T e m p e ra tu re ( aC) 0 mg/m 3 5 mg/m 3 30 mg/m 3 100 mg/m3 E xposure Mean S.D . Range n Mean S.D . Range n Mean S.D . 1 Range n Mean S.D . Range n 1 24 1 .3 22 26 24 21 0 .4 0 21 22 24 24 0 .4 9 23 25 24 25 0 .2 8 24 25 24 2 2 4 1 . 1 2 1 - 2 6 2 4 1 9 0 . 2 6 1 8 - 1 9 2 4 2 4 0 . 8 1 2 2 - 2 5 2 4 24 0 . 6 7 2 2 - 2 5 2 4 3 24 0 .6 4 23 - 26 24 21 0 .3 3 20 - 21 24 24 0 .4 1 23 - 25 24 25 0 .3 7 24 - 25 24 4 2 3 0 . 4 8 2 2 - 2 4 2 4 2 2 0 . 3 2 21 - 2 2 2 4 2 4 0 . 3 5 2 4 - 2 5 2 4 2 5 0 . 4 6 2 4 - 2 6 2 4 5 24 0 .5 8 22 - 25 24 22 0 .3 4 21 " 22 24 25 0 .2 6 24 - 25 24 25 0 .3 0 24 - 25 24 Week l a 6 7 8 9 10 Week 2 11 12 13 14 15 Week 3 16 17 18 19 20 24 0 .1 7 23 - 24 5 21 0 .4 6 19 - 22 5 24 24 0 .5 0 23 _ 25 24 20 0 .4 1 19 _ 21 24 24 24 1 .0 22 - 25 24 20 1 .2 17 - 21 24 24 24 0 .8 4 21 - 26 24 22 0 .3 3 21 - 23 24 24 22 0 .4 2 21 - 23 24 21 0 .4 0 20 - 21 24 24 23 1 .5 19 - 25 24 20 1 .2 17 - 22 24 24 0 .17 24 - 25 5 25 0 .3 9 23 - 25 24 24 0.93 22 - 25 24 24 0 .28 24 - 25 24 25 0 .3 1 23 - 24 24 24 1 .1 21 - 25 24 24 0 .17 24 - 25 5 0 .6 1 1 .1 0 .4 2 0 .3 7 1.0 23 _ 25 22 - 25 24 _ 26 24 - 25 21 25 24 24 24 24 24 24 0 .40 22 - 24 5 21 0 .3 7 20 - 22 5 24 23 0 .81 20 _ 24 24 22 0 .3 6 21 _ 22 24 24 24 0 .3 5 23 - 24 24 22 0 .2 4 21 22 24 24 24 0 .80 21 ~ 25 24 22 0 .2 8 21 - 22 24 24 24 0 .3 1 23 - 25 24 22 0 .2 7 21 - 22 24 24 24 0 .4 6 23 - 25 24 21 0 .3 4 21 22 24 24 0 .13 24 5 0 .4 0 0 .2 8 0 .2 4 0 .2 7 0 .2 6 23 _ 25 24 - 25 24 - 25 24 - 25 24 - 25 24 24 24 24 24 24 25 25 25 25 25 0.18 24 - 25 5 0.58 24 _ 26 24 0.4 5 24 - 26 24 0.45 24 _ 26 24 0 .3 7 24 - 25 24 0 .5 0 23 - 26 24 24 0 .1 2 23 - 24 5 22 0 .1 0 21 - 22 5 24 0 .0 4 0 24 5 25 0.050 25 5 24 0 .8 1 23 _ 28 24 22 0 .4 3 21 _ 23 24 24 24 0 .3 9 23 - 25 24 23 0 .2 7 22 - 23 24 24 24 1 .2 22 - 26 24 20 0 .4 1 20 - 21 24 23 25 1 .1 22 - 28 24 22 0 .4 1 21 - 22 24 24 24 0 .7 0 23 25 24 21 0 .3 1 20 21 24 23 0 .2 6 23 _ 24 24 0.37 23 - 24 24 0 .5 1 22 - 24 24 0 .2 3 23 - 24 24 0.28 23 24 24 25 25 24 24 24 0 .4 6 23 - 25 24 0 .3 4 24 ~ 25 24 0 .4 8 23 - 25 24 0 .3 3 23 - 25 24 0 .2 7 24 25 24 Week 4 24 0 .2 0 24 - 25 5 21 0 .4 0 20 - 23 5 24 0 .1 0 23 - 24 5 24 0 .1 1 24 - 25 5 -95- ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 D a ily C h a m b e r E n v ir o n m e n ta l C o n d it io n s - R e la t iv e H u m id it y (%) 0 m g/m 3 E xp o su re Mean S .D . Range 5 m g/m 3 n Mean S .D . R ange 30 m g/m 3 n Mean S .D . 1 R ange 100 m g/m 3 n Mean S .D . R ange n 1 67 2 .6 61 71 24 74 1 .6 71 76 24 41 2 .0 38 _ 45 24 61 0 .8 59 . 62 24 2 3 63 64 2 .0 60 67 22 71 1 .5 61 - 67 24 71 2 .3 64 74 24 41 1 .5 69 - 74 24 37 6 .5 35 - 51 24 58 1 .6 34 - 39 24 58 1 .4 1 .5 55 56 - 62 60 24 24 4 66 1 .3 62 - 69 24 70 1 .3 68 - 73 24 39 1 .5 37 - 43 24 60 1 .3 58 - 65 24 5 64 1 .5 61 - 66 24 71 2 .0 67 - 74 24 41 0 .9 0 39 - 42 24 60 2 .0 58 " 67 24 W eek l a 65 0 .7 5 63 - 67 5 71 0 .6 4 70 - 74 5 40 0 .6 8 37 - 41 5 59 0 .5 5 58 - 61 5 6 59 1 .7 56 _ 64 24 67 2 .7 63 _ 72 24 39 1 .6 36 - 41 24 59 1 .3 57 - 63 24 7 60 2 .4 56 - 65 24 68 2 .0 64 - 72 24 37 1 .2 35 - 40 24 60 4 .6 55 - 73 24 8 61 1 .4 58 - 64 24 68 1 .9 65 - 72 24 36 0 .5 5 35 - 37 24 56 1 .0 54 - 59 24 9 64 1 .5 59 - 66 24 68 1 .6 65 - 71 24 37 1 .5 35 - 40 24 57 1 .3 56 - 60 24 10 60 1 .9 58 - 67 24 68 1 .2 65 - 70 24 36 1 .0 34 - 38 24 56 1 .1 55 - 59 24 Week 2 61 0 .9 0 59 - 64 5 68 0 .2 9 67 - 68 5 37 0 .5 4 36 - 39 5 58 0 .7 9 56 - 60 5 11 64 1 .7 60 _ 68 24 72 1 .8 69 _ 77 24 39 1 .2 37 - 43 24 61 1 .9 60 - 67 24 12 62 1 .5 60 - 66 24 72 1 .5 69 _ 75 24 36 1 .2 34 - 39 24 61 3 .2 57 - 72 24 13 14 60 60 1 .1 57 - 62 24 67 1 .5 58 - 63 24 66 1 .9 63 - 71 24 36 2 .4 33 - 40 24 59 1 .5 64 - 70 24 35 0 .8 7 34 - 37 24 60 2 .9 55 - 69 24 3 .0 57 - 72 24 A 15 58 1 .5 55 61 24 68 1 .1 65 - 69 24 34 0 .7 7 33 - 36 24 57 3 .5 55 - 70 24 o T333) W eek 3 61 1 .0 58 - 64 5 69 1 .2 66 - 72 5 36 0 .8 4 34 - 39 5 60 0 .7 4 57 - 61 5 16 48 1 .7 44 _ 51 24 55 1 .3 53 _ 58 24 38 1 .2 35 _ 40 24 57 1 .9 49 - 59 24 17 47 1 .1 44 - 48 24 56 1 .1 54 - 58 24 36 0 .9 2 34 - 37 24 56 2 .4 54 - 66 24 3fCi>O 18 19 45 45 2 .2 42 - 49 24 53 1 .2 43 - 47 24 54 1 .5 1 .7 51 51 - 56 57 24 24 34 34 1 .1 32 - 36 24 57 1 .5 55 - 60 24 1 .3 31 - 36 24 58 0 .9 5 56 - 59 24 20 46 2 .4 42 - 49 24 52 1 .7 48 - 55 24 33 0 .6 31 - 34 24 55 1 .2 53 - 59 24 aoeN W e e k 4 4 6 0 . 4 9 4 5 _ 4 8 5 54 0 . 7 6 52 _ 5 6 5 3 5 0 . 8 5 33 _ 3 8 5 57 0 .3 9 5 5 _ 5 8 5 oo not contain TSCACBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 D a ily Cham ber E n v iro n m e n ta l C o n d itio n s - A ir flo w (L /m in ) 0 m g/m 3 E xp o su re M ean | S .D . R ange 1 35 0 .0 1 3 35 2 35 0 .0 1 5 35 3 35 0 .0 1 5 35 4 35 0 .0 1 8 35 5 35 0 .0 1 3 35 n Mean 24 50 24 50 24 50 24 50 24 50 5 m g/m 3 30 m g/m 3 S .D . R ange n M ean S .D . R ange 1 n M ean 0 .0 2 6 0 .0 2 3 0 .0 2 3 0 .0 3 0 0 .0 1 4 50 24 50 0 .0 3 0 50 24 50 50 24 50 0 .0 3 6 50 24 50 50 24 50 0 .0 3 5 50 24 50 50 24 50 0 .0 2 8 50 24 50 50 24 50 0 .0 2 1 50 24 50 100 m g/m 3 S .D . R ange n 0 .0 3 4 0 .0 3 8 0 .0 4 8 0 .0 3 9 0 .0 2 5 50 24 50 24 50 24 50 24 50 24 Week l a 35 0 .0 0 31 35 5 50 0 .0 0 5 0 50 5 50 0 .0 2 0 50 5 50 0 .0 2 5 50 5 6 35 0 .0 1 3 35 24 50 0 .0 2 3 50 24 50 0 .0 2 5 50 24 50 0 .0 3 4 50 24 7 35 0 .0 1 2 35 24 50 0 .0 4 8 50 24 50 0 .0 3 1 50 24 50 0 .0 4 3 50 24 8 35 0 .0 1 4 35 24 50 0 .0 2 2 50 24 50 0 .0 3 2 50 24 50 0 .0 3 4 50 24 9 35 0 .0 1 7 35 24 50 0 .0 3 1 50 24 50 0 .0 3 0 50 24 50 0 .0 2 5 50 24 10 35 0 .0 1 2 35 24 50 0 .0 5 2 50 24 50 0 .0 3 3 50 24 50 0 .0 4 1 50 24 Week 2 35 0 .0 0 3 6 35 5 50 0 .0 2 1 50 5 50 0 .0 2 2 50 5 50 0 .0 1 4 50 5 11 35 0 .0 2 4 35 24 50 0 .0 2 0 50 24 50 0 .0 2 1 50 24 50 0 .0 3 2 50 24 12 35 0 .0 1 2 35 24 50 0 .0 2 1 50 24 50 0 .0 2 8 50 24 50 0 .0 2 7 50 24 13 35 0 .0 1 8 35 24 50 0 .0 2 6 50 24 50 0 .0 3 1 50 24 50 0 .0 3 7 50 24 14 35 0 .0 1 5 35 24 50 0 .0 2 0 50 24 50 0 .0 3 4 50 24 50 0 .0 3 4 50 24 15 . 35 0 .0 0 9 35 24 50 0 .0 2 2 50 24 50 0 .0 2 5 50 24 50 0 .0 2 1 50 24 i 1 Week 3 35 0 .0 0 67 35 5 50 0 .0 1 2 50 5 50 0 .0 2 0 50 5 50 0 .0 1 2 50 5 <1 16 35 0 .0 5 7 35 24 50 0 .0 3 2 50 24 50 0 .0 3 3 50 24 50 0 .0 2 9 50 24 3QWi 17 35 0 .0 4 4 35 24 50 0 .0 3 0 50 24 50 0 .0 2 7 50 24 50 0 .0 3 1 50 24 18 35 0 .0 8 7 35 - 36 24 50 0 .0 3 6 50 24 50 0 .0 3 7 50 24 50 0 .0 3 1 50 24 19 35 0 .0 9 6 35 - 36 24 50 0 .0 2 8 50 24 50 0 .0 2 5 50 24 50 0 .0 3 1 50 24 20 35 0 .1 0 35 24 50 0 .0 3 3 50 24 50 0 .0 2 7 50 24 50 0 .0 3 2 50 24 ,<a$ W e e k 4 3 5 0 . 0 6 9 3 5 5 5 0 0 . 0 2 3 5 0 5 5 0 0 .0 2 3 5 0 5 5 0 0 . 0 0 5 4 5 0 5 8 TScA 8 - 97- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX C Individual Body Weights Company saniti*. oes not contain TSCACB - 98- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 " ssq pexjjju^ iCwduiojj <* oo .'J *a id J" CO $ 3 B ody W e ig h t g Day 0 M a le , I 0 m g/m 3 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 664822 664823 664824 664825 664826 2 45.3 2 83 .1 2 99 .1 2 91 .4 2 56 .0 2 75 .6 2 70 .0 2 82 .0 2 77 .9 2 66 .6 2 82 .7 2 79 .1 2 80 .0 2 73.2 2 70 .4 B ody W e ig h t g Day 7 2 69 .1 3 19 .8 3 48 .5 3 41 .1 2 85 .9 3 13 .4 2 90 .9 3 19 .5 3 04 .6 2 93 .0 2 97 .4 3 11 .7 2 90 .6 2 97 .6 2 87 .7 B ody W e ig h t g Day 14 2 98 .0 3 52 .0 3 91 .0 3 78 .4 3 15 .4 3 46 .2 3 07 .2 3 47 .9 3 28 .8 3 25 .6 3 10 .6 3 42 .1 3 15 .0 3 33 .0 3 07 .2 In d iv id u a l B ody W e ig h ts B ody W e ig h t B ody W e ig h t B ody W e ig h t g Day 21 g Day 25 g Day 28 3 19 .6 3 84 .2 4 30 .2 4 01 .1 3 24 .7 3 77 .6 3 24 .7 3 52 .4 3 54.3 3 56 .1 3 38 .9 3 74 .3 3 37 .6 3 67 .7 3 30 .2 3 10 .1 3 65 .4 4 14 .8 3 80 .1 3 10 .4 3 48 .1 3 08 .9 3 35 .8 3 37 .4 3 25 .9 3 38 .7 3 89 .0 3 51 .7 3 74 .6 3 45.3 B ody W e ig h t g Day 35 3 5 0 .1 4 29 .8 3 9 7 .7 4 1 7 .9 3 9 1 .6 B ody W e ig h t g Day 42 3 94 .6 4 62 .2 4 2 4 .9 4 36 .2 4 3 4 .9 B od y W e ig g Day 49 4 32 .1 4 90 .1 4 50 .5 4 61 .5 4 6 8 .0 B ody W e ig h t g Day 56 M a le , I 0 m g/m 3 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 664822 664823 664824 664825 664826 4 22 .0 4 75 .7 4 34 .0 4 44 .8 4 58 .8 -99- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 B ody W e ig h t g Day 0 M a le , :I I I 5 m g /m 3 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 664837 664838 664839 664840 664841 2 48.7 2 68 .4 3 02.3 2 88.3 2 58.0 2 74 .7 2 71 .7 2 70 .2 2 76 .4 2 67 .0 2 90 .2 2 66 .2 2 82.3 2 59.9 2 56 .6 B ody W e ig h t g Day 7 2 76 .4 2 96 .9 3 38 .8 3 14 .8 2 76 .7 3 07 .9 2 89 .9 2 9 6 .0 3 06 .5 2 95 .2 3 0 3 .5 2 87 .9 3 0 4 .6 2 72 .9 2 69 .0 B ody W e ig h t g Day 14 3 08 .3 3 21 .7 3 71 .9 3 45 .6 3 00 .9 3 37 .4 2 99 .5 3 2 2 .5 3 35.3 3 14 .9 3 22 .2 3 17 .7 3 29 .6 2 95 .9 2 87 .1 In d iv id u a l B ody W e ig h ts B ody W e ig h t B ody w e ig h t B ody W e ig h t g Day 21 g Day 25 g Day 28 3 28 .4 3 5 4 .3 4 03 .9 3 76.3 3 16 .9 3 68 .5 3 20 .7 3 40 .8 3 64 .0 3 40 .2 3 39 .5 3 44 .6 3 49 .6 3 23 .7 3 08 .7 3 07.3 3 39 .3 3 79 .6 3 46 .2 2 90.3 3 44 .4 2 97 .4 3 18 .6 3 42 .8 3 24 .0 3 53 .0 3 57 .9 3 61 .7 3 34 .8 3 26 .4 B ody W e ig h t g Day 35 3 8 8 .8 4 0 1 .2 4 08 .1 3 7 4 .5 3 61 .9 B od y W e ig h t g Day 42 4 2 7 .4 4 2 5 .8 4 2 7 .4 4 0 7 .8 3 83 .6 B ody W e ig h t g Day 49 4 5 2 .7 4 5 2 .1 4 47 .9 4 42 .4 3 9 9 .5 B ody W e ig h t g Day 56 M a le , I I I 5 m g/m 3 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 664837 664838 664839 664840 664841 4 37 .6 4 31 .8 4 3 4 .2 4 21.9 3 85.1 Company Sanitized. Does not contain TSCA CB1 -100- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 B ody W e ig h t g Day 0 M a le , V 30 m g/m 3 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 664852 664853 664854 664855 664856 2 54 .6 2 84 .6 3 05 .7 2 90 .5 2 57.4 2 7 2 .5 2 70 .9 2 71.2 2 8 2 .4 2 6 5 .8 2 78 .7 2 64.0 2 79 .9 2 66 .6 2 5 6 .5 B ody W e ig h t g Day 7 2 71 .4 3 15.3 3 33 .3 3 19.3 2 67 .8 2 92 .4 2 94 .7 3 05 .4 3 03 .0 2 80 .9 3 02 .7 2 84 .1 3 06 .2 2 8 7 .1 2 72 .8 B ody W e ig h t g Day 14 2 87 .4 3 37 .6 3 55 .8 3 37 .6 2 72.0 3 05 .6 3 14 .4 3 30 .5 3 22 .0 2 96 .7 3 29 .1 3 01.7 3 26 .5 3 18.3 2 87 .5 In d iv id u a l B ody W e ig h ts B ody W e ig h t B ody W e ig h t B ody W e ig h t g Day 21 g Day 25 g Day 28 2 92 .9 3 69 .0 3 72 .8 3 67 .1 2 79 .9 3 18 .2 3 33 .6 3 52 .7 3 43 .8 3 15 .9 3 49 .7 3 19 .9 3 42 .1 3 41 .4 3 05 .5 2 76 .8 3 39 .8 3 54 .7 3 46 .1 2 67 .4 3 07 .4 3 10.3 3 30 .4 3 21 .4 2 97 .7 3 72 .2 3 4 0 .3 3 58 .8 3 59 .7 3 20 .7 B ody W e ig h t g Day 35 4 15 .9 3 93 .8 3 96 .3 3 9 9 .2 3 5 9 .2 B ody W e ig h t g Day 42 4 54 .7 4 3 3 .8 4 2 3 .4 4 28 .6 3 9 3 .4 B o d y W eigl g Day 49 4 8 5 .2 4 7 3 .3 4 4 7 .2 4 60 .8 4 13 .5 B ody W e ig h t g Day 56 M a le , V 30 m g/m 3 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 664852 664853 664854 664855 664856 4 71.4 4 55 .1 4 34.6 4 38 .5 3 98.9 Company Sanitized. Does not contain TSCA CBI -101 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 B ody W e ig h t g Day 0 M a le , V II 100 m g/m 3 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 664867 664868 664869 664870 664871 2 48.3 2 86 .3 2 96 .8 2 92 .2 2 4 9 .1 2 71 .1 2 74 .7 2 73.9 2 81 .2 2 45 .3 2 77 .6 2 74 .2 2 78 .0 2 70 .1 2 57 .0 B ody W e ig h t 9 Day 7 2 6 9 .3 3 11 .6 3 17 .5 3 31 .4 2 57 .8 2 93 .6 3 00 .4 2 98 .9 321.6 2 55 .0 3 04 .7 2 99 .7 3 04 .3 2 93 .3 2 58 .8 B ody W e ig h t g Day 14 2 90 .8 3 29 .3 3 4 4 .6 3 5 6 .5 2 6 4 .4 3 24 .1 3 2 4 .6 3 18 .6 3 60 .7 2 69 .2 3 28 .4 3 23 .9 3 43 .0 3 1 5 .6 2 84 .7 In d iv id u a l B ody W e ig h ts B ody W e ig h t B ody W e ig h t B ody W e ig h t g Day 21 g Day 25 g Day 28 3 08 .4 3 50 .3 3 71 .3 3 81 .0 2 81 .4 3 55 .2 3 46 .5 3 33 .8 3 90 .1 2 90 .2 3 50 .1 3 40.3 3 75 .1 3 33 .7 3 02 .8 2 93 .9 3 32 .2 352.0 3 60 .6 2 68.3 3 3 7 .7 3 22.3 3 1 5 .6 3 7 5 .1 2 75 .7 3 7 2 .8 3 64 .9 3 9 8 .5 3 3 2 .8 3 16 .2 B ody W e ig h t 3 Day 35 4 1 2 .4 4 1 3 .8 4 33 .3 3 7 2 .5 3 43 .8 B ody W e ig h t g Day 42 4 42 .8 4 54 .4 4 7 0 .5 4 06 .9 3 71 .2 B ody W e ig h t g Day 49 4 6 8 .6 4 9 0 .4 4 9 9 .7 4 26 .8 3 86 .8 B od y W e ig h t g Day 56 M a le , V II 100 m g/m 3 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 664867 664868 664869 664870 664871 4 61 .5 4 80.7 4 78 .9 4 0 8 .9 3 77 .8 Company Sanitised. Does not contain TSCA CBI - 102- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX D Individual Food Consumption Company Sanitized, d o e s not contain TSCA CBI - 103 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 INDIVIDUAL FOOD CONSUMPTION EXPLANATORY NOTES ABBREVIATIONS: Cons. - consumption g/anm/day - grams of food consumed per animal per day NOTES: Since only a partial food consumption period would have occurred at the end o f the in-life period, and since that period would have included fasting prior to sacrifice, food consumption measurements were discontinued after test day 21. Company anftizad. Dons ,,o , cnm,,, TSCA CB , -104- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Food Cons. g /a n m /d a y Day 7 M a le , I 0 m g/m 3 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 664822 664823 664824 664825 664826 2 1 ..5 2 6..2 2 9 ..5 2 8 ..7 22 . 1 2 4 ..4 2 1 ,.8 24 .2 24 .4 24 .2 2 5 ..0 2 6 ,.1 2 2 ..9 2 3 ..4 24 .1 Food Cons, g /a n m /d a y Day 14 2 1 .,5 2 4..6 2 9..4 2 8 ..9 23 .2 2 3..8 2 1 ..1 2 5 ..4 2 4 ..4 2 5 ..7 2 0 .,6 2 4 ..6 2 3..3 25,. 5 22.. 1 I n d iv id u a l F ood C o n s u m p tio n Food Cons, g /a n m /d a y Day 21 2 1 .,5 2 4 .,5 3 1 ,.5 2 5 ..8 1 9 ,.8 2 4 ..7 2 2 ..3 2 3..3 2 4 ..7 2 6 ..9 2 2 ..1 2 6 ..8 23 .9 2 6 ,.8 22 .1 DuPont-11414 Company Sanitized. Does not contain TSCACBi - 105- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Food Cons. g /a n m /d a y Day 7 M a le , I I I 5 m g/m 3 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 664837 664838 664839 664840 664841 2 3 .2 2 4 .3 2 7 .2 2 5 .8 2 3 .8 2 5 .3 2 5 .1 2 2 .0 2 5 .7 2 5 .7 2 4 .1 2 3 .0 2 3 .1 2 1 .3 2 2 .1 Food Cons. g /a n m /d a y Day 14 2 4 .2 2 5 .6 2 7 .6 2 5 .4 2 2 .6 2 5 .8 2 1 .9 2 2 .8 2 6 .0 2 4 .8 2 4 .1 2 3 .2 2 3 .8 2 2 .1 2 1 .9 I n d iv id u a l F ood C o n s u m p tio n Food C ons. g /a n m /d a y Day 21 2 4 .6 2 6 .4 2 7 .5 2 6 .5 21.1 2 6 .4 22.6 2 2 .5 2 7 .1 2 4 .5 2 3 .3 2 2 .5 2 5 .4 2 4 .4 2 1 .5 DuPont-11414 .Company Sanitized. Does not contain TSC A CB1 - 106- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Food Cons. g /a n m /d a y Day 7 M a le , V 30 m g/m 3 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 664852 664853 664854 664855 664856 2 3 .2 2 3 .5 2 8 .0 2 4 .2 1 9 .9 2 3 .6 2 2 .0 2 5 .8 2 4 .9 2 2 .8 2 3 .7 2 3 .0 2 5 .6 2 4 ,8 2 1 .7 Food Cons. g /a n m /d a y D ay 14 2 2 .1 2 2 .0 2 3 .9 2 3 .1 1 8 .3 2 1 .9 2 0 .8 2 5 .6 2 3 .9 2 1 .0 2 4 .5 2 2 .5 2 4 .6 2 3 .0 2 1 .7 In d iv id u a l F ood C o n s u m p tio n Food Cons. g /a n m /d a y Day 21 2 0 .1 2 2 .1 2 1 .9 2 3 .9 1 7 .7 2 1 .7 2 1 .9 2 6 .3 2 3 .7 2 2 .1 2 3 .7 2 3 .6 2 2 .4 2 4 .0 2 1 .9 DuPont-11414 ComHm) SanilM . Does not contain TSCACBi - 107- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Food Cons. g /a n m /d a y Day 7 Food Cons. g /a n m /d a y Day 14 M a le , V II 100 m g/m 3 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 664867 664868 664869 664870 664871 2 1 .6 2 6 .3 2 3 .5 2 6 .2 2 1 .6 2 1 .8 2 4 .6 2 5 .9 2 7 .4 1 8 .8 2 3 .8 2 5 .1 2 4 .7 2 5 .4 is :2 2 1 .6 2 3 .8 2 4 .0 2 5 .3 2 0 .4 2 1 .9 2 3 .2 2 2 .2 2 7 .0 1 9 .2 2 4 .2 2 3 .7 2 6 .6 2 3 .7 2 2 .8 I n d iv id u a l F ood C o n s u m p tio n Food Cons. g /a n m /d a y Day 21 2 1 .4 2 3 .7 2 3 .1 2 6 .5 2 1 .2 2 4 .2 2 2 .8 2 2 .4 2 6 .5 2 1 .0 2 4 .7 2 4 .2 2 7 .2 2 4 .2 2 2 .8 DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 108- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX E Individual Clinical Observations and Mortality Records Company Sanitized. Does nof contain TSCA CBf H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MI 664812 MI 664813 MI 664814 MX 664815 MI 664816 MI 664817 MI 664818 MI 664819 MI 664820 MI 664821 In d iv id u a l C lin ic a l O b s e rv a tio n s P rio r to E xpo sure and M o r ta lity R e cords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , H a ir L o ss, F o re lim b , B ila te r a l H a ir L o ss, F orepaw , B ila te r a l S a c r ific e d b y d e s ig n R ig h t 0 -7 25 1 4 -2 5 1 4 -2 5 25 DuPont-11414 P82/|.ues Auedmo -110- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MI 664822 MI MI MI MI O 664823 664824 664825 664826 In d iv id u a l C lin ic a l O b s e rv a tio n s P r io r to E xpo sure and M o r ta lity R e cords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , E n o p h th a lm u s , R ig h t Eye O b s e rv a tio n s , E x o p h th a lm u s , R ig h t Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , D is c h a rg e , E ye r ig h t. B la c k H a ir L o ss, F ace, R ig h t S a c r ific e d b y d e s ig n L e ft 0 -2 1 4 2 -5 6 2 8 -3 5 56 35 4 2 -5 6 56 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 DuPont-11414 1Doe* fK>tcontain TSCA CBI - Ill - ) H-2S134: Four-Week Inhalation Toxicity Study in Male Rats ) In d iv id u a l C lin ic a l O b s e rv a tio n s P r io r to E xp o su re and M o r ta lity R e cords S ex G roup A n im a l O b s e rv a tio n Days M III 664827 G e n e ra l, o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664828 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664829 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664830 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t H a ir L o ss, F o re lim b , B ila te r a l H a ir L o ss, F orepaw , B ila te r a l S a c r ific e d b y d e s ig n 0 -7 25 25 1 4 -2 5 25 M III 664831 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664832 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 Company Sanitized. Does not M III 664833 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664834 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664835 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 M III 664836 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 3OO tt S' M III 664837 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 0 -5 6 56 56 5 S - 112- DuPont-11414 ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l M III 664838 M III 664839 M III 664840 M III 664841 In d iv id u a l C lin ic a l O b s e rv a tio n s P rio r to E xpo sure and M o r ta lity R ecords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c rific e d b y .d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t W ound, S u p e rfic ia l, T a il S a c r ific e d b y d e s ig n 0 -1 4 ,4 9 -5 6 56 2 1 -4 2 56 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t D is c h a rg e , N ose, B la c k S a c r ific e d b y d e s ig n 0 -2 1 ,3 5 -5 6 56 28 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 DuPont-11414 -113 - Company Sanitized, Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) Sex G roup A n im a l MV 664842 MV 664843 MV 664844 MV MV MV MV 664845 664846 664847 664848 MV MV 664849 664850 MV MV 664851 664852 In d iv id u a l C lin ic a l O b s e rv a tio n s P rio r to E xpo sure a nd M o r ta lity R e cords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y .d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t H a ir L o ss, F orepaw , B ila te r a l S a c r ific e d b y d e s ig n 0 25. 7 -2 5 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , H a ir L o ss, F orepaw , B ila te r a l W ound, S u p e rfic ia l, T a il S a c r ific e d b y d e s ig n R ig h t 0 -7 25 25 1 4 -2 5 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , Wound, S u p e rfic ia l, T a il W ound, Deep, T a il S a c r ific e d b y d e s ig n R ig h t 0 25 2 1 -2 5 7 -1 4 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 -114- DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MV 664853 MV 664854 MV 664855 MV 664856 In d iv id u a l C lin ic a l O b s e rv a tio n s P r io r to E xpo sure and M o r ta lity R e cords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t D is c h a rg e , N ose, B la c k S a c r ific e d b y d e s ig n 0 -2 1 ,3 5 -5 6 56 28 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , H a ir L o ss, F o re lim b , B ila te r a l H a ir L oss, Forepaw , B ila te r a l S a c r ific e d b y d e s ig n R ig h t 0 -2 1 56 2 8 -5 6 2 8 -5 6 56 DuPont-11414 Company Sanitized. Does not contain TSCA CBi -115- Company Sanitized. Does not contain TSCA CBJ H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l M V II 664857 M V II 664858 M V II 664859 M V II 664860 M V II 664861 M V II 664862 M V II 664863 M V II 664864 M V II 664865 M V II 664866 M V II 664867 In d iv id u a l C lin ic a l O b s e rv a tio n s P r io r to E xpo sure and M o r ta lity R ecords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t H a ir L o ss, S h o u ld e r, R ig h t S a c r ific e d b y d e s ig n 0 -1 4 25 2 1 -2 5 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25' 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -2 5 25 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , H a ir L o ss, Forepaw , B ila te r a l H a ir L o ss, Forepaw , L e ft S a c r ific e d b y d e s ig n R ig h t 0 25 2 1 -2 5 7 -1 4 25 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 -116- DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l M V II 664868 M V II 664869 M V II 664870 M V II 664871 In d iv id u a l C lin ic a l O b s e rv a tio n s P rio r to E xp o su re a nd M o r ta lity R e cords O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d E ye O b s e rv a tio n s , E n o p h th a lm u s , R ig h t E ye O b s e rv a tio n s , E x o p h th a lin u s , R ig h t Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , D is c h a rg e , Eye r ig h t, B la c k H a ir L o ss, F ace, R ig h t S a c r ific e d b y d e s ig n L e ft 0 -2 1 4 2 -5 6 2 8 -3 5 56 2 8 -3 5 42 56 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d Eye O b s e rv a tio n s , B le d v ia O r b ita l fo r C lin P a th , R ig h t S a c r ific e d b y d e s ig n 0 -5 6 56 56 DuPont-11414 Company Sanitized. Does not contain TSCA CBI -117- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MI 664812 MI 664813 Mi Mi Mi 664814 664815 664816 Mi MX MI 664817 664818 664819 MI MI 664820 664821 MI MI 664822 664823 In d iv id u a l C lin ic a l O b s e rv a tio n s i O b s e rv a tio n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila te r a l, B row n D is c h a rg e , N ose, Red D is c h a rg e , Eye le f t . B la c k D is c h a rg e , Eye le f t , Brow n D is c h a rg e , Eye r ig h t, Brow n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila te r a l, B row n D is c h a rg e , Eye l e f t , Brow n D is c h a rg e , Eye r ig h t, B la c k G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye le f t , B row n G e n e ra l o b s e rv a tio n , NO A bnorm a1 i ty D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , E ye b ila te r a l, B row n D is c h a rg e , Eye le f t , B la c k D is c h a rg e , Eye l e f t . Brow n D e te cte d G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te cte d D is c h a rg e , Eye b ila te r a l. Brow n D is c h a rg e , Eye r ig h t. Brow n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye r ig h t, Brow n Company Sanitized. Does not contain TSCA CBI -118- M ite r E xposure Days 0 ,2 -2 5 1 2 ,8 ,2 3 9 -2 1 1 ,3 -7 0 2 4 -2 5 22 0 0 -2 5 0 -2 5 0 -1 0 ,1 4 -1 5 ,1 7 ,2 1 -2 2 ,2 5 18 2 3 -2 4 16 11 0 -2 5 0 -1 7 ,2 2 ,2 4 1 8 -2 1 ,2 3 ,2 5 0 ,3 -4 ,8 ,1 0 ,1 5 ,2 1 -2 5 2 ,1 6 -1 8 1 7 ,9 1 1 -1 4 0 ,2 -2 5 1 0 ,2 -1 6 ,2 1 ,2 4 1 ,2 2 -2 3 ,2 5 1 7 -1 8 0 -2 1 ,2 3 -2 5 22 3 -7 ,2 2 -2 4 0- 2, 8-21 25 DuPont-11414 > H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) In d iv id u a l C lin ic a l O b s e rv a tio n s A fte r E xpo sure Sex G roup A n im a l O b s e rv a tio n Days MI 664824 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , E ye b ila t e r a l, B row n D is c h a rg e , Eye le f t , B la c k D is c h a rg e , Eye r ig h t, B la c k 0 ,2 -3 ,8 -9 ,1 7 1 0 -1 6 ,1 8 -2 5 1 7 4 M. I 664825 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B row n 0 ,2 -2 1 ,2 4 -2 5 1 ,2 2 -2 3 MI 664826 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l. B la c k D is c h a rg e , Eye b ila t e r a l. B row n D is c h a rg e , Eye l e f t , B row n 2 -2 2 ,2 4 0 1 2 3,2 5 oo 3 s 3 83CO M CO 2 2 -119- ) DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l C lin ic a l O b s e rv a tio n s . Sex G roup A n im a l O b s e rv a tio n M III 664827 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye l e f t , Brow n M III 664828 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l. Brow n D is c h a rg e , Eye l e f t , Brow n M III 664829 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila t e r a l, Brow n D is c h a rg e , Eye le f t , B la c k M III 664830 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , E ye b ila t e r a l, Brow n D is c h a rg e , N ose, B row n M III 664831 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d M III 664832 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , E ye b ila t e r a l, B row n D is c h a rg e , Eye l e f t , B la c k D is c h a rg e , Eye le f t . B row n Company Sanitized. Does not M III 664833 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , E ye b ila t e r a l, B row n D is c h a rg e , Eye le f t , B la c k D is c h a rg e , Eye r ig h t. Brow n M III 664834 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , Eye l e f t , Brow n D is c h a rg e , Eye r ig h t, Brow n M III 664835 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila t e r a l, Brow n D is c h a rg e , Eye r ig h t, B la c k o 9*o3+)> M III 664836 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye le f t , Brow n D is c h a rg e , Eye r ig h t, Brow n 5' M III 664837 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d to D is c h a r g e , E y e b i l a t e r a l . B ro w n 2 D is c h a rg e , Eye le f t , Brow n -120- A fte r E xposure Days 0 -2 2 ,2 4 -2 5 23 0 ,2 -8 ,1 6 -1 8 ,2 3 -2 5 1 9 -1 5 ,2 1 -2 2 0 -3 ,9 ,1 8 -2 3 ,2 5 4 -8 ,1 4 -1 7 24 10-11 0 -1 1 ,1 5 -1 6 ,1 8 -2 5 17 14 14 0 -2 5 2 ,4 ,2 3 1 0 -2 2 ,2 4 -2 5 1 .3 7 -9 0 2 ,4 ,8 ,2 5 9 -2 4 1 .3 7 0 0 -1 5 ,1 8 -2 2 1 6 -1 7 2 3 -2 4 25 0 -1 ,4 9 1 0 -2 5 2 -3 ,7 -8 0 -8 ,1 0 -1 4 ,1 6 -2 2 ,2 4 -2 5 23 9 ,1 5 0 -1 4 ,1 6 ,2 4 -2 5 2 2 -2 3 1 5 ,1 7 -2 1 DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l M III 664838 M III M III 664839 664840 M III 664841 In d iv id u a l C lin ic a l O b s e rv a tio n s A fte r E xpo sure O b s e rv a tio n Days G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , Eye l e f t , Brow n 0 ,2 -8 ,1 1 ,1 5 -1 7 ,2 3 -2 4 1 , 10,22 9 ,1 4 ,1 8 -2 1 ,2 5 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d W ound, S u p e r f ic ia l, H in d p a w , L e f t 0 -7 8 -2 5 G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , Eye b ila te r a l, B row n D is c h a rg e , Eye le f t , B la c k D is c h a rg e , Eye le f t , Brow n 0 -3 ,7 -8 ,1 0 ,1 4 ,1 8 ,2 2 ,2 4 -2 5 23 1 5 -1 7 4. 9 ,1 1 ,2 1 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila t e r a l. B row n D is c h a rg e , Eye r ig h t. Brow n 0 ,2 -8 ,1 1 -2 2 ,2 4 -2 5 23 1 9 -1 0 DuPont-11414 I I aaCO a tSo -121 - 130 V O S l uiejuoo H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MV 664842 .M V 664843 MV MV 664844 664845 MV MV MV 664846 664847 664848 MV MV 664849 664850 MV 664851 MV 664852 In d iv id u a l C lin ic a l O b s e rv a tio n s , O b s e rv a tio n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , Eye l e f t , B row n D is c h a rg e , Eye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , E ye l e f t , B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , E ye b ila t e r a l. B row n D is c h a rg e , E ye le f t . B la c k D is c h a rg e , Eye l e f t , B row n D is c h a rg e , E ye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e r v a tio n . NO A b n o r m a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , E ye b ila t e r a l. B row n D is c h a rg e , E ye l e f t , B la c k D is c h a rg e , Eye le f t , B row n Wound, S u p e rfic ia l, T a il G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , Eye le f t , B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, Brow n D is c h a rg e , Eye l e f t , B row n W ound, Deep, T a il G e n e ra l o b s e rv a tio n , No A b n o rm a lity D is c h a rg e , Eye b ila t e r a l. B la c k D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , Eye le f t , B row n D is c h a rg e , Eye r ig h t, B row n D e te cte d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, Brow n Company Sanitized. Does not contain TSCA CBI - 122- filte r E xposure Days 0 -2 5 0 - 4 ,8 -1 0 ,1 5 ,1 7 ,2 4 2 1 -2 3 7 ,1 6 1 1 -1 4 ,2 5 18 0 ,4 -9 ,1 4 -1 7 ,2 1 -2 5 1 - 3 ,1 0 -1 1 ,1 8 1 ,4 -9 ,1 1 ,1 7 ,2 2 ,2 4 23 2 - 3 ,1 6 0 1 0 ,1 4 -1 5 ,2 5 1 8 -2 1 0 -2 5 0 -2 5 0 ,2 -3 ,7 -9 1 ,2 2 -2 3 4 ,1 0 -1 7 21 1 4 - 25 0 - 8 ,1 0 -1 4 ,1 8 -2 5 1 5 - 17 9 0 ,4 1 - 3 ,9 -1 1 ,1 6 -2 1 2 3 -2 5 7 -2 5 0 ,4 -1 4 ,1 6 -1 7 ,2 1 ,2 4 15 I - 3 ,2 2 -2 3 18 25 0 -1 0 ,2 1 -2 2 ,2 4 -2 5 I I - 1 8,2 3 DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l MV 664853 MV MV MV 664854 664855 664856 In d iv id u a l C lin ic a l O b s e rv a tio n s A fte r E xpo sure O b s e rv a tio n Days G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila t e r a l, Brow n D is c h a rg e , Eye le f t , B la c k 4 ,1 7 ,2 1 -2 2 7 ,9 -1 6 .1 -3 ,1 8 ,2 3 -2 5 0 ,8 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, Brow n 0 ,2 ,4 -1 4 ,1 7 -2 5 1 ,3 ,1 5 -1 6 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye r ig h t, B row n 0 ,2 -8 ,1 0 -2 1 ,2 4 -2 5 1 ,9 ,2 2 -2 3 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l, B la c k D is c h a rg e , Eye b ila t e r a l, Brow n D is c h a rg e , Eye r ig h t, B la c k D is c h a rg e , Eye r ig h t, B row n 2 -3 ,7 ,1 5 0 ,8 -9 1 1 -1 4 ,1 7 -2 5 4 ,1 0 1 ,1 6 DuPont-11414 .Company Sanitfced. Does not contain CHO -123- H-25134: Four-Week Inhalation Toxicity Study in Male Rats Sex G roup A n im a l M V II 664857 M V II 664858 M V II M V II M V II 664859 664860 664861 M V II 664862 M V II M V II 664863 664864 M V II 664865 M V II M V II 664866 664867 M V II M V II 664868 664869 In d iv id u a l C lin ic a l O b s e rv a tio n s i O b s e rv a tio n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye l e f t . B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye l e f t , B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , Eye le f t . Brow n D is c h a rg e , Eye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l. B row n D is c h a rg e , Eye r ig h t, B la c k G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , Eye b ila t e r a l, B row n D is c h a rg e , N ose, B row n D is c h a rg e , Eye r ig h t, B la c k D is c h a rg e , Eye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l. B la c k D is c h a rg e , Eye b ila t e r a l, B row n G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye l e f t . Brow n G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila te r a l. Brow n D is c h a rg e , Eye r ig h t, Brow n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye r ig h t, B row n G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , Eye b ila t e r a l, B la c k D is c h a rg e , Eye b ila te r a l, B row n W ound, S u p e r fic ia l, H in d p a w , L e ft Company Sanlftea* Doss not contain TSCA CSf -124- lifte r E xposure Days 0 ,2 -4 ,1 1 -2 1 ,2 3 ,2 5 1 .7 - 1 0 ,2 2 ,2 4 0 -1 0 ,1 4 -2 5 11 0 -2 5 0 -2 5 0 -1 ,4 -1 6 ,1 8 1 7 ,2 2 -2 5 21 2 -3 4 3 .7 - 25 0-2 0 - 25 0 ,1 0 ,1 5 9 3 ,1 1 -1 4 ,1 6 -2 5 4 -8 7- 8 1- 2 0 -8 ,1 0 -1 1 ,1 5 -1 8 ,2 5 9 1 4 ,2 1 -2 4 0 -9 ,1 1 -2 5 10 0 ,2 ,4 -8 ,1 0 -2 5 3 1 ,9 0 - 8 ,1 1 -2 5 9 -1 0 0 ,7 8 - 25 1- 4 4 ) DuPont-11414 ))) H-25134: Four-Week Inhalation Toxicity Study in Male Rats_____________________________________________________________________ DuPont-11414 Sex G roup A n im a l M V II 664870 M V II 664871 In d iv id u a l C lin ic a l O b s e rv a tio n s A fte r E xpo sure O b s e rv a tio n Days G e n e ra l o b s e rv a tio n . No A b n o rm a lity D e te c te d D is c h a rg e , E ye b ila t e r a l, Brow n D is c h a rg e , Eye r ig h t. B la c k D is c h a rg e , Eye r ig h t, Brow n 0 -1 ,3 -1 0 ,1 5 -1 7 ,2 5 2 ,1 1 14 1 8 -2 4 G e n e ra l o b s e rv a tio n , No A b n o rm a lity D e te c te d D is c h a rg e , E ye le f t , B row n 0 -1 0 ,1 4 -2 5 11 Company Sanitized. Does not contain TSCA OBI -125- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX F Individual Animal Clinical Pathology Data Company Sanitized. Does not contain TSCA GBl H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 IN D IV ID U A L AN IM AL CLINICAL PATH OLOG Y D A T A EXPLANATORY NOTES ABBR EVIATIO N S : General: ADEQ - a d e q u a te CLOT DECR _ s a m p le c lo t te d d e c re a s e d NT - n o t ta k e n o r n o t p e rfo rm e d NT-HEM OL - n o t ta k e n d u e t o h e m o ly s is OK - s a m p le c o n d itio n OK f o r t e s tin g QNS " q u a n t it y n o t s u f f ic i e n t f o r t e s t in g RNV - r e s u lt n o t v a lid < - le s s th a n Individual Hematology Values: COND - s a m p le c o n d itio n RBC - re d b lo o d c e ll c o u n t HGB ~ h e m o g lo b in HOT - h e m a to c r it MCV - m ean c o r p u s c u la r v o lu m e MCH m ean c o r p u s c u la r h e m o g lo b in MCHC - m ean c o r p u s c u la r h e m o g lo b in c o n c e n tr a tio n RDW - r e d c e l l d i s t r i b u t i o n w id t h ARET - a b s o lu te r e tic u lo c y te c o u n t PLT p la te le t c o u n t WBC ANEU -_ w h ite b lo o d c e ll c o u n t a b s o lu te n e u tro p h il ( a ll fo rm s) ALYM - a b s o lu te ly m p h o c y te AMDN - a b s o lu te m o n o c y te AEOS - a b s o lu te e o s in o p h il ABAS - a b s o lu te b a s o p h il ALUC - a b s o lu te la rg e u n s ta in e d c e ll Individual Red Blood Cell Morphology Values: NORM N orm al A N IS a n is o c y to s is M IC m ic r o c y te s MAC m a c ro c y te s POLY p o ly c h ro m a s ia HYPO h y p o c h ro m a s ia ECHI e c h in o c y te s ACAN a c a n th o c y te s TARG T a rg e t c e lls RX ro u le a u x HJB - H o w e ll-J o lly 1 n o t o b s e rv e d o r n o t e x a m in e d ; se e w h o le b lo o d s a m p le c o n d itio n Individual White Blood Cell / Platelet Morphology Values: NORM N orm al SM S m udge w h it e b lo o d c e l l s TOX to x ic n e u tro p h ils DB D o h le b o d ie s VC v a c u o la te d c y to p la s m BC b a s o p h ilic c y to p la s m PCE p la t e le t c lu m p s / e s tim a te GP g ia n t p la t e le t s BP b iz a r r e .p la t e le t s n o t o b s e rv e d o r n o t e xa m in e d ; see w h o le b lo o d s a m p le c o n d itio n C om pany S a n itized . D o e s not contain TSCA C 'Bf H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 IN D IV ID U A L A N IM A L CLINICAL PATHOLOGY D A T A EXPLANATORY NOTES (Continued) ABBR EVIATIO N S : (C o n tin u e d ) Individual Coagulation Values: PHEM - p la s m a h e m o ly s is P LIP p la s m a lip e m ia P IC T p la s m a ic te r u s PT - p ro th ro m b in tim e APTT a c tiv a te d p a r tia l th ro m b o p la s tin tim e Individual Clinical Chemistry Values: SHEM - s e ru m h e m o ly s is S LIP - serum lip e m ia S IC T - s e ru m ic t e r u s AST - a s p a rta te a m in o tra n s fe ra s e ALT - a la n in e a m in o tra n s fe ra s e SDH - s o r b it o l d e h y d ro g e n a s e ALKP - a lk a lin e p h o s p h a ta s e B IL I - to ta l b ilir u b in BUN - u re a n itr o g e n CREA - c re a tin in e CHOL - c h o le s te r o l TR IG - t r ig ly c e r id e s GLUC - g lu c o s e TP - to ta l p ro te in ALB - a lb u m in GLOB - g lo b u lin CALC - c a lc iu m IPH S - in o r g a n ic p h o s p h o ro u s NA - so d iu m K - p o ta s s iu m CL PHEM -- c h lo rid e p la s m a h e m o ly s is fro m b lo o d s a m p le f o r f lu o r id e d e te rm in a tio n P LIP - p la s m a lip e m ia fro m b lo o d s a m p le f o r f lu o r id e d e te rm in a tio n P IC T - p la s m a ic t e r u s fro m b lo o d s a m p le f o r f lu o r id e d e te rm in a tio n PFLU - p la s m a f lu o r id e Individual Urinalysis Values: QUAL - q u a lit y (m o d ifie s c o lo r) COL - c o lo r CLAR - c la r it y VOL - v o lu m e UOSM " u r in e o s m o la lity pH - th e lo g a rith m o f th e re c ip ro c a l o f th e h yd ro g e n io n c o n c e n tra tio n UGLU - u r in e g lu c o s e KET - ke to n e U B IL - u rin e b ilir u b in BLD - b lo o d URO - u r o b ilin o g e n UFLU - u rin e flu o r id e UMTP - u r in e p r o te in SPEC - s p e c ia l o b s e rv a tio n s Individual Urine microscopic Examination Values: E P IT - e p it h e lia l c e lls UWBC - u r in e w h it e b lo o d c e l l s URBC - u r in e re d b lo o d c e lls NCRY - n o rm a l c r y s ta ls M ICR - m ic ro o rg a n is m s SPER - sperm Company Sanitized. D oes not contain TSCA CB( - 128- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 IN D IV ID U A L A N IM A L CLINICAL PATHOLOGY D A TA EXPLANATORY NOTES (Continued) NOTES : When in d iv id u a l a n im a l d a ta a re n o t re p o rte d , i t m ay be due to one o f th e fo llo w in g re a s o n s o r o th e r re a s o n s , a l l o f w h ic h a re e x p la in e d in th e s tu d y re c o rd s : th e s a m p le w as c lo t t e d (CLOT) th e r e w a s i n s u f f i c i e n t s a m p le f o r t e s t in g (QNS) a v a lid r e s u l t c o u ld n o t b e o b ta in e d (RNV) th e s a m p le w as n o t s u ita b le f o r te s tin g th e a n im a l d ie d p r io r to s a m p le c o lle c tio n n o s a m p le w as a v a ila b le f o r t e s t in g (NSR) When an in d iv id u a l o b s e rv a tio n w as re c o rd e d as b e in g le s s th a n a c e r ta in v a lu e , c a lc u la tio n s w e re p e rfo rm e d on h a lf th e re c o rd e d v a lu e . F o r e x a m p le , i f b ilir u b in w as re p o rte d as < 0 .1 , 0 .0 5 was used fo r any c a lc u la tio n s p e rfo rm e d w ith th a t b ilir u b in d a ta . Company Sanitized. Does not contain TSCA CBl - 129- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l H e m a to lo g y V a lu e s A n im a l COND RBC HGB HCT MCV MCH MCHC RDW AR ET P LT WBC N um ber x l0 6/pX. g /d L % fL pg g /d L % x 103/ uL x l0 3/p L x IO V u L M a le , G roup I - 0 m g/m 3 - Day 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 OK OK OK OK OK OK OK OK OK OK 8 .3 3 1 6 .5 4 8 .3 5 8 .0 1 9 .8 3 4 .1 1 1 .2 1 9 4 .6 1422 1 2 .7 9 7 .6 8 1 5 .4 4 5 .7 5 9 .5 2 0 .0 3 3 .6 1 1 .4 2 0 6 .6 1017 1 1 .6 0 7 .8 5 1 5 .7 4 7 .2 6 0 .1 2 0 .0 3 3 .3 1 0 .6 2 7 0 .2 1136 1 0 .3 6 7 .9 9 1 5 .9 4 5 .6 5 7 .0 1 9 .8 3 4 .8 1 0 .7 1 8 6 .5 1266 1 0 .3 7 7 .8 6 1 5.3 4 5 .1 5 7 .4 1 9 .4 3 3 .9 1 0 .7 1 4 9 .2 KNV 1 1 .3 6 7 .9 4 1 5 .1 4 4 .8 5 6 .4 1 9 .0 3 3 .7 1 1 .2 1 3 7 .6 RNV 1 4 .1 8 8 .1 4 1 6 .0 4 6 .8 5 7 .5 1 9 .7 3 4 .2 1 0 .8 1 2 5 .5 1226 8 .7 4 7 .4 6 1 5 .6 4 5 .0 6 0 .3 2 0 .9 3 4 .6 1 0 .9 1 1 1 .6 1173 7 .8 6 8 .2 2 1 6 .2 4 7 .6 5 7 .9 1 9 .7 3 4 .1 1 0 .3 1 6 3 .3 RNV 1 0 .9 7 7 .8 1 1 5 .3 4 4 .6 5 7 .1 1 9 .6 3 4 .3 1 1 .2 1 4 9 .9 RNV 1 6 .6 1 M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 OK 7 .9 9 1 5 .5 4 5 .0 5 6 .3 1 9 .4 3 4 .5 1 0 .9 1 7 6 .1 1425 1 1 .7 4 664828 OK 7 .4 3 1 4 .7 4 4 .1 5 9 .3 1 9 .8 3 3 .4 1 1 .0 2 2 7 .4 RNV 1 0 .4 2 664829 OK 7 .7 2 1 5 .7 4 7 .0 6 0 .8 2 0 .4 3 3 .5 1 1 .7 2 0 8 .2 1096 1 3 .0 4 664830 OK 8 .2 2 1 5 .8 4 6 .5 5 6 .5 1 9 .2 3 4 .0 1 0 .0 1 55 .4 1265 1 4 .6 5 664831 OK 7 .7 7 1 5 .8 4 6 .1 5 9 .4 2 0 .4 3 4 .3 1 0 .5 1 53 .4 1259 1 1 .9 6 664832 CLOT NT NT NT NT NT NT NT NT NT NT 664833 OK 8 .3 0 1 6 .2 4 6 .7 5 6 .3 1 9 .6 3 4 .7 1 0 .8 1 2 7 .0 RNV 9 .4 6 C564834 OK 7 .6 7 1 5 .8 4 4 .9 5 8 .5 2 0 .6 3 5 .1 1 1 .0 1 6 9 .3 RNV 1 3 .2 1 64835 OK 7 .6 5 1 6 .0 4 5 .9 6 0 .0 2 0 .9 3 4 .8 1 0 .4 1 6 2 .6 RNV 1 1 .6 0 4564836 OK 7 .9 2 1 5 .4 4 4 .2 5 5 .8 1 9 .4 3 4 .8 1 0 .6 1 9 7 .5 RNV 1 2 .6 5 3 ) DuPont-11414 -130- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l N um ber COND RBC x l0 6/p L HGB g /d L M a le , G roup V - 30 m g/m 3 - Day 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 OK OK OK OK OK OK OK OK OK OK 8 .5 4 1 6 .8 7 .7 7 1 5 .3 8 .1 5 1 5 .5 7 .4 8 1 5 .3 8 .4 4 1 6 .2 8 .0 2 1 6 .1 8 .4 6 1 6 .1 8 .1 2 1 5 .3 8 .4 8 1 5 .8 7 .8 1 1 5 .6 M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 OK OK OK OK OK OK OK OK OK OK 7 .8 9 1 6 .3 8 .1 6 1 6 .5 7 .8 1 1 5 .1 8 .0 0 1 5 .3 7 -8 5 1 5 .4 7 .4 6 1 5 .0 7 .8 2 1 5 .8 7 .9 7 1 5 .5 8 .2 3 1 6 .8 8 .3 2 1 5 .3 HCT % 4 8 .1 4 4 .2 4 6 .0 4 3 .7 4 6 .8 4 7.3 4 6.3 4 5 .2 4 6 .6 4 5 .5 4 6 .9 4 7 .9 4 4.3 4 5 .6 4 4 .9 4 2 .7 4 6 .7 4 6 .2 4 8.3 4 5 .2 In d iv id u a l H e m a to lo g y V a lu e s MCV MCH MCHC RDW fL pg g /d L % ARET x lo V u L PLT x lo V p L WBC x 1 0 3/ u L 5 6.3 1 9 .7 3 5 .0 1 0 .5 1 1 0 .5 1313 9 .2 9 5 6 .8 1 9 .7 3 4 .7 1 1 .0 1 4 7 .9 KNV 1 3.6 2 5 6 .4 1 9 .0 3 3 .6 1 1.3 1 5 3 .3 1004 1 1 .8 3 5 8 .5 2 0 .5 3 5 .0 1 0 .6 1 6 3 .3 RNV 1 4 .1 9 5 5 .5 1 9 .1 3 4 .5 1 0 .7 1 0 3 .2 904 1 1.5 2 5 9 .0 2 0 .1 3 4 .0 1 1 .0 1 7 6 .5 RNV 8 .6 4 5 4 .7 1 9 .0 3 4 .8 1 1 .3 1 4 4 .3 RNV 1 1 .7 2 5 5 .7 1 8 .8 3 3 .7 1 0 .9 8 1 .5 1089 1 2.2 7 54.9 1 8.7 3 4 .0 1 1.9 8 8 .6 RNV 1 0 .3 5 5 8 .2 2 0 .0 3 4 .3 1 0 .6 1 7 0 .7 1189 1 8 .6 6 5 9 .4 2 0 .7 3 4 .8 1 0 .6 1 6 7 .9 1055 1 6.3 8 5 8 .7 2 0 .3 3 4 .5 1 0 .2 1 62 .3 1311 1 6 .4 0 5 6 .8 1 9.3 3 4 .0 1 0 .7 1 3 8 .6 1151 9 .9 4 5 7 .0 1 9 .1 3 3 .5 1 1 .2 1 4 2 .0 1011 1 4 .0 6 5 7 .3 1 9 .6 3 4 .3 1 1.3 1 31 .7 1165 1 1 .9 6 5 7.3 2 0 .2 3 5 .2 1 0 .6 1 3 5 .9 1140 9 .4 5 5 9 .8 2 0 .2 3 3 .8 1 0 .6 1 3 0 .1 RNV 1 0 .4 4 5 8 .0 1 9 .5 3 3 .6 1 0 .9 1 6 6 .2 1027 1 3 .5 0 5 8 .7 2 0 .4 3 4 .8 1 0 .8 1 9 3 .2 RNV 1 1 .4 8 5 4.3 1 8 .4 3 3 .9 1 0 .4 1 2 6 .9 1200 9 .0 8 ) DuPont-11414 Sanitized. Does .O3 -tot 5 -131 - Company Sanitised. Does not contain TSCA H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l ANEU ALYM AMON Num ber x l0 3/p L x lo V p L x lo V p L M a le , G roup I - 0 m g/m 3 - Day 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 1 .5 4 1 .4 5 0 .5 1 1 .2 6 2 .3 4 1 .8 4 1 .3 8 1 .0 8 1 .0 4 2 .4 9 1 0.8 4 9 .8 1 9 .3 4 8 .6 8 8 .5 8 1 1.7 6 6 .9 6 6 .4 7 9 .4 1 1 3.1 8 0 .1 6 0 .1 9 0 .3 1 0 .2 6 0 .1 6 0 .3 2 0 .1 6 0 .1 4 0 .2 9 0 .5 0 M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 664828 664829 664830 664831 664832 664833 664834 664835 0664836 0 .9 7 1 .5 4 1 .9 8 1 .5 1 3 .0 5 NT 0 .8 6 1 .2 9 1 .3 4 1 .6 2 1 0.4 4 8 .4 8 1 0.6 5 1 2.5 1 8 .3 8 NT 8 .3 0 1 1.4 8 9 .7 5 1 0.53 0 .1 1 0 .2 1 0 .1 7 0 .3 5 0 .3 2 NT 0 .1 5 0 .1 7 0 .2 1 0 .2 4 AEOS x l0 3/p L 0 .1 2 0 .0 3 0 .0 7 0 .0 6 0 .1 2 0 .0 9 0 .0 8 0 .0 8 0 .0 6 0 .2 1 0 .0 7 0 .1 1 0 .1 2 0 .0 6 0 .0 9 NT 0 .0 7 0 .1 2 0 .1 2 0 .0 9 In d iv id u a l H e m a to lo g y V a lu e s ABAS ALUC x lo V p L x l0 3/p L 0 .0 6 0 .0 7 0 .0 5 0 .0 8 0 .0 3 0 .1 1 0 .0 4 0 .0 7 0 .0 5 0 .1 0 0 .0 7 0 .1 0 0 .0 8 0 .0 9 0 .0 4 0 .0 4 0 .1 0 0 .0 8 0 .1 3 0 .0 9 0 .0 7 0 .0 8 0 .0 3 0 .0 5 0 .0 6 0 .0 6 0 .1 1 0 .1 0 0 .0 4 0 .0 8 NT NT 0 .0 4 0 .0 6 0 .0 6 0 .1 0 0 .0 8 0 .0 9 0 .1 0 0 .0 8 DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l ANEU ALYM AMON N u m b e r x 1 0 3/ vlL x l 0 3/ u L x l 0 3/ y L M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 0 .9 4 1 .0 9 1 .4 1 1 .2 8 0 .8 0 0 .8 6 1 .0 6 1 .4 4 0 .7 9 2 .3 6 7 .9 9 1 1.6 7 9 .7 9 1 2.2 2 1 0.1 9 7 .7 8 1 0.2 9 1 0.2 8 8 .8 8 1 5.5 0 0 .1 0 0 .1 7 0 .2 0 0 .3 2 0 .2 1 0 .0 0 0 .2 0 0 .3 1 0 .2 3 0 .4 4 M a le , G r o u p V I I - 1 0 0 m g /m 3, - D a y 2 5 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 1 .8 0 0 .7 6 1 .1 5 1 .4 0 1 .4 3 1 .0 1 1 .4 7 1 .4 0 0 .8 0 1 .6 9 1 3 .9 5 1 5.0 8 8 .4 2 1 2.13 1 0.0 6 8 .0 3 8 .6 3 1 1.6 8 1 0.1 0 6 .9 8 0 .2 9 0 .1 2 0 .1 8 0 .2 2 0 .1 5 0 .1 7 0 .1 7 0 .2 2 0 .5 7 0 .1 2 AEOS x l0 3/u L 0 .1 1 0 .0 6 0 .1 9 0 .1 5 0 .1 3 0 .0 0 0 .0 7 0 .0 6 0 .1 9 0 .0 8 0 .1 1 0 .1 0 0 .1 2 0 .1 3 0 .0 8 0 .1 3 0 .0 7 0 .0 4 0 .0 0 0 .1 6 In d iv id u a l H e m a to lo g y V a lu e s ABAS ALUC x l0 3/y L x l0 3/y L 0 .0 7 0 .0 8 0 .1 7 0 .4 5 0 .1 2 0 .1 2 0 .1 1 0 .1 1 0 .1 0 0 .0 9 0 .0 0 0 .0 0 0 .0 5 0 .0 5 0 .0 8 0 .1 0 0 .1 5 0 .1 0 0 .0 9 0 .1 9 0 .1 3 0 .1 0 0 .1 3 0 .2 1 0 .0 4 0 .0 4 0 .0 9 0 .0 9 0 .0 9 0 .1 4 0 .0 7 0 .0 4 0 .0 4 0 .0 6 0 .1 0 0 .0 7 0 .0 0 0 .0 0 0 .0 7 0 .0 5 DuPont-11414 Company SanHized. Does not contain TSCA C61 - 133 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber NORM A N IS M IC M a le , G roup I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 NO NO NO NO NO NO NO NO NO NO - - - - - M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 664828 664829 664830 664831 664832 664833 664834 0664835 2 664836 3o NO NO NO NO NO CLOT NO NO NO NO NT _ NT - - In d iv id u a l Red B lo o d C e ll M o rp h o lo g y V a lu e s MAC POLY HYPO ECHI ACAN TARG _ TRACE _ TRACE FEW - - TRACE - TRACE - - - TRACE - TRACE - - - TRACE - FEW MODERATE - - TRACE - - - - - TRACE - MANY FEW - - TRACE - MANY - - - TRACE - - - - _ TRACE - TRACE - - - TRACE - - TRACE - _ TRACE _ MODERATE TRACE - - TRACE - FEW TRACE - - TRACE - TRACE - MANY - FEW _ - - TRACE - - - - NT NT NT NT NT NT - TRACE - FEW MODERATE - - TRACE - - - - - TRACE - FEW TRACE - - TRACE - - FEW - RX _ - - - - - _ NT - HJB - - - NT - DuPont-11414 I. Does not contain TSCA CBl -134- ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l N um ber NORM A N IS M IC M a le , G roup V - 30 m g/m 3 - D ay 25 664842 NO - - 664843 NO - - 664844 NO - - 664845 NO _ - 664846 NO - - 664847 NO - - 664848 NO - - 664849 NO - - 664850 NO TRACE TRACE 664851 NO _ - M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 oo 6 6 4 8 6 6 3 NO NO NO NO NO NO NO NO NO NO _ ~ - - - - - 3 C3O 8a In d iv id u a l Red B lo o d C e ll M o rp h o lo g y V a lu e s MAC POLY HYPO ECHI ACAN TARG - TRACE - - TRACE - - TRACE - MANY FEW - - TRACE - FEW - - TRACE - FEW MODERATE - TRACE - TRACE - - - TRACE - - - - - TRACE - - - - - TRACE - - - - - TRACE - FEW FEW - - TRACE - - - - - TRACE - TRACE - - - TRACE - - - - - TRACE - TRACE MODERATE - - TRACE - - - - - TRACE - TRACE - - - TRACE - FEW MODERATE - - TRACE - MANY - - - TRACE - - - - - TRACE - - - - - TRACE - - - - RX - - HJB DuPont-11414 Does not contain TSCA CBI -135- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber NORM SM TOX 4 a le , G roup I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 YES YES YES YES NO NO YES YES NO NO _ - - _ - tfa le , G roup I I I - 5 m g/m 3 - D ay 2 5 664827 664828 664829 664830 664831 664832 664833 664834 664835 I 664836 YES NO YES YES YES CLOT NO NO NO NO _ NT - _ NT - 1 In d iv id u a l W h ite B lo o d C e ll / P la te le t M o rp h o lo g y V a lu e s DB VC BC PCE GP BP ______ ----------- ----- - - YES/ADEQ - - - _ YES/DECR _ - - _- - - - -- - - - - YES/ADEQ - - - - YES/ADEQ - - ___- - _ - - - YES/ADEQ - - - --- ------ - ---NT NT NT NT NT NT - - - YES/ADEQ - - - - YES/ADEQ - - - - YES/ADEQ - _ - - YES/AD EQ - - S30Q -P*'U8S I\ 1- tofl > --ir es - 136- DuPont-11414 )) ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats______________________________________________________________________DuPont-11414 A n im a l N um ber NORM SM TOX M a le , G roup V - 30 m g/m 3 - Day 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 YES NO YES NO YES NO NO YES NO YES - - - - _ - M a le , G r o u p V I I - 1 0 0 m g /m 3 - D a y 2 5 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 YES YES YES YES YES YES NO YES NO YES - - - _ _ - In d iv id u a l W h ite B lo o d C e ll / P la te le t M o rp h o lo g y V a lu e s DB VC BC PCE GP BP ------ - - YES/ADEQ - ----- - - - YES/ADEQ - -- - --- - - YES/DECR - - - YES/ADEQ ~ . - - --- - - - YES/ADEQ - - - -- -- ------------------------------- - - YES/ADEQ - -- -- - - - - YES/DECR - ------ pao sanate1 -137- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l C o a g u la tio n V a lu e s A n im a l PHEM P LIP P IC T PT APTT N um ber sec sec M a le , G roup I - 0 m g/m 3 - D ay 25 664812 TRACE NONE NONE 1 5 .3 2 3 .8 664813 NONE NONE NONE 1 5 .1 1 9 .5 664814 NONE NONE NONE 1 4 .4 2 0 .1 664815 NONE NONE NONE 1 3 .8 2 0 .1 664816 NONE NONE NONE 1 5 .1 1 9.9 664817 NONE NONE NONE 1 6 .8 2 1 .8 664818 NONE NONE NONE 1 8 .0 2 2 .9 664819 NONE NONE NONE 1 8 .0 2 0 .4 664820 NONE NONE NONE 1 5 .1 2 1 .2 664821 NONE NONE NONE 1 5.3 1 9 .6 M a le , G ro u p I I I - 5 m g /m 3 - D a y 2 5 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 1 5 .6 1 5 .6 1 5 .6 1 4 .8 1 5 .1 1 7 .1 2 1 .6 1 5 .4 1 4 .9 1 4.9 2 1 .9 1 8.1 2 1 .2 2 0 .2 1 9 .9 2 3 .6 2 2 .3 2 0 .9 2 0 .4 1 9 .9 DuPont-11414 Santttted-Does -138- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber PHEM P LIP P IC T M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PT sec 1 6 .1 1 4 .6 1 5 .1 1 5.2 1 7.3 1 5.9 1 5.7 1 5 .1 1 5.9 1 4.4 1 5 .5 1 5.3 1 5.9 1 5.2 1 4 .8 1 5.1 1 5.1 1 6.0 1 4.9 1 5 .8 In d iv id u a l C o a g u la tio n V a lu e s APTT sec 2 3 .5 1 7 .8 1 9 .9 1 8 .1 2 1 .9 1 9 .6 1 9 .6 1 8 .6 2 0 .4 1 9 .7 2 2 .8 2 1 .2 1 9.9 2 1 .1 1 9 .5 1 8.7 1 7.7 1 9.4 1 8.5 1 8.3 DuPont-11414 Company Sanitized. Does not contain TSC A CBI -139- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber SHEM S LIP S IC T M a le , G ro up I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 NONE NONE TRACE NONE NONE NONE NONE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 TRACE NONE NONE 664828 TRACE NONE NONE 664829 TRACE NONE NONE 664830 TRACE NONE NONE oo 664831 664832 664833 NONE NONE TRACE NONE NONE NONE NONE NONE NONE 664834 TRACE NONE NONE 664835 TRACE NONE NONE 664836 TRACE NONE NONE In d iv id u a l AST ALT /L U /L 109 27 87 27 88 28 82 23 110 35 133 35 94 31 106 29 136 37 86 34 111 40 93 27 92 32 120 40 114 39 90 28 100 28 93 30 93 31 93 34 mitized. Doe* not contain C lin ic a l C h e m is try V a lu e s SDH ALKP B IL I U /L U /L m g/dL BUN m g/dL CREA m g/dL CHOL m g/dL 6 .4 219 0 .1 0 16 0 .4 4 48 1 9 .5 249 < 0 .1 0 16 0 .3 2 40 1 7 .1 257 < 0.1 0 15 0 .3 6 49 1 2 .0 192 0 .1 1 15 0 .3 0 49 6 .5 165 < 0 .1 0 14 0 .3 0 60 1 1 .1 162 0 .1 0 15 0 .3 4 56 1 2 .5 177 0 .1 1 13 0 .3 1 45 6 .2 191 0 .1 2 14 0 .3 3 46 2 1 .1 184 0 .1 0 12 0 .3 0 42 1 1 .1 170 < 0 .1 0 15 0 .2 3 40 1 3 .4 231 0 .1 1 15 0 .3 8 35 RNV 237 0 .1 2 16 0 .3 2 31 2 3 .2 212 < 0 .1 0 13 0 .3 3 47 RNV 225 0 .1 0 16 0 .3 9 45 9 .0 181 < 0.1 0 16 0 .3 1 49 1 0 .5 197 0 .1 0 14 0 .3 9 45 RNV 187 0 .1 1 15 0 .2 1 38 8 .4 191 < 0.1 0 16 0 .2 8 63 1 1 .3 271 < 0 .1 0 14 0 .2 7 44 1 3 .0 216 < 0 .1 0 12 0 .2 2 33 DuPont-11414 - 140- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber SHEM S LIP S IC T M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 TRACE TRACE TRACE MODERATE TRACE TRACE NONE TRACE SMALL SMALL NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 NONE TRACE TRACE TRACE NONE NONE SMALL TRACE 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 C lin ic a l C h e m is try V a lu e s AST ALT SDH ALKP B IL I U /L U /L U /L U /L m g/dL 95 35 1 0.2 189 0 .1 0 93 39 2 2 .5 143 0 .1 0 101 27 7 .9 145 < 0.1 0 NT-HEM OL NT-HEM OL RNV NT-HEM OL NT-HEM OL 107 33 1 0 .9 226 0 .1 3 98 31 1 0 .9 129 < 0 .1 0 132 31 5 .1 165 0 .1 0 122 50 1 4.2 179 0 .1 3 118 47 8 .4 187 0 .1 1 118 33 RNV 200 0 .1 3 100 32 2 2 .6 287 0 .1 0 96 27 1 0 .2 202 0 .1 0 111 41 8 .7 201 < 0.1 0 110 40 1 3 .5 128 0 .1 2 84 33 1 6 .6 218 0 .1 3 112 33 RNV 198 < 0 .1 0 121 41 1 0 .5 248 0 .1 1 86 28 8 .7 225 < 0.1 0 86 28 1 4 .3 217 < 0.1 0 106 48 1 2 .7 209 < 0.1 0 BUN m g/dL 14 17 14 15 14 17 17 16 14 16 14 15 17 16 13 12 13 12 16 15 CREA m g /dL 0 .3 1 0 .2 8 0 .3 7 0 .3 2 0 .3 4 0 .4 5 0 .3 2 0 .2 6 0 .3 0 0 .3 1 0 .3 7 0 .3 4 0 .3 9 0 .4 1 0 .2 8 0 .2 9 0 .2 9 0 .2 6 0 .3 5 0 .2 9 CHOL m g/dL 29 53 44 56 39 40 53 32 48 49 29 21 28 42 49 32 43 20 26 38 DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 141 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber TR IG m g/dL GLUC m g/dL TP g /d L M a le , G roup I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 19 48 49 51 39 26 31 29 34 33 99 6 .4 96 6 .1 85 6 .2 81 6 .4 81 6 .1 97 6 .3 84 6 .4 79 6 .6 98 6 .4 84 6 .1 M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 16 85 6 .1 664828 21 82 5 .9 664829 23 77 5 .8 664830 44 82 6 .4 664831 12 79 5 .8 664832 11 2 6 6 .4 664833 17 95 5 .8 664834 16 96 6 .4 664835 20 98 6 .4 664836 15 98 6 ,1 In d iv id u a l C lin ic a l C h e m is try V a lu e s ALB GLOB CALC IPH S NA K CL g /d L g /d L m g/dL m g /dL m m o l/L m m o l/L m m o l/L 4 .7 1 .7 1 0 .6 1 1.4 1 4 5 .1 5 .7 7 1 0 1 .4 4 .2 1 .9 1 0 .7 9 .9 1 46.2 5 .5 6 9 9 .8 4 .4 1 .8 1 0 .9 1 0 .4 1 44 .9 6 .6 4 1 0 1 .5 4 .4 2 .0 1 0 .8 9 .1 1 4 6 .1 5 .8 7 1 0 1 .4 4 .1 2 .0 1 0 .5 9 .5 1 47 .2 5 .5 8 1 0 3 .9 4 .2 2 .1 1 0.2 8 .3 1 46.1 5 .8 5 9 9 .9 4 .3 2 .1 1 0 .8 8 .9 1 48 .0 6 .2 1 1 0 1 .3 4 .5 2 .1 1 1 .1 9 .5 1 47 .9 5 .9 7 1 0 2 .9 4 .3 2 .1 1 1 .6 1 0 .0 1 49.3 6 .4 2 1 0 3 .4 4 .0 2 .1 1 0.9 8 .9 1 4 8 .4 5 .8 1 1 04 .7 4 .3 1 .8 1 0.3 8 .7 1 4 4 .0 5 .6 5 1 01 .2 4 .1 1 .8 1 0 .5 9 .6 145.7 6 .1 6 1 0 4 .6 4 .0 1 .8 1 1 .0 1 1 .6 1 48 .4 6 .9 6 1 0 2 .4 4 .6 1 .8 1 0 .8 8 .5 1 48 .2 5 .8 0 1 0 2 .9 4 .1 1 .7 1 0 .6 9 .1 1 50.3 6 .1 6 1 0 7 .5 4 .5 1 .9 1 0.9 9 .5 1 45 .0 5 .3 8 1 02 .3 4 .3 1 .5 1 0 .6 9 .9 1 4 6 .1 6 .8 9 1 0 4 .2 4 .4 2 .0 1 0 .9 9 .1 1 47 .9 5 .5 4 1 0 4 .4 4 .4 2 .0 1 1 .0 9 .6 1 49 .1 6 .3 8 1 0 2 .8 4 .3 1 .8 1 1 .0 1 0.4 1 49 .7 6 .0 2 1 0 7 .7 DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 142- H-25134: Four-Week Inhalation Toxicity Study in Male Rats_______________________________________ ___ _____________________ _____ DuPont-11414 In d iv id u a l C lin ic a l C h e m is try V a lu e s A n im a l TR IG GLUC TP ALB GLOB CALC IPH S NA K Num ber m g/dL m g/dL g /d L g /d L g /d L m g/dL m g /d L m m o l/L m m o l/L M a le , G roup V - 30 m g/m 3 - D ay 25 664842 22 98 6 .3 4 .4 1 .9 1 0 .5 664843 21 88 6 .1 4 .2 1 .9 1 0.2 664844 32 88 6 .3 4 .0 2 .3 1 1 .0 6 6 4 8 4 5 NT-HEMOL 84 NT-HEM OL NT-HEM OL NT-HEM OL 1 0 .2 664846 25 87 6 .4 4 .6 1 .8 1 0 .6 664847 10 106 6 .5 4 .4 2 .1 1 0.7 664848 23 98 6 .2 4 .3 1 .9 1 0.2 664849 20 86 6 .0 4 .4 1 .6 1 0.8 664850 23 88 6 .6 4 .4 2 .2 1 1.1 664851 29 94 6 .9 4 .6 2 .3 1 1 .1 8 .4 1 45.3 5 .8 8 8 .3 1 46 .2 5 .2 2 8 .3 1 51 .9 5 .9 2 8 .6 1 4 7 .4 NT-HEM OL 8 .4 1 50 .0 5 .8 7 1 0 .7 1 4 6 .1 5 .5 2 8 .5 1 4 5 .9 . 5 .6 0 8 .5 1 49.3 6 .0 9 8 .9 1 50 .2 6 .4 5 8 .2 1 51 .2 6 .4 4 M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 O 664864 664865 664866 31 21 31 27 37 30 23 20 17 30 82 6 .1 87 6 .5 94 6 .1 97 6 .2 80 6 .3 81 5 .5 82 6 .3 93 5 .8 117 6 .7 94 6 ,9 4 .2 1 .9 1 0.4 9 .6 1 46 .1 6 .0 4 4 .2 2 .3 1 0 .6 9 .5 1 46 .5 5 .6 0 4 .2 1 .9 1 0.3 9 .7 1 47 .1 6 .1 8 4 .2 2 .0 1 0 .5 8 .4 1 49 .9 5 .8 3 4 .5 1 .8 1 0.6 8 .0 1 52 .1 6 .0 6 3 .7 1 .8 1 0 .5 9 .4 1 46.3 6 .0 0 4 .2 2 .1 1 0.4 7 .9 1 49 .6 5 .9 3 4 .0 1 .8 1 0.5 8 .6 1 50 .7 5 .5 0 4 .3 2 .4 1 1 .4 1 0 .9 1 50 .1 5 .8 9 4 .6 2 .3 1 1.3 8 .0 1 53.3 5 .8 6 CL m m o l/L 1 0 1 .5 9 9 .6 1 04 .3 1 0 1 .8 1 03 .3 1 02 .0 1 02 .5 1 01 .3 1 0 2 .9 1 04 .0 1 0 0 .2 1 01 .7 1 03 .3 1 0 2 .6 1 03 .1 1 0 2 .4 1 0 4 .8 1 06 .2 1 03 .2 1 05 .2 contain TSCACBI - 143 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l PHEM P LIP P IC T N um ber M a le , G roup I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G ro u p I I I - 5 m g /m 3 - D a y 2 5 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PFLU pg/m L In d iv id u a l C lin ic a l C h e m is try V a lu e s 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .0 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .0 0 .1 DuPont-11414 ooO o OO Company Sanitized. Does net contain TSCA CBI -144- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber PHEM F L IP P IC T M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PFLU pg/m L In d iv id u a l C lin ic a l C h e m is try V a lu e s 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 QNS 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 0 .1 Company Sanitized. Does not OO 3 T -i >oCO o 03 - 145- DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l SHEM S LIP S IC T N um ber M a le , G roup I - 0 m g/m 3 - D ay 56 664822 664823 664824 664825 664826 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup I I I - 5 m g/m 3 - D ay 56 664837 664838 664839 664840 664841 NONE TRACE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE M a le , G roup V - 301 m g/m 3 - D ay 56 664852 TRACE NONE 664853 TRACE NONE 664854 NONE NNE 664855 NONE NONE 664856 TRACE . NONE NONE NONE NONE NONE NONE ! M a le , G ro up V I I - 100 m g/m 3 - D ay. 56 3< 664867 TRACE NONE NONE $ 664868 NONE NONE 9 664869 TRACE NONE SK 6 6 4 8 7 0 NONE NONE NONE NONE NONE N* 6 6 4 8 7 1 TR AC E NONE NONE CHOL m g /dL In d iv id u a l C lin ic a l C h e m is try V a lu e s TR IG TP ALB GLOB m g/dL g /d L g /d L g /d L 45 57 6 .7 4 .3 2 .4 66 63 6 .7 4 .3 2 .4 48 47 6 .4 4 .3 2 .1 53 63 6 .8 4 .2 2 .6 47 38 6 .4 4 .0 2 .4 52 84 6 .9 4 .7 2 .2 52 34 6 .2 4 .2 2 .0 46 51 6 .5 4 .3 2 .2 62 65 6 .7 4 .2 2 .5 46 27 6 .8 4 .5 2 .3 51 46 6 .4 4 .2 2 .2 71 89 6 .4 4 .4 2 .0 47 73 6 .5 4 .4 2 .1 50 71 6 .2 3 .9 2 .3 35 28 6 .2 4 .0 2 .2 60 96 7 .1 4 .6 2 .5 49 78 6 .4 4 .2 2 .2 73 64 6 .4 4 .1 2 .3 23 34 6 .4 4 .2 2 .2 51 49 6 .4 4 .0 2 .4 -146- ) DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l QUAL COL CLAR N um ber M a le , G roup 1 - 0 m g/m 3 - Dy 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 M E D IU M LIG H T LIG H T LIG H T M E D IU M LIG H T LIG H T M E D IU M LIG H T DARK YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLOUDY HAZY HAZY HAZY HAZY HAZY CLEAR HAZY HAZY M a le , G roup H H H 1 5 m g/m 3 - D ay 25 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 LIG H T LIG H T LIG H T M E D IU M LIG H T LIG H T LIG H T LIG H T LIG H T LIG H T YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR CLOUDY CLEAR CLEAR CLEAR HAZY CLOUDY CLOUDY In d iv id u a l VOL UOSM mL m O sm /kg pH 6 .2 1061 7 .0 6 .2 1261 7 .0 1 7.4 528 7 .0 7 .4 1028 7 .0 1 .8 2866 6 .0 5 .4 1185 6 .0 4 .0 1478 7 .5 3 .6 1790 6 .5 9 .0 706 7 .0 1 .0 3570 6 .0 2 .4 1185 3 .4 1163 12.0 691 1 .4 3516 4 .2 974 8 .2 785 1 1.0 454 4 .2 1328 5 .0 1412 4 .0 1793 6 .5 6 .5 6 .5 6 .5 6 .5 7 .0 6 .5 7 .0 8 .0 7 .5 ipany Sanitized. Does not contain TSCA ao U r in a ly s is V a lu e s UGLU m g/dL KET m g/dL OBIL BLD URO E U /d L ooo o oo oo o CO CO to to CO CO CO to CO (M CM oo NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5 5 5 15 5 15 5 5 5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE MODERATE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0 .2 0 .2 0 .2 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5 15 5 NEGATIVE 15 5 NEGATIVE 15 15 15 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE SMALL SMALL 0 .2 0 .2 0 .2 0 .2 0 .2 0 .2 DuPont-11414 ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l QAL COL CLAR N um ber M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 LIG H T LIG H T M E D IU M LIG H T LIG H T LIG H T LIG H T LIG H T M E D IU M LIG H T YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR CLEAR CLEAR CLEAR CLEAR HAZY HAZY M a le , G roup V II - 100 m g/m 3 - D ay 25 6 6 4 8 5 7 MEDIUM YELLOW CLEAR 664858 LIG H T YELLOW HAZY 664859 LIG H T YELLOW CLEAR 664860 LIG H T YELLOW HAZY 6 6 4 8 6 1 MEDIUM YELLOW CLEAR 664862 LIG H T YELLOW CLEAR 664863 LIG H T YELLOW CLEAR 664864 LIG H T YELLOW CLEAR 664865 LIG H T YELLOW CLEAR 664866 LIG H T YELLOW HAZY U3fi) A2oco' N* In d iv id u a l VOL UOSM mL m O sm /kg pH 4 .4 1125 7 .0 1 0 .8 775 7 .0 1 .4 2930 6 .0 5 .0 1396 6 .5 5 .6 718 7 .5 3 .2 1153 6 .5 5 .6 839 6 .0 3 .4 1441 6 .5 1 .4 2894 6 .0 7 .4 633 6 .5 2 .4 1824 6 .5 2 .2 1645 6 .5 9 .4 560 7 .0 1 2 .0 524 7 .5 1 .6 2521 6 .5 5 .0 1267 6 .5 1 1 .4 471 6 .0 4 .0 1077 6 .5 13.2 463 6 .0 5 .2 940 6 .0 contain TSCACBf U r in a ly s is V a lu e s UGLU m g/dL KET m g/dL UBIL BLD URO E U /d L o oo o to to to to NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5 5 NEGATIVE 5 NEGATIVE 15 NEGATIVE 5 5 5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0 .2 0 .2 0 .2 0 .2 0 .2 0 .2 oooo to tSJ to to NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 15 5 5 5 5 5 NEGATIVE 15 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE SHALL NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0 .2 0 .2 0 .2 0 .2 oo CO CO DuPont-11414 - 148- ) H-25134; Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l U r in a ly s is V a lu e s A n im a l N um ber UFLU pg UMTP SPEC m g/dL M a le , G ro up I - 0 m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 1 1 .7 1 2 .6 1 9.3 1 4.7 QNS 1 1 .6 QNS 1 0.4 1 2.3 QNS 52 163 FECAL CO NTAM INATIO N OBSERVED 27 110 276 67 120 146 153 180 a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 5 .6 8 .6 2 0 .1 QNS 7 .7 1 6.1 1 9.0 1 0 .6 13 .4 1 4.3 131 95 32 250 64 39 15 86 1 44 FECAL CO NTAM INATIO N OBSERVED 165 FECAL CO NTAM INATIO N OBSERVED ) DuPont-11414 Company Sanitized. Does not contain TS C A CBI - 149- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) A n im a l N um ber UFLU pg UM TP m g /d L SPEC M a le , G roup V - 30 m g/m 3 - D ay 25 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 1 7 .7 3 0.3 QNS 2 0 .5 1 4 .6 1 7 .9 1 3 .6 1 7.3 QNS 1 6 .5 75 25 212 97 29 108 38 82 164 34 M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 1 8.2 QNS 1 7 .8 3 7 .9 QNS 2 8 .5 2 5 .4 2 5.4 2 7.8 1 0.2 170 173 26 17 156 57 17 77 20 41 I n d iv id u a l U r in a ly s is V a lu e s Company Sanitized. Does not contain 5 2 - 150n DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats 10 3< ato N a oo A nim al N um ber UFLU pg M a le , G ro up I - 0 m g/m 3 - D ay 56 664822 664823 664824 664825 664826 1 5 .5 9 .4 2 2 .7 1 3.8 1 2 .1 M a le , G ro up I I I - 5 m g/m 3 - D ay 56 664837 664838 664839 664840 664841 9 .4 1 2.1 1 5.4 1 7.4 1 0 .8 M a le , G roup V - 30 m g/m 3 - D ay 56 664852 664853 664854 664855 664856 1 4 .5 1 1.9 1 2.2 1 0.7 9 .0 M a le , G roup V II - 100 m g/m 3 - Day. 56 664867 664868 664869 664870 664871 1 8.7 1 2 .6 1 5.5 9 .3 1 3.6 In d iv id u a l U r in a ly s is V a lu e s "ot contain TSCA s - 151 - DuPont-11414 jou S90Q 'P9 2 j,,UBS XlJBd| H 1 O H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber E P IT UWBC URBC M a le , G roup m g/m 3 - D ay 25 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 NONE NONE FEW NONE QNS NONE FEW NONE NONE QNS NONE NONE NONE NONE NT NONE NONE FEW NONE NT NONE NONE NONE NONE NT NONE NONE NONE NONE NT M a le , G roup I I I - 5 m g/m 3 - D ay 25 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 QNS QNS NONE QNS NONE NONE NONE NONE NONE NONE NT NT NONE NT NONE NONE NONE NONE NONE NONE NT NT NONE NT NONE NONE NONE NONE NONE NONE NCRY In d iv id u a l U rin e M ic ro s c o p ic V a lu e s MXCR SPER FEW MODERATE FEW FEW NT FEW FEW FEW MODERATE NT FEW MODERATE FEW FEW NT FEW FEW FEW FEW NT MODERATE FEW MODERATE MODERATE NT MANY MODERATE FEW MODERATE NT NT NT NT NT NT NT FEW FEW FEW NT NT NT FEW FEW FEW MODERATE FEW MODERATE FEW FEW FEW FEW FEW FEW FEW FEW NONE FEW FEW FEW DuPont-11414 - 152- H-25134: Four-Week Inhalation Toxicity Study in Male Rats A n im a l N um ber E P IT UWBC URBC M a le , G roup V - 30 m g/m 3 - D ay 2 5 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 NONE NONE QNS NONE NONE QNS NONE QNS QNS NONE NONE NONE NT NONE NONE NT NONE NT NT NONE NONE NONE NT NONE NONE NT NONE NT NT NONE M a le , G roup V II - 100 m g/m 3 - D ay 25 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 QNS QNS FEW FEW QNS NONE NONE NONE NONE NONE NT NT NONE NONE NT NONE NONE NONE NONE NONE NT NT NONE NONE NT NONE NONE NONE NONE NONE NCRY In d iv id u a l U rin e M ic ro s c o p ic V a lu e s M ICR SPER FEW MODERATE NONE FEW FEW , MODERATE NT NT NT FEW FEW FEW FEW FEW MANY NT NT NT FEW FEW FEW NT NT NT NT NT NT FEW FEW FEW NT NT NT NT NT NT FEW FEW FEW FEW FEW MODERATE NT NT NT FEW FEW NONE FEW FEW FEW FEW FEW FEW FEW FEW FEW MODERATE FEW FEW Pv feed. no| C3n(an CO o > DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX G Individuai Animal Blood Fluorine - 154 - Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL ANIMAL BLOOD FLUORINE FOOTNOTES: EXPLANATORY NOTES a Insufficient sample size for accurate analysis, b Sample not analyzed. DuPont-11414 -155- Company Sanitized. D o es not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats B lo o d F lu o rin e ppm Day 0 M a le , G ro up I - 0 m g/m 3 664822 664823 664824 664825 664826 1 .3 1 .2 1 .5 1 .3 1 .3 M a le , G ro up I I I - 5 m g/m 3 664837 664838 664839 664840 664841 M a le , G ro u p V - 30 m g/m 3 664852 664853 664854 64855 364856 o M J.e, G ro u p V I I 100 m g/m 3 ^4867 4868 64870 &4871 o % 1 .7 1.8 1 .9 1 .9 1 .4 B lo o d F lu o rin e ppm Day 7 1 .3 1 .4 1 .4 1 .2 1 .5 1 .9 2.0 2.1 2 .5 1 .9 OO3 e> 3 at o > o00 In d iv id u a l A n im a l B lo o d F lu o rin e B lo o d F lu o rin e ppm Day 14 B lo o d F lu o rin e ppm Day 25 B lo o d F lu o rin e PPm D ay 54 1 .0 1 .1 1 .6 0 .9 1 .2 1 .4 0 .9 1 .1 1 .1 0 .8 1 .1 1 .1 1 .3 1 .1 1 .2 1 .4 1 .1 1 .4 1 .3 1 .3 1 .7 a 1 .5 1 .3 1 .3 1 .1 2 . 7 1.8 2 . 6 1.8 2 .b6 2.1 1 .7 2.1 1 .7 2 .4 3 .2 3 .3a 4 .3a 2 .3 2 .9 4 .3 3 .9 4 .6a 3 .2 1 .5 1 .7 2.2 1.8 1 .4 -156- DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX H Individual Animal Final Body and Organ Weights Company Sanitized. Doe not contain TS C A CBI - 157- H-25134: Four-Week Inhalation Toxicity Study in Male Rats______________________________________________________________________ DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rg an W e ig h ts - D ay 25 S a c r ific e G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x : MALES 1 ANIM AL 1 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 FBW (G m s) 3 10.10 3 65.40 4 14.80 3 80.10 3 10 .40 3 48 .10 3 08 .90 3 35.80 3 37.40 3 25.90 BR AIN (G m s) %FBW 2 .0 4 9 0 .6 6 0 8 2 .1 1 4 0 .5 7 8 5 2 .0 6 4 0 .4 9 7 6 1 .9 4 5 0 .5 1 1 7 1 .6 9 7 0 .5 4 6 7 1 .8 5 1 0 .5 3 17 1 .8 5 4 0 .6 0 02 2 .1 4 7 0 .6 3 9 4 1 .9 2 3 0 .5 6 9 9 1 .9 2 4 0 .5 9 0 4 ADRENAL GLANDS (G m s) %FBW %B R A IN 0 .0 4 1 0 .0 6 0 0 .0 5 7 0 .0 5 3 0 .0 4 6 0 .0 4 4 0 .0 4 6 0 .0 5 7 0 .0 7 0 0 .0 7 7 0 .0 1 3 2 0 .0 1 6 4 0 .0 1 3 7 0 .0 1 3 9 0 .0 1 4 8 0 .0 1 2 6 0 .0 1 4 9 0 .0 1 7 0 0 .0 2 0 7 0 .0 2 3 6 2 .0 0 1 0 2 .8 3 8 2 2 .7 6 1 6 2 .7 2 4 9 2 .7 1 0 7 2 .3 7 7 1 2 .4 8 1 1 2 .6 5 4 9 3 .6 4 0 1 4 .0 0 2 1 EPID ID Y M ID E S (G m s) %FBW % BRAIN 0 .8 3 6 1 .0 5 2 0 .9 5 9 0 .9 7 4 0 .8 9 6 1 .0 0 2 1 .0 7 1 1 .1 8 0 1 .1 1 7 1 .0 9 3 0 .2 6 9 6 0 .2 8 7 9 0 .2 3 1 2 0 .2 5 6 2 0 .2 8 8 7 0 .2 8 7 8 0 .3 4 6 7 0 .3 5 1 4 0 .3 3 1 1 0 .3 3 5 4 4 0.8 00 4 9.7 63 4 6.4 63 5 0.0 77 5 2.7 99 5 4.133 5 7.7 67 5 4.9 60 5 8.0 86 5 6.8 09 HEART (G m s) %FBW % BR AIN 1 .1 9 9 1 .6 4 7 1 .7 3 1 1 .4 7 3 0 .9 7 5 1 .3 1 9 1 .3 5 8 1 .3 2 1 1 .3 0 1 1 .4 0 5 0 .3 8 6 6 0 .4 5 0 7 0 .4 1 73 0 .3 8 7 5 0 .3 1 4 1 0 .3 7 8 9 0 .4 3 9 6 0 .3 9 3 4 0 .3 8 5 6 0 .4 3 1 1 5 8 .5 1 6 7 7 .9 0 9 8 3.8 66 7 5.7 33 5 7.4 54 7 1.2 59 7 3.2 47 6 1 .5 2 8 6 7.6 55 7 3.0 25 Mean S .D . 3 4 3 .6 9 1 .9 5 7 0 .5 7 2 7 3 4 .5 4 2 0 .1 3 8 0 .0 5 2 7 0 .0 5 5 0 .0 1 6 1 2 .8 1 9 2 0 .0 1 2 0 .0 0 3 5 0 .5 8 7 2 1 .0 1 8 0 .2 9 8 6 5 2 .1 6 6 0 .1 0 5 0 .0 4 0 8 5 .4 9 6 4 1 .3 7 3 0 .3 9 8 5 7 0 .0 1 9 0 .2 1 4 0 .0 3 9 2 8 .6 6 3 6 KID N EYS I (G m s) %FBW % BR AIN 1 2 .7 0 2 3 .0 7 9 3 .2 2 4 3 .5 3 9 2 .0 6 4 2 .7 3 9 2 .6 6 4 3 .0 8 3 2 .8 9 4 3 .2 2 3 0 .8 7 1 3 0 .8 4 2 6 0 .7 7 7 2 0 .9 3 1 1 0 .6 6 4 9 0 .7 8 6 8 0 .8 6 2 4 0 .9 1 8 1 0 .8 5 7 7 0 .9 8 9 0 1 31 .87 145 .65 1 5 6 .2 0 181 .95 1 21 .63 1 47 .97 1 43 .69 1 4 3 .6 0 1 5 0 .4 9 1 67 .52 2 .9 2 1 0 .8 5 0 1 1 4 9 .0 6 0 .4 0 8 0 .0 9 1 1 1 6 .9 8 1 G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S ex MALES 1 ANIM AL i FBW B R A IN (G m s) (G m s) %FBW ADRENAL GLANDS (G m s) %FBW % BRAIN E PID ID YM ID ES (G m s) %FBW % BR AIN (G m s) HEART %FBW % BR AIN KID NEYS 1 (G m s) %FBW % BR AIN 1 664827 3 0 7 .3 0 1.93 0 .6 2 8 1 0 .0 7 3 0 .0 2 3 8 3 .7 8 2 4 0 .9 1 6 0 .2 9 8 1 4 7 .4 6 1 1 .2 3 2 0 .4 0 0 9 6 3 .8 3 4 2 .5 4 6 0 .8 2 8 5 1 3 1 .9 2 664828 3 39 .30 1 .9 2 2 0 .5 6 65 0 .0 6 2 0 .0 1 8 3 3 .2 2 5 8 0 .9 2 3 0 .2 7 2 0 4 8 .0 2 3 1 .3 5 1 0 .3 9 8 2 7 0 .2 9 1 3 .0 2 9 0 .8 9 2 7 1 5 7 .6 0 664829 3 7 9 .6 0 2 .1 2 8 0 .5 6 06 0 .0 7 6 0 .0 2 0 0 3 .5 7 1 4 1 .5 6 2 0 .4 1 1 5 7 3 .4 0 2 1 .5 5 6 0 .4 0 9 9 7 3 .1 2 0 3 .6 9 2 0 .9 7 2 6 1 7 3 .5 0 664830 3 4 6 .2 0 2 .0 0 3 0 .5 7 8 6 0 .0 6 6 0 .0 1 9 1 3 .2 9 5 1 1 .0 7 6 0 .3 1 0 8 5 3 .7 1 9 1 .6 2 1 0 .4 6 8 2 8 0 .9 2 9 3 .3 1 9 0 .9 5 8 7 1 6 5 .7 0 664831 2 9 0 .3 0 1 .9 5 4 0 .6 7 3 1 0 .0 5 8 0 .0 2 0 0 2 .9 6 83 0 .9 8 2 0 .3 3 8 3 5 0 .2 5 6 1 .2 6 9 0 .4 3 7 1 6 4 .9 4 4 2 .5 4 5 0 .8 7 6 7 1 3 0 .2 5 664832 3 4 4 .4 0 2 .0 7 3 0 .6 0 1 9 ' 0 .0 6 6 0 .0 1 9 2 3 .1 8 3 8 1 .0 1 0 0 .2 9 3 3 4 8 .7 2 2 1 .5 6 0 0 .4 5 3 0 7 5 .2 5 3 3 .1 5 9 0 .9 1 7 2 1 5 2 .3 9 o0 664833 2 9 7 .4 0 1 .8 6 5 0 .6 2 7 1 664834 3 1 8 .6 0 1 .8 9 4 0 .5 9 45 0 .0 6 2 0 .0 2 0 8 3 .3 2 4 4 0 .0 6 5 0 .0 2 0 4 3 .4 3 1 9 0 .9 5 0 0 .3 1 9 4 5 0 .9 3 8 1 .2 1 4 0 .3 8 1 0 6 4 .0 9 7 1 .2 4 4 0 .4 1 8 3 6 6 .7 0 2 1 .1 6 5 0 .3 6 5 7 6 1 .5 1 0 2 .8 7 3 0 .9 6 6 0 1 5 4 .0 5 2 .9 5 4 0 .9 2 7 2 1 5 5 .9 7 10 664835 3 42.80 664836 3 24 .00 2 .0 5 9 0 .6 0 0 6 1 .9 4 3 0 .5 9 9 7 0 .0 6 4 0 .0 1 8 7 3 .1 0 8 3 0 .0 6 3 0 .0 1 9 4 3 .2 4 2 4 1 .0 0 5 0 .2 9 3 2 4 8 .8 1 0 1 .1 3 5 0 .3 5 0 3 5 8 .4 1 5 1 .4 2 9 0 .4 1 6 9 6 9 .4 0 3 1 .2 2 5 0 .3 7 8 1 6 3 .0 4 7 2 .8 5 4 0 .8 3 2 6 1 3 8 .6 1 2 .8 4 7 0 .8 7 8 7 1 46 .53 3 t03n Mean S .D . 3 2 8 .9 9 1 .9 7 7 0 .6 0 31 2 6 .8 5 4 0 .0 8 5 0 .0 3 32 0 .0 6 6 0 .0 2 0 0 3 .3 1 3 4 0 .0 0 5 0 .0 0 1 5 0 .2 3 37 1 .0 7 7 0 .3 2 6 8 5 4 .3 8 4 0 .1 9 5 0 .0 4 3 7 8 .5 1 9 0 1 .3 6 5 0 .4 1 4 6 6 8 .9 0 3 0 .1 6 5 0 .0 3 1 8 6 .1 4 7 0 2 .9 8 2 0 .9 0 5 1 1 5 0 .6 5 0 .3 4 6 0 .0 5 2 2 1 4 .0 1 9 FBW - F in a l B o d y W e ig h t Does not contain TSCA CBI -158- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rg an W e ig h ts - D ay 25 S a c r ific e G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: MALES 1 ANIM AL 1 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 FBW (G m s) 2 76 .80 3 39 .80 3 54.70 3 46 .10 267 .40 3 07.40 3 10 .30 3 30 .40 321 .40 2 9 7 .7 0 BR AIN (G m s) %FBW 1 .8 4 6 2 .1 6 3 2 .0 0 8 1 .9 0 0 1 .8 7 1 1 .9 1 8 2 .0 3 6 1 .9 7 2 1 .9 2 1 2 .0 0 7 0 .6 6 6 9 0 .6 3 6 6 0 .5 6 6 1 0 .5 4 9 0 0 .6 9 9 7 0 .6 2 3 9 0 .6 5 61 0 .5 9 6 9 0 .5 9 77 0 .6 7 4 2 ADRENAL GLANDS (G m s) %FBW % BRAIN 0 .0 4 6 0 .0 1 6 6 2 .4 9 1 9 0 .0 7 6 0 .0 2 2 4 3 .5 1 3 6 0 .0 5 9 0 .0 1 6 6 2 .9 3 8 2 0 .0 6 2 0 .0 1 7 9 3 .2 6 3 2 0 .0 4 5 0 .0 1 6 8 2 .4 0 5 1 0 .0 8 6 0 .0 2 8 0 4 .4 8 3 8 0 .0 7 6 0 .0 2 4 5 3 .7 3 2 8 0 .0 5 8 0 .0 1 7 6 2 .9 4 1 2 0 .0 4 0 0 .0 1 2 4 2 .0 8 2 2 0 .0 4 9 0 .0 1 6 5 2 .4 4 1 5 E PID ID Y M ID E S (G m s) %FBW %B R A IN 0 .8 5 3 0 .3 0 8 2 4 6 .2 0 8 1 .1 1 8 0 .3 2 9 0 5 1 .6 8 7 0 .8 3 9 0 .2 3 6 5 4 1 .7 8 3 0 .9 2 7 0 .2 6 7 8 4 8 .7 8 9 0 .9 4 3 0 .3 5 2 7 5 0 .4 0 1 1 .1 1 9 0 .3 6 4 0 5 8.3 42 1 .0 7 3 0 .3 4 5 8 5 2 .7 0 1 0 .9 3 3 0 .2 8 2 4 4 7 .3 1 2 0 .9 5 9 0 .2 9 8 4 4 9 .9 2 2 1 .0 2 2 0 .3 4 3 3 5 0 .9 2 2 HEART (G m s) %FBW %B R A IN 1 .1 4 6 0 .4 1 4 0 6 2 .0 8 0 1 .3 0 0 0 .3 8 2 6 6 0 .1 0 2 1 .1 1 0 0 .3 1 2 9 5 5 .2 7 9 1 .2 8 9 0 .3 7 2 4 6 7 .8 4 2 0 .9 6 3 0 .3 6 0 1 5 1 .4 7 0 1 .2 6 2 0 .4 1 0 5 6 5 .7 9 8 1 .1 0 2 0 .3 5 5 1 5 4 .1 2 6 1 .2 6 5 0 .3 8 2 9 6 4 .1 4 8 1 .2 1 7 0 .3 7 8 7 6 3 .3 5 2 1 .3 3 2 0 .4 4 7 4 6 6 .3 6 8 Mean S .D . 315 .20 2 8.9 45 1 .9 6 4 0 .6 2 6 7 0 .0 9 4 0 .0 4 9 0 0 .0 6 0 0 .0 1 8 9 3 .0 2 9 4 0 .0 1 5 0 .0 0 4 6 0 .7 3 3 1 0 .9 7 9 0 .3 1 2 8 4 9 .8 0 7 0 .1 0 1 0 .0 4 1 5 4 .3 5 8 5 1 .1 9 9 0 .3 8 1 7 6 1 .0 5 6 0 .1 1 6 0 .0 3 6 8 5 .6 4 5 5 KID N EYS 1 (G m s) %FBW %B R A IN | 2 .6 9 0 0 .9 7 1 8 1 4 5 .7 2 2 .8 4 9 0 .8 3 8 4 1 3 1 .7 2 2 .8 8 2 0 .8 1 2 5 1 43 .53 2 .8 8 8 0 .8 3 4 4 1 5 2 .0 0 2 .2 3 3 0 .8 3 5 1 1 1 9 .3 5 3 .0 7 2 0 .9 9 9 3 1 6 0 .1 7 2 .8 4 9 0 .9 1 8 1 1 39 .93 3 .0 6 2 0 .9 2 6 8 1 5 5 .2 7 2 .5 1 4 0 .7 8 2 2 1 3 0 .8 7 2 .9 6 1 0 .9 9 4 6 1 4 7 .5 3 2 .8 0 0 0 .8 9 1 3 1 4 2 .6 1 0 .2 5 9 0 .0 8 0 4 1 2 .4 5 6 G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: MALES 1 ANIM AL 1 FBW B R A IN (G m s) (G m s) %FBW ADRENAL GLANDS (G m s) %FBW %B R A IN E PID ID Y M ID E S (G m s) %FBW % BRAIN 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 2 9 3 .9 0 3 3 2 .2 0 3 52 .00 3 60 .60 2 6 8 .3 0 3 3 7 .7 0 3 22 .30 3 15.60 3 75.10 2 7 5 .7 0 2 .0 6 7 0 .7 0 33 2 .0 4 7 0 .6 1 6 2 2 .0 5 6 0 .5 8 41 1 .9 6 1 0 .5 4 3 8 1 .9 8 0 0 .7 3 8 0 1 .8 2 0 0 .5 3 8 9 2 .0 1 8 0 .6 2 61 1 .8 6 5 0 .5 9 0 9 1 .9 3 2 0 .5 1 5 1 2 .0 5 4 0 .7 4 5 0 0 .0 7 0 0 .0 2 3 8 3 .3 8 6 6 0 .0 7 6 0 .0 2 2 9 3 .7 1 2 8 0 .0 7 2 0 .0 2 0 5 3 .5 0 1 9 0 .1 1 2 0 .0 3 1 1 5 .7 1 1 4 0 .0 6 4 0 .0 2 3 9 3 .2 3 2 3 0 .0 5 4 0 .0 1 6 0 2 .9 6 7 0 0 .0 7 4 0 .0 2 3 0 3 .6 6 7 0 0 .0 5 6 0 .0 1 7 7 3 .0 0 2 7 0 .0 6 2 0 .0 1 6 5 3 .2 0 9 1 0 .0 6 0 0 .0 2 1 8 2 .9 2 1 1 0 .9 8 1 0 .3 3 3 8 4 7 .4 6 0 1 .1 9 4 0 .3 5 9 4 5 8 .3 2 9 1 .1 9 9 0 .3 4 0 6 5 8 .3 1 7 1 .1 9 4 0 .3 3 1 1 6 0 .8 8 7 0 .8 2 3 0 .3 0 6 7 4 1 .5 6 6 0 .9 5 6 0 .2 8 3 1 5 2 .5 2 7 1 .1 4 0 0 .3 5 3 7 5 6 .4 9 2 1 .0 5 8 0 .3 3 5 2 5 6 .7 2 9 0 .9 4 8 0 .2 5 2 7 4 9 .0 6 8 1 .0 9 9 0 .3 9 8 6 5 3 .5 0 5 Mean S .D . 3 23 .34 1 .9 8 0 0 .6 2 01 3 5 .5 9 1 0 .0 8 6 0 .0 8 3 0 0 .0 7 0 0 .0 2 1 7 3 .5 3 1 2 0 .0 1 7 0 .0 0 4 4 0 .8 1 5 8 1 .0 5 9 0 .3 2 9 5 5 3 .4 8 8 0 .1 2 9 0 .0 4 0 8 5 .9 6 2 6 HEART (G m s) %FBW % BRAIN 1.1 8 9 0.4 0 4 6 5 7 .5 2 3 1 .4 2 3 0 .4 2 8 4 6 9 .5 1 6 1 .3 3 8 0 .3 8 0 1 6 5 .0 7 8 1 .3 2 4 0 .3 6 7 2 6 7 .5 1 7 1 .1 6 1 0 .4 3 2 7 5 8 .6 3 6 1 .1 3 7 0 .3 3 6 7 6 2 .4 7 3 1 .3 5 6 0 .4 2 0 7 6 7 .1 9 5 1 .1 0 6 0 .3 5 0 4 5 9 .3 0 3 1 .3 9 5 0 .3 7 1 9 7 2 .2 0 5 0 .9 6 1 0 .3 4 8 6 4 6 .7 8 7 1 .2 3 9 0 .3 8 4 1 6 2.6 23 0 .1 5 0 0 .0 3 5 2 7 .4 0 8 3 KID N EYS | (G m s) %FBW % BR AIN | 2 .8 8 5 3 .2 3 4 3 .2 6 3 3 .2 9 3 2 .4 5 2 3 .0 9 5 2 .9 6 1 2 .7 3 2 3 .3 9 3 2 .3 5 1 0 .9 8 1 6 0 .9 7 3 5 0 .9 2 7 0 0 .9 1 3 2 0 .9 1 3 9 0 .9 1 6 5 0 .9 1 8 7 0 .8 6 5 7 0.9046 0 .8 5 2 7 139 .57 1 57 .99 1 5 8 .7 1 1 6 7 .9 2 1 23 .84 1 7 0 .0 5 1 46 .73 1 4 6 .4 9 1 7 5 .6 2 1 1 4 .4 6 2 .9 6 6 0 .9 1 6 7 1 5 0 .1 4 0 .3 6 1 0 .0 4 0 0 1 9 .9 9 6 ompany sanitized. FBW - F in a l B o d y W e ig h t ? U) O3 3oO sr 3' 5 8 -159- H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rgan W e ig h ts - D ay 25 S a c r ific e G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: MALES 1 ANIM AL 1 664812 664813 664814 664815 664816 664817 664818 664819 664820 664821 LIV E R (G m s) %FBW % BRAIN 9 .6 4 1 3 .1 0 9 0 4 70 .52 1 0.3 86 2 .8 4 2 4 4 91 .30 1 1.8 31 2 .8 5 2 2 5 73 .21 1 1.727 3 .0 8 5 2 6 02.93 7 .7 6 4 2 .5 0 1 3 4 5 7 .5 1 9 .3 8 8 2 .6 9 6 9 5 0 7 .1 9 8 .5 4 9 2 .7 6 7 6 4 6 1 .1 1 1 0.0 70 2 .9 9 8 8 469 .03 9 .7 7 6 2 .8 9 7 5 508 .37 1 0.7 71 3 .3 0 5 0 559 .82 LUNGS (G m s) %FBW % BR AIN 1 .6 6 5 0 .5 3 6 9 8 1 .2 5 9 2 .0 7 3 0 .5 6 7 3 9 8 .0 6 1 1 .9 1 9 0 .4 6 2 6 9 2 .9 7 5 1 .8 2 2 0 .4 7 9 3 9 3 .6 7 6 1 .3 4 9 0 .4 3 4 6 7 9.4 93 1 .5 6 2 0 .4 4 8 7 8 4 .3 8 7 1 .5 6 3 0 .5 0 6 0 8 4 .3 0 4 1 .6 6 9 0 .4 9 7 0 7 7 .7 3 6 1 .6 4 5 0 .4 8 7 6 8 5.5 43 1 .6 3 8 0 .5 0 2 6 8 5 .1 3 5 SPLEEN (G m s) %FBW % BRAIN 0 .4 5 9 0 .1 4 8 0 2 2 .4 0 1 0 .8 1 2 0 .2 2 2 2 3 8 .4 1 1 0 .6 5 1 0 .1 5 6 9 3 1 .5 4 1 0 .7 8 7 0 .2 0 7 1 4 0.4 63 0 .4 3 2 0 .1 3 9 2 2 5 .4 5 7 0 .5 2 9 0 .1 5 2 0 2 8 .5 7 9 0 .4 8 4 0 .1 5 6 7 2 6 .1 0 6 0 .5 7 9 0 .1 7 2 4 2 6 .9 6 8 0 .5 2 8 0 .1 5 6 5 2 7 .4 5 7 0 .5 6 8 0 .1 7 43 2 9 .5 2 2 TESTES (G m s) %FBW % BRAIN 2 .9 6 0 3 .1 3 5 3 .2 2 1 3 .3 5 7 2 .5 2 4 3 .1 7 1 3 .1 8 4 3 .3 3 0 3 .1 6 4 2 .5 2 1 0 .9 5 4 5 0 .8 5 8 0 0 .7 7 6 5 0 .8 8 3 2 0 .8 1 3 1 0 .9 1 0 9 1 .0 3 0 8 0 .9 9 1 7 0 .9 3 7 8 0 .7 7 3 6 1 4 4 .4 6 1 48 .30 1 56 .06 1 7 2 .6 0 1 48 .73 1 71 .31 1 71 .74 1 5 5 .1 0 1 64 .53 1 31 .03 Mean S .D . 9 .9 9 0 2 .9 0 5 6 5 10 .10 1 .2 8 0 0 .2 2 9 7 5 1.4 85 1 .6 9 1 0 .4 9 2 3 8 6 .2 5 7 0 .2 0 3 0 .0 3 9 8 6 .5 9 8 8 0 .5 8 3 0 .1 6 8 5 2 9 .6 9 0 0 .1 3 0 0 .0 2 6 6 5 .7 0 6 5 3 .0 5 7 0 .8 9 3 0 1 5 6 .3 9 0 .3 0 2 0 .0 8 8 4 1 3 .7 3 8 THYMUS 1 (G m s) %FBW % B R AIN | 0 .3 2 2 0 .1 0 3 8 1 5 .7 1 5 0 .2 8 1 0 .0 7 6 9 1 3 .2 9 2 0 .5 8 6 0 .1 4 1 3 2 8 .3 9 1 0 .4 7 4 0 .1 2 4 7 2 4 .3 7 0 0 .3 1 6 0 .1 0 1 8 1 8 .6 2 1 0 .4 2 0 0 .1 2 0 7 2 2 .6 9 0 0 .2 5 1 0 .0 8 1 3 1 3 .5 3 8 0 .3 3 7 0 .1 0 0 4 1 5 .6 9 6 0 .3 9 4 0 .1 1 6 8 2 0 .4 8 9 0 .3 6 7 0 .1 1 2 6 1 9 .0 7 5 0 .3 7 5 0 .1 0 8 0 1 9 .1 8 8 0 .0 9 9 0 .0 1 9 6 4 .9 0 7 9 G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: MALES 1 ANIM AL 1 664827 664828 664829 664830 664831 664832 664833 664834 664835 664836 LIV E R (Gm s) %FBW % BRAIN 9 .4 7 7 9 .9 9 3 1 1.118 1 0.566 8 .9 5 1 9 .7 6 0 8 .5 2 3 9 .2 2 4 9 .4 9 8 8 .9 6 0 3 .0 8 4 0 2 .9 4 5 2 2 .9 2 8 9 3 .0 5 2 0 3 .0 8 3 4 2 .8 3 3 9 2 .8 6 5 8 2 .8 9 5 2 2 .7 7 0 7 2 .7 6 5 4 4 91 .04 519 .93 5 2 2 .4 6 5 2 7 .5 1 4 58 .09 4 70 .82 4 57 .00 4 87 .01 4 61 .29 4 61 .14 LUNGS (G m s) %FBW % BRAIN 1 .4 5 0 1 .5 0 8 1 .8 0 8 1 .8 2 9 1 .6 0 4 1 .7 6 9 1 .3 9 5 1 .7 3 4 2 .0 3 7 1 .5 9 4 0 .4 7 1 9 0 .4 4 4 4 0 .4 7 63 0 .5 2 83 0 .5 5 2 5 0 .5 1 3 6 0 .4 6 9 1 0 .5 4 4 3 0 .5 9 4 2 0 .4 9 2 0 75.1 30 78.4 60 8 4.962 9 1.313 8 2.088 8 5.3 35 74.7 99 9 1.5 52 9 8.932 8 2.0 38 SPLEEN (G m s) %FBW % BRAIN 0 .5 4 3 0 .1 7 6 7 2 8 .1 3 5 0 .5 6 9 0 .1 6 7 7 2 9 .6 0 5 0 .7 0 5 0 .1 8 5 7 3 3 .1 3 0 0 .6 6 9 0 .1 9 3 2 3 3 .4 0 0 0 .5 7 1 0 .1 9 6 7 2 9.2 22 0 .6 1 3 0 .1 7 8 0 2 9 .5 7 1 0 .4 7 4 0 .1 5 9 4 2 5 .4 1 6 0 .5 7 9 0 .1 8 1 7 3 0 .5 7 0 0 .6 6 7 0 .1 9 4 6 3 2 .3 9 4 0 .6 6 8 0 .2 0 6 2 3 4 .3 8 0 Mean S .D . 9 .6 0 7 2 .9 2 2 4 4 8 5 .6 3 0 .7 8 7 0 .1 1 9 6 2 8 .4 9 5 1 .6 7 3 0 .5 0 8 7 8 4 .4 6 1 0 .1 9 8 0 .0 4 6 3 7 .7 1 4 3 0 .6 0 6 0 .1 8 4 0 3 0 .5 8 2 0 .0 7 2 0 .0 1 4 2 2 .7 6 1 8 TESTES (G m s) %FBW % BRAIN 3 .3 8 8 3 .5 8 0 3 .6 2 3 2 .9 3 5 2 .8 5 3 3 .3 0 7 3 .1 1 3 3 .3 2 6 3 .1 2 6 3 .1 5 8 1 .1 0 2 5 1 .0 5 5 1 0 .9 5 4 4 0 .8 4 7 8 0 .9 8 2 8 0 .9 6 0 2 1 .0 4 6 7 1 .0 4 3 9 0 .9 1 1 9 0 .9 7 4 7 1 75 .54 1 8 6 .2 6 170 .25 1 46 .53 1 4 6 .0 1 1 59 .53 1 6 6 .9 2 1 75 .61 1 51 .82 1 62 .53 3 .2 4 1 0 .9 8 8 0 1 6 4 .1 0 0 .2 5 3 0 .0 7 5 8 1 3 .3 7 7 THYMUS 1 (G m s) %FBW % BR AIN | 0 .4 6 1 0 .4 1 8 0 .4 9 1 0 .4 7 8 0 .3 3 8 0 .4 8 2 0 .4 2 2 0 .3 3 7 0 .4 4 0 0 .4 2 3 0 .1 5 0 0 0 .1 2 3 2 0 .1 2 9 3 0 .1 3 8 1 0 .1 1 6 4 0 .1 4 0 0 0 .1 4 1 9 0 .1 0 5 8 0 .1 2 8 4 0 .1 3 0 6 23.8 86 21.7 48 2 3.0 73 2 3.8 64 17.2 98 23.2 51 22.6 27 1 7.7 93 21.3 70 21.7 70 0 .4 2 9 0 .1 3 0 4 2 1 .6 6 8 0 .0 5 5 0 .0 1 3 0 2 .3 4 2 0 FBW - F in a l B o d y W e ig h t Company Sanitized. Does no*contain TSCA CEI 160- ).. ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats_________________ DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rg an W e ig h ts - D ay 25 S a c r ific e G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: MALES 1 ANIM AL 1 664842 664843 664844 664845 664846 664847 664848 664849 664850 664851 LIV E R (G ins) %FBW % BRAIN 7 .8 0 4 9 .1 8 0 9 .3 7 8 10.3 44 6 .8 9 8 1 0.162 9 .2 5 2 9 .2 7 3 9 .4 7 3 9 .3 8 7 2 .8 1 9 4 2 .7 0 1 6 2 .6 4 3 9 2 .9 8 8 7 2 .5 7 9 7 3 .3 0 5 8 2 .9 8 1 6 2 .8 0 6 6 2 .9 4 7 4 3 .1 5 3 2 4 22 .75 424 .41 467 .03 544 .42 3 68 .68 529 .82 4 54 .42 470 .23 4 9 3 .1 3 4 67 .71 LONGS (G m s) %FBW %B R A IN 1 .3 1 0 1 .6 8 8 1 .7 3 5 1 .6 7 5 1 .2 6 2 1 .5 9 2 1 .8 2 9 1 .6 0 6 1 .4 3 3 1 .4 8 1 0 .4 7 3 3 0 .4 9 6 8 0 .4 8 91 0 .4 8 4 0 0 .4 7 20 0 .5 1 7 9 0 .5 8 9 4 0 .4 8 6 1 0 .4 4 5 9 0 .4 9 7 5 7 0.9 64 7 8.0 40 8 6 .4 0 4 8 8.1 58 6 7.4 51 83.0 03 89.8 33 8 1.440 74.5 97 7 3.792 SPLEEN (G m s) %FBW % BRAIN 0 .3 2 7 0 .1 1 8 1 1 7.7 14 0 .6 4 8 0 .1 9 0 7 2 9 .9 5 8 0 .4 7 7 0 .1 3 4 5 2 3 .7 5 5 0 .7 3 3 0 .2 1 1 8 3 8 .5 7 9 0 .4 7 7 0 .1 7 8 4 2 5 .4 9 4 0 .7 1 0 0 .2 3 1 0 3 7 .0 1 8 0 .5 6 4 0 .1 8 1 8 2 7 .7 0 1 0 .5 7 2 0 .1 7 3 1 2 9 .0 0 6 0 .5 1 8 0 .1 6 1 2 2 6 .9 6 5 0 .7 2 4 0 .2 4 3 2 3 6 .0 7 4 TESTES (G m s) %FBW % BRAIN 3 .1 7 9 4 .0 4 9 2 .8 7 1 3 .2 6 6 2 .8 0 9 3 .3 9 3 3 .4 4 1 3 .3 5 2 3 .1 4 9 3 .0 1 3 1 .1 4 8 5 1 .1 9 1 6 0 .8 0 9 4 0 .9 4 3 7 1 .0 5 0 5 1 .1 0 3 8 1 .1 0 8 9 1 .0 1 4 5 0 .9 7 9 8 1 .0 1 2 1 1 7 2 .2 1 1 8 7 .1 9 1 4 2 .9 8 1 7 1 .8 9 1 50 .13 1 7 6 .9 0 1 6 9 .0 1 1 6 9 .9 8 1 63 .93 1 50 .12 Mean S .D . 9 .1 1 5 2 .8 9 2 8 4 6 4 .2 6 1 .0 3 1 0 .2 2 8 0 5 1 .8 0 8 1 .5 6 1 0 .4 9 5 2 7 9 .3 6 8 0 .1 8 5 0 .0 3 8 2 7 .6 1 63 0 .5 7 5 0 .1 8 2 4 2 9 .2 2 6 0 .1 3 1 0 .0 3 9 4 6 .4 9 3 5 3 .2 5 2 1 .0 3 6 3 1 6 5 .4 4 0 .3 5 2 0 .1 1 1 1 1 3 .7 4 8 THYMUS | (G m s) %FBW % BRAIN | 0 .2 4 6 0 .0 8 8 9 1 3 .3 2 6 0 .4 7 4 0 .1 3 9 5 2 1 .9 1 4 0 .3 4 1 0 .0 9 6 1 1 6 .9 8 2 0 .3 3 7 0 .0 9 7 4 1 7 .7 3 7 0 .4 3 0 0 .1 6 0 8 2 2 .9 8 2 0 .4 6 5 0 .1 5 1 3 2 4 .2 4 4 0 .3 3 1 0 .1 0 6 7 1 6 .2 5 7 0 .4 9 9 0 .1 5 1 0 2 5 .3 0 4 0 .4 4 8 0 .1 3 9 4 2 3 .3 2 1 0 .4 4 5 0 .1 4 9 5 2 2 .1 7 2 0 .4 0 2 0 .1 2 8 1 2 0 .4 2 4 0 .0 8 2 0 .0 2 7 5 4 .0 1 9 9 G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: MALES 1 ANIM AL 1 664857 664858 664859 664860 664861 664862 664863 664864 664865 664866 LIV E R (G m s) %FBW % BRAIN 9 .5 7 0 3 .2 5 6 2 4 6 2 .9 9 1 0.179 3 .0 6 4 1 4 9 7 .2 6 1 0 .2 4 5 2 .9 1 0 5 4 9 8 .3 0 1 1.1 13 3 .0 8 1 8 5 66 .70 8 .2 3 5 3 .0 6 9 3 4 1 5 .9 1 8 .8 2 1 2 .6 1 2 1 4 8 4 .6 7 9 .7 9 0 3 .0 3 7 5 4 8 5 .1 3 8 .5 9 3 2 .7 2 2 8 4 6 0 .7 5 1 1 .4 0 6 3 .0 4 0 8 5 90 .37 7 .3 9 7 2 .6 8 3 0 3 6 0 .1 3 LUNGS (G m s) %FBW % BRAIN 1 .8 7 5 1 .8 2 4 1 .7 7 2 1 .7 3 5 1 .4 3 9 1 .5 1 2 1 .7 0 3 1 .5 3 2 1 .8 2 4 1 .3 5 3 0 .6 3 8 0 0 .5 4 9 1 0 .5 0 3 4 0 .4 8 1 1 0 .5 3 63 0 .4 4 7 7 0 .5 2 8 4 0 .4 8 5 4 0 .4 8 63 0 .4 9 0 8 9 0.711 8 9.1 06 8 6.187 8 8.4 75 7 2.6 77 8 3.077 8 4.390 8 2.1 45 9 4.410 6 5.871 SPLEEN (G m s) %FBW %B R A IN 0 .6 1 0 0 .2 0 7 6 2 9 .5 1 1 0 .6 2 9 0 .1 8 9 3 3 0 .7 2 8 0 .6 5 1 0 .1 8 4 9 3 1 .6 6 3 0 .7 2 8 0 .2 0 1 9 3 7 .1 2 4 0 .4 4 6 0 .1 6 6 2 2 2 .5 2 5 0 .4 8 5 0 .1 4 3 6 2 6 .6 4 8 0 .5 4 4 0 .1 6 8 8 2 6 .9 5 7 0 .6 1 0 0 .1 9 3 3 3 2 .7 0 8 0 .6 5 5 0 .1 7 4 6 3 3 .9 0 3 0 .4 3 4 0 .1 5 7 4 2 1 .1 3 0 Mean S .D . 9 .5 3 5 2 .9 4 7 8 4 8 2 .2 2 1 .2 7 5 0 .2 0 9 0 6 6 .2 2 2 1 .6 5 7 0 .5 1 4 7 8 3 .7 0 5 0 .1 8 3 0 .0 5 2 7 8 .5 9 41 0 .5 7 9 0 .1 7 8 8 2 9 .2 9 0 0 .0 9 8 0 .0 2 0 2 5 .0 2 05 TESTES (G m s) %FBW % BRAIN 2 .8 8 7 0 .9 8 2 3 1 3 9 .6 7 3 .3 3 6 1 .0 0 42 1 6 2 .9 7 3 .5 5 6 1 .0 1 0 2 1 7 2 .9 6 3 .4 4 2 0 .9 5 4 5 1 7 5 .5 2 2 .7 8 1 1 .0 3 6 5 1 4 0 .4 5 3 .3 8 3 1 .0 0 1 8 1 8 5 .8 8 3 .3 0 1 1 .0 2 4 2 1 6 3 .5 8 2 .9 9 1 0 .9 4 7 7 1 6 0 .3 8 3 .6 3 7 0 .9 6 9 6 1 8 8 .2 5 3 .1 9 8 1 .1 6 0 0 1 5 5 .7 0 3 .2 5 1 1 .0 0 9 1 1 6 4 .5 4 0 .2 8 5 0 .0 6 0 4 1 6 .6 8 8 THYMUS 1 (G m s) %FBW % BR AIN | 0 .4 7 7 0 .4 6 5 0 .5 0 6 0 .5 6 2 0 .3 6 8 0 .4 2 5 0 .4 5 7 0 .4 7 5 0 .4 7 7 0 .3 3 9 0 .1 6 2 3 0 .1 4 0 0 0 .1 4 3 8 0 .1 5 5 9 0 .1 3 7 2 0 .1 2 5 9 0 .1 4 1 8 0 .1 5 0 5 0 .1 2 7 2 0 .1 2 3 0 2 3 .0 7 7 2 2.7 16 2 4 .6 1 1 2 8 .6 5 9 1 8.5 86 2 3.3 52 2 2 .6 4 6 2 5 .4 6 9 2 4.6 89 1 6.5 04 0 .4 5 5 0 .1 4 0 7 2 3 .0 3 1 0 .0 6 5 0 .0 1 3 1 3 .4 2 4 9 FBW - F in a l B o d y W e ig h t Company Sanitized. Does not contain TSCACBI -161 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats_____________________________________________________________________ DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rgan W e ig h ts - D ay 56 S a c r ific e G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: MALES 1 ANIM AL 1 664822 664823 664824 664825 664826 FBW (G m s) 4 2 2 .0 0 4 7 5 .7 0 4 3 4 .0 0 4 4 4 .8 0 458 .80 BR AIN (G m s) %FBW 2 .0 4 2 1 .9 1 0 2 .1 6 2 1 .8 6 5 2 .1 6 2 0 .4 8 3 9 0 .4 0 15 0 .4 9 8 2 0 .4 1 9 3 0 .4 7 1 2 ADRENAL GLANDS (G m s) %FBW %BRA I N 0 .0 5 3 0 .0 4 9 0 .0 4 7 0 .0 4 5 0 .0 6 0 0 .0 1 2 6 0 .0 1 0 3 0 .0 1 0 8 0 .0 1 0 1 0 .0 1 3 1 2 .5 9 5 5 2 .5 6 54 2 .1 7 3 9 2 .4 1 29 2 .7 7 52 E PID ID Y M ID E S (G m s) %FBW % BRAIN 1 .2 0 9 1 .1 2 2 1 .2 3 6 1 .2 8 6 1 .5 4 3 0 .2 8 6 5 0 .2 3 5 9 0 .2 8 4 8 0 .2 8 9 1 0 .3 3 63 5 9.2 07 5 8 .7 4 3 5 7.1 69 6 8.9 54 71.3 69 HEART (G m s) %FBW % BRAIN 1 .5 9 7 1 .6 6 3 1 .4 5 9 1 .4 8 6 1 .5 5 9 0 .3 7 8 4 0 .3 4 9 6 0 .3 3 6 2 0 .3 3 4 1 0 .3 3 9 8 7 8 .2 0 8 8 7.0 68 6 7 .4 8 4 7 9 .6 7 8 7 2 .1 0 9 Mean S .D . 4 47 .06 2 0.987 2 .0 2 8 0 .4 5 48 0 .1 3 8 0 .0 4 21 0 .0 5 1 0 .0 1 1 4 2 .5 0 4 6 0 .0 0 6 0 .0 0 1 4 0 .2 2 5 3 1 .2 7 9 0 .2 8 6 5 6 3 .0 8 9 0 .1 5 9 0 .0 3 5 5 6 .5 5 6 7 1 .5 5 3 0 .3 4 7 6 7 6 .9 0 9 0 .0 8 3 0 .0 1 8 2 7 .4 9 0 6 KID NEYS 1 (G m s) %FBW % BR AIN | 3 .2 1 2 3 .7 0 6 3 .1 8 8 3 .4 7 3 4 .0 3 8 0 .7 6 1 1 0 .7 7 9 1 0 .7 3 4 6 0 .7 8 0 8 0 .8 8 0 1 1 5 7 .3 0 1 9 4 .0 3 147 .46 1 86 .22 1 8 6 .7 7 3 .5 2 3 0 .7 8 7 1 1 7 4 .3 6 0 .3 5 7 0 .0 5 5 2 2 0 .5 9 5 G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: MALES 1 ANIM AL 1 664837 664838 664839 664840 664841 FBW (G m s) 4 3 7 .6 0 4 3 1 .8 0 4 3 4 .2 0 4 2 1 .9 0 3 8 5 .1 0 BR AIN (G m s) %FBW 2 .2 1 4 2 .1 8 8 1 .9 6 7 2 .0 2 1 2 .1 7 5 0 .5 0 59 0 .5 0 6 7 0 .4 5 3 0 0 .4 7 9 0 0 .5 6 4 8 ADRENAL GLANDS (G m s) %FBW % BRAIN 0 .0 7 0 0 .0 5 5 0 .0 4 5 0 .0 4 8 0 .0 4 3 0 .0 1 6 0 0 .0 1 2 7 0 .0 1 0 4 0 .0 1 1 4 0 .0 1 1 2 3 .1 6 1 7 2 .5 1 37 2 .2 8 7 7 2 .3 7 5 1 1 .9 7 70 Mean S .D . 4 2 2 .1 2 2 1.5 05 2 .1 1 3 0 .5 0 19 0 .1 1 1 0 .0 4 16 0 .0 5 2 0 .0 1 2 3 2 .4 6 30 0 .0 1 1 0 .0 0 2 2 0 .4 3 74 E PID ID Y M ID E S (G m s) %FBW % BRAIN 1 .3 0 3 1 .3 0 5 1 .3 6 7 1 .2 7 9 1 .2 1 2 0 .2 9 7 8 0 .3 0 2 2 0 .3 1 4 8 0 .3 0 32 0 .3 1 4 7 5 8.853 5 9 .6 4 4 69.4 97 6 3.2 86 5 5.7 24 1 .2 9 3 0 .3 0 6 5 6 1 .4 0 1 0 .0 5 6 0 .0 0 7 8 5 .2 6 5 5 HEART (Gm s) %FBW % BRAIN 1 .8 7 9 1 .5 6 6 1 .8 1 7 1 .3 9 9 1 .4 2 7 0 .4 2 9 4 0 .3 6 2 7 0 .4 1 8 5 0 .3 3 1 6 0 .3 7 0 6 8 4 .8 6 9 7 1 .5 7 2 9 2 .3 7 4 6 9.2 23 6 5 .6 0 9 1 .6 1 8 0 .3 8 2 5 7 6 .7 3 0 0 .2 2 1 0 .0 4 0 7 1 1 .3 7 6 KID NEYS 1 (G m s) %FBW % BR AIN | 3 .6 1 9 3 .3 6 6 3 .5 6 1 3 .4 3 4 3 .1 3 4 0 .8 2 7 0 0 .7 7 9 5 0 .8 2 0 1 0 .8 1 3 9 0 .8 1 3 8 163 .46 1 5 3 .8 4 1 8 1 .0 4 1 69 .92 1 4 4 .0 9 3 .4 2 3 0 .8 1 0 9 1 6 2 .4 7 0 .1 9 0 0 .0 1 8 3 1 4 .2 6 0 FBW - F in a l B od y W e ig h t Company Sanitized. Does not contain TSCA CBI -162- ) H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rg an W e ig h ts - D ay 56 S a c r ific e G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: MALES 1 ANIM AL 1 664852 664853 664854 664855 664856 FBW (G m s) 4 71 .40 4 5 5 .1 0 4 34.60 4 38 .50 3 98.90 BR AIN (G m s) %FBW 2 .1 4 5 0 .4 5 50 2 .2 0 1 0 .4 8 36 1 .9 9 0 0 .4 5 79 2 .0 4 6 0 .4 6 6 6 2 .1 9 2 0 .5 4 95 ADRENAL GLANDS (G m s) %FBW % BRAIN 0 .0 5 9 0 .0 1 2 5 2 .7 5 0 6 0 .0 6 3 0 .0 1 3 8 2 .8 6 2 3 0 .0 6 6 0 .0 1 52 3 .3 1 6 6 0 .0 6 8 0 .0 1 5 5 3 .3 2 3 6 0 .0 6 2 0 .0 1 5 5 2 .8 2 8 5 E PID ID Y M ID E S (G m s) %FBW % BRAIN 1 .4 6 0 1 .2 9 5 1 .4 7 8 1 .3 7 6 1 .2 8 4 0 .3 0 9 7 0 .2 8 4 6 0 .3 4 0 1 0 .3 1 3 8 0 .3 2 1 9 6 8.0 65 5 8.8 37 7 4.2 71 67.2 53 5 8.577 HEART (Gm s) %FBW % BRAIN 1 .6 2 7 1 .7 6 2 1 .5 5 1 1 .5 3 6 1 .4 8 0 0 .3 4 5 1 0 .3 8 7 2 0 .3 5 6 9 0 .3 5 0 3 0 .3 7 1 0 75.8 51 80.0 55 77.9 40 7 5.0 73 6 7 .5 1 8 Mean S .D . 4 39 .70 2 .1 1 5 0 .4 8 25 2 7.0 84 0 .0 9 3 0 .0 3 91 0 .0 6 4 0 .0 1 4 5 3 .0 1 6 3 0 .0 0 4 0 .0 0 1 3 0 .2 8 0 3 1 .3 7 9 0 .3 1 4 0 6 5 .4 0 1 0 .0 9 0 0 .0 2 0 2 6 .6 8 7 1 1 .5 9 1 0 .3 6 2 1 7 5 .2 8 7 0.109 0 .0 1 7 0 4 .7 5 6 1 KID NEYS 1 (G m s) %FBW % BRAIN | 4 .0 2 1 3 .6 2 9 3 .6 5 6 3 .6 2 4 3 .2 4 6 0 .8 5 3 0 0 .7 9 7 4 0 .8 4 1 2 0 .8 2 6 5 0 .8 1 3 7 1 8 7 .4 6 1 64 .88 1 83 .72 1 77 .13 1 4 8 .0 8 3 .6 3 5 0 .8 2 6 4 1 7 2 .2 5 0 .2 7 4 0 .0 2 2 0 1 6 .0 0 7 G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: MALES 1 ANIM AL 1 664867 664868 664869 664870 664871 FBW (G m s) 4 61 .50 4 80 .70 4 7 8 .9 0 4 08.90 3 77.80 BR AIN (G m s) %FBW 1 .9 9 3 0 .4 3 19 2 .1 6 9 0 .4 5 1 2 2 .2 6 4 0 .4 7 28 2 .0 4 2 0 .4 9 94 1 .9 4 4 0 .5 1 46 ADRENAL GLANDS (G m s) %FBW % BRAIN 0 .0 5 3 0 .0 1 1 5 2 .6 5 9 3 0 .0 7 4 0 .0 1 5 4 3 .4 1 1 7 0 .0 7 4 0 .0 1 5 5 3 .2 6 8 6 0 .0 7 3 0 .0 1 7 9 3 .5 7 4 9 0 .0 7 5 0 .0 1 9 9 3 .8 5 8 0 E PID ID Y M ID E S (G m s) %FBW %B R A IN 1 .3 0 9 0 .2 8 3 6 6 5 .6 8 0 1 .5 9 6 0 .3 3 2 0 7 3 .5 8 2 1 .4 7 0 0 .3 0 7 0 6 4 .9 2 9 1 .1 7 9 0 .2 8 8 3 5 7 .7 3 8 1 .1 7 4 0 .3 1 0 7 6 0 .3 9 1 Mean S .D . 4 41 .56 4 5.9 78 2 .0 8 2 0 .4 7 4 0 0 .1 3 2 0 .0 3 3 9 0 .0 7 0 0 .0 1 6 0 3 .3 5 4 5 0 .0 0 9 0 .0 0 3 1 0 .4 4 6 1 1 .3 4 6 0 .3 0 4 3 6 4.4 64 0 .1 8 5 0 .0 1 9 4 6 .0 5 5 4 HEART (G m s) %FBW % BRAIN 1 .5 8 3 0 .3 4 3 0 7 9 .4 2 8 1 .9 5 7 0 .4 0 7 1 9 0 .2 2 6 2 .0 6 1 0 .4 3 0 4 9 1 .0 3 4 1 .4 2 5 0 .3 4 8 5 6 9 .7 8 5 1 .4 7 8 0 .3 9 1 2 7 6 .0 2 9 1 .7 0 1 0 .3 8 4 0 8 1 .3 0 0 0 .2 8 9 0 .0 3 7 7 9 .1 9 6 6 KID NEYS 1 (G m s) %FBW % BR AIN | 3 .7 3 3 4 .3 0 6 4 .5 9 0 3 .3 0 6 3 .3 9 1 0 .8 0 8 9 0 .8 9 5 8 0 .9 5 8 4 0.8085 0 .8 9 7 6 1 8 7 .3 1 1 98 .52 2 0 2 .7 4 161.90 1 7 4 .4 3 3 .8 6 5 0 .8 7 3 8 1 8 4 .9 8 0 .5 6 5 0 .0 6 4 6 1 6 .9 4 2 FBW - F in a l B od y W e ig h t Company Sanitized. Does not contain T S C A C I -163- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rgan W e ig h ts - D ay 56 S a c r ific e G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: MALES I ANIM AL 1 664822 664823 664824 664825 664826 Mean S .D . LIV E R (G m s) %FBW % BRAIN 12.2 60 13.3 34 12.2 82 1 2 .4 6 1 13.9 12 2 .9 0 5 2 2 .8 0 3 0 2 .8 3 0 0 2 .8 0 1 5 3 .0 3 2 3 600 .39 698 .12 568 .09 6 68.15 643 .48 1 2.8 50 2 .8 7 4 4 6 35 .64 0 .7 3 9 0 .0 9 7 8 5 2.0 28 LUNGS (G m s) %FBW % BRAIN 1 .8 3 0 1 .8 8 8 1 .5 6 8 1 .9 0 1 2 .2 0 5 0 .4 3 3 6 0 .3 9 6 9 0 .3 6 1 3 0 .4 2 7 4 0 .4 8 0 6 8 9 .6 1 8 9 8 .8 4 8 7 2.5 25 101 .93 101 .99 1 .8 7 8 0 .4 2 0 0 9 2.9 82 0 .2 2 7 0 .0 4 4 4 1 2.5 04 SPLEEN (G m s) %FBW % BRAIN 0 .8 4 1 0 .9 5 0 0 .8 3 6 0 .8 8 0 0 .8 2 8 0 .1 9 93 0 .1 9 9 7 0 .1 9 2 6 0 .1 9 7 8 0 .1 8 0 5 4 1.1 85 4 9.7 38 3 8.668 4 7.1 85 3 8.2 98 0 .8 6 7 0 .1 9 4 0 4 3 .0 1 5 0 .0 5 1 0 .0 0 8 1 5 .1 7 42 TESTES (G m s) %FBW %B R A IN 3 .4 6 1 2 .8 8 1 3 .2 1 5 3 .6 7 8 3 .3 8 4 0 .8 2 0 1 0 .6 0 5 6 0 .7 4 0 8 0 .8 2 6 9 0 .7 3 7 6 1 69 .49 1 50 .84 1 48 .70 1 9 7 .2 1 1 56 .52 3 .3 2 4 0 .7 4 6 2 1 6 4 .5 5 0 .2 9 8 0 .0 8 9 2 1 9 .9 6 7 THYMUS 1 (G m s) %FBW % BRAIN | 0 .4 6 6 0 .1 1 0 4 2 2 .8 2 1 0 .6 1 3 0 .1 2 8 9 3 2 .0 9 4 0 .5 7 7 0 .1 3 2 9 2 6 .6 8 8 0 .5 2 7 0 .1 1 8 5 2 8 .2 5 7 0 .5 3 0 0 .1 1 5 5 2 4 .5 1 4 0 .5 4 3 0 .1 2 1 2 2 6 .8 7 5 0 .0 5 6 0 .0 0 9 4 3 .5 7 7 6 G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: MALES 1 ANIM AL 1 664837 664838 664839 664840 664841 LIV E R (G m s) %FBW % BRAIN 1 2.851 10.3 43 1 4.254 11.8 63 1 0.405 2 .9 3 6 7 2 .3 9 5 3 3 .2 8 2 8 2 .8 1 1 8 2 .7 0 1 9 580 .44 4 72 .71 7 24.66 586 .99 4 78 .39 LUNGS (G m s) %FBW %B R A IN 2 .3 9 1 2 .0 3 2 2 .0 0 9 1 .7 7 6 1 .7 9 9 0 .5 4 6 4 0 .4 7 0 6 0 .4 6 2 7 0 .4 2 1 0 0 .4 6 7 2 1 07.99 9 2.870 102 .14 87.8 77 82.7 13 SPLEEN (G m s) %FBW % BRAIN 0 .7 2 4 0 .7 5 7 0 .8 2 2 0 .8 5 1 0 .5 7 5 0 .1 6 5 4 0 .1 7 53 0 .1 8 93 0 .2 0 1 7 0 .1 4 93 32.7 01 3 4.5 98 4 1.7 90 4 2.1 08 2 6.4 37 Mean S .D . 11.943 2 .8 2 5 7 5 68 .64 1 .6 6 6 0 .3 2 4 8 1 02 .67 2 .0 0 1 0 .4 7 3 6 9 4.7 18 0 .2 4 7 0 .0 4 5 4 1 0 .3 1 5 0 .7 4 6 0 .1 7 6 2 3 5 .5 2 7 0 .1 0 8 0 .0 2 0 4 6 .5 9 5 6 TESTES (G m s) %FBW % BRAIN 3 .6 3 2 3 .6 5 9 3 .4 6 6 3 .2 9 0 3 .2 1 5 0 .8 3 0 0 0 .8 4 7 4 0 .7 9 8 2 0 .7 7 9 8 0 .8 3 4 8 1 6 4 .0 5 1 67 .23 1 76 .21 1 62 .79 1 47 .82 3 .4 5 2 0 .8 1 8 1 1 63 .62 0 .1 9 9 0 .0 2 8 0 1 0.2 73 THYMUS [ (G m s) %FBW % BR AIN | 0 .5 4 3 0 .1 2 4 1 2 4 .5 2 6 0 .5 7 7 0 .1 3 3 6 2 6 .3 7 1 0 .3 0 6 0 .0 7 0 5 1 5 .5 5 7 0 .4 4 4 0 .1 0 5 2 2 1 .9 6 9 0 .3 9 9 0 .1 0 3 6 1 8 .3 4 5 0 .4 5 4 0 .1 0 7 4 2 1 .3 5 4 0 .1 1 0 0 .0 2 4 2 4 .4 2 3 6 FBW F in a l B o d y W e ig h t A 3;QQ*PlttU*S s - 164- ). H-25134: Four-Week Inhalation Toxicity Study in Male Rats ) DuPont-11414 In d iv id u a l A n im a l F in a l B ody a nd O rgan W e ig h ts - D ay 56 S a c r ific e G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: MALES 1 ANIM AL 1 664852 664853 664854 664855 664856 LIV E R (G m s) %FBW % BRAIN 1 5.837 1 3.4 36 1 3.302 1 4.177 1 1.882 3 .3 5 9 6 2 .9 5 2 3 3 .0 6 0 7 3 .2 3 3 1 2 .9 7 8 7 7 38.32 6 10.45 6 68.44 6 92.91 5 42.06 LUNGS (G m s) %FBW % BRAIN 2 .0 6 7 2 .6 6 9 2 .0 1 8 2 .0 2 9 1 .9 6 8 0 .4 3 8 5 0 .5 8 6 5 0 .4 6 43 0 .4 6 2 7 0 .4 9 3 4 9 6.364 1 21 .26 1 01.41 9 9.169 8 9.7 81 SPLEEN (G m s) %FBW % BRAIN 1 .0 0 5 0 .7 8 6 0 .6 3 1 0 .8 5 3 0 .8 6 4 0 .2 1 3 2 0 .1 7 2 7 0 .1 4 5 2 0 .1 9 4 5 0 .2 1 6 6 4 6.853 3 5.7 11 3 1.7 09 4 1.6 91 3 9.4 16 TESTES (G m s) %FBW % BRAIN 3 .3 9 3 3 .0 1 5 3 .6 6 3 3 .4 2 2 3 .2 9 6 0 .7 1 9 8 0 .6 6 2 5 0 .8 4 2 8 0 .7 8 0 4 0 .8 2 63 1 5 8 .1 8 1 3 6 .9 8 1 8 4 .0 7 167 .25 150 .36 Mean S .D . 1 3.7 27 3 .1 1 6 9 6 50 .44 1 .4 4 3 0 .1 7 4 4 7 6.1 52 2 .1 5 0 0 .4 8 9 1 101 .60 0 .2 9 2 0 .0 5 7 8 1 1.8 29 0 .8 2 8 0 .1 8 8 4 3 9 .0 7 6 0 .1 3 6 0 .0 2 9 8 5 .7 6 7 2 3 .3 5 8 0 .7 6 6 4 1 5 9 .3 7 0 .2 3 4 0 .0 7 5 2 1 7 .7 2 0 THYMUS 1 (G m s) %FBW % BR AIN | 0 .4 3 2 0 .3 9 6 0 .4 3 1 0 .4 4 1 0 .3 8 9 0 .0 9 1 6 0 .0 8 7 0 0 .0 9 9 2 0 .1 0 0 6 0 .0 9 7 5 2 0 .1 4 0 1 7.9 92 21.6 58 21.5 54 1 7 .7 4 6 0 .4 1 8 0 .0 9 5 2 1 9 .8 1 8 0 .0 2 4 0 .0 0 5 7 1 .8 7 9 6 G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: MALES 1 ANIM AL 1 664867 664868 664869 664870 664871 LIV E R (G m s) %FBW % BRAIN 14.2 33 3 .0 8 4 1 7 1 4 .1 5 1 7.4 96 3 .6 3 9 7 806 .64 1 6.8 80 3 .5 2 4 7 7 4 5 .5 8 1 0.9 64 2 .6 8 1 3 5 36 .92 9 .9 8 1 2 .6 4 1 9 5 13 .43 LUNGS (G m s) %FBW % BRAIN 2 .2 5 4 2 .4 7 8 2 .4 9 8 1 .5 1 0 1 .6 3 8 0 .4 8 8 4 0 .5 1 5 5 0 .5 2 1 6 0 .3 6 93 0 .4 3 3 6 1 13.10 1 14.25 1 10.34 7 3.9 47 8 4.259 SPLEEN (G m s) %FBW % BRAIN 0 .8 3 2 0 .9 7 3 1 .2 0 5 0 .6 2 8 0 .6 5 5 0 .1 8 0 3 0 .2 0 2 4 0 .2 5 1 6 0 .1 5 3 6 0 .1 7 3 4 4 1.7 46 4 4.8 59 5 3.224 3 0.7 54 3 3.693 TESTES (G m s) %FBW %B R A IN 3 .2 0 0 3 .2 9 7 3 .3 8 5 2 .9 0 6 3 .3 8 8 0 .6 9 3 4 0 .6 8 5 9 0 .7 0 6 8 0 .7 1 0 7 0 .8 9 6 8 1 6 0 .5 6 1 5 2 .0 1 149 .51 1 4 2 .3 1 1 7 4 .2 8 THYMUS 1 (G m s) %FBW % BR AIN | 0 .3 9 3 0 .0 8 5 2 1 9 .7 1 9 0 .4 2 7 0 .0 8 8 8 1 9 .6 8 6 0 .4 9 1 0 .1 0 2 5 2 1 .6 8 7 0 .3 7 5 0 .0 9 1 7 1 8 .3 6 4 0 .3 5 6 0 .0 9 4 2 1 8.3 13 Mean S .D . 1 3.9 11 3 .1 1 43 6 63 .34 3 .3 8 7 0 .4 6 2 6 1 30 .71 2 .0 7 6 0 .4 6 5 7 9 9.1 77 0 .4 7 0 0 .0 6 4 1 1 8 .7 3 8 0 .8 5 9 0 .1 9 2 3 4 0 .8 5 5 0 .2 3 9 0 .0 3 7 5 8 .9 8 8 1 3 .2 3 5 0 .7 3 8 7 1 5 5 .7 3 0 .2 0 0 0 .0 8 8 9 1 2 .2 4 8 0 .4 0 8 0 .0 9 2 5 1 9 .5 5 4 0 .0 5 3 0 .0 0 6 5 1 .3 7 4 0 oo3 ? FBW - F in a l B o d y W e ig h t 3 Sanitized- Doe* not conta"1" Wo > o09 - 165- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 APPENDIX I Individual Animal Pathology Data not contain T S C A C B 1 Company Sanitized. Does H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 INDIVIDUAL ANIMAL PATHOLOGY DATA KEY TO APPENDIX L E S IO N G RADING : H is to p a th o lo g y changes a re d e s c rib e d a c c o rd in g to t h e ir m o rp h o lo g ic c h a ra c te r, d is t r ib u t io n and s e v e r ity . The d is tr ib u tio n (e x te n t o f tis s u e in v o lv e m e n t) is in d ic a te d , w h ere a p p ro p ria te , b y m o d ifie rs such as fo c a l, m u ltifo c a l, d iffu s e , u n ila te ra l, b ila te r a l, e tc . A s e v e rity s c o re , i f a p p ro p ria te , is a ls o a s s ig n e d as fo llo w s : M IN IM A L: M ILD : MODERATE : SEVERE : The am ount o f ch an ge p re s e n t b a r e ly e xce e d s th a t w h ic h is c o n s id 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 is e a s ily id e n tifie d b u t o f lim ite d s e v e rity . The le s io n p ro b a b ly does n o t p ro d u c e a n y fu n c tio n a l im p a irm e n t. The le s io n is p ro m in e n t b u t th e re is s ig n ific a n t p o te n tia l fo r in c re a s e d s e v e r ity . L im ite d tis s u e o r o rg a n d y s fu n c tio n is p o s s ib le . The d e g re e o f change is e ith e r as c o m p le te as c o n s id 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 e x p e c t s ig n ific a n t tis s u e o r o rg an d y s fu n c tio n . COMMENT : G rades m in im a l th ro u g h s e 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 a lo n g a c o n tin u u m w ith m in im a l le s io n s b e in g th e le a s t s e v e re a nd s e v e re le s io n s b e in g th e m o st s e v e re . W h ile th e g ra d e s r e fe r to th e m o rp h o lo g ic 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 ir r e la tiv e b io lo g ic s ig n ific a n c e . G ross o b s e rv a tio n s lis t in g m u ltip le m asses fo r a tis s u e a re d is tin g u is h e d w ith le tte r s ( i. e . . A, b, c, d, e tc .). not contain TSCA CBi Company Sanitized- Does - 167- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664812 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/ CHRO NIC, FOCAL, m in im a l. THYMUS : M IS S IN G . No M ic ro s c o p ic A b n o rm a lity O bse rve d : KID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PH AR YN X/LAR YN X, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE ORGANS NOT EXAM INED: THYMUS DuPont-11414 Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664813 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. HEART : CARDIOMYOPATHY, m in im a l. PROSTATE : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID G L A N D ,. PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , SEM INAL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 ComPan* Santti***-0065 nl conla' TSCA CB* - 169- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664814 T e rm in a l S a c r ific e K ille d on D ay : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N E Y S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PANCREAS : ATROPHY, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Sawttzed.Ooes r .0 , e o n . . . |J S C A C B ' C o tflp a n ^ - 170- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664815 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , KID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. KID N EYS : NEPHROPATHY, CHRONIC PRO GRESSIVE, m in im a l. PARATHYROID GLANDS : M IS S IN G . No M ic ro s c o p ic A b n o rm a lity O bse rve d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE ORGANS NOT EXAM INED: PARATHYROID GLANDS DuPont-11414 D oe.no. contai^SC A C B I Company Sanitize - 171 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664816 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. KID N EYS : NEPHROPATHY, CHRONIC PRO G RESSIVE, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 tscacbi Company 3anltized. Does not contain H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664817 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. KID N EYS : NEPHROPATHY, CHRONIC PRO G RESSIVE, m in im a l. PANCREAS : ATROPHY, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 173 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664818 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : E P ID ID Y M ID E S : D IS C O LO R A TIO N , YELLOW , R A IS E D , R IG H T , 5MM D I A . . No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. E P ID ID Y M ID E S : SPERMATOCELE, m o d e ra te . No M ic ro s c o p ic A b n o rm a lity O b se rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYRO ID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TE STE S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Company Sanitized. Does not contain TSCACBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 r' In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664819 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVAR Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : KID N EYS : NEPHROPATHY, CHRONIC PRO G RESSIVE, m in im a l. HYDRONEPHROSIS, U N IL A T E R A L , m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : LIV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM INAL V E S IC L E S , U RINARY BLADDER, TE STE S , E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE Company Sanitized Does not contain ' SC CB1 - 175 - /""N H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664820 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro u p : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , KID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM INAL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/ CHRO NIC, FOCAL, m in im a l. PARATHYROID GLANDS : M IS S IN G . No M ic ro s c o p ic A b n o rm a lity O b se rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE ORGANS NOT EXAM INED: PARATHYROID GLANDS DuPont-11414 Company Sanitized. Does not contain TSCA CBI -176- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : X C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664821 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ! W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, E Y E ( S) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 177- />***,, H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D ata G roup: I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664822 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : E Y E (S ) W ITH O PTIC NERVE : RUPTURE, R IG H T. No M a c ro s c o p ic A b n o rm a lity O b se rve d : D IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, S K IN , PROSTATE, SEM INAL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X 664823 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X DuPont-11414 nparty Sanitized -178- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D ata G roup : I C o n c e n tra tio n : 0 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664824 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th 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 : L IV E R , K ID N EY S , LONGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X 664825 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O bse rve d : PHARYNX/ LARYNX DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 179- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : I C o n c e n tra tio n : 0 m g/m 3 S e x : M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664826 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O b se rve d : PHARYNX/ LARYNX DuPont-11414 Company Sanitized. Does not contain TSCA CBI - 180- H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664827 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : KID N EYS : D ILA T A T IO N , R IG H T. No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : KID N EYS : HYDRONEPHROSIS, U N ILA T E R A L, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. 664828 ; T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : KID N EYS : D ILA T A T IO N , R IG H T, m ild . No M a c ro s c o p ic A b n o rm a lity O b se rve d : LIV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PH AR YNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : KID N EYS : NEPHROPATHY, CHRONIC PRO G RESSIVE, m ild . HYDRONEPHROSIS, U N ILA T E R A L, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E TA P LA S IA ,' m in im a l. Company Sanitized. Does not contain TSCA CBt - 181 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664829 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : KID N EYS : D ILA T A T IO N , R IG H T, m ild . E P ID ID Y M ID E S : D ISC O LO R ATIO N , TAN, R A IS E D , R IG H T, 7 MM D IA . . No M a c ro s c o p ic A b n o rm a lity O b se rve d : LIV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TE STE S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : KID NEYS : HYDRONEPHROSIS, U N ILA T E R A L, m ild . PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. E P ID ID Y M ID E S : SPERMATOCELE, m ild . 664830 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o su re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID G LAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : PHARYNX / LARYNX DuPont-11414 Company Sanitized. Does not contain TSCA CBI -182- H-25134: Four-Week Inhalation Toxicity Study in Male Rats___________ In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664831 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYRO ID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O b se rve d : P H A R Y N X /L A R Y N X 664832 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l DuPont-11414 Company Sanitized. Does not contain TSCA CBI H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664833 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM INAL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E T A P LA S IA , m in im a l. 664834 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. DuPont-11414 Company * . ,, ,, 4 D s comain T S M ^ - 184- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664835 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. 664836 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o su re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID G LAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X DuPont-11414 Companys ,, ili2 6 < 1 " " '"o'conlamTSCAce, -185- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x : M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664837 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE 664838 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE DuPont-11414 Company Sanitized. Does not contain TSCA CB1 - 186- / "S H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: I I I C o n c e n tra tio n : 5 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664839 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, EYE ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE 664840 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE 664841 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE ( S) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE DuPont-11414 Company Sin'tTM ,, " " ' c ^ {a?nTSCAcBi -187- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664842 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N E Y S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O b se rve d : P H A R Y N X /L A R Y N X 664843 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E TA P LA S IA , m in im a l. DuPont-11414 Con,P *nysanmi0ti 0 o e s " o t C O R fe?n A Cfif - 188- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D ata G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664844 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro u p : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X 664845 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N E Y S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID G LAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. DuPont-11414 2mpany Sanitized, Does n? contain TSC4 - 189- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664846 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. 664847 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYRO ID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. DuPont-11414 Company Sanitized. 0088 not contain TSCA CBI -190- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664848 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. 664849 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X DuPont-11414 &8fly e '0 & S r>ot TS ca CBi -191 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D ata G roup : V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664850 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. 664851 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. DuPont-11414 - 192- I']Party $ ed. n o t cntat r CA H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M i c r o s c o p i c Si M a c r o s c o p ic F i n d i n g s 664852 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E { S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE 664853 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM INAL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE 664854 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ! W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TE STE S , E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE DuPont-11414 Co>nPanyS, e * o e < n o t ntam T S C A CBf -193- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup : V C o n c e n tra tio n : 30 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664855 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : KID N EYS : D ILA T A T IO N , R IG H T, s e v e re . No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE 664856 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE DuPont-11414 - 194- C O n,* n T s c * c a i H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 5 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664857 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th 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 : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 - 195 - H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664858 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U RINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 -196- .V H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664859 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. E Y E (S ) W ITH O PTIC NERVE : O PTIC NERVE NOT PRESENT. PROSTATE : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P T IC NERVE, S K IN , SEM INAL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Company Sanitized. Does not contain TSCACBI - 197- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II A n im a l R e f C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664860 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FO CAL, m in im a l. HEART : CARDIOMYOPATHY, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bserved : K ID N EY S , LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P T IC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 con,a'n rsc4 C B I  ""S H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664861 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o ff fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQUAM OUS M E TA P LA S IA , m in im a l. TESTES : DEG ENERATIO N /ATRO PHY, SEM IN IFER O U S TUBULES, m in im a l. E PID ID Y M ID E S : O LIG O SPERM IA/G ERM CELL D E B R IS , m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U RINARY BLADDER, FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 - 199- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664862 T e rm in a l S a c r ific e K ille d on Day : 25 E x p o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. PARATHYROID GLANDS : M IS S IN G . E Y E ( S ) W ITH O PTIC NERVE : O PTIC NERVE NOT PRESENT. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE ORGANS NOT EXAM INED: PARATHYROID GLANDS DuPont-11414 H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 ` S e x : M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664863 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : L IV E R , K ID N E Y S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, E Y E ( S ) W ITH O P T IC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TE STE S , E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 ,!otcntQin -201 - /' " N H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664864 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o s u re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th 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 : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FOCAL, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. PROSTATE : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE ( S ) W ITH O PTIC NERVE, S K IN , SEM INAL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 -202- n r Oht8fn H-25134: Four-Week Inhalation Toxicity Study in Male Rats i' In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664865 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G ro up : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : LIV E R : IN FLAM M ATIO N , SUBACUTE/CHRO NIC, FO CAL, m in im a l. PHARYNX/LARYNX : HYPERPLASIA/SQ UAM OUS M E T A P LA S IA , m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM INAL V E S IC L E S , U RINARY BLADDER, TE STE S , E P ID ID Y M ID E S , FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE DuPont-11414 Coni] -203 - Does n o t e 0 ln t ! n H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664866 T e rm in a l S a c r ific e K ille d on Day : 25 E xp o su re G roup : SAC1 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, THYRO ID G LAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E {S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , U R IN AR Y BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y KID N EYS : NEPHROPATHY, CHRONIC PRO GRESSIVE, m in im a l. PARATHYROID GLANDS : M IS S IN G . TESTES : DEG ENERATIO N /ATRO PHY, SEM IN IFER O U S TUBULES, U N ILA T E R A L, m in im a l. No M ic ro s c o p ic A b n o rm a lity O bse rve d : L IV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , S P IN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE ORGANS NOT EXAM INED: PARATHYROID GLANDS DuPont-11414 -204- / '""' "N H-25134: Four-Week Inhalation Toxicity Study in Male Rats DuPont-11414 In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664867 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N E Y S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E ( S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H AR YN X/ LARYNX 664868 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th 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 : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S A LIV A R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHAR YNX/LARYNX, EYE (S ) W ITH O P TIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y No M ic ro s c o p ic A b n o rm a lity O bse rve d : PHARYNX/ LARYNX 664869 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ross P a th o lo g y : No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R A IN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O PTIC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC LE S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bserved : P H A R Y N X /L A R Y N X $H)j>ai9 Sanitized. Does not contain TSGA GBI -205- H-25134: Four-Week Inhalation Toxicity Study in Male Rats In d iv id u a l A n im a l P a th o lo g y D a ta G roup: V II C o n c e n tra tio n : 100 m g/m 3 S e x: M a le s A n im a l R e f M ic ro s c o p ic & M a c ro s c o p ic F in d in g s 664870 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : E Y E (S ) W ITH O PTIC NERVE : RUPTURE, R IG H T. No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , K ID N EY S , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , SPIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILE U M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, S ALIVA R Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P ITU ITA R Y GLAND, TH YR O ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, S K IN , PROSTATE, SEM IN AL V E S IC L E S , URINARY BLADDER, TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X 664871 T e rm in a l S a c r ific e K ille d on Day : 56 A n im a l is s ig n e d o f f fro m n e c ro p s y G ro ss P a th o lo g y : KID N EYS : D ILA TA TIO N , LE FT. URINARY BLADDER : C A LC U LU S!C A LC U LI. No M a c ro s c o p ic A b n o rm a lity O b se rve d : L IV E R , LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, B R AIN , S PIN A L CORD, STOMACH, DUODENUM, JEJUNUM, ILEU M , PANCREAS, CECUM, COLON, RECTUM, M ESENTERIC LYMPH NODE, SALIVAR Y GLANDS, M ANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, S C IA T IC NERVE, P IT U IT A R Y GLAND, THYRO ID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, E Y E (S ) W ITH O P T IC NERVE, S K IN , PROSTATE, SEM IN AL V E S IC L E S , TESTES, E P ID ID Y M ID E S , FEM UR/KNEE J O IN T , STERNUM, NOSE H is to p a th o lo g y : No M ic ro s c o p ic A b n o rm a lity O bse rve d : P H A R Y N X /L A R Y N X DuPont-11414 -inp-Wf Sanitized. Does net contain T s c c a t -206-