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AR226-3168 DuPont-4292 TRADE SECRET Study Title H-24267: Two-Week Inhalation Toxicity Study in Male Rats Laboratory Project ID: DuPont-4292 AUTHOR: David P. Kelly, B.S. Study Completed on: October 6,2000 Performing Laboratory: E.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number^ Service Code Number^ B P J Clinical Pathology Number: J Page 1 of 181 Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards except for the items documented below. None of the items listed impact the validity of the study. 1. The test substance was characterized by the sponsor prior to the initiation of this study and a report was supplied, however, records of the characterization are not available. Although the characterization was not performed under Good Laboratory Practice Standards, based on the familiarity with the laboratory and the techniques used, the data is considered sufficient for the purposes of this study. 2. Prior to the daily experiments, samples of the test compound were transferred to holding containers. These intermediate containers were used for convenience in transferring the test compound into syringes that were used in metering the test chemical into the atmosphere generation system. The intermediate containers were not labeled in compliance with Good Laboratory Practice Standards. In addition, the weights of the test substance were recorded on sample containers and later transferred to the study notebook and labels were discarded. Submitter / Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S .A. Q -Z /o T -im Date DuPont Registration Representative:____________________ __________________ _________ Date -2Com panf Sanitized. Does not contain TSCA CBt H-24267: Two-Week Inhalation Toxicity Study in Male Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24267 Dates of Inspections: Conduct: May 2,4,17,2000 Records, Reports: September 13-15,18-21,2000 Dates Findings Reported to: Study Director: September 21,2000 Management: October 6,2000 DuPont-4292 Reported by: Joseph C. Hannill Senior Quality Assurance Auditor O ct* Date -3- Companf Sanitized. Boe not eontaln TSC CBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Clinical Pathology Evaluations Reported by: Nancy H. Rverds, D.V.M. Diplomate A.C.V.P. Principal Research Scientist (o 0 c t3 & Date Anatomic Pathology Evaluations Reported by: ^ Anatomic Pathology Evaluations Peer Review by: s/r ^ Steven R. Fnfme, D.V.M., Ph.D. Diplomate A.C.VP. Director -T M G. Tracy Makoveo? D.V.M. Diplomate A.C.V.P. Senior Research Scientist :/ Date { k^a a o Date Approved by: /a Scot^E. Loveless, Ph D. Director (0 O o t 3 o o O Date Issued by Study Director: b a ^ f P /k s U y , B.S. /Research Scientist O rT J 0*q Date 4- Company Sanitized. Dees not eenfa'n TSC C l! H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEM ENT__________________ 2 QUALITY ASSURANCE STATEM ENT____________________________________________3 C E R T IF IC A T IO N ------------------------------------ 4 LIST OF T A B L E S................................................. ...........7 LIST OF FIGURES___________ LIST OF APPENDICES---------------------------------------------------------------------------------------- 8 STUDY INFORM ATION...................................... 9 STUDY PERSONNEL__ __________________________________________________________10 SUM M ARY_____________________________________________________________________11 INTRODUCTION..............................................................................................................................12 MATERIALS AND M ETHODS. < .12 A. Test Substance.......................................................................................................................... 12 B. Animals...................................................................................................................................... 12 C. Animal Husbandry....................................................................................................................12 1. Temporary Animal Identification and Quarantine..................................................................................... 12 2. Housing.........................................................................................................................................................13 3. Animal Room Environment.........................................................................................................................13 4. Animal Selection and Permanent Identification......................................................................................... 13 5. Feed and Water............................................................................................................................................. 13 6. Health Monitoring Program.................................................................................................................. 13 D. Study Design............................................................................................................................. 14 E. Inhalation Exposure System..................................................................................................... 14 1. Atmosphere Generation...............................................................................................................................14 2. Chamber Construction and Design.............................................................................................................. 14 3. Exposure M ode............................................................................................................................................ 15 F. Characterization of Chamber Atmosphere.............. 15 1. Test Substance Sampling and Analysis..................................................................................................... 15 2. Environmental Monitoring.......................................................................................................................... 15 G. Body Weights and Clinical Observations...................................................................... 15 H. Clinical Pathology Evaluations................. 16 1. Hematology........................................................................................ 16 2. Coagulation Parameters................................................................................................................................16 3. Serum Chemistry........................................................................................................................................ 16 4. Urinalysis.......................................................................................................................................................17 I. Anatomic Pathology Evaluations............................................................................................ 17 J. Statistical Analyses............................................................................................... 18 -5- impffflf S a n d e d . Does not mnsin TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE O F CONTENTS (Continued) Page RESULTS AND DISCUSSION 20 In-Life Animal M easurem ents..... ..20 I A. Chamber Atmosphere Analysis of H-24267 ..........................................................................20 B. Body Weights and Clinical Observations................................................................ ............. 20 Clinical Pathology Evaluations 21 A. Hematology/Coagulation.........................................................................................................21 B. Serum Chemistry.......................................................................................................................21 C. Urinalysis...................................................................................................................................22 D. Conclusions............................................................................................................................... 23 A natom ic Pathology E valuations. ....23 I A. Organ W eights..........................................................................................................................23 B. Gross Observations.................................................................................................................. 23 C. Microscopic Findings............................................................................................................... 24 D. Conclusions...................................................................... 24 CONCLUSIONS ..25 RECORDS AND SAMPLE STORAGE.............. ..................25 R E FE R EN C E S..... ____ 26a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a e a a a a a a a a a e a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a i T A B L E S 27 a FIGURES 73 APPENDICES a76 -6Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 LIST OF TABLES Page 1. CHAMBER CONCENTRATIONS OF H-24267 ...................................................................................................31 2. PARTICLE SIZE DISTRIBUTION OF H-24267.................................................................................................... 31 3. CHAMBER ENVIRONMENTAL CONDITIONS.................................................................................................. 31 4. MEAN BODY WEIGHTS OF MALE RATS.................................................... 32 5. MEAN BODY WEIGHT GAINS OF MALE RATS...............................................................................................34 6. SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS AT WEIGHING.......................................... 36 7. SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS......................................................................... 37 8. SUMMARY OF COAGULATION VALUES FOR MALE R A TS........................................................................42 9. SUMMARY OF SERUM CHEMISTRY VALUES FOR MALE RATS............................................................... 43 10. SUMMARY OF URINALYSIS VALUES FOR MALE RATS............................................................................. 46 11. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 11 SACRIFICE.....................47 12. MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 25 SACRIFICE...................... 49 13. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE................................... 51 14. INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE................................... 56 15. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE.................................................................................................................................................60 16. INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE.................................................................................................................................................70 LIST OF FIGURES Page 1. SCHEMATIC OF EXPOSURE SYSTEM............................................................................................................... 74 2. MEAN BODY WEIGHTS OF MALE RATS.......................................................................................................... 75 -7 - Convany S a n t * . ^ TS 081 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 LIST OF APPENDICES Page A. DAILY ATMOSPHERIC ANALYSES.................................................................................................................... 77 B. DAILY ENVIRONMENTAL CONDITIONS..........................................................................................................81 C. INDIVIDUAL BODY W EIGHTS............................................................................................................................ 85 D. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS.................................................90 E. INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA................................................................... 95 F. INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS...................................................................135 G. INDIVIDUAL ANIMAL PATHOLOGY DATA................................................................................................... 140 -8 Gompany Sanitized. Does not contain T8 CA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats STUDY INFORMATION DuPont-4292 Haskell Number: 24267 Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: May 4, 2000 / (see report cover page) In-Life Initiated/Completed: May 8, 2000 / June 2,2000 -9 - Compaiw sf<zed. Boas not e-- S H-24267: Two-Week Inhalation Toxicity Study in Male Rats STUDY PERSONNEL Study Director: David P. Kelly, B.S. - Management: Scott E. Loveless, Ph.D. Nancy C. Chromey, Ph.D. Primary Technician: Thomas A. Kegelman, A.A. Clinical Pathologist: Nancy E. Everds, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Pathologist: Steven R. Frame, D.V.M., Ph.D. Management: Steven R. Frame, D.V.M., Ph.D. Robert W. Rickard, Ph.D., D.A.B.T. Peer Review Pathologist: G. Tracy Makovec, D.V.M. Toxicology Report Preparation: Maryanne M. Wilford, B.A. Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-4292 - 10- 'Cwwpawp Vtam* mit ermfsfn TOGA OBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 SUMMARY Groups of 10 male Crl:CD(SD)IGS BR rats were exposed for 6 hours/day, for a total of 9 exposures over a 2-week period to design concentrations of 25,125, or 600 mg/m3 (actual mean concentrations were 23,110, and 600 mg/m3) of H-24267 aerosol. The mass median aerodynamic equivalent diameter of the aerosols ranged from 2.6 to 4.2 fim. A control group of 10 male rats was exposed simultaneously to houseline air. At the end of the exposure period, blood and urine samples were collected for clinical analyses, and 5 rats per group were sacrificed for pathologic examination. After a 2-week recovery period, the surviving rats were also given clinical and pathologic examinations. During the exposure period a dose-related body weight depression occurred primarily in the 125 and 600 mg/m3groups and all 3 test groups gained less weight than the controls. The H-24267 exposed rats resumed a normal weight gain rate during the recovery period. Clinical pathology evaluations at both evaluation times showed no toxieologically significant changes in hematology, clinical chemistry, or urinalysis parameters, including urinary fluoride. Weight analysis of the major organs showed no effects attributable to the test compound. Histological findings were confined to the respiratory tract; there were no significant findings in any other evaluated organs. Minimal, dose-related histologic effects attributable to the test compound were detected in the respiratory tract of all treated groups at the end of the 2-week exposure period. The effects were consistent with minimal irritation and were slightly more apparent with increasing dose. These effects occurred throughout the respiratory tract, including the nose, larynx, and lung. In the lung, inflammation was characterized by mild thickening of alveolar duct bifurcations and adjacent alveolar septa due to mononuclear inflammatory cell infiltration. Slight hypertrophy of terminal bronchiolar epithelium was also present in association with the centriacinar inflammatory response. In the larynx, minimal squamous metaplasia was present in all treated groups. Necrosis of cartilage overlying the laryngeal saccule was present in 1 rat in the 600 mg/m group. In the nose, hypertrophy of goblet cells was present in all treated groups and was most apparent in the mucosa of the pharyngeal duct. Following an approximate 2-week recovery period, respiratory tract lesions were essentially reversible. Single occurrences of focal, very slight thickening of alveolar duct septa occurred in the 125 and 600 mg/m3recovery groups. In addition, focal residual cartilage necrosis in the larynx occurred in 2/5 rats in the 600 mg/m3recovery group. Based on the finding of minimal respiratory tract inflammation observed in all exposed groups, including the lowest concentration tested, 25 mg/m3, a no-observed-adverse- effect-level (NOAEL) was not determined for repeated aerosol exposures to H-24267 in rats. -11 - Sampany m l eomfefe TS6 B1 INTRODUCTION The purpose of this 2-week inhalation study was to investigate the effect nf rpnp,t a u , exposure exnosure "inTJ rh"a.ts8.t*o0 highh ccoonncceennTttrraattiioonnss onofffHHH--22w4422e66n77.. ItInnhuhaal,laa?ttiioonn.iiss aannt teexxptpseec"ctteerdderproeeunattteeedooifnfhhhuaumlmaatainno n exposure. The data will be used to provide infomiadon for safee hhaannddlliinngg ooff tthhe test s u b s TM . rats died after exposure to 2.3 mgfL (DuPont h<"l T9 m* ? roantsr n i -mpouudwwasasj.3y.9mmg^gtt.; no a5s=S S S S a' expenment weight loss was observed in rats exposed for 3 t o ! Y 111another MATERIALS AND METHODS A. Test Substance The test substance, H-24267, was supplied by the sponsor as batch analysis was provided by the sponsor. The test substancR S?assum ed to lie stahl throughout die exposure phase of die study; no evidence o f in s ta b S " B. Animals i t a * c t S T f n f ^ BR Were reCeiVed ft0m Charles R iw r " oratories, Inc., Raleigh North Carolina. T heratsw ereapproxm iateIy7w eeksoldonthedayofairival. H ie C. Animal Husbandry 1 Temporaiy Animal Identification and Quarantine S ; r a S S e d r r c l e teR r ^ ' 1_ 10 S die quarantine period rats w i e identification number, which was Company Sanitized. Does not contain TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 2. Housing Rats were housed either singly or in pairs in suspended, stainless steel, wire-mesh cages. 3. Animal Room Environment Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted to be within a temperature range of 23 2C and a relative humidity range of 50 10%. Excursions outside of these ranges were of insufficient magnitude and/or duration to have adversely affected the validity of the study. 4. Animal Selection and Permanent Identification Prior to the end of the quarantine period, rats were assigned to 4 groups of 10 male rats each. Rats were divided into groups with the aid of a computerized, stratified, randomization program, so that mean body weights for each group were similar. Rats were approximately 8 weeks old and weighed between 257 and 333 grams at the start of the exposures. Upon grouping, each rat was assigned a unique 6-digit animal number. Following grouping, a 1to 2-digit identification number was tattooed onto the tail of each rat. Both numbers were recorded on a card affixed to the cage. 5. Feed and Water Except during exposure, tap water was available ad libitum. PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 was available ad libitum except during exposure and fasting periods prior to necropsy. 6. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to assure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage .racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. -13- G ow panf Samifeod, B@@s noeenSah TSC CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. D. Study Design Four groups of 10 male rats each were exposed to concentrations of H-24267 targeted to 0,25, 125, or 600 mg/m3. Rats were exposed nose-only for 6 hours per day for a total of 9 exposures. On the day of the last exposure, collection of an overnight urine specimen was initiated for each rat. On the day following the last exposure, blood samples were collected for clinical analyses, and 5 rats per group were sacrificed for anatomic pathology examination. All remaining rats were allowed to recover for a 14-day period. At the end of the recovery period, blood and urine samples were collected for clinical analyses, and all surviving rats were sacrificed for anatomic pathology examination. All rats were weighed and individually observed for clinical signs of toxicity throughout the exposure period. Group clinical signs were observed during each exposure. In addition, the alerting response to an auditory stimulus was checked during each exposure. After each exposure, rats were checked for the alerting response to an auditory stimulus prior to removal from chambers and were observed for clinical signs immediately after they were returned to their cages. Surviving rats were weighed and individually observed for clinical signs of toxicity throughout the recovery period. E. Inhalation Exposure System (Figure 1) 1. Atmosphere Generation Chamber atmospheres were generated by nebulization of H-24267 in air with a Spraying Systems nebulizer. The test substance was metered into the nebulizer with a Harvard Model 22 syringe drive. The syringe containing the test substance was heated (as high as 60C) to facilitate liquid spraying. Filtered houseline air, introduced at the nebulizer, atomized the test substance and carried the aerosol into the exposure chamber. Dilution air was added to the chamber turret so that the total airflow to each chamber was 30 liters per minute. A baffle placed at the bottom of the chamber turret was used to promote uniform aerosol distribution throughout the chamber. Varying the test substance feed rate to the aerosol generator controlled chamber concentrations of H-24267. Test atmospheres were exhausted through a dry-ice cold trap and an MSA filter prior to discharge into the fume hood. 2. Chamber Construction and Design The exposure chamber was constructed of stainless steel and glass (NYU style) with a nominal internal of 150 liters. A tangential air feed on the chamber promoted uniform chamber distribution of the test atmosphere. - 14- Company SanftteedI. Does not contain TSC CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 3. Exposure Mode During exposure, rats were individually restrained in stainless steel cylinders with conical nose pieces. The restrainers were inserted into the polymethylmethacrylate faceplate of the exposure chamber so that only the nose of each rat extended into the chamber. F. Characterization o f Chamber Atmosphere 1. Test Substance Sampling and Analysis The atmospheric concentration of H-24267 was determined at approximately 60-minute intervals by gravimetric analysis o f the test chambers. The control chamber was sampled once daily. Known volumes of chamber atmosphere were drawn from the breathing zone of the rats through 25 mm filter cassettes that contained preweighed Gelman glass fiber (Type A/E) filters. The filters were weighed on a Cahn Model C-26 Electrobalance. The atmospheric concentrations of H-24267 were calculated from the difference in the pre- and post-sampling filter weights. An air sample was taken from each exposure chamber1once per week to determine the particle size distribution (mass median aerodynamic diameter and geometric standard deviation) using a Sierra Series 210 cyclone preseparator/cascade impactor and Sierra Series 110 Constant How Air Sampler.(1) 2. Environmental Monitoring Chamber airflow was set at the beginning of each exposure to achieve at least 12 air changes per hour. The airflow was monitored continually with a calibrated Brooks model 1355 Sho-Rate Rotometer and recorded initially and whenever changes were made. Chamber temperature was targeted at 22 2C. The temperature was monitored continually with an Omega model DP41TC Thermocouple Thermometer and recorded 3 times during each exposure. Chamber relative humidity was targeted at 50 10%. The relative humidity was measured with an Omega model RH5100C Digital Psychrometer and recorded twice during each exposure. Chamber oxygen concentration was targeted to at least 19%. The oxygen concentration was measured with a Biosystems model 3100R Oxygen Analyzer and recorded twice during each exposure. G. Body W eights and Clinical Observations During the exposure phase of the study, all rats were weighed daily and individually observed for clinical signs of toxicity before and after each exposure. Group clinical observations were made during exposures. In addition, rats were checked for an alerting response to an auditory stimulus 3 times during each exposure and after each exposure. During the recovery period, all remaining rats were weighed and individually observed daily. a Particle size samples were not taken from the control chamber. - 15- Sanitized. Doe not tain T iO CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 H. Clinical Pathology Evaluations A clinical pathology evaluation was conducted on all rats after the last exposure and from all remaining rats on the last day of recovery. The day before collection of blood samples for the clinical pathology evaluation, the rats were placed in metabolism cages. These rats were fasted overnight and urine was collected from each rat. Blood samples for hematology and clinical chemistry measurements were collected from the orbital sinus of each rat while the rat was under light carbon dioxide anesthesia. Blood samples for coagulation parameters and fluoride analysis were collected under carbon dioxide immobilization from the abdominal vena cava at sacrifice. Blood samples were evaluated for quality by visual examination prior to analysis. 1. Hematology The following hematology parameters were determined: red blood cell count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count white blood cell count absolute differential white blood cell count percent differential white blood cell count platelet count microscopic blood smear examination Complete blood counts were determined on a Bayer (Technicon) H-1E hematology analyzer, calculated within the Xybion data collection system using the hematology analyzer's results, or determined from microscopic evaluation of the blood smear. Wright-stained blood smears from all rats were examined microscopically for confirmation of automated results and evaluation of cellular morphology. Reticulocyte counts were determined on a Sysmex R-3000. New methylene blue-stained blood smears were prepared from all hematology samples but were not needed for evaluation. 2. Coagulation Parameters The following coagulation parameters were determined: prothrombin time activated partial thromboplastin time Coagulation times were determined on a Sysmex CA-1000. 3. Serum Chemistry The following serum chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase sorbitol dehydrogenase total protein albumin globulin -16- Company Sanitised. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats alkaline phosphatase total bilirubin urea nitrogen creatinine cholesterol triglycerides glucose calcium inorganic phosphorus sodium potassium chloride fluorideb DuPont-4292 Clinical chemistry parameters were measured on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer or calculated using results of chemistry tests within the Xybion data collection system. 4. Urinalysis The following urinalysis parameters were determined: quality color transparency volume osmolality specific gravity pH protein glucose ketone bilirubin blood urobilinogen fluoride0 microscopic urine examination Urine volume, color and transparency were evaluated visually. All other urine parameters were semi-quantitatively measured on a Bayer Clinitek AtlasTM Automated Urine Chemistry, utilizing Ames Multistix chemistry dipsticks. Sediments from all urine specimens were evaluated microscopically. I. Anatomic Pathology Evaluations After the last exposure, 5 rats per group were euthanized by carbon dioxide anesthesia and exsanguination ad given gross and histopathology evaluations. On the last day of the recovery period, the remaining rats of each group were similarly sacrificed and evaluated. All rats on study were given a complete gross examination and representative samples of the following tissues were saved at necropsy: Hematopoietic System Circulatory System Respiratory System - bone marrow (femur and sternum), mesenteric lymph nodes, spleen, thymus - heart - trachea, lungs, nose, larynx, pharynx b Fluoride determination was analyzed from plasma with F.DTA added, c Fluoride determination was analyzed from urine with EDTA added. -17- Gom pany SanBtaed. Boe* m l stain TSCft 11 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Digestive System Urinary System Endocrine System Reproductive System Nervous System Other esophagus, stomach, liver, pancreas (exocrine and islets), small intestine (duodenum, jejunum, and ileum), large intestine (cecum, colon, and rectum) kidneys, urinary bladder thyroid gland (cortex and medulla), parathyroid glands, adrenal glands, prostate, testes, epididymides, seminal vesicles brain (cerebrum, midbrain, cerebellum, medulla/pons), spinal cord (cervical, thoracic, lumbar), sciatic nerve eyes and selected gross lesions Liver, kidneys, lungs, brain, and testes from rats sacrificed by design at the end of the exposure and recovery periods were weighed wet at necropsy. Gross lesions which were diagnosed at necropsy and for which microscopic examination was not appropriate (e.g., missing anatomic parts) were not collected. Selected gross lesions for which a microscopic diagnosis would not be additive (e.g., deformity of tail) were saved but were not processed for microscopic evaluation. All tissues were fixed in 10% neutral buffered formalin except testes, epididymides, and eyes which were fixed in Bouin's solution. The lungs were inflated with 10% neutral buffered formalin after weighing. All tissues were processed, embedded in paraffin, cut at a nominal thickness of 5 micrometers, stained with hematoxylin and eosin (H&E) and examined microscopically. J. Statistical Analyses Descriptive statistics including mean, standard deviation, and standard error of the mean were used to summarize experimental data. Significance was judged at p < 0.05. -18Crdnipawy Sanitised, Dees not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Parameter Exposure Concentration Data Particle Size Data Body Weight Body Weight Gain Organ Weight Clinical Pathology0 Incidence of Clinical Observations Preliminary Test None None Test for lack of trend(2) Levene's test for homogeneity(5) and Shapiro-Wilk test(6) for normality15 Levene's test for homogeneity*51 and Shapiro-Wilk test(6) for normality15 None Method of Statistical Analysis If preliminary test is If preliminary test is not significant significant Descriptive statistics (e.g., mean, standard deviation) Regression analysis or probit analysis(1) Sequential application(3) of the Preliminary tests for Jonckheere-Terpstra pairwise comparison trend test*41 ORa One-way analysis of Kruskall-Wallis test(9) variance(7) followed followed with Dunn's with Dunnett's test*81 test*101 One-way analysis of variance*-71followed with Dunnett's test(8) Kruskall-Wallis test*91 followed with Dunn's test(10) Cochran-Armitage test for trend(7)d a Pairwise comparisons and associated preliminary tests were only conducted if the test for lack of trend was significant. b If the Shapiro-Wilk test was not significant but Levene's test was significant, a robust version of Dunnett's test was used. c 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. d If the incidence was not significant, but a significant lack of fit occurred, then Fisher's Exact test(11) with a Bonferroni correction was used. - 19- iam toed. D@@s ^ T??(SA6 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 RESULTS AND DISCUSSION In-Life Anim al M easurements A. Chamber Atmosphere Analysis o f H-24267 (Tables 1-3, Appendices A-B) Mean aerosol concentrations, particle size measurements, and chamber environmental conditions results are in tables 1,2, and 3, respectively. Mean analytically determined aerosol concentrations of H-24267 for the 3 test chambers were 23,110 and 600 mg/m3(2 significant figures) for design concentrations of 25,125, and 600 mg/m3, respectively. Based on 2 measurements per test concentration, the mass median aerodynamic equivalent diameter of the H-24267 aerosol ranged from 2.6 to 4.2 fim. The chamber oxygen concentration measurements were 21%, The relative humidity for the chambers was between 35 and 84% and the chamber temperatures were between 21 and 26C. The temperature and humidity in the chambers were close to that targeted with the exception of the %RH in the 600 mg/m3chamber, and this was appreciably higher than targeted due to the presence of a high percentage of water (60 to 85%) in the test sample. Although the chamber humidity was high, these conditions are frequently encountered in inhalation studies with water- based aerosols and this was not expected to affect the study outcome. - B. Body W eights and Clinical Observations (Tables 4-6, Figure 2, Appendices C-D) During the exposure period, there was a dose-related body weight depression that occurred especially in the 125 and 600 mg/m3 groups and all 3 groups gained less weight than controls. The H-24267 exposed rats appeared to resume a normal weight gain rate during the recovery period. After the third exposure, slight lung noise occurred in 2 rats in the 600 mg/m3 group. These effects were not observed in the other test groups. Sporadic incidences of alopecia were observed in some rats during the study. These findings were not dose-related and are frequently seen in inhalation studies where the animals are exposed in body restrainers. -20- mpaby Sanitized. Does contatti TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats Clinical Pathology Evaluations DuPont-4292 A. Hem atology/Coagulation (Tables 7-8, Appendix E) , There were no toxicologically significant changes in male rats for hematologic or coagulation parameters. All statistically significant changes were considered not toxicologically significant (non-adverse) or not related to compound administration. These changes are detailed below. The statistically significant minimal decreases in reticulocytes at day 11 in rats exposed to 125 or 600 mg/m3were not correlated with any other supportive changes in erythrocyte parameters. Therefore, these changes were considered toxicologically insignificant and not compound related. Reticulocyte counts in H-24267-exposed rats at recovery were similar to control group values. Statistically significant changes in the following parameters were minimal, did not occur in a concentration-dependent manner, and therefore were toxicologically insignificant: Decreased absolute neutrophils in rats exposed to 25 or 125 mg/m3 at day 11 Decreased platelets in rats exposed to 25 mg/m3at day 11 Increased relative lymphocytes in rats exposed to 25 (day 11 only) or 125 (days 11 and 25) mg/m3 Decreased relative neutrophils in rats exposed to 25 (day 11 only) or 125 (days 11 and 25) mg/m3. B. Serum Chemistry (Table 9, Appendix E) There were no toxicologically significant changes in male rats for clinical chemistry parameters. All statistically significant changes were considered not toxicologically significant (non-adverse) or not related to compound. These changes are detailed below. Statistically significant minimally decreased sodium, with minimally increased urea nitrogen and creatinine, occurred in rats exposed to 600 mg/m3 at day 11. These changes were mostly due to 1 animal (637830) who had moderate alterations in these 3 parameters. This rat also had dilute urine and nephropathy on histologic examination (grade mild), a background lesion that is commonly seen in CD-CRLIGS rats. The histologic lesion in this rat was not considered treatment related; therefore, the clinical pathology changes were also not considered related to treatment. Two other rats in the 600 mg/mg3group had minimally increased urea nitrogen and creatinine (637835 and 637837) at day 11. These rats also had mildly increased albumin (with resulting -21 - npifflf S ariizei. Does cw***' TSfCCB! H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 increased total protein and calcium,d and decreased chloride at this same time-point. The renal concentrating ability of these rats was intact, and they had no histologic evidence of nephropathy. Therefore, although the changes discussed above were possibly related to treatment, they were not considered toxicologically significant in this group because there were no treatment related alterations in renal function (as measured by concentrating ability) or renal histology at either time-point. Minimally increased albumin in rats exposed to 25 or 125 mg/m3(or 600 mg/m3, see burger dot 2 above) at day 11 was possibly related to treatment, but was not considered toxicologically significant because the changes were very slight (approximately 0.2 g/dl greater than the control group mean). At recovery (day 25), albumin concentrations in H-24267-exposed rats were similar to control group values, and within the reference range for the parameter (reference range: 4.3-4.9 g/dl). Minimally increased cholesterol in rats exposed to 125 or 600 mg/m3 at day 11, although possibly related to treatment, was not considered toxicologically significant because the change was slight and individual values generally were within the reference range for this parameter (reference range: 46-102 mg/dl). At recovery (day 25), cholesterol concentrations in H-24267-exposed rats were similar to control group values. Statistically significant changes in the following parameters were minimal and did not occur in a concentration-dependant manner, or only occurred during the recovery phase, and therefore were toxicologically insignificant: Increased urea nitrogen and creatinine in rats exposed to 25 mg/m3at day 11 Decreased triglycerides in rats exposed to 25 mg/m3 at day 11 Decreased globulins in rats exposed to 125 mg/m3 at day 25 Increased chloride in rats exposed to 25 mg/m3at day 11. C. Urinalysis (Table 10, Appendix E) There were no toxicologically significant changes in male rats for urinalysis parameters. All statistically significant changes were considered not toxicologically significant (non-adverse) or not related to compound. These changes are detailed below. Urine pH was moderately decreased (statistically significant) in rats exposed to 125 or 600 mg/m3at day 11. Although decreased urine pH was possibly related to treatment, there were no correlative changes in other parameters (chloride, sodium, potassium) to suggest d Calcium exists in serum in 2 forms, either bound to albumin or unbound ("ionized" calcium). Ionized calcium is the physiologically active form, and is tightly regulated. Increased albumin is necessarily associated with physiologically appropriate increased bound calcium, with resultant increased total calcium. However, ionized calcium is unaffected; therefore this change is not toxicologically significant. -22omPany Sanfttesd. Donot contata TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 alterations in systemic acid/base homeostasis. Therefore, this change was considered toxicologicaily insignificant. Urine pH was similar in all groups at the end of recovery (day 25). Total urinary fluoride was minimally increased in rats exposed to 125 mg/m3 at day 11. This statistically significant change did not occur in a concentration-dependant manner, and therefore was toxicologicaily insignificant: D. Conclusions There were no toxicologicaily significant changes in hematology, clinical chemistry, or urinalysis parameters. Therefore, under the conditions of this study and for the clinical pathology parameters measured, the no-observed-effect level (NOEL) was greater than 600 mg/m3, the highest exposure tested. Anatomic Pathology Evaluations A. Organ W eights (Tables 11-12, Appendix F) There were no compound-related changes in organ weights. At the end of the exposure period, statistically significant increases in all organ weights relative to body weight were present in the 125 and/or 600 mg/m3 groups. These changes were secondary to decreases in final body weights and thus were not indicative of direct target organ toxicity. All other statistically significant organ weight changes in the exposure groups were neither concentration-related nor associated with correlative microscopic changes and were thus considered spurious findings. In the recovery groups, a statistically significant increase in lung weight relative to body weight was present in the 600 mg/m3group. This change was not associated with changes in other lung weight parameters in this group or with correlative microscopic changes. The minimal findings in some rats in this group would not be expected to produce lung weight changes. Therefore, this finding was not considered to be compound-related. B. Gross Observations (Tables 13-14, Appendix G) , There were no compound-related gross findings. Only a few gross lesions were noted in the study. These occurred as single instances in treated and control groups and were lesions common to rats of this strain and age. -23GOmpm* * noi o onM , t sc * CUI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 C. M icroscopic Findings (Tables 15-16, Appendix G) Compound-related microscopic changes consistent with slight irritation were present in the respiratory tract of rats in all treated groups. In the lungs, minimal inflammation confined to the centriacinar regions was present in all treated groups. Inflammation was characterized by mild thickening of alveolar duct bifurcations and adjacent alveolar septa due to mononuclear inflammatory cell infiltration. Slight hypertrophy of terminal bronchiolar epithelium was also present in association with the centriacinar inflammatory response. Lesions in the lungs were minimal at all exposure concentrations; however, changes were slightly more apparent with increasing concentration. In the larynx, minimal squamous metaplasia was present in all treated groups. Metaplasia occurred most consistently in the ventral laryngeal mucosa at the base of the epiglottis. Necrosis of cartilage overlying the laryngeal saccule was present in 1 rat in the 600 mg/m3group. In the nose, hypertrophy of goblet cells was present in all treated groups and was most apparent in the mucosa of the pharyngeal duct. Following an approximately 2-week recovery period, respiratory tract lesions were essentially reversible. Single occurrences of focal, very slight thickening of alveolar duct septa occurred in the 125 and 600 mg/m3recovery groups. In addition, focal residual cartilage necrosis in the larynx occurred in 2/5 rats in the 600 mg/m3 recovery group. All other microscopic changes observed occurred in low incidences across treated and control groups and/or are spontaneous lesions common to rats of this strain and age. D. Conclusions Under the conditions of this study, a no-observed-adverse effect level for pathology was not determined based on the presence of irritant lesions in the respiratory tract at all exposure concentrations tested. These changes were minimal and mostly reversible following a 2-week recovery period. -24- Company Sanitized. Does no! contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 CONCLUSIONS During the exposure period there was a dose-related body weight depression occurred primarily in the 125 and 600 mg/m3 groups and all 3 test groups gained less weight than the controls. The H-24267 exposed rats resumed a normal weight gain rate during the recovery period. Clinical pathology evaluations at both evaluation times showed no toxicologically significant changes in hematology, clinical chemistry, or urinalysis parameters, including urinary fluoride. Weight analysis of major organs showed no effects attributable to the test compound. Histological findings were confined to the respiratory tract; no significant findings were observed in any other evaluated organs. Minimal, dose-related histologic effects attributable to the test compound were found in the respiratory tract of all treated groups at the end of the 2-week exposure period. The effects were consistent with minimal irritation and were slightly more apparent with increasing dose. These effects occurred throughout the respiratory tract, including the nose, larynx, and lung. In the lungs, inflammation was characterized by mild thickening of alveolar duct bifurcations and adjacent alveolar septa due to mononuclear inflammatory cell infiltration. Slight hypertrophy of terminal bronchiolar epithelium was also present in association with the centriacinar inflammatory response. In the larynx, m inim al squamous metaplasia was present in all treated groups. Necrosis of cartilage overlying the laryngeal saccule was present in 1 rat in the 600 mg/m group. In the nose, hypertrophy of goblet cells was present in all treated groups and was most apparent in the mucosa of the pharyngeal duct. Following an approximately 2-week recovery period, respiratory tract lesions were essentially reversible. Single occurrences of focal, very slight thickening of alveolar duct septa occurred in the 125 and 600 mg/m3recovery groups. In addition, focal residual cartilage necrosis in the larynx occurred in 2/5 rats in the 600 mg/m3recovery group. Based on the finding of minimal respiratory tract inflammation observed in all exposed groups including the lowest concentration tested, 25 mg/m3, a no-observed-adverse- effect-level (NOAEL) was not determined for repeated aerosol exposures to H-24267 in rats. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Clinical pathology slides and raw data will be retained at Haskell Laboratory, Newark, Delaware. Wet specimens and records related to clinical pathology analyses were retained by DuPont Pharmaceuticals Company. -25C*paKiy Samiioed. Does net contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 REFERENCES 1. Calculation described in Sierra Instruments, Inc., Bulletin 7-79-2I9IM, Instruction Manual: Series 210 Ambient Cascade Impactors and Cyclone Preseparators. 2. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 3. 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. 4. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41,133-145. 5. Levene, H. (1960). Robust test for equality of variances. Contributions to Probability and Statistics (J. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. 6. Shapiro, S.S. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. 7. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 246-248 and 349-352. The Iowa State University Press, Iowa. 8. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50, 1096-1121.' 9. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. 10. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 11. Fisher, R.A. (1985). Statistical Methods fo r Research Workers, 13th edition. Haffner, New York. -26- Company SanStked. Does not contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLES -27wmpajif Sanitized. Doss not contain TSCA OBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats ________ TABLES________ ABBREVIATIONS: EXPLANATORY NOTES Tables 1 and 3 S.D. - standard deviation S.E.M. - standard error of the mean mg/m3 - milligrams per cubic meter n - number of samples Table 7 RBC HGB HCT MCV MCH MCHC RDW ARET NRBC WBC ANEU ANPR ALYM AMON AEOS ABAS ALUC ABLT AMSC PLT BASO BLST EOS LUC LYMP MISC MONO NEUT NPRE - red blood cell count - hemoglobin - hematocrit - mean corpuscular volume - mean corpuscular hemoglobin - mean corpuscular hemoglobin concentration - red cell distribution width - absolute reticulocyte count -- nucleated red blood cell count - white blood cell count - absolute neutrophil (all forms) - absolute neutrophil precursor - absolute lymphocyte absolute monocyte - absolute eosinophil -- absolute basophil absolute large unstained cell -- absolute blast leukocyte - absolute miscellaneous leukocyte - platelet count - percent basophil percent blast leukocyte - percent eosinophil ' -- percent large unstained cell - percent lymphocyte - percent miscellaneous leukocyte - percent monocyte - percent neutrophil - percent neutrophil precursor DuPont-4292 -28- Company SanHteed- r**"*- TSCA CBI Company Sanitized. Does not contain TSCA C B f H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLES - EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued! Table 8 PT - prothrombin time APTT - activated partial thromboplastin time Table 9 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 Table 10 VOL - volume UOSM - urine osmolality SG - specific gravity pH - the logarithm of the reciprocal of the hydrogen ion concentration URO - urobilinogen UFLU urine fluoride -29- Company SanWzed. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLES NOTES: EXPLANATORY NOTES (Continued) Tables 1 - 3 Values are reported to 2 significant figures. Means and standard errors of the mean were calculated prior to rounding values to 2 significant figures. Tables 7 -1 0 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. -30- Cefflpaisy Sanitized. B@>not contain TSC OSI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 1 CHAMBER CONCENTRATIONS OF H-24267 DESIGN CONCENTRATIONi (mg/m3) 0 25 125 600 MEASURED CONCENTRATION" (mg/m3) MEAN S.E.M. RANGE n 00 0 54 23 2.0 4.0 - 70 54 n o 4.6 18-200 54 600 25 85 - 960 54 a Values represent the mean, standard error of the mean (S.E.M.), and range for all samples obtained from n exposures. TABLE 2 PARTICLE SIZE DISTRIBUTION OF H-24267 DESIGN CONCENTRATION (mg/m3) 25 125 600 TEST DAY 4 11 3 10 2 9 MASS MEDIAN GEOMETRIC AERODYNAMIC STANDARD DIAMETER (ixm) DEVIATION 3.2 2.5 2.6 2.2 4.0 3.1 2.6 2.2 3.9 3.0 4.2 2.2 % PARTICLES BY MASS <1 m <3 m <10 m 13 48 86 12 58 96 11 40 84 14 62 96 11 42 82 3.0 33 88 TABLE 3 CHAMBER ENVIRONMENTAL CONDITIONS DESIGN CONCENTRATION (mg/m3)a 0 25 125 600 TEMPERATURE (C) 22-26 22-26 22-25 21-24 RELATIVE HUMIDITY (%) 35-50 38-54 37-61 65-84 AIRFLOW (L/min) 30 30 30 30 n 9 9 9 9 a Values represent the range for all samples obtained from n exposures. -31 - Company SanWzed. Poos not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAYS ON TEST EXPOSURE DAYO DAY 1 DAY 2 DAY 3 DAY 4 DAY 7 DAY 8 DAY 9 DAY 10 TABLE 4 MEAN BODY WEIGHTS OF MALE RATS Group I 0 mg/m3 MEAN BODY WEIGHTS (g) Group III Group V 25 mg/m3 125 mg/m3 291.8 23.4(10) 294.4 23.3(10) 301.6 25.0(10) 306.9 24.7(10) 309.8 25.1(10) 328.4 28.6(10) 332.6 28.0(10) 332.6 29.7(10) 338.7 29.0(10) 288.9 16.3(10) 284.6 16.3(10) 287.2 15.2(10) 289.3 15.4(10) 293.7 16.7(10) 315.8 18.0(10) 316.7# 18.2(10) 317.9 19.5(10) 320.5 21.3(10) 295.5 10.2(10) 288.0 9.7(10) 291.1 10.7(10) 296.7 9.2(10) 299.2 10.6(10) 322.9 11.6(10) 319.1# 10.2(10) 315.8# 11.6(10) 318.7# 13.1(10) Group VH 600 mg/m3 298.5 17.4(10) 286.1 18.1(10) 287.1 19.3(10) 285.9# 21.0(10) 287.4# 22.1(10) 313.2 22.5(10) 309.1# 24.5(10) 309.7# 24.5(10) 309.0# 25.6(10) - 32'Gosnpany Sanitized. Dees net eentafe TSC SIS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAYS ON TEST RECOVERY DAY 11 DAY 14 DAY 18 DAY 22 DAY 25 TABLE 4 (Continued) MEAN BODY WEIGHTS OF MALE RATS Group I 0 mg/m3 MEAN BODY WEIGHTS (g) Group III Group V 25 mg/m3 125 mg/m3 306.4 25.7(10) 338.6 38.9(5) 367.3 44.0(5) 391.7 45.0(5) 375.8 47.2(5) 286.8# 17.7(10) 313.8 25.9(5) 340.9 29.3(5) 360.6 32.5(5) 348.9 35.8(5) 287.1# 14.7(10) 337.2 16.4(5) 366.9 21.1(5) 391.8 23.8(5) 379.3 22.2(5) Group VII 600 mg/m3 272.2# 22.6(10) 310.6 37.3(5) 343.0 44.2(5) 363.5 47.2(5) 354.0 47.2(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). -33- Company Sanitized. Does not contain ISCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 5 MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group I 0 mg/m3 MEAN BODY WEIGHT GAINS (g) Group in Group V 25 mg/m3 125 mg/m3 Group VH 600 mg/m3 EXPOSURE DAY 0 - DAY 1 2.6 6.1(10) -4.3# 3.8(10) -7.6# 3.9(10) -12.4# 6.1(10) DAY 1 - DAY 2 7.2 2.8(10) 2.6# 2.5(10) 3.1# 2.8(10) 1.0# 4.9(10) DAY 2 - DAY 3 5.3 2.7(10) 2.1 2.5(10) 5.7 4.5(10) -1.1# 3.5(10) DAY3 -D A Y 4 2.9 3.7(10) 4.4 1.8(10) 2.4 2.9(10) 1.4 6.5(10) DAY 4 - DAY 7 18.6 5.3(10) 22.1 5.1(10) 23.7# 4.3(10) 25.9# 6.1(10) DAY 7 - DAY 8 4.2 3.2(10) 0.9# 2.0(10) -3.8# 5.0(10) -4.1# 3.6(10) DAY 8 - DAY 9 -0.1 10.5(10) 1.2 2.9(10) -3.2# 3.7(10) 0.6# 4.0(10) DAY 9 -D A Y 10 6.1 7.5(10) 2.6 2.8(10) 2.9 3.3(10) -0.7 6.1(10) DAY 10 - DAY l l a -32.3 8.6(10) -33.7 7.5(10) -31.6 5.0(10) -36.8 5.8(10) - 34- Company SanU tod Does not contain TSGACB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 5 (Continued) MEAN BODY WEIGHT GAINS OF MALE RATS DAYS ON TEST Group I 0 mg/m3 MEAN BODY W EIGHT GAINS (g) Group III Group V 25 mg/m3 125 mg/m3 Group VII 600 mg/m3 RECOVERY DAY 1 1 -D A Y 14 37.6 11.3(5) 34.6 5.7(5) 43.2 8.6(5) 42.6 7.7(5) DAY 14 - DAY 18 28.7 7.6(5) 27.1 5.1(5) 29.7 6.8(5) 32.4 7.4(5) DAY 18 - DAY 22 24.4 3.3(5) 19.7 5.6(5) 24.9 5.2(5) 20.5 5.5(5) DAY 22 - DAY 25a -15.9 2.9(5) -11.7 4.9(5) -12.4# 1.9(5) -9.5# 2.1(5) OVERALL DAY 0 - DAY 10 46.9 14.7(10) 31.6# 13.1(10) 23.2# 9.1(10) 10.5# 10.8(10) DAY 11 - DAY 25 74.5 17.1(5) 69.7 16.2(5) 85.3 11.6(5) 86.0 16.6(5) DAY 0 - DAY 25 89.8 23.6(5) 67.9 30.3(5) 84.1 13.0(5) 59.6 23.7(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). a Weight losses due to fasting of rats prior to clinical pathology evaluations. -35- ontnwnv Doss wot contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE SUMMARY OF CLINICAL OBSERVATIONS IN MALE RATS AT WEIGHING GROUP: I ill V VII DESIGN CONCENTRATION (mg/m3): 0 25 125 600 ANIMAL COUNT: 10 10 10 10 Hair Loss Face, Right Incidence Observed Mean onset (Days) Forepaw, Left Incidence Observed Mean onset (Days) Forepaw, Bilateral Incidence Observed Mean onset (Days) Forelimb, Bilateral Incidence O bserved Mean onset (Days) H air Loss Totals Incidence O bserved Mean onset (Days) W ound, Superficial, Face Incidence O bserved Mean onset (Days) 0 (0%) 0 - 1 (10%) 3 8 0 (0%) 0 - 0 (0%) 0 - 0 (0%) 0 - 0 (0%) 0 - 1 (10%) 1 7 0 (0%) 0 - 0 (0%) 0 - 0 (0%) 0 - 2 (20%) 10 5 0 (0%) 0 - 0 (0%) 0 - 0 (0%) 0 - 1 (10%) 5 4 0 (0%) 0 - 0 (0%) 0 - 1 (10%) 3 8 2 (20%) 16 5 0 (0%) 0 - 0 (0%) 0 -_ 1 (10%) 5 1 0 (0%) 0 0 (0%) 0 - Incidence - The number of animals (percent of group) for which an observation was recorded. Observed - The total number of test days the observation was recorded for animals in the group. 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. -36- smpasw Sanitised. wotSQfitaiss TSCGBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 7 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I Omg/m3 G roupm 25 mg/m3 Group V 125 mg/m3 Group VU 600 mg/m3 RBC (xloV/xL) DAY 11 DAY 25 HGB (g/dL) DAY 11 DAY 25 HCT (%) DAY 11 DAY 25 MCV (fl) DAY 11 DAY 25 MCH (pg) DAY 11 DAY 25 MCHC (g/dL) DAY 11 DAY 25 RDW (%) DAY 11 DAY 25 7.57 0.32(10) 8.12 0.42(5) 15.2 0.7(10) 15.8 0.4(5) 47.3 2.0(10) 48.2 1.8(5) 62.4 1.6(10) 59.4 1.2(5) 20.1 0.5(10) 19.4 0.6(5) 32.1 0.6(10) 32.8 0.5(5) 13.0 0.6(10) 13.3 0.5(5) 7.74 0.64(10) 8.51 0.31(5) 15.2 0.9(10) 15.9 0.6(5) 47.4 3.2(10) 49.5 1.7(5) 61.3 2.1(10) 58.2 0.3(5) 19.7 0.7(10) 18.7 0.3(5) 32.1 0.5(10) 32.1 0.5(5) 13.1 0.6(10) 13.3 0.2(5) 7.60 0.35(10) 7.67 0.30(5) 15.3 0.4(10) 15.4 0.4(5) 47.1 1.3(10) 47.2 1.3(5) 62.0 1.8(10) 61.6 1.8(5) 20.2 0.8(10) 20.1 0.6(5) 32.5 0.6(10) 32.7 0.4(5) 13.4 0.7(10) 13.2 0.3(5) 8.05 0.49(10) 8.05 0.38(5) 15.9 0.7(10) 15.5 0.2(5) 49.2 2.0(10) 47.7 0.6(5) 61.2 1.7(10) 59.3 2.2(5) 19.8 0.5(10) 19.3 0.8(5) 32.3 0.5(10) 32.5 0.4(5) 13.5 0.5(10) 13.6 0.4(5) -37- eem'*<*ny Sanitised- "t ew aln TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 7 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/m3 Group DI 25 mg/m3 Group V 125 mg/m3 Group VII 600 mg/m3 ARET (x l0 3//tL) DAY 11 DAY 25 NRBC (/100 WBC) DAY l l a DAY 25b 234.9 30.6(10) 261.4 28.6(5) 203.7 29.0(10) 266.2 11.2(5) 174.1* 31.3(10) 258.2 31.6(5) 159.6* 35.1(10) 253.2 35.5(5) WBC (x103//xL) DAY 11 DAY 25 ANEU (xl07/iL) DAY 11 DAY 25 ANPR (x l0 3/fih) DAY l l a DAY 25b 13.11 2.63(10) 14.68 5.23(5) 2.09 0.84(10) 2.65 1.30(5) 12.77 2.93(10) 14.91 4.15(5) 1.38 0.49(10) 2.47 0.67(5) 12.32 1.56(10) 14.38 3.25(5) 1.27 0.26(10) 1.77 0.63(5) 13.05 4.43(10) 14.47 2.68(5) 1.66 0.75(10) 2.00 0.29(5) ALYM (x103//xL) DAY 11 DAY 25 AMON (x l0 3//xL) DAY 11 DAY 25 10.24 2.04(10) 11.23 3.75(5) 0.37 0.10(10) 0.35 0.16(5) 10.65 2.59(10) 11.48 3.37(5) 0.29 0.16(10) 0.43 0.08(5) 10.23 1.37(10) 11.75 2.58(5) 0.35 0.15(10) 0.37 0.10(5) 10.53 3.66(10) 11.59 2.39(5) 0.35 0.25(10) 0.38 0.03(5) -38- empanf Sanitized. Does not contain TSC CSS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 7 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I O m g/m 3 Group in 25 mg/m3 Group V 125 mg/m3 Group VH 600 mg/m3 AEOS (x103//xL) DAY 11 DAY 25 ABAS (x103//xL) DAY 11 DAY 25 ALUC (x103//xL) DAY 11 DAY 25 ABLT (x103/juL) DAY I I a DAY 25b 0.12 0.04(10) 0.14 0.04(5) 0.08 0.03(10) 0.09 0.04(5) 0.22 0.06(10) 0.23 0.07(5) 0.11 0.04(10) 0.15 0.07(5) 0.09 0.06(10) 0.09 0.06(5) 0.24 0.13(10) 0.29 0.18(5) 0.20 0.23(10) 0.10 0.03(5) 0.04 0.03(10) 0.09 0.03(5) 0.17 0.10(10) 0.29 0.06(5) 0.15 0.08(10) 0.10 0.04(5) 0.07 0.05(10) 0.09 0.02(5) 0.24 0.21(10) 0.31 0.13(5) AMSC (x103/juL) TDAAVY II II aa DAY 25b PLT (x l0 3/piL) DAY 11 DAY 25 BASO (%) DAY 11 DAY 25 1082 145(7) 1088 99(4) 0.6 0.2(10) 0.6 0.3(5) 919* 148(9) 946 109(3) 0.7 0.5(10) 0.6 0.2(5) 946 120(9) 1004 113(5) 0.4 0.3(10) 0.6 0.2(5) 926 95(9) 943 88(5) 0.5 0.3(10) 0.6 0.1(5) -39- g@8mpamf S a lit e s i. 0s noi contain TSC CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 7 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS TEST/ ' Group I Group m Group V Group VH PERIOD_______________ Omg/m3________ 25 mg/m3_______ 125 mg/m3______ 600 mg/m3 BLST (%) DAY l l a DAY 25b EOS (%) DAY 11 DAY 25 LUC (%) DAY 11 DAY 25 LYMP (%) DAY 11 DAY 25 MISC (%) DAY l l a DAY 25b 0.9 0.3(10) 1.0 0.3(5) 1.7 0.5(10) 1.6 0.4(5) 78.2 5.0(10) 76.9 3.0(5) 0.9 0.3(10) 1.0 0.5(5) 1.9 1.0(10) 1.8 0.6(5) 83.2* 3.6(10) 76.7 3.1(5) 1.6 1.9(10) 0.7 0.1(5) 1.4 0.8(10) 2.0 0.3(5) 83.0* 3.2(10) 81.9* 1.4(5) 1.2 0.7(10) 0.7 0.3(5) 1.8 1.2(10) 2.1 0.7(5) 80.5 4.1(10) 79.9 2.1(5) MONO (%) DAY 11 DAY 25 NEUT (%) DAY 11 DAY 25 2.9 0.7(10) 2.4 0.6(5) 15.7 4.5(10) 17.6 2.9(5) 2.2 0.9(10) 2.9 0.5(5) 11.0* 3.7(10) 16.9 3.1(5) 2.9 1.3(10) 2.7 0.9(5) 10.3* 1.6(10) 12.1* 2.2(5) 2.6 1.6(10) 2.7 0.4(5) 13.0 3.6(10) 14.1 2.2(5) -40Company SanWzed. H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 7 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS TEST/ Group I Group HI Group V Group VH PERIOD_______________ Omg/m3________ 25 mg/m3_______ 125 mg/m3______ 600 mg/m3 NPRE (%) DAY l l a DAY 25b Data arranged as: Mean Standard deviation (Number of values included in calculation) a When this analysis was performed, valid measurements were taken on only a few animals from the group. Data from this small sample size did not add value to this summary table. Individual data are reported in the Clinical Pathology appendix. b Measurements for all animals were not taken or not performed. Data o f this type did not add value to this summary table. Individual data are reported in the Clinical Pathology appendix. * Statistically significant difference from control at p < 0.05 by parametric test (Dunnett/Tamhane-Dunnett). @ Statistically significant difference from control at p < 0.05 by nonparametric test (Dunn's). -41 - Cknnpany Sanitized. Dees not eorslafe TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 8 SUMMARY OF COAGULATION VALUES FOR MALE RATS TEST/ Group I Group HI Group V Group VU PERIOD_______________ Omg/m3________ 25 mg/m3_______ 125 mg/m3______ 600 mg/m3 PT (seconds) DAY 11 DAY 25 APTT (seconds) DAY 11 DAY 25 15.8 1.5(5) 14.8 0.6(5) 19.9 6.1(5) 19.0 2.8(5) 15.2 0.3(5) 15.4 0.8(5) 21.0 3.6(5) 19.1 4.0(5) 15.5 1.0(4) 14.5 0.3(5) 17.2 1.8(4) 16.7 1.4(5) 15.1 0.4(5) 14.7 0.9(5) 20.1 3.6(5) 17.1 2.4(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. -42- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 9 SUMMARY OF SERUM CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I Omg/m3 Group m 25 mg/m3 Group V 125 mg/m3 Group VII 600 mg/m3 AST (U/L) DAY 11 DAY 25 ALT (U/L) DAY 11 DAY 25 SDH (U/L) DAY 11 DAY 25 ALKP (U/L) DAY 11 DAY 25 BILI (mg/dL) DAY 11 DAY 25 BUN (mg/dL) DAY 11 DAY 25 CREA (mg/dL) DAY 11 DAY 25 95 16(10) 95 13(5) 38 6(10) 45 4(5) 17.6 3.1(10) 21.5 2.3(5) 219 38(10) 200 39(5) 0.08 0.03(10) 0.11 0.04(5) 13 2(10) 14 2(5) 0.33 0.05(10) 0.42 0.05(5) 98 19(10) 104 13(5) 43 5(10) 44 4(5) 16.3 2.7(10) 22.5 4.1(5) 193 27(10) 185 17(5) 0.08 0.04(10) 0.13 0.05(5) 17 2(10) 16 1(5) 0.40 @ 0.05(10) 0.48 0.06(5) 83 12(10) 92 16(5) 35 5(10) 40 3(5) 15.5 2.8(10) 20.2 3.0(5) 199 51(10) 192 38(5) 0.07 0.03(10) 0.10 0.03(5) 15 2(10) 14 1(5) 0.38 0.05(10) 0.42 0.03(5) 89 15(10) 97 19(5) 45 11(10) 43 6(5) 16.2 3.6(10) 19.7 6.1(5) 181 33(10) 169 36(5) 0.10 0.05(10) 0.13 0.02(5) 21@ 6(10) 16 2(5) 0.45 @ 0.10(10) 0.37 0.05(5) - 43- CNwnpany Sanitised. Does svoficontain TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 9 (Continued) TEST/ PERIOD SUMMARY OF SERUM CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/m3 Group HI 25 mg/m3 Group V 125 mg/m3 Group VII 600 mg/m3 CHOL (mg/dL) DAY 11 DAY 25 TRIG (mg/dL) DAY 11 DAY 25 GLUC (mg/dL) DAY 11 DAY 25 TP (g/dL) DAY 11 DAY 25 ALB (g/dL) DAY 11 DAY 25 GLOB (g/dL) DAY 11 DAY 25 CALC (mg/dL) DAY 11 DAY 25 65 20(10) 68 12(5) 45 14(10) 60 28(5) 90 7(10) 95 11(5) 6.1 0.2(10) 6.9 0.4(5) 4.2 0.1(10) 4.6 0.2(5) 1.9 0.2(10) 2.2 0.3(5) 10.9 0.4(10) 10.9 0.2(5) 65 12(10) 75 16(5) 32* 12(10) 61 16(5) 85 6(10) 89 10(5) 6.3 0.3(10) 7.0 0.2(5) 4.4* 0.2(10) 4.8 0.1(5) 1.9 0.2(10) 2.2 0.1(5) 10.9 0.3(10) 10.9 0.2(5) 83* 18(10) 76 18(5) 40 10(10) 72 24(5) 89 10(10) 95 11(5) 6.2 0.2(10) 6.6 0.2(5) 4.4* 0.1(10) 4.7 0.2(5) 1.8 0.1(10) 1.9* 0.0(5) 11.0 0.2(10) 10.8 0.3(5) 85* 15(10) 76 13(5) 38 9(10) 43 7(5) 89 5(10) 92 9(5) 6.5* 0.3(10) 6.8 0.2(5) 4.5* 0.2(10) 4.7 0.2(5) 2.0 0.2(10) 2.1 0.2(5) 11.3 0.3(10) 10.9 0.3(5) -44- wwpany Santtfeed. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 9 (Continued) TEST/ PERIOD SUMMARY OF SERUM CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/m3 Group HI 25 mg/m3 Group V 125 mg/m3 Group VII 600 mg/m3 IPHS (mg/dL) DAY 11 DAY 25 NA (mmol/L) DAY 11 DAY 25 K (mmol/L) DAY 11 DAY 25 CL (mmol/L) DAY 11 DAY 25 PFLU (/xg/mL) DAY 11 DAY 25 10.0 1.0(10) 8.8 0.7(5) 149.1 1.4(10) 150.5 1.1(5) 6.21 0.33(10) 5.98 0.41(5) 95.4 1.0(10) 95.9 1.7(5) 0.1 0.0(5) 0.1 0.0(5) 9.7 0.4(10) 8.7 0.7(5) 149.0 1.4(10) 150.5 0.9(5) 6.18 0.30(10) 6.27 0.07(5) 97.8* 1.3(10) 97.0 2.0(5) 0.1 0.0(5) 0.1 0.0(5) 9.7 0.4(10) 8.6 0.5(5) 148.6 1.0(10) 150.9 1.4(5) 6.04 0.24(10) 5.96 0.36(5) 96.4 2.1(10) 96.8 1.0(5) 0.1 0.0(5) 0.1 0.0(5) 9.6 0.7(10) 9.2 0.6(5) 147.2* 2.2(10) 150.1 1.4(5) 5.93 0.31(10) 6.00 0.20(5) 93.4 2.4(10) 97.0 1.2(5) 0.1 0.0(5) 0.1 0.0(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by parametric test (Dunnett/Tamhane-Dunnett). @ Statistically significant difference from control at p < 0.05 by nonparametric test (Dunn's). -45- g@mpanf Sanitized. P@es rasi contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 10 SUMMARY OF URINALYSIS VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/m3 Group HI 25 mg/m3 Group V 125 mg/m3 Group VII 600 mg/m3 VOL (mL) DAY 11 DAY 25 UOSM (mOsm) DAY 11 DAY 25 SG DAY 11 DAY 25 pH DAY 11 DAY 25 URO (EU/dL) DAY 11 DAY 25 UFLU (jig) DAY 11 DAY 25 9.6 6.7(9) 12.5 7.6(5) 914 342(9) 868 444(5) 1.029 0.011(9) 1.028 0.014(5) 6.4 0.6(9) 6.5 0.4(5) 0.3 0.3(9) 0.2 0.0(5) 9.4 3.3(9) 11.5 4.1(5) 9.0 3.5(10) 12.7 5.7(5) 830 223(10) 705 248(5) 1.026 0.006(10) 1.022 0.007(5) 6.2 0.4(10) 6.3 0.3(5) 0.2 0.0(10) 0.2 0.0(5) 10.8 3.1(10) 12.1 2.6(5) 9.3 5.4(10) 13.8 4.4(5) 854 461(10) 661 209(5) 1.029 0.015(10) 1.021 0.005(5) 5.5* 0.5(10) 6.1 0.5(5) 0.2 0.0(10) 0.2 0.0(5) 14.8* 4.9(10) 15.3 2.7(5) 10.6 3.7(10) 10.6 8.3(5) 732 270(10) 957 425(5) 1.024 0.008(10) 1.030 0.013(5) 5.4* 0.3(10) 6.0 0.4(5) 0.2 0.0(10) 0.2 0.0(5) 12.9 2.8(10) 12.5 4.4(5) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by parametric test (Dunnett/Tamhane-Dunnett). -46- Comneny Sanitized. Does w*fw fa 'n TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 11 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 11 SACRIFICE TEST/ Group I Group HI Group V Group VII PERIOD_______________ Omg/m3________ 25 mg/m3_______ 125 mg/m3______ 600 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER KIDNEYS LUNGS 10.54880 0.55032(5) 2.83220 0.31214(5) 1.80220 0.12323(5) 9.50840 0.56907(5) 2.76240 0.25635(5) 1.49680 0.08472(5) 9.85100 1.02333(5) 2.66800 0.19941(5) 2.01000 0.33803(5) 10.03180 0.67382(5) 2.76800 0.10556(5) 1.80380 0.20042(5) BRAIN TESTES 1.93720 0.05766(5) 2.84160 0.38756(5) 1.86640 0.08421(5) 3.33860* 0.19602(5) 1.92360 0.09308(5) 3.28120 0.09154(5) 1.90600 0.07562(5) 2.97040 0.30940(5) FINAL BODY WEIGHT (grams) 311.80000 11.18928(5) 294.40000*# 6.22896(5) 280.20000*# 10.40192(5) 276.40000*# 10.31019(5) MEAN RELATIVE ORGAN WEIGHTS ( % o f body weight) LIVER/ FINAL BODY* 100 3.38205 0.08260(5) 3.22938 0.17369(5) 3.50953 0.24956(5) 3.62979# 0.20580(5) KIDNEYS/ FINAL BODY* 100 0.90831 0.09411(5) 0.93744 0.07309(5) 0.95157 0.04758(5) 1.00204# 0.03924(5) LUNGS/ FINAL BODY* 100 0.57810 0.03517(5) 0.50818 0.01956(5) 0.71656* 0.11089(5) 0.65263# 0.06705(5) -47- Company Sanitized. Does not contain TSA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 11 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS DAY 11 SACRIFICE TEST/ Group I Group EH Group V Group VII PERIOD_______________ 0 mg/m3________ 25 mg/m3_______ 125 mg/m3_____ 600 mg/m3 MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) BRAIN/ FINAL BODY* 100 0.62189 0.02732(5) 0.63389 0.02293(5) 0.68680*# 0.03039(5) 0.68962*# 0.01266(5) TESTES/ FINAL BODY* 100 0.91322 0.13523(5) 1.13395*# 0.05970(5) 1.17268*# 0.06463(5) 1.07356*# 0.08925(5) MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/BRAIN 5.44863 0.31536(5) 5.09267 0.12069(5) 5.11662 0.40345(5) 5.26273 0.26177(5) KIDNEYS/BRAIN 1.46104 0.14027(5) 1.47861 0.10078(5) 1.38671 0.07224(5) 1.45356 0.06636(5) LUNGS/BRAIN TESTES/BRAIN 0.93029 0.05627(5) 1.46377 0.16187(5) 0.80245* 0.04060(5) 1.79131* 0.12406(5) 1.04812 0.18989(5) 1.70816* 0.07573(5) 0.94588 0.08873(5) 1.55774 0.14152(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. # Statistically significant difference from control at p < 0.05 by trend test (Jonckheere-Terpstra). * Statistically significant difference from control at p < 0.05 by parametric test (Dunnett/Tamhane-Dunnett). - 48- wspamy ianHUzed Doss n8omalBTSCA GBl H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 ~) 1 ! 1 !; TABLE 12 MEAN FINAL BODY AND ORGAN WEIGHT'S FROM MALE RATS . DAY 25 SACRIFICE TEST/ Group I Group IH Group V Group VII PERIOD_______________ 0 mg/m3________ 25 mg/m3_______ 125 mg/m3______ 600 mg/m3 MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) LIVER 11.81520 1.54485(5) 10.82700 1.99882(5) 12.56100 0.95760(5) 11.87300 2.05716(5) KIDNEYS 3.18140 0.42244(5) 2.87560 0.34528(5) 3.32220 0.24865(5) 3.18700 0.42985(5) LUNGS 1.78640 0.25665(5) 1.69700 0.19552(4) 1.87220 0.14939(5) 1.91360 0.29441(5) BRAIN 1.94560 0.16046(5) 2.00780 0.11708(5) 2.06580 0.10822(5) 1.99020 0.10492(5) TESTES 3.17320 0.31452(5) 3.29320 0.34343(5) 2.82860 0.52816(5) 3.27060 0.28905(5) FINAL BODY WEIGHT (grams) 375.80000 47.17112(5) 348.90000 35.83001(5) 379.32000 22.24718(5) 354.00000 47.17536(5) MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) LIVER/ FINAL BODY* 100 3.14308 0.11223(5) 3.08887 0.32592(5) 3.30980 0.11230(5) 3.34305 0.25029(5) KIDNEYS/ FINAL BODY* 100 0.84605 0.02050(5) 0.82327 0.02397(5) 0.87592 0.04028(5) 0.90275 0.07877(5) LUNGS/ FINAL BODY* 100 0.47483 0.01857(5) 0.48396 0.06297(4) 0.49457 0.04540(5) 0.53948# 0.02622(5) - 49- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 12 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS . DAY 25 SACRIFICE TEST/ PERIOD Group I O m g/m 3 Group DI 25 mg/m3 Group V 125 mg/m3 Group VH 600 mg/m3 BRAIN/ FINAL BODY* 100 0.52227 0.06124(5) 0.57859 0.04583(5) 0.54580 0.03818(5) 0.56807 0.05830(5) TESTES/ FINAL BODY* 100 0.85014 0.09459(5) 0.94481 0.04910(5) 0.74234 0.10856(5) 0.93325 0.11274(5) MEAN RELATIVE ORGAN WEIGHTS ( organ to brain weight ratio) LIVER/BRAIN 6.07890 0.66519(5) 5.36315 0.69015(5) 6.09520 0.56827(5) 5.94192 0.80947(5) KIDNEYS/BRAIN 1.63796 0.19474(5) 1.42971 0.11537(5) 1.61037 0.12665(5) 1.59608 0.14198(5) LUNGS/BRAIN 0.91981 0.12105(5) 0.83631 0.11746(4) 0.91065 0.11247(5) 0.95879 0.11860(5) TESTES/BRAIN 1.64389 0.25262(5) 1.64009 0.14469(5) 1.37226 0.26123(5) 1.64189 0.08712(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). -50 pf Sanitized. Does nl eortafb TSCA CM H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 13 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED DEFORMITY, IRREGULAR, MIDDLE. DISCOLORATION, YELLOW, LEFT. KIDNEYS NO ABNORMALITY DETECTED DILATATION, UNILATERAL, PELVIS. LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED DEFORMITY, IRREGULAR. BRAIN NO ABNORMALITY DETECTED (5) (5) (5) (5) 4555 1 1 (5) (5) (5) (5) 54 5 5 1 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5455 1 (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 -51Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DA Y 11 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII 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 CECUM NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5 5 55 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5 555 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 -52Sfflpaisf Sanitised. mi contain TSGA C8I H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DA Y 11 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 55 55 (5) (5) (5) (5) 55 55 (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 -53- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS D A Y 11 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY'DETECTED E Y E (S ) NO ABNORMALITY DETECTED PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 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 - 54- CwPnySanitized. Does not contain TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 13 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS D A Y 11 SACRIFICE LESIONS URINARY BLADDER NO ABNORMALITY DETECTED TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED DISCOLORATION, MOTTLED, TAIL, RIGHT. DISCOLORATION, TAN, FIRM, TAIL. STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) TREATMENT ' 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 4554 1 1 (5) (5) (5) 555 (5) 5 (5) (5) (5) (5) 55 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 - 55- Company Sanitized. Does notcontain T6CA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 14 INCIDENCES OF GROSS OBSERVATIONS IN M ALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (Numeric) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LIVER NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 55 55 (5) (5) (5) (5) 5555 (5) (5) (5) 555 (5) 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5 555 (5) (5) (5) (5) 55 55 (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 -56- Cosnpany Switfeed. Does no*contain TSCA C ll H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS RECTUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY' DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED LUNGS NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) TREATMENT ' 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) 55 (5) (5) 55 (5) (5) (5) (5) 5555 (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 -57- ompany Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII HEART NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (5) (5) (5) 555 (5) 5 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5555 (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 -58- Company Sanitized. Does not contain TSCA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 14 (Continued) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS | LESION INCIDENCE (Numeric) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY' DETECTED PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES 'NO ABNORMALITY DETECTED TESTES NO ABNORMALITY DETECTED E Y E (S ) NO ABNORMALITY DETECTED (5) (5) (5) (5) 5 555 (5) (5) 55 (5) (5) 55 (5) (5) (5) (5) 5 555 (5) (5) (5) (5) 5555 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) (5) (5) 5555 (5) (5) (5) (5) 5 5. 5 5 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 -59- Ctanpany Sanitized. Does not contain TSC C il H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS D A Y 11 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII DIGESTIVE SYSTEM LIVER INFLAMMATION, SUBACUTE/CHRONIC. minimal -total observations per lesion INFLAMMATION, GRANULOMATOUS, with mineralization. minimal total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal ' total observations per lesion PANCREAS NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED (5) (5) (5) (5) 5555 5555 1 1 1 1 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -60Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS D A Y 11 SACRIFICE LESIONS TREATMENT LES101<r INCIDI3NCE (NTJMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII DIGESTIVE SYSTEM DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON. NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -61- Sanitized. Dees not mntati. t /** H-24267; Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS D A Y 11 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. .minimal mild total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal total observations per lesion URINARY BLADDER NO ABNORMALITY DETECTED RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR. minimal total observations per lesion (5) (5) (5) (5) 34 1 1 2 43 1 2 44 1 1 (5) (5) 55 (5) (5) (5) (5) 42 355 355 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 62- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN M ALE RATS DA Y 11 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM LUNGS INFLAMMATION, SUBACUTE/CHRONIC, FOCAL. minimal total observations per lesion INFLAMMATION, ACUTE, PERIVASCULAR. minimal total observations per lesion HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL. minimal total observations per lesion TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED NECROSIS, CARTILAGE. minimal total observations per lesion METAPLASIA, SQUAMOUS. minimal (5) (5) (5) (5) 12 12 2 2 55 55 (5) (5) 55 (5) (5) (5) (5) 531 1 1 244 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 63- Qompany Sanitized. Does not contain TSG SII H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY II SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM PHARYNX/LARYNX METAPLASIA, SQUAMOUS. total observations per lesion NOSE I & II NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion HYPERTROPHY, GOBLET CELL. minimal total observations per lesion HYPERPLASIA/HYPERTROPHY, RESPIRATORY. minimal total observations per lesion DEGENERATION/NECROSIS, OLFACTORY. minimal total observations per lesion NOSE III & IV NO ABNORMALITY DETECTED (5) (5) (5) (5) 244 (5) (5) (5) (5) 5552 1 1 2 2 2 2 1 1 (5) (5) (5) (5) 511 Figure in parentheses is number of animals microsbopically examined for this tissue The absence of a number indicates the lesion specified was not identified -64Conspany Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM NOSE III & IV HYPERTROPHY, GOBLET CELL. minimal -total observations per lesion CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY' DETECTED LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED (5) (5) 4 4 (5) (5) 45 45 (5) (5) 55 (5) (1) 51 (5) 5 (5) 5 (5) 5 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -65- Company Sanitized. Does not contain TSCA CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII LYMPHATIC AND HEMATOPOIETIC SYSTEM MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED NOT PRESENT. ADRENAL GLANDS NO ABNORMALITY DETECTED NOT PRESENT, MEDULLA. (5) 5 (5) 5 (5) 5 (5) 4 1 (5) 3 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 (5) 5 (5) 5 (5) 5 (5) 3 2 (5) 5 -66- Ssmttaed Bees net contain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED MUSCULAR AND SKELETAL SYSTEM STERNUM NO ABNORMALITY DETECTED REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) 55 (5) (5) (5) (5) 3552 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -67- Company Sanitized. Does not contain TSCA CBI J*- H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII REPRODUCTIVE SYSTEM TESTES DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL. minimal .mild total observations per lesion PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion EPIDIDYMIDES NO ABNORMALITY DETECTED OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL. minimal total observations per lesion OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL. minimal mild total observations per lesion (5) (5) (5) (5) 2 21 23 (5) (5) 45 1 1 (5) (5) 21 1 1 13 1 23 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 68empany S an lted , 0 @snot eontaSn TSCACM H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 15 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 11 SACRIFICE LESIONS | LESION INCIDENCE (NUMERIC) TREATMENT 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII REPRODUCTIVE SYSTEM EPIDIDYMIDES GRANULOMA, SPERM. SEMINAL VESICLES NO ABNORMALITY DETECTED SPECIAL SENSES SYSTEM E Y E (S ) NO ABNORMALITY DETECTED (5) (5) 1 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 69- Gompany Sanitized. Does not contain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 16 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII DIGESTIVE SYSTEM LIVER INFLAMMATION, SUBACUTE/CHRONIC. minimal .total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal mild total observations per lesion URINARY SYSTEM KIDNEYS NO-ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. minimal total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal total observations per lesion (5) 5 5 1 1 2 (5) 1 4 4 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified (5) 5 5 1 1 (5) 1 3 3 1 1 -70- C PS? SsnSized. Owes not contain TSCACBS H-24267; Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 16 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR. . minimal total observations per lesion INFLAMMATION, SUBACUTE/CHRONIC, FOCAL. minimal total observations per lesion PHARYNX/LARYNX NO ABNORMALITY DETECTED NECROSIS, CARTILAGE. minimal total observations per lesion NOSE I & II NO ABNORMALITY DETECTED NOSE III & IV NO ABNORMALITY DETECTED (5) (5) (5) (5) 4534 11 11 11 11 (5) (5) (5) (5) 5553 2 2 (5) (5) 55 (5) (5) 55 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified -71- Cw pany Sanitized. Does notcontain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 TABLE 16 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS DAY 25 SACRIFICE LESIONS TREATMENT LESION INCIDENCE (NUMERIC) 0 25 125 600 mg/m3 mg/m3 mg/m3 mg/m3 I III V VII REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL. -minimal total observations per lesion (5) 4 1 1 (5) 5 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 72- Company Sanitized. Does not contain TSCCB H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 FIGURES 73- H-24267: Two-Week Inhalation Toxicity Study in Male Rats FIGURE 1 SCHEMATIC OF EXPOSURE SYSTEM Spraying Systems nebulizer houseline air syringe drive DuPont-4292 -74- cold trap Company Sanitized. Does not contain TSCA C3i H-24267: Two-Week Inhalation Toxicity Study in Male Rats FIGURE 2 MEAN BODY WEIGHTS OF MALE RATS DuPont-4292 --0--0mg/m3 ----25mg/m3 B 125mg/m3 -- 600mg/m3 * Weight losses due to fasting of rats prior to clinical pathology evaluations. - 75- HpgffifSsnffita@&D@notcontain TSCA031 H-24267: Two-Week Inhalation Toxicity Study in Mate Rats DuPont-4292 APPENDICES -76- Csm panf SanHbed. es m l TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX A Daily Atmospheric Analyses , -77- B@sm i eortata 1 SA 11 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DAILY ATMOSPHERIC ANALYSES ABBREVIATIONS: EXPLANATORY NOTES S.D. - standard deviation n - number of samples mg/m3 - milligrams per cubic meter NOTES: Values are reported to 2 significant figures. DuPont-4292 -78- Company Sanitized. Does not contain TSCA CBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAILY ATMOSPHERIC ANALYSES GROUP: I DESIGN CONCENTRATION: Omg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 0 1 2 3 4 7 8 9 10 MEASURED CONCENTRATION (mg/m3) MEAN S.D. RANGE n 00 01 00 01 00 01 00 01 00 01 00 01 00 01 00 01 00 01 GROUP: m DESIGN CONCENTRATION: 25 mg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 0 1 2 3 4 7 8 9 10 MEASURED CONCENTRATION (mg/m3) MEAN S.D. RANGE n 15 9.8 4.0 - 27 6 26 8.7 13-36 6 34 26 8.4 - 70 6 17 7.7 5.0 - 27 6 24 6.7 18-36 6 31 17 7.9 - 58 6 19 14 6.4 - 45 6 19 10 8.4 - 39 6 24 18 8.4 - 55 6 - 79- e m pf Sani?d. D nesrtate TSS 6f H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAILY ATMOSPHERIC ANALYSES GROUP: V DESIGN CONCENTRATION: 125 mg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 0 1 2 3 4 7 8 9 10 MEASURED CONCENTRATION (mg/m3) MEAN S.D. RANGE n 120 22 110-170 6 99 41 50 -160 6 140 46 62 - 200 6 110 25 94 -160 6 120 34 73 -160 6 120 37 80 -170 6 110 17 94 - 140 6 79 36 18 -120 6 96 12 84-110 6 GROUP: VH DESIGN CONCENTRATION: 600 mg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 0 1 2 3 4 7 8 9 10 MEASURED CONCENTRATION (mg/m3) MEAN S.D. RANGE n 720 150 460 - 840 6 650 70 560-720 6 460 250 85 - 840 6 460 160 280 - 72 6 520 180 380 - 860 6 720 260 290 - 960 6 620 150 440 - 850 6 600 120 470 - 780 6 620 100 490 - 740 6 - 80- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX B Daily Environmental Conditions -81 - H-24267: Two-Week Inhalation Toxicity Study in Male Rats DAILY ENVIRONMENTAL CONDITIONS ABBREVIATIONS: EXPLANATORY NOTES n - number of observations NOTES: Values are reported to 2 significant figures. DuPont-4292 -82- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAILY ENVIRONMENTAL CONDITIONS GROUP: I DESIGN CONCENTRATION: Omg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 1 2 3 4 5 8 9 10 11 TEMPERATURE (C) 24-26 23-25 23-25 23-24 23-25 24-24 23-24 23 - 24 22-23 RELATIVE HUMIDITY n (%) 3 37-50 3 46-47 3 43-49 3 40-44 3 38-42 3 43-46 3 35-39 3 43-45 3 37-39 TOTAL AIRFLOW n (L/MIN) 2 30 2 30 2 30 2 30 2 30 2 30 2 30 2 30 2 30 n 1 1 1 1 1 1 1 1 1 GROUP: m DESIGN CONCENTRATION: 25 mg/m3 RELATIVE TOTAL EXPOSURE TEST TEMPERATURE HUMIDITY AIRFLOW NUMBER DAY (C) n (%) n (L/MIN) n 1 1 24-26 3 42-54 2 30 1 2 2 23-24 3 46-51 2 30 2 3 3 22-24 3 5 1 -5 4 2 30 1 4 4 22-23 3 4 0 -4 1 2 30 1 5 5 24-24 3 41-51 2 30 2 6 8 24-24 3 4 0 -5 0 2 30 1 7 9 23-24 3 4 0 -4 2 2 30 1 8 10 23-24 3 3 9 -4 3 2 30 1 9 11 22-24 3 3 8 -4 2 2 30 1 -83- ttifflpanf Sanifeed, Pqnet cortaln T8C C H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 DAILY ENVIRONMENTAL CONDITIONS GROUP: V DESIGN CONCENTRATION: 125 mg/m3 EXPOSURE NUMBER 1 2 3 4 5 6 7 8 9 TEST DAY 1 2 3 4 5 8 9 10 11 TEMPERATURE (C) 23-25 22-24 22-23 22-23 23-23 23-24 22-23 22 - 24 22-23 RELATIVE TOTAL HUMIDITY AIRFLOW n (%) n (L/MIN) n 3 5 0 -6 1 2 30 1 3 5 4 -5 6 2 30 1 3 5 6 -5 8 2 30 1 3 5 0 -5 4 2 30 1 3 5 3 -5 7 2 30 1 3 4 8 -5 7 2 30 1 3 48-58 2 30 1 3 3 7 -4 3 2 30 1 3 3 9 -4 1 2 30 1 GROUP: VU DESIGN CONCENTRATION: 600 mg/m3 RELATIVE TOTAL EXPOSURE TEST TEMPERATURE HUMIDITY AIRFLOW NUMBER DAY (C) n (%) n (L/MIN) n 1 1 23-24 3 6 9 -8 1 2 30 1 2 2 21-23 3 7 1 -7 3 2 30 1 3 3 21-22 3 7 2 -7 8 2 30 1 4 4 21-22 3 6 5 -7 0 2 30 1 5 5 21 - 22 3 7 5 -7 8 2 30 1 6 8 21-22 3 7 0 -7 2 2 30 1 7 9 21-22 3 7 2 -7 6 2 30 1 8 10 21-22 3 7 7 -8 2 2 30 1 9 11 22-22 3 8 2 -8 4 2 30 1 - 84- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX C Individual Body Weights -85- iSwmpamySanMteed. 0e@s msrrato TSCA CIS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Body Weights Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight ggggggggg Day 0 Day 1 Day 2 Day 3 Day 4 Day 7 Day 8 Day 9 Day 10 Male, I - 0 mg/m3 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 291.0 305.0 302.0 292.0 298.0 267.0 309.0 257.0 333.0 264.0 305.1 300.3 308.8 292.0 306.2 273.3 310.0 254.9 329.0 264.0 309.4 305.1 317.9 300.2 312.7 282.0 318.7 260.4 341.9 267.8 316.1 313.2 322.1 310.6 313.7 287.8 324.7 264.8 344.4 271.9 325.8 310.0 323.3 314.8 314.2 295.1 327.1 268.0 348.2 271.9 346.3 330.9 341.4 332.3 332.8 322.0 343.1 279.5 373.7 282.4 355.1 337.8 348.0 335.0 334.4 326.0 346.5 281.0 372.3 290.1 360.1 308.2 350.6 340.1 338.2 329.1 350.2 284.2 374.5 290.5 366.6 333.3 353.7 343.0 340.2 329.5 350.1 286.1 384.0 300.3 Body Weight Body Weight Body Weight Body Weight Body Weight ggggg Day 11 Day 14 Day 18 Day 22 Day 25 Male, I - 0 mg/m3 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 327.0 303.0 317.0 313.0 299.0 304.0 332.0 264.0 340.0 265.0 340.0 355.0 298.0 394.0 306.0 378.0 388.4 319.0 424.0 327.0 406.1 409.7 339.5 449.8 353.2 388.5 393.6 320.6 438.5 337.8 -86Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Body Weights Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight g g gg gggg g Day 0 Day 1 Day 2 Day 3 Day 4 Day 7 Day 8 Day 9 Day 10 Male, III - 25 mg/m3 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 296.0 298.0 303.0 292.0 295.0 270.0 305.0 259.0 301.0 270.0 296.8 296.7 299.7 290.9 285.3 267.5 298.9 253.6 290.0 266.5 298.0 300.3 300.8 294.0 283.9 272.2 299.6 256.0 293.0 274.1 297.1 302.5 303.0 296.9 288.7 273.0 298.4 255.6 298.0 279.4 301.9 308.4 308.8 302.8 292.0 274.4 301.4 258.4 305.0 283.6 329.1 331.3 335.0 326.3 309.0 294.7 321.5 277.3 319.2 314.7 326.8 330.8 337.2 .325.4 308.6 295.4 325.1 277.2 322.0 318.1 331.5 330.9 339.7 326.8 312.0 299.6 324.1 272.4 321.0 320.8 335.8 339.0 345.5 327.6 314.7 299.8 323.4 272.1 322.8 324.0 Body Weight Body Weight Body Weight Body Weight Body Weight ggggg Day 11 Day 14 Day 18 Day 22 Day 25 Male, III - 25 mg/m3 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 293.0 298.0 303.0 291.0 287.0 273.0 302.0 243.0 285.0 293.0 299.0 337.0 276.0 323.0 334.0 328.4 368.7 297.4 344.8 365.3 346.3 384.1 311.3 369.7 391.6 332.4 370.0 296.2 357.4 388.5 -87- mpawf Sanitized. Does net contain TSC CM H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Body Weights Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight ggggggggg Day 0 Day 1 Day 2 Day 3 Day 4 Day 7 Day 8 Day 9 Day 10 Male, V - 125 mg/m3 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 301.0 294.0 302.0 290.0 292.0 294.0 316.0 277.0 300.0 289.0 288.2 281.9 289.8 287.7 287.7 286.6 307.3 271.0 297.7 281.6 286.8 283.3 296.3 291.2 292.1 288.1 310.2 271.0 302.7 289.0 300.9 288.4 296.1 294.3 293.4 296.4 311.8 281.6 310.8 293.7 308.3 291.9 298.4 295.7 290.9 295.3 316.6 282.8 313.4 298.2 330.1 315.4 319.4 321.7 310.9 323.1 346.1 304.8 330.0 327.4 328.4 304.6 320.4 322.6 '312.4 317.0 332.7 301.4 326.0 325.1 320.2 303.1 314.0 317.4 307.0 311.1 336.8 298.4 326.1 324.0 321.5 299.8 318.1 321.7 311.8 317.1 344.0 299.9 324.7 328.6 Body Weight Body Weight Body Weight Body Weight Body Weight ggggg Day 11 Day 14 Day 18 Day 22 Day 25 Male, V - 125 mg/m3 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 288.0 264.0 282.0 290.0 277.0 290.0 320.0 276.0 293.0 291.0 326.0 356.0 315.0 344.0 345.0 360.0 394.1 336.5 368.6 375.1 377.1 419.7 359.4 397.0 405.6 364.9 405.4 349.2 385.9 391.2 -88- Company Sanitised. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Body Weights Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body Weight Body weight ggg gggggg Day 0 Day 1 Day 2 Day 3 Day 4 Day 7 Day 8 Day 9 Day 10 Male, VII - 600 mg/m3 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 295.0 293.0 315.0 308.0 302.0 292.0 311.0 261.0 322.0 286.0 284.7 280.6 290.0 294.2 286.2 276.3 300.9 247.8 318.3 281.6 289.7 285.1 298.9 293.9 278.7 271.0 305.1 248.6 318.4 281.3 285.0 291.3 295.9 294.8 278.1 266.7 304.2 242.7 319.0 281.6 276.7 282.6 294.2 296.9 287.8 275.1 309.4 243.4 326.5 281.2 306.1 310.1 328.8 332.7 314.0 293.8 329.9 267.9 345.9 303.1 306.0 305.8 322.5 327.3 307.1 293.0 328.9 257.3 346.3 296.8 302.5 308.1 330.2 329.9 302.2 291.0 325.3 260.9 347.0 299.7 308.0 306.2 315.5 332.4 307.0 291.4 326.6 257.2 351.2 294.1 Body Weight Body Weight Body Weight Body Weight Body Weight ggggg Day 11 Day 14 Day 18 Day 22 Day 25 Male, VII - 600 mg/m3 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 264.0 270.0 283.0 290.0 275.0 257.0 295.0 226.0 304.0 258.0 296.0 334.0 263.0 360.0 300.0 330.9 370.6 285.3 400.7 327.5 358.7 393.6 299.7 422.6 343.1 345.5 384.6 291.1 413.8 335.0 -89- empany SanSfteed. Does not onfafn TSC CBF H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX D Individual Clinical Observations and M ortality Records - 90- Gompany Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Clinical Observations and Mortality Records Sex Group Animal Observation MI MI 637800 . 637801 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637802 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637803 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637804 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Sacrificed by design MI 637805 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637806 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637807 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637808 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design MI 637809 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design Days 0-11 11 11 0-11 11 11 0-11 11 11. 0-11 11 11 0-11 11 11 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 -91- Sanitized. si! contain TSC CB8 H-24267: Two-Week Inhalation Toxicity Study in Male Rats Individual Clinical Observations and Mortality Records Sex Group Animal Observation M III 637810 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637811 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637812 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637813 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637814 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637815 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Hair Loss, Face, Right Wound, Superficial, Face Sacrificed by design M III 637816 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637817 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637818 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design M III 637819 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design DuPont-4292 Days 0-11 11 11 0-11 11 11 0-11 11 11. 0-11 11 11 0-11 11 11 0,11-25 11,25 8-10 1-7 25 0-25 11,25 25 0-25 11,25 25 ' 0-25 11,25 25 0-25 11,25 25 -92- Company SanfFsed. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats Sex Group Animal MV 637820 MV 637821 MV 637822 MV 637823 MV 637824 MV 637825 MV 637826 MV 637827 MV 637828 MV 637829 Individual Clinical Observations and Mortality Records Observation General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design DuPont-4292 Days 0-11 11 11 0-11 11 11 0-4,11 11 8-10 7 11 0-1,11 11 4-10 2-10 11 0-11 11 11 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 -93- snpanf Sanitized. 0g noieentelm TSCACM H-24267: Two-Week Inhalation Toxicity Study in Male Rats Sex Group Animal M VII 637830 M VII 637831 M VII 637832 M VII 637833 M VII 637834 M VII 637835 M VII 637836 M VII 637837 M VII 637838 M VII 637839 Individual Clinical Observations and Mortality Records Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Sacrificed by design DuPont-4292 Days 0-11 11 11 0-11 11 11 0-11 11 11. 0-11 11 11 0-11 11 11 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 0-25 11,25 25 -94- Cesnpm f Sanitised. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX E Individual Animal Clinical Pathology Data -95- oaspany Sanitized. Does not contain TSS CB H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES ABBREVIATIONS : G en eral: ADEQ - DECR NSR NT OK - ENV UTD - <- adequate decreased no sample re ceiv ed fo r te s tin g not taken or not performed sample c o n d itio n OK fo r t e s t in g result not valid unable to determine le s s than . In d ivid u al Hematology Values : COND - sample c o n d itio n 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 NRBC - nucleated red blood cell count WBC - white blood cell cotint ANEU - absolute neutrophil (all forms) ANPR - absolute neutrophil precursor ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell ABLT - absolute blast leukocyte AMSC - absolute miscellaneous leukocyte PLT - platelet count BASO - percent basophil BLST - percent blast leukocyte EOS - percent eosinophil LUC - percent large unstained cell LYMP - percent lymphocyte MISC - percent miscellaneous leukocyte MONO - percent monocyte NET - percent neutrophil NPRE - percent neutrophil precursor In d iv id u a l Red Blood C e ll Morphology V alues NORM - normal ANIS - a n is o c y to s is MICR - m icro cy tes MACR - m acrocytes POLY - polychrom asia i HYPO - hypochromas ia ECHI - e c h in o c y te s ACAN - acan th ocytes TARG - ta r g e t c e l l s RX - rou leau x HJB - H o w e ll-J o lly body not observed or not examined; see whole blood sample con d ition -96- Company Sai?*feed. Does not contain TSCA CB H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) In d iv id u a l White Blood C e ll / P la t e le t Morphology V alues: NORM - normal SM - smudge w h ite b lood c e l l s TG - t o x ic g ra n u la tio n (w hite b lood c e l l s ) DB - Dohle b o d ies VN - v a cu o la ted n e u tr o p h ils PC - p l a t e l e t clumps GP - g ia n t p l a t e l e t s BP - b iz a r r e p l a t e l e t s not observed or not examined; see whole blood sample con d ition Individual Coagulation Values: PHEM - plasma h em olysis PLIP - plasma lip em ia PICT - plasma ic te r u s PT - prothrombin tim e APTT - a c t iv a t e d p a r t ia l throm boplastin tim e In d iv id u a l Serum Chem istry V alues: SHEM - serum h em olysis SLIP - serum lip em ia SICT - serum ic te r u s AST - a sp a r ta te am in otran sferase ALT - a la n in e am in otran sferase SDH - s o r b it o l dehydrogenase ALKP - a lk a lin e phosphatase BILI - t o t a l b ilir u b in BUN - urea n itr o g e n CREA - c r e a tin in e CHOL - ' c h o le s te r o l TRIG - t r ig ly c e r id e s GLUC - g lu c o se TP - t o t a l p r o te in ALB - albumin GLOB - g lo b u lin CALC - calcium IPHS - in o rg a n ic phosphorous NA - sodium K - potassium CL - c h lo r id e PFLU - plasma flu o r id e FHEM - plasma h em olysis from b lood sample fo r flu o r id e d eterm in ation FLIP - plasma lip e m ia from b lood sample fo r flu o r id e d eterm in ation FICT - plasma ic t e r u s from b lood sample fo r flu o r id e d eterm in ation -97- @mpany SanSted. Boss ? esnfeisi TSC OBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) Individual U rin alysis Values : QUAL - q u a lit y (m od ifies c o lo r ) COL - c o lo r CLAR - c l a r i t y VOL - volume UOSM - u r in e o s m o la lity SG - s p e c i f i c g r a v ity pH - th e logarith m o f th e r e c ip r o c a l o f th e hydrogen io n co n ce n tra tio n UPRO - u rin e p r o te in UGLU - u rin e g lu c o se KET - ketone UBIL - u rin e b ilir u b in BLD - b lood URO - u ro b ilin o g en UFLU - u rin e flu o r id e Individual Urine M icroscopic Examination Values : EPIT - e p i t h e l i a l c e l l s WBC - u r in e w h ite blood c e l l s URBC - u rin e red blood c e l l s NCRY - normal c r y s t a ls MICR - microorganism s -98- Casmparsf Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) KEY: Red Blood C e ll Morphology V alu es, White Blood C e ll / P l a t e l e t Morphology V alu es, and Special Observations: 1 - few 2 - moderate 3 - many 4 - a ll NOTES: When in d iv id u a l animal d ata a re n ot rep o rted , i t may be due to one o f th e fo llo w in g reasons or other reasons, a l l of which are explained in the study records: th e sample was c l o t t e d (fo r hem atology or c o a g u la tio n data) (CLOT) th ere was in s u f f ic ie n t sample fo r a n a ly sis a v a lid r e s u lt cou ld n ot be ob tain ed (RNV) th e sample was n ot s u ita b le fo r ev a lu a tio n th e animal d ied p rio r to sample c o lle c tio n no sample was a v a ila b le fo r a n a ly s is (NSR) When an in d iv id u a l o b serv a tio n i s recorded as b eing l e s s than a c e r ta in v a lu e , c a lc u la tio n s are performed on h a lf th e recorded v a lu e . For example, i f b ilir u b in i s reported as <0.1, 0.05 i s used for any ca lcu la tio n s performed w ith that b iliru b in data. -99- H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal Number COND RBC x 10~6/m L HGB g/dL Male, Group: I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 OK 7.40 14.5 OK 7.34 14.3 OK 7.70 15.9 OK 7.51 14.8 OK 7.91 16.1 OK 7.51 15.2 OK 7.51 15.0 OK 7.81 15.4 OK 6.96 14.6 OK 8.08 16.0 Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 OK 7.44 OK 7.47 .OK 7.08 OK 7.21 OK 7.14 OK 8.74 OK 7.89 OK 8.68 OK 8.33 OK 7.37 15.6 14.7 14.5 14.5 14.3 16.6 14.9 16.5 16.0 14.3 HCT % 46.6 44.6 50.1 46.6 50.5 47.2 46.5 47.5 44.4 48.5 49.3 45.9 44.0 45.1 43.6 51.5 46.8 52.5 50.0 45.0 MCV fL 63.0 60.8 65.1 62.0 63.8 62.8 61.9 60.8 63.8 60.0 66.3 61.5 62.1 62.6 61.0 58.9 59.3 60.5 60.0 61.1 MCH pg 19.6 19.5 20.6 19.7 20.4 20.2 20.0 19.7 21.0 19.8 21.0 19.7 20.5 20.1 20.0 19.0 18.9 19.0 19.2 19.4 MCHC g/dL 31.1 32.0 31.7 31.8 31.9 32.2 32.3 32.4 32.9 33.0 31.6 32.0 33.0 32.1 32.8 32.2 31.8 31.4 32.0 31.8 RDW ARET NRBC WBC % x 10"'3/m L /100 WBC x 10~3/mL 13.0 13.2 12.3 12.7 12.5 13.4 14.2 12.6 13.6 12.6 262.5 199.1 231.6 239.0 212.0 298.4 216.2 204.9 257.0 228.2 13.3 13.3 13.1 13.4 13.7 11.8 13.4 12.7 12.8 13.7 193.4 176.7 217.5 189.4 194.0 250.7 213.6 178.5 171.8 251.3 NT 16.07 NT 12.02 NT 11.19 NT 13.19 NT 14.93 NT 17.83 NT 10.06 NT 11.89 NT 14.14 NT 9.77 NT 12.43 NT 9.51 NT 10.48 NT 11.74 NT 11.73 NT 11.82 NT 20.28 NT 13.46 NT 13.88 0 12.40 - 100- Compiy Sanftlzed. Does notcontain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal Number COND RBC XlO^S/iiL HGB g/dL Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 OK 7.46 15.1 OK 7.86 14.7 OK 7.70 15.4 OK 7.57 15.1 OK 8.31 15.8 OK 7.73 15.8 OK 6.96 14.6 OK 7.57 15.5 OK 7.33 15.6 OK 7.55 15.5 Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 OK 8.72 17.0 OK 8.01 16.2 OK 8.23 16.0 OK 7.67 15.2 OK 8.26 16.0 OK 7.91 15.5 OK 7.68 15.4 OK 8.83 16.9 OK 7.18 15.0 OK 8.05 15.8 HCT % 47.0 46.1 47.3 46.8 50.1 48.2 45.2 47.0 47.2 46.5 51.4 49.5 50.9 47.0 50.3 47.4 48.1 52.0 46.2 49.2 MCV fL 63.0 58.6 61.4 61.8 60.3 62.3 64.9 62.1 64.4 61.6 58.9 61.8 61.8 61.3 60.9 59.9 62.6 58.9 64.4 61.1 MCH per 20.2 18.7 20.0 19.9 19.0 20.4 21.0 20.5 21.3 20.5 19.5 20.2 19.4 19.8 19.4 19.6 20.1 19.1 20.9 19.6 MCHC g/dL 32.1 31.9 32.6 32.3 31.5 32.8 32.3 33.0 33.0 33.3 33.1 32.7 31.5 32.3 31.8 32.7 32.0 32.5 32.4 32.1 ROW ARET NRBC WBC % xlOA3//iL /100 WBC x 10,'3/m L 14.5 14.0 13.5 12.8 12.1 12.8 13.4 13.3 13.5 14.0 207.0 132.6 187.7 161.5 119.8 189.5 167.6 203.6 160.4 211.2 14.0 13.7 12.8 12.6 13.2 13.7 14.3 13.5 13.1 13.9 202.4 132.5 171.2 157.2 206.9 153.6 168.6 82.6 167.3 154.0 NT 12.76 0 12.51 NT 14.60 0 11.14 NT 10.58 NT 11.74 NT 14.70 NT 13.16 NT 11.92 NT 10.05 0 11.31 NT 10.10 NT 16.11 NT 7.63 NT 15.32 0 10.58 NT 19.39 NT 20.03 NT 8.09 NT 11.94 - 101- gMpfflrssr SartUwd. B@@@no retato TSCA CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal ANEU ANPR ALYM AMON AEOS ABAS ALUC ABLT AMSC PLT Number xlOA3//xL x!0A3/iib x 10a3/mL xlOA3/iiL xlOA3/ML x 10a3/m L xlOA3/fiL xl0A3/ML x 10a3/m L xlOA3/(iL Male, Group : I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 2.15 2.01 1.24 3.32 1.85 3.80 1.18 1.68 1.97 1.69 NT 12.92 NT 9.17 NT 9.21 NT 9.00 NT 12.47 NT 13.00 NT 8.32 NT 9.62 NT 11.35 NT 7.30 Male, Group:: III - 25 mg/m21 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 0.98 1.01 1.40 0.93 1.82 1.39 2.05 1.01 0.94 2.23 NT NT NT NT NT NT NT NT NT 0.00 10.79 7.90 8.63 10.14 9.02 9.34 17.04 11.76 11.95 9.92 0.50 0.46 0.41 0.40 0.36 0.45 0.16 0.25 0.38 0.36 0.26 0.24 0.16 0.22 0.31 0.37 0.59 0.36 0.37 0.00 0.18 0.14 0.07 0.08 0.07 0.12 0.07 0.17 0.16 0.12 0.12 0.06 0.10 0.07 0.16 0.09 0.10 0.08 0.19 0.12 0.08 0.05 0.07 0.09 0.04 0.14 0.11 0.05 0.06 0.07 0.06 0.10 0.04 0.12 0.09 0.20 0.12 0.05 0.12 0.00 0.26 0.19 0.18 0.30 0.13 0.30 0.22 0.12 0.23 0.22 0.20 0.20 0.14 0.26 0.33 0.43 0.39 0.19 0.29 0.00 NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT 0.00 NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT 0.12 RNV 941 RNV 1187 RNV 1221 827 1126 1104 1171 1034 919 840 1079 1008 RNV 1106 707 722 860 BASO % 0.5 0.4 0.6 0.7 0.3 0.8 1.1 0.4 0.4 0.7 0.5 1.0 0.4 1.0 0.8 1.7 0.6 0.4 0.9 0.0 - 102- Gotopmy Sanitized. Does *contain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal ANEU ANPR ALYM AMON AEOS ABAS ALUC ABLT AMSC PLT Number xlO -3/mL xlO A3/iiL x !0~3/mL x 10*3/h xl0"3//ib x!0A3/iiL x!0A3/h xlO^/fiL xlO^/h xlOA3//iL Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 1.12 1.13 1.74 1.23 1.09 0.83 1.41 1.59 1.36 1.19 NT 0.00 NT 0.00 NT NT NT NT NT NT 10.77 10.76 12.02 9.58 8.69 10.17 12.26 10.86 9.04 8.11 Male, Group: VII - 600 ing/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 1.58 1.50 1.47 1.40 1.93 1.16 3.66 1.54 0.91 1.49 0.00 NT NT NT NT 0.00 NT NT NT NT 9.05 7.91 13.95 5.66 12.29 9.10 14.62 16.67 6.64 9.42 0.47 0.25 0.39 0.00 0.41 0.35 0.46 0.26 0.49 0.41 0.00 0.31 0.31 0.25 0.55 0.00 0.54 0.74 0.20 0.57 0.18 0.00 0.20 0.11 0.14 0.06 0.19 0.17 0.83 0.09 0.11 0.10 0.13 0.11 0.20 0.32 0.12 0.18 0.02 0.17 0.03 0.00 0.04 0.00 0.04 0.09 0.10 0.05 0.04 0.05 0.00 0.07 0.08 0.05 0.06 0.00 0.14 0.14 0.07 0.04 0.19 0.00 0.20 0.00 0.21 0.23 0.29 0.21 0.18 0.20 NT 0.00 NT 0.00 NT NT NT NT NT NT 0.00 0.20 0.18 0.16 0.31 0.00 0.29 0.76 0.23 0.25 0.00 NT NT NT NT 0.00 NT NT NT NT NT 0.38 NT 0.22 NT NT NT NT NT NT 0.57 NT NT NT NT 0.00 NT NT NT NT 858 1061 1113 740 841 965 903 988 RNV 1042 RNV 867 841 954 1074 893 778 980 1040 905 BASO % 0.2 0.0 0.3 0.0 0.4 0.8 0.7 0.4 0.3 0.5 0.0 0.7 0.5 0.6 0.4 0.0 0.7 0.7 0.9 0.3 -103- smspan^Sanitized. Ooess not contain SCA CSI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal BLST EOS LUC Number % % % Male, Group: I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 NT 1.1 NT 1.2 NT 0.6 NT 0.6 NT 0.5 NT 0.7 NT 0.7 NT 1.4 NT 1.1 NT 1.2 Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 NT 1.0 NT 0.6 -NT 1.0 NT 0.6 NT 1.4 NT 0.8 NT 0.5 NT 0.6 NT 1.4 0 1.0 1.6 1.6 1.6 2.3 0.9 1.7 2.2 1.0 1.6 2.3 1.6 2.1 1.3 2.2 2.83.6 1.9 1.4 2.1 0.0 LYMP % MISC % 80.4 76.3 82.3 68.2 83.5 72.9 82.7 80.9 80.3 74.7 NT NT NT NT NT NT NT NT NT NT 86.8 83.1 82.3 86.4 76.9 79.0 84.0 87.4 86.1 80.0 NT NT NT NT NT NT NT < NT NT 1 MONO % 3.1 3.8 3.7 3.0 2.4 2.5 1.6 2.1 2.7 3.7 2.1 2.5 1.5 1.9 2.6 3.1 2.9 2.7 2.7 0.0 NEUT % NPRE % SPECIAL OBSERVATIONS 13.4 16.7 11.1 25.2 12.4 21.3 11.7 14.1 13.9 17.3 7.9 10.6 13.4 7.9 15.5 11.8 10.1 7.5 6.8 18.0 NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT 0 1%-ATYPICAL LYMPHOCYTE -104- Company Sanitised. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal Nun'ber BLST % EOS LUC %% Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 NT 1.4 1.5 0 0.0 0.0 NT 1.4 1.4 0 1.0 0.0 NT 1.3 2.0 NT 0.5 2.0 NT 1.3 2.0 NT 1.3 1.6 NT 7.0 1.5 NT 0.9 2.0 Male, Group : VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 0 1.0 0.0 NT 1.0 2.0 -NT 0.8 1.1 NT 1.4 2.1 NT 1.3 2.0 0 3.0 0.0 NT 0.6 1.5 NT 0.9 3.8 NT 0.3 2.9 NT 1.4 2.1 LYMP % MISC MONO NEUT %%%% NPRE SPECIAL OBSERVATIONS 84.4 86.0 82.3 86.0 82.1 86.6 83.4 82.5 75.8 80.7 80.0 78.3 86.6 74.2 80.2 86.0 75.4 83.2 82.1 78.9 NT 3.7 8.8 NT 3 2.0 9.0 0 3%- ATYPICAL LYMPHOCYTE NT 2.7 11.9 NT 2 0.0 11.0 0 2%- ATYPICAL LYMPHOCYTE NT 3.9 10.3 NT NT 3.0 7.1 NT NT 3.1 9.6 NT NT 2.0 12.1 NT NT 4.1 11.4 NT NT 4.1 11.8 NT 5 0.0 14.0 NT 3.1 14.9 NT 1.9 9.1 NT 3.3 18.4 NT 3.6 12.6 0 0.0 11.0 NT 2.8 18.9 NT 3.7 7.7 NT 2.5 11.3 NT 4.8 12.5 0 5%-HYPERSEGMENTED NEUTROPHILS NT NT NT NT 0 NT NT NT NT -105- Cosnpaisy Sanitized. Boss not contain TSCA Cif H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal Number COND RBC x!0A6/jtiL HGB g/6L Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 OK 8.09 16.0 OK 8.22 15.6 OK 8.51 16.2 OK 7.43 15.1 OK 8.37 16.0 Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 OK 8.79 16.5 OK 8.54 15.7 OK 8.65 16.4 OK 8.58 15.6 OK 7.97 15.1 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 OK 7.91 15.7 OK 7.34 14.8 OK 7.97 15.6 OK 7.35 15.5 OK 7.77 15.5 Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 OK 8.19 15.5 OK 8.10 15.7 OK 8.41 15.5 OK 7.41 15.2 OK 8.13 15.5 HOT % 48.8 48.7 49.8 45.2 48.5 51.2 49.4 50.4 49.7 46.8 47.3 45.1 48.1 47.3 48.3 48.2 47.5 48.4 46.8 47.6 MCV L 60.3 59.2 58.5 60.9 57.9 58.2 57.9 58.3 57.9 58.7 59.8 61.5 60.3 64.3 62.1 58.8 58.6 57.6 63.1 58.6 MCH pg 19.8 19.0 19.0 20.3 19.1 18.8 18.4 19.0 18.2 18.9 19.8 20.2 19.6 21.1 19.9 18.9 19.4 18.4 20.5 19.1 MCHC g/dL ROW ARET NRBC WBC % X1CT3/ML /100 WBC xlOA3/*iL 32.8 32.1 32.5 33.4 33.0 13.9 13.7 13.3 12.6 12.9 308.5 235.4 242.0 258.8 262.2 32.3 31.8 32.5 31.4 32.3 13.1 13.4 13.1 13.2 13.6 279.5 249.1 266.4 271.7 264.4 33.2 32.8 32.5 32.8 32.1 13.0 13.0 13.4 13.1 13.6 219.8 238.8 267.8 261.1 303.3 32.2 33.1 32.0 32.5 32.5 13.7 14.2 13.8 13.0 13.4 267.3 300.8 209.9 260.3 227.7 NT 23.02 NT 12.37 NT 9.91 NT 16.39. NT 11.73 NT 10.88 NT 21.09 NT 11.95 NT 16.97 NT 13.65 NT 13.01 NT 16.78 NT 18.42 NT 13.49 NT 10.19 NT 12.95 NT 17.98 NT 16.70 NT 12.60 NT 12.11 -106- Company Sanitised. Does not contain TSCA CBJ H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS DuPont-4292 Animal ANEU ANPR ALYM AMON AEOS ABAS ALUC ABLT AMSC PLT Number xlOA3/fiL xlOA3//iL xlOA3/(iL x 10a 3//iL x 10a3/L x 10a 3/mL x 10a3/m L x 10a3/jL x 10a3/mL x 10a3/mL Male, Group : I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 4.81 1.62 1.72 2.84 2.24 NT 16.94 NT 9.93 NT 7.70 NT 12.92 NT 8.68 Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 2.14 3.65 2.31 2.05 2.20 NT 8.07 NT 15.99 NT 8.91 NT 13.92 NT 10.51 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 l.*37 2.55 2.21 1.74 0.99 NT 10.84 NT 13.52 NT 15.09 NT 10.83 NT 8.49 Male, Group : VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 1.85 2.50 1.75 1.95 1.95 NT 10.32 NT 14.49 NT 13.86 NT 9.93 NT 9.36 0.62 0.33 0.19 0.26 0.34 0.35 0.53 0.35 0.41 0.49 0.40 0.23 0.42 0.49 0.32 0.35 0.43 0.35 0.39 0.36 0.21 0.11 0.13 0.11 0.16 0.07 0.17 0.13 0.14 0.25 0.09 0.10 0.13 0.11 0.06 0.16 0.11 0.10 0.05 0.06 0.12 0.10 0.03 0.08 0.12 0.04 0.19 0.07 0.12 0.05 0.07 0.08 0.15 0.07 0.08 0.08 0.11 0.12 0.06 0.10 0.32 0.27 0.14 0.20 0.20 0.20 0.59 0.17 0.34 0.16 0.25 0.29 0.39 0.26 0.24 0.19 0.32 0.52 0.21 0.29 NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT 1011 NT RNV NT 1182 NT 1164 NT 995 NT RNV NT 1057 NT 840 NT 941 NT RNV NT 1000 NT 879 NT 1047 NT 924 NT 1170 NT 851 NT 880 NT 979 NT 1075 NT 930 BASO % 0.5 0.8 0.3 0.5 1.0 0.4 0.9 0.6 0.7 0.4 0.5 0.5 0.8 0.5 0.8 0.6 0.6 0.7 0.5 0.8 -107- g@pan^ tted,, D@^not contain TSCA CBl H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL HEMATOLOGY VALUES FOR MALE RATS Animal BLST EOS LUC Number % % % Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NT 0.9 1.4 NT 0.9 2.2 NT 1.3 1.4 NT 0.7 1.2 NT 1.4 1.7 Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NT 0.6 1.8 NT 0.8 2.8 NT 1.1 1.4 NT 0.8 2.0 NT 1.8 1.2 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 NT 0.7 1.9 NT 0.6 1.7 NT 0.7 2.1 NT 0.8 1.9 NT 0.6 2.4 Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 NT 1.2 1.5 NT 0.6 1.8 NT 0.6 3.1 NT 0.4 1.7 NT 0.5 2.4 LYMP % 73.6 80.3 77.7 78.8 74.0 74.2 75.8 74.6 82.0 77.0 83.3 80.6 81.9 80.3 83.3 79.7 80.6 83.0 78.8 77.3 MISC % NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT MONO % 2.7 2.7 1.9 1.6 2.9 3.2 2.5 2.9 2.4 3.6 3.1 1.4 2.3 3.6 3.1 2.7 2.4 2.1 3.1 3.0 NEUT % 20.9 13.1 17.4 17.3 19.1 19.7 17.3 19.3 12.1 16.1 10.5 15.2 12.0 12.9 9.7 14.3 13.9 10.5 15.5 16.1 NPRE % SPECIAL OBSERVATIONS NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT DuPont-4292 -108- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL RED BLOOD CELL MORPHOLOGY VALUES FOR MALE RATS Animal Number NORM ANIS MICE Male, Group: I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 -- -- NORMAL __ __ -- NORMAL -- -- -- -- 1 -- --- -- Male, Group : III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 -- __ -- NORMAL -- NORMAL NORMAL -- 1 -- 1 -- -- -- -- -- _ -- -- -- 1 -- __ -- -- -- 1 -- 1 -- -- __ --- __ MACR POLY ---- ---- ---- -- -- __ -- -- --- -- -- --- --- -- ---- ---- -- -- -- ----- ---- r -- __ -- HYPO --- --- -- -- --- --- -- -- -- -- -- -- -- -- -- ECHI ACAN 2 2 1 -2 2 1 1 -- 1 4 2 1 2 2 -- --- -- 2 1 1 -- -1 1 1 -- -- 1 1 -- 1 1 -- 1 -- -- 1 TARG --- -- -- -- --- --- __ -- -- -- -- -- -- -- -- -- DuPont-4292 RX HJB -- ----- -- __ -- "" -- -- ---- ---- -- --- ---- ---- ---- -- -- -- -- -- ----- ---- -109- Company Sanitized. Does not contain TSCA CSi H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL RED BLOOD CELL MORPHOLOGY VALUES FOR MALE RATS Animal Number NORM ANIS MICR Male, Group: V - 125 mg/m3 - Day 11 637820 -- _ 637821 -- 1 637822 637823 -- -- __ _ 637824 -- __ 637825 -- 637826 -- __ 637827 -- _ 637828 __ 1 637829 1 Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 -- NORMAL -- NORMAL -- NORMAL NORMAL -- _ _ _ -- -- --- _ 1 __ __ _ __ _ _ 1 1 _ __ _ __ __ __ _ -- MACR _ --_ _ _ __ __ -__ -- __ _ __ _ __ _ _ -- POLY -- __ _ __ __ _ -- __ _ _ _ _ -- HYPO -- -- -- -- -- _ _ --- __ _ __ -- _ -- ECHI ACAN 2 1 1 1 2 2 1 3 1 1 2 1 _2 _2 _ -- 1 2 1 1 1 1 1 1 1 --- 2 _1 _1 1 -- -- TARG --- -- -- -- -- -- ---- -- __ -- -- -- DuPont-4292 RX HJB ---- ---- ---- -- --- ----- -- -- -- -- ---- ---- -- -- -- ---- -- -- -- --- -- -110- Coraipany Sanitized. Does notcontain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL RED BLOOD CELL MORPHOLOGY VALUES FOR MALE RATS Animal Number NORM ANIS MICR Male, Group: I - 0 mg/m3 - Day 25 637805 -- _ 637806 -- -- 637807 -- -- 637808 -- 2 637809 -- 1 Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 Male, Group: VII - 600 mg/m3'- Day 25 637835 637836 637837 637838 637839 -- -- -- 1 1 MACR POLY HYPO ECHI ACAN TARG 2 2 1 2' 1 31 2 11 21 11 31 21 22 42 21 21 21 21 21 1 21 DuPont-4292 RX HJB - Ill - Company Sanitized. Does not contain TSCA CBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL WHITE BLOOD CELL / PLATELET MORPHOLOGY VALUES FOR MALE RATS DuPont-4292 Animal NORM SM TG DB VN PC GP BP SPECIAL Number OBSERVATIONS Male, Group: I - 0 mg/m3 - Day 11 637800 -- - - ___ __ 1 _ DECR PLATELET 637801 NORMAL -- -- -- -- -- -- -- 637802 -- -- -- -- -- 1 -- DECR PLATELET 637803 NORMAL -- -- -- -- -- -- -- 637804 -- -- -- -- -- 1-- -- DECR PLATELET 637805 NORMAL -- -- -- -- -- -- -- 637806 NORMAL -- -- -- -- -- -- __ 637807 NORMAL -- -- -- -- -- -- -- 637808 NORMAL -- -- -- -- __ -- -- 637809 NORMAL -- -- -- -- -- -- -- Male, Group: III - 25 mg/m3 - Day 11 637810 NORMAL __ _ _ __ _ 637811 NORMAL _ _ ___ -- ___ ___ _ _ 637812 NORMAL ___ ___ ___ ___ ___ ___ ___ 637813 NORMAL ___ ___ ___ ___ _ _ ___ ___ 637814 NORMAL -- - - ___ - - ___ _ _ ___ 637815 -- -- -- -- -- 1-- -- DECR PLATELET 637816 NORMAL ___ ___ ___ __ ___ ___ ___ 637817 NORMAL ___ __ __ __ 637818 NORMAL ' ___ ___ ___ _ _ _ ... _ __ 637819 NORMAL -- -- ___ _ _ _ _ _ _ ___ -112- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL WHITE BLOOD CELL / PLATELET MORPHOLOGY VALUES FOR MALE RATS DuPont-4292 Animal NORM SM TG DB VN PC GP BP SPECIAL Number OBSERVATIONS Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL 1-- 1-- -- otd -- DECR PLATELET -113 - Company Sanitized. Does notcontain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL WHITE BLOOD CELL / PLATELET MORPHOLOGY VALUES FOR MALE RATS DuPont-4292 Animal NORM SM TG Number Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NORMAL -- NORMAL NORMAL NORMAL -- Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NORMAL NORMAL NORMAL Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 NORMAL NORMAL NORMAL NORMAL NORMAL DB -- VN -- PC -- 1 1 GP BP SPECIAL OBSERVATIONS 1 -- -- DECRPLATELET -- -- DECR PLATELET -- -- ADEQ PLATELET -114- Qofl^pany Sanitized. DretretainTSCCBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL COAGULATION VALUES FOR MALE RATS Animal Number PHEM PLXP PICT Male, Group : I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 NONE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: III - 25 mg/m:3 - Day 11 637810 637811 637812 637813 637814 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 MODERATE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 NONE NONE -TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PT sec 14.3 15.3 18.0 16.5 14.7 15.5 14.9 15.0 15.5 15.0 15.2 14.6 16.9 15.1 15.2 14.8 15.0 15.8 14.7 APTT sec 20.0 14.5 28.8 22.1 13.9 25.9 22.5 21.5 17.1 18.0 17.8 17.2 19.0 14.8 25.8 17.7 19.5 20.8 16.5 DuPont-4292 -115- Contpany Sanitized. Does not contain TSCA CBt H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL COAGULATION VALUES FOR MALE RATS Animal Number PHEM PLIP PICT Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 NONE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PT sec 14.2 15.2 15.7 14.3 14.8 14.9 15.8 16.4 15.5 14.2 14.6 14.1 14.3 14.7 14.8 14.1 14.5 16.2 13.9 14.6 APTT sec 18.0 19.0 23.5 18.6 15.9 18.0 23.0 23.3 17.3 13.8 17.3 15.4 15.9 16.1 19.0 14.9 17.7 21.0 15.7 16.1 DuPont-4292 -116- C W W Sanitized. Doe, not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number SHEM SLIP SICT Male, Group: I - 0 mg/m:1 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 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 Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 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 AST IU/L 88 86 90 81 135 85 105 84 100 100 122 86 76 83 100 87 131 113 83 98 ALT IU/L 35 32 39 27 44 34 48 35 41 42 40 44 44 36 51 40 51 40 37 43 SDH IU/L 18.1 20.5 20.7 16.2 23.4 14.1 17.6 14.0 16.2 15.2 12.7 15.7 14.8 14.0 19.9 17.4 20.7 15.0 14.3 18.3 ALKP IU/L BILI mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 241 236 172 ' 209 186 165 275 239 263 208 <0.10 0.11 <0.10 <0.10 <0.10 0.13 0.10 0.10 <0.10 0.12 155 <0.10 174 <0.10 256 <0.10 200 0.14 196 0.10 176 0.10 190 0.11 187 <0.10 211 0.14 183 <0.10 15 0.31 12 0.33 17 0.42 10 0.30 14 0.37 15 0.39 11 0.28 12 0.28 13 0.27 12 0.34 14 0.40 15 0.44 17 0.32 16 0.41 18 0.38 17 0.39 16 0.39 17 0.50 21 0.41 14 0.34 76 110 40 56 53 63 59 45 74 70 81 58 70 52 54 67 69 48 69 84 -117- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number SHEM SLIP SICT Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 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 Male, Group: VII - 600 mg/m3 - Day il 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 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 AST IU/L 66 79 81 105 74 79 78 87 104 81 81 108 75 74 93 75 114 78 98 98 ALT IU/L 29 39 37 42 40 27 39 34 31 36 36 38 43 36 72 44 37 38 51 52 SDH IU/L 16.6 15.9 18.2 21.1 11.0 14.6 15.3 14.2 14.6 13.3 17.6 11.4 14.2 11.7 17.0 15.0 21.4 14.3 16.6 22.3 ALKP IU/L BILI mg/dL BUN mg/dL GREA mg/dL CHOL mg/dL 125 <0.10 273 0.11 186 <0.10 218 <0.10 193 0.12 232 <0.10 273 <0.10 130 <0.10 185 <0.10 174 0.11 171 <0.10 184 0.11 184 <0.10 178 0.14 207 0.19 127 0.10 199 <0.10 243 0.10 176 <0.10 141 0.11 11 0.37 16 0.34 16 0.47 16 0.40 17 0.34 14 0.34 17 0.41 12 0.31 15 0.40 12 0.40 37 0.71 20 0.39 16 0.41 22 0.39 19 0.36 19 0.43 15 0.45 21 0.51 16 0.39 21 0.45 93 69 89 69 80 80 108 113 78 53 72 68 91 76 88 79 94 71 89 117 -118- 0nH>ijrSanltbad. D@es not contain TSCA CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Male, Group: I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 73 94 46 93 36 78 38 84 44 104 38 87 50 94 22 91 44 82 63 90 Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 56 26 -49 19 24 29 34 24 22 41 69 88 87 91 90 85 86 85 87 83 5.7 5.8 6.0 6.0 6.4 6.3 6.2 5.9 5.9 6.3 6.3 5.8 6.1 6.1 6.3 6.8 5.8 6.6 6.7 6.2 ALB g/dL 4.0 4.2 4.0 4.1 4.3 4.2 4.3 4.1 4.0 4.3 4.3 4.2 4.3 4.2 4.1 4.7 4.2 4.5 4.6 4.4 GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 1.7 10.8 10.3 147.6 6.33 94.2 1.6 10.6 9.4 149.0 5.68 95.0 2.0 10.7 10.0 ' 148.9 6.12 93.9 1.9 10.5 8.6 150.3 6.17 96.3 2.1 11.9 12.0 150.0 6.91 96.9 2.1 11.0 10.3 148.2 6.30 94.8 1.9 10.8 8.9 149.9 5.96 96.2 1.8 10.8 9.7 151.0 6.07 95.1 1.9 11.0 10.0 149.7 ' 6.46 95.2 2.0 10.7 10.7 146.5 6.09 96.3 2.0 10.8 10.3 146.3 6.46 99.4 1.6 10.6 10.0 148.8 5.74 98.1 1.8 11.3 9.7 150.5 5.95 95.0 1.9 11.0 9.5 149.7 6.04 98.3 2.2 10.5 9.4 148.0 5.72 97.5 2.1 11.2 9.0 149.5 6.50 98.2 1.6 10.8 10.1 148.1 6.50 97.5 2.1 10.7 9.5 148.6 6.30 99.7 2.1 11.2 9.8 150.0 6.19 97.1 1.8 11.1 9.3 150.8 6.37 97.6 -119- Company Sanitized. Does nof contain TSCA CBl H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 40 81 6.3 34 82 6.3 31 93 6.4 47 81 6.0 35 77 6.4 23 97 6.1 54 109 5.9 34 90 5.9 49 85 6.0 51 92 6.2 Male, Group : VII - 600 mg/m3 - Day 11 637830 54 83 6.7 637831 38 81 6.2 637832 53 93 6.2 637833 -30 92 6.4 637834 38 89 6.6 637835 27 95 6.8 637836 35 94 5.9 637837 32 91 7.0 637838 36 88 6.7 637839 40 '88 6.8 ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K jnmol/L CL mmol/L 4.5 1.8 10.9 9.4 149.0 6.18 94.8 4.3 2.0 11.0 9.6 149.2 6.09 95.2 4.6 1.8 11.1 9.6 148.3 5.82 96.2 4.3 1.7 11.0 10.0 148.7 6.18 97.1 4.4 2.0 11.5 9.1 149.4 5.94 96.7 4.4 1.7 10.7 9.8 147.9 6.43 97.9 4.3 1.6 11.0 10.3 146.5 5.72 94.9 4.3 1.6 10.8 9.3 147.9 5.67 96.9 4.2 1.8 11.1 10.3 149.9 6.23 101.0 4.4 1.8 11.1 9.7 149.1 6.12 93.6 4.7 2.0 11.0 11.2 143.1 6.21 89.6 4.4 1.8 11.1 9.2 145.2 5.50 93.6 4.2 2.0 11.2 9.1 149.0 6.04 96.1 4.5 1.9 11.2 8.6 146.4 5.35 91.0 4.7 1.9 11.8 9.8 147.8 6.11 92.0 4.8 2.0 11.4 9.4 146.3 5.70 92.0 4.3 1.6 10.9 10.0 149.3 5.93 97.2 4.8 2.2 11.5 9.9 150.7 6.11 93.5 4.5 2.2 11.3 9.3 148.0 6.02 96.2 4.3 2.5 11.2 9.5 146.6 6.28 93.2 -120 ConPany S an fe ed . Does net earsfatn TSC CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS Animal Number PFLU FHEM FLIP Male, Group: I - 0 mg/m3 - Day 11 637800 0.1 NONE NONE 637801 0.1 NONE NONE 637802 0.1 TRACE NONE 637803 0.1 NONE NONE 637804 0.1 NONE NONE Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 0.1 0.1 0.1 0.1 0.1 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: V - 125 mg/m:' - Day 11 637820 0.1 TRACE NONE 637821 0.1 NONE NONE 637822 0.1 NONE NONE 637823 0.1 NONE NONE 637824 0.1 NONE NONE Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 0.1 0.1 0.1 0.1 0.1 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE FICT NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE DuPont-4292 - 121- Companjr SanWzed. Does not contain TSCACBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number SHEM SLIP SICT Male, Group : I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group : VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE AST ITJ/L 87 107 77 94 109 102 94 126 98 100 119 90 87 88 77 110 125 83 85 82 ALT IU/L 44 44 40 48 51 37 46 47 43 47 38 39 44 42 37 51 35 45 46 38 SDH ITJ/L 24.3 21.7 18.0 21.5 21.9 24.2 22.5 15.4 24.8 25.7 24.8 19.7 16.7 20.9 18.9 24.4 10.0 19.2 19.7 25.2 ALKP IU/L BILI mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 148 239 210 230 173 0.12 0.15 0.12 <0.10 0.11 155 0.12 189 <0.10 188 0.13 195 0.16 199 0.17 215 0.12 238 0.13 138 0.10 186 0.12 181 <0.10 126 0.14 184 0.14 212 0.11 186 0.15 138 0.10 18 0.51 13 0.38 12 0.41 14 0.42 13 0.39 16 0.45 15 0.44 17 0.53 15 0.55 16 0.41 13 0.44 14 0.41 14 0.45 15 0.43 13 0.38 15 0.45 19 0.38 17 0.35 15 0.37 16 0.32 73 61 50 73 82 65 73 58 80 100 64 86 102 74 56 65 94 64 73 85 - 122- empaity Saimffiteed. Does netscontain TSC CBB H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS DuPont-4292 Animal Number TRIG itvg/dL GLUC mg/dL TP g/dL Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 49 83 7.5 61 100 6.9 22 95 6.8 71 109 6.3 99 86 6.9 Male, Group: III - 25 mg/m3 - Day 25 637815 55 76 7.0 637816 83 97 6.9 637817 53 82 7.2 637818 42 91 7.2 637819 73 99 6.8 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 32 80 6.8 76 110 6.3 78 98 6.6 78 93 6.5 95 94 6.7 Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 45 95 7.1 54 104 6.5 37 90 6.8 38 93 6.8 43 78 6.6 ALB g/dL 4.8 4.7 4.8 4.3 4.6 4.7 4.8 4.8 5.0 4.7 4.9 4.5 4.7 4.6 4.8 4.9 4.7 4.6 4.7 4.4 GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.7 11.3 2.2 10.9 2.0 10.8 2.0 10.7 2.3 10.8 9.0 8.6 8.7 9.7 7.9 151.5 149.3 151.9 150.1 149.8 5.99 5.61 5.73 6.66 5.92 93.0 96.7 95.8 97.1 97.1 2.3 10.7 2.1 10.8 2.4 10.7 2.2 11.2 2.1 10.9 8.2 151.8 9.4 150.1 7.8 149.7 9.3 151.0 8.9 150.1 6.15 6.30 6.25 6.30 6.34 99.1 95.0 98.4 94.7 98.0 1.9 10.6 1.8 10.4 1.9 10.9 1.9 10.9 1.9 11.2 8.0 150.0 8.9 149.1 8.5 152.6 8.5 151.0 9.2 151.6 5.88 5.64 5.61 6.26 6.41 95.1 96.8 97.4 97.6 97.0 2.2 10.7 8.4 149.3 5.73 96.2 1.8 10.6 9.1 148.0 6.03 98.5 2.2 11.2 9.1 151.2 6.11 96.4 2.1 11.1 10.0 151.3 5.88 95.8 2.2 11.0 9.3 150.7 6.23 97.9 -123- Cemparay Sanitized. Does not contain TSCA CBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL SERUM CHEMISTRY VALUES FOR MALE RATS Animal Number PFLU FHEM FLIP Male, Group : I - 0 mg/m3 - Day 25 637805 0.1 TRACE NONE 637806 0.1 NONE NONE 637807 0.1 NONE NONE 637808 0.1 NONE NONE 637809 0.1 NONE TRACE ale, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 0.1 0.1 0.1 0.1 0.1 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group;: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 0.1 NONE O-.l TRACE 0.1 NONE 0.1 NONE 0.1 NONE NONE NONE NONE NONE NONE Male, Group;; VII - 600 mg/m3 - Day 25 637835 0.1 TRACE NONE 637836 0.1 TRACE NONE 637837 0.1 NONE NONE 637838 0.1 NONE NONE 637839 0.1 NONE NONE FICT NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE DuPont-4292 -124- Company Sanitized. Does not contain TSC CB H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS DuPont-4292 Animal Number QUAL COL CLAR Male, Group: I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 DARK LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT NSR BROWN YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT CLOUDY HAZY HAZY CLEAR CLEAR CLEAR CLEAR CLEAR HAZY NT Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR HAZY CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR VOL UOSM mL mOsm/kg SG 6.3 9.4 5.2 5.5 26.0 3.2 12.2 9.1 9.2 NT 6.0 8.2 11.0 8.3 9.8 12.8 3.9 4.0 12.0 13.6 1475 808 999 1233 330 1149 688 696 851 NT 1.046 1.025 1.030 1.039 1.012 1.037 1.022 1.021 1.025 NT 1003 852 685 849 826 555 1006 1278 672 578 1.031 1.026 1.023 1.026 1.025 1.019 1.031 1.040 1.022 1.019 pH UPRO UGLU RET mg/dL mg/dL mg/dL UBIL 7.5 6.5 6.06.5 6.0 6.0 5.5 6.5 7.0 NT 30 TRACE 30 30 NEGATIVE 30 TRACE TRACE 30 NT NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NT 15 5 15 5 NEGATIVE 5 NEGATIVE 5 5 NT SMALL NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NT 6.0 30 NEGATIVE 5 NEGATIVE 7.0 TRACE NEGATIVE 5 NEGATIVE 6.0 TRACE NEGATIVE 5 NEGATIVE 6.5 TRACE NEGATIVE NEGATIVE NEGATIVE 6.5 TRACE NEGATIVE 5 NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.5 30 NEGATIVE NEGATIVE NEGATIVE 6.0 30 NEGATIVE 5 NEGATIVE 6.5 TRACE NEGATIVE NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE -125- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS DuPont-4292 Animal Number QUAL COL CLAR Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 MEDIUM LIGHT LIGHT MEDIUM LIGHT LIGHT MEDIUM LIGHT MEDIUM LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR CLEAR HAZY HAZY CLEAR CLEAR CLEAR CLEAR Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLEAR CLEAR HAZY HAZY CLEAR CLEAR HAZY CLEAR VOL UOSM mL mOsm/kg SG 1.7 15.8 13.4 4.5 9.7 13.0 6.7 8.0 3.0 17.2 9.3 11.8 7.9 12.6 7.3 5.3 10.0 10.0 18.0 14.0 1023 365 499 1416 779 617 1179 522 1717 427 1.036 1.012 1.018 1.047 1.025 1.021 1.038 1.018 1.055 1.015 699 621 766 500 1227 1166 791 602 460 486 1.022 1.021 1.025 1.018 1.039 1.038 1.025 1.019 1.017 1.017 pH UPRO UGLU KET mg/dL mg/dL mg/dL 5.0 TRACE 5.5 NEGATIVE 5.0 NEGATIVE 5.5 ' 30 6.0 NEGATIVE 6.5 NEGATIVE 6.0 30 5.0 NEGATIVE 5.5 30 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5 NEGATIVE 5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.0 TRACE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.5 TRACE NEGATIVE 5 NEGATIVE 5.5 TRACE NEGATIVE NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE -126- o^anySanRfeed. Des notconfa?*! TSCACBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS Animal Number BLD URO EU/dL UFLU ms Male, Group : I - 0 mg/m3 - Day 11 637800 637801 637802 637803 637804 637805 637806 637807 637808 637809 MODERATE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NT 1.0 6.6 0.2 9.2 0.2 6.7 0.2 8.6 0.2 13.2 0.2 4.9 0.2 15.1 0.2 10.4 0.2 10.2 NT NSR Male, Group : III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 NEGATIVE NEGATIVE NEGATIVE TRACE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.3 0.2 10.1 0.2 10.9 0.2 13.0 0.2 14.8 0.2 11.7 0.2 5.7 0.2 7.4 0.2 12.6 0.2 14.2 SPECIAL OBSERVATIONS FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED DuPont-4292 -127- Companysanfffeed. Does not contain TSCACBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS Animal Number BLD URO EU/dL UFLU g Male, Group: V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 4.1 0.2 15.7 0.2 17.6 0.2 13.3 0.2 18.4 0.2 21.8 0.2 17.8 0.2 12.5 0.2 11.6 0.2 15.3 Male, Group : VII ~ 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE TRACE NEGATIVE NEGATIVE 0.2 8.1 0.2 13.9 0.2 11.2 0.2 10.9 0.2 12.9 0.2 11.7 0.2 14.7 0.2 13.2 0.2 18.9 0.2 13.6 SPECIAL OBSERVATIONS DuPont-4292 - 128- Ssysfifesd Does nofeoitialnTSCACB! H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 -129- Company Sanitized. Does not eontaln TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS DuPont-4292 Animal Number QUAL COL CLAR Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 MEDIUM MEDIUM LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW yellow HAZY CLEAR CLEAR CLOUDY CLEAR Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 LIGHT LIGHT MEDIUM LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR CLOUDY HAZY Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLOUDY CLOUDY CLEAR Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 LIGHT MEDIUM MEDIUM LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR HAZY CLEAR CLEAR CLEAR VOL UOSM mL mOsm/kg SG 6.4 4.3 15.4 13.4 23.2 14.2 9.7 5.4 20.8 13.2 20.6 9.2 10.8 13.4 15.2 24.0 6.7 2.5 12.4 7.3 1274 1394 551 729 390 1.041 1.044 1.018 1.023 1.014 483 882 1030 462 670 1.015 1.026 1.031 1.015 1.022 470 1016 567 648 605 1.015 1.030 1.020 1.022 1.020 355 1386 1329 760 956 1.012 1.044 1.042 1.024 1.029 pH UPRO UGLU KET , UBIL mg/dL mg/dL mg/dL 6.5 30 NEGATIVE 6.5 30 NEGATIVE 6.5 TRACE NEGATIVE 7.0 TRACE NEGATIVE 6.0 TRACE NEGATIVE 15 NEGATIVE 15 NEGATIVE 5 NEGATIVE 5 NEGATIVE 5 NEGATIVE 6.0 NEGATIVE NEGATIVE 5 NEGATIVE 6.5 30 NEGATIVE 5 NEGATIVE 6.5 30 NEGATIVE 5 NEGATIVE 6.5 TRACE NEGATIVE NEGATIVE NEGATIVE 6.0 TRACE NEGATIVE n e g a t i v e NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 30 NEGATIVE 5 NEGATIVE 6.0 TRACE NEGATIVE NEGATIVE NEGATIVE 6.0 TRACE NEGATIVE 5 NEGATIVE 5.5 NEGATIVE NEGATIVE 5 NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.0 30 NEGATIVE 5 NEGATIVE 5.5 30 NEGATIVE 5 NEGATIVE 6.0 TRACE NEGATIVE 5 NEGATIVE 6.5 TRACE NEGATIVE 5 NEGATIVE -130- iSSSpst^' Sanitized. 0@ ostiate TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINALYSIS VALUES FOR MALE RATS Animal Number BLD URO EU/dL UFLU Mg Male, Group:: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.7 0.2 7.1 0.2 12.1 0.2 14.5 0.2 16.3 Male, Group:: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NEGATIVE TRACE NEGATIVE TRACE NEGATIVE 0.2 12.2 0.2 10.9 0.2 8.5 0.2 15.4 0.2 13.5 Male, Group:: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 NEGATIVE NEGATIVE SMALL TRACE NEGATIVE 0.2 16.2 0.2 15.1 0.2 11.0 0.2 18.3 0.2 16.1 Male, Group:: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 16.8 0.2 13.4 0.2 5.3 0.2 15.0 0.2 12.0 SPECIAL OBSERVATIONS FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED DuPont-4292 -131- epany Sanitized. Does not contain TSCACBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINE MICROSCOPIC VALUES FOR MALE RATS DuPont-4292 Animal Number EPIT UWBC URBC Male, Group: I - 0 mg/m3 - Day 11 637800 NT NT 637801 637802 637803 637804 637805 637806 637807 637808 637809 FEW 0 FEW 1-10 FEW 0 FEW 0 FEW 0 FEW 0 FEW 0 FEW 0 NSR NT Male, Group: III - 25 mg/m3 - Day 11 637810 637811 637812 637813 637814 637815 637816 637817 637818 637819 FEW FEW NONE FEW NONE NONE NONE NONE FEW FEW 0 0 0 0 0 1-10 1-10 0 0 0 NT 0 0 0 0 0 0 0 0 NT 0 0 0 0 0 0 0 0 0 0 NCRY MICR SPECIAL OBSERVATIONS NT NONE NONE NONE NONE NONE NONE NONE NONE NT NT GROSSLY CONTAMINATED WITH FECAL MATERIAL, UNABLE TO DETERMINE CELLULAR MATERIAL. FEW 1-SPERM FEW 1-SPERM FEW FEW FEW 1-SPERM FEW 1-SPERM FEW FEW NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE FEW FEW FEW MODERATE FEW FEW FEW FEW NONE NONE 1-SPERM 1-SPERM 1-SPERM 1-SPERM 1-SPERM -132 - Gorapany Sanitized. Does not contain TSCA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINE MICROSCOPIC VALUES FOR MALE RATS Animal Number EPIT UWBC URBC Male, Group : V - 125 mg/m3 - Day 11 637820 637821 637822 637823 637824 637825 637826 637827 637828 637829 FEW 0 FEW 0 FEW 1-10 FEW 0 FEW 1-10 FEW 0 FEW 0 FEW 0 FEW 0 FEW 0 Male, Group: VII - 600 mg/m3 - Day 11 637830 637831 637832 637833 637834 637835 637836 637837 637838 637839 FEW FEW NONE FEW FEW NONE NONE NONE FEW FEW 0 0 0 1-10 1-10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NCRY FEW NONE NONE NONE NONE NONE NONE NONE NONE NONE FEW NONE NONE NONE NONE NONE NONE NONE NONE NONE MICR SPECIAL OBSERVATIONS FEW FEW FEW FEW FEW FEW FEW NONE FEW FEW Sample status 1-SPERM 1-SPERM 1-SPERM 1-SPERM l-SPERM BELOW RECOMMENDED VOLUME 1-SPERM FEW 1-SPERM FEW FEW FEW FEW FEW 1-SPERM FEW 1-SPERM FEW FEW FEW DuPont-4292 -133- CompanySanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats INDIVIDUAL URINE MICROSCOPIC VALUES FOR MALE RATS Animal Number EPIT UWBC URBC Male, Group: I - 0 mg/m3 - Day 25 637805 637806 637807 637808 637809 NONE NONE NONE NONE NONE 0 0 0 0 0 Male, Group: III - 25 mg/m3 - Day 25 637815 637816 637817 637818 637819 NONE NONE NONE FEW FEW 0 1-10 0 0 0 Male, Group: V - 125 mg/m3 - Day 25 637825 637826 637827 637828 637829 FEW NONE FEW NONE NONE 0 0 0 0 0 Male, Group: VII - 600 mg/m3 - Day 25 637835 637836 637837 637838 637839 FEW FEW NONE NONE NONE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NCRY MICR SPECIAL OBSERVATIONS NONE NONE NONE FEW NONE MODERATE MODERATE FEW FEW FEW 2-SPERM 2-SPERM; 1-MUCUS 1-SPERM; 1-MUCUS 1-SPERM 1-SPERM NONE NONE NONE NONE NONE FEW MODERATE MODERATE MANY FEW 2-SPERM; 1-MUCUS 1-MUCUS 1-MUCUS 2-SPERM 1-SPERM; 1-MUCUS NONE FEW NONE NONE NONE FEW FEW MODERATE MANY FEW 1-SPERM 1-SPERM 1-MUCUS NONE NONE NONE NONE NONE FEW MODERATE FEW FEW MODERATE 1-SPERM; 1-MUCUS 2-SPERM; 1-MUCUS 2-SPERM; 1-MUCUS 1-MUCUS 2-SPERM; 1-MUCUS DuPont-4292 - 134- Gompany Sanitized. Does not contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX F Individual Animal Final Body and Organ Weights - 135- ICompany Sanitized. Does no! contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Final Body and Organ Weights Group : I - 0 mg/xn3 Treatment : 0 mg/m3 I Sex :MALES I ANIMAL 1 637800 637801 637802 637803 637804 FINA (Gms) 327.00 303.00 317.00 313.00 299.00 BRAIN (Gms) %FINA 1.887 0.5771 1.954 0.6449 1.963 0.6192 2.011 0.6425 1.871 0.6258 KIDNEYS (Gms) %FINA %BRAIN 2.932 0.8966 155.38 2.734 0.9023 139.92 2.566 0.8095 130.72 3.328 1.0633 165.49 2.601 0.8699 139.02 LIVER (Gms} %FINA %BRAIN 11.066 3.3841 586.43 10.028 3.3096 513.20 11.165 3.5221 568.77 10.472 3.3457 520.74 10.013 3.3488 535.17 LUNGS (Gms) %FINA %BRAIN 1.760 0.5382 93.270 1.727 0.5700 88.383 2.013 0.6350 102.55 1.803 0.5760 89.657 1.708 0.5712 91.288 Mean S.D. 311.80 1.937 0.6219 11.19 0.058 0.0273 2.832 0.9083 146.10 10.549 3.3821 544.86 0.312 0.0941 14.027 0.550 0.0826 31.536 1.802 0.5781 93.029 0.123 0.0352 5.6268 TESTES '1 (Gms) %FINA %BRAIN | 2.449 0.7489 129.78 3.093 1.0208 158.29 2.701 0.8521 137.60 3.385 1.0815 168.32 2.580 0.8629 137.89 2.842 0.9132 146.38 0.388 0.1352 16.187 Group : III - 25 mg/m3 Treatment : 25 mg/m3 III Sex -.MALES I ANIMAL 1 637810 637811 637812 637813 637814 FINA (Gms) 293.00 298.00 303.00 291.00 287.00 BRAIN (Gms) %FINA 1.964 0.6703 1.868 0.6268 1.918 0.6330 1.840 0.6323 1.742 0.6070 KIDNEYS (Gms) %FINA %BRAIN 2.780 0.9488 141.55 2.931 0.9836 156.91 2.948 0.9729 153.70 2.832 0.9732 153.91 2.321 0.8087 133.24 LIVER (Gms) %FINA %BRAIN 10.326 3.5242 525.76 9.305 3.1225 498.13 9.844 3.2488 513.24 9.138 3.1402 496.63 8.929 3.1111 512.57 Mean S.D. 294.40 1.866 0.6339 6.23 0.084 0.0229 2.762 0.9374 147.86 0.256 0.0731 10.078 9.508 3.2294 509.27 0.569 0.1737 12.069 LUNGS (Gms) %FINA %BRAIN 1.488 0.5078 75.764 1.510 0.5067 80.835 1.631 0.5383 85.036 1.407 0.4835 76.467 1.448 0.5045 83.123 1.497 0.5082 80.245 0.085 0.0196 4.0602 TESTES I (Gms) %FINA %BRAIN | 3.226 1.1010 164.26 3.677 1.2339 196.84 3.282 1.0832 171.12 3.321 1.1412 180.49 3.187 1.1105 182.95 3.339 1.1340 179.13 0.196 0.0597 12.406 136- 0,nPanySnnlll*od. Does notcontain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Final Body and Organ Weights Group : V - 125 mg/m3 Treatment : 125 mg/m3 V Sex :MALES 1 ANIMAL 1 637820 637821 637822 637823 637824 FINA (Gms) 288.00 264.00 282.00 290.00 277.00 BRAIN (Gms) %FINA 1.932 0.6708 1.902 0.7205 1.834 0.6504 2.077 0.7162 1.873 0.6762 KIDNEYS (Gms) %FINA %BRAIN 2.667 0.9260 138.04 2.489 0.9428 130.86 2.722 0.9652 148.42 2.972 1.0248 143.09 2.490 0.8989 132.94 LIVER {Gms) %FINA %BRAIN 10.901 3.7851 564.23 8.605 3.2595 452.42 9.355 3.3174 510.09 10.921 3.7659 525.81 9.473 3.4199 505.77 LUNGS (Gms) %FINA %BRAIN 2.478 0.8604 128.26 1.666 0.6311 87.592 1.903 0.6748 103.76 1.769 0.6100 85.171 2.234 0.8065 119.27 Mean S.D. 280.20 1.924 0.6868 10.40 0.093 0.0304 2.668 0.9516 138.67 0.199 0.0476 7.2241 9.851 3.5095 511.66 1.023 0.2496 40.345 2.010 0.7166 104.81 0.338 0.1109 18.989 TESTES I (Gms) %FINA %BRAIN | 3.334 1.1576 172.57 3.398 1.2871 178.65 3.202 1.1355 174.59 3.294 1.1359 158.59 3.178 1.1473 169.67 3.281 1.1727 170.82 0.092 0.0646 7.5735 Group : VII - 600 mg/m3 Treatment : 600 mg/m3 VII Sex :MALES 1 ANIMAL i 637830 637831 637832 637833 637834 FINA (Gms) 264.00 270.00 283.00 290.00 275.00 BRAIN (Gms) %FINA 1.793 0.6792 1.868 0.6919 1.980 0.6996 1.955 0.6741 1.934 0.7033 KIDNEYS (Gms) %FINA %BRAIN 2.750 1.0417 153.37 2.642 0.9785 141.43 2.697 0.9530 136.21 2.886 0.9952 147.62 2.865 1.0418 148.14 LIVER (Gms) %FINA %BRAIN 9.650 3.6553 538.20 9.616 3.5615 514.78 11.220 3.9647 566.67 9.905 3.4155 506.65 9.768 3.5520 505.07 Mean S.D. 276.40 1.906 0.6896 10.31 0.076 0.0127 2.768 1.0020 145.36 10.032 3.6298 526.27 0.106 0.0392 6.6362 0.674 0.2058 26.177 LUNGS (Gms) %FINA %BRAIN 1.695 0.6420 94.534 1.775 0.6574 95.021 2.157 0.7622 108.94 1.698 0.5855 86.854 1.694 0.6160 87.590 1.804 0.6526 94.588 0.200 0.0671 8.8731 TESTES I (Gms) %FINA %BRAIN | 2.584 0.9788 144.12 3.165 1.1722 169.43 2.901 1.0251 146.52 3.381 1.1659 172.94 2.821 1.0258 145.86 2.970 1.0736 155.77 0.309 0.0893 14.152 -137 - Company Sanitized. Poes not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Final Body and Organ Weights Group : I - 0 mg/m3 Treatment : 0 mg/m3 I Sex :MALES I ANIMAL 1 FINA BRAIN (Gms) (Gms) %FINA KIDNEYS (Gms) %FINA %BRAIN 637805 637806 637807 637808 637809 388.50 393.60 320.60 438.50 337.80 2.007 0.5166 2.087 0.5302 1.982 0.6182 1.983 0.4522 1.669 0.4941 3.224 0.8299 160.64 3.452 0.8770 165.40 2.649 0.8263 133.65 3.698 0.8433 186.49 2.884 0.8538 172.80 LIVER (Gms) %FINA %BRAIN 12.558 3.2324 625.71 12.921 3.2828 619.12 9.789 3.0533 493.90 13.255 3.0228 668.43 10.553 3.1240 632.29 LUNGS (Gms) %FINA %BRAIN 1.906 0.4906 94.968 1.759 0.4469 84.284 1.526 0.4760 76.993 2.159 0.4924 108.88 1.582 0.4683 94.787 Mean S.D. 375.80 1.946 0.5223 47.17 0.160 0.0612 3.181 0.8460 163.80 11.815 3.1431 607.89 0.422 0.0205 19.474 1.545 0.1122 66.519 1.786 0.4748 91.981 0.257 0.0186 12.105 TESTES .1 (Gms) %FINA %BRAIN | 3.177 0.8178 158.30 3.378 0.8582 161.86 2.632 0.8210 132.80 3.287 0.7496 165.76 3.392 1.0041 203.24 3.173 0.8501 164.39 0.315 0.0946 25.262 Group : III - 25 mg/m3 Treatment : 25 mg/m3 III Sex :MALES 1 ANIMAL 1 FINA BRAIN (Gms) (Gms) %FINA KIDNEYS (Gms) %FINA %BRAIN (Gms) LIVER %FINA %BRAIN 637815 637816 637817 637818 637819 332.40 370.00 296.20 357.40 388.50 1.894 0.5698 2.115 0.5716 1.947 0.6573 1.931 0.5403 2.152 0.5539 2.749 0.8270 145.14 3.052 0.8249 144.30 2.410 0.8136 123.78 2.832 0.7924 146.66 3.335 0.8584 154.97 9.229 2.7765 487.28 13.003 3.5143 614.80 8.944 3.0196 459.37 10.014 2.8019 518.59 12.945 3.3320 601.53 Mean S.D. 348.90 2.008 0.5786 35.83 0.117 0.0458 2.876 0.8233 142.97 10.827 3.0889 536.31 0.345 0.0240 11.537 1.999 0.3259 69.015 NW = NOT WEIGHED LUNGS (Gms) %FINA %BRAIN NW 1.490 0.4027 70.449 1.579 0.5331 81.099 1.910 0.5344 98.912 1.809 0.4656 84.061 1.697 0.4840 83.631 0.196 0.0630 11.746 TESTES I (Gms) %FINA %BRAIN | 2.998 0.9019 158.29 3.596 0.9719 170.02 2.856 0.9642 146.69 3.577 1.0008 185.24 3.439 0.8852 159.80 3.293 0.9448 164.01 0.343 0.0491 14.469 -138- & p a n f Sanitized D@net contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Final Body and Organ Weights Group : V - 125 mg/m3 Treatment : 125 mg/m3 V Sex :MALES 1 ANIMAL 1 637825 637826 637827 637828 637829 FINA (Gms) 364.90 405.40 349.20 385.90 391.20 BRAIN (Gms) %FINA 2.215 0.6070 2.058 0.5076 1.916 0.5487 2.102 0.5447 2.038 0.5210 KIDNEYS (Gms) %FINA %BRAIN 3.246 0.8896 146.55 3.726 0.9191 181.05 3.094 0.8860 161.48 3.376 0.8748 160.61 3.169 0.8101 155.50 LIVER (Gms) %FINA %BRAIN 11.459 3.1403 517.34 13.358 3.2950 649.08 11.643 3.3342 607.67 12.835 3.3260 610.61 13.510 3.4535 662.90 LUNGS (Gms) %FINA %BRAIN 1.682 0.4609 75.937 2.040 0.5032 99.125 1.986 0.5687 103.65 1.764 0.4571 83.920 1.889 0.4829 92.689 Mean S.D. 379.32 2.066 0.5458 22.25 0.108 0.0382 3.322 0.8759 161.04 12.561 3.3098 609.52 0.249 0.0403 12.665 0.958 0.1123 56.827 1.872 0.4946 91.065 0.149 0.0454 11.247 TESTES (Gms) %FINA %BRAIN | 2.216 0.6073 100.05 3.025 0.7462 146.99 2.312 0.6621 120.67 3.298 0.8546 156.90 3.292 0.8415 161.53 2.829 0.7423 137.23 0.528 0.1086 26.123 Group : VII - 600 mg/m3 Treatment : 600 mg/m3 VII Sex MALES 1 ANIMAL 1 637835 637836 637837 637838 637839 FINA (Gms) 345.50 384.60 291.10 413.80 335.00 BRAIN (Gms) %FINA 2.042 0.5910 1.968 0.5117 1.816 0.6238 2.068 0.4998 2-.057 0.6140 KIDNEYS (Gms) %FINA %BRAIN 3.318 0.9603 162.49 3.029 0.7876 153.91 2.555 0.8777 140.69 3.717 0.8983 179.74 3.316 0.9899 161.21 LIVER (Gms) %FINA %BRAIN 12.712 3.6793 622.53 12.175 3.1656 618.65 8.896 3.0560 489.87 14.462 3.4949 699.32 11.120 3.3194 540.59 Mean S.D. 354.00 1.990 0.5681 47.18 0.105 0.0583 3.187 0.9027 159.61 11.873 3.3431 594.19 0.430 0.0788 14.198 2.057 0.2503 80.947 LUNGS (Gms) %FINA %BRAIN 1.834 0.5308 89.814 2.142 0.5569 108.84 1.466 0.5036 80.727 2.210 0.5341 106.87 1.916 0.5719 93.145 1.914 0.5395 95.879 0.294 0.0262 11.860 TESTES I (Gms) %FINA %BRAIN j 3.649 1.0562 178.70 3.080 0.8008 156.50 2.908 0.9990 160.13 3.421 0.8267 165.43 3.295 0.9836 160.18 3.271 0.9333 164.19 0.289 0.1127 8.7117 -139- Company Sanitized. Does not contain TSCACBt H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 APPENDIX G Individual Animal Pathology Data -140- om pany Sanitized. Does not contain TSCA C0I H-24267: Two-Week Inhalation Toxicity Study in Male Rats KEY TO APPENDIX INDIVIDUAL ANIMAL PATHOLOGY DATA DuPont-4292 LESION GRADING: HistopathoTogical changes are described according to their morphologic character, distribution and severity. The distribution (extent of tissue involvement) is indicated, where appropriate, by modifiers such as focal, multifocal, diffuse, unilateral, bilateral, etc. A severity score, if appropriate, is also assigned as follows: MINIMAL : the amount of change present barely exceeds that which is considered to be within normal limits. MILD: in general, the lesion is easily identified but of limited severity, the lesion probably does not produce any functional impairment. MODERATE : the lesion is prominent but there is significant potential for increased severity. limited tissue or organ dysfunction is possible. SEVERE : the degree of change is either as complete as considered possible or great enough in intensity or extent to expect significant tissue or organ dysfunction. COMMENT : Grades minimal through severe represent progressive involvement/severity along a continuum with minimal lesions being the least severe and severe lesions being the most severe. While the grades refer to the morphological characteristics of lesions, they also indicate their relative biological significance. Gross observations listing multiple masses for a tissue are distinguished with letters (i.e.. A, b, c, d, etc.). -141- @mpMfrSanitized. Boss not eonteln TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637800 ' Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LONGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. ADRENAL GLANDS : NOT PRESENT, MEDULLA. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, mild. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, mild. No Microscopic Abnormality Observed : LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, STERNUM, BONE MARROW, NOSE I & II, NOSE III & IV - 142- Con>paay Sanitized.Does no*contain TSCACBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637801 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : . LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S ), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), SEMINAL VESICLES, ' URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, BONE MARROW, NOSE I & II, NOSE III & IV - 143- Q m pm j Sanltbed. Ds not M r s ? S CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637802 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, ' STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, BONE MARROW, NOSE I & II, NOSE III & IV -144 Company Sanitized. Does not contain TSCA CPI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637803 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : EPIDIDYMIDES : DISCOLORATION, MOTTLED, TAIL, RIGHT, 3MM dia. No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. PARATHYROID GLANDS : NOT PRESENT. EPIDIDYMIDES : GRANULOMA, SPERM. No Microscopic Abnormality Observed : KIDNEYS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE{S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, BONE MARROW, NOSE I & II, NOSE III & IV -145- Csmparsy Sanitized. Does not contain TSC CBt i H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637804 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : LIVER : DISCOLORATION, YELLOW, LEFT, 4 MM dia. DEFORMITY, IRREGULAR, MIDDLE, only one lobe evident. No Macroscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. INFLAMMATION, GRANULOMATOUS, minimal, with mineralization. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. ADRENAL GLANDS : NOT PRESENT, MEDULLA. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, mild. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, minimal. No Microscopic Abnormality Observed : LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, STERNUM, BONE MARROW, NOSE I & II, NOSE III & IV ) -146- Company Sanitized. Does not contain TSCA CB! H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637805 . Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -147- Company Sanitized. Does not contain TSCA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637806 . Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : . LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV - 148- Cempanf' SawSfized, Etes nt ain TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637807 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed.off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL, minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, PHARYNX/LARYNX, NOSE I & II, NOSE III & IV -149- COmpany Sanf!,2ed- Des not contain TSCA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637808 . Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, mild. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. No Microscopic Abnormality Observed : PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -150 CoBBpany HanfffeedL Bees not contain ee H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : I - 0 mg/m3 Treatment: 0 mg/m3 I Sex: Males Animal Ref Microscopic & Macroscopic Findings 637809 ' Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -151- Company Sanitized. Does no! contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group :: III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637810 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. INFLAMMATION, ACUTE, PERIVASCULAR, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : KIDNEYS, PHARYNX/LARYNX, TESTES, NOSE I & II - 152- empani? Sanitized, De not eanMr* T sc eaP H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group :: III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637811 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. INFLAMMATION, ACUTE, PERIVASCULAR, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : KIDNEYS, PHARYNX/LARYNX, TESTES, NOSE I & II - 153- Company Santtfeed. Does not contain TSCA 6 8! H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637812 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. No Microscopic Abnormality Observed : KIDNEYS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -154- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637813 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, TESTES, NOSE I & II - 155 - Company S a n lta S * B e at net conM n TSC CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637814 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : KIDNEYS : DILATATION, UNILATERAL, PELVIS, mild. SPLEEN : DEFORMITY, IRREGULAR. No M acroscopic Abnormality Observed : LIVER, LUNGS, HEART, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : HYDRONEPHROSIS, UNILATERAL, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : LUNGS, SPLEEN, TESTES, NOSE I & II -156- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637815 - Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : LUNGS : Inflated, not weighed, protocol deviation. No Macroscopic Abnormality Observed : LIVER, KIDNEYS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX - 157- Gomipany Sanitized. Doesnot contain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637816 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : No M icroscop ic Abnorm ality Observed : LUNGS, PHARYNX/LARYNX - 158- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637817 ' Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX -159 - Company Sanitised. Does not contain TSC CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref Microscopic & Macroscopic Findings 637818 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No M acroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : No M icroscop ic Abnormality Observed : LUNGS, PHARYNX/LARYNX -160- Company Sanitized. Does not contain TSCA CEI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : III - 25 mg/m3 Treatment: 25 mg/m3 III Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637819 - Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX -161- Company Sanitized. Deesnotcontain TSCA CBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637820 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : TESTES, NOSE I & II - 162- Comptny Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637821 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : TESTES, NOSE I & II -163- ompamf SanM sed, D oes m i eo tfefe T iC H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637822 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. No Microscopic Abnormality Observed : TESTES, NOSE I & II, NOSE III & IV -164- Company Sanitized. Does not contain TSCA CBl H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637823 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : KIDNEYS, TESTES, NOSE I & II - ! -165 ornpanf Sanlffeed. B@8not eonflata TSC CB1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637824 - Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : PHARYNX/LARYNX, TESTES, NOSE I & II -166- Company Sanitized. Does not contain TSGA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group :: V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637825 - Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : Ho Microscopic Abnormality Observed LUNGS, PHARYNX/LARYNX -167- Com panf Sanitized, Does not esntaln TSG B1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637826 ' Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. No Microscopic Abnormality Observed : PHARYNX/LARYNX -168- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637827 _ Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LXJNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX -169- Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637828 . Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No M acroscopic Abnorm ality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. No M icroscop ic Abnormality Observed : PHARYNX/LARYNX -170- CoMapanf Sanftlzedl. Dot net cortis? TSC CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : V - 125 mg/m3 Treatment: 125 mg/m3 V Sex: Males Animal Ref Microscopic & Macroscopic Findings 637829 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LONGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX - 171- Company Sanitized. Does not contain TSCA CBf H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637830 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, mild. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, mild. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, STERNUM, BONE MARROW, NOSE I & II - 172- Cewapanj? Sani!feed. Does not eoRfafe TSC C li H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637831 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. NOSE I & II : HYPERTROPHY, GOBLET CELL, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : KIDNEYS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, BONE MARROW - 173 - Gomoany SaitHhed. Does not contain TSfiA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637832 Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : EPIDIDYMIDES : DISCOLORATION, TAN, FIRM, TAIL. No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LONGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PHARYNX/LARYNX : NECROSIS, CARTILAGE, minimal. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL, minimal. NOSE I & II : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/HYPERTROPHY, RESPIRATORY, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, STERNUM, BONE MARROW -174- C@mpany Sanitized. Does nSesraiaSn TSC C ll H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 In d iv id u a l Animal L is tin g Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref M icroscopic & Macroscopic Findings 637833 - Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : . LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PARATHYROID GLANDS : NOT PRESENT. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, minimal. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, minimal. NOSE I & II : DEGENERATION/NECROSIS, OLFACTORY, minimal. HYPERPLASIA/HYPERTROPHY, RESPIRATORY, minimal. HYPERTROPHY, GOBLET CELL, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, TRACHEA, ESOPHAGUS, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, STERNUM, BONE MARROW - 175 - Company Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 In d iv id u a l Animal L is tin g Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637834 . Terminal Sacrifice Killed on Day : 11 Exposure Group : MAIN Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE H istopathology : , LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : HYPERTROPHY, BRONCHIOLAR EPITHELIAL CELL, minimal. INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. PARATHYROID GLANDS : NOT PRESENT. PHARYNX/LARYNX : METAPLASIA, SQUAMOUS, minimal. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, minimal. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, minimal. NOSE III & IV : HYPERTROPHY, GOBLET CELL, minimal. No Microscopic Abnormality Observed : HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, TRACHEA, ESOPHAGUS, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, STERNUM, BONE MARROW, NOSE I & II . -176- ontosBiy Sanitized. Does notcontain TSC CBt H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 rag/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637835 - Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LONGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENOM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. No Microscopic Abnormality Observed : LUNGS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV - 177- SsnllmL Deanet contain TSCA CBi H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637836 _ Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. PHARYNX/LARYNX : NECROSIS, CARTILAGE, minimal. No Microscopic Abnormality Observed : LUNGS, TESTES, NOSE I & II, NOSE III & IV - 178- Compai Sanitized. Does not contain TSCA CBI H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637837 . Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. PHARYNX/LARYNX : NECROSIS, CARTILAGE, minimal. No Microscopic Abnormality Observed : LUNGS, TESTES, NOSE I & II, NOSE III & IV -179- wnpMf Sanitized Does no! contain T1CCBS H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637838 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : HYDRONEPHROSIS, UNILATERAL, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, CENTRIACINAR, minimal. No Microscopic Abnormality Observed : PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -180- Company Sanitized. Does not contain TAC1 H-24267: Two-Week Inhalation Toxicity Study in Male Rats DuPont-4292 Individual Animal Listing Dose Group : VII - 600 mg/m3 Treatment: 600 mg/m3 VII Sex: Males Animal Ref Microscopic & Macroscopic Findings 637839 Terminal Sacrifice Killed on Day : 25 Exposure Group : RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SPLEEN, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S), PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, STERNUM, NOSE Histopathology : , LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, PHARYNX/LARYNX, TESTES, NOSE I & II, NOSE III & IV -181fflMpf i IS zed ,, e8 not cortain TSCA C
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