## F INAL REPORT

Study Title 

## REPEATED DOSE 28

- DAY ORAL TOXICITY ST UDY WITH

M

- (2,3

- EPOXYPROPOXY)

- N,N

- BIS(2,3

- EPOXYPROPYL)ANILINE

BY DAILY GAVAGE

IN THE RAT

Author

Dr. C.G.M. Beerens

- Heijnen

Test Facility

WIL Research Europe B.V. Hambakenwetering 7 5231 DD ‘s

- Hertogenbosch The Netherlands

Laboratory Project Identification

Project 501432 Substance 204415/Am-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 2 - 1. CONTENTS

1. CONTENTS

...................................................................................................................................... 2 2. STATEMENT OF GLP COMPLIANCE

............................................................................................. 3 3. LEAD QUALITY ASSURANCE STATEMENT

.................................................................................. 4 4. SUMMARY

................................................................ ........................................................................ 5 5. INTRODUCTION

.............................................................................................................................. 7 5.1. Preface

..................................................................................................................................... 7 5.2. Study plan

................................................................................................................................ 7 5.3. Aim of the study

....................................................................................................................... 8 5.4. Guidelines

................................................................................................................................ 8 5.5. Storage and retention of records and materials

....................................................................... 8 6. MATERIALS AND METHODS

.......................................................................................................... 9 6.1. Test substance

......................................................................................................................... 9 6.1.1. Test substance information

............................................................................................. 9 6.1.2. Study specific test substance information

...................................................................... 9 6.1.3. Test substance preparation

............................................................................................ 9 6.1.4. Chemical analysis of dose preparations

......................................................................... 9 6.2. Test system

............................................................................................................................ 10 6.3. Al location

................................................................................................................................ 10 6.4. Animal husbandry

.................................................................................................................. 10 6.5. Treatment

............................................................................................................................... 11 6.6. Observations

.......................................................................................................................... 11 6.7. Clinical laboratory investigations

............................................................................................ 12 6.8. Pathology

............................................................................................................................... 13 6.8.1. Necropsy

....................................................................................................................... 13 6.8.2. Organ weights

............................................................................................................... 14 6.8.3. Histotechnology

............................................................................................................ 14 6.8.4. Histopathology

.............................................................................................................. 14 6.9. Electronic data capture

.......................................................................................................... 14 6.10. Interpretation

.......................................................................................................................... 15 6.11. List of deviations

.................................................................................................................... 15 6.11.1. List of protocol deviations

........................................................................................ 15 6.11.2. List of standard operating procedures deviations

.................................................... 15 7. RESULTS

....................................................................................................................................... 16 7.1. Analysis of dose preparations (see also APPENDIX 3)

......................................................... 16 7.2. Observations

.......................................................................................................................... 16 7.2.1. Mortality

........................................................................................................................ 16 7.2.2. Clinical signs

................................................................................................................. 16 7.2.3. Functional observations

................................................................................................ 16 7.2.4. Body weights

................................................................................................................. 16 7.2.5. Food consumption

........................................................................................................ 17 7.3. Clinical laboratory investigations

............................................................................................ 17 7.3.1. Haematology

................................................................................................................. 17 7.3.2. Clinical biochemistry

..................................................................................................... 17 7.4. Pathology

............................................................................................................................... 18 7.4.1. Macroscopic examination

............................................................................................. 18 7.4.2. Organ weights

............................................................................................................... 19 7.4.3. Microscopic examination (see also APPENDIX 4)

....................................................... 19 8. DISCUSSION AND CONCLUSION

................................................................................................ 21 9. REFERENCES

............................................................................................................................... 23

APPENDICES

APPENDIX 1 FIGURES AND SUMMARY TABLES APPENDIX 2 INDIVIDUAL DATA TABLES APPENDIX 3 FORMULATION ANALYSIS REPORT APPENDIX 4 HISTOPATHOLOGY REPORT APPENDIX 5 SUMMARY OF DOSE RANGE FINDING STUDYm-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 5 - 4. SUMMARY

Title Repeated dose 28-day oral toxicity study with m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline by daily gavage in the rat.

Guidelines The study was based on the following guidelines. - EC No 440/2008, B.7 Repeated Dose (28 days) Toxicity (oral), 2008. - OECD 407, Repeated Dose 28-day Oral Toxicity Study in Rodents, 2008. - OPPTS 870.3050, Repeated dose 28-day oral toxicity study in rodents. Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712-C- 00 -366, 2000.

Rationale for dose levels Based on the results of a 5- to 10 -day range finding study (Project 501433; See APPENDIX 5) , the dose levels for this 28-day oral gavage study were selected to be 0, 50

, 150 and 450 mg/kg.

Study outline The test substance, formulated in propylene glycol, was administered daily for 28 days by oral gavage to SPF-bred Wistar rats. One control group and three treated groups were tested, each consisting of 5 males and 5 females.

Evaluated parameters Chemical analyses of formulations were conducted once during the study to assess accuracy, ho mogeneity and stability over 6 hours. The following parameters were evaluated: clinical signs daily; functional observation tests in week 4 ; body weight and food consumption weekly; clinical pathology and macroscopy at termination; organ weights and histopathology on a selection of tissues.

RESULTS

Formulation analyses confirmed that formulations of test substance in propylene glycol were prepared accurately and homogenously, and were stable over at least 6 hours.

No mortality occurred in the study.

At 50 mg/kg, treatment resulted in changes in the gastro-intestinal tract and changes in organ weights of the male reproductive system.

The local gastro-intestinal tract findings were noted consisting of hemorrhage and hypertrophy with villous stunting in the duodenum in males and females. In addition, lymphoid atrophy in the Peyer’s patches and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes was noted.

At 150 mg/kg, treatment resulted in clinical signs, changes in the gastro-intestinal tract, changes in blood parameters, changes in the reproductive organs of females, changes in organ weights of the male reproductive system and slight changes in the adrenal glands.

During the in-life phase, hunched posture (with or without lethargy) was observed in all animals on two treatment days. Local effects in the gastro-intestinal tract consisted of hemorrhage in the duodenum, hypertrophy with villous stunting, gelatinous content and thickened wall in the duodenum and in the jejunum. In the stomach effects included ulcer, hyperplasia, foci and irregular surface of the forestomach. In addition, lymphoid atrophy in the Peyer’s patches, increased mast cells in the mesenteric lymph node, lymphoid hyperplasia of the pancreatic lymph node and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes were noted. Centrilobular hypertrophy in the liver was noted in one female, although not correlating to higher liver weight or effects at the macroscopicm-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 6 - examinations. Changes in the female reproductive organs consisted of atrophy of the uterus (with lower uterus weight), cervix and vagina. Effects on blood parameters included higher bilirubin, potassium, cholesterol and bile acid levels in males and/or females.

At 450 mg/kg , treatment resulted in poor health status of the animals during the study period, in changes in the gastro-intestinal tract, changes in blood parameters, changes in the male and female reproductive organs and in changes in liver and renal system

.

Reduced b ody weight gain and food consumption, reduced motor activity and several symptoms indicative of ill health including lethargy, hunched posture, piloerection, pale faeces, lean appearance and ptosis were noted among all animals. All animals survived the scheduled study duration. Local effects in the gastro-intestinal tract consisted of hemorrhage and hypertrophy with villous stunting, gelatinous content and thickened wall in the duodenum and in the jejunum. In the stomach effects included ulcer, hyperplasia, foci and irregular surface of the forestomach. In addition, lymphoid atrophy in the Peyer’s patches, increased mast cells in the mesenteric lymph node, lymphoid hyperplasia of the pancreatic lymph node and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes were noted. Changes in the reproductive organs consisted of atrophy in the uterus, cervix and vagina (macroscopically seen as reduced size and/or weight of ovaries and uterus), a small prostate gland (with normal histology), and reduced contents of the seminal vesicles and coagulating glands were noted

. Macroscopically

, a reduced size and weight of the prostate and seminal vesicles was observed. Other mi croscopic findings consisted of centrilobular hypertrophy in the liver (correlating to higher liver weight), discoloration of kidney, vacuolation of the zona fasciculata of the adrenal glands (with macroscopic discolouration

, enlargement and increase in weight) , and lymphoid hyperplasia of the renal lymph nodes (macroscopically supported by enlargement)

. Effects on blood parameters consisted of changes in red blood cell parameters, platelet counts and activated partial thromboplastin time, and higher bilirubin, cholesterol, potassium and bile acid levels, and lower albumin, creatinine, glucose, sodium and chloride levels in one or both sexes.

The lower prostate and seminal vesicle weight observed at 50 and 150 mg/kg was slight in nature and had no microscopic correlate. As such they were considered not adverse at these dose levels.

The shift in type of white blood cells (i.e. higher neutrophil counts with lower lymphocyte counts observed in males at 150 and 450 mg/kg and females at 50, 150 and 450 mg/kg) was considered to be re lated to the lymphoid atrophy in the thymus and spleen as recorded at 450 mg/kg. This lymphoid atrophy was considered to be a secondary non-specific response to stress associated with treatment. Therefore, the change in white blood cells may be considered not to be of primary toxicological significance.

CONCLUSION

Based on the local effects in the gastrointestinal tract (duodenum, P eyer’s patches and lymph nodes)

, likely to be secondary effects due to the irritation potential of the test substance, starting at the lowest dose level of 50 mg/kg/day, a local No Observed Adverse Effect Level (NOAEL) could not be established in this study.

The systemic NOAEL is considered to be 50 mg/kg/day, essentially based on atrophy of the female reproductive organs (uterus, cervix and vagina) observed at 150 mg/kg/day.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 7 - 5. INTRODUCTION

Information concerning the dose range finding study (project 501433) is given in APPENDIX 5.

5.1. Preface

Sponsor Huntsman Advanced Materials (Switzerland) GmbH Conta ct person: Dr. Rita Petschel Klybeckstrasse 200 4057 BASEL Switzerland

Study Monitor Mr. Matthieu Ott

Study Director Dr. C.G.M. Beerens

- Heijnen WIL Research Europe B.V. Hambakenwetering 7 5231 DD 's

- Hertogenbosch The Netherlands Tel: +31 7 3 640 6700 Fax: +31 73 640 6799 Email: chantal.beerens@wilresearch.com

Coordinating Biotechnician C. Gerritsen ( WIL Research Europe B.V.)

Clinical Pathology Dr. M. Stitzinger (WIL Research Eu rope B.V.)

Analytical Chemistry Dr. Ir. E. Baltussen (Principal Scientist, WIL Research Europe B.V.)

Necrops y Ing T.A. Mijnders (WIL Research Europe B.V .)

Histotechnology W. Verhoef (WIL Research Europe B.V.)

Histopathology Drs. J.F.M. Len sen (Principal Scientist, WIL Research Europe B.V )

QA C.J. Mitchell, B.Sc. ( WIL Research Europe B.V.): christine.mitchell@wilresearch.com

Test facility Management H.H. Emmen, M.Sc. ( WIL Rese arch Europe B.V.): harry.emmen@wilresearch.com

Test Facility WIL Research Europe B.V. Hambakenwetering 7 5231 DD ‘s

- Hertogenbosch The Netherlands

5.2. Study plan

Experimental starting date 27 October 2012 (allocation dose range finding study )

Treatment 09 November 2012 to 0 6 December 2012 Blood sampling 07 December 2012 Necropsy 07 December 2012

Experimental completion date 07 December 2012 (end o f in

- life phase)m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 8 - 5.3. Aim of the study

The nature and purpose of this toxicity study was to assess the toxic potential of the test substance when administered to rats by daily oral gavage for a period of 28 days. A No Observed Adverse Effect Level (NOAEL) was evaluated.

This study should provide a rational basis for toxicological risk assessment in man. The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test substance.

5.4. Guidelines

As required by the Dutch Act on Animal Experimentation (February 1997), the protocol was reviewed and agreed by the Animal Welfare Officer and the Ethical Committee (DEC 97- 03 -15). The study procedures described in this report were based on the following guidelines:

1. Co mmission regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and other Health Effects; B.7: "Repeated Dose (28 days) Toxicity (oral)". Official Journal of the European Union No. L142, May 2008.

2. Organization for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Section 4, Health Effects, No. 407: "Repeated Dose 28-day Oral Toxicity Study in Rodents", Paris Cedex, 03 October 2008.

3. United States Environmental Protection Agency (EPA). Health Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28-day oral toxicity study in rodents. Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712-C- 00 -366, July 2000.

5.5. Storage and retention of records and materials

Records and materials pertaining to the study including protocol, raw data, specimens (except specimens requiring refrigeration or freezing) and the final report are retained in the WIL Research Europe archives for a period of at least 10 years after finalization of the report. After this period, the sponsor will be contacted to determine how the records and materials should be handled. WIL Research Europe will retain information concerning decisions made.

Those specimens requiring refrigeration or freezing will be retained by WIL Research Europe for as long as the quality of the specimens permits evaluation but no longer than three months after finalization of the report.

WIL Research Europe will retain a test substance sample until the expiry date, but no longer than 10 years after finalization of the report. After this period the sample will be destroyed.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 9 - 6. MATERIALS AND METHODS

6.1. Test substance

6.1.1. Test substance information

Identification m

- (2,3

- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline Description Clear slightly yellow very v iscous liquid Batch AAB0581300 Purity/Composition 100% Mono constituent substance Test substance storage In refrigerator (2

- 8 ° C) in the dark Stability under storage conditions Stable Expiry date 10 April 2013

6.1.2. Study specific test substance information

Purity/composition correction factor required No

Hygroscopic Not indicated Volatile Yes, vapour pressure: <13 Pa at 293K Specific Gravity / Density 1.215

- 1.225 g/cm 3 (25 ° C) pH (1% in water, indicative range) 7.9

- 8.6 (determined at WIL Resea rch Europe B.V.) Stability at higher temperatures Yes, maximum temperature: 50 ° C, maximum duration: 1 h Stability in vehicle:

 Propylene glycol Stable at a concentration range of 1 to 90 mg/g during storage at room temperature under normal laboratory light conditions for at least 6 hours

. Solubility in vehicle:

 Propylene glycol Not indicated

6.1.3. Test substance preparation

Vehicle Propylene glycol (Merck, Darmstadt, Germany), specific gravity 1.036.

Rationale for vehicle Based on trial formulations performed at WIL Research Europe and on information provided by the sponsor.

Method of formulation Formulations (w/w) were prepared daily within 6 hours prior to dosing, and were homogenized to visually acceptable levels. Adjustment was made for specific gravity/density of the test substance (1.220, average of range 1.215-1.225 g/cm 3 ) and specific gravity of the vehicle. No correction was made for the purity of the test substance.

Storage conditions At ambient temperature.

6.1.4. Chemical analysis of dose preparations

Analyses were conducted on a single occasion during the treatment phase, according to a validated method (project 501424). Samples of formulations were analyzed for homogeneity (highest and lowest concentration) and accuracy of preparation (all concentrations). Stability in vehicle over 6 hours at room temperature under normal laboratory light conditions was also determined (highest and lowest concentration).

The accuracy of preparation was considered acceptable if the mean measured concentrations were 85 -115% for suspensions. Homogeneity was demonstrated if the coefficient of variation was ≤ 10%. Formulations were considered stable if the relative difference before and after storage was maximally 10%.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 10 - 6.2. Test system

Test system Rat: Crl:WI(Han) (outbred, SPF-Quality).

Rationale Recognized by international guidelines as the recommended test system (e.g. EPA, FDA, OECD and EC).

Source Charles River Deutschland, Sulzfeld, Germany.

Total number of animals 20 males and 20 females (females were nulliparous and non-pregnant).

Age at start of treatment Approximately 6 weeks.

Identification Earmark and tattoo.

Randomization By computer-generated random algorithm according to body weight, with all animals within ± 20% of the sex mean.

Acclimatization period At least 5 days before the start of treatment under laboratory conditions.

Health inspection Upon receipt of the animals.

6.3. Allocation

Group Dose level 1 Dose volume Number of animals Animal numbers

mg/kg mL/kg Males Females Males Females 1 0 (vehicle) 5 5 5 1

- 5 21

- 25 2 50 5 5 5 6

- 10 26

- 30 3 150 5 5 5 11

- 15 31

- 35 4 450 5 5 5 16

- 20 36

- 40
1 Dose levels we re based on results of a dose range finding study with m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline (project 50143 3 ). A summary of the results is included in this report (see APPENDIX 5 )

.

6.4. Animal husbandry

Room number A0 .10 (A0.23 for motor activity measurements).

Conditions Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation Group housing of 5 animals per sex in Macrolon cages (MIV type, height 18 cm) with sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lilico & Son (Wonham Mill Ltd), Surrey, United Kingdom). During locomotor activity monitoring, animals were housed individually in a Hi-temp polycarbonate cage (Ancare corp., USA; dimensions: 48.3 x 26.7 x 20.3 cm) without cage-enrichment or bedding material.

Diet Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany). During motor activity measurements, animals had no access to food.

Water Free access to tap water except during motor activity measurements.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 11 - Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

6.5. Treatment

Method Oral gavage, using a plastic feeding tube. Formulations were placed for at least 10 minutes on a magnetic stirrer during dosing.

Dose volume 5 mL/kg body weight. Actual dose volumes were calculated weekly according to the latest body weight.

Frequency Once daily, 7 days per week, approximately the same time each day wit h a maximum of 6 hours difference between the earliest and latest dose.

Duration of treatment At least 28 days. Animals were dosed up to the day prior to necropsy.

6.6. Observations

Mortality / Viability At least twice daily.

Clinical signs At least once daily from start of treatment onwards, detailed clinical observations were made in all animals immediately (0 -15 minutes) after dosing (as no peak effect of clinical signs occurred in the range finding study, see APPENDIX 5) . Once prior to start of treatment and at weekly intervals, this was also performed outside the home cage in a standard arena. The time of onset, grade and duration of any observed signs were recorded. Signs we re graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) w as scored. In the data tables, the scored grades ar e reported, as well as the percentage of animals affected in summary tables.

Functional Observations During week 4 of treatment, the following tests were performed on all animals. - hearing ability (HEARING), pupillary reflex (PUPIL L/R), static righting reflex (STATIC R) and grip strength (GRIP) (Score 0 = normal/present, score 1 = abnormal/absent). - locomotor activity (recording period: 1-hour under normal laboratory light conditions, using a computerized monitoring system, Kinder Scientific LLC, Poway, USA). Total movements and ambulations are reported. Ambulations represent movements characterized by a relocation of the entire body position like walking, whereas total movements represent all movements made by the animals, including ambulations but also smaller or more fine movements like grooming, weaving or movements of the head. No specific time for functional observations was applied

, as no peak effect of cli nical signs occurred in the range finding study, see APPENDIX 5.

Body weights Weekly.

Food consumption Weekly.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 12 - Water consumption Subjective appraisal was maintained during the study, but no quantitative investigation introduced as no effect was suspected.

6.7. Clinical laboratory investigations

Blood samples were collected under anaesthesia using isoflurane (Abbott B.V., Hoofddorp, The Netherlands) between 7.00 and 10.30 a.m. on the day of necropsy at the end of the treatment

. Animals were deprived of food overnight (for a maximum of 24 hours), but water was available. Blood samples were drawn from the retro-orbital sinus and collected into tubes (Greiner Bio-One GmbH, Kremsmünster, Austria) prepared with EDTA for haematological parameters (0.5 mL), with citrate for clotting tests (0.45 mL) and Li-heparin treated tubes for clinical biochemistry parameters (0.5 mL). An additional blood sample (0.25 mL) was collected into untreated tubes for determination of bile acids. The following parameters were determined:

Parameter Abbreviation Unit

Haematology a White blo od cells WBC 10 9 /L Differential leucocyte count %WBC neutrophils, lymphocytes, monocytes, eosinophils, basophils Red blood cells 10 12 /L Reticulocytes %RBC %RBC Red blood cell distribution width RDW % Haemoglobin mmol/L Haematocrit L/L Mean corpuscular volume MCV fL Mean corpuscular haemoglobin MCH fmol Mean corpuscular haemoglobin concentration MCHC mmol/L

Platelets 10 9 /L

Clotting Potential b
Prothrombin time PT s Activated Partial thromboplastin time APTT s

Clinical Biochemistry c Alanine aminotransferase ALAT U/L Aspartate aminotransferase ASAT U/L Alkaline phosphatase ALP U/L Total Protein g/L Albumin g/L Total Bilirubin μmol/L Urea mmol/L Creatinine μmol/L Glucose mmol/L Cholesterol mmol/L Sodi um mmol/L Potassium mmol/L Chloride mmol/L Calcium mmol/L Inorganic Phosphate Inorg. Phos mmol/L

a Instrumentation: ADVIA 120 (Siemens Healthcare Diagnostics B.V., Breda, The Netherlands ).

b Instrumentation: STA Compact (Diagnostica Stago S.A.S., Asnières, France).

c Instrumentation: Olympus AU400 (Beckman Coulter Nederland B.V., Woerden, The Netherlands ). Bile acids μmol/Lm-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 13 - 6.8. Pathology

6.8.1. Necropsy

All animals were deeply anaesthetized using isoflurane (Abbott B.V., Hoofddorp, The Netherlands) and subsequently exsanguinated and subjected to a full post mortem examination. Animals were deprived of food overnight (with a maximum of 24 hours) prior to scheduled necropsy. All animals assigned to the study were necropsied and descriptions of all macroscopic abnormalities recorded. Samples of the following tissues and organs were collected from all animals at necropsy and fixed in 10% buffered formalin (neutral phosphate buffered 4% formaldehyde solution, Klinipath, Duiven, The Netherlands):

Identifi cation marks: not processed Ovaries Adrenal glands (Pancreas) (Aorta) Peyer's patches [jejunum, ileum] if detectable Brain [cerebellum, mid

- brain, cortex] (Pituitary gland) Caecum (Preputial gland) Cervix Prostate gland (Clitoral gland) Rectum Colon (Salivary glands

- mandibular, sublingual) Duodenum Sciatic nerve Epididymides * Seminal vesicles including coagulating gland Eyes (including optic nerve [if detectable] and harderian gland) * Skeletal muscle (Skin) (Female mammary gland area) Spinal cord

- cervical, midthoracic, lumbar Femur including joint Spleen Heart Sternum with bone marrow Ileum Stomach Jejunum Testes * Kidneys Thymus (Larynx) Thyroid including parathyroid [if detectable] (Lacrimal gland, exorbital) (Tongue) Liver Trachea Lung, infused with formalin Urinary bladder Lymph nodes

- mandibular, mesenteric Uterus (Nasopharynx) Vagina (Oesophagus) All gross lesions

* Fixed in modified Davidson's solution, prepared at WIL Research Europe using Formaldehyde 37-40%, Ethanol, Acetic acid - glacial (all Merck, Darmstadt, Germany) and Milli-Ro water (Millipore Corporation, Bedford, USA). Tissues were transferred to formalin after fixation for at least 24 hours.

Tissues/organs mentioned in parentheses were not examined by the pathologist, since no signs of toxicity were noted at macroscopic examination.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 14 - 6.8.2. Organ weights

The following organ weights and terminal body weight were recorded from all animals on the scheduled day of necropsy:

Adrenal glands Spleen Brain Testes Epid idymides Thymus Heart Uterus (including cervix) Kidneys Prostate 1
Liver Seminal vesicles including coagulating glands 1
Ovaries Thyroid including parathyroid 1

1 weighed when fixed for at least 24 hours.

6.8.3. Histotechnology

All organ and tissue samples, as defined under Histopathology (following), were processed, embedded in paraffin wax (Klinipath, Duiven, The Netherlands), cut at a thickness of 2-4 micrometers and stained with haematoxylin and eosin (Klinipath, Duiven, The Netherlands).

6.8.4. Histopathol ogy

The following slides were examined by a pathologist: - all tissues collected at the scheduled sacrifice from all group 1 and 4 animals,- the following organs of all males and/or females of group 2 and 3, based on (possible) treatmentrelated changes in these organs in group 4 : Thymus, stomach, duodenum, jejunum, p eyer’s patches

, spleen, mesenteric lymph node , m andibular lymph nodes, adrenal glands, femur including joint

, prostate gland, seminal vesicles

, coagulating glands

, liver , u terus, cervix and vagina, - all gross lesions.

All abnormalities were described and included in the report. An attempt was made to correlate gross observations with microscopic findings.

Histopathology was subjected to a peer review.

6.9. Electronic data capture

Observations/measurements in the study were recorded electronically using the following programme(s): - REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, USA): Environmental monitoring. - TOXDATA version 8.0 (WIL Research Europe B.V., ‘s -Hertogenbosch, The Netherlands): Mortality / Clinical signs / Body weights (Body weight for health monitoring purposes were recorded manually) / Food consumption / Organ weight s. - Motor Monitor version 08356-14 (Kinder Scientific LLC, Poway, USA): Motor activity measurement - Advia 120 version V.3.1.8.0.MS (Siemens Healthcare Diagnostics B.V., Breda, The Netherlands): Haematology - STA Compact® version 107.07 (Diagnostica Stago S.A.S., Asnières, France): Clotting parameters. - Olympus AU 400 version 8.2A (Beckman Coulter Nederland B.V., Woerden, The Netherlands ): Clinical biochemistry. - Pathdata version 6.2D (Pathology Data Systems, Basel, Switzerland): Histopathology - Empower version 7.00 (Waters, Milford, MA, USA): Formulation analysism-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 15 - 6.10. Interpretation

The following statistical methods were used to analyze the data:

 If the variables could be assumed to follow a normal distribution, the Dunnett-test (Ref. 1; manyto -one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.

 The Steel-test (Ref. 2; many- to -one rank test) was applied if the data could not be assumed to follow a normal distribution.

 The Fisher Exact-test (Ref. 3) was applied to frequency data.

 The Kruskal-Wallis nonparametric ANOVA test (Ref. 4) was applied to motor activity data to determine intergroup differences. In case intergroup differences were seen, the Wilcoxon test (Ref. 5) was applied to compare the treated groups to the control group.

All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables. Test statistics were calculated on the basis of exact values for means and pooled variances. Individual values, means and standard deviations may have been rounded off before printing. Therefore, two groups may display the same printed means for a given parameter, yet display different test statistics values.

6.11. List of deviations

6.11.1. List of protocol deviations

1 Prior to necropsy t he terminal body weight of animal nos. 26, 27 and 28 was not determined

. Evaluation: S ufficient information is available to evaluate the organ weight data in t his study.

The study integrity was not adversely affected by the deviation.

6.11.2. List of standard operating procedures deviations

Any deviations from standard operating procedures were evaluated and filed in the study file. There were no deviations from standard operating procedures that affected the integrity of the study.m- (2,3

- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline Project 501432

- Page 16 - 7. RESULTS

For further detail on summary data, see APPENDIX 1 and on individual data, see APPENDIX 2

.

7.1. Analysis of dose preparations (see also APPENDIX 3 )

The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement with target concentrations (i.e. mean accuracies between 85% and 115%). No test substance was detected in the Group 1 formulation. The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%). Formulations at the entire range were stable when stored at room temperature under normal laboratory light conditions for at least 6 ho urs.

7.2. Observations

7.2.1. Mortality

No mortality occurred during the study period.

7.2.2. Clinical signs

At 450 mg/kg, le thargy, hunched posture, piloerection, pale faeces, lean appearance and ptosis were noted among all animals during the study period.

At 150 mg/kg h unched posture (with or without lethargy) was observed in all animals on two treatment days.

Salivation seen after dosing among animals of the 50, 150 and 450 mg/kg dose group during the treatment period was considered to be a physiological response rather than a sign of systemic toxicity considering the nature and minor severity of the effect and its time of occurrence (i.e. after dosing). This sign may be related to irritancy/taste of the test substance.

Other findings that were noted in these animals consisted of rales , chromodacryorrhoea and scabs on the shoulder

. These findings were observed in individual animals only and were considered to be within the normal range of biological variation for rats of this age and strain.

7.2.3. Functional observations

A l ower motor activity was recorded for males and females at 450 mg/kg, as shown by a statistically significant l ower number of total movements and ambulation s ( ambulation counts not statistically significant in males)

. This difference appeared essentially confined to the habituation phase (i.e. the first 10 minutes of the measurement). The other groups showed a normal motor activity habituation profile with high activity in the first interval that decreased over the duration of the test period.

Hearing ability, pupillary reflex, static righting reflex and grip strength were normal in all animals.

7.2.4. Body weights

All animals at 450 mg/kg showed lower body weight gain compared to control animals throughout the treatment period

. Slight body weight loss (up to

- 4% ) was noted in three males at 450 mg/kg during the first week, which slightly recovered thereafter. B ody weight loss (up to

- 10%) was also noted in f our females at 450 mg/kg in Week 4 when compared to Week 3

. Mean body weights at the end of the treatment period were approximately 40 and 20% lower than controls in males and females respectively.

No treatment

- related findings on body weights and body weight gain were noted at 50 and 150 mg/kg. The slight lower body weight gain observed in males treated at 150 mg/kg (achieving a level of statistical significance for weight gain) w as slight and within the normal range of variation. Therefore th is finding w as considered to be of no toxicological relevance.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 17 - 7.2.5. Food consumption

At 450 mg/kg, food consumption before or after correction for body weight was lower than controls in males and females throughout the treatment period.

No toxicologically significant changes in food consumption before or after correction for body weight were noted at 50 and 150 mg/kg.

7.3. Clinical laboratory investigations

7.3.1. Haematology

Treatment with 50 mg/kg resulted in the following (statistically significant) changes in haematology parameters, compared to controls: - Higher relative neutrophil count in females

Treatment with 150 mg/kg resulted in the following (statistically significant) changes in haematology parameters, compared to controls: - Higher relative neutrophil count in males and females - Lower relative lymphocyte count in males and in females (not statistically significant for females)

Treatment with 450 mg/kg resulted in the following (statistically significant) changes in haematology parameters, compared to controls: - Higher relative neutrophil count in males and females - Lower relative lymphocyte count in males and females (not statistically significant for females) - Higher relative monocyte count in females - Lower red blood cell count in males and females - Higher reticulocyte count in males and females - Higher red blood cell distribution width (RDW) in males - Lower haemoglobin level in males and females - Lower haematocrit in males and females (not statistically significant for females) - Lower mean corpuscular h ae moglobin concentration (MCHC) in males (not statistically significant ) and females - Higher platelet count in males and females - Shortened activated partial thromboplastin time (APTT) in males ( not statistically significant) and females

No treatment related changes in haematology parameters were noted in males treated at 50 mg/kg.

7.3.2. Clinical biochemistry

Treatment with 150 mg/kg resulted in the following (statistically significant) changes in clinical biochemistry parameters, compared to control s: - Higher bilirubin level in males (not statistically significant) and females - Higher cholesterol level in females - Higher bile acid level in females (not statistically significant) - Higher potassium level in males and females

Treatment with 450 mg/kg resulted in the following (statistically significant) changes in clinical biochemistry parameters, compared to controls: - Lower albumin level in males and females - Higher bilirubin level in males and females - Lower creatinine level in males and females - Lower glucose level in males and females (not statistically significant for females) - Higher cholesterol level in males and females - Higher bile acid level in males and females ( not statistically significant for females) - Lower sodium level in males - Lower chloride level in males and females - Higher potassium level in females (not statistically significant)m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 18 - No treatment related changes in clinical biochemistry parameters were noted in animals treated at 50 mg/kg.

All other (statistically significant) changes in clinical biochemistry parameters between treated and control animals were considered to be of no toxicological significance as these changes occurred in the absence of a treatment-related distribution and/or were within the normal range of variation.

7.4. Pathology

7.4.1. Macroscopic examination

Treatment with 50 mg/kg resulted in the following macroscopic findings:

- Pancreatic lymph node

, discolouration reddish was noted in 1/5 female.

Treatment with 150 mg/kg resulted in the following macroscopic findings

- Stomach

, forestomach irregular surface was no ted in 5/5 male and 3/5 female.

- Stomach

, forestomach focus/foci, yellowish/tan, reddish/dark red was noted in 1/5 male.

- Duodenum

, wall thickened/dilation was noted in 3/5 male and 3/5 female.

- Duodenum

, contents gelatinous was note d in 3/5 male and 2/5 female.

- Jejunum

, wall thickened/dilation was note d in 2/5 male and 2/5 female.

- Jejunum

, contents gelatinous was noted in 2/5 male and 1/5 female. There was no microscopic correlate to this finding.

- Mesenteric lymph node

, discolouration reddish/dark red/purple was noted in 4/5 male and 2/5 female.

- Pancreatic lymph node

, enlarged was noted in 2/5 male and 1/5 female.

- Pancr eatic lymph node

, discolouration reddish was noted in 1/5 male and 2/5 female.

- Uterus

, reduced in size was noted in 1/5 female.

Treatment with 450 mg/kg resulted in the following macroscopic findings

- Emaciated was noted in 4/5 male and 5/5 female.

- Thymus

, reduced in size was noted i n 5/5 male and 4/5 female.

- Stomach

, forestomach irregular surface was note d in 4/5 male and 5/5 female.

- Stomach

, forestomach focus/foci, yellowish/tan, reddish/dark red was noted in 3/5 female.

- Duodenum

, wall thickened/dilation was noted in 4/5 male and 4/5 female.

- Duodenum

, contents gelatinous was note d in 3/5 male and 1/5 female.

- Jejunum

, wall thickened/dilation was noted in 4/5 male and 4/5 female.

- Jejunum

, contents gelatinous was noted in 4/5 male and 2/5 female. There was no microscopic correlate to this finding.

- Mesenteric lymph node

, discolouration reddish/dark red/purple was noted in 5/5 male and 4/5 female.

- Pancreatic lymph node

, enlarged was noted in 3/5 male and 4/5 female.

- Renal lymph node

, e nlarged was noted in 1/5 male and 1/5 female.

- Adrenal glands

, discolouration pale was noted in 4/5 male and 4/5 female.

- Kidneys

, discolourati on greenish was noted in 5/5 male and 5/5 female.

- Uterus

, reduced in size was noted in 5/5 female.

- Ovaries

, reduced in size was noted in 3/5 female.

- Prostate gland

, reduced in size w as noted in 5/5 male.

- Seminal vesicles

, reduced in size was noted in 5/5 male.

All other macroscopic findings recorded were considered to be within the normal range of background pathology encountered in rats of this age and strain.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 19 - 7.4.2. Organ weights

Treatment with 50 mg/kg resulted in the following organ weight changes, when compared to controls: - Lower prostate weights and a trend towards lower seminal vesicle weights.

Treatment with 150 mg/kg resulted in the following organ weight changes, when compared to controls: - Lower prostate weights, lower prostate to body weight ratio, lower seminal vesicle weights and a trend towards lower seminal vesicle weights to body weight ratio. - Lower uterus weight, lower uterus to body weight ratio (not statistically significant)

Treatment with 450 mg/kg resulted in the following changes in organ weight which were considered to be related to treatment: - Lower terminal body weight in males and females. - Higher liver weights in females and higher liver to body weight ratio in males and females. - Higher adrenal gland weights and higher adrenal gland to body weight ratio in males and females (not statistically significant in females regarding the ratio) - Lower thymus weight and thymus to body weight ratio in males and females - Lower prostate weight and prostate to body weight ratio, seminal vesicles weight and seminal vesicles weight to body weight ratio. - Lower uterus weight and uterus to body weight ratio.

Higher liver and kidney to body weight ratios were noted in males at 150 mg/kg. Lower thymus weight and thymus to body weight ratio was observed in females at 150 mg/kg. In the lack of any relevant corroborative findings at the microscopic examinations, these organ weight changes were considered to be without toxicological significance.

The higher brain, heart, thyroid, kidney, testes and epididymides weight at 450 mg/kg was considered to be related to the lower terminal body weight and occurred in the absence of microscopic correlates. In addition, lower spleen weight in both sexes occurred without any corroborative findings. Therefore, these findings were considered not to be toxicologically relevant.

7.4.3. Microscopic examination (see also APPENDIX 4)

Treatment resulted in the following microscopic findings in males or females starting at 50 mg/kg:

- Duodenum

, hemorrhage was present i n 4/5 male (4 minimal) and 3/5 female (3 minimal) rats at 50 mg/kg, in 3/5 male (3 minimal) and 4/5 female (1 minimal, 3 slight) rats at 150 mg/kg and in 5/5 male (2 minimal, 3 slight) and 4/5 female (2 minimal, 2 slight) rats treated at 450 mg/kg.

- Duodenum

, hypertrophy with villous stunting was present i n 5/5 male (4 minimal, 1 slight) and 5/5 female (2 minimal, 3 slight) rats treated at 50 mg/kg, in 5/5 male (5 slight) and 5/5 female (1 minimal, 3 slight, 1 moderate) rats treated at 150 mg/kg and in 5/5 male (1 slight, 4 moderate) and 5/5 female (4 slight, 1 moderate) rats treated at 450 mg/kg. This finding corresponded with the macroscopic finding wall thickened.

- Peyer’s patches

, lymphoid atrophy was present in 1/5 female (1 slight) treated at 50 mg/kg , i n 1/5 male (1 slight) and 1/5 female (1 moderate) rats treated at 150 and in 3/5 male (2 minimal, 1 slight) and 4/5 female (1 minimal, 3 slight) rats at 450 mg/kg.

- Mesenteric lymph node

, erythrophagocytosis was present in 1/5 male (slight) and 1/5 female (minimal) rats treated at 50 mg/kg, in 5/5 male (3 slight, 2 moderate) and 3/5 female (3 slight) rats at 150 mg/kg and in 5/5 male (5 moderate) and 5/5 female (3 slight, 2 moderate) rats at 450 mg/kg. This finding correlated with the macroscopic finding discolouration reddish/dark red/purple

. Treatment resulted in the following microscopic findings in males or females starting at 150 mg/kg:

- Stomach

, ulcer forestomach was present in 2/5 male rat (1 slight, 1 moderate) treated at 150 mg/kg and in 5/5 male (1 moderate, 4 marked) and 5/5 female (5 marked) rats at 450 mg/kg. This finding corresponded with the macroscopic finding forestomach discoloured focus/foci

.

- Stomach

, hyperplasia forestomach was present at increased incidence and severity in 5/5 male (3 slight, 2 moderate) and 5/5 female (3 minimal, 1 slight, 1 moderate) rats treated at 150 mg/kg and in 5/5 male (2 slight, 3 moderate) and 5/5 female (4 moderate, 1 marked) rats at 450 mg/kg. This finding was present at a background incidence and severity in 1/5 male (minimal) 50 mg/kg treated. This finding corresponded with the macroscopic finding forestomach irregular surface

.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 20 - - Jejunum

, hypertrophy with villous stunting was pres ent in 2/5 male (1 minimal, 1 slight) and 1/5 female (1 minimal) rats at 150 mg/kg and in 5/5 male (3 slight, 2 moderate) and 5/5 female (1 minimal, 4 slight) rats at 450 mg/kg. This finding corresponded with the macroscopic finding wall thickened.

- Mesenteric lymph node

, lymphoid atrophy was present in 3/5 male (3 minimal) and 2/5 female (2 minimal) rats treated at 150 mg/kg and in 5/5 male (1 minimal, 2 slight, 2 moderate) and 4/5 female (2 minimal, 2 slight) rats at 450 mg/kg.

- Mesenteric lymph node

, increased mast cells were present in 5/5 male (3 slight, 2 moderate ) and 3/5 female (3 sl ight) rats treated at 150 mg/kg and in 1/5 male (1 slight) and 2/5 female (2 slight) rats at 450 mg/kg.

- Uterus

, cervix and vagina

, atrophy was present in 2/5 female rats treated at 150 and 5/5 female rats at 45 0 mg/kg.

- Liver

, centrilobular hypertrophy was pres ent in 1/5 female (minimal) at 150 mg/kg and in 5/5 female (1 minimal, 4 slight) rats.

Treatment resulted in the following microscopic findings in males or females at 450 mg/kg:

- Thymus

, lymphoid atrophy was present in 5/5 male ( 1 minimal, 3 slight, 1 marked) and 5/5 female (1 minimal, 2 slight, 2 moderate) rats. This finding corresponded with the macroscopic finding reduced in size

.

- Jejunum

, hemorrhage was presen t in 3/5 male (2 minimal, 1 slight) and 3/5 female (3 slight) rats.

- Spleen

, lymphoid atrop hy was present in 5/5 male (1 minimal, 4 slight) and 1/5 female (minimal) rats.

- Adrenal glands

, vacuolation zona fasciculata was pres ent at increased incidence and severity in 4/5 male (2 minimal, 2 slight) and 4/5 female (1 minimal, 3 slight) rats. This finding was present at a background incidence and severity in 1/5 male (minimal) at 50 mg/kg and 1/5 male (minimal) at 150 mg/kg. This finding corresponded with the macroscopic finding discoloured.

- Femur including joint

, decreased bone, secondary spongiosa was present in 5/5 male (2 slight, 3 moderate) and 5/5 female (1 minimal, 3 slight, 1 moderate) rats. This was likely related to the emaciation

.

- Prostate gland

, small with normal histology was present in 5/5 male rats. This finding corresponded with the macroscopic finding reduced in size

.

- Seminal vesicles

, reduced contents was bilaterally present in 5/5 male (5 slight) rats and, as background finding, it was unilaterally present in 1/5 (moderate) control Group rat. This finding corresponded with the macroscopic finding reduced in size

.

- Coagulating glands

, reduced contents was present in 5/5 male (5 slight) rats.

In addition, there were microscopic findings in organs that were only sampled in animals which showed macroscopic findings at 50, 150 and 450 mg/kg:

- Pancreatic lymph node

, erythrophagocytosis was pres ent in 1/5 female at 50 mg/kg (1 lymph node sampled), in 2/5 female and 1/5 male at 150 mg/kg (3 and 2 lymph nodes sampled respectively) treated rats. This correlated with the macroscopic finding discolouration reddish.

- Pancreatic lymph node

, lymphoid hyperplasia was pres ent 2/5 male and 3/5 female at 150 mg/kg (2 and 3 lymph nodes sampled respectively) and in 3/5 male and 4/5 female at 450 mg/kg (3 and 4 lymph nodes sampled respectively) treated rats. This correlated with the macroscopic finding enlarged.

- Renal lymph node

, lymphoid hyperplasia was present 1/5 male and 1/5 female at 450 mg/kg (both 1 lymph node sampled) treated rats. This correlated with the macroscopic finding enlarged.

All other microscopic findings recorded were considered to be within the normal range of background pathology encountered in rats of this age and strain.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 21 - 8. DISCUSSION AND CONCLUSION

Wistar rats were treated with m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline for 2 8 consecutive days by daily oral gavage at dose levels of 50, 150 and 450 mg/kg.

Formulation analyses confirmed that formulations of test substance in propylene glycol were prepared accurately and homogenously, and were stable over at least 6 hours.

At 50 mg/kg, local gastro-intestinal tract findings were noted consisting of hemorrhage and hypertrophy with villous stunting in the duodenum in males and females. In addition, lymphoid atrophy in the Peyer’s patches and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes was noted.

At 150 mg/kg, during the in-life phase, hunched posture (with or without lethargy) was observed in all animals on two treatment days. Local effects in the gastro-intestinal tract consisted of hemorrhage in the duodenum, hypertrophy with villous stunting, gelatinous content and thickened wall in the duodenum and in the jejunum. In the stomach effects included ulcer, hyperplasia, foci and irregular surface of the forestomach. In addition, lymphoid a trophy in the Peyer’s patches, increased mast cells in the mesenteric lymph node, lymphoid hyperplasia of the pancreatic lymph node and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes were noted. Centrilobular hypertrophy in the liver was noted in one female, although not correlating to higher liver weight or effects at the macroscopic examinations. Changes in the female reproductive organs consisted of atrophy of the uterus (with lower uterus weight), cervix and vagin a. Effects on blood parameters included higher bilirubin, potassium, cholesterol and bile acid levels in males and/or females.

At 450 mg/kg , reduced body weight gain and food consumption, reduced motor activity and several symptoms indicative of ill health including lethargy, hunched posture, piloerection, pale faeces, lean appearance and ptosis were noted among all animals. All animals survived the scheduled study duration. Local effects in the gastro-intestinal tract consisted of hemorrhage and hypertrophy with villous stunting, gelatinous content and thickened wall in the duodenum and in the jejunum. In the stomach effects included ulcer, hyperplasia, foci and irregular surface of the forestomach. In addition, lymphoid atrophy in the Peyer’s patches, i ncreased mast cells in the mesenteric lymph node, lymphoid hyperplasia of the pancreatic lymph node and erythrophagocytosis and/or discolouration in the mesenteric and pancreatic lymph nodes were noted. Changes in the reproductive organs consisted of atrophy in the uterus, cervix and vagina (macroscopically seen as reduced size and/or weight of ovaries and uterus), a small prostate gland (with normal histology), and reduced contents of the seminal vesicles and coagulating glands were noted

. Macroscopically

, a reduced size and weight of the prostate and seminal vesicles was observed. Other mi croscopic findings consisted of centrilobular hypertrophy in the liver (correlating to higher liver weight), discoloration of kidney, vacuolation of the zona fasciculata of the adrenal glands (with macroscopic discolouration

, enlargement and increase in weight) , and lymphoid hyperplasia of the renal lymph nodes (macroscopically supported by enlargement)

. Effects on blood parameters consisted of changes in red blood cell parameters, platelet counts and activated partial thromboplastin time, and higher bilirubin, cholesterol, potassium and bile acid levels, and lower albumin, creatinine, glucose, sodium and chloride levels in one or both sexes.

The lower prostate and seminal vesicle weight observed at 50 and 150 mg/kg was slight in nature and had no microscopic correlate. As such they were considered not adverse at these dose levels.

The shift in type of white blood cells (i.e. higher neutrophil counts with lower lymphocyte counts observed in males at 150 and 450 mg/kg and females at 50, 150 and 450 mg/kg) was considered to be related to the lymphoid atrophy in the thymus and spleen as recorded at 450 mg/kg. This lymphoid atrophy was considered to be a secondary non-specific response to stress associated with treatment. Therefore, the change in white blood cells may be considered not to be of primary toxicological significance.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 22 - CONCLUSION

Based on the local effects in the gastrointestinal tract (duodenum, P eyer’s patche s and lymph nodes)

, likely to be secondary effects due to the irritation potential of the test substance, starting at the lowest dose level of 50 mg/kg/day, a local No Observed Adverse Effect Level (NOAEL) could not be established in this study.

The systemic NOAEL is considered to be 50 mg/kg/day, essentially based on atrophy of the female reproductive organs (uterus, cervix and vagina) observed at 150 mg/kg/day.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 23 - 9. REFERENCES

Ref. 1 C.W. Dunnett, A Multiple Comparison Procedure for Comparing Several Treatments

with a Control, J. Amer. Stat. Assoc. 50, 1096-1121 (1955).

Ref. 2 R.G. Miller, Simultaneous Statistical Inference, Springer Verlag, New York (1981).

Ref. 3 R.A. Fisher, Statistical Methods for Research Workers, Oliver and Boyd, Edinburgh

(1950).

Ref. 4 Kruskal W.H. and Wallis W.A.. Use of ranks in one-criterion variance analysis. Journal

of the American Statistical Association 47 (260): 583-621, December (1952).

Ref. 5 Wilcoxon, F. Individual comparisons by ranking methods. Biometrics

, 1 , 80 -83 (1945).m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 1

- Page 1 - APPENDIX 1 FIGURES AND SUMMARY TABLESProject 501432 APPENDIX 1

− Page 2

− 08Feb13 14h24Project 501432 APPENDIX 1

− Page 3

− 08Feb13 14h24Project 501432 APPENDIX 1

− Page 4

− 08Feb13 14h24Project 501432 APPENDIX 1

− Page 5

− 08Feb13 14h24Project 501432 APPENDIX 1

CLINICAL SIGNS SUMMARY

.: Observation performed, sign not present %: Percent of affected animals (0=less than 5%, 1=between 5% and 15%,..., A=more than 95%) G: Median value of the highest individual daily grades MALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 1 (CONTROL) No clinical signs noted

GROUP 2 (50 MG/KG) Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . . . . . . 2 A A A A A A A A A A A A A A A A

GROUP 3 (150 MG/KG) Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . %: . . . . . . . . . . . . A A

. . . . . . . . . . . . . . Skin / fur

Piloerection (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . %: . . . . . . . . . . . . 2 2

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 %: . . . 2 6 6 4 4 4 6 6 6 A A A A A A A A A A A A A A A A

GROUP 4 (450 MG/KG) Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . %: . . . . . . . . . . . . . 8 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . A A A A A A A A A A A A A A A A A A A A A A Skin / fur

Piloerection (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . 4 A A A A A A A A A A A A 8 A A A A A A A A Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 %: . . . 8 A A A A A A A A A A A A A A A A A A A A A A A A Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . . . . . 6 8 A A A A A A A A A A A A A A A A Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . 1 1 1 1 1 %:

. . . . . . . . . . . . . . . . . . . . . . . 2 2 2 2 A

Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . %: . . . . . . . . . . . . . A . . . . . . .

. . . . . . .

FEMALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 1 (CONTROL) No clinical signs noted

GROUP 2 (50 MG/KG) Breathing

Rales (3) G: . . . . . . . . . . . . . . . . . . 1 1 .

. . . . . . . %: . . . . . . . . . . . . . . . . . . 2 2 .

. . . . . . . Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . . . . . . 6 A A A A A A A A A A A A A A A A

− Page 6

− 08Feb13 15h00Project 501432 APPENDIX 1

CLINICAL SIGNS SUMMARY

.: Observation performed, sign not present %: Percent of affected animals (0=less than 5%, 1=between 5% and 15%,..., A=more than 95%) G: Median value of the highest individual daily grades FEMALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 3 (150 MG/KG) Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . %: . . . . . . . . . . . . A A

. . . . . . . . . . . . . . Breathing

Rales (3) G: . . . . . . . . . . . . . . . . . . 1 . .

. . . . . . . %: . . . . . . . . . . . . . . . . . . 2 . .

. . . . . . . Skin / fur

Scabs (3) G: . . . . . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1

. . .

(Shoulder right) %: . . . . . . . . . . . . . . . . 2 2 2 2 2 2 2 2 2

. . . Secretion / excretion

Salivation (3) G: . . . . 1 1 1 1 1 1 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 %: . . . . 4 6 2 2 2 2 4 4 A A A A A A A A A A A A A A A A

GROUP 4 (450 MG/KG) Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . %: . . . . . . . . . . . . . A . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . 8 8 A A A A A A A A A A A A A A A A A A A A Breathing

Rales (3) G:

. . . . . . . . . . . . . . . . . . . . . . . . 1 1 1 . %:

. . . . . . . . . . . . . . . . . . . . . . . . 2 2 2 . Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . . . . . . . . A A A A A A A 2 2 2 2 2 6 6 8 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 %: . . . 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 Chromodacryorrhoea (3) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1

(Snout) %:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 %: . . . . . . . . . . 8 A A A A A A A A A A A A A A A A A Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . 1 1 1 %:

. . . . . . . . . . . . . . . . . . . . . . . . . 4 4 A

Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . %: . . . . . . . . . . . . . A . . . . . . .

. . . . . . .

− Page 7

− 08Feb13 15h00Project 501432 APPENDIX 1

FUNCTIONAL OBSERVATIONS SUMMARY

+/++ Steel

− test significant at 5% (+) or 1% (++) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

AT WEEK4 HEARING MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

PUPIL L MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

PUPIL R MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

STATIC R MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

GRIP MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

AT WEEK4 HEARING MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

PUPIL L MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

PUPIL R MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

STATIC R MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

GRIP MEDIAN 0 0 0 0 SCORE 0/1 N 5 5 5 5

− Page 8

− 08Feb13 15h00- Page 9 - Project 501432 APPENDIX 1

MOTOR ACTIVITY TEST SUMMARY MALES AT WEEK 4

GROUP 1
CONTROL

Total Movements MEAN 1 2991 4012 3697 1201* ST.DEV 992 1159 1695 417 N 5 5 5 5

Ambulations MEAN 1 625 903 852 338
ST.DEV 249 249 306 126
N 5 5 5 5

*/** Wilcoxon test significant at 5% (*) or 1% (**) level

1 Group mean of all intervals combined

2 Mean counts per interval. GROUP 2
50 MG/KG GROUP 3
150 MG/KG GROUP 4
450 MG/KG

0 200 400 600 800 1000 1200 1400 1600 1800

1 2 3 4 5 6 7 8 9 10 11 12Counts

Interval (5 min) 

### Total Movements Males 2

Group 1
Group 2
Group 3
Group 4

0 50 100 150 200 250 300 350 400 450

1 2 3 4 5 6 7 8 9 10 11 12Counts

Interval (5 min) 

### Ambulations Males 2

Group 1

Group 2

Group 3

Group 4- Page 10 - Project 501432 APPENDIX 1

MOTOR ACTIVITY TEST SUMMARY FEMALES WEEK 4

GROUP 1
CONTROL

MEAN 1 5171 5394 4343 1228* ST.DEV 1246 1104 1568 512 N 5 5 5 5

Ambulations MEAN 1 1345 1609 1313 390*
ST.DEV 311 406 505 196
N 5 5 5 5

*/** Wilcoxon test significant at 5% (*) or 1% (**) level

1 Group mean of all intervals combined

2 Mean counts per interval. Total Movements GROUP 2
50 MG/KG GROUP 3
150 MG/KG GROUP 4
450 MG/KG

0 200 400 600 800 1000 1200 1400 1600 1800

1 2 3 4 5 6 7 8 9 10 11 12Counts

Interval (5 min) 

### Total Movements Females 2

Group 1 Group 2 Group 3 Group 4

0 100 200 300 400 500 600 700

1 2 3 4 5 6 7 8 9 10 11 12Counts

Interval (5 min) 

### Ambulations Females 2

Group 1 Group 2 Group 3 Group 4Project 501432 APPENDIX 1

BODY WEIGHTS (GRAM) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAY 1 MEAN 171 168 170 165 WEEK 1 ST.DEV 5.1 9.6 8.1 9.6 N 5 5 5 5

DAY 8 MEAN 213 206 201 166 ** WEEK 2 ST.DEV 6.6 14.8 11.6 17.4 N 5 5 5 5

DAY 15 MEAN 253 240 236 179 ** WEEK 3 ST.DEV 9.3 19.5 15.2 21.2 N 5 5 5 5

DAY 22 MEAN 284 265 264 187 ** WEEK 4 ST.DEV 14.0 28.6 15.3 21.0 N 5 5 5 5

DAY 28 MEAN 305 281 276 187 ** WEEK 4 ST.DEV 14.4 32.9 15.2 20.7 N 5 5 5 5

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAY 1 MEAN 134 135 138 134 WEEK 1 ST.DEV 5.6 6.5 7.3 6.7 N 5 5 5 5

DAY 8 MEAN 150 155 154 139 WEEK 2 ST.DEV 9.9 8.6 8.6 3.8 N 5 5 5 5

DAY 15 MEAN 171 170 174 149 ** WEEK 3 ST.DEV 11.4 6.8 7.3 1.8 N 5 5 5 5

DAY 22 MEAN 182 183 188 158 ** WEEK 4 ST.DEV 6.9 7.6 12.1 9.3 N 5 5 5 5

DAY 28 MEAN 192 192 192 151 ** WEEK 4 ST.DEV 14.9 11.8 7.8 14.6 N 5 5 5 5

− Page 11

− 08Feb13 15h07Project 501432 APPENDIX 1

BODY WEIGHT GAIN (%) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAY 1 MEAN 0 0 0 0 WEEK 1 ST.DEV 0.0 0.0 0.0 0.0 N 5 5 5 5

DAY 8 MEAN 24 23 18 * 0 ** WEEK 2 ST.DEV 2.0 3.2 1.4 5.6 N 5 5 5 5

DAY 15 MEAN 48 43 39 * 8 ** WEEK 3 ST.DEV 3.2 5.9 4.5 7.8 N 5 5 5 5

DAY 22 MEAN 66 58 55 13 ** WEEK 4 ST.DEV 5.3 10.6 6.0 7.9 N 5 5 5 5

DAY 28 MEAN 78 67 63 * 13 ** WEEK 4 ST.DEV 5.9 12.5 6.7 8.1 N 5 5 5 5

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAY 1 MEAN 0 0 0 0 WEEK 1 ST.DEV 0.0 0.0 0.0 0.0 N 5 5 5 5

DAY 8 MEAN 11 15 11 4 ** WEEK 2 ST.DEV 3.1 2.5 1.0 4.0 N 5 5 5 5

DAY 15 MEAN 28 25 26 12 ** WEEK 3 ST.DEV 4.9 3.7 3.0 6.1 N 5 5 5 5

DAY 22 MEAN 36 35 36 18 ** WEEK 4 ST.DEV 1.0 4.4 3.4 11.3 N 5 5 5 5

DAY 28 MEAN 43 41 39 13 ** WEEK 4 ST.DEV 5.7 5.0 3.3 15.1 N 5 5 5 5

− Page 12

− 08Feb13 15h07Project 501432 APPENDIX 1

FOOD CONSUMPTION (G/ANIMAL/DAY) SUMMARY MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAYS 1

− 8 MEAN 19 18 17 11 WEEKS 1

− 2 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 8

− 15 MEAN 21 20 20 11 WEEKS 2

− 3 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 15

− 22 MEAN 21 21 21 12 WEEKS 3

− 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 22

− 28 MEAN 22 21 21 12 WEEK 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

MEAN OF MEANS OVER TREATMENT MEAN 21 20 20 11

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAYS 1

− 8 MEAN 14 14 13 10 WEEKS 1

− 2 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 8

− 15 MEAN 15 14 14 10 WEEKS 2

− 3 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 15

− 22 MEAN 14 14 14 11 WEEKS 3

− 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 22

− 28 MEAN 15 16 13 10 WEEK 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

MEAN OF MEANS OVER TREATMENT MEAN 14 15 14 10

− Page 13

− 08Feb13 15h07Project 501432 APPENDIX 1

RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY) SUMMARY MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAYS 1

− 8 MEAN 90 87 86 65 WEEKS 1

− 2 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 8

− 15 MEAN 83 82 83 59 WEEKS 2

− 3 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 15

− 22 MEAN 75 78 78 64 WEEKS 3

− 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 22

− 28 MEAN 72 75 76 64 WEEK 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

MEAN OF MEANS OVER TREATMENT MEAN 80 80 81 63

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

TREATMENT DAYS 1

− 8 MEAN 92 91 85 73 WEEKS 1

− 2 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 8

− 15 MEAN 86 83 80 65 WEEKS 2

− 3 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 15

− 22 MEAN 79 79 75 68 WEEKS 3

− 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

DAYS 22

− 28 MEAN 76 81 70 65 WEEK 4 ST.DEV

−−− −−− −−− −−− N (CAGE) 1 1 1 1

MEAN OF MEANS OVER TREATMENT MEAN 83 83 78 68

− Page 14

− 08Feb13 15h07Project 501432 APPENDIX 1

HAEMATOLOGY SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level +/++ Steel

− test significant at 5% (+) or 1% (++) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT WBC MEAN 8.1 7.6 9.3 9.5 10E9/L ST.DEV 1.8 0.8 2.1 2.8 N 5 5 5 5 Neutrophils MEAN 11.2 12.2 30.4 + 76.2 + %WBC ST.DEV 1.9 3.1 8.7 12.6 N 5 5 5 5 Lymphocytes MEAN 85.7 85.0 66.0 + 20.4 + %WBC ST.DEV 2.1 3.5 8.7 11.0 N 5 5 5 5 Monocytes MEAN 2.0 1.7 2.9 3.0 %WBC ST.DEV 0.1 0.4 0.6 1.4 N 5 5 5 5 Eosinophils MEAN 0.8 0.8 0.6 0.3 %WBC ST.DEV 0.2 0.3 0.1 0.3 N 5 5 5 5 Basophils MEAN 0.2 0.3 0.2 0.1 %WBC ST.DEV 0.1 0.1 0.1 0.1 N 5 5 5 5

Red blood cells MEAN 8.13 8.38 7.88 6.77 ** 10E12/L ST.DEV 0.30 0.27 0.28 0.34 N 5 5 5 5 Reticulocytes MEAN 2.5 2.4 2.4 7.4 + %RBC ST.DEV 0.2 0.5 0.6 0.9 N 5 5 5 5

RDW MEAN 11.7 11.4 11.7 14.2 ** % ST.DEV 1.1 0.5 1.4 0.9 N 5 5 5 5 Haemoglobin MEAN 9.7 9.9 9.2 7.8 ** mmol/L ST.DEV 0.1 0.3 0.4 0.8 N 5 5 5 5

Haematocrit MEAN 0.435 0.446 0.421 0.362 ** L/L ST.DEV 0.009 0.016 0.021 0.033 N 5 5 5 5

MCV MEAN 53.6 53.2 53.5 53.4 fL ST.DEV 2.3 0.7 1.6 3.0 N 5 5 5 5

MCH MEAN 1.19 1.18 1.17 1.15 fmol ST.DEV 0.05 0.03 0.03 0.07 N 5 5 5 5

MCHC MEAN 22.20 22.10 21.92 21.56 mmol/L ST.DEV 0.58 0.40 0.61 0.26 N 5 5 5 5

Platelets MEAN 904 934 991 1441 ** 10E9/L ST.DEV 56 103 142 290 N 5 5 5 5

PT MEAN 17.3 16.4 16.8 17.8 s ST.DEV 0.7 0.8 0.9 1.1 N 5 5 5 5

APTT MEAN 15.1 15.1 16.5 12.0 s ST.DEV 2.7 2.1 2.6 2.6 N 5 5 5 5

− Page 15

− 08Feb13 15h07Project 501432 APPENDIX 1

HAEMATOLOGY SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level +/++ Steel

− test significant at 5% (+) or 1% (++) level FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT WBC MEAN 4.5 4.9 5.7 6.5 10E9/L ST.DEV 1.2 1.8 1.7 1.4 N 4 5 5 5 Neutrophils MEAN 8.8 13.7 + 19.5 + 68.9 + %WBC ST.DEV 1.6 3.8 6.0 7.9 N 4 5 5 5 Lymphocytes MEAN 88.4 83.2 76.4 26.8 %WBC ST.DEV 2.2 3.9 6.2 7.8 N 4 5 5 5 Monocytes MEAN 1.6 1.7 2.7 3.7 + %WBC ST.DEV 0.4 0.6 0.8 0.3 N 4 5 5 5 Eosinophils MEAN 1.1 1.2 1.2 0.5 %WBC ST.DEV 0.2 0.2 0.4 0.3 N 4 5 5 5 Basophils MEAN 0.1 0.1 0.1 0.0 %WBC ST.DEV 0.1 0.1 0.1 0.1 N 4 5 5 5

Red blood cells MEAN 7.75 7.71 8.29 6.54 ** 10E12/L ST.DEV 0.25 0.21 0.31 0.78 N 4 5 5 5 Reticulocytes MEAN 2.0 2.3 2.1 6.6 + %RBC ST.DEV 0.4 0.4 0.9 1.4 N 4 5 5 5

RDW MEAN 13.4 10.7 11.3 13.3 % ST.DEV 6.2 0.4 1.5 0.5 N 4 5 5 5 Haemoglobin MEAN 9.1 9.0 9.4 7.6 ** mmol/L ST.DEV 0.4 0.2 0.4 0.9 N 4 5 5 5

Haematocrit MEAN 0.405 0.401 0.425 0.358 L/L ST.DEV 0.008 0.011 0.024 0.046 N 4 5 5 5

MCV MEAN 52.3 51.9 51.2 54.6 fL ST.DEV 2.6 0.8 1.5 1.7 N 4 5 5 5

MCH MEAN 1.18 1.16 1.13 1.16 fmol ST.DEV 0.08 0.02 0.02 0.03 N 4 5 5 5

MCHC MEAN 22.49 22.41 22.08 21.18 ** mmol/L ST.DEV 0.49 0.18 0.36 0.26 N 4 5 5 5

Platelets MEAN 946 881 1050 1311 * 10E9/L ST.DEV 169 114 113 228 N 4 5 5 5

PT MEAN 16.7 16.2 16.4 16.8 s ST.DEV 0.7 0.5 0.7 1.0 N 5 5 5 4

APTT MEAN 15.7 15.2 13.6 12.4 ** s ST.DEV 0.8 1.2 1.8 0.8 N 5 5 5 4

− Page 16

− 08Feb13 15h07Project 501432 APPENDIX 1

CLINICAL BIOCHEMISTRY SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT ALAT MEAN 43.3 39.6 73.9 * 50.9 U/L ST.DEV 10.1 9.7 19.3 23.4 N 5 5 5 5

ASAT MEAN 76.6 77.1 90.6 73.7 U/L ST.DEV 6.5 6.3 20.3 10.1 N 5 5 5 5

ALP MEAN 197 189 175 136 U/L ST.DEV 51 68 33 48 N 5 5 5 5 Total protein MEAN 64.2 63.7 61.3 63.4 g/L ST.DEV 2.5 1.1 2.0 2.4 N 5 5 5 5

Albumin MEAN 32.8 32.7 31.2 29.6 ** g/L ST.DEV 1.3 0.7 1.0 1.2 N 5 5 5 5

Total bilirubin MEAN 2.6 2.4 3.4 4.4 ** umol/L ST.DEV 0.2 0.2 0.7 0.9 N 5 5 5 5

Urea MEAN 8.4 6.3 8.2 8.3 mmol/L ST.DEV 1.8 1.0 0.8 1.4 N 5 5 5 5

Creatinine MEAN 37.2 35.0 35.9 32.8 ** umol/L ST.DEV 2.6 1.1 1.0 2.4 N 5 5 5 5

Glucose MEAN 7.55 8.21 7.62 5.72 ** mmol/L ST.DEV 0.80 0.67 1.00 0.32 N 5 5 5 5

Cholesterol MEAN 2.01 2.04 2.07 3.23 ** mmol/L ST.DEV 0.22 0.21 0.31 0.45 N 5 5 5 5

Bile Acids MEAN 41.4 23.7 51.9 111.8 * umol/L ST.DEV 16.1 13.9 7.7 68.2 N 5 5 5 5

Sodium MEAN 142.0 141.4 141.8 140.2 * mmol/L ST.DEV 0.6 1.1 0.6 1.7 N 5 5 5 5

Potassium MEAN 4.15 4.18 4.61 * 4.10 mmol/L ST.DEV 0.20 0.25 0.28 0.31 N 5 5 5 5

Chloride MEAN 100 101 101 97 ** mmol/L ST.DEV 1 1 2 2 N 5 5 5 5

Calcium MEAN 2.74 2.72 2.73 2.70 mmol/L ST.DEV 0.05 0.04 0.03 0.04 N 5 5 5 5 Inorg.Phos MEAN 2.55 2.35 2.36 2.71 mmol/L ST.DEV 0.17 0.13 0.22 0.31 N 5 5 5 5

− Page 17

− 08Feb13 15h07Project 501432 APPENDIX 1

CLINICAL BIOCHEMISTRY SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT ALAT MEAN 41.6 37.3 56.8 46.5 U/L ST.DEV 7.8 7.0 22.8 11.3 N 5 5 5 5

ASAT MEAN 96.4 71.9 82.2 77.3 U/L ST.DEV 24.1 5.3 11.7 13.0 N 5 5 5 5

ALP MEAN 107 100 107 81 U/L ST.DEV 21 27 40 16 N 5 5 5 5 Total protein MEAN 64.2 66.3 62.8 61.1 g/L ST.DEV 2.7 4.3 1.6 2.8 N 5 5 5 5

Albumin MEAN 34.7 35.6 33.4 29.4 ** g/L ST.DEV 1.8 2.0 0.3 1.4 N 5 5 5 5

Total bilirubin MEAN 2.4 2.4 3.5 ** 3.4 * umol/L ST.DEV 0.3 0.3 0.8 0.4 N 5 5 5 5

Urea MEAN 8.2 8.0 9.7 8.0 mmol/L ST.DEV 0.4 1.0 1.7 1.6 N 5 5 5 5

Creatinine MEAN 38.2 38.2 39.8 33.6 * umol/L ST.DEV 1.6 2.2 1.8 3.4 N 5 5 5 5

Glucose MEAN 6.83 6.09 7.28 5.93 mmol/L ST.DEV 0.59 0.72 0.72 1.03 N 5 5 5 5

Cholesterol MEAN 1.11 1.63 2.01 * 2.57 ** mmol/L ST.DEV 0.30 0.42 0.75 0.09 N 5 5 5 5

Bile Acids MEAN 22.4 18.4 71.8 70.7 umol/L ST.DEV 8.2 8.9 59.0 51.8 N 5 5 5 5

Sodium MEAN 140.9 142.2 141.6 140.9 mmol/L ST.DEV 0.8 1.1 1.7 1.6 N 5 5 5 5

Potassium MEAN 3.82 3.67 4.17 * 4.13 mmol/L ST.DEV 0.20 0.19 0.10 0.26 N 5 5 5 5

Chloride MEAN 102 104 101 99 ** mmol/L ST.DEV 1 1 1 1 N 5 5 5 5

Calcium MEAN 2.66 2.70 2.72 2.70 mmol/L ST.DEV 0.05 0.11 0.03 0.10 N 5 5 5 5 Inorg.Phos MEAN 2.21 2.00 2.24 2.45 mmol/L ST.DEV 0.26 0.18 0.25 0.49 N 5 5 5 5

− Page 18

− 08Feb13 15h07Project 501432 APPENDIX 1

MACROSCOPIC FINDINGS SUMMARY

# / ## Fisher's Exact test significant at 5% (#) or 1% (##) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT Animals examined 5 5 5 5 Animals without findings 3 5 0 0

Animals affected 2 0 5 5

General observations

Emaciated 0 0 0 4 # Stomach

Focus/foci 0 0 1 0 Grown together with: 0 0 0 1 Irregular surface 0 0 5 ## 4 # Duodenum

Focus/foci 0 0 1 0 Thickened 0 0 3 4 # Contents: 0 0 0 1 Gelatinous 0 0 3 3 Jejunum

Thickened 0 0 2 4 # Gelatinous 0 0 2 4 # Liver

Reduced in size 0 0 1 0 Kidneys

Pelvic dilation 0 0 1 0 Focus/foci 0 0 1 0 Discolouration 0 0 0 5 ## Epididymides

Nodule(s) 1 0 0 0 Prostate

Reduced in size 0 0 0 5 ## Seminal vesicles

Reduced in size 1 0 0 5 # Adrenal glands

Discolouration 0 0 0 4 # Thymus

Reduced in size 0 0 0 5 ## Mesenteric lymph n

Discolouration 0 0 4 # 5 ## Mandibular lymph n

Discolouration 0 0 1 0 Renal lymph node

Enlarged 0 0 0 1 Pancreatic lymph n

Enlarged 0 0 2 3 Discolouration 0 0 1 0

FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT Animals examined 5 5 5 5 Animals without findings 3 3 0 0

Animals affected 2 2 5 5

General observations

Emaciated 0 0 0 5 ##

− Page 19

− 08Feb13 15h07Project 501432 APPENDIX 1

MACROSCOPIC FINDINGS SUMMARY

# / ## Fisher's Exact test significant at 5% (#) or 1% (##) level FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT Stomach

Focus/foci 0 0 0 3 Grown together with: 0 0 0 1 Irregular surface 0 0 3 5 ## Duodenum

Thickened 0 0 3 3 Contents: 0 0 0 3 Dilation 0 0 0 1 Gelatinous 0 0 2 1 Jejunum

Thickened 0 0 2 3 Contains fluid 0 0 0 1 Contents: 0 0 0 2 Dilation 0 0 0 1 Gelatinous 0 0 1 2 Liver

Focus/foci 0 0 1 0 Kidneys

Pelvic dilation 0 0 0 1 Discolouration 0 0 0 5 ## Ovaries

Reduced in size 0 0 0 3 Uterus

Reduced in size 0 0 1 5 ## Contains fluid 2 1 0 0 Adrenal glands

Enlarged 0 0 0 1 Discolouration 0 0 1 4 # Thymus

Reduced in size 0 0 0 4 # Mesenteric lymph n

Discolouration 0 0 2 4 # Renal lymph node

Enlarged 0 0 0 1 Discolouration 0 0 0 1 Pancreatic lymph n

Enlarged 0 0 1 4 # Discolouration 0 1 2 0

− Page 20

− 08Feb13 15h07Project 501432 APPENDIX 1

ORGAN WEIGHTS (GRAM) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT BODY W. MEAN 285 260 257 170 ** (GRAM) ST.DEV 13 30 16 20 N 5 5 5 5

BRAIN MEAN 2.05 1.95 1.99 1.78 ** (GRAM) ST.DEV 0.11 0.11 0.06 0.08 N 5 5 5 5

HEART MEAN 0.869 0.782 0.793 0.585 ** (GRAM) ST.DEV 0.052 0.058 0.074 0.087 N 5 5 5 5

LIVER MEAN 8.53 8.02 8.47 7.25 (GRAM) ST.DEV 0.66 1.11 0.56 0.72 N 5 5 5 5

THYROIDS MEAN 0.024 0.023 0.023 0.019 (GRAM) ST.DEV 0.002 0.003 0.002 0.004 N 5 5 5 5

THYMUS MEAN 0.529 0.417 0.403 0.081 ** (GRAM) ST.DEV 0.067 0.070 0.108 0.065 N 5 5 5 5

KIDNEYS MEAN 2.25 2.16 2.25 1.78 ** (GRAM) ST.DEV 0.23 0.22 0.16 0.17 N 5 5 5 5

ADRENALS MEAN 0.058 0.056 0.058 0.078 ** (GRAM) ST.DEV 0.008 0.002 0.005 0.012 N 5 5 5 5

SPLEEN MEAN 0.573 0.511 0.484 0.335 ** (GRAM) ST.DEV 0.035 0.086 0.034 0.059 N 5 5 5 5

TESTES MEAN 3.04 3.20 3.16 2.61 * (GRAM) ST.DEV 0.14 0.17 0.37 0.24 N 5 5 5 5

PROSTATE MEAN 0.529 0.353 * 0.305 ** 0.182 ** (GRAM) ST.DEV 0.146 0.062 0.061 0.046 N 5 5 5 5

EPIDIDYMIDES MEAN 0.751 0.747 0.733 0.597 ** (GRAM) ST.DEV 0.038 0.065 0.035 0.035 N 5 5 5 5

SEMINAL VES MEAN 0.990 0.797 0.685 ** 0.265 ** (GRAM) ST.DEV 0.151 0.109 0.112 0.151 N 5 5 5 5

− Page 21

− 08Feb13 15h07Project 501432 APPENDIX 1

ORGAN/BODY WEIGHT RATIOS (%) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level MALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT BODY W. MEAN 285 260 257 170 ** (GRAM) ST.DEV 13 30 16 20 N 5 5 5 5

BRAIN MEAN 0.72 0.76 0.78 1.06 ** (%) ST.DEV 0.01 0.08 0.05 0.12 N 5 5 5 5

HEART MEAN 0.305 0.302 0.308 0.343 * (%) ST.DEV 0.017 0.019 0.013 0.021 N 5 5 5 5

LIVER MEAN 2.99 3.07 3.29 * 4.27 ** (%) ST.DEV 0.10 0.09 0.19 0.26 N 5 5 5 5

THYROIDS MEAN 0.008 0.009 0.009 0.011 ** (%) ST.DEV 0.001 0.001 0.001 0.002 N 5 5 5 5

THYMUS MEAN 0.186 0.160 0.156 0.046 ** (%) ST.DEV 0.022 0.011 0.033 0.031 N 5 5 5 5

KIDNEYS MEAN 0.79 0.83 0.87 * 1.05 ** (%) ST.DEV 0.06 0.05 0.03 0.04 N 5 5 5 5

ADRENALS MEAN 0.020 0.022 0.023 0.046 ** (%) ST.DEV 0.003 0.003 0.003 0.007 N 5 5 5 5

SPLEEN MEAN 0.202 0.195 0.188 0.196 (%) ST.DEV 0.016 0.015 0.013 0.017 N 5 5 5 5

TESTES MEAN 1.07 1.24 1.23 1.54 ** (%) ST.DEV 0.05 0.12 0.18 0.19 N 5 5 5 5

PROSTATE MEAN 0.185 0.138 0.119 * 0.106 ** (%) ST.DEV 0.049 0.032 0.025 0.024 N 5 5 5 5

EPIDIDYMIDES MEAN 0.264 0.289 0.286 0.353 ** (%) ST.DEV 0.023 0.027 0.024 0.028 N 5 5 5 5

SEMINAL VES MEAN 0.349 0.309 0.267 0.152 ** (%) ST.DEV 0.061 0.053 0.048 0.077 N 5 5 5 5

− Page 22

− 08Feb13 15h07Project 501432 APPENDIX 1

ORGAN WEIGHTS (GRAM) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT BODY W. MEAN 176 179 176 138 ** (GRAM) ST.DEV 11 1 9 13 N 5 2 5 5

BRAIN MEAN 1.85 1.82 1.87 1.77 (GRAM) ST.DEV 0.05 0.08 0.06 0.07 N 5 5 5 5

HEART MEAN 0.573 0.601 0.589 0.518 (GRAM) ST.DEV 0.082 0.025 0.101 0.081 N 5 5 5 5

LIVER MEAN 5.02 5.45 5.59 6.12 ** (GRAM) ST.DEV 0.45 0.17 0.59 0.39 N 5 5 5 5

THYROIDS MEAN 0.022 0.021 0.023 0.022 (GRAM) ST.DEV 0.004 0.002 0.004 0.004 N 5 5 5 5

THYMUS MEAN 0.443 0.397 0.329 * 0.093 ** (GRAM) ST.DEV 0.060 0.079 0.057 0.037 N 5 5 5 4

KIDNEYS MEAN 1.48 1.49 1.51 1.48 (GRAM) ST.DEV 0.12 0.13 0.16 0.08 N 5 5 5 5

ADRENALS MEAN 0.061 0.066 0.060 0.079 (GRAM) ST.DEV 0.012 0.008 0.011 0.010 N 5 5 5 5

SPLEEN MEAN 0.372 0.360 0.351 0.269 * (GRAM) ST.DEV 0.066 0.056 0.036 0.058 N 5 5 5 5

OVARIES MEAN 0.193 0.125 0.105 0.088 * (GRAM) ST.DEV 0.108 0.014 0.024 0.015 N 5 5 5 5

UTERUS MEAN 0.662 0.462 0.294 0.149 * (GRAM) ST.DEV 0.484 0.196 0.111 0.028 N 5 5 5 5

− Page 23

− 08Feb13 15h07Project 501432 APPENDIX 1

ORGAN/BODY WEIGHT RATIOS (%) SUMMARY

*/** Dunnett

− test based on pooled variance significant at 5% (*) or 1% (**) level FEMALES

GROUP 1 CONTROL GROUP 2 50 MG/KG GROUP 3 150 MG/KG GROUP 4 450 MG/KG

END OF TREATMENT BODY W. MEAN 176 179 176 138 ** (GRAM) ST.DEV 11 1 9 13 N 5 2 5 5

BRAIN MEAN 1.05 1.01 1.07 1.29 ** (%) ST.DEV 0.05 0.08 0.06 0.09 N 5 2 5 5

HEART MEAN 0.324 0.331 0.334 0.376 (%) ST.DEV 0.037 0.002 0.048 0.044 N 5 2 5 5

LIVER MEAN 2.85 3.00 3.19 4.45 ** (%) ST.DEV 0.21 0.11 0.31 0.20 N 5 2 5 5

THYROIDS MEAN 0.013 0.012 0.013 0.016 (%) ST.DEV 0.002 0.002 0.002 0.004 N 5 2 5 5

THYMUS MEAN 0.250 0.218 0.187 ** 0.066 ** (%) ST.DEV 0.023 0.037 0.025 0.021 N 5 2 5 4

KIDNEYS MEAN 0.84 0.82 0.86 1.07 ** (%) ST.DEV 0.05 0.06 0.07 0.06 N 5 2 5 5

ADRENALS MEAN 0.035 0.034 0.034 0.058 ** (%) ST.DEV 0.005 0.002 0.005 0.009 N 5 2 5 5

SPLEEN MEAN 0.210 0.186 0.200 0.194 (%) ST.DEV 0.025 0.034 0.013 0.028 N 5 2 5 5

OVARIES MEAN 0.112 0.072 0.060 0.063 (%) ST.DEV 0.067 0.013 0.013 0.008 N 5 2 5 5

UTERUS MEAN 0.366 0.345 0.167 0.108 * (%) ST.DEV 0.249 0.130 0.062 0.019 N 5 2 5 5

− Page 24

− 08Feb13 15h07m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 1

- Page 1 - APPENDIX 2 INDIVIDUAL DATA TABLESProject 501432 APPENDIX 2

MORTALITY DATA MALES

ANIMAL SCHEDULED SACRIFICE TREATMENT FROM TO

GROUP 1 (CONTROL) 1 07DEC12 09NOV12 06DEC12 2 07DEC12 09NOV12 06DEC12 3 07DEC12 09NOV12 06DEC12 4 07DEC12 09NOV12 06DEC12 5 07DEC12 09NOV12 06DEC12

GROUP 2 (50 MG/KG) 6 07DEC12 09NOV12 06DEC12 7 07DEC12 09NOV12 06DEC12 8 07DEC12 09NOV12 06DEC12 9 07DEC12 09NOV12 06DEC12 10 07DEC12 09NOV12 06DEC12

GROUP 3 (150 MG/KG) 11 07DEC12 09NOV12 06DEC12 12 07DEC12 09NOV12 06DEC12 13 07DEC12 09NOV12 06DEC12 14 07DEC12 09NOV12 06DEC12 15 07DEC12 09NOV12 06DEC12

GROUP 4 (450 MG/KG) 16 07DEC12 09NOV12 06DEC12 17 07DEC12 09NOV12 06DEC12 18 07DEC12 09NOV12 06DEC12 19 07DEC12 09NOV12 06DEC12 20 07DEC12 09NOV12 06DEC12

FEMALES

ANIMAL SCHEDULED SACRIFICE TREATMENT FROM TO

GROUP 1 (CONTROL) 21 07DEC12 09NOV12 06DEC12 22 07DEC12 09NOV12 06DEC12 23 07DEC12 09NOV12 06DEC12 24 07DEC12 09NOV12 06DEC12 25 07DEC12 09NOV12 06DEC12

GROUP 2 (50 MG/KG) 26 07DEC12 09NOV12 06DEC12 27 07DEC12 09NOV12 06DEC12 28 07DEC12 09NOV12 06DEC12 29 07DEC12 09NOV12 06DEC12 30 07DEC12 09NOV12 06DEC12

GROUP 3 (150 MG/KG) 31 07DEC12 09NOV12 06DEC12 32 07DEC12 09NOV12 06DEC12 33 07DEC12 09NOV12 06DEC12 34 07DEC12 09NOV12 06DEC12 35 07DEC12 09NOV12 06DEC12

GROUP 4 (450 MG/KG) 36 07DEC12 09NOV12 06DEC12 37 07DEC12 09NOV12 06DEC12 38 07DEC12 09NOV12 06DEC12 39 07DEC12 09NOV12 06DEC12 40 07DEC12 09NOV12 06DEC12

− Page 2

− 08Feb13 15h09Project 501432 APPENDIX 2

CLINICAL SIGNS

.: Observation performed, sign not present G: Highest daily grades MALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 1 (CONTROL) ANIMAL 1 No clinical signs noted ANIMAL 2 No clinical signs noted ANIMAL 3 No clinical signs noted ANIMAL 4 No clinical signs noted ANIMAL 5 No clinical signs noted

GROUP 2 (50 MG/KG) ANIMAL 6 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 7 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 8 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 9 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 10 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

GROUP 3 (150 MG/KG) ANIMAL 11 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Skin / fur

Piloerection (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . 1 1 1 1 1 1 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 12 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . . . 1 1 1 1 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 13 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . 1 . . . . 1 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 14 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . . 1 . . . . . . 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 15 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . 1 1 1 . . . . . . 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2

− Page 3

− 08Feb13 15h09Project 501432 APPENDIX 2

CLINICAL SIGNS

.: Observation performed, sign not present G: Highest daily grades MALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 4 (450 MG/KG) ANIMAL 16 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 17 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . 1 1 1 1 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 18 Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 19 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 20 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 . 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . . 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

− Page 4

− 08Feb13 15h09Project 501432 APPENDIX 2

CLINICAL SIGNS

.: Observation performed, sign not present G: Highest daily grades MALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 4 (450 MG/KG)

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . .

FEMALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 1 (CONTROL) ANIMAL 21 No clinical signs noted ANIMAL 22 No clinical signs noted ANIMAL 23 No clinical signs noted ANIMAL 24 No clinical signs noted ANIMAL 25 No clinical signs noted

GROUP 2 (50 MG/KG) ANIMAL 26 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 27 Breathing

Rales (3) G: . . . . . . . . . . . . . . . . . . 1 1 .

. . . . . . . Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 28 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 29 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ANIMAL 30 Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

GROUP 3 (150 MG/KG) ANIMAL 31 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Breathing

Rales (3) G: . . . . . . . . . . . . . . . . . . 1 . .

. . . . . . . Secretion / excretion

Salivation (3) G: . . . . . . . . . . 1 1 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 32 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . . 1 . . . . . . 1 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2

− Page 5

− 08Feb13 15h09Project 501432 APPENDIX 2

CLINICAL SIGNS

.: Observation performed, sign not present G: Highest daily grades FEMALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 3 (150 MG/KG) ANIMAL 33 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . . . . . . . . . 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 34 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Secretion / excretion

Salivation (3) G: . . . . 1 1 . . . . . . 2 2 1 1 1 2 2 2 2 2 2 2 2 2 2 2 ANIMAL 35 Posture

Hunched posture (1) G: . . . . . . . . . . . . 1 1

. . . . . . . . . . . . . . Skin / fur

Scabs (3) G: . . . . . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1

. . .

(Shoulder right) Secretion / excretion

Salivation (3) G: . . . . 1 1 1 1 1 1 1 1 2 2 1 1 1 2 2 1 2 2 2 2 2 2 2 2

GROUP 4 (450 MG/KG) ANIMAL 36 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 . . . . . 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 2 3 3 3 3 3 3 3 3 3 Chromodacryorrhoea (3) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1

(Snout) Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . 1 1 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 37 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 . . . . . 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 38 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . .

− Page 6

− 08Feb13 15h09Project 501432 APPENDIX 2

CLINICAL SIGNS

.: Observation performed, sign not present G: Highest daily grades FEMALES

TREATMENT SIGN (MAX. GRADE) (LOCATION) WEEK: DAY: 1 1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 .

1 . 2 .

3 .

4 .

5 .

6 .

7 4

1 . 2 .

3 .

4 .

5 .

6 .

7

GROUP 4 (450 MG/KG) ANIMAL 39 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 . . . . . . . 1 Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 3 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . 1 1 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . ANIMAL 40 Behavior

Lethargy (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . . Posture

Hunched posture (1) G: . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Breathing

Rales (3) G:

. . . . . . . . . . . . . . . . . . . . . . . . 1 1 1 . Skin / fur

Piloerection (1) G: . . . . . . . . . . . . . 1 1 1 1 1 1 1 .

. . . . . . . Secretion / excretion

Salivation (3) G: . . . 1 1 1 1 1 1 1 1 2 2 2 1 1 2 2 3 3 2 3 3 3 3 3 3 3 Faeces pale (1) G: . . . . . . . . . . 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Various

Lean (1) G:

. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ptosis (3) G: . . . . . . . . . . . . . 1 . . . . . . .

. . . . . . .

− Page 7

− 08Feb13 15h09Project 501432 APPENDIX 2

FUNCTIONAL OBSERVATIONS MALES AT WEEK4

ANIMAL HEARING SCORE 0/1 PUPIL L SCORE 0/1 PUPIL R SCORE 0/1 STATIC R SCORE 0/1 GRIP SCORE 0/1

GROUP 1 (CONTROL) 1 0 0 0 0 0 2 0 0 0 0 0 3 0 0 0 0 0 4 0 0 0 0 0 5 0 0 0 0 0

GROUP 2 (50 MG/KG) 6 0 0 0 0 0 7 0 0 0 0 0 8 0 0 0 0 0 9 0 0 0 0 0 10 0 0 0 0 0

GROUP 3 (150 MG/KG) 11 0 0 0 0 0 12 0 0 0 0 0 13 0 0 0 0 0 14 0 0 0 0 0 15 0 0 0 0 0

GROUP 4 (450 MG/KG) 16 0 0 0 0 0 17 0 0 0 0 0 18 0 0 0 0 0 19 0 0 0 0 0 20 0 0 0 0 0

FEMALES AT WEEK4

ANIMAL HEARING SCORE 0/1 PUPIL L SCORE 0/1 PUPIL R SCORE 0/1 STATIC R SCORE 0/1 GRIP SCORE 0/1

GROUP 1 (CONTROL) 21 0 0 0 0 0 22 0 0 0 0 0 23 0 0 0 0 0 24 0 0 0 0 0 25 0 0 0 0 0

GROUP 2 (50 MG/KG) 26 0 0 0 0 0 27 0 0 0 0 0 28 0 0 0 0 0 29 0 0 0 0 0 30 0 0 0 0 0

GROUP 3 (150 MG/KG) 31 0 0 0 0 0 32 0 0 0 0 0 33 0 0 0 0 0 34 0 0 0 0 0 35 0 0 0 0 0

− Page 8

− 08Feb13 15h09Project 501432 APPENDIX 2

FUNCTIONAL OBSERVATIONS FEMALES AT WEEK4

ANIMAL HEARING SCORE 0/1 PUPIL L SCORE 0/1 PUPIL R SCORE 0/1 STATIC R SCORE 0/1 GRIP SCORE 0/1

GROUP 4 (450 MG/KG) 36 0 0 0 0 0 37 0 0 0 0 0 38 0 0 0 0 0 39 0 0 0 0 0 40 0 0 0 0 0

− Page 9

− 08Feb13 15h09- Page 10 - Project 501432 APPENDIX 2

MOTOR ACTIVITY TEST - TOTAL MOVEMENTS MALES AT WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

1 1510 986 665 495 46 93 26 0 0 62 0 0 3883 2 590 224 270 66 44 327 9 0 2 45 0 6 1583 3 1285 552 174 421 9 27 4 5 7 10 4 1 2499 4 1117 938 554 351 276 230 94 0 55 309 1 23 3948 5 601 429 414 22 247 158 18 132 422 470 10 117 3040

6 1199 651 223 63 448 139 23 193 171 0 11 1 3122 7 927 543 427 234 344 300 216 272 284 15 399 346 4307 8 1651 1076 633 556 490 334 430 173 66 8 312 7 5736 9 1534 397 170 4 215 290 11 24 48 87 0 4 2784 10 1352 1029 337 514 202 409 11 104 61 59 2 31 4111

11 890 466 198 19 157 4 54 0 23 10 0 319 2140 12 1132 805 366 636 329 275 191 818 534 56 0 222 5364 13 846 384 68 38 647 335 0 51 35 17 12 2 2435 14 1051 585 256 209 371 0 13 151 45 41 114 17 2853 15 966 841 513 489 703 256 532 597 245 289 256 7 5694

16 108 51 60 133 79 26 125 238 34 68 3 0 925
17 295 41 252 70 195 19 23 18 12 67 0 3 995 18 259 236 246 58 101 135 118 72 17 30 10 6 1288 19 440 230 160 162 240 130 138 40 265 15 30 45 1895 20 210 110 45 15 85 40 3 46 142 164 16 27 903 GROUP 4 (450 MG/KG) GROUP 3 (150 MG/KG) ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (50 MG/KG)- Page 11 - Project 501432 APPENDIX 2

MOTOR ACTIVITY TEST - AMBULATIONS MALES AT WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

1 355 223 139 130 2 35 1 0 0 23 0 0 908
2 162 15 50 5 8 20 0 0 0 3 0 0 263 3 296 112 34 82 0 0 0 0 0 0 0 0 524
4 311 206 106 45 9 32 0 0 18 63 0 0 790
5 184 155 85 3 35 39 1 1 0 138 0 0 641

6 342 242 53 0 123 6 1 16 52 0 1 0 836
7 230 101 88 39 55 55 38 61 42 0 99 46 854 8 424 344 120 155 55 86 85 29 0 0 0 0 1298 9 339 89 51 0 44 90 0 0 0 0 0 0 613 10 316 257 86 138 46 52 1 0 1 7 0 11 915

11 265 171 73 0 9 0 0 0 0 0 0 104 622
12 245 169 70 95 83 61 20 185 112 0 0 43 1083 13 300 138 7 7 164 86 0 0 0 0 0 0 702
14 282 114 56 36 91 0 1 2 0 0 2 0 584 15 298 215 122 50 142 43 116 113 57 47 67 0 1270

16 18 5 5 60 28 5 33 81 1 39 0 0 275
17 89 7 83 7 52 0 0 0 0 1 0 0 239 18 73 59 77 5 26 59 48 15 3 18 0 0 383 19 135 59 43 42 74 29 23 4 112 6 5 7 539 20 71 41 10 8 37 1 0 0 47 34 1 4 254 GROUP 3 (150 MG/KG)

GROUP 4 (450 MG/KG) ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (50 MG/KG)- Page 12 - Project 501432 APPENDIX 2

MOTOR ACTIVITY TEST - TOTAL MOVEMENTS FEMALES WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

21 1710 981 796 217 588 77 2 17 359 485 232 42 5506
22 1054 581 439 460 449 337 45 7 0 575 381 273 4601 23 1610 1004 566 893 1132 832 652 124 23 2 1 183 7022
24 723 542 890 139 591 65 12 2 273 336 47 21 3641 25 1610 874 605 656 461 98 213 3 498 63 0 2 5083

26 1150 1056 440 455 712 536 364 473 166 244 749 318 6663
27 1207 619 724 677 716 519 5 580 37 305 581 510 6480 28 1536 849 655 545 719 550 3 0 4 5 10 0 4876 29 1587 724 879 344 612 509 38 22 0 7 6 2 4730 30 1222 652 474 100 761 206 7 68 645 36 1 47 4219

31 713 544 198 64 187 397 77 10 2 67 4 7 2270 32 1266 839 641 636 268 213 405 259 39 46 19 176 4807 33 1169 906 539 604 241 803 183 748 564 248 150 358 6513 34 1175 738 601 415 97 421 6 117 527 37 11 394 4539 35 827 1055 396 256 349 169 469 7 8 32 17 1 3586

36 203 1 32 163 13 176 1 2 56 9 81 136 873 37 342 60 21 148 61 142 0 44 136 1 0 36 991 38 280 201 169 33 95 15 31 106 40 22 58 166 1216 39 330 312 198 241 134 192 176 163 131 111 117 10 2115 40 295 127 165 95 0 67 102 8 3 15 66 4 947 GROUP 3 (150 MG/KG)

GROUP 4 (450MG/KG) ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (50 MG/KG)- Page 13 - Project 501432 APPENDIX 2

MOTOR ACTIVITY TEST - AMBULATIONS FEMALES WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

21 652 340 260 30 164 0 0 1 98 121 28 0 1694
22 356 150 103 151 91 73 0 0 0 173 83 96 1276 23 443 268 76 256 237 167 97 0 0 1 1 26 1572
24 215 129 229 6 157 4 1 0 38 108 2 2 891 25 450 266 118 161 112 1 10 0 171 2 0 0 1291

26 397 320 139 175 246 168 117 138 59 29 260 112 2160
27 404 208 243 204 200 157 0 159 3 54 133 131 1896 28 497 218 198 132 205 109 1 0 0 0 0 0 1360 29 441 188 213 58 134 139 0 0 0 0 0 0 1173 30 399 214 158 20 284 80 0 23 273 0 1 6 1458

31 206 153 16 4 7 136 7 0 0 1 0 1 531 32 468 310 186 226 81 61 132 10 0 1 0 38 1513 33 337 260 123 189 72 229 58 243 163 61 1 78 1814 34 507 254 165 129 26 157 2 2 202 6 0 141 1591 35 286 342 105 81 113 76 111 0 0 0 0 0 1114

36 62 0 0 48 0 77 0 0 13 4 18 5 227 37 115 9 5 92 37 31 0 0 43 0 0 0 332 38 79 82 51 4 20 0 0 27 12 0 4 3 282 39 95 113 69 96 45 68 64 48 39 56 32 0 725 40 120 76 84 48 0 6 34 0 1 0 13 0 382 GROUP 4 (450 MG/KG) ANIMAL Interval (5 min)

GROUP 2 (50 MG/KG)

GROUP 3 (150 MG/KG) GROUP 1 (CONTROL)Project 501432 APPENDIX 2

BODY WEIGHTS (GRAM) MALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 1 (CONTROL) 1 173 219 263 301 324 2 171 216 257 287 309 3 169 209 245 270 296 4 164 203 241 269 286 5 178 217 258 292 308

GROUP 2 (50 MG/KG) 6 171 213 254 286 306 7 182 225 262 297 317 8 167 207 239 263 277 9 159 198 233 258 271 10 159 186 212 223 233

GROUP 3 (150 MG/KG) 11 165 194 235 265 276 12 165 195 225 259 277 13 173 203 229 251 262 14 183 221 262 290 301 15 164 194 227 256 266

GROUP 4 (450 MG/KG) 16 167 177 191 199 185 17 151 145 157 168 175 18 162 155 167 170 167 19 169 164 171 179 185 20 177 189 210 217 221

FEMALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 1 (CONTROL) 21 126 137 163 173 176 22 137 157 179 185 203 23 141 162 186 191 211 24 132 145 158 178 180 25 135 147 171 184 191

GROUP 2 (50 MG/KG) 26 137 154 167 190 196 27 137 158 172 190 201 28 125 141 159 172 171 29 143 163 174 184 194 30 135 160 176 180 196

GROUP 3 (150 MG/KG) 31 129 144 167 175 185 32 135 148 174 186 190 33 147 165 185 200 202 34 144 160 177 200 197 35 136 152 168 177 184

− Page 14

− 08Feb13 15h14Project 501432 APPENDIX 2

BODY WEIGHTS (GRAM) FEMALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 4 (450 MG/KG) 36 132 138 147 154 146 37 136 137 148 164 165 38 124 137 151 164 163 39 142 146 150 143 129 40 137 138 151 164 151

− Page 15

− 08Feb13 15h14Project 501432 APPENDIX 2

BODY WEIGHT GAIN (%) MALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 1 (CONTROL) 1 0 27 52 74 87 2 0 26 50 68 81 3 0 24 45 60 75 4 0 24 47 64 74 5 0 22 45 64 73

GROUP 2 (50 MG/KG) 6 0 25 49 67 79 7 0 24 44 63 74 8 0 24 43 57 66 9 0 25 47 62 70 10 0 17 33 40 47

GROUP 3 (150 MG/KG) 11 0 18 42 61 67 12 0 18 36 57 68 13 0 17 32 45 51 14 0 21 43 58 64 15 0 18 38 56 62

GROUP 4 (450 MG/KG) 16 0 6 14 19 11 17 0

− 4 4 11 16 18 0

− 4 3 5 3 19 0

− 3 1 6 9 20 0 7 19 23 25

FEMALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 1 (CONTROL) 21 0 9 29 37 40 22 0 15 31 35 48 23 0 15 32 35 50 24 0 10 20 35 36 25 0 9 27 36 41

GROUP 2 (50 MG/KG) 26 0 12 22 39 43 27 0 15 26 39 47 28 0 13 27 38 37 29 0 14 22 29 36 30 0 19 30 33 45

GROUP 3 (150 MG/KG) 31 0 12 29 36 43 32 0 10 29 38 41 33 0 12 26 36 37 34 0 11 23 39 37 35 0 12 24 30 35

− Page 16

− 08Feb13 15h14Project 501432 APPENDIX 2

BODY WEIGHT GAIN (%) FEMALES

TREATMENT DAYS WEEKS ANIMAL 1 1 8 2 15 3 22 4 28 4

GROUP 4 (450 MG/KG) 36 0 5 11 17 11 37 0 1 9 21 21 38 0 10 22 32 31 39 0 3 6 1

− 9 40 0 1 10 20 10

− Page 17

− 08Feb13 15h14Project 501432 APPENDIX 2

FOOD CONSUMPTION (G/ANIMAL/DAY) MALES

TREATMENT DAYS WEEKS CAGE 1

− 8 1

− 2 8

− 15 2

− 3 15

− 22 3

− 4 22

− 28 4

GROUP 1 (CONTROL) 1 19 21 21 22

GROUP 2 (50 MG/KG) 2 18 20 21 21

GROUP 3 (150 MG/KG) 3 17 20 21 21

GROUP 4 (450 MG/KG) 4 11 11 12 12

FEMALES

TREATMENT DAYS WEEKS CAGE 1

− 8 1

− 2 8

− 15 2

− 3 15

− 22 3

− 4 22

− 28 4

GROUP 1 (CONTROL) 5 14 15 14 15

GROUP 2 (50 MG/KG) 6 14 14 14 16

GROUP 3 (150 MG/KG) 7 13 14 14 13

GROUP 4 (450 MG/KG) 8 10 10 11 10

− Page 18

− 08Feb13 15h14Project 501432 APPENDIX 2

RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY) MALES

TREATMENT DAYS WEEKS CAGE 1

− 8 1

− 2 8

− 15 2

− 3 15

− 22 3

− 4 22

− 28 4

GROUP 1 (CONTROL) 1 90 83 75 72

GROUP 2 (50 MG/KG) 2 87 82 78 75

GROUP 3 (150 MG/KG) 3 86 83 78 76

GROUP 4 (450 MG/KG) 4 65 59 64 64

FEMALES

TREATMENT DAYS WEEKS CAGE 1

− 8 1

− 2 8

− 15 2

− 3 15

− 22 3

− 4 22

− 28 4

GROUP 1 (CONTROL) 5 92 86 79 76

GROUP 2 (50 MG/KG) 6 91 83 79 81

GROUP 3 (150 MG/KG) 7 85 80 75 70

GROUP 4 (450 MG/KG) 8 73 65 68 65

− Page 19

− 08Feb13 15h14Project 501432 APPENDIX 2

HAEMATOLOGY MALES END OF TREATMENT

ANIMAL WBC 10E9/L Neutrophils %WBC Lymphocytes %WBC Monocytes %WBC Eosinophils %WBC

GROUP 1 (CONTROL) 1 7.1 11.6 85.3 1.9 1.0 2 10.5 10.2 87.1 1.9 0.6 3 6.2 11.5 85.3 2.1 0.9 4 9.3 13.9 82.8 2.1 0.9 5 7.2 8.9 88.2 2.1 0.5

GROUP 2 (50 MG/KG) 6 8.5 11.8 85.4 1.8 0.6 7 6.6 14.6 82.2 1.8 1.3 8 7.3 15.6 81.4 1.8 1.0 9 7.1 11.1 85.9 2.0 0.6 10 8.4 7.7 90.3 1.0 0.7

GROUP 3 (150 MG/KG) 11 11.7 28.4 69.0 2.0 0.4 12 6.5 29.8 65.9 3.4 0.6 13 11.1 42.0 54.5 2.7 0.6 14 8.1 33.5 62.3 3.5 0.6 15 8.9 18.1 78.3 2.7 0.7

GROUP 4 (450 MG/KG) 16 14.2 90.0 9.0 1.0 0.0 17 8.6 73.3 22.6 3.8 0.3 18 9.2 88.4 9.2 2.2 0.2 19 6.7 68.0 27.1 4.1 0.7 20 8.7 61.5 33.9 4.1 0.4

MALES END OF TREATMENT

ANIMAL Basophils %WBC Red blood cells 10E12/L Reticulocytes %RBC RDW % Haemoglobin mmol/L

GROUP 1 (CONTROL) 1 0.1 7.79 2.6 11.0 9.6 2 0.2 8.42 2.3 10.7 9.7 3 0.2 8.21 2.4 12.1 9.7 4 0.3 8.40 2.8 11.2 9.5 5 0.2 7.84 2.6 13.3 9.8

GROUP 2 (50 MG/KG) 6 0.4 8.39 2.4 11.2 9.8 7 0.2 8.02 3.2 11.9 9.4 8 0.1 8.50 2.0 10.9 10.1 9 0.3 8.74 2.4 11.9 10.0 10 0.3 8.25 2.1 11.1 10.1

GROUP 3 (150 MG/KG) 11 0.3 8.27 2.1 10.8 9.7 12 0.2 7.95 2.4 11.5 9.3 13 0.2 7.53 3.2 12.1 8.8 14 0.2 7.71 1.7 10.3 8.8 15 0.3 7.93 2.7 13.8 9.6

− Page 20

− 08Feb13 15h14Project 501432 APPENDIX 2

HAEMATOLOGY MALES END OF TREATMENT

ANIMAL Basophils %WBC Red blood cells 10E12/L Reticulocytes %RBC RDW % Haemoglobin mmol/L

GROUP 4 (450 MG/KG) 16 0.0 6.22 6.9 14.0 6.6 17 0.1 6.88 8.0 15.3 8.6 18 0.0 6.82 7.0 13.8 7.4 19 0.1 6.80 8.7 15.0 8.2 20 0.1 7.14 6.4 13.0 8.3

MALES END OF TREATMENT

ANIMAL Haematocrit L/L MCV fL MCH fmol MCHC mmol/L Platelets 10E9/L

GROUP 1 (CONTROL) 1 0.443 56.9 1.24 21.72 893 2 0.444 52.8 1.15 21.76 972 3 0.422 51.4 1.18 22.94 819 4 0.435 51.8 1.13 21.88 921 5 0.431 55.0 1.25 22.70 915

GROUP 2 (50 MG/KG) 6 0.450 53.7 1.17 21.74 992 7 0.420 52.4 1.17 22.30 805 8 0.457 53.7 1.18 22.06 847 9 0.459 52.5 1.14 21.71 1049 10 0.444 53.8 1.22 22.67 979

GROUP 3 (150 MG/KG) 11 0.451 54.5 1.17 21.42 1049 12 0.424 53.4 1.18 22.03 1111 13 0.414 55.0 1.16 21.17 1040 14 0.392 50.9 1.14 22.42 1007 15 0.425 53.6 1.21 22.55 746

GROUP 4 (450 MG/KG) 16 0.313 50.4 1.07 21.15 1909 17 0.391 56.9 1.24 21.87 1225 18 0.343 50.3 1.08 21.56 1428 19 0.379 55.7 1.20 21.57 1175 20 0.385 53.9 1.17 21.67 1469

MALES END OF TREATMENT

ANIMAL PT

s APTT

s

GROUP 1 (CONTROL) 1 18.1 16.7 2 17.9 17.6 3 16.4 13.0 4 17.1 16.6 5 16.8 11.4

− Page 21

− 08Feb13 15h14Project 501432 APPENDIX 2

HAEMATOLOGY MALES END OF TREATMENT

ANIMAL PT

s APTT

s

GROUP 2 (50 MG/KG) 6 16.3 13.5 7 15.5 12.6 8 16.8 17.3 9 17.5 17.1 10 16.1 14.9

GROUP 3 (150 MG/KG) 11 16.9 16.9 12 16.0 12.0 13 16.1 18.4 14 18.2 17.3 15 16.8 18.0

GROUP 4 (450 MG/KG) 16 19.0 16.1 17 18.8 13.1 18 17.8 9.5 19 16.7 10.5 20 16.7 10.8

FEMALES END OF TREATMENT

ANIMAL WBC 10E9/L Neutrophils %WBC Lymphocytes %WBC Monocytes %WBC Eosinophils %WBC

GROUP 1 (CONTROL) 21 5.9 7.0 90.8 1.1 1.0 22 3.4 9.0 88.5 1.5 1.0 23 3.6 10.9 85.5 2.1 1.4 24

−−− −−− −−− −−− −−− 25 4.9 8.4 88.8 1.6 1.1

GROUP 2 (50 MG/KG) 26 7.8 12.6 83.7 2.5 1.0 27 3.9 18.6 78.6 1.6 1.0 28 5.1 9.4 88.3 0.9 1.3 29 4.2 16.5 80.1 1.8 1.5 30 3.3 11.4 85.5 1.7 1.2

GROUP 3 (150 MG/KG) 31 5.2 18.6 78.4 2.3 0.5 32 7.1 25.0 70.6 2.9 1.4 33 7.7 10.7 84.6 3.3 1.2 34 3.6 18.1 78.7 1.6 1.6 35 5.1 25.3 69.7 3.4 1.4

GROUP 4 (450 MG/KG) 36 6.8 58.5 37.6 3.6 0.3 37 8.0 74.4 21.7 3.5 0.4 38 7.0 64.3 31.1 3.7 0.7 39 4.3 78.3 17.8 3.6 0.3 40 6.5 68.8 26.0 4.2 0.9

− Page 22

− 08Feb13 15h14Project 501432 APPENDIX 2

HAEMATOLOGY FEMALES END OF TREATMENT

ANIMAL Basophils %WBC Red blood cells 10E12/L Reticulocytes %RBC RDW % Haemoglobin mmol/L

GROUP 1 (CONTROL) 21 0.1 8.04 1.7 9.7 8.9 22 0.1 7.85 1.9 10.1 8.7 23 0.1 7.47 2.5 22.7 9.5 24

−−− −−− −−− −−− −−− 25 0.2 7.63 1.8 11.2 9.3

GROUP 2 (50 MG/KG) 26 0.1 7.37 2.0 10.4 8.7 27 0.1 7.90 2.9 11.4 9.1 28 0.2 7.71 1.9 10.3 9.1 29 0.1 7.85 2.5 10.8 9.1 30 0.2 7.74 2.4 10.8 8.9

GROUP 3 (150 MG/KG) 31 0.2 8.19 2.2 10.1 9.3 32 0.1 7.87 3.3 11.9 9.0 33 0.2 8.73 2.6 10.4 10.1 34 0.0 8.26 1.1 13.6 9.3 35 0.1 8.39 1.5 10.5 9.3

GROUP 4 (450 MG/KG) 36 0.0 6.81 5.4 12.9 7.5 37 0.0 7.26 5.1 12.7 8.6 38 0.1 6.99 7.6 13.7 8.2 39 0.0 5.26 6.7 13.7 6.2 40 0.1 6.40 8.4 13.6 7.3

FEMALES END OF TREATMENT

ANIMAL Haematocrit L/L MCV fL MCH fmol MCHC mmol/L Platelets 10E9/L

GROUP 1 (CONTROL) 21 0.400 49.8 1.11 22.37 788 22 0.397 50.6 1.10 21.84 980 23 0.414 55.5 1.27 22.85 1169 24

−−− −−− −−− −−− −−− 25 0.407 53.4 1.22 22.90 846

GROUP 2 (50 MG/KG) 26 0.384 52.1 1.18 22.57 983 27 0.411 52.0 1.15 22.20 862 28 0.410 53.1 1.18 22.24 920 29 0.401 51.1 1.15 22.60 693 30 0.397 51.3 1.15 22.43 946

GROUP 3 (150 MG/KG) 31 0.426 52.0 1.13 21.78 949 32 0.404 51.3 1.14 22.18 929 33 0.465 53.3 1.15 21.64 1090 34 0.415 50.2 1.13 22.49 1205 35 0.415 49.4 1.10 22.31 1079

− Page 23

− 08Feb13 15h14Project 501432 APPENDIX 2

HAEMATOLOGY FEMALES END OF TREATMENT

ANIMAL Haematocrit L/L MCV fL MCH fmol MCHC mmol/L Platelets 10E9/L

GROUP 4 (450 MG/KG) 36 0.354 51.9 1.11 21.31 1603 37 0.409 56.4 1.19 21.03 1229 38 0.390 55.8 1.18 21.16 983 39 0.288 54.7 1.18 21.55 1336 40 0.348 54.4 1.14 20.87 1402

FEMALES END OF TREATMENT

ANIMAL PT

s APTT

s

GROUP 1 (CONTROL) 21 16.3 15.1 22 15.7 15.0 23 17.4 15.4 24 16.7 17.0 25 17.3 15.9

GROUP 2 (50 MG/KG) 26 15.4 13.8 27 16.7 16.4 28 15.9 15.3 29 16.6 16.2 30 16.2 14.2

GROUP 3 (150 MG/KG) 31 16.8 13.9 32 17.2 15.8 33 16.8 14.6 34 16.0 12.8 35 15.4 11.0

GROUP 4 (450 MG/KG) 36 18.1 12.4 37 16.8 13.1 38 16.7 12.9 39

−−− −−− 40 15.6 11.3

− Page 24

− 08Feb13 15h14Project 501432 APPENDIX 2

CLINICAL BIOCHEMISTRY MALES END OF TREATMENT

ANIMAL ALAT U/L ASAT U/L ALP U/L Total protein g/L Albumin g/L

GROUP 1 (CONTROL) 1 50.5 67.4 179 67.0 34.5 2 55.2 76.7 188 64.4 32.0 3 30.0 84.3 138 61.5 31.3 4 43.4 73.7 201 66.3 33.7 5 37.2 80.8 277 61.8 32.4

GROUP 2 (50 MG/KG) 6 54.3 79.3 296 63.3 32.0 7 41.3 80.0 140 63.8 32.7 8 35.7 75.7 142 62.9 32.1 9 38.8 66.9 151 65.6 33.3 10 27.7 83.5 216 62.9 33.4

GROUP 3 (150 MG/KG) 11 73.7 88.8 223 63.2 31.7 12 90.7 99.3 173 63.6 31.7 13 41.2 61.5 130 60.3 29.5 14 84.5 117.1 173 60.1 31.5 15 79.6 86.1 176 59.3 31.6

GROUP 4 (450 MG/KG) 16 29.2 62.5 200 64.3 28.0 17 85.6 69.4 116 60.3 29.2 18 35.9 88.8 171 66.0 29.9 19 39.9 77.9 104 61.4 29.6 20 64.0 69.7 87 65.0 31.3

MALES END OF TREATMENT

ANIMAL Total bilirubin umol/L Urea mmol/L Creatinine umol/L Glucose mmol/L Cholesterol mmol/L

GROUP 1 (CONTROL) 1 2.4 8.5 37.0 6.49 2.23 2 2.6 10.0 41.0 8.33 2.06 3 2.8 5.6 35.6 7.10 1.73 4 2.7 9.9 34.3 8.32 2.19 5 2.4 8.0 38.3 7.49 1.84

GROUP 2 (50 MG/KG) 6 2.4 7.3 34.3 7.28 2.28 7 2.6 5.9 36.3 7.86 1.92 8 2.3 5.2 35.6 8.80 2.23 9 2.3 7.4 35.0 8.25 1.95 10 2.6 5.7 33.6 8.87 1.81

GROUP 3 (150 MG/KG) 11 2.7 7.7 35.6 8.37 2.27 12 3.9 9.3 35.6 7.31 1.95 13 2.6 8.3 37.7 8.58 2.43 14 4.0 7.2 35.0 7.77 2.07 15 3.6 8.6 35.6 6.08 1.63

− Page 25

− 08Feb13 15h14Project 501432 APPENDIX 2

CLINICAL BIOCHEMISTRY MALES END OF TREATMENT

ANIMAL Total bilirubin umol/L Urea mmol/L Creatinine umol/L Glucose mmol/L Cholesterol mmol/L

GROUP 4 (450 MG/KG) 16 3.6 6.2 28.9 5.51 2.87 17 4.3 9.8 33.0 5.29 3.22 18 6.0 9.3 35.0 5.83 3.41 19 3.9 8.3 34.3 6.08 2.76 20 4.2 8.0 33.0 5.90 3.87

MALES END OF TREATMENT

ANIMAL Bile Acids umol/L Sodium mmol/L Potassium mmol/L Chloride mmol/L Calcium mmol/L Inorg.Phos mmol/L

GROUP 1 (CONTROL) 1 25.9 142.3 4.23 100 2.81 2.77 2 33.8 142.4 4.22 100 2.74 2.64 3 68.3 141.2 4.22 100 2.67 2.59 4 41.6 142.5 3.80 99 2.75 2.37 5 37.6 141.7 4.30 101 2.74 2.38

GROUP 2 (50 MG/KG) 6 24.7 140.1 4.17 100 2.72 2.50 7 21.1 142.0 4.51 101 2.69 2.18 8 15.8 141.9 4.22 102 2.75 2.26 9 46.5 140.4 4.16 101 2.77 2.44 10 10.3 142.6 3.82 102 2.68 2.37

GROUP 3 (150 MG/KG) 11 50.5 141.8 4.42 103 2.76 2.06 12 46.1 141.3 4.40 100 2.77 2.40 13 52.2 141.5 4.55 100 2.72 2.24 14 64.8 141.6 5.08 99 2.70 2.47 15 46.1 142.8 4.61 102 2.72 2.62

GROUP 4 (450 MG/KG) 16 70.2 137.3 3.74 94 2.69 2.41 17 53.9 141.5 3.81 98 2.68 2.85 18 197.6 140.5 4.13 95 2.71 3.16 19 173.7 141.1 4.42 98 2.66 2.69 20 63.7 140.7 4.38 98 2.77 2.43

FEMALES END OF TREATMENT

ANIMAL ALAT U/L ASAT U/L ALP U/L Total protein g/L Albumin g/L

GROUP 1 (CONTROL) 21 31.7 81.8 114 62.5 33.6 22 50.5 90.0 116 68.9 37.8 23 48.4 138.7 107 63.5 34.1 24 38.2 80.4 73 63.2 34.6 25 39.0 91.0 127 62.9 33.6

− Page 26

− 08Feb13 15h14Project 501432 APPENDIX 2

CLINICAL BIOCHEMISTRY FEMALES END OF TREATMENT

ANIMAL ALAT U/L ASAT U/L ALP U/L Total protein g/L Albumin g/L

GROUP 2 (50 MG/KG) 26 25.4 63.8 66 72.2 38.1 27 36.4 77.3 112 65.7 35.3 28 41.7 69.9 78 68.9 37.2 29 41.4 73.3 123 62.8 33.9 30 41.7 75.1 123 62.0 33.7

GROUP 3 (150 MG/KG) 31 59.3 76.2 107 63.7 33.7 32 51.2 67.4 96 64.5 33.6 33 53.7 79.3 100 60.8 32.9 34 28.1 93.5 61 63.6 33.4 35 91.6 94.6 170 61.4 33.2

GROUP 4 (450 MG/KG) 36 43.9 69.3 73 60.7 29.9 37 58.8 97.6 100 64.0 30.4 38 57.2 83.0 94 64.0 30.5 39 40.0 69.8 62 58.2 27.2 40 32.4 66.9 76 58.5 29.0

FEMALES END OF TREATMENT

ANIMAL Total bilirubin umol/L Urea mmol/L Creatinine umol/L Glucose mmol/L Cholesterol mmol/L

GROUP 1 (CONTROL) 21 2.5 8.6 36.3 7.04 1.03 22 2.8 7.6 39.0 6.59 1.59 23 2.4 8.3 37.0 6.09 1.05 24 2.1 8.1 40.3 6.77 1.12 25 2.2 8.5 38.3 7.68 0.77

GROUP 2 (50 MG/KG) 26 2.6 8.4 38.3 4.99 1.19 27 2.2 6.2 39.0 6.42 2.07 28 2.0 8.2 37.7 5.83 2.01 29 2.5 8.6 41.0 6.29 1.23 30 2.7 8.7 35.0 6.90 1.63

GROUP 3 (150 MG/KG) 31 4.0 9.5 41.7 6.81 1.44 32 3.7 8.8 39.0 8.40 1.62 33 2.7 10.8 41.7 7.57 2.52 34 2.6 7.5 39.0 6.64 1.39 35 4.4 11.7 37.7 7.00 3.08

GROUP 4 (450 MG/KG) 36 3.7 10.2 35.0 5.28 2.49 37 3.9 8.0 35.0 4.96 2.57 38 3.5 8.6 35.6 6.01 2.72 39 3.1 6.0 27.6 5.79 2.55 40 3.0 7.1 35.0 7.63 2.53

− Page 27

− 08Feb13 15h14Project 501432 APPENDIX 2

CLINICAL BIOCHEMISTRY FEMALES END OF TREATMENT

ANIMAL Bile Acids umol/L Sodium mmol/L Potassium mmol/L Chloride mmol/L Calcium mmol/L Inorg.Phos mmol/L

GROUP 1 (CONTROL) 21 18.1 140.2 3.68 101 2.63 2.48 22 30.7 141.2 3.79 102 2.75 1.80 23 18.7 139.9 4.02 102 2.63 2.35 24 13.2 141.6 3.59 101 2.65 2.26 25 31.4 141.6 4.04 104 2.64 2.16

GROUP 2 (50 MG/KG) 26 7.8 142.8 3.69 103 2.84 2.10 27 10.4 143.0 3.36 104 2.66 1.81 28 26.0 143.0 3.74 105 2.77 2.21 29 21.1 140.5 3.73 104 2.56 1.82 30 26.9 141.6 3.85 102 2.67 2.06

GROUP 3 (150 MG/KG) 31 53.7 139.8 4.23 100 2.70 1.99 32 51.1 140.2 4.05 102 2.71 2.14 33 50.8 143.0 4.31 103 2.76 2.32 34 27.9 141.3 4.13 101 2.72 2.14 35 175.7 143.7 4.15 100 2.69 2.63

GROUP 4 (450 MG/KG) 36 52.6 141.5 4.31 100 2.73 2.53 37 160.0 138.9 3.94 97 2.79 2.54 38 68.6 142.8 4.07 99 2.80 3.16 39 40.5 139.6 4.49 99 2.58 1.86 40 31.6 141.6 3.85 100 2.61 2.17

− Page 28

− 08Feb13 15h14Project 501432 APPENDIX 2

MACROSCOPIC FINDINGS MALES ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

GROUP 1 (CONTROL) 1 Seminal vesicles Left side: reduced in size. Scheduled sacrifice, 07Dec2012 2 No findings noted Scheduled sacrifice, 07Dec2012 3 Epididymides Left side, tail: nodule(s), d=6x5 mm, Scheduled sacrifice, 07Dec2012 yellowish, soft. 4 No findings noted Scheduled sacrifice, 07Dec2012 5 No findings noted Scheduled sacrifice, 07Dec2012

GROUP 2 (50 MG/KG) 6 No findings noted Scheduled sacrifice, 07Dec2012 7 No findings noted Scheduled sacrifice, 07Dec2012 8 No findings noted Scheduled sacrifice, 07Dec2012 9 No findings noted Scheduled sacrifice, 07Dec2012 10 No findings noted Scheduled sacrifice, 07Dec2012

GROUP 3 (150 MG/KG) 11 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Wall: thickened. Contents: gelatinous. Mesenteric lymph n Discolouration, reddish. 12 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Kidneys Right side: pelvic dilation. Mesenteric lymph n Discolouration, dark red. Pancreatic lymph n Enlarged. Discolouration, reddish. 13 Stomach Forestomach: focus/foci, d=12x5 mm, Scheduled sacrifice, 07Dec2012 tan. Forestomach: irregular surface. Kidneys Left side: focus/foci, isolated, reddish. Mesenteric lymph n Discolouration, dark red. Pancreatic lymph n Enlarged. 14 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Liver Left lateral lobe: reduced in size. Mandibular lymph n Left side: discolouration, reddish. 15 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Focus/foci, d=4x3 mm, reddish. Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Mesenteric lymph n Discolouration, dark red.

GROUP 4 (450 MG/KG) 16 Stomach Grown together with: liver processus Scheduled sacrifice, 07Dec2012 papilaris. Kidneys Both sides: discolouration, greenish. Prostate Reduced in size. Seminal vesicles Both sides: reduced in size. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. 17 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Prostate Reduced in size. Seminal vesicles Both sides: reduced in size.

− Page 29

− 08Feb13 15h14Project 501432 APPENDIX 2

MACROSCOPIC FINDINGS MALES ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

GROUP 4 (450 MG/KG) Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Pancreatic lymph n Enlarged. 18 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Prostate Reduced in size. Seminal vesicles Both sides: reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, purple. 19 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Prostate Reduced in size. Seminal vesicles Both sides: reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Renal lymph node Both sides: enlarged. Pancreatic lymph n Enlarged. 20 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Prostate Reduced in size. Seminal vesicles Both sides: reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Pancreatic lymph n Enlarged.

FEMALES ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

GROUP 1 (CONTROL) 21 No findings noted Scheduled sacrifice, 07Dec2012 22 Uterus Contains fluid. Scheduled sacrifice, 07Dec2012 23 Uterus Contains fluid. Scheduled sacrifice, 07Dec2012 24 No findings noted Scheduled sacrifice, 07Dec2012 25 No findings noted Scheduled sacrifice, 07Dec2012

GROUP 2 (50 MG/KG) 26 No findings noted Scheduled sacrifice, 07Dec2012 27 No findings noted Scheduled sacrifice, 07Dec2012 28 Pancreatic lymph n Discolouration, reddish. Scheduled sacrifice, 07Dec2012

− Page 30

− 08Feb13 15h14Project 501432 APPENDIX 2

MACROSCOPIC FINDINGS FEMALES ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

GROUP 2 (50 MG/KG) 29 No findings noted Scheduled sacrifice, 07Dec2012 30 Uterus Contains fluid. Scheduled sacrifice, 07Dec2012

GROUP 3 (150 MG/KG) 31 Pancreatic lymph n Enlarged. Scheduled sacrifice, 07Dec2012 32 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Wall: thickened. Contents: gelatinous. Pancreatic lymph n Discolouration, reddish. 33 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Wall: thickened. Jejunum Wall: thickened. Liver Left lateral lobe: focus/foci, many, red

− brown. Uterus Reduced in size. Mesenteric lymph n Discolouration, dark red. 34 Stomach Forestomach: irregular surface. Scheduled sacrifice, 07Dec2012 Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Adrenal glands Both sides: discolouration, pale. 35 Mesenteric lymph n Discolouration, dark red. Scheduled sacrifice, 07Dec2012 Pancreatic lymph n Discolouration, reddish.

GROUP 4 (450 MG/KG) 36 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Contents: gelatinous. Wall: dilation. Jejunum Wall: dilation. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Ovaries Both sides: reduced in size. Uterus Reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Pancreatic lymph n Enlarged. 37 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Right side: pelvic dilation. Both sides: discolouration, greenish. Uterus Reduced in size. Adrenal glands Both sides: discolouration, pale. Mesenteric lymph n Discolouration, purple. Pancreatic lymph n Enlarged. 38 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach, wall: focus/foci, d=3x3 mm, yellowish, dark red. Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Uterus Reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size.

− Page 31

− 08Feb13 15h14Project 501432 APPENDIX 2

MACROSCOPIC FINDINGS FEMALES ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

GROUP 4 (450 MG/KG) Pancreatic lymph n Enlarged. 39 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach: focus/foci, yellowish, reddish. Grown together with: liver, processus papillarus. Forestomach: irregular surface. Jejunum Contains fluid, gelatinous. Kidneys Both sides: discolouration, greenish. Ovaries Both sides: reduced in size. Uterus Reduced in size. Adrenal glands Enlarged. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Renal lymph node Left side: discolouration, dark red. 40 General observations Emaciated. Scheduled sacrifice, 07Dec2012 Stomach Forestomach, wall: focus/foci, d=9x7 mm, yellowish, dark red. Forestomach: irregular surface. Duodenum Wall: thickened. Contents: gelatinous. Jejunum Wall: thickened. Contents: gelatinous. Kidneys Both sides: discolouration, greenish. Ovaries Both sides: reduced in size. Uterus Reduced in size. Adrenal glands Both sides: discolouration, pale. Thymus Reduced in size. Mesenteric lymph n Discolouration, dark red. Renal lymph node Both sides: enlarged. Pancreatic lymph n Enlarged.

− Page 32

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN WEIGHTS (GRAM) MALES END OF TREATMENT

ANIMAL BODY W. (GRAM) BRAIN (GRAM) HEART (GRAM) LIVER (GRAM) THYROIDS (GRAM)

GROUP 1 (CONTROL) 1 302 2.15 0.954 9.52 0.027 2 291 2.14 0.818 8.84 0.023 3 277 1.95 0.859 8.11 0.022 4 269 1.92 0.871 7.86 0.021 5 286 2.09 0.841 8.32 0.025

GROUP 2 (50 MG/KG) 6 282 1.84 0.843 9.03 0.023 7 296 2.07 0.798 9.13 0.027 8 255 1.95 0.799 7.72 0.019 9 251 2.04 0.786 7.79 0.025 10 218 1.84 0.686 6.43 0.020

GROUP 3 (150 MG/KG) 11 257 2.07 0.805 7.83 0.022 12 255 1.91 0.802 9.01 0.022 13 246 1.96 0.760 8.43 0.021 14 284 2.01 0.900 9.07 0.022 15 245 2.04 0.698 8.01 0.026

GROUP 4 (450 MG/KG) 16 173 1.75 0.632 7.11 0.023 17 156 1.68 0.482 6.70 0.019 18 153 1.81 0.537 7.20 0.018 19 166 1.88 0.567 6.75 0.013 20 204 1.79 0.708 8.47 0.022

MALES END OF TREATMENT

ANIMAL THYMUS (GRAM) KIDNEYS (GRAM) ADRENALS (GRAM) SPLEEN (GRAM) TESTES (GRAM)

GROUP 1 (CONTROL) 1 0.496 2.66 0.054 0.589 3.06 2 0.558 2.13 0.047 0.531 3.20 3 0.484 2.18 0.059 0.541 2.82 4 0.473 2.15 0.062 0.606 3.00 5 0.632 2.12 0.067 0.600 3.11

GROUP 2 (50 MG/KG) 6 0.458 2.35 0.056 0.573 3.11 7 0.507 2.25 0.054 0.587 3.44 8 0.425 2.27 0.054 0.543 3.30 9 0.361 2.17 0.060 0.472 3.10 10 0.336 1.78 0.056 0.378 3.05

GROUP 3 (150 MG/KG) 11 0.450 2.17 0.053 0.436 3.15 12 0.294 2.36 0.054 0.499 3.64 13 0.323 2.08 0.063 0.500 2.86 14 0.563 2.48 0.057 0.522 2.76 15 0.387 2.18 0.062 0.461 3.39

− Page 33

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN WEIGHTS (GRAM) MALES END OF TREATMENT

ANIMAL THYMUS (GRAM) KIDNEYS (GRAM) ADRENALS (GRAM) SPLEEN (GRAM) TESTES (GRAM)

GROUP 4 (450 MG/KG) 16 0.011 1.89 0.098 0.307 2.84 17 0.053 1.64 0.075 0.291 2.42 18 0.075 1.62 0.069 0.288 2.37 19 0.080 1.73 0.068 0.364 2.88 20 0.187 2.02 0.082 0.424 2.52

MALES END OF TREATMENT

ANIMAL PROSTATE (GRAM) EPIDIDYMIDES (GRAM) SEMINAL VES (GRAM)

GROUP 1 (CONTROL) 1 0.479 0.722 0.808 2 0.770 0.704 0.907 3 0.556 0.800 0.995 4 0.414 0.769 1.027 5 0.427 0.761 1.212

GROUP 2 (50 MG/KG) 6 0.289 0.721 0.701 7 0.324 0.817 0.888 8 0.455 0.817 0.688 9 0.348 0.704 0.930 10 0.347 0.678 0.780

GROUP 3 (150 MG/KG) 11 0.303 0.735 0.586 12 0.246 0.791 0.605 13 0.252 0.725 0.638 14 0.331 0.701 0.739 15 0.395 0.713 0.855

GROUP 4 (450 MG/KG) 16 0.182 0.594 0.462 17 0.130 0.544 0.163 18 0.217 0.595 0.181 19 0.143 0.613 0.128 20 0.236 0.639 0.392

− Page 34

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN/BODY WEIGHT RATIOS (%) MALES END OF TREATMENT

ANIMAL BODY W. (GRAM) BRAIN (%) HEART (%) LIVER (%) THYROIDS (%)

GROUP 1 (CONTROL) 1 302 0.71 0.316 3.15 0.009 2 291 0.73 0.281 3.04 0.008 3 277 0.71 0.310 2.93 0.008 4 269 0.71 0.324 2.92 0.008 5 286 0.73 0.294 2.91 0.009

GROUP 2 (50 MG/KG) 6 282 0.65 0.299 3.20 0.008 7 296 0.70 0.270 3.08 0.009 8 255 0.77 0.313 3.03 0.007 9 251 0.81 0.313 3.10 0.010 10 218 0.85 0.315 2.95 0.009

GROUP 3 (150 MG/KG) 11 257 0.80 0.313 3.05 0.009 12 255 0.75 0.315 3.53 0.009 13 246 0.80 0.309 3.43 0.009 14 284 0.71 0.317 3.19 0.008 15 245 0.83 0.285 3.27 0.011

GROUP 4 (450 MG/KG) 16 173 1.01 0.365 4.11 0.013 17 156 1.08 0.309 4.30 0.012 18 153 1.19 0.351 4.71 0.012 19 166 1.13 0.342 4.07 0.008 20 204 0.88 0.347 4.15 0.011

MALES END OF TREATMENT

ANIMAL THYMUS (%) KIDNEYS (%) ADRENALS (%) SPLEEN (%) TESTES (%)

GROUP 1 (CONTROL) 1 0.164 0.88 0.018 0.195 1.01 2 0.192 0.73 0.016 0.182 1.10 3 0.175 0.79 0.021 0.195 1.02 4 0.176 0.80 0.023 0.225 1.12 5 0.221 0.74 0.023 0.210 1.09

GROUP 2 (50 MG/KG) 6 0.162 0.83 0.020 0.203 1.10 7 0.171 0.76 0.018 0.198 1.16 8 0.167 0.89 0.021 0.213 1.29 9 0.144 0.87 0.024 0.188 1.23 10 0.154 0.82 0.026 0.173 1.40

GROUP 3 (150 MG/KG) 11 0.175 0.84 0.021 0.170 1.23 12 0.115 0.92 0.021 0.196 1.43 13 0.131 0.85 0.026 0.203 1.16 14 0.198 0.87 0.020 0.184 0.97 15 0.158 0.89 0.025 0.188 1.38

− Page 35

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN/BODY WEIGHT RATIOS (%) MALES END OF TREATMENT

ANIMAL THYMUS (%) KIDNEYS (%) ADRENALS (%) SPLEEN (%) TESTES (%)

GROUP 4 (450 MG/KG) 16 0.006 1.09 0.057 0.177 1.64 17 0.034 1.05 0.048 0.187 1.55 18 0.049 1.06 0.045 0.188 1.55 19 0.048 1.04 0.041 0.219 1.74 20 0.092 0.99 0.040 0.208 1.23

MALES END OF TREATMENT

ANIMAL PROSTATE (%) EPIDIDYMIDES (%) SEMINAL VES (%)

GROUP 1 (CONTROL) 1 0.159 0.239 0.268 2 0.265 0.242 0.312 3 0.201 0.289 0.359 4 0.154 0.286 0.382 5 0.149 0.266 0.424

GROUP 2 (50 MG/KG) 6 0.102 0.256 0.249 7 0.109 0.276 0.300 8 0.178 0.320 0.270 9 0.139 0.280 0.371 10 0.159 0.311 0.358

GROUP 3 (150 MG/KG) 11 0.118 0.286 0.228 12 0.096 0.310 0.237 13 0.102 0.295 0.259 14 0.117 0.247 0.260 15 0.161 0.291 0.349

GROUP 4 (450 MG/KG) 16 0.105 0.343 0.267 17 0.083 0.349 0.104 18 0.142 0.389 0.118 19 0.086 0.369 0.077 20 0.116 0.313 0.192

− Page 36

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN WEIGHTS (GRAM) FEMALES END OF TREATMENT

ANIMAL BODY W. (GRAM) BRAIN (GRAM) HEART (GRAM) LIVER (GRAM) THYROIDS (GRAM)

GROUP 1 (CONTROL) 21 163 1.83 0.583 5.14 0.020 22 188 1.89 0.598 5.41 0.021 23 187 1.93 0.684 5.23 0.021 24 167 1.82 0.461 4.26 0.021 25 177 1.80 0.539 5.05 0.029

GROUP 2 (50 MG/KG) 26

−−− 1.85 0.593 5.63 0.023 27

−−− 1.86 0.644 5.60 0.019 28

−−− 1.75 0.581 5.29 0.020 29 180 1.72 0.594 5.27 0.019 30 178 1.90 0.592 5.47 0.023

GROUP 3 (150 MG/KG) 31 170 1.93 0.493 5.41 0.019 32 179 1.93 0.741 6.60 0.023 33 186 1.83 0.616 5.58 0.021 34 179 1.85 0.594 5.15 0.027 35 164 1.81 0.499 5.22 0.027

GROUP 4 (450 MG/KG) 36 133 1.79 0.439 5.84 0.022 37 150 1.84 0.653 6.26 0.016 38 151 1.75 0.515 6.67 0.023 39 120 1.66 0.486 5.66 0.022 40 135 1.80 0.495 6.17 0.027

FEMALES END OF TREATMENT

ANIMAL THYMUS (GRAM) KIDNEYS (GRAM) ADRENALS (GRAM) SPLEEN (GRAM) OVARIES (GRAM) UTERUS (GRAM)

GROUP 1 (CONTROL) 21 0.400 1.48 0.055 0.334 0.168 0.423 22 0.531 1.56 0.059 0.432 0.132 0.875 23 0.438 1.64 0.077 0.448 0.161 1.415 24 0.377 1.36 0.047 0.294 0.383 0.305 25 0.467 1.37 0.069 0.350 0.123 0.290

GROUP 2 (50 MG/KG) 26 0.491 1.48 0.070 0.430 0.114 0.328 27 0.421 1.66 0.078 0.382 0.124 0.476 28 0.293 1.35 0.060 0.318 0.128 0.273 29 0.440 1.56 0.063 0.379 0.146 0.456 30 0.341 1.38 0.057 0.289 0.111 0.777

GROUP 3 (150 MG/KG) 31 0.300 1.34 0.045 0.307 0.113 0.351 32 0.320 1.70 0.068 0.372 0.137 0.390 33 0.372 1.51 0.070 0.372 0.084 0.186 34 0.398 1.65 0.067 0.386 0.114 0.380 35 0.255 1.36 0.051 0.319 0.077 0.161

− Page 37

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN WEIGHTS (GRAM) FEMALES END OF TREATMENT

ANIMAL THYMUS (GRAM) KIDNEYS (GRAM) ADRENALS (GRAM) SPLEEN (GRAM) OVARIES (GRAM) UTERUS (GRAM)

GROUP 4 (450 MG/KG) 36 0.092 1.40 0.066 0.262 0.068 0.116 37 0.108 1.51 0.072 0.292 0.101 0.159 38 0.130 1.59 0.087 0.334 0.105 0.186 39 0.043 1.41 0.082 0.177 0.083 0.158 40

−−− 1.47 0.089 0.281 0.081 0.126

− Page 38

− 08Feb13 15h14 !

! Thymus weight was excluded due to a biologi c ally unrealistic valueProject 501432 APPENDIX 2

ORGAN/BODY WEIGHT RATIOS (%) FEMALES END OF TREATMENT

ANIMAL BODY W. (GRAM) BRAIN (%) HEART (%) LIVER (%) THYROIDS (%)

GROUP 1 (CONTROL) 21 163 1.12 0.358 3.15 0.012 22 188 1.00 0.318 2.88 0.011 23 187 1.03 0.366 2.80 0.011 24 167 1.09 0.276 2.55 0.013 25 177 1.02 0.305 2.85 0.016

GROUP 2 (50 MG/KG) 26

−−− −−− −−− −−− −−− 27

−−− −−− −−− −−− −−− 28

−−− −−− −−− −−− −−− 29 180 0.96 0.330 2.93 0.011 30 178 1.07 0.333 3.07 0.013

GROUP 3 (150 MG/KG) 31 170 1.14 0.290 3.18 0.011 32 179 1.08 0.414 3.69 0.013 33 186 0.98 0.331 3.00 0.011 34 179 1.04 0.332 2.88 0.015 35 164 1.10 0.304 3.18 0.016

GROUP 4 (450 MG/KG) 36 133 1.34 0.330 4.39 0.017 37 150 1.23 0.435 4.17 0.011 38 151 1.16 0.341 4.42 0.015 39 120 1.38 0.405 4.72 0.018 40 135 1.33 0.367 4.57 0.020

FEMALES END OF TREATMENT

ANIMAL THYMUS (%) KIDNEYS (%) ADRENALS (%) SPLEEN (%) OVARIES (%) UTERUS (%)

GROUP 1 (CONTROL) 21 0.245 0.91 0.034 0.205 0.103 0.260 22 0.282 0.83 0.031 0.230 0.070 0.465 23 0.234 0.88 0.041 0.240 0.086 0.757 24 0.226 0.81 0.028 0.176 0.229 0.183 25 0.264 0.77 0.039 0.198 0.069 0.164

GROUP 2 (50 MG/KG) 26

−−− −−− −−− −−− −−− −−− 27

−−− −−− −−− −−− −−− −−− 28

−−− −−− −−− −−− −−− −−− 29 0.244 0.87 0.035 0.211 0.081 0.253 30 0.192 0.78 0.032 0.162 0.062 0.437

GROUP 3 (150 MG/KG) 31 0.176 0.79 0.026 0.181 0.066 0.206 32 0.179 0.95 0.038 0.208 0.077 0.218 33 0.200 0.81 0.038 0.200 0.045 0.100 34 0.222 0.92 0.037 0.216 0.064 0.212 35 0.155 0.83 0.031 0.195 0.047 0.098

− Page 39

− 08Feb13 15h14Project 501432 APPENDIX 2

ORGAN/BODY WEIGHT RATIOS (%) FEMALES END OF TREATMENT

ANIMAL THYMUS (%) KIDNEYS (%) ADRENALS (%) SPLEEN (%) OVARIES (%) UTERUS (%)

GROUP 4 (450 MG/KG) 36 0.069 1.05 0.050 0.197 0.051 0.087 37 0.072 1.00 0.048 0.195 0.067 0.106 38 0.086 1.05 0.058 0.221 0.070 0.123 39 0.036 1.17 0.068 0.148 0.069 0.132 40

−−− 1.09 0.066 0.208 0.060 0.093

− Page 40

− 08Feb13 15h14 !

! Thymus weight was excluded due to a biologi c ally unrealistic valuem- (2,3

- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline Project 501432 APPENDIX 2

- Page 41 - KEY TO MISSING VALUES/REMARKS CLINICAL LABORATORY INVESTIGATIONS

End of Treatment

Haematology: Animal(s):
39

--- = Citrate sample clotted
24

--- = EDTA sample clotted
16 Differential leucocyte count was also performed manually because of a techni cal error in the automated count and these results are reported

Clinical Biochemistry: No remarksm-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 3

- Page 1 - APPENDIX 3 FORMULATION ANALYSIS REPORTm-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 2 - 1. CONTENTS

1. CONTENTS

...................................................................................................................................... 2 2. REPORT APPROVAL

................................................................ ...................................................... 3 3. SUMMARY

........................................................................................................................................ 4 4. INTRODUCTION

.............................................................................................................................. 5 4.1. Preface

...................................................................................................................................... 5 4.2. Aim of the study

................................................................ ........................................................ 5 5. MATERIALS AND METHODS

.......................................................................................................... 5 5.1. Reagents

................................................................................................................................... 5 5.2. Samples

.................................................................................................................................... 5 5.3. Analytical method

................................................................ ...................................................... 5 5.3.1. Analytical conditions

....................................................................................................... 5 5.3.2. Preparation of solutions

.................................................................................................. 6 5.3.3. Sample injections

............................................................................................................ 6 5.4. Electronic data capture

............................................................................................................. 6 5.5. Formulas

................................................................................................................................... 7 5.6. Specifications

............................................................................................................................ 7 6. RESULTS

......................................................................................................................................... 8 6.1. Calibration curves

................................................................ ..................................................... 8 6.2. Samples

.................................................................................................................................... 8 6.2.1. Procedural recovery samples

......................................................................................... 8 6.2.2. Test samples

................................................................ ................................................... 8

TABLES Table 1 Procedural recovery samples

.............................................................................................. 9 Table 2 Accuracy and homogeneity test

......................................................................................... 10 Table 3 Stability test

................................................................ ........................................................ 10m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 4 - 3. SUMMARY

The purpose of this part of the study was to determine the accuracy of preparation, homogeneity and stability of the test substance in formulations.

Accuracy of preparation The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement with target concentrations (i.e. mean accuracies between 85% and 115%).

No test substance was detected in the Group 1 formulation.

Homogeneity The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%).

Stability Formulations at the entire range were stable when stored at room temperature under normal laboratory light conditions for at least 6 hours.m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 5 - 4. INTRODUCTION

4.1. Preface
Study plan analytical phase Start : 27 November 2012 Completion : 28 November 2012

4.2. Aim of the study
The purpose of the analytical phase was to determine the accuracy of preparation, homogeneity and stability of the test substance in formulations.

5. MATERIALS AND METHODS

5.1. Reagents

Water Tap water purified by a Milli-Q water purification system (Millipore, Bedford, MA, USA)

Acetonitrile Biosolve, Valkenswaard, The Netherlands

All reagents were of analytical grade, unless specified otherwise.

5.2. Samples
Accuracy, homogeneity and stability were determined for formulations prepared for use during treatment.

Duplicate samples (approximately 500 mg), which were taken from the formulations using a pipette, were accurately weighed into volumetric flasks of 20 or 50 ml. For determination of accuracy, samples were taken at middle position (50% height) or at top, middle and bottom position (90%, 50% and 10% height). The samples taken at 90%, 50% and 10% height were also used for the determination of the homogeneity of the formulations. For determination of stability, additional samples were taken at 50% height and stored at room temperature under normal laboratory light conditions for 6 hours.

The volumetric flasks were filled up to the mark with acetonitrile. The solutions were further diluted to obtain an end solution of 30/70 (v/v) acetonitrile/water and concentrations within the calibration range.

5.3. Analytical method 5.3.1. Analytical conditions
Quantitative analysis was based on the analytical method validated for the test substance in project 501424

.
Analytical conditions: Instrument Alliance Separation Module 2695 (Waters, Milford, MA, USA) Detector Dual λ Absorbance Detector 2487 (Waters) Column Symmetry Shield RP-18, 100 mm  4.6 mm i.d., dp = 3.5 μm (Waters) Column temperature 40°C  1°C Injection volume 100 μl Mobile phase 30/70 (v/v) acetonitrile/water Flow 1 ml/min UV detection 253 nmm-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 6 - 5.3.2. Preparation of solutions
Stock and spiking solutions Stock and spiking solutions of the test substance were prepared in acetonitrile at concentrations of 835 - 4035 mg/l.

Calibration solutions Calibration solutions in the concentration range of 0.0400 – 59.7 mg/l were prepared from two stock solutions. The end solution of the calibration solutions was 30/70 (v/v) acetonitrile/water

. Procedural recovery samples Approximately 500 mg blank vehicle was spiked with the test substance at a target concentration of 1

or 90 mg/g. The accuracy samples were treated similarly as the test samples (see paragraph 5.2 ‘Samples’).

5.3.3. Sample injections
Calibration solutions were injected in duplicate. Test samples and procedural recovery samples were analysed by single injection.

5.4. Electronic data capture
System control, data acquisition and data processing were performed using the following programme: - Empower version 7.00 (Waters, Milford, MA, USA).

Temperature, relative humidity and/or atmospheric pressure during sample storage and/or performance of the studies was monitored continuously using the following programme: - REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, USA).m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 7 - 5.5. Formulas
Response (R) Peak area test substance [units]

Calibration curve

where: C N = nominal concentration [mg/l]

a = slope [units  l/mg] b = intercept [units]

Analysed concentration (C A )

where: w = weight sample [mg] V = volume volumetric flask [ml] d = dilution factor

Recovery

where: C N = nominal concentration [mg/g]

Accuracy

where: C T = target concentration [mg/g]
Relative difference (relative diff.)

where: C t = mean concentration of stored samples [mg/g] C 0 = mean concentration of non-stored samples [mg/g]

5.6. Specifications
Preparation of formulations was considered acceptable if the mean accuracy was in the range 85 -115% of the target concentration and if the coefficient of variation was ≤ 10%. Formulations were considered stable if the relative difference between the stored and freshly taken samples was ≤ 10%.m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 8 - 6. RESULTS

6.1. Calibration curves
A calibration curve was constructed using five concentrations. For each concentration, two responses were used. Linear regression analysis was performed using the least squares method with a 1/concentration 2 weighting factor. The coefficient of correlation (r) was > 0.99.

6.2. Samples
6.2.1. Procedural recovery samples

The results of

the procedural recovery samples are given in Table 1

.
The mean recoveries of the procedural recovery samples fell within the criterion of 85 -115%. It demonstrated that the analytical method was adequate for the determination of the test substance in the test samples.

6.2.2. Test samples The results of the test samples are given in Table 2 and Table 3

.
Accuracy of preparation In the Group 1 formulation, no test substance was detected.

The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement with target concentrations (i.e. mean accuracies between 85% and 115%).

Homogeneity The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%).

Stability Analysis of Group 2 and Group 4 formulations after storage yielded a relative difference of ≤ 10%. Based on this, the formulations were found to be stable during storage at room temperature under normal laboratory light conditions for at least 6 hours.m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 9 - TABLES

Table 1 Procedural recovery samples

Date of preparation [dd

- mm

- yy] Date of

analysis [dd

- mm

- yy] Target

concentration [mg/g] Nominal

concentration [mg/g] Analysed

concentration [mg/g] Recovery

[%] Mean

recovery [%]

27

- 11

- 12 27

- 11

- 12 1 0.980 1.02 104 105 1.01 1.06 105

27

- 11

- 12 27

- 11

- 12 90 96.5 105 108 109 85.0 92.6 109m-( 2,3 -epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

- Page 10 - Table 2 Accuracy and homogeneity test
Group Date of

analysis

[dd

- mm

- yy] Sample

position Concentration

[mg/g] Accuracy

[%] Homogeneity

(coefficient of variation) [%] Target Analysed Individual Mean

1 27

- 11

- 12 50% height 0 n.d. n.a. 0 n.d. n.a.

2 27

- 11

- 12 90% height 9.64 8.64 89.7 95.1 4.3 9.64 8.94 92.7 50% height 9.64 8.96 92.9

9.64 9.23 95.7 10% height 9.64 9.55 99.1

9.64 9.65 100

3 27

- 11

- 12 50% height 28.8 28.2 97.7 98.6 n.a. 28.8 28.7 99.4

4 27

- 11

- 12 90% height 85.7 86.6 101 103 1.1 85.7 88.2 103 50% height 85.7 87.8 102

85.7 87.5 102 10% height 85.7 89.1 104

85.7 89.0 104

n.d. Not detected. n.a. Not applicable.

Table 3 Stability test
Group Date of analysis

[dd

- mm

- yy] Analysed concentration [mg/g] Relative diff.

[%] t=0 1 t= 6 hours

2 27

- 11

- 12 9.16 9.30 2 1.5

4 27

- 11

- 12 88.0 87.9 3

- 0.18

1 Mean of six samples at t=0 taken at 10%, 50% and 90% height.

2 Mean of two samples at t=6 hours taken at 50% height. Individual results were 9.22 and 9.39 mg/g.

3 Mean of two samples at t=6 hours taken at 50% height. Individual results were 87.0 and 88.7 mg/g.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 4

- Page 1 - APPENDIX 4 HISTOPATHOLOGY REPORTPATHOLOGY REPORT PAGE : 2/ 151
TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF CONTENTS

————————————————————————————————————————————————————————————————————————— PAGE :

AUTHENTICATION 3

PRINCIPAL SECTION SUMMARY 4

METHODS 6

RESULTS 8

CONCLUSIONS 11

EXPLANATION OF CODES AND SYMBOLS 12

SUMMARY TABLES SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades 13

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings 23

INDIVIDUAL ANIMAL DATA TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 31

ANIMAL HEADING DATA DOSE GROUP 01 43

TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 01 44

ANIMAL HEADING DATA DOSE GROUP 02 71

TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 02 72

ANIMAL HEADING DATA DOSE GROUP 03 91

TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 03 92

ANIMAL HEADING DATA DOSE GROUP 04 115

TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 04 116PATHOLOGY REPORT PAGE : 4/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY

————————————————————————————————————————————————————————————————————————— Pathomorphologic examination was performed on 40 Wistar -Han rats (20 males, 20 females) which had been subjected to a 28 day oral (gavage) toxicity study with the test item m- (2,3

- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline

. The rats were assigned to four dose groups, each containing 5 males and 5 females. The test item was administered once daily by gavage at doses of 50, 15 0 and 45 0 mg/kg (dose Groups 2, 3 and 4 respectively) for 28 days. The rats of the control Group 1 received the vehicle, propylene glycol, alone.
At the end of the treatment period all rat s from all Groups were kill ed and subjected to complete necropsies. Histopathologic examination was performed on an extensive list of organs and tissues from all Group 1 and 4 animals as well as the thymus, stomach, duodenum, jejunum, Peyer’s patches, spleen, mesenteric lymph node, mandibular lymph nodes, adrenal glands and femur including joint from all Group 2 and 3 rats, the prostate gland, coagulating glands and seminal vesicles from all male Group 2 and 3 rats, the liver, uterus, cervix and vagina from all female Group 2 and 3 rats and all organs with macroscopic findings from all rats.

There were no unscheduled deaths.

There were treatment

- related macroscopic findings present at

- 50 and 150 mg/kg in the pancreatic lymph node ( discoloured ). - 150 and 450 mg/kg in the stomach ( forestomach

– irregular surface and

– discoloured focus/foci ), duodenum and jejunum

( wall thickened and contents gelatinous ), mesenteric lymph node ( discoloured ), pancreatic lymph node ( enlarged and discoloured ), adrenal glands ( discoloured ) and uterus ( reduced in size ). - 450 mg/kg as general emaciation , in the thymus ( reduced in size ), renal lymph node ( enlarged ), kidneys ( discoloured ), ovaries ( reduced in size ), prostate gland ( reduced in size ) and seminal vesicles ( reduced in size ).

There were treatment- related microscopic findings present in males and/or females starting at

- 50 mg/kg (Group 2) Duodenum , hemorrhage was present in male and female rats treated at 50, 150 and at 450 mg/kg up to slight degree. Duodenum , hypertrophy with villous stunting was present in male and female rats treated at 50, 150 and at 450 mg/kg up to moderate degree. This finding corresponded with the macroscopic finding wall thickened. Peyer’s patches , lymphoid atrophy was present in females treated at 50 mg/kg and in males and females treated at 150 and at 450 mg/kg up to moderate degree. Mesenteric lymph node , erythrophagocytosis was present in male and female rats treated at 50, 150 and at 450 mg/kg up to moderate degree. This finding correlated with the macroscopic finding d iscolouration reddish/dark red/purple

.

- 150 mg/kg (Group 3) Stomach , ulcer forestomach was present in male rats treated at 150 mg/kg and in male and female rats at 450 mg/kg up to marked degree. This finding corresponded with the macroscopic finding forestomach discoloured focus/foci

.PATHOLOGY REPORT PAGE : 5/ 151

PRINCIPAL SECTION TOX : 501432

———————————————————————————————————————————————————————————————————————— — TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY

—————————————————————————————————————————————————————————————————————————

- 150 mg/kg Continued Stomach , hyperplasia forestomach was present in male and female rats treated at 150 and at 450 mg/kg up to marked degree. This finding was also present as a background finding in one 50 mg/kg treated male rat at minimal degree. This finding corresponded with the macroscopic finding forestomach irregular surface

. Jejunum , hypertrophy with villous stunting was present in male and female rats treated at 150 and at 450 mg/kg up to moderate degree. This finding corresponded with the macroscopic finding wall thickened. Mesenteric lymph node , lymphoid atroph y was present in male and female rats treated at 150 and at 450 mg/kg up to moderate degree. Mesenteric lymph node , increased mast cells were present in male and female rats treated at 150 and at 450 mg/kg up to moderate degree. Liver , centrilob ular hypertrophy was present in female rats treated at 150 and 450 mg/kg up to slight degree.
Uterus , cervix and vagina , atrophy was present in female rats treated at 150 and 450 mg/kg.

- 450 mg/kg (Group 4) Thymus , lymphoid atrophy was present in male and female rats treated at 450 mg/kg up to marked degree. This finding corresponded with the macroscopic finding reduced in size

. Jejunum , hemorrhage was present in male and female rats treated at 450 mg/kg up to slight degree. Spleen , lymphoid atrophy was present in male and female rats treated at 450 mg/kg up to slight degree. Adrenal glands , vacuolation zona fasciculata was present at increased incidence and severity in male and female rats treated at 450 mg/kg up to slight degree. The minimal incidence (1/5) and severity (minimal) present in males treated at 50 and 150 mg/kg is considered to be within background. This findin g corresponded with the macroscopic finding discoloured. Femur including joint , decreased bone, secondary spongiosa was present in male and female rats treated at 450 mg/kg up to moderate degree. This was likely related to the emaciation. Prostate gland , small with normal histology was present in male rats treated at 450 mg/kg. This finding corresponded with the macroscopic finding reduced in size

. Seminal vesicles , reduced contents was bilaterally present in male rats treated at 450 mg/kg at slight degree and, as background finding, it was unilaterally present in 1/5 control Group rats at moderate degree. This finding corresponded with the macroscopic finding reduced in size

. Coagulating glands , reduced contents was present in male rats treated at 450 mg/kg at slight degree.

After 28 days treatment with test item m- (2,3 -epoxypropoxy) - N,N

bis(2,3

- epoxypropyl)aniline there are adverse finding in the form o f hemorrhage and hypertrophy with villous stunting in the duodenum in both sexes at 50 mg/kg; therefore, no dose Group is without adverse findings

.PATHOLOGY REPORT PAGE : 6/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— METHODS

—————————————————————————————————————————————————————————————————————————

Study Design Group Dose level Dose volume Number of animals Animal numbers

mg/kg mL/kg Males Females Males Females
1 0 (vehicle) 5 5 5 1

- 5 21

- 25
2 50 5 5 5 6

- 10 26

- 30
3 150 5 5 5 11

- 15 31

- 35
4 450 5 5 5 16

- 20 36

- 40

Administration of the Test Item The test item m-(2,3- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline was administered once daily by gavage for 28 days. The rats of the control Group 1 received the vehicle, propylene glycol, alone.

Necropsy and Histopathology At the end of the treatment period all animals from all Groups were killed. All rats were subjected to complete necropsies. All macroscopic abnormalities observed were recorded.

From the surviving animals, the terminal body weight and the weights of the adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries, spleen, testes, thymus and uterus (including cervix) were recorded at necropsy. Weights of prostate gland, seminal vesicles with coagulating glands and thyroid including parathyroid were recorded after fixation for at least 24 hours. Body and organ weights are reported in the main toxicology report.

Representative tissue samples were preserved from all animals/sex/group. Testes, epididymides and eyes (with opti c nerves and Harderian glands) were initially fixed in Modified Davidson's solution for at least 24 hours. All other organ samples were fixed in 4% phosphate buffered neutral formaldehyde solution (10% formalin). Adrenal glands(2), [aorta], brain (cerebell um, mid-brain, cortex)(3), [clitoral gland], epididymides(2), [esophagus], eyes [with optic nerve and Harderian glands](2), femur including joint(1), heart(1), kidneys(2), [lacrimal gland, exorbital], [larynx], large intestine(3): caecum, colon and rectum, liver(2), lungs(2), lymph nodes: mandibular(1),

- mesenteric(1), [nasopharynx], [female mammary gland area], ovaries(2), [pancreas], [pituitary gland], [preputial gland], prostate gland(1), [salivary glands: mandibular, sublingual], sciatic nerve(1), semin al vesicles with coagulating glands(2), skeletal muscle(1), [skin], spinal cord(3): cervical, midthoracic and lumbar, small intestine(3): duodenum, jejenum and ileum with Peyer's patches, spleen(1), sternum with bone marrow(1), stomach(1), testes(2), thymu s(1), thyroid glands(2) with parathyroid glands(2), [tongue], trachea(1), urinary bladder(1), uterus(3), cervix(1), vagina(1) and all gross lesions.

Following fixation, organs (except those listed in brackets) from all Group 1 and 4 rats as well as all organs with macroscopic findings from all rats were trimmed, processed and embedded in paraffin wax. After histopathologic examination slides of the thymus, stomach, duodenum, jejunum, Peyer’s patches, spleen, mesenteric lymph node, mandibular lymph nodes , adrenal glands and femur including joint from all Group 2 and 3 rats, the prostate gland, coagulating glands and seminal vesicles from all male Group 2 and 3 rats, the liver, uterus, cervix and vagina from all female Group 2 and 3 rats were prepared and examined.PATHOLOGY REPORT PAGE : 7/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— METHODS

—————————————————————————————————————————————————————————————————————————

All sections were cut at a thickness of 2-4 micrometers and stained with hematoxylin and eosin. Number of sections made are given in parentheses.

All sections were examined by light microscopy in the period 28 January

– 20 February 2013.

Data Compilation The animal data and macroscopic findings were electronically transferred from the necropsy raw data files of Toxdata system® into the computer system PathData© where the microscopic findings were recorded by the undersigned pathologist using on -line input under pathology number: 41310 JOL.

All macroscopic and microscopic findings are given for each animal in text form under "Text of Gross and Microscopic Findings" . The incidence of microscopic findings is also presented in tabular form: “ Incidence table - all microscopic findings ” and “ Incidence table

– Selected findings with grades ” . Incidence tables were created by computer.

Histopathological changes were described according to distribution, severity and morphological character.

Severity scores were assigned as follows : Grade "1": Minimal/very few/very small. Grade "2": Slight/few/small. Grade "3": Moderate/moderate number/moderate size. Grade "4": Marked/many/large. Grade "5": Massive/extensive number/extensive size. Grade "p": Finding present, grading not scored.

In the case of findings in bilaterally affected paired organs, the severity score of the worst affected organ was recorded and a comment was made listing the severity score in the contralateral organ.

Peer Review Microscopic findings were subjected to a review by Eric van Esch (reviewing pathologist; InSight Pathology B.V.) whereby the reviewer and study pathologist reached consensus.PATHOLOGY REPORT PAGE : 8/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— RESULTS

—————————————————————————————————————————————————————————————————————————

Mortality

There were no unscheduled deaths.

Macroscopic Findings

Treatment

- related macroscopic findings present were

General Observations , e maciated was noted in 4/5 male and 5/5 female 450 mg/kg treated rats

. Thymus , reduced in size was noted in 5/5 male and 4/5 female 450 mg/kg
treated rats. Stomach , forestomach irregular surface was noted in 5/5 male and 3/5 female 150 mg/kg and in 4/5 male and 5/5 female 450 mg/kg treated rats. Stomach , forestomach focus/f oci, yellowish/tan, reddish/dark red was noted in 1/5 male 150 mg/kg and in 3/5 female 450 mg/kg treated rats. Duodenum , wall thickened/dilation was noted in 3/5 male and 3/5 female 150 mg/kg and in 4/5 male and 4/5 female 450 mg/kg treated rats. Duodenum , contents gelatinous was noted in 3/5 male and 2/5 female 150 mg/kg and in 4/5 male and 4/5 female 450 mg/kg treated rats. Jejunum , wall thickened/dilation was noted in 2/5 male and 2/5 female 150 mg/kg and in 4/5 male and 4/5 female 450 mg/kg treated rats

. Jejunum , contents/contains fluid gelatinous was noted in 2/5 male and 1/5 female 150 mg/kg and in 4/5 male and 5/5 female 450 mg/kg treated rats. There was no microscopic correlate to this finding. Mesenteric lymph node , discolouration reddish/dark red/p urple was noted in 4/5 male and 2/5 female 150 mg/kg and in 5/5 male and 4/5 female 450 mg/kg treated rats. Pancreatic lymph node , enlarged was noted in 2/5 male and 1/5 female 150 mg/kg and 3/5 male and 4/5 female 450 mg/kg treated rats. Pancreatic lymph node , discolouration reddish was noted in 1/5 female 50 mg/kg and in 1/5 male and 2/5 female 150 mg/kg treated rats. Renal lymph node , enlarged was noted in 1/5 male and 1/5 female 450 mg/kg treated rats. Adrenal glands , discolouration pale was noted in 1/5 female 150 mg/kg and in 4/5 male and 4/5 female 450 mg/kg treated rats. Kidneys , discolouration greenish was noted in 5/5 male and 5/5 female 450 mg/kg treated rats.
Uterus , reduced in size was noted in 1/5 150 mg/kg and in 5/5 450 mg/kg
treated rats. Ovaries , reduced in size was noted in 3/5 450 mg/kg treated rats.
Prostate gland , reduced in size was noted in 5/5 450 mg/kg treated rats. Seminal vesicles , reduced in size was noted in 5/5 450 mg/kg treated

rats.PATHOLOGY REPORT PAGE : 9/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JO L
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— RESULTS

—————————————————————————————————————————————————————————————————————————

Microscopic Findings

There were treatment- related microscopic findings present in males and/or females starting at

- 50 mg/kg (Group 2)
Duodenum , hemorrhage was present in 4/5 male (4 minimal) and 3/5 female (3 minimal) rats at 50 mg/kg, in 3/5 male (3 minimal) and 4/5 female (1 minimal, 3 slight) rats at 150 mg/kg and in 5/5 male (2 minimal, 3 slight) and 4/5 female (2 minimal, 2 slight) rats treated at 450 mg/kg. Duodenum , hypertrophy with villous stunting was present in 5/5 male (4 minimal, 1 slight) and 5/5 female (2 minimal, 3 slight) rats treated at 50 mg/kg, in 5/5 male (5 slight) and 5/5 female (1 minimal, 3 slight, 1 moderate) rats tr eated at 150 mg/kg and in 5/5 male (1 slight, 4 moderate) and 5/5 female (4 slight, 1 moderate) rats treated at 450 mg/kg. This finding corresponded with the macroscopic finding wall thickened. Peyer’s patches , lymphoid atrophy was present in 1/5 female (1 slight) treated at 50 mg/kg , in 1/5 male (1 slight) and 1/5 female (1 moderate) rats treated at 150 and in 3/5 male (2 minimal, 1 slight) and 4/5 female (1 minimal, 3 slight) rats at 450 mg/kg. Mesenteric lymph node , erythrophagocytosis was present in 1 /5 male ( slight) and 1/5 female (minimal) rats treated at 50 mg/kg, in 5/5 male (3 slight, 2 moderate) and 3/5 female (3 slight) rats at 150 mg/kg and in 5/5 male (5 moderate) and 5/5 female (3 slight , 2 moderate) rats at 450 mg/kg. This finding correlated with the macroscopic finding discolouration reddish/dark red/purple

.

- 150 mg/kg (Group 3) Stomach , ulcer forestomach was present in 2/5 male rat (1 slight, 1 moderate) treated at 150 mg/kg and in 5/5 male (1 moderate, 4 marked) and 5/5 female (5 marked) rats at 450 mg/kg. This finding corresponded with the macroscopic finding forestomach discoloured focus/foci

. Stomach , hyperplasia forestomach was present at increased incidence and severity in 5/5 male (3 slight, 2 moderate) and 5/5 female (3 minimal, 1 slig ht, 1 moderate) rats treated at 150 mg/kg and in 5/5 male (2 slight, 3 moderate) and 5/5 female (4 moderate, 1 marked) rats at 450 mg/kg. This finding was present at a background incidence and severity in 1/5 male (minimal) 50 mg/kg treated. This finding c orresponded with the macroscopic finding forestomach irregular surface

. Jejunum , hypertrophy with villous stunting was present in 2/5 male (1 minimal, 1 slight) and 1/5 female (1 minimal) rats at 150 mg/kg and in 5/5 male (3 slight, 2 moderate) and 5/5 female (1 minimal, 4 slight) rats at 450 mg/kg. This finding corresponded with the macroscopic finding wall thickened. Mesenteric lymph node , lymphoid atrophy was present in 3/5 male (3 minimal) and 2/5 female (2 minimal) rats treated at 150 mg/kg and in 5/5 male (1 minimal, 2 slight, 2 moderate) and 4/5 female (2 minimal, 2 slight) rats at 450 mg/kg. Mesenteric lymph node , increased mast cells were present in 5/5 male (3 slight, 2 moderate ) and 3/5 female (3 slight) rats treated at 150 mg/kg and in 1 /5 male (1 slight) and 2 /5 female (2 slight) rats at 450 mg/kg.PATHOLOGY REPORT PAGE : 10/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

———————

—————————————————————————————————————————————————————————————————— RESULTS

—————————————————————————————————————————————————————————————————————————

Liver , centrilobular hypertrophy was present in 1/5 female (minimal) at 150 mg/kg and in 5/5 female (1 minimal, 4 slight) rats treated at 450 mg/kg.
Uterus , cervix and vagina , atrophy was present in 2/5 female rats treated at 150 and 5/5 female rats at 450 mg/kg.

- 450 mg/kg (Group 4) Thymus , lym

phoid atrophy

was present in 5/5 male ( 1 minimal, 3 slight, 1 marked) and 5/5 female (1 minimal, 2 slight, 2 moderate) rats treated at 450 mg/kg. This finding corresponded with the macroscopic finding reduced in size

. Jejunum , hemorrhage was present in 3/5 male (2 minimal, 1 slight) and 3/5 female (3 slight) rats treated at 450 mg/kg. Spleen , lymphoid atrophy was present in 5/5 male (1 minimal, 4 slight) and 1/5 female (minimal) rats treated at 450 mg/kg. Adrenal glands , vacuolation zona fasciculata was present at increased incidence and severity in 4/5 male (2 minimal, 2 slight) and 4/5 female (1 minimal, 3 slight) rats treated at 450 mg/kg. This finding was present at a background incidence and severity in 1/5 male (minimal) at 50 mg/kg and 1/5 male (minimal) at 150 mg/kg. This finding corresponded with the macroscopic finding discoloured. Femur including joint , decreased bone, secondary spongiosa was present in 5/5 male (2 slight, 3 moderate) and 5/5 female (1 minimal, 3 slight, 1 moderate) rats treated at 450 mg/kg. This was likely related to the emaciation

. Prostate gland , small with normal histology was present in 5/5 male rats treated at 450 mg/kg. This finding corresponded with the macroscopic finding reduced in size

. Seminal vesicles , reduced contents was bilaterally present in 5/5 male rats (5 slight) treated at 450 mg/kg and, as background finding, it was unilaterally present in 1/5 (moderate) control Group rat. This finding corresponded with the macroscopic finding reduced in size

. Coagulating glands , reduced contents was present in 5/5 male (5 slight) rats treated at 450 mg/kg.

In addition, there were mi croscopic findings in organs that were only sampled in animals where they had macroscopic findings. Pancreatic lymph node , erythrophagocytosis was present in 1/5 female 50 mg/kg (1 lymph node sampled), in 2/5 female and 1/5 male 150 mg/kg (3 and 2 lymph nodes sampled respectively) treated rats. This correlated with the macroscopic finding discolouration reddish. Pancreatic lymph node , lymphoid hyperplasia was present 2/5 male and 3/5 female 150 mg/kg (2 and 3 lymph nodes sampled respectively) and in 3/5 male and 4/5 female 450 mg/kg (3 and 4 lymph nodes sampled respectively) treated rats. This correlated with the macroscopic finding enlarged. Renal lymph node , lymphoid hyperplasia was present 1/5 male and 1 /5 female 450 mg/kg (both 1 lymph node sampled) treated rats. This correlated with the macroscopic finding enlarged.

All other microscopic findings recorded were considered to be within the normal range of background pathology encountered in rats of this age and strain.PATHOLOGY REPORT PAGE : 11/ 151

PRINCIPAL SECTION TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— CONCLUSIONS

—————————————————————————————————————————————————————————————————————————

Treatment

- relat ed morphologic alterations following the administration of m- (2,3

- epoxypropoxy)

- N,N

- bis(2,3

- epoxypropyl)aniline for 28 days to Wistar (HAN) rats, were present in all treated Groups starting at 50 mg/kg.

Treatment

- related morphologic alterations consisted of hemorrhage and hypertrophy with villous stunting in the duodenum , lymphoid atrophy in the Peyer’s patches and erythrophagocytosis in the mesenteric lymph node starting at 50 mg/kg (Group 2) of; ulcer forestomach and hyperplasia forestomach in the stomach , hypertrophy with villous stunting in the jejunum , lymphoid atrophy and increased mast cells in the mesenteric lymph node , centrilobular hypertrophy

in the liver and atrophy in the uterus , cervix and vagina starting at 150 mg/kg (Group 3) and of; lymp hoid atrophy

in the thymus , hemorrhage in the jejunum , lymphoid atrophy

in the spleen , vacuolation zona fasciculat a in the adrenal glands , decreased bone, secondary spongiosa in the femur , small prostate gland with normal histology and of reduced contents in the seminal vesicles and coagulating glands at 450 mg/kg (Group 4)

.

After 28 days treatment with test item m- (2,3 -epoxypropoxy) - N,N

bis(2,3

- epoxypropyl) aniline there are adverse findings in both sexes starting at 50 mg/kg; therefore, no dose Group is without adverse findings

.PATHOLOGY REPORT PAGE : 12/ 151
TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— EXPLANATION OF CODES AND SYMBOLS

—————————————————————————————————————————————————————————————————————————

CODES AND SYMBOLS USED AT ANIMAL LEVEL:

———————————————————————————————————————— M = Male animal F = Female animal K0 = Terminal sacrifice group

CODES AND SYMBOLS USED AT ORGAN LEVEL:

——————————————————————————————————————— G = Gross observation checked off histologically * = Comment in text of individual animal data 0 = Tissue not present for histologic examination ' = Histologic examination not required + = Organ examined, findings present

— = Organ examined, no pathologic findings noted (AOFT only) ( = Only one of paired organs examined/present

CODES AND SYMBOLS USED AT FINDING LEVEL:

————————————————————————————————————————— GRADE 1 = Minimal / very few / very small GRADE 2 = Slight / few / small GRADE 3 = Moderate / moderate number / moderate size GRADE 4 = Marked / many / large P = Finding present, severity not scored ( = Finding unilateral in paired organs * = Comment in text of individual animal dataPATHOLOGY REPORT PAGE : 13/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— THYMUS : 5 5 5 5

— Lymphoid atrophy GRADE 1 :

— — — 1 GRADE 2 :

— — — 3 GRADE 4 :

— — — 1

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 2.2

————————————————————————————————————————————————————————————————————————— STOMACH : 5 5 5 5

— Ulcer, forestomach GRADE 2 :

— — 1

— GRADE 3 :

— — 1 1 GRADE 4 :

— — — 4

TOTAL AFFECTED :

— — 2 5 MEAN GRADE/TISS.AFF.:

— — 2.5 3.8

.........................................................................

— Hyperpl., forestom. GRADE 1 :

— 1

— — GRADE 2 :

— — 3 2 GRADE 3 :

— — 2 3

TOTAL AFFECTED :

— 1 5 5 MEAN GRADE/TISS.AFF.:

— 1.0 2.4 2.6

————————————————————————————————————————————————————————————————————————— DUODENUM : 5 5 5 5

— Hemorrhage GRADE 1 :

— 4 3 2 GRADE 2 :

— — — 3

TOTAL AFFECTED :

— 4 3 5 MEAN GRADE/TISS.AFF.:

— 1.0 1.0 1.6

.........................................................................PATHOLOGY REPORT PAGE : 14/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

—————————————————————————————————————————————————————————————————————— ——— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— DUODENUM CONT'D. 5 5 5 5

— Hypertrophy GRADE 1 :

— 4

— — GRADE 2 :

— 1 5 1 GRADE 3 :

— — — 4

TOTAL AFFECTED :

— 5 5 5 MEAN GRADE/TISS.AFF.:

— 1.2 2.0 2.8

————————————————————————————————————————————————————————————————————————— JEJUNUM : 5 5 5 5

— Hemorrhage GRADE 1 :

— — — 2 GRADE 2 :

— — — 1

TOTAL AFFECTED :

— — — 3 MEAN GRADE/TISS.AFF.:

— — — 1.3

.........................................................................

— Hypertrophy GRADE 1 :

— — 1

— GRADE 2 :

— — 1 3 GRADE 3 :

— — — 2

TOTAL AFFECTED :

— — 2 5 MEAN GRADE/TISS.AFF.:

— — 1.5 2.4

————————————————————————————————————————————————————————————————————————— PEYER'S PATCHES : 5 5 4 3

— Lymphoid atrophy GRADE 1 :

— — — 2 GRADE 2 :

— — 1 1

TOTAL AFFECTED :

— — 1 3 MEAN GRADE/TISS.AFF.:

— — 2.0 1.3

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 15/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— SPLEEN : 5 5 5 5

— Hemopoietic foci GRADE 1 : 5 2 5 2 GRADE 2 :

— — — 3

TOTAL AFFECTED : 5 2 5 5 MEAN GRADE/TISS.AFF.: 1.0 1.0 1.0 1.6

.........................................................................

— Lymphoid atrophy GRADE 1 :

— — — 1 GRADE 2 :

— — — 4

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 1.8

————————————————————————————————————————————————————————————————————————— MESENT. LYMPH NODE : 5 5 5 5

— Lymphoid atrophy GRADE 1 :

— — 3 1 GRADE 2 :

— — — 2 GRADE 3 :

— — — 2

TOTAL AFFECTED :

— — 3 5 MEAN GRADE/TISS.AFF.:

— — 1.0 2.2

........................................................................ .

— Increased mast cells GRADE 2 :

— — 3 1 GRADE 3 :

— — 2

—

TOTAL AFFECTED :

— — 5 1 MEAN GRADE/TISS.AFF.:

— — 2.4 2.0

.........................................................................

— Erythrophagocytosis GRADE 2 :

— 1 3

— GRADE 3 :

— — 2 5

TOTAL AFFECTED :

— 1 5 5 MEAN GRADE/TISS.AFF.:

— 2.0 2.4 3.0

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 16/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————

————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— ADRENAL GLANDS : 5 5 5 5

— Vacuolation, z.fas. GRADE 1 :

— 1 1 2 GRADE 2 :

— — — 2

TOTAL AFFECTED :

— 1 1 4 MEAN GRADE/TISS.AFF.:

— 1.0 1.0 1.5

————————————————————————————————————————————————————————————————————————— SEMINAL VESICLES : 5 5 5 5

— Reduced contents GRADE 2 :

— — — 5 GRADE 3 : 1

— — —

TOTAL AFFECTED : 1

— — 5 MEAN GRADE/TISS.AFF.: 3.0

— — 2.0

———————————————————————————————————————————————————————————————— ————————— COAGULATING GLANDS : 5 5 5 5

— Reduced contents GRADE 2 :

— — — 5

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 2.0

————————————————————————————————————————————————————————————————————————— FEMUR : 5 5 5 5

— Decreased bone, GRADE 2 :

— — — 2 GRADE 3 :

— — — 3

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 2.6

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 17/ 151

SUMMARY TABLES TOX : 501432

—————— ——————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— PANCREATIC LYMPH NO. :

— — 2 3

— Erythrophagocytosis GRADE 3 :

— — 1

—

TOTAL AFFECTED :

— — 1

— MEAN GRADE/TISS.AFF.:

— — 3.0

—

.........................................................................

— Lymphoid hyperplasia GRADE 1 :

— — 1

— GRADE 2 :

— — — 1 GRADE 3 :

— — 1 1 GRADE 4 :

— — — 1

TOTAL AFFECTED :

— — 2 3 MEAN GRADE/TISS.AFF.:

— — 2.0 3.0

————————————————————————————————————————————————————————————————————————— RENAL LYMPH NODE :

— — — 1

— Lymphoid hyperplasia GRADE 2 :

— — — 1

TOTAL AFFECTED :

— — — 1 MEAN GRADE/TISS.AFF.:

— — — 2.0

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 18/ 151

SUMMARY TABLES TOX : 501432

———— ————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— THYMUS : 5 5 5 5

— Lymphoid atrophy GRADE 1 :

— — — 1 GRADE 2 :

— — — 2 GRADE 3 :

— — — 2

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 2.2

————————————————————————————————————————————————————————————————————————— STOMACH : 5 5 5 5

— Ulcer, forestomach GRADE 4 :

— — — 5

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 4.0

.........................................................................

— Hyperpl., forestom. GRADE 1 :

— — 3

— G RADE 2 :

— — 1

— GRADE 3 :

— — 1 4 GRADE 4 :

— — — 1

TOTAL AFFECTED :

— — 5 5 MEAN GRADE/TISS.AFF.:

— — 1.6 3.2

————————————————————————————————————————————————————————————————————————— DUODENUM : 5 5 5 5

— Hemorrhage GRADE 1 :

— 3 1 2 GRADE 2 :

— — 3 2

TOTAL AFFECTED :

— 3 4 4 MEAN GRADE/TISS.AFF.:

— 1.0 1.8 1.5

.........................................................................PATHOLOGY REPORT PAGE : 19/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— DUODENUM CONT'D. 5 5 5 5

— Hypertrophy GRADE 1 :

— 2 1

— GRADE 2 :

— 3 3 4 GRADE 3 :

— — 1 1

TOTAL AFFECTED :

— 5 5 5 MEAN GRADE/TISS.AFF.:

— 1.6 2.0 2.2

————————————

————————————————————————————————————————————————————————————— JEJUNUM : 5 5 5 5

— Hemorrhage GRADE 2 :

— — — 3

TOTAL AFFECTED :

— — — 3 MEAN GRADE/TISS.AFF.:

— — — 2.0

.........................................................................

— Hypertrophy GRADE 1 :

— — 1 1 GRADE 2 :

— — — 4

TOTAL AFFECTED :

— — 1 5 MEAN GRADE/TISS.AFF.:

— — 1.0 1.8

————————————————————————————————————————————————————————————————————————— PEYER'S PATCHES : 5 5 5 5

— Lymphoid atrophy GRADE 1 :

— — — 1 GRADE 2 :

— 1

—

3 GRADE 3 :

— — 1

—

TOTAL AFFECTED :

— 1 1 4 MEAN GRADE/TISS.AFF.:

— 2.0 3.0 1.8

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 20/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

——————————

——————————————————————————————————————————————————————————————— LIVER : 5 5 5 5

— Hypertrophy, centril GRADE 1 :

— — 1 1 GRADE 2 :

— — — 4

TOTAL AFFECTED :

— — 1 5 MEAN GRADE/TISS.AFF.:

— — 1.0 1.8

————————————————————————————————————————————————————————————————————————— SPLEEN : 5 5 5 5

— Hemopoietic foci GRADE 1 : 1 2 2 4 GRADE 2 :

— — — 1

TOTAL AFFECTED : 1 2 2 5 MEAN GRADE/TISS.AFF.: 1.0 1.0 1.0 1.2

.........................................................................

— Lymphoid atrophy GRADE 1 :

— — — 1

TOTAL AFFECTED :

— — — 1 MEAN GRADE/TISS.AFF.:

— — — 1.0

————————————————————————————————————————————————————————————————————————— MESENT. LYMPH NODE : 5 5 5 5

— Lymphoid atrophy GRADE 1 :

— — 2 2 GRADE 2 :

— — — 2

TOTAL AFFECTED :

— — 2 4 MEAN GRADE/TISS.AFF.:

— — 1.0 1.5

.........................................................................

— Increased mast cells GRADE 2 :

— — 3 2

TOTAL AFFECTED :

— — 3 2 MEAN GRADE/TISS.AFF.:

— — 2.0 2.0

.........................................................................PATHOLOGY REPORT PAGE : 21/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

—————————————————————————————————————————————————————————————————————— ——— MESENT. LYMPH NODE : 5 5 5 5

— Erythrophagocytosis GRADE 1 :

— 1

— — GRADE 2 :

— — 3 3 GRADE 3 :

— — — 2

TOTAL AFFECTED :

— 1 3 5 MEAN GRADE/TISS.AFF.:

— 1.0 2.0 2.4

————————————————————————————————————————————————————————————————————————— ADRENAL GLANDS : 5 5 5 5

— Vacuolation, z.fas. GRADE 1 :

— — — 1 GRADE 2 :

— — — 3

TOTAL AFFECTED :

— — — 4 MEAN GRADE/TISS.AFF.:

— — — 1.8

————————————————————————————————————————————————————————————————————————— FEMUR : 5 5 5 5

— Decreased bone, GRADE 1 :

— — — 1 GRADE 2 :

— — — 3 GRADE 3 :

— — — 1

TOTAL AFFECTED :

— — — 5 MEAN GRADE/TISS.AFF.:

— — — 2.0

————————————————————————————————————————————————————————————————————————— PANCREATIC LYMPH NO. :

— 1 3 4

— Erythrophagocytosis GRADE 2 :

— 1 1

— GRADE 3 :

— — 1

—

TOTAL AFFECTED :

— 1 2

— MEAN GRADE/TISS.AFF.:

— 2.0 2.5

—

.........................................................................PATHOLOGY REPORT PAGE : 22/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— Selected findings with grades

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— PANCREATIC LYMPH NO. :

— 1 3 4

— Lymphoid hyperplasia GRADE 2 :

— — 2 1 GRADE 3 :

— — 1 3

TOTAL AFFECTED :

— — 3 4 MEAN GRADE/TISS.AFF.:

— — 2.3 2.8

————————————————————————————————————————————————————————————————————————— RENAL LYMPH NODE :

— — — 2

— Lymphoid hyperplasia GRADE 2 :

— — — 1

TOTAL AFFECTED :

— — — 1 MEAN GRADE/TISS.AFF.:

— — — 2.0

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 23/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— GENERAL OBSERVATIONS :

— — — 4

— Macro Noted :

— — — 4

————————————————————————————————————————————————————————————————————————— HEART : 5

— — 5

— Inflamm. lymphocytic: 1

— — —

————————————————————————————————————————————————————————————————————————— LUNG : 5

— — 5

— Alv. macrophages : 1

— — 3

— Inflamm. infiltrate : 2

— — —

— Alveolar inflamm. : 1

— — —

— Lymphoid hyperplasia: 1

— — —

————————————————————————————————————————————————————————————————————————— THYMUS : 5 5 5 5

— Lymphocytolysis :

— — — 3

— Lymphoid atrophy :

— — — 5

————————————————————————————————————————————————————————————————————————— TRACHEA : 5

— — 5

— Inflamm. lymphogran.: 3

— — —

————————————————————————————————————————————————————————————————————————— THYROID GLAND : 5

— — 5

— Hyperpl./hypertrophy: 2

— — 1

————————

————————————————————————————————————————————————————————————————— PARATHYROID GLANDS : 5

— — 5

————————————————————————————————————————————————————————————————————————— STOMACH : 5 5 5 5

— Forestom. inflamm. :

— — 3

—

— Ulcer, forestomach :

— — 2 5

— Hyperpl., forestom. :

— 1 5 5

— Hemorrhage :

— — — 1

— Cyst(s) : 1

— — —

————————————————————————————————————————————————————————————————————————— DUODENUM : 5 5 5 5

— Hemorrhage :

— 4 3 5

— Hypertrophy :

— 5 5 5

—————————————————————————————————————————————————————————————————————— ———PATHOLOGY REPORT PAGE : 24/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— e poxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

—————————————————— ——————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— JEJUNUM : 5 5 5 5

— Hemorrhage :

— — — 3

— Hypertrophy :

— — 2 5

————————————————————————————————————————————————————————————————————————— ILEUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— PEYER'S PATCHES : 5 5 4 3

— Lymphoid atrophy :

— — 1 3

— Vacuolation : 1

— — —

—————— ——————————————————————————————————————————————————————————————————— CECUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— COLON : 5

— — 5

————————————————————————————————————————————————————————————————————————— RECTUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— LIVER : 5

— 1 5

— Inflamm. cell foci : 4

— — 3

— Apoptos/s.cell necro:

— — — 1

————————————————————————————————————————————————————————————————————————— SPLEEN : 5 5 5 5

— Hemopoietic foci : 5 2 5 5

— Hemosiderin pigment : 3 4 3 2

— Lymphoid atrophy :

— — — 5

————————————————————————————————————————————————————————————————————————— MESENT. LYMPH NODE : 5 5 5 5

— Lymphoid atrophy :

— — 3 5

— Increased mast cells:

— — 5 1

— Lymphatic ectasia :

— — — 2

— Macrophage foci : 2

— — —

— Erythrophagocytosis :

— 1 5 5

————————————————————————————————————————————————————————————————————————— MANDIB.LYMPH NODES : 5 5 5 4

— Lymphoid atrophy :

— — 1 4

— Erythrophagocytosis : 1

— 1

—

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 25/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— KIDNEYS : 5

— 2 5

— Pelvic dilation :

— — 1

—

— Hyaline droplets : 3

— 2

—

— Inflamm., interstit.: 2

— — 1

— Basophilia, tubular : 3

— — 2

————————————————————————————————————————————————————————————————————————— URINARY BLADDER : 5

— — 5

————————————————————————————————————————————————————————————————————————— ADRENAL GLANDS : 5 5 5 5

— Vacuolation, z.fas. :

— 1 1 4

————————————————————————————————————————————————————————————————————————— BRAIN : 5

— — 5

————————————————————————————————————————————————————————————————————————— SCIATIC NERVE : 5

— — 5

————————————————————————————————————————————————————————————————————————— TESTES : 5

— — 5

— Sperm. giant cells :

— — — 1

————————————————————————————————————————————————————————————————————————— EPIDIDYMIDES : 5

— — 5

— Sperm granuloma : 1

— — —

— Semin. cell debris :

— — — 1

— Inflamm. lymphocytic:

— — — 1

————————————————————————————————————————————————————————————————————————— PROSTATE GLAND : 5 5 5 5

— Small, normal histo.:

— — — 5

— Inflamm. lymphocytic:

— 1

— —

————————————————————————————————————————————————————————————————————————— SEMINAL VESICLES : 5 5 5 5

— Reduced contents : 1

— — 5

————————————————————————————————————————————————————————————————————————— COAGULATING GLANDS : 5 5 5 5

— Reduced contents :

— — — 5

————————————————————————————————————————————————————————————————————————— SKELETAL MUSCLE : 5

— — 5

————————

————————————————————————————————————————————————————————————————— EYES : 5

— — 5

— Retinal rosettes :

— — — 1

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 26/ 151

SUMMARY TABLES TOX : 501432

—————————————————————————————————————————————————————————————————————— ——— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : MALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— BONE, STERNUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— BONE MARROW

— STERN. : 5

— — 5

— Adipocytes : 1

— — 3

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— THOR. : 5

— — 5

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— LUMBAR : 5

— — 5

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— CERV. : 5

— — 5

————————————————————————————————————————————————————————————————————————— FEMUR : 5 5 5 5

— Decreased bone, :

— — — 5

————————————————————————————————————————————————————————————————————————— JOINTS, KNEE : 5 5 5 5

————————————————————————————————————————————————————————————————————————— PANCREATIC LYMPH NO. :

— — 2 3

— Erythrophagocytosis :

— — 1

—

— Lymphatic ectasia :

— — 2 2

— Lymphoid hyperplasia:

— — 2 3

————————————————————————————————————————————————————————————————————————— RENAL LYMPH NODE :

— — — 1

— Lymphoid hyperplasia:

— — — 1

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 27/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— GENERAL OBSERVATIONS :

— — — 5

— Macro Noted :

— — — 5

————————————————————————————————————————————————————————————————————————— HEART : 5

— — 5

————————————————

————————————————————————————————————————————————————————— LUNG : 5

— — 5

— Alv. macrophages : 1

— — 2

— Inflamm. infiltrate : 2

— — —

— Alveolar inflamm. : 2

— — 2

————————————————————————————————————————————————————————————————————————— THYMUS : 5 5 5 5

— Lymphocytolysis : 1

— — 3

— Lymphoid atrophy :

— — — 5

————————————————————————————————————————————————————————————————————————— TRACHEA : 5

— — 5

————————————————————————————————————————————————————————————————————————— THYROID GLAND : 5

— — 5

— Ectopic thymus : 1

— — —

———— ————————————————————————————————————————————————————————————————————— PARATHYROID GLANDS : 5

— — 5

————————————————————————————————————————————————————————————————————————— STOMACH : 5 5 5 5

— Forestom. inflamm. :

— — 1

—

— Ulcer, forestomach :

— — — 5

— Edema :

— — 2

—

— Hyperpl., forestom. :

— — 5 5

— Vacuol. lim. ridge : 1

— — —

— Hemorrhage :

— — — 1

————————————————————————————————————————————————————————————————————————— DUODENUM : 5 5 5 5

— Hemorrhage :

— 3 4 4

— Hypertrophy :

— 5 5 5

————————————————————————————————————————————————————————————————————————— JEJUNUM : 5 5 5 5

— Hemorrhage :

— — — 3

— Hypertrophy :

— — 1 5

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 28/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— ILEUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— PEYER'S PATCHES : 5 5 5 5

— Lymphoid atrophy :

— 1 1 4

—— ——————————————————————————————————————————————————————————————————————— CECUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— COLON : 5

— — 5

————————————————————————————————————————————————————————————————————————— RECTUM : 5

— — 5

—————————————————————————————————————————————————————————————————————— ——— LIVER : 5 5 5 5

— Inflamm. cell foci : 4 5 5 1

— Apoptos/s.cell necro: 2

— 2

—

— Hypertrophy, centril:

— — 1 5

— Necrosis, coag. :

— — 1

—

————————————————————————————————————————————————————————————————————————— SPLEEN : 5 5 5 5

— Hemopoietic foci : 1 2 2 5

— Hemosiderin pigment : 3 5 5 1

— Lymphoid atrophy :

— — — 1

————————————————————————————————————————————————————————————————————————— MESENT. LYMPH NODE : 5 5 5 5

— Lymphoid atrophy :

— — 2 4

— Increased mast cells:

— — 3 2

— Lymphatic ectasia :

— — — 1

— Erythrophagocytosis :

— 1 3 5

————————————————————————————————————————————————————————————————————————— MANDIB.LYMPH NODES : 5 5 5 5

— Lymphoid atrophy :

— — — 5

— Erythrophagocytosis :

— — — 1

— Plasmacytosis :

— — 1

—

————————————————————————————————————————————————————————————————————————— KIDNEYS : 5

— — 5

— Pelvic dilation :

— — — 1

— Inflamm., interstit.: 1

— — 2

— Basophilia, tubular : 2

— — 1

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 29/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

———————————————————————————————————————————————————————————————————— ————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

————————————————————————————————————————————————————————————————————————— URINARY BLADDER : 5

— — 5

————————————————————————————————————————————————————————————————————————— ADRENAL GLANDS : 5 5 5 5

— Extracapsular nodule:

— — 1

—

— Vacuolation, z.fas. :

— — — 4

— Inflamm. lymphocytic: 1

— — —

————————————————————————————————————————————————————————————————————————— BRAIN : 5

— — 5

————————————————————————————————————————————————————————————————————————— SCIATIC NERVE : 5

— — 5

————————————————————————————————————————————————————————————————————————— OVARIES : 5

— — 5

————————————————————————————————————————————————————————————————————————— UTERUS : 5 5 5 5

— Atrophy :

— — 2 5

— Cyclic dilation : 2 1

— —

————————————————————————————————————————————————————————————————————————— CERVIX : 5 5 5 5

— Atrophy :

— — 2 5

————————————————————————————————————————————————————————————————————————— VAGINA : 5 5 5 5

— Atrophy :

— — 2 5

— Proestrus epithelium: 2 1

— —

————————————————————————————————————————————————————————————————————————— SKELETAL MUSCLE : 5

— — 5

————————————————————————————————————————————————————————————————————————— EYES : 5

— — 5

———— ————————————————————————————————————————————————————————————————————— BONE, STERNUM : 5

— — 5

————————————————————————————————————————————————————————————————————————— BONE MARROW

— STERN. : 5

— — 5

— Adipocytes : 2

— — 2

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— THOR. : 5

— — 5

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— LUMBAR : 5

— — 5

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 30/ 151

SUMMARY TABLES TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0 Incidence table

— All microscopic findings

————————————————————————————————————————————————————————————————————————— SEX : FEMALE DOSE GROUP: 01 02 03 04 NO.ANIMALS: 5 5 5 5

——————————————

——————————————————————————————————————————————————————————— SPINAL CORD

— CERV. : 5

— — 5

————————————————————————————————————————————————————————————————————————— FEMUR : 5 5 5 5

— Decreased bone, :

— — — 5

————————————————————————————————————————————————————————————————————————— JOINTS, KNEE : 5 5 5 5

————————

————————————————————————————————————————————————————————————————— PANCREATIC LYMPH NO. :

— 1 3 4

— Erythrophagocytosis :

— 1 2

—

— Lymphatic ectasia :

— — — 1

— Lymphoid hyperplasia:

— — 3 4

————————————————————————————————————————————————————————————————————————— RENAL LYMPH NODE :

— — — 2

— Erythrophagocytosis :

— — — 1

— Lymphoid hyperplasia:

— — — 1

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 31/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 01, CONTROL

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 1 2 3 4 5 21 22 23 24 25 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— HEART

— — — +

— — — — — —

— Inflamm. lymphocytic . . . 1. . . . . . .

......................................................................... LUNG +

— + + + +*

— + + +

— Alv. macrophages . . 1. . . . . . . 1.

— Inflamm. infiltrate . . 2. 1. . . . 1. 2. .

— Alveolar inflamm. . . . . 1. 1. . . . 1.

— Lymphoid hyperplasia 1. . . . . . . . . .

......................................................................... THYMUS

— — — — — +

— — — —

— Lymphocytolysis . . . . . 1. . . . .

......................................................................... TRACHEA + +

— — +

— — — — —

— Inflamm. lymphogran. 1. 1. . . 1. . . . . .

......................................................................... THYROID GLAND

— + +

— — — — +

— —

— Ectopic thymus . . . . . . . ( P. . .

— Hyperpl./hypertrophy . 1. 1.

. . . . . . .

......................................................................... PARATHYROID GLANDS

— — — (

— —

(

— — — — —

......................................................................... STOMACH

— — +

— — — — — +

—

— Vacuol. lim. ridge . . . . . . . . 1. .

— Cyst(s) . . 1. . . . . . . .

......................................................................... DUODENUM

— — — — — — — — — —

......................................................................... JEJUNUM

— — — — — — — — — —

......................................................................... ILEUM

— — — — — — — — — —

......................................................................... PEYER'S PATCHES

— — +

— — — — — — —

— Vacuolation . . 1. . . . . . . .

......................................................................... CECUM

— — — — — — — — — —

......................................................................... COLON

— — — — — — — — — —

......................................................................... RECTUM

— — — — — — — — — —

.........................................................................PATHOLOGY REPORT PAGE : 32/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 01, CONTROL

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 1 2 3 4 5 21 22 23 24 25 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— LIVER + + +

— + + + + +

—

— Inflamm. cell foci 1. 1. 1. . 1. 1. 1. 1. 1. .

— Apoptos/s.cell necro . . . . . 1. . 1. . .

......................................................................... SPLEEN + + + + +

— + + +

—

— Hemopoietic foci 1. 1. 1. 1. 1. . . 1. . .

— Hemosiderin pigment . 1. . 1. 1. . 1. 1. 1. .

......................................................................... MESENT. LYMPH NODE

— +

—

+

— — — — — —

— Macrophage foci . 1. . 1. . . . . . .

......................................................................... MANDIB.LYMPH NODES

— — — — +

— — — — —

— Erythrophagocytosis . . . . ( 1. . . . . .

......................................................................... KIDNEYS + + + + + +

— — +

—

— Hyaline droplets 1. . 1. 2. . . . . . .

— Inflamm., interstit. ( 1. . 1. . . . . . ( 1. .

— Basophilia, tubular ( 1. 1. . . ( 1. ( 1. . . ( 1. .

......................................................................... URINARY BLADDER

— — — — — — — — — —

......................................................................... ADRENAL GLANDS

— — — — — +

— — — —

— Inflamm. lymphocytic . . . . . ( 1. . . . .

......................................................................... BRAIN

— — — — — — — — — —

......................................................................... SCIATIC NERVE

— — — — — — — — — —

......................................................................... TESTES

— — — — —

......................................................................... EPIDIDYMIDES

— — +G

— —

— Sperm granuloma . . 3* . .

......................................................................... OVARIES

— — — — —

......................................................................... PROSTATE GLAND

— — — — —

......................................................................... SEMINAL VESICLES +G

— — — —

— Reduced contents ( 3. . . . .

.........................................................................PATHOLOGY REPORT PAGE : 33/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

—————————————————————————————————————————————————————————————————————— ——— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 01, CONTROL

———————————————————————————————————————————————————————————————— ————————— ANIMAL NUMBER : 1 2 3 4 5 21 22 23 24 25 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— COAGULATING GLANDS

— — — — —

......................................................................... UTERUS

— +G +G

— —

— Cyclic dilation . P. P. . .

......................................................................... CERVIX

— — — — —

......................................................................... VAGINA

— + +

— —

— Proestrus epithelium . P. P. . .

......................................................................... SKELETAL MUSCLE

— — — — — — — — — —

......................................................................... EYES

— — — — — — — — — —

......................................................................... BONE, STERNUM

— — — — — — — — — —

......................................................................... BONE MARROW

— STERN.

— — — — + +

— — — +

— Adipocytes . . . . 1. 1. . . . 1.

......................................................................... SPINAL CORD

— THOR.

— — — — — — — — — —

......................................................................... SPINAL CORD

— LUMBAR

— — — — — — — — — —

......................................................................... SPINAL CORD

— CERV.

— — — — — — — — — —

......................................................................... FEMUR

— — — — — — — — — —

......................................................................... JOINTS, KNEE

— — — — — — — — — —

......................................................................... PANCREATIC LYMPH NO. . . . . . . . . . .

......................................................................... RENAL LYMPH NODE . . . . . . . . . .

.........................................................................PATHOLOGY REPORT PAGE : 34/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 2 8

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 02, 50 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 6 7 8 9 10 26 27 28 29 30 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— THYMUS

— — — — — — — — — —

......................................................................... STOMACH

— +

— — — — — — — —

— Hyperpl., forestom. . 1. . . . . . . . .

......................................................................... DUODENUM + + + + + + + + + +

— Hemorrhage 1. 1. 1. . 1. . . 1. 1. 1.

— Hypertrophy 1. 2. 1. 1. 1. 1. 1. 2. 2. 2.

......................................................................... JEJUNUM

— — — — — — — — — —

......................................................................... PEYER'S PATCHES

— — — — — — — +

— —

— Lymphoid atrophy . . . . . . . 2. . .

......................................................................... LIVER ' ' ' ' ' + + + + +

— Inflamm. cell foci 1. 1. 1. 1. 1.

......................................................................... SPLEEN + +

— + + + + + + +

— Hemopoietic foci . 1. . 1. . . 1. . 1. .

— Hemosiderin pigment 1. 1. . 1. 1. 1. 1. 1. 1. 1.

......................................................................... MESENT. LYMPH NODE

— — — +

— — — — — +

— Erythrophagocytosis . . . 2. . . . . . 1.

......................................................................... MANDIB.LYMPH NODES

— — — — — — — — (

— —

......................................................................... ADRENAL GLANDS

— — — — +

— — — — —

— Vacuolation, z.fas. . . . . 1. . . . . .

......................................................................... OVARIES . . . . .

......................................................................... PROSTATE GLAND

— — +

— —

— Inflamm. lymphocytic . . 1. . .

......................................................................... SEMINAL VESICLES

— — — — —

......................................................................... COAGULATING GLANDS

— — — — —

.........................................................................PATHOLOGY REPORT PAGE : 35/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 02, 50 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 6 7 8 9 10 26 27 28 29 30 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— UTERUS

— — — — +G

— Cyclic dilation . . . . P.

......................................................................... CERVIX

— — — — —

......................................................................... VAGINA

— — — — +

— Proestrus epithelium . . . . P.

......................................................................... SKELETAL MUSCLE . . . . . . . . . .

......................................................................... EYES . . . . . . . . . .

......................................................................... BONE, STERNUM . . . . . . . . . .

......................................................................... BONE MARROW

— STERN. . . . . . . . . . .

......................................................................... SPINAL CORD

— THOR. . . . . . . . . . .

......................................................................... SPINAL CORD

— LUMBAR . . . . . . . . . .

......................................................................... SPINAL CORD

— CERV. . . . . . . . . . .

......................................................................... FEMUR

— — — — — — — — — —

......................................................................... JOINTS, KNEE

— — — — — — — — — —

......................................................................... PANCREATIC LYMPH NO. . . . . . . . +G . .

— Erythrophagocytosis . . . . . . . 2. . .

......................................................................... RENAL LYMPH NODE . . . . . . . . . .

.........................................................................PATHOLOGY REPORT PAGE : 36/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 03, 150 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 11 12 13 14 15 31 32 33 34 35 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— THYMUS

— — — — — — — — — —

......................................................................... STOMACH +G +G +G +G +G + +G +G +G +

— Forestom. inflamm. . 1. 2. 2. . . . . 3. .

— Ulcer, forestomach . . 3. 2. . . . . . .

— Edema . . . . . . 2. . 2. .

— Hyperpl., forestom. 2. 3. 2. 3. 2. 1. 1. 2. 3. 1.

......................................................................... DUODENUM +G + + +G +G + +G +G +G +

— Hemorrhage . 1. 1. . 1. . 1. 2. 2. 2.

— Hypertrophy 2. 2. 2. 2. 2. 1. 2. 3. 2. 2.

......................................................................... JEJUNUM +

— — +G

— G

— — +G

— G

—

— Hypertrophy 1. . . 2. . . . 1. . .

......................................................................... PEYER'S PATCHES

— — — + 0

—

+

— — —

— Lymphoid atrophy . . . 2. . . 3. . . .

......................................................................... LIVER ' ' '

— G ' + + +G + +

— Inflamm. cell foci . 1. 1. 1. 1. 1.

— Apoptos/s.cell necro . . . 2. . 1.

— Hypertrophy, centril . . . 1. . .

— Necrosis, coag. . . . . . 1.

......................................................................... SPLEEN + + + + + + + + + +

— Hemopoietic foci 1. 1. 1. 1. 1. . 1. . . 1.

— Hemosiderin pigment 1. 1. . 1. . 1. 1. 2. 1. 1.

......................................................................... MESENT. LYMPH NODE +G +G +G + +G + + +G

— +G

— Lymphoid atrophy . 1. 1. . 1. . 1. 1. . .

— Increased mast cells 3. 2. 2. 2. 3. 2. . 2. . 2.

— Erythrophagocytosis 2. 2. 3. 2. 3. 2. . 2. . 2.

......................................................................... MANDIB.LYMPH NODES

— +

—

+G

— — — — +

—

— Lymphoid atrophy . 1. . . . . . . . .

— Erythrophagocytosis . . . ( 1. . . . . . .

— Plasmacytosis . . . . . . . . 1. .

.........................................................................PATHOLOGY REPORT PAGE : 37/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 03, 150 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 11 12 13 14 15 31 32 33 34 35 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— KIDNEYS ' +G +G ' ' ' ' ' ' '

— Pelvic dilation ( P. .

— Hyaline droplets 1. 1.

......................................................................... ADRENAL GLANDS +

— — — — — — — +G

—

— Extracapsular nodule . . . . . . . . ( P. .

— Vacuolation, z.fas. 1. . . . . . . . . .

......................................................................... OVARIES . . . . .

......................................................................... PROSTATE GLAND

— — — — —

......................................................................... SEMINAL VESICLES

— — — — —

......................................................................... COAGULATING GLANDS

— — — — —

......................................................................... UTERUS

— — +G

—

+

— Atrophy . . P. . P.

......................................................................... CERVIX

— — +

—

+

— Atrophy . . P. . P.

......................................................................... VAGINA

— — +

—

+

— Atrophy . . P. . P.

......................................................................... SKELETAL MUSCLE . . . . . . . . . .

......................................................................... EYES . . . . . . . . . .

......................................................................... BONE, STERNUM . . . . . . . . . .

......................................................................... BONE MARROW

— STERN. . . . . . . . . . .

......................................................................... SPINAL CORD

— THOR. . . . . . . . . . .

......................................................................... SPINAL CORD

— LUMBAR . . . . . . . . . .

......................................................................... SPINAL CORD

— CERV. . . . . . . . . . .

.........................................................................PATHOLOGY REPORT PAGE : 38/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—————— ——————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 03, 150 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 11 12 13 14 15 31 32 33 34 35 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— FEMUR

— — — — — — — — — —

......................................................................... JOINTS, KNEE

— — — — — — — — — —

......................................................................... PANCREATIC LYMPH NO. . +G +G . . +G +G . . +G

— Erythrophagocytosis . 3. . . . . 2. . . 3.

— Lymphatic ectasia . 1. 3. . . . . . . .

— Lymphoid hyperplasia . 1. 3. . . 2. 2. . . 3.

......................................................................... RENAL LYMPH NODE . . . . . . . . . .

.........................................................................PATHOLOGY REPORT PAGE : 39/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 04, 450 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 16 17 18 19 20 36 37 38 39 40 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— GENERAL OBSERVATIONS ' +G +G +G +G +G +G +G +G +G

— Macro Noted . P. P. P. P. P. P. P. P. P.

......................................................................... HEART

— — — — — — — — — —

......................................................................... LUNG

— + +

—

+

—

+ +

—

+

— Alv. macrophages . 1. 1. . 2. . . 1. . 1.

— Alveolar inflamm. . . . . . . 1. 1. . .

......................................................................... THYMUS +G +G +G +G +G +G + +G +G +G

— Lymphocytolysis . 2. 1. 1. . 1. . 1. 3. .

— Lymphoid atrophy 4. 2. 2. 2. 1. 2. 1. 2. 3. 3.

......................................................................... TRACHEA

— — — — — — — — — —

......................................................................... THYROID GLAND

— — — — +

— — — — —

— Hyperpl./hypertrophy . . . . 1. . . . . .

......................................................................... PARATHYROID GLANDS

— — — (

— — — — — — (

—

......................................................................... STOMACH +G +G +G +G +G +G +G +G +G +G

— Ulcer, forestomach 4. 4. 3. 4. 4. 4. 4. 4. 4. 4.

— Hyperpl., forestom. 2. 3. 2. 3. 3. 3. 3. 4. 3. 3.

— Hemorrhage . . . . 2. . . . 3. .

......................................................................... DUODENUM + +G +G +G +G +G +G +G + +G

— Hemorrhage 2. 1. 1. 2. 2. 1. 1. 2. . 2.

— Hypertrophy 3. 3. 2. 3. 3. 2. 2. 2. 2. 3.

......................................................................... JEJUNUM + +G +G +G +G +G +G +G +G +G

— Hemorrhage 1. . . 1. 2. . 2. 2. . 2.

— Hypertrophy 2. 2. 3. 2. 3. 1. 2. 2. 2. 2.

......................................................................... ILEUM

— — — — — — — — — —

......................................................................... PEYER'S PATCHES 0 + 0 + + + +

— + +

— Lymphoid atrophy . 2. . 1. 1. 2. 2. . 2. 1.

......................................................................... CECUM

— — — — — — — — — —

.........................................................................PATHOLOGY REPORT PAGE : 40/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 04, 450 MG/KG

—————————————————————————————————————————————————————————————————————— ——— ANIMAL NUMBER : 16 17 18 19 20 36 37 38 39 40 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— COLON

— — — — — — — — — —

......................................................................... RECTUM

— — — — — — — — — —

......................................................................... LIVER

— — + + + + + + + +

— Inflamm. cell foci . . 1. 1. 1. . 1. . . .

— Apoptos/s.cell necro . . . . 1. . . . . .

— Hypertrophy, centril . . . . . 2. 2. 2. 1. 2.

......................................................................... SPLEEN + + + + + + + + + +

— Hemopoietic foci 1. 1. 2. 2. 2. 1. 1. 1. 1. 2.

— Hemosiderin pigment . 2. . 1. . . . 1. . .

— Lymphoid atrophy 2. 2. 2. 1. 2. . . . 1. .

......................................................................... MESENT. LYMPH NODE +G +G +G +G +G +G +G + +G +G

— Lymphoid atrophy 2. 3. 3. 2. 1. 2. 1. . 2. 1.

— Increased mast cells . . . . 2. 2. . . . 2.

— Lymphatic ectasia . 2. 3. . . . . 1. . .

— Erythrophagocytosis 3. 3. 3. 3. 3. 2. 3. 2. 3. 2.

......................................................................... MANDIB.LYMPH NODES 0 + + + + + + + + +

— Lymphoid atrophy . 3. 3. 2. 2. 2. 2. 1. 3. 2.

— Erythrophagocytosis . . . . . . . . . ( 2.

......................................................................... KIDNEYS +G +G

— G

— G

— G

— G +G

— G

— G +G

— Pelvic dilation . . . . . . ( P. . . .

— Inflamm., interstit. . ( 1. . . . . ( 1. . . ( 1.

— Basophilia, tubular ( 1. ( 1. . . . . . . . ( 1.

......................................................................... URINARY BLADDER

— — — — — — — — — —

......................................................................... ADRENAL GLANDS + +G +G

— G +G

— G +G +G +G +G

— Vacuolation, z.fas. 2. 2. 1. . 1. . 1. 2. 2. 2.

......................................................................... BRAIN

— — — — — — — — — —

......................................................................... SCIATIC NERVE

— — — — — — — — — —

.........................................................................PATHOLOGY REPORT PAGE : 41/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 04, 450 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 16 17 18 19 20 36 37 38 39 40 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————

————————————————————————————————————————————————————————— TESTES

— +

— — —

— Sperm. giant cells . ( 1. . . .

......................................................................... EPIDIDYMIDES + +

— — —

— Semin. cell debris ( 1. . . . .

— Inflamm. lymphocytic . ( 1. . . .

......................................................................... OVARIES

— G

— — — G

— G

......................................................................... PROSTATE GLAND +G +G +G +G +G

— Small, normal histo. P. P. P. P. P.

......................................................................... SEMINAL VESICLES +G +G +G +G +G

— Reduced contents 2. 2. 2. 2. 2.

......................................................................... COAGULATING GLANDS + + + ( + +

— Reduced contents 2. 2. 2. ( 2. 2.

......................................................................... UTERUS +G +G +G +G +G

— Atrophy P. P. P. P. P.

......................................................................... CERVIX + + + + +

— Atrophy P. P. P. P. P.

......................................................................... VAGINA + + + + +

— Atrophy P. P. P. P. P.

......................................................................... SKELETAL MUSCLE

— — — — — — — — — —

......................................................................... EYES

— — +

— — — — — — —

— Retinal rosettes . . ( 1. . . . . . . .

......................................................................... BONE, STERNUM

— — — — — — — — — —

......................................................................... BONE MARROW

— STERN. + +

— +

—

+

— —

+

—

— Adipocytes 1. 1. . 1. . 1. . . 2. .

......................................................................... SPINAL CORD

— THOR.

— — — — — — — — — —

.........................................................................PATHOLOGY REPORT PAGE : 42/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 04, 450 MG/KG

————————————————————————————————————————————————————————————————————————— ANIMAL NUMBER : 16 17 18 19 20 36 37 38 39 40 MK0 MK0 MK0 MK0 MK0 FK0 FK0 FK0 FK0 FK0

————————————————————————————————————————————————————————————————————————— SPINAL CORD

— LUMBAR

— — — — — — — — — —

......................................................................... SPINAL CORD

— CERV.

— — — — — — — — — —

......................................................................... FEMUR + + + + + + + + + +

— Decreased bone, 3. 3. 2. 2. 3. 2. 2. 1. 3. 2.

......................................................................... JOINTS, KNEE

— — — — — — — — — —

......................................................................... PANCREATIC LYMPH NO. . +G . +G +G +G +G +G . +G

— Lymphatic ectasia . 2. . 1. . . . 2. . .

— Lymphoid hyperplasia . 4. . 2. 3. 3. 3. 3. . 2.

......................................................................... RENAL LYMPH NODE . . . +G . . . . +G +G

— Erythrophagocytosis . . . . . . . . 2. .

— Lymphoid hyperplasia . . . 2. . . . . . 2.

.........................................................................PATHOLOGY REPORT PAGE : 43/ 151

INDIVIDUAL ANIMAL DATA T OX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— ANIMAL HEADING DATA DOSE GROUP : 01, CONTROL

—————————————————————————————————————————————————————————————————————————

ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 1 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 2 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 3 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 4 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 5 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

......................................................................... 21 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 22 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 23 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 24 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 25 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

.........................................................................PATHOLOGY REPORT PAGE : 44/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 1

.........................................................................

* NECROPSY FINDINGS

SEMINAL VESICLES: 01: LEFT SIDE: REDUCED IN SIZE.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Lymphoid (BALT) hyperplasia, grade 1
THYMUS: Organ examined, no pathologic findings noted
TRACHEA:

— Inflammation, lymphogranulocytic, grade 1
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 45/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 1

.........................................................................

RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Hyaline droplets, bilateral, grade 1

— Inflammation, interstitial lymphocytic, unilateral, grade 1

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES:

— Reduced contents, unilateral, grade 3 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 46/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— ( 2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 1

.........................................................................

EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 2

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.PATHOLOGY REPORT PAGE : 47/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 2

.........................................................................

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG: Organ examined, no pathologic findings noted
THYMUS: Organ examined, no pathologic findings noted
TRACHEA:

— Inflammation, lymphogranulocytic, grade 1
THYROID GLANDS:

— Hyperplasia/hypertrophy, follicular diffuse, bilateral, grade 1
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:
O rgan examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1PATHOLOGY REPORT PAGE : 48/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—— ——————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 2

.........................................................................

MESENTERIC LYMPH NODE:

— Macrophage foci, grade 1
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Basophilia, tubular, corticomedullary, bilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 49/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 2

.........................................................................

SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0
DAYS ON TEST : 28 * ANIMAL NO. : 3

.........................................................................

* NECROPSY FINDINGS

EPIDIDYMIDES: 01: LEFT SIDE, TAIL: NODULE(S), D=6X5 MM, YELLOWISH, SOFT.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar macrophage foci, grade 1

— Inflammatory cell infiltrate, peri

— vascular/bronchial, grade 2
THYMUS: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 50/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

——————————————————————————————————————————————————————————————————— ——————

CONT./FF. ANIMAL NO. : 3

.........................................................................

TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS:

— Hyperplasia/hypertrophy, follicular diffuse, bilateral, grade 1
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Cyst(s), glandular stomach, grade 1
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Vacuolation, grade 1
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Hyaline droplets, bilateral, grade 1

— Inflammation, interstitial lymphocytic, bilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 51/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 3

.........................................................................

ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES:

— Sperm granuloma, bilateral, grade 3 Grade 2 in contralateral organ This finding corresponds to necropsy observation no: 01.
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 52/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 3

.........................................................................

PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 4

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

HEART:

— Inflammation lymphocytic, grade 1
LUNG:

— Inflammatory cell infiltrate, peri

— vascular/bronchial, grade 1
THYMUS: Organ examined, no pathologic findings noted
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Only one of paired organs examined/present Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 53/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 4

.........................................................................

DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Macrophage foci, grade 1
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Hyaline droplets, bilateral, grade 2
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 54/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 4

.........................................................................

EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 55/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 5

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar inflammation, mononuclear, grade 1
THYMUS: Organ examined, no pathologic findings noted
TRACHEA:

— Inflammation, lymphogranulocytic, grade 1
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS : Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 56/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————————————————————————————————————————————————————————————————————— — TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————— ———————

CONT./FF. ANIMAL NO. : 5

.........................................................................

LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES:

— Erythrophagocytosis, unilateral, grade 1
KIDNEYS:

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 57/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 5

.........................................................................

BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 58/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————————————————————————————————————————————————————————————————————— — TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————— ———————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 21

.........................................................................

* NECROPSY FINDINGS

N O NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG: One lung badly inflated with formalin

— Alveolar inflammation, mononuclear, grade 1
THYMUS:

— Lymphocytolysis, grade 1
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Only one of paired organs examined/present Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 59/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 21

.........................................................................

RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Apoptosis/single cell necrosis, hepatocellular, grade 1
SPLEEN:
O rgan examined, no pathologic findings noted
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Inflammation, lymphocytic, unilateral, grade 1
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 60/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 21

.........................................................................

BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 22

.........................................................................

* NECROPSY FINDINGS

UTERUS: 01: CONTAINS FLUID.
NO OTHER NECROPSY OBSERVATIONS NOTEDPATHOLOGY REPORT PAGE : 61/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 22

.........................................................................

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG: Organ examined, no pathologic findings noted
THYMUS: Organ examined, no pathologic findings noted
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 62/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 22

.........................................................................

MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS: Organ examined, no pathologic findings noted
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS:

— Cyclic dilation This finding corresponds to necropsy observation no: 01.
CERVIX: Organ examined, no pathologic findings noted
VAGINA:

— Proestrus epithelium
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 63/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 22

.........................................................................

FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 23

.........................................................................

* NECROPSY FINDINGS

UTERUS: 01: CONTAINS FLUID.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Inflammatory cell infiltrate, peri

— vascular/bronchial, grade 1
THYMUS: Organ examined, no pathologic findings noted
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS:

— Ectopic thymus, unilateralPATHOLOGY REPORT PAGE : 64/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————

————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 23

.........................................................................

PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Apoptosis/single cell necrosis, hepatocellular, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS: Organ examined, no pathologic findings noted
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 65/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————— ———————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

———————————

——————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 23

.........................................................................

SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS:

— Cyclic dilation This finding corresponds to necropsy observation no: 01.
CERVIX: Organ examined, no pathologic findings noted
VAGINA:

— Proestrus epithelium
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

——————————

———————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 66/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 24

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Inflammatory cell infiltrate, peri

— vascular/bronchial, grade 2
THYMUS: Organ examined, no pathologic findings noted
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Vacuolation, limiting ridge, grade 1
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 67/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 24

.........................................................................

RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS:

— Inflammation, interstitial lymphocytic, unilateral, grade 1

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 68/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 24

.........................................................................

BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 25

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar macrophage foci, grade 1

— Alveolar inflammation, mononuclear, grade 1PATHOLOGY REPORT PAGE : 69/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

———————————————————— —————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 25

.........................................................................

THYMUS: Organ examined, no pathologic findings noted
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM: Organ examined, no pathologic findings noted
JEJUNUM: Organ examined, no pathologic findings noted
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER: Organ examined, no pathologic findings noted
SPLEEN: Organ examined, no pathologic findings noted
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS: Organ examined, no pathologic findings noted
URINARY BLADDER: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 70/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 01, CONTROL FEMALE

————————————————————— ————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 25

.........................................................................

ADRENAL GLANDS: Organ examined, no pathologic findings noted
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted
B ONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 71/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— ANIMAL HEADING DATA DOSE GROUP : 02, 50 MG/KG

—————————————————————————————————————————————————————————————————————————

ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 6 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 7 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 8 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 9 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 10 M K0 K0 28 09

— NOV

— 1 2 06

— DEC

— 12 07

— DEC

— 12

......................................................................... 26 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 27 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 28 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 29 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 30 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

.........................................................................PATHOLOGY REPORT PAGE : 72/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————————————————————————————————————————————————————————————————————— — TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————— ———————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 6

.........................................................................

* NECROPSY FINDINGS

N O NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examinedPATHOLOGY REPORT PAGE : 73/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 6

.........................................................................

EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 7

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.PATHOLOGY REPORT PAGE : 74/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 7

.........................................................................

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 1
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examinedPATHOLOGY REPORT PAGE : 75/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———— ————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MAL E

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 7

.........................................................................

SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 8

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 1PATHOLOGY REPORT PAGE : 76/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 8

.........................................................................

JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN: Organ examined, no pathologic findings noted
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND:

— Inflammation lymphocytic, grade 1
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 77/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 8

.........................................................................

PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 9

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Erythrophagocytosis, grade 2
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 78/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 9

.........................................................................

ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————— ———————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 79/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————— ———————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 10

........................................................................ .

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 1
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examinedPATHOLOGY REPORT PAGE : 80/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 10

.........................................................................

EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 81/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 26

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic fi ndings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 82/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 26

.........................................................................

SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR : Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 27

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.PATHOLOGY REPORT PAGE : 83/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————— ———————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 27

.........................................................................

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examinedPATHOLOGY REPORT PAGE : 84/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 27

.........................................................................

BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 28

.........................................................................

* NECROPSY FINDINGS

PANCREATIC LYMPH NODE: 01: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTEDPATHOLOGY REPORT PAGE : 85/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 28

.........................................................................

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examinedPATHOLOGY REPORT PAGE : 86/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 28

.........................................................................

BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE):
O rgan examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 29

.........................................................................

* NECROPSY FINDINGS

NO NECROPSY OBSERVATIONS NOTED.PATHOLOGY REPORT PAGE : 87/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————

————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 29

.........................................................................

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES: Only one of paired organs examined/present Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examinedPATHOLOGY REPORT PAGE : 88/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 4 1310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 29

.........................................................................

EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 30

.........................................................................

* NECROPSY FINDINGS

UTERUS: 01: CONTAINS FLUID.
NO OTHER NECROPSY OBSERVATIONS NOTEDPATHOLOGY REPORT PAGE : 89/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 30

.........................................................................

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH: Organ examined, no pathologic findings noted
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Erythrophagocytosis, grade 1
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS:

— Cyclic dilation This finding corresponds to necropsy observation no: 01.
CERVIX: Organ examined, no pathologic findings noted
VAGINA:

— Proestrus epithelium
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examinedPATHOLOGY REPORT PAGE : 90/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 02, 50 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 30

.........................................................................

BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 91/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— ANIMAL HEADING DATA DOSE GROUP : 03, 150 MG/KG

——————————————————————————————————————————————————————————————————————— ——

ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 11 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 12 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 13 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 0 7

— DEC

— 12 14 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 15 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

......................................................................... 31 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 32 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 33 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 34 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 35 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

.........................................................................PATHOLOGY REPORT PAGE : 92/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 11

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: CONTENTS: GELATINOUS. 02: WALL: THICKENED.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 2 This finding corresponds to necropsy observation no: 01.
DUODENUM: No microscopic finding corresponding to necropsy observation no. 01.

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 02.
JEJUNUM:

— Hypertophy, jejunal villi with villous stunting, grade 1 PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Increased mast cells, grade 3

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 93/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

——————————————————————————————————————————————————————————————————— —————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 11

.........................................................................

MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 1
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 94/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 12

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: RIGHT SIDE: PELVIC DILATION.
PANCREATIC LYMPH NODE: 01: ENLARGED. 02: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Forestomach inflammation, lymphogranulocytic, grade 1

— Hyperplasia, squamous epithelium, diffuse, grade 3 This finding corresponds to necropsy observation no: 01.
DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2PATHOLOGY REPORT PAGE : 95/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————— ———————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 12

.........................................................................
This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 1
KIDNEYS:

— Pelvic dilation, unilateral This finding corresponds to necropsy observation no: 01.

— Hyaline droplets, bilateral, grade 1
ADRENAL GLANDS: Organ examined, no pathologic findings noted
P ROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 02.

— Lymphatic ectasia, grade 1PATHOLOGY REPORT PAGE : 96/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

————————————————————— ————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 12

.........................................................................

— Lymphoid hyperplasia, grade 1 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0
DAYS ON TEST : 28 * ANIMAL NO. : 13

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE. 02: FORESTOMACH: FOCUS/FOCI, D=12X5 MM, TAN.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: LEFT SIDE: FOCUS/FOCI, ISOLATED, REDDISH.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Forestomach inflammation, lymphogranulocytic, grade 2

— Ulcer, forestomach mucosa, grade 3 This finding corresponds to necropsy observation no: 02.

— Hyperplasia, squamous epithelium, diffuse, grade 2 This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 97/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 13

.........................................................................

DUODENUM:

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
KIDNEYS: No microscopic finding corresponding to necropsy observation no. 01.

— Hyaline droplets, bilateral, grade 1
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examinedPATHOLOGY REPORT PAGE : 98/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JO L
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 13

.........................................................................

SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphatic ectasia, grade 3

— Lymphoid hyperplasia, grade 3 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 14

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: CONTENTS: GELATINOUS. 02: WALL: THICKENED.
JEJUNUM: 01: CONTENTS: GELATINOUS. 02: WALL: THICKENED.PATHOLOGY REPORT PAGE : 99/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 14

.........................................................................

LIVER: 01: LEFT LATERAL LOBE: REDUCED IN SIZE.
MANDIBULAR LYMPH NODES: 01: LEFT SIDE: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Forestomach inflammation, lymphogranulocytic, grade 2

— Ulcer, forestomach mucosa, grade 2

— Hyperplasia, squamous epithelium, diffuse, grade 3 This finding corresponds to necropsy observation no: 01.
DUODENUM: No microscopic finding corresponding to necropsy observation no. 01.

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 02.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 01.

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 02. PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
LIVER: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2PATHOLOGY REPORT PAGE : 100/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS
DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 14

.........................................................................

MANDIBULAR LYMPH NODES:

— Erythrophagocytosis, unilateral, grade 1 This finding corresponds to necropsy observation no: 01.
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 101/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

————————————————— ————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 15

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: FOCUS/FOCI, D=4X3 MM, REDDISH. 02: CONTENTS: GELATINOUS. 03: WALL: THICKENED.
JEJUNUM: 01: CONTENTS: GELATINOUS. 02: WALL: THICKENED.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 2 This finding corresponds to necropsy observation no: 01.
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1 This finding corresponds to necropsy observation no: 01.

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 03.
JEJUNUM: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01,02. PEYER'S PATCHES: Tissue not present for histologic examinationPATHOLOGY REPORT PAGE : 102/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 15

.........................................................................

SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 3

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
PROSTATE GLAND: Organ examined, no pathologic findings noted
SEMINAL VESICLES: Organ examined, no pathologic findings noted COAGULATING GLANDS (ANTERIOR PROSTATE): Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 103/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2, 3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 15

.........................................................................

PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 104/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—————————————

———————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 31

.........................................................................

* NECROPSY FINDINGS

PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 1
DUODENUM:

— Hypertrophy, duodenal villi with villous stunting, grade 1
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 105/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 31

.........................................................................

CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphoid hyperplasia, grade 2 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 106/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 32

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
PANCREATIC LYMPH NODE: 01: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Edema, fore and glandular stomach, grade 2

— Hyperplasia, squamous epithelium, diffuse, grade 1 This finding corresponds to necropsy observation no: 01.
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 3
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1PATHOLOGY REPORT PAGE : 107/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 32

.........................................................................

MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA: Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.

— Lymphoid hyperplasia, grade 2PATHOLOGY REPORT PAGE : 108/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 32

.........................................................................

RENAL LYMPH NODE: Organ not examined

———————————————————— —————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 33

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED.
JEJUNUM: 01: WALL: THICKENED.
LIVER: 01: LEFT LATERAL LOBE: FOCUS/FOCI, MANY, RED

— BROWN.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
UTERUS: 01: REDUCED IN SIZE.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 2 This finding corresponds to necropsy observation no: 01.
DUODENUM:

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 3PATHOLOGY REPORT PAGE : 109/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 33

.........................................................................
This finding corresponds to necropsy observation no: 01.
JEJUNUM:

— Hypertophy, jejunal villi with villous stunting, grade 1 This finding corresponds to necropsy observation no: 01. PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Apoptosis/single cell necrosis, hepatocellular, grade 2 This finding corresponds to necropsy observation no: 01.

— Hypertrophy, centrilobular, hepatocellular, grade 1
SPLEEN:

— Hemosiderin pigment, grade 2
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— Atrophy
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examinedPATHOLOGY REPORT PAGE : 110/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————

————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—— ———————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 33

.........................................................................

BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 34

.........................................................................

* NECROPSY FINDINGS

STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.PATHOLOGY REPORT PAGE : 111/ 151

INDIVIDUAL ANIMAL DATA T OX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 34

.........................................................................

ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Forestomach inflammation, lymphogranulocytic, grade 3

— Edema, forestomach, grade 2

— Hyperplasia, squamous epithelium, diffuse, grade 3 This finding corresponds to necropsy observation no: 01.
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
JEJUNUM: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01,02. PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE: Organ examined, no pathologic findings noted
MANDIBULAR LYMPH NODES:

— Plasmacytosis, bilateral, grade 1
ADRENAL GLANDS: No microscopic finding corresponding to necropsy observation no. 01.

— Extracapsular nodule, unilateralPATHOLOGY REPORT PAGE : 112/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 34

.........................................................................

OVARIES: Organ not examined
UTERUS: Organ examined, no pathologic findings noted
CERVIX: Organ examined, no pathologic findings noted
VAGINA : Organ examined, no pathologic findings noted
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 113/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 35

.........................................................................

* NECROPSY FINDINGS

MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
PANCREATIC LYMPH NODE: 01: DISCOLOURATION, REDDISH.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

THYMUS: Organ examined, no pathologic findings noted
STOMACH:

— Hyperplasia, squamous epithelium, diffuse, grade 1
DUODENUM:

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Apoptosis/single cell necrosis, hepatocellular, grade 1

— Necrosis, coagulative, focal, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 114/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 03, 150 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 35

.........................................................................

ADRENAL GLANDS: Organ examined, no pathologic findings noted
OVARIES: Organ not examined
UTERUS:

— Atrophy, diffuse
CERVIX:

— Atrophy
V AGINA:

— Atrophy
SKELETAL MUSCLE: Organ not examined
EYES: Organ not examined BONE (STERNUM): Organ not examined
BONE MARROW

— STERNAL: Organ not examined
SPINAL CORD

— THORACIC SEGMENT: Organ not examined
SPINAL CORD

— LUMBAR SEGMENT: Organ not examined
SPINAL CORD

— CERVICAL SEGMENT: Organ not examined
FEMUR: Organ examined, no pathologic findings noted JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.

— Lymphoid hyperplasia, grade 3
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 115/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————— ——— ANIMAL HEADING DATA DOSE GROUP : 04, 450 MG/KG

—————————————————————————————————————————————————————————————————————————

ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 16 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 17 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 18 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 19 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 20 M K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

......................................................................... 36 F K0 K0 28 09

— NOV

— 12 06

— DE C

— 12 07

— DEC

— 12 37 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 38 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 39 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12 40 F K0 K0 28 09

— NOV

— 12 06

— DEC

— 12 07

— DEC

— 12

.........................................................................PATHOLOGY REPORT PAGE : 116/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 16

.........................................................................

* NECROPSY FINDINGS

THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: GROWN TOGETHER WITH: LIVER PROCESSUS PAPILARIS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
PROSTATE GLAND: 01: REDUCED IN SIZE.
SEMINAL VESICLES: 01: BOTH SIDES: REDUCED IN SIZE.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

HEART: Organ examined, no pathologic findings noted
LUNG: Organ examined, no pathologic findings noted
THYMUS:

— Lymphoid atrophy (involution), grade 4 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Noted

— Ulcer, forestomach mucosa, grade 4

— Hyperplasia, squamous epithelium, diffuse, grade 2PATHOLOGY REPORT PAGE : 117/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—————————————————————————————————————————————————————————————————— ——————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 16

.........................................................................

DUODENUM:

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 3
JEJUNUM:

— Hemorrhage, grade 1

— Hypertophy, jejunal villi with villous stunting, grade 2
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Tissue not present for histologic examination
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Lymphoid atrophy, grade 2
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES: Tissue not present for histologic examination
KIDNEYS : No microscopic finding corresponding to necropsy observation no. 01.

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 2
BRAIN: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 118/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

—————— ——————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 16

.........................................................................

SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES:

— Seminiferous cell debris, unilateral, grade 1
PROSTATE GLAND:

— Small organ with normal histology This finding corresponds to necropsy observation no: 01.
SEMINAL VESICLES:

— Reduced contents, bilateral, grade 2 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE):

— Reduced contents, bilateral, grade 2
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 3 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 119/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————— ———————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 17

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
PROSTATE GLAND: 01: REDUCED IN SIZE.
SEMINAL VESICLES: 01: BOTH SIDES: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 120/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 17

.........................................................................

HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar macrophage foci, grade 1
THYMUS:

— Lymphocytolysis, grade 2

— Lymphoid atrophy (involution), grade 2 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 3
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 121/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————————————————— ————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

——————————————

———————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 17

.........................................................................

RECTUM: Organ examined, no pathologic findings noted
LIVER: Organ examined, no pathologic findings noted
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 2

— Lymphoid atrophy, grade 2
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 3

— Lymphatic ectasia, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 3
KIDNEYS: No microscopic finding corresponding to necropsy observation no. 01.

— Inflammation, interstitial lymphocytic, unilateral, grade 1

— Basophilia, tubular, corticomedullary, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 2 This finding corresponds to necropsy observation no: 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES:

— Spermatidic giant cells, unilateral, grade 1
EPIDIDYMIDES:

— Inflammation, lymphocytic, unilateral, grade 1
PROSTATE GLAND:

— Small organ with normal histology This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 122/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— P ATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 17

.........................................................................

SEMINAL VESICLES:

— Reduced contents, bilateral, grade 2 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE):

— Reduced contents, bilateral, grade 2
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 3 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphatic ectasia, grade 2

— Lymphoid hyperplasia, grade 4 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 123/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 18

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, PURPLE.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
PROSTATE GLAND: 01: REDUCED IN SIZE.
SEMINAL VESICLES: 01: BOTH SIDES: REDUCED IN SIZE.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
HEART: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 124/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————

—————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

— ————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 18

.........................................................................

LUNG:

— Alveolar macrophage foci, grade 1
THYMUS:

— Lymphocytolysis, grade 1

— Lymphoid atrophy (involution), grade 2 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 3 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 2
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hypertophy, jejunal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Tissue not present for histologic examination
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 125/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————— ———————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 18

.........................................................................

LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 2

— L ymphoid atrophy, grade 2
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 3

— Lymphatic ectasia, grade 3

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 3
KIDNEYS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 1 This finding corresponds to necropsy observation no: 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND:

— Small organ with normal histology This finding corresponds to necropsy observation no: 01.
SEMINAL VESICLES:

— Reduced contents, bilateral, grade 2 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE):

— Reduced contents, bilateral, grade 2PATHOLOGY REPORT PAGE : 126/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 18

.........................................................................

SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES:

— Retinal rosettes, unilateral, grade 1 BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

—

S TERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT : Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 2 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 19

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.PATHOLOGY REPORT PAGE : 127/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 19

.........................................................................

THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
PROSTATE GLAND: 01: REDUCED IN SIZE.
SEMINAL VESICLES: 01: BOTH SIDES: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
RENAL LYMPH NODE: 01: BOTH SIDES: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
THYMUS:

— Lymphocytolysis, grade 1

— Lymphoid atrophy (involution), grade 2 This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 128/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 19

.........................................................................

PARATHYROID GLANDS: Only one of paired organs examined/present
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 3
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01. PEYER'S PATCHES:

— L ymphoid atrophy, grade 1
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 2

— Hemosiderin pigment, grade 1

— Lymphoid atrophy, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 2
KIDNEYS: No microscopic finding corresponding to necropsy observation no. 01.
ADRENAL GLANDS: No microscopic finding corresponding to necropsy observation no. 01.
PROSTATE GLAND:

— Small organ with normal histology This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 129/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 19

.........................................................................

SEMINAL VESICLES:

— Reduced contents, bilateral, grade 2 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE): Only one of paired organs examined/present

— Reduced contents, unilateral, grade 2
BONE MARROW

— STERNAL:

— Adipocytes, grade 1
FEMUR:

— Decreased bone, secondary spongiosa, grade 2
PANCREATIC LYMPH NODE:

— Lymphatic ectasia, grade 1

— Lymphoid hyperplasia, grade 2 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE:

— Lymphoid hyperplasia, grade 2 This finding corresponds to necropsy observation no: 01.
ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 20

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.PATHOLOGY REPORT PAGE : 130/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 20

.........................................................................

DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
PROSTATE GLAND: 01: REDUCED IN SIZE.
SEMINAL VESICLES: 01: BOTH SIDES: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar macrophage foci, grade 2
THYMUS:

— Lymphoid atrophy (involution), grade 1 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 131/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 20

.........................................................................

THYROID GLANDS:

— Hyperplasia/hypertrophy, follicular diffuse, bilateral, grade 1
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 3

— Hemorrhage, mucosal, focal, grade 2
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertophy, jejunal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 1
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Apoptosis/single cell necrosis, hepatocellular, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 2

— Lymphoid atrophy, grade 2PATHOLOGY REPORT PAGE : 132/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 20

.........................................................................

MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 2
KIDNEYS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 1 This finding corresponds to necropsy observation no: 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
TESTES: Organ examined, no pathologic findings noted
EPIDIDYMIDES: Organ examined, no pathologic findings noted
PROSTATE GLAND:

— Small organ with normal histology This finding corresponds to necropsy observation no: 01.
SEMINAL VESICLES:

— Reduced contents, bilateral, grade 2 This finding corresponds to necropsy observation no: 01. COAGULATING GLANDS (ANTERIOR PROSTATE):

— Reduced contents, bilateral, grade 2
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 133/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

——————————————

——————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 20

.........................................................................

BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 3 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphoid hyperplasia, grade 3 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 134/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS
D OSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 36

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: DILATION. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: DILATION. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
OVARIES: 01: BOTH SIDES: REDUCED IN SIZE.
UTERUS: 01: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 135/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

—— ——————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 36

.........................................................................

HEART: Organ examined, no pathologic findings noted
LUNG: Organ examined, no pathologic findings noted
THYMUS:

— Lymphocytolysis, grade 1

— Lymphoid atrophy (involution), grade 2 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 3
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hypertophy, jejunal villi with villous stunting, grade 1 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 136/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————— ——— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 36

.........................................................................

RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Hypertrophy, centrilobular, hepatocellular, grade 2
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 2

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 2
KIDNEYS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— AtrophyPATHOLOGY REPORT PAGE : 137/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————————————————————————————————————————————————————————————————————— — TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————— ———————

CONT./FF. ANIMAL NO. : 36

.........................................................................

SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL:

— Adipocytes, grade 1
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 2 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphoid hyperplasia, grade 3 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 138/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————— ———————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 37

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
STOMACH: 01: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: CONTENTS: GELATINOUS. 02: WALL: THICKENED.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, PURPLE.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH. 02: RIGHT SIDE: PELVIC DILATION.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
UTERUS: 01: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar inflammation, mononuclear, grade 1PATHOLOGY REPORT PAGE : 139/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 37

.........................................................................

THYMUS:

— Lymphoid atrophy (involution), grade 1
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 01.

— Hyperplasia, squamous epithelium, diffuse, grade 3
DUODENUM: No microscopic finding corresponding to necropsy observation no. 01.

— Hemorrhage, grade 1

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 02.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Inflammatory cell foci, lymphocytic, grade 1

— Hypertrophy, centrilobular, hepatocellular, grade 2PATHOLOGY REPORT PAGE : 140/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

———————

—————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

— ————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 37

.........................................................................

SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 2
K IDNEYS: No microscopic finding corresponding to necropsy observation no. 01.

— Pelvic dilation, unilateral This finding corresponds to necropsy observation no: 02.

— Inflammation, interstitial lymphocytic, unilateral, grade 1
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 1 This finding corresponds to necropsy observation no: 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— Atrophy
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 141/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 37

.........................................................................

BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

—

L UMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 2 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphoid hyperplasia, grade 3 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————— ———

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 38

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH, WALL: FOCUS/FOCI, D=3X3 MM, YELLOWISH, DARK
RED. 02: FORESTOMACH: IRREGULAR SURFACE.PATHOLOGY REPORT PAGE : 142/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 38

.........................................................................

DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
UTERUS: 01: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
HEART: Organ examined, no pathologic findings noted
LUNG:

— Alveolar macrophage foci, grade 1

— Alveolar inflammation, mononuclear, grade 1
THYMUS:

— Lymphocytolysis, grade 1

— Lymphoid atrophy (involution), grade 2 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 143/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO. : 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 38

.........................................................................

PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observations nos: 01,02.

— Hyperplasia, squamous epithelium, diffuse, grade 4
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01.
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES: Organ examined, no pathologic findings noted
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Hypertrophy, centrilobular, hepatocellular, grade 2
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Hemosiderin pigment, grade 1
MESENTERIC LYMPH NODE:

— Lymphatic ectasia, grade 1

— Erythrophagocytosis, grade 2
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 1PATHOLOGY REPORT PAGE : 144/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral D ATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 38

.........................................................................

KIDNEYS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS:

— V acuolation, zona fasciculata, multifocal, bilateral, grade 2 This finding corresponds to necropsy observation no: 01.
BRAIN: Organ examined, no pathologic findings noted
SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— Atrophy
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL: Organ examined, no pathologic findings noted
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 145/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 38

.........................................................................

FEMUR:

— Decreased bone, secondary spongiosa, grade 1 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE:

— Lymphatic ectasia, grade 2

— Lymphoid hyperplasia, grade 3 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE: Organ not examined

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 39

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: GROWN TOGETHER WITH: LIVER PROCESSUS PAPILLARUS. 02: FORESTOMACH: IRREGULAR SURFACE. 03: FORESTOMACH: FOCUS/FOCI, YELLOWISH, REDDISH.
JEJUNUM: 01: CONTAINS FLUID, GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.PATHOLOGY REPORT PAGE : 146/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————— ———————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

———————————————

——————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 39

.........................................................................

ADRENAL GLANDS: 01: ENLARGED.
OVARIES: 01: BOTH SIDES: REDUCED IN SIZE.
UTERUS: 01: REDUCED IN SIZE.
RENAL LYMPH NODE: 01: LEFT SIDE: DISCOLOURATION, DARK RED.
NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
HEART: Organ examined, no pathologic findings noted
LUNG: Organ examined, no pathologic findings noted
THYMUS:

— Lymphocytolysis, grade 3

— Lymphoid atrophy (involution), grade 3 This finding corresponds to necropsy observation no: 01.
TRACHEA: Organ examined, no pathologic findings noted
THYROID GLANDS: Organ examined, no pathologic findings noted
PARATHYROID GLANDS: Organ examined, no pathologic findings noted
STOMACH: Noted

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observation no: 02.

— Hyperplasia, squamous epithelium, diffuse, grade 3

— Hemorrhage, diffuse, grade 3 This finding corresponds to necropsy observation no: 03.PATHOLOGY REPORT PAGE : 147/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 39

.........................................................................

DUODENUM:

— Hypertrophy, duodenal villi with villous stunting, grade 2
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 01.

— Hypertophy, jejunal villi with villous stunting, grade 2
ILEUM: Organ examined, no pathologic findings noted PEYER'S PATCHES:

— Lymphoid atrophy, grade 2
CECUM: Organ examined, no pathologic findings noted
COLON: Organ examined, no pathologic findings noted
RECTUM: Organ examined, no pathologic findings noted
LIVER:

— Hypertrophy, centrilobular, hepatocellular, grade 1
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 1

— Lymphoid atrophy, grade 1
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 2

— Erythrophagocytosis, grade 3 This finding corresponds to necropsy observation no: 01.
MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 3
KIDNEYS: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
URINARY BLADDER: Organ examined, no pathologic findings noted
ADRENAL GLANDS: No microscopic finding corresponding to necropsy observation no. 01.

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 2
BRAIN: Organ examined, no pathologic findings notedPATHOLOGY REPORT PAGE : 148/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 39

.........................................................................

SCIATIC NERVE: Organ examined, no pathologic findings noted
OVARIES: Organ examined, no pathologic findings noted No microscopic finding corresponding to necropsy observation no. 01.
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— Atrophy
SKELETAL MUSCLE: Organ examined, no pathologic findings noted
EYES: Organ examined, no pathologic findings noted BONE (STERNUM): Organ examined, no pathologic findings noted
BONE MARROW

— STERNAL:

— Adipocytes, grade 2
SPINAL CORD

— THORACIC SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— LUMBAR SEGMENT: Organ examined, no pathologic findings noted
SPINAL CORD

— CERVICAL SEGMENT: Organ examined, no pathologic findings noted
FEMUR:

— Decreased bone, secondary spongiosa, grade 3 JOINTS (KNEE): Organ examined, no pathologic findings noted
PANCREATIC LYMPH NODE: Organ not examined
RENAL LYMPH NODE:

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.

—————————————————————————————————————————————————————————————————————————PATHOLOGY REPORT PAGE : 149/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 DAYS ON TEST : 28 * ANIMAL NO. : 40

.........................................................................

* NECROPSY FINDINGS

GENERAL OBSERVATIONS: 01: EMACIATED.
THYMUS: 01: REDUCED IN SIZE.
STOMACH: 01: FORESTOMACH, WALL: FOCUS/FOCI, D=9X7 MM, YELLOWISH, DARK
RED. 02: FORESTOMACH: IRREGULAR SURFACE.
DUODENUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
JEJUNUM: 01: WALL: THICKENED. 02: CONTENTS: GELATINOUS.
MESENTERIC LYMPH NODE: 01: DISCOLOURATION, DARK RED.
KIDNEYS: 01: BOTH SIDES: DISCOLOURATION, GREENISH.
ADRENAL GLANDS: 01: BOTH SIDES: DISCOLOURATION, PALE.
OVARIES: 01: BOTH SIDES: REDUCED IN SIZE.
UTERUS: 01: REDUCED IN SIZE.
PANCREATIC LYMPH NODE: 01: ENLARGED.
RENAL LYMPH NODE: 01: BOTH SIDES: ENLARGED.
NO OTHER NECROPSY OBSERVATIONS NOTEDPATHOLOGY REPORT PAGE : 150/ 151

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 40

.........................................................................

* MICROSCOPIC FINDINGS

GENERAL OBSERVATIONS:

— Macro observation noted This finding corresponds to necropsy observation no: 01.
LUNG:

— Alveolar macrophage foci, grade 1
THYMUS:

— Lymphoid atrophy (involution), grade 3 This finding corresponds to necropsy observation no: 01.
PARATHYROID GLANDS: Only one of paired organs examined/present
STOMACH:

— Ulcer, forestomach mucosa, grade 4 This finding corresponds to necropsy observations nos: 01,02.

— Hyperplasia, squamous epithelium, diffuse, grade 3
DUODENUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertrophy, duodenal villi with villous stunting, grade 3 This finding corresponds to necropsy observation no: 01.
JEJUNUM: No microscopic finding corresponding to necropsy observation no. 02.

— Hemorrhage, grade 2

— Hypertophy, jejunal villi with villous stunting, grade 2 This finding corresponds to necropsy observation no: 01. PEYER'S PATCHES:

— Lymphoid atrophy, grade 1
LIVER:

— Hypertrophy, centrilobular, hepatocellular, grade 2
SPLEEN:

— Hemopoietic foci, primarily erythropoiesis, grade 2
MESENTERIC LYMPH NODE:

— Lymphoid atrophy, grade 1

— Increased mast cells, grade 2

— Erythrophagocytosis, grade 2 This finding corresponds to necropsy observation no: 01.PATHOLOGY REPORT PAGE : 151/ 15 1

INDIVIDUAL ANIMAL DATA TOX : 501432

————————————————————————————————————————————————————————————————————————— TEST ITEM : m

— (2,3

— epoxypropoxy)

— N,N

— bis(2,3

— PATHOL. NO.: 41310 JOL
TEST SYSTEM : RAT, 28

— Day, Oral DATE : 08

— OCT

— 13
SPONSOR : Huntsman Advanced Materials PathData©System V6.2d1

————————————————————————————————————————————————————————————————————————— TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 04, 450 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

CONT./FF. ANIMAL NO. : 40

.........................................................................

MANDIBULAR LYMPH NODES:

— Lymphoid atrophy, bilateral, grade 2

— Erythrophagocytosis, unilateral, grade 2
KIDNEYS: No microscopic finding corresponding to necropsy observation no. 01.

— Inflammation, interstitial lymphocytic, unilateral, grade 1

— Basophilia, tubular, corticomedullary, unilateral, grade 1
ADRENAL GLANDS:

— Vacuolation, zona fasciculata, multifocal, bilateral, grade 2 This finding corresponds to necropsy observation no: 01.
OVARIES: No microscopic finding corresponding to necropsy observation no. 01.
UTERUS:

— Atrophy, diffuse This finding corresponds to necropsy observation no: 01.
CERVIX:

— Atrophy
VAGINA:

— Atrophy
FEMUR:

— Decreased bone, secondary spongiosa, grade 2
PANCREATIC LYMPH NODE:

— Lymphoid hyperplasia, grade 2 This finding corresponds to necropsy observation no: 01.
RENAL LYMPH NODE:

— Lymphoid hyperplasia, grade 2 This finding corresponds to necropsy observation no: 01.
ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

—————————————————————————————————————————————————————————————————————————m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 5

- Page 1

-

APPENDIX 5 SUMMARY OF DOSE RANGE FINDING STUDYm-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 5

- Page 2 - 

### Summary of Dose Range Finding Study

Study Plan Treatment: 27 October 2012 to 07 November 2012

Necropsy: 31 October 2012, 05 November 2012, 07 November 2012

Aim of the study In order to set the dose levels for the main study (Project 501432), a dose range finding study was performed (Project 501433 ).

Guidelines No guidelines were applicable as this study was intended for dose level selection purposes only.

Materials and methods If not mentioned otherwise, test system, procedures and techniques were identical to those used during the main study.

Test System/Animal husbandry Number of rats/group 3 females (group-housed, allocated at random and identified by

ear - and tailmark

. Age at s tart of treatment Approximately 6-8 weeks. Room number A0.10 Environmental Conditions Actual temperature range: 19.0

– 22.0° C. Actual relative humidity range: 42 - 68 %.

Treatment Duration of treatment 10 days for group 1 (500 mg/kg) 5 days for group 2 (1000 mg/kg) 5 days for group 3 (250 mg/kg) Dose levels 250, 500 and 1000 mg/kg body weight. No chemical analyses of dose preparations were conducted. Dose volume 5 mL/kg body weight/day. Vehicle Propylene glycol.

Observations Clinical signs: Daily, at 0-15 minutes, 1 hour (±15 minutes) and 3 hours (± 30 minutes ) after dosing. Mortality: At least twice daily. Body weights: On Day 1 prior to dosing and on Day 5 a nd /or 10

. Food consumption: Over days 1- 5 and /or 5- 10.

Pathology Necropsy: On Day 5 (group 2 and 3) or 10 (group 1) after the last observation of clinical signs (scheduled necropsy) or sooner (decedents). No organs were fixed. Animals were not fasted prior to necropsy. Organ weights: Terminal body weight, kidney, and liver weight.

List of protocol deviations

1 On Day 4 the 3 hours after dosing observation was too late performed (approximately 10

min)

. Evaluation: The slight and incidental deviation from the time schedule was considered not to have influenced the dose level selection for the main study.m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline Project 501432

APPENDIX 5

- Page 3 - Results (see also individual data tables on following pages).

Parameter 250 mg/kg 500 mg/kg 1000 mg/kg

Mortality No mortality. No mortality. No mortality.

Clinical appearance No findings. Lethargy, hunched posture, piloerection, salivation Lethargy, hunched posture, piloerection, salivation lean appearance and ptosis Body weight Normal. Reduced body weight gain Body weight loss Food consumption Normal. Slightly lower low

Macros copic examination No abnormalities noted. No abnormalities noted. GI

- tract distended with gas and many dark red foci in glandular mucosa of the stomach.
Organ weights Liver and kidney weights considered to be normal. Liver and kidney weights considere d to be normal. Liver and kidney weights considered to be normal.

Conclusion

Based on the results of this range finding study, dose levels for the main study were 50, 150 and 45 0 mg/kg body weight.

N o clear peak effect of occurrence of clinical signs was observed in the range finding study. Therefore, clinical observations in the main study were conducted immediately after dosing, and functional observation tests were conducted after dosing at no specific time point, but within a similar time period after dosing for the respective animals.