FINAL REPORT 

Volume 1 of 2 

(Text, Figures 1-2, Tables 1-27 and Appendix A - Tables A1-A31) 

STUDY TITLE

A 5-DAY REPEATED-DOSE INHALATION TOXICITY 

STUDY OF IN SPRAGUE-DAWLEY RATS 

STUDY NUMBER

STUDY DIRECTOR

STUDY INITIATION DATE

9 January 2008 

STUDY COMPLETION DATE

14 May 2008 

PERFORMING LABORATORY

SPONSOR

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STATEMENT OF NO DATA CONFIDENTIALITY CLAIMS

No claim of confidentiality is made for any information contained in this study on the 

basis of its falling within the scope of FIFRA 10 (d) 1(A), (B) or (C). 

 Sponsor: 

Sponsor's Agent: _______________________________ _____________ 

 Signature Date 

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53401 1 

COMPLIANCE STATEMENT 

This study, designated was conducted in compliance with the United States 

Environmental Protection Agency (EPA) Good Laboratory Practice Standards 

(40 CFR Part 792), 18 September 1989; the Organisation for Economic Cooperation and 

Development (OECD) Principles of Good Laboratory Practice [ C (97) 1 86/Final], 

26 November 1997; the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF) 

Good Laboratory Practice for Agricultural Chemicals (1 1 Nousan No. 6283), 

1 October 1999; the standard operating procedures of 

and the protocol as approved by the sponsor. A Certificate of Analysis was provided by 

the sponsor (presented in Appendix B); the characterization analyses were conducted 

according to unknown standards. 

Director, Inhalath Toxicology 

Study Director 

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TABLE OF CONTENTS

VOLUME 1 Page

Statement Of No Data Confidentiality Claims........................................2

Compliance Statement...............................................................................3

Table Of Contents......................................................................................4

Index Of Figures ........................................................................................7

Index Of Tables..........................................................................................8

Index Of Appendices ...............................................................................10

1. Summary...................................................................................................13

1.1. Objective....................................................................................................13

1.2. Study Design..............................................................................................13

1.3. Results........................................................................................................14

1.4. Conclusions................................................................................................14

2. Introduction..............................................................................................15

2.1. General Study Information ........................................................................15

2.2. Key Study Dates ........................................................................................15

3. Study Design.............................................................................................16

4. Experimental Procedures - Materials And Methods............................17

4.1. Test Substance Identification.....................................................................17

4.2. Exposure Methods .....................................................................................17

4.3. Test Atmosphere Generation And Monitoring ..........................................18

4.4. Methods For Characterization Of Exposure Atmospheres ........................18

4.4.1. Nominal Exposure Concentrations ............................................................18

4.4.2. Analyzed Exposure Concentrations...........................................................19

4.5. Test System................................................................................................19

4.6. Organization Of Test Groups, Exposure Levels And Treatment

Regimen .....................................................................................................20

4.7. Animal Receipt And Acclimation/Pretest Period ......................................21

4.8. Animal Housing.........................................................................................21

4.9. Diet, Drinking Water And Maintenance....................................................21

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VOLUME 1 (continued) Page

4.10. Environmental Conditions .........................................................................22

4.11. Assignment Of Animals To Treatment Groups.........................................22

5. Parameters Evaluated .............................................................................24

5.1. Clinical Observations And Survival ..........................................................24

5.2. Body Weights.............................................................................................24

5.3. Food Consumption.....................................................................................25

5.4. Clinical Pathology......................................................................................25

5.4.1. Hematology And Coagulation ...................................................................26

5.4.2. Serum Chemistry .......................................................................................26

5.5. Anatomic Pathology...................................................................................27

5.5.1. Macroscopic Examination .........................................................................27

5.5.2. Organ Weights ...........................................................................................29

5.6. Statistical Methods.....................................................................................29

5.7. Data Retention ...........................................................................................30

6. Results And Discussion............................................................................31

6.1. Clinical Observations And Survival ..........................................................31

6.2. Body Weights.............................................................................................31

6.3. Food Consumption.....................................................................................32

6.4. Clinical Pathology......................................................................................32

6.4.1. Hematology And Coagulation ...................................................................32

6.4.2. Serum Chemistry .......................................................................................33

6.5. Anatomic Pathology...................................................................................33

6.5.1. Macroscopic Examination .........................................................................33

6.5.2. Organ Weights ...........................................................................................33

7. Conclusions...............................................................................................35

8. Key Study Personnel And Report Submission......................................36

9. Quality Assurance Unit Statement.........................................................37

9.1. Phases Inspected ........................................................................................37

9.2. Approval ....................................................................................................39

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VOLUME 1 (continued) Page

10. References.................................................................................................40

11. Deviations From The Protocol................................................................41

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INDEX OF FIGURES

VOLUME 1 (continued) Page

1. Summary Of Body Weights [G] (Males)...................................................................43

2. Summary Of Body Weights [G] (Females) ...............................................................44

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INDEX OF TABLES

VOLUME 1 Page

1. Summary Of Survival And Disposition (Groups 1-4)...............................................46

2. Summary Of Survival And Disposition (Group 5)....................................................48

3. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(Detailed Physical Examinations/Dispositions - Groups 1-4) ...................................50

4. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(Detailed Physical Examinations/Dispositions - Group 5) ........................................52

5. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(At Time Of Exposure - Groups 1-4).........................................................................54

6. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(At Time Of Exposure - Group 5)..............................................................................56

7. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(Approximately 15-30 Minutes Into Exposure - Groups 1-4)...................................58

8. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(Approximately 15-30 Minutes Into Exposure - Group 5)........................................60

9. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(End Of Exposure - Groups 1-4)................................................................................62

10. Summary Of Clinical Findings: Total Occurrence/No. Of Animals

(End Of Exposure - Group 5).....................................................................................66

11. Summary Of Body Weights [G] (Groups 1-4) ..........................................................68

12. Summary Of Body Weights [G] (Group 5) ...............................................................72

13. Summary Of Body Weight Changes [G] (Groups 1-4).............................................74

14. Summary Of Body Weight Changes [G] (Group 5)..................................................76

15. Summary Of Cumulative Body Weight Changes [G] (Groups 1-4) .........................78

16. Summary Of Cumulative Body Weight Changes [G] (Group 5)..............................80

17. Summary Of Food Consumption [G/Animal/Day] (Groups 1-4) .............................82

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VOLUME 1 (continued) Page

18. Summary Of Food Consumption [G/Animal/Day] (Group 5) ..................................84

19. Summary Of Hematology Values (Groups 1-4)........................................................86

20. Summary Of Hematology Values (Group 5).............................................................98

21. Summary Of Serum Chemistry Values (Groups 1-4)..............................................110

22. Summary Of Serum Chemistry Values (Group 5)...................................................120

23. Summary Of Macroscopic Findings (Unscheduled Death).....................................130

24. Summary Of Macroscopic Findings (Groups 1-4) ..................................................131

25. Summary Of Macroscopic Findings (Group 5) .......................................................133

26. Summary Of Organ Weights And Relative Organ Weights (Groups 1-4)..............135

27. Summary Of Organ Weights And Relative Organ Weights (Group 5)...................141

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INDEX OF APPENDICES

VOLUME 1 (continued) Page

A. Individual Animal Data............................................................................................147

A1. Individual Survival And Disposition (Groups 1-4) ...........................................148

A2. Individual Survival And Disposition (Group 5) ................................................150

A3. Individual Clinical Observations

(Detailed Physical Examinations/Dispositions - Groups 1-4)...........................152

A4. Individual Clinical Observations

(Detailed Physical Examinations/Dispositions - Group 5)................................157

A5. Individual Clinical Observations (At Time Of Exposure - Groups 1-4)...........159

A6. Individual Clinical Observations (At Time Of Exposure - Group 5)................161

A7. Individual Clinical Observations

(Approximately 15-30 Minutes Into Exposure - Groups 1-4)...........................162

A8. Individual Clinical Observations

(Approximately 15-30 Minutes Into Exposure - Group 5)................................163

A9. Individual Clinical Observations (End Of Exposure - Groups 1-4)..................164

A10. Individual Clinical Observations (End Of Exposure - Group 5).......................168

A11. Individual Body Weights [G] (Groups 1-4).......................................................169

A12. Individual Body Weights [G] (Group 5)............................................................177

A13. Individual Body Weight Changes [G] (Groups 1-4) .........................................179

A14. Individual Body Weight Changes [G] (Group 5) ..............................................187

A15. Individual Cumulative Body Weight Changes [G] (Groups 1-4) .....................189

A16. Individual Cumulative Body Weight Changes [G] (Group 5) ..........................197

A17. Individual Food Consumption [G/Animal/Day] (Groups 1-4)..........................199

A18. Individual Food Consumption [G/Animal/Day] (Group 5)...............................207

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VOLUME 1 (continued) Page

A19. Individual Hematology Values (Groups 1-4) ....................................................209

A20. Individual Hematology Values (Group 5) .........................................................233

A21. Individual Serum Chemistry Values (Groups 1-4)............................................239

A22. Individual Serum Chemistry Values (Group 5).................................................255

A23. Individual Macroscopic Findings (Unscheduled Death)...................................259

A24. Individual Macroscopic Findings (Groups 1-4).................................................260

A25. Individual Macroscopic Findings (Group 5) .....................................................299

A26. Individual Organ Weights And Final Body Weights [G] (Groups 1-4)............309

A27. Individual Organ Weights And Final Body Weights [G] (Group 5).................317

A28. Individual Organ Weights Relative To Final Body Weights [G/100 G]

(Groups 1-4) .......................................................................................................319

A29. Individual Organ Weights Relative To Final Body Weights [G/100 G]

(Group 5) ............................................................................................................327

A30. Individual Organ Weights Relative To Brain Weights [G/100 G]

(Groups 1-4) .......................................................................................................329

A31. Individual Organ Weights Relative To Brain Weights [G/100 G]

(Group 5) ............................................................................................................337

VOLUME 2

B. Certificate Of Analysis (Sponsor Provided Data)....................................................340

C. Exposure Atmosphere Generation Report

( .........................................................................342

D. Pretest Clinical Observations ...................................................................................369

E. Animal Room Environmental Conditions ...............................................................372

F. Unscheduled Clinical Observations .........................................................................377

G. Clinical Pathology Methods, Procedures And References ......................................382

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VOLUME 2 (continued) Page

H. Historical Control Data ( ..................................387

I. Study Protocol ..........................................................................................................412

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1. SUMMARY

1.1. OBJECTIVE

The objective of this dose range-finding study was to evaluate potential toxic effects of

the test substance when administered via whole-body inhalation to rats for 5 consecutive

days. Standard hematology and serum chemistry evaluations were performed at the time

of scheduled necropsy. Standard tissues were harvested from all animals at necropsy and

preserved, but were not examined microscopically.

1.2. STUDY DESIGN

 was administered as a vapor via whole-body inhalation for a

6-hour/day exposure period once daily for up to 5 consecutive days to 3 groups

(Groups 2-4) of Crl:CD(SD) rats. The first day of administration was study day 0. The

target exposure levels were 1250, 2500 and 5000 ppm. A concurrent control group

(Group 1) was exposed to the vehicle, filtered air, on a comparable regimen. Based on

excessive toxicity, test substance exposure for all Group 4 animals was discontinued after

the study day 1 exposure period and an additional group (Group 5) was added to the

study. Group 5 was administered the test substance, via

whole-body inhalation at a target exposure level of 1800 ppm according to the same

regimen as Groups 2-4. Each group (Groups 1-5) consisted of 5 animals/sex. Following

5 days of test substance exposure, all rats in Groups 1, 2, 3 and 5 were euthanized and

subjected to necropsy. All surviving Group 4 animals were euthanized and subjected to

necropsy after 2 days of test substance exposure and a 3-day non-exposure period.

All animals were observed twice daily for mortality and moribundity. Clinical

examinations were performed prior to exposure, approximately 15-30 minutes after the

initiation of exposure and 0-1 hour following exposure on exposure days. Detailed

physical examinations were performed prior to test substance exposure for randomization

and twice during the exposure phase (including prior to scheduled necropsy). Individual

body weights were recorded during pretest and prior to the first, third and fifth exposures,

and food consumption was recorded on study day 4. Clinical pathology evaluations

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(hematology, coagulation and serum chemistry) were performed on all animals at the

time of necropsy. Complete necropsies were conducted on all animals, and selected

organs were weighed at the scheduled necropsies.

1.3. RESULTS

There were no test substance-related effects on body weights, organ weights or clinical

pathology parameters, nor were there any macroscopic findings in the test

substance-exposed groups.

One male in the 5000 ppm group was found dead on study day 1. All other animals

survived to the scheduled necropsy. Test substance-related clinical observations

consisted of convulsions and/or tremors in the 2500 and 5000 ppm males and females and

dried and/or wet red, yellow and/or brown material on various body surfaces in the

5000 ppm group males and females. Slightly lower food consumption was noted in the

2500 ppm males and females from study days 0 to 4.

1.4. CONCLUSIONS

Based on the results of this study, systemic toxicity of 

administered via whole-body inhalation exposure to Crl:CD(SD) rats for up to 5 days was

observed at dose levels of 2500 and 5000 ppm as evidenced by lethality in the 5000 ppm

group, convulsions and/or tremors in the 2500 and 5000 ppm groups and decreased food

consumption in the 2500 ppm group males and females. The no-observed-effect level

(NOEL) for administered via whole-body inhalation exposure to

Crl:CD(SD) rats for up to 5 days was 1800 ppm. Therefore, the maximum concentration

for a subsequent 28-day study should be no higher than 2500 ppm.

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2. INTRODUCTION

2.1. GENERAL STUDY INFORMATION

This report presents the data from “A 5-Day Repeated-Dose Inhalation Toxicity Study Of

 In Sprague-Dawley Rats”. Due to software spacing constraints,

the study title appears as “A 5-Day Inhalation Study In Rats” on the report tables.

The following computer protocols were used for data collection during the study:

Computer Protocol Type of Data Collected

........................................... Main study data (Groups 1-4)

534011A ........................................ Main study data (Group 5)

534011P......................................... Pretest data

534011U ........................................ Unscheduled Clinical Observations

2.2. KEY STUDY DATES

Date(s) Event(s)

22 January 2008...................................... Experimental starting date (animal receipt

for Group 1-5 animals)

4 February 2008...................................... Assignment to study groups (Groups 1-4)

6 February 2008...................................... Experimental start date (initiation of dose

administration for Groups 1-4;

study day 0)

8 February 2008...................................... Transfer of Group 5 females from 

stock colony; randomization of Group 5

animals

9 February 2008...................................... Initiation of dose administration for

Group 5; study day 0

11 February 2008.................................... Primary necropsy

(study day 5; Groups 1-4)

14 February 2008.................................... Experimental termination (completion) date

(Group 5 Primary necropsy, study day 5)

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3. STUDY DESIGN

5 animals/sex/group (Group 4) exposed

for 2 days; 5 animals/sex/group

(Groups 1, 2, 3 and 5) for

5 consecutive days

Clinical observations recorded daily;

body weights recorded prior to the first,

third and fifth exposures; food intake

recorded on study day 4

Clinical pathology evaluations

conducted prior to necropsy

Necropsies performed on animal found

dead; selected tissues retained for

possible histological examination

Necropsies performed on all

animals/sex/group on study day 5;

selected organs weighed; selected tissues

retained for possible histological

examination

Acclimation/pretest period

Assignment of animals to

study groups

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4. EXPERIMENTAL PROCEDURES - MATERIALS AND METHODS

4.1. TEST SUBSTANCE IDENTIFICATION

The test substance, (chemical name

 was received from 

 via Nippon EXP ORD, Des Plaines, Illinois, on 21 January

2008, as follows:

Identification

Quantity

Received

Physical

Description

[

15 drums

Total gross weight:

330.0 lb

Clear, colorless

liquid

Documentation regarding the purity and stability of the test substance are on file with the

sponsor and A Certificate of Analysis for the test

substance was provided by the sponsor and is presented in Appendix B. The test

substance was stored at room temperature and was considered stable under this condition.

A reserve sample of the test substance (22.7 g) was collected on 28 January 2008, and

stored in the Archives of 

4.2. EXPOSURE METHODS

Exposures were conducted in four 500-L stainless steel and glass whole-body inhalation

exposure chambers. One chamber was dedicated for each group with the exception of

Chamber 4. Following the termination of Group 4, an additional group (Group 5) was

added to the study and was exposed in Chamber 4. The following table presents the

chambers used for each group:

Group Number 1 2 3 4 5

Chamber Number 1 2 3 4 4

Target Exposure Concentration (ppm) 0 1250 2500 5000 1800

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Chamber supply air was provided from a HEPA- and charcoal-filtered, temperature- and

humidity-controlled source. All test atmosphere chamber exhaust passed through carbon

scrubbers (Environtrol, Inc., Sewickley, PA) prior to the facility exhaust system, which

consisted of charcoal and HEPA filtration. The exposure period was 6 hours per day for

5 consecutive days for Groups 1-3 and 5 and 6 hours per day for 2 consecutive days for

Group 4. For the exposure each day, the animals were transferred to exposure caging,

transported to the exposure chamber room, exposed for the requisite duration and

returned to their home cages in the animal colony room. The cage batteries were rotated

on a daily basis between 2 battery positions in the chambers to help ensure a similar

exposure for all animals within each group over the duration of the exposure period.

Food and water were withheld during each daily exposure period. Exposure methods and

conditions are detailed in Appendix C.

4.3. TEST ATMOSPHERE GENERATION AND MONITORING

Vapors of the test substance were generated using a glass-bead column-type vaporization

system. The vaporization column was wrapped with an electric heating tape (Omega

Engineering Co., Stamford, CT) controlled using a J-type thermocouple and digital

temperature controller. Using a regulator and calibrated rotameter-type flowmeters,

nitrogen was metered to the bottom of each vaporization column. Vaporization occurred

as the liquid test substance coated the surface of the heated beads and nitrogen flowed up

through the column. The concentrated vapors were piped to the chamber inlet and

diluted to the desired concentration by mixing with the chamber supply air. For Group 1,

nitrogen was supplied to the chamber inlet and dilated with chamber supply air. Refer to

Appendix C for a complete description of the generation and exposure systems.

4.4. METHODS FOR CHARACTERIZATION OF EXPOSURE ATMOSPHERES

4.4.1. NOMINAL EXPOSURE CONCENTRATIONS

A nominal exposure concentration was calculated daily for each test substance group

from the total amount of test substance used during the exposure and the total volume of

air passed through the chamber during that day’s exposure. The amount of test substance

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used was obtained by weighing the test substance reservoir prior to and after each day’s

exposure. The total volume of air passed through each chamber was calculated from the

daily average chamber ventilation flowrate in LPM and the exposure duration. The

nominal concentration was calculated as follows.

WT × MV × 106

Concentration (ppm) = GMW × CVR × DUR

Where:

WT = Weight of test substance used, grams

MV = Molar volume at 730 mmHg and 21oC, 25.11 L/mole

106 = ppm conversion factor

GMW = Test substance gram molecular weight, 200.05 g/mole

CVR = Daily mean chamber ventilation rate for a given day, LPM

DUR = Duration of the daily exposure, minutes

4.4.2. ANALYZED EXPOSURE CONCENTRATIONS

Analyzed exposure concentrations were determined at approximately 30-minute intervals

using a gas chromatograph (GC). Samples were collected from the approximate

animal-breathing zone of the inhalation exposure chambers via 1/8-inch Teflon® tubing.

Samples were collected manually using an external multi-position valve (Model E16,

Valco Instruments Co., Inc., Houston, TX) and a Hewlett Packard Model 3396 Series II

integrator (with BASIC program). Gas sample injection onto the chromatography

column occurred via an internal gas-sampling valve with a sample loop. The

chromatograph was displayed and the area under the sample peak was calculated and

stored. The concentration in parts per million (ppm) was calculated using an ln-quadratic

equation based on the GC calibration curve. Refer to Appendix C for a complete

description of the exposure analyses.

4.5. TEST SYSTEM

Crl:CD(SD) rats from Charles River Laboratories, Inc., Raleigh, North Carolina were

used as the test system on this study. This species and strain of animal is recognized to

be appropriate for inhalation toxicity studies. The Sprague Dawley rat was selected

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because it is a widely used strain for which historical control data are available. The

animals were approximately 9 weeks old at the initiation of exposure.

4.6. ORGANIZATION OF TEST GROUPS, EXPOSURE LEVELS AND

TREATMENT REGIMEN

Five males and 5 females per group in Groups 1-3 and 5 were exposed for 6 hours daily

for 5 days, through the day prior to the scheduled necropsy. Animals in Group 4 were

exposed for 6 hours daily for 2 days and euthanized 4 days later on study day 5. The first

day of exposure was study day 0.

The following table presents the study group assignment:

Group Number of Animals

Number Test Substance

Target Exposure

Level (ppm) Males Females

1 Filtered Air 0 5 5

2 1250 5 5

3 2500 5 5

4 5000 5 5

5 1800 5 5

The target exposure levels for Groups 1-4 were selected by the sponsor representative

based on the results of previous inhalation toxicology studies. The target exposure level

for Group 5 was selected based on the excessive toxicity in the 2500 and 5000 ppm

groups.

The selected route of administration for this study was inhalation exposure since this is a

potential route of human exposure. The number of animals selected for this study was

the minimum number required to yield statistically valid and scientifically meaningful

data.

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4.7. ANIMAL RECEIPT AND ACCLIMATION/PRETEST PERIOD

For Groups 1-4 and the Group 5 males, 25 male and 25 female Crl:CD(SD) rats were

received in good health on 22 January 2008 from Charles River Laboratories, Inc.,

Raleigh, North Carolina. The animals were approximately 7 weeks old at receipt. Each

animal was examined by a qualified technician on the day of receipt and weighed 3 days

later. Five females for use in Group 5 were transferred from the stock rat colony on

8 February 2008.

Each animal was uniquely identified by a Monel® metal ear tag displaying the permanent

identification number. In addition to an ear tag, each Group 5 female had a subcutaneous

microchip (BMDS system). All animals in Groups 1-4 and 5 were housed for an

acclimation/pretest period of 15 or 18 days, respectively. During this period, each animal

was observed twice daily for mortality and changes in general appearance or behavior.

Pretest data collection began on 25 January 2008. Individual body weights were recorded

and detailed physical examinations were performed periodically during the pretest period

for animals in Groups 1-4. Food consumption data was also recorded for pretest animals

in Groups 1-4 prior to the initiation of dose administration. Pretest clinical data are

presented in Appendix D. Pretest data collection was not performed for the Group 5

females.

4.8. ANIMAL HOUSING

Upon arrival, all animals were single-housed in clean, stainless steel, wire mesh cages

suspended above cage board. Animals were maintained in accordance with the Guide for

the Care and Use of Laboratory Animals (National Research Council, 1996). The animal

facilities at are accredited by the Association for

Assessment and Accreditation of Laboratory Animal Care International (AAALAC

International).

4.9. DIET, DRINKING WATER AND MAINTENANCE

The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent

LabDiet® 5002 (meal), is a certified feed with appropriate analyses performed by the

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manufacturer and provided to Reverse osmosis

treated (on site) drinking water, delivered by an automatic watering system, and the basal

diet were provided ad libitum throughout the study, except during exposures and the

period of fasting prior to blood collection when food, but not water, was withheld. Food

was also withheld overnight from all Group 4 animals on study day 1 for possible blood

collection on study day 2; food was replaced the following morning because animals

were held for blood collection on study day 5 instead of study day 2. Municipal water

supplying the facility was sampled for contaminants according to the standard operating

procedures. The results of the diet and water analyses are maintained at 

 No contaminants were present in animal feed or water at

concentrations sufficient to interfere with the objectives of this study.

4.10. ENVIRONMENTAL CONDITIONS

All animals were housed throughout the acclimation period and during the study in an

environmentally controlled room. The room temperature and humidity controls were set

to maintain daily averages of 71 ± 5oF (22 ± 3oC) and 50 ± 20% relative humidity. Room

temperature and relative humidity were controlled and monitored using the Metasys®

DDC Electronic Environmental control system. These data were recorded approximately

hourly and are summarized in Appendix E. Actual mean daily temperature ranged from

70.0oF to 72.0oF (21.1oC to 22.2oC) and mean daily relative humidity ranged from 36.1%

to 41.6% during the study. Fluorescent lighting provided illumination for a 12 hour light

(0600 hours to 1800 hours)/12 hour dark photoperiod. Air handling units were set to

provide a minimum of 10 fresh air changes per hour.

4.11. ASSIGNMENT OF ANIMALS TO TREATMENT GROUPS

Two days prior to the initiation of exposure for Groups 1-4 (4 February 2008), all

available rats were weighed and examined in detail for physical abnormalities. These

data were collected using the Toxicology Data Management System (WTDMSTM)

and reviewed by the study director. The animals judged suitable for assignment to the

study were selected for use in a computerized randomization procedure. A printout

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containing the animal numbers, corresponding body weights and individual group

assignments was generated based on body weight stratification in a block design. The

animals were then arranged into groups according to the printout. On 8 February 2008,

the males excluded from Groups 1-4 were returned to the study and additional females

from the stock rat colony were selected for the study in the same fashion as

Groups 1-4 (randomized by computer program). Individual body weights at

randomization were within ± 20% of the mean for each sex. Each group consisted of

5 males and 5 females. Individual body weights on study day 0 ranged from 288 g to

367 g for males and from 186 g to 240 g for females.

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5. PARAMETERS EVALUATED

5.1. CLINICAL OBSERVATIONS AND SURVIVAL

All animals were observed twice daily, once in the morning and once in the afternoon, for

mortality and moribundity.

Clinical observations were performed 3 times daily on the days of exposure. Time points

included an observation prior to exposure and 0-1 hour following exposure (designated

as1 hour following exposure for report presentation purposes). In addition, an

observation was performed 15-30 minutes after the initiation of exposure (Groups 1-3

and 5 only). This observation time point was initiated on 8 February 2008 (study day 3);

however, observations had been recorded as unscheduled observations during this time

point on study days 0-2. The unscheduled observations recorded 15-30 minutes after the

initiation of exposure on study days 0-2 are presented with observations from this time

point on study days 3 and 4. Because an official observational time point was not

designated for the first 3 days of dosing, the absence of findings (designated as no

significant clinical observations) was not recorded for any animals 15-30 minutes after

the initiation of exposure until study day 3. During the non-exposure days for Group 4

animals, examinations were performed at the same time as the observations for the

animals being exposed to the test substance. Detailed physical examinations were

conducted on all animals prior to test substance administration for randomization and

twice during the exposure phase, including an examination prior to the scheduled

necropsy. Observations prior to exposure were not performed on the days of detailed

physical examinations. The presence or absence of significant findings were recorded for

individual animals.

5.2. BODY WEIGHTS

Individual body weights were recorded during the pretest period beginning approximately

2 weeks prior to test substance exposure, at randomization (Groups 1-4 only), and prior to

the first, third and fifth exposures. Mean body weights and mean body weight changes

were calculated for the corresponding intervals. Final body weights (fasted) were

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recorded prior to the scheduled necropsies. The exposures for the 5000 ppm group were

terminated following the second exposure (study day 1). To prepare for possible blood

collection and necropsy on the following day, the animals in this group were fasted

overnight from study day 1 to 2. On study day 2, the decision was made to evaluate the

5000 ppm group animals for clinical pathology and necropsy on study day 5 according to

the original schedule. However, the scheduled study day 2 body weight for the 5000 ppm

group animals was effectively a fasted body weight.

5.3. FOOD CONSUMPTION

Individual food consumption was recorded during pretest and on study day 4 for all

animals in Groups 1-3 and 5, and on study days 1 and 4 for Group 4 animals. Food

intake was calculated as g/animal/day. Due to food consumption data collection on study

day 1, additional food consumption data for Group 4 animals is located in Appendix F.

5.4. CLINICAL PATHOLOGY

Blood samples for clinical pathology evaluations (hematology, coagulation and serum

chemistry) were collected from all animals at the scheduled necropsy (study day 5). The

animals were fasted overnight prior to blood collection. Blood was collected for

hematology and serum chemistry evaluation via the retro-orbital sinus of animals

anesthetized by inhalation of isoflurane. Blood was collected for coagulation parameters

at the time of euthanasia via the vena cava of animals euthanized by inhalation of

isoflurane. Blood was collected into tubes containing EDTA (hematology), sodium

citrate (clotting determinations) or no anticoagulant (serum chemistry). Clinical

pathology methods, procedures and references are presented in Appendix G. The

following parameters were evaluated:

25 of 435
5.4.1. HEMATOLOGY AND COAGULATION

Total leukocyte count (White Cells)

Erythrocyte count (Red Cells)

Hemoglobin

Hematocrit

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin

(MCH)

Mean corpuscular hemoglobin

concentration (MCHC)

Platelet count (Platelet)

Prothrombin time (ProTime)

Activated partial thromboplastin time

(APTT)

Reticulocyte count

Percent (Reticulocyte)

Absolute (Retic Absolute)

Differential leukocyte count -

Percent and absolute

-Neutrophil

-Lymphocyte

-Monocyte

-Eosinophil

-Basophil

-Large unstained cell

Platelet estimatea

Red cell morphology

(RBC Morphology)a

( ) - Designates tabular abbreviation

a

 - Presented on individual tables if a manual differential was performed, and the

manual data were accepted and reported instead of the automated differential

data

5.4.2. SERUM CHEMISTRY

Albumin

Total protein

Globulin [by calculation]

Albumin/globulin ratio (A/G Ratio)

[by calculation]

Total bilirubin (Total Bili)

Urea nitrogen

Creatinine

Alkaline phosphatase

(AlkalinePhos’tse)

Alanine aminotransferase

(Alanine Transfer)

Aspartate aminotransferase

(AspartatTransfer)

Glucose

Total cholesterol (Cholesterol)

Calcium

Chloride

Phosphorus

Potassium

Sodium

Triglycerides (Triglyceride)

( ) - Designates tabular abbreviation

26 of 435
5.5. ANATOMIC PATHOLOGY

5.5.1. MACROSCOPIC EXAMINATION

A complete necropsy was conducted on all animals. Animals were euthanized by

isoflurane anesthesia and exsanguinated. The necropsies included, but were not limited

to, examination of the external surface, all orifices, and the cranial, thoracic, abdominal

and pelvic cavities, including viscera. Clinical findings that were confirmed

macroscopically were designated CEO (correlates with externally observed) on the

individual macroscopic data tables. The following tissues and organs were collected and

placed in 10% neutral-buffered formalin (except as noted):

27 of 435
Adrenals (2)

Aorta

Bone with marrow (sternebrae)

Bone with marrow (femur with joint)

Bone marrow smear (taken from

femur)a

Brain

Cerebrum 2 levels

Cerebellum with medulla/pons

Cervix

Epididymides (2) b

Exorbital lacrimal glands (2)

Eyes with optic nerves (2) c

Gastrointestinal tract

Esophagus

Stomach

Duodenum

Jejunum

Ileum with Peyer’s patches

Cecum

Colon

Rectum

Harderian glands (2)

Heart

Kidneys (2)

Larynx

Liver (sections of 2 lobes)

Lungs (including bronchi, fixed by

inflation with fixative)

Lymph nodes

Mediastinal and bronchial (if visible)

Mesenteric and mandibular (2)

Mammary gland (females only)

Nasal Cavityd

Ovaries/oviducts (2)e

Pancreas

Peripheral nerve (sciatic)

Pituitary

Pharynx

Prostate

Salivary glands [mandibular (2)]

Seminal vesicles (2)

Skeletal muscle (rectus femoris)

Skin

Spinal cord (cervical, thoracic, lumbar)

Spleen

Testes (2) b

Thymus

Thyroid [with parathyroids (2)]e

Trachea

Urinary bladder

Uterus

Vagina

Gross lesions (when possible)

a

 - Bone marrow smears were obtained at scheduled necropsy, but not placed in

formalin; slides were not examined.

b

 - Fixed in Bouin’s solution

c

 - Fixed in Davidson’s solution

d

 - Following collection of the appropriate protocol-specified tissues, the entire

head was removed and preserved. e

 - Parathyroids and oviducts were retained for possible microscopic examination

if in the plane of section and in all cases when a gross lesion of the organ was

present.

28 of 435
5.5.2. ORGAN WEIGHTS

The following organs were weighed from all animals at the scheduled necropsy:

Brain

Kidneys

Liver

Lungs*

* = Weighed prior to inflation with fixative

Paired organs were weighed together. Organ-to-final-body-weight and

organ-to-brain-weight ratios were calculated.

5.6. STATISTICAL METHODS

All statistical tests were performed using appropriate computing devices or programs.

Analyses were conducted using two-tailed tests (except as noted otherwise) for minimum

significance levels of 1% and 5%, comparing each test substance-treated group to the

control group by sex. Each mean was presented with the standard deviation (S.D.),

standard error (S.E.) and the number of animals (N) used to calculate the mean. In

addition, percent difference from control is presented for body weights, clinical

pathology and organ weight values. Statistical analyses were not conducted if the

number of animals was 2 or less. Due to the different rounding conventions inherent in

the types of software used, the means and standard deviations on the summary and

individual tables may differ by ±1 in the last significant figure.

Due to the absence of a concurrent control group, all Group 5 data was qualitatively

compared to the appropriate version of historical control data.

Body weight, body weight change, food consumption, clinical pathology and organ

weight data from Groups 1-4 were subjected to a parametric one way analysis of variance

(ANOVA) (Snedecor and Cochran, 1980) to determine intergroup differences. If the

ANOVA revealed statistically significant (p<0.05) intergroup variance, Dunnett's test

(Dunnett, 1964) was used to compare the test substance treated groups to the control

group.

29 of 435
5.7. DATA RETENTION

The sponsor has title to all documentation records, raw data, specimens, slides or other

work product generated during the performance of the study. All work product generated

by including raw paper data and specimens, are

retained in the Archives at as specified in the study

protocol.

Reserve samples of the test substance, pertinent electronic storage media and the original

final report are retained in the Archives at in

compliance with regulatory requirements.

30 of 435
6. RESULTS AND DISCUSSION

6.1. CLINICAL OBSERVATIONS AND SURVIVAL

Summary Data: Tables 1 through 10

Individual Data: Tables A1 through A10

Male no. 95554 (Group 4, 5000 ppm) was found dead on study day 1. This animal had

been noted with intermittent tremors during exposure on study day 0 and intermittent and

continuous convulsions during exposure on study day 1. These observations and the

animal’s death were considered to be test substance-related.

All other animals survived to the scheduled necropsies. Intermittent tremors and

intermittent/continuous convulsions were noted during the exposure period in the

5000 ppm group males and females. Intermittent convulsions were also noted in one

2500 ppm group male on study days 2, 3 and 4 and in one 2500 ppm group female on

study days 2 and 4. Dried and/or wet red, yellow and/or brown material on various body

surfaces was noted in the 5000 ppm group males and females and was considered to be

likely related to the stress of convulsions and/or tremors.

There were no other test substance-related clinical observations. All clinical findings in

the test substance-treated groups were not noted in a dose-related manner and/or were

common findings for laboratory rats of this age and strain.

6.2. BODY WEIGHTS

Summary Data: Tables 11, 12, 13, 14, 15 16

Individual Data: T ables A11, A12, A13, A14, A15 A16

There were no test substance-related effects on body weights throughout the study. A

significantly lower mean body weight was noted in the 5000 ppm group males and

females on study day 2; however, these animals had been fasted for possible blood

collection and this is likely the cause of the difference from the control group (see

Section 5.3 for further explanation).

31 of 435
6.3. FOOD CONSUMPTION

Summary Data: Tables 17, 18

Individual Data: Tables A17, A18

Statistically significantly lower mean food consumption was noted from study days 0 to 4

in the 2500 ppm group males and females. Food consumption was unaffected by test

substance exposure in the 1250 and 1800 ppm group males and females.

6.4. CLINICAL PATHOLOGY

6.4.1. HEMATOLOGY AND COAGULATION

Summary Data: Tables 19, 20

Individual Data: Tables A19, A20

Hematology parameters were unaffected by test substance administration. When

compared to the control group, mean absolute and percent reticulocyte values were

statistically significantly lower in the 2500 ppm group males; in addition, mean absolute

reticulocyte values were also statistically significantly lower in the 1250 ppm group

females. There were no effects on other red blood cell parameters and because all

absolute and percent reticulocyte values for all groups fell within the range of 

historical control data (version 2.5); therefore, these findings were not considered to be

test substance-related. The mean percent basophil count was statistically significantly

higher in the 1250 ppm group males; however, this value was within the range of 

historical control data and was not considered test substance-related. There were no other

effects on hematology and coagulation parameters. Due to the absence of a concurrent

control group, all 1800 ppm group data was qualitatively compared to the appropriate

version of historical control data. Based on these comparisons, there were no

effects on hematology and coagulation parameters in the 1800 ppm group.

32 of 435
6.4.2. SERUM CHEMISTRY

Summary Data: Tables 21, 22

Individual Data: Tables A21, A22

Serum chemistry parameters were unaffected by test substance administration. When the

control and test substance-treated groups were compared there were statistically

significant lower values in the 5000 ppm group female mean total protein value, the

2500 ppm group female urea nitrogen value and the 1250 ppm male glucose value.

However, these differences were not noted in a dose-related trend and/or all were within

the range of the historical control data (version 2.5) and were not considered test

substance-related. Due to the absence of a concurrent control group, all 1800 ppm group

data was qualitatively compared to the appropriate version of historical control data.

Based on these comparisons, there were no effects on serum chemistry parameters in the

1800 ppm group.

6.5. ANATOMIC PATHOLOGY

6.5.1. MACROSCOPIC EXAMINATION

Summary Data: Tables 23, 24, 25

Individual Data: Tables A23, A24, A25

There were no test substance-related macroscopic findings at the scheduled necropsy.

All macroscopic findings noted were considered to be spontaneous and/or incidental in

nature and unrelated to test substance administration.

6.5.2. ORGAN WEIGHTS

Summary Data: Tables 26, 27

Individual Data: Tables A26, A27, A28, A29, A30, A31

Organ weights were unaffected by exposure to There were no

statistically significant differences when Groups 2-4 were compared to the control group,

nor were there any remarkable organ weight effects noted in the Group 5 (1800 ppm)

males and females based on comparison to historical control data (version 2.4). In

33 of 435
addition, all mean organ weight values were within the range of the historical

control data.

34 of 435
7. CONCLUSIONS

Based on the results of this study, systemic toxicity of 

administered via whole-body inhalation exposure to Crl:CD(SD) rats for up to 5 days was

observed at dose levels of 2500 and 5000 ppm as evidenced by lethality in the 5000 ppm

group, convulsions and/or tremors in the 2500 and 5000 ppm groups and decreased food

consumption in the 2500 ppm group males and females. The no-observed-effect level

(NOEL) for administered via whole-body inhalation exposure to

Crl:CD(SD) rats for up to 5 days was 1800 ppm. Therefore, the maximum concentration

for a subsequent 28-day study should be no higher than 2500 ppm.

35 of 435
8. 

435
9. QUALITY ASSURANCE UNIT STATEMENT

9.1. PHASES INSPECTED

Date(s) of 

Inspection(s) Phase Inspected

Date(s) 

Findings 

Reported to 

Study Director

Date(s) 

Findings 

Reported to 

Management Auditor(s)

06-Feb-2008 Test Substance Exposure 06-Feb-2008 26-Mar-2008 M.Stauffer 

14-Apr-2008 

15-Apr-2008 

16-Apr-2008 

17-Apr-2008 Study Records (I-1) 17-Apr-2008 14-May-2008 J.Godby 

16-Apr-2008 Study Records (C-1) 16-Apr-2008 14-May-2008 J.Godby 

16-Apr-2008 Study Records (N-1) 16-Apr-2008 14-May-2008 J.Godby 

16-Apr-2008 

17-Apr-2008 Draft Report without 

Inhalation Report 

17-Apr-2008 14-May-2008 J.Godby 

28-Apr-2008 

29-Apr-2008 

30-Apr-2008 Inhalation Report 30-Apr-2008 14-May-2008 J.Godby 

28-Apr-2008 

29-Apr-2008 

30-Apr-2008 Study Records (EX-1, EX-2) 30-Apr-2008 14-May-2008 J.Godby 

This study was inspected in accordance with the U.S. EPA Good Laboratory Practice 

Standards (40 CFR Parts 160 and 792), the OECD Principles of Good Laboratory 

Practice, the standard operating procedures of and the 

sponsor's protocol and protocol amendments, with the following exception. The data 

located in Appendix B (Certificate Of Analysis) were the responsibility of the sponsor. 

Quality Assurance findings, derived from the inspections during the conduct of the study 

and from the inspections of the raw data and draft report, are documented and have been 

reported to the study director. A status report is submitted to management monthly. 

This report accurately reflects the data generated during the study. The methods and 

procedures used in the study were those specified in the protocol, its amendments and the 

standard operating procedures of

37 of 435
The raw data, the retention sample and the final report will be stored in the Archives at

 or another location specified by the sponsor.

38 of 435
53401 1 

9.2. APPROVAL 

This study was inspected according to the criteria discussed in Section 9.1. 

39 of 435
10. REFERENCES

Dunnett, C.W. New tables for multiple comparisons with a control. Biometrics

1964, 20, 482-491.

National Research Council. Guide for the Care and Use of Laboratory Animals,

Institute of Laboratory Animal Resources, Commission on Life Sciences; National

Academy Press: Washington, DC, 1996.

Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In

Statistical Methods, 7th ed.; The Iowa State University Press: Ames, IA, 1980;

pp 215-237.

40 of 435
11. DEVIATIONS FROM THE PROTOCOL

This study was conducted in accordance with the protocol and protocol amendments,

except for the following.

• Protocol Section 5.5 states that at the initiation of exposure, male rat body weights

will range from 250 to 350 g. Body weights for male nos. 95577, 95554, 95562 and

95575 were above 350 g on study day 0.

• Protocol Section 7.1 states that animals will be allowed a pretreatment week (as part

of the acclimation period) during which body weights and food consumption will be

recorded and general health will be monitored, but they will not receive the test

substance. Because the Group 5 females were originally received for use on another

study, pretest data for these animals was collected but not transferred for use on this

study.

• Protocol Section 7.7.1 states that the nominal test substance concentration will be

within ± 10% of the measured chamber concentration. The nominal concentration for

Group 5 was not within this range.

• Protocol Section 8.4 states that a final body weight will be determined prior to

necropsy. On 7 February 2008 (study day 1), a final body weight was recorded for

male no. 95554 (Group 4, 5000 ppm) which was found dead.

• Protocol Section 8.4 states that individual body weights will be recorded during the

pretest phase for randomization and group assignment. On 8 February 2008 (study

day -1), weights for the 5 female animals used for Group 5 were hand-entered to

allow for randomization. The weights entered were collected on 6 February 2008;

weights from 8 February 2008 should have been used.

These deviations did not negatively impact the quality or integrity of the data nor the

outcome of the study.

.

41 of 435
FIGURES 1 - 2

42 of 435
 PROJECT NO.: FIGURE 1

SUMMARY OF BODY WEIGHTS (G) - MALES

a = Test substance exposure was discontinued for the 5000 ppm group following exposure on study day 1; tfasted for possible blood collection from study day 1-2 

150200250300350

-12 -8 -2 0 2 

STUDY DAY

BODY WEIGHT (GRAMS)

0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM

a

43 of 435
 PROJECT NO.: FIGURE 2

SUMMARY OF BODY WEIGHTS (G) - FEMALES

a = Test substance exposure was discontinued for the 5000 ppm group following exposure on study day 1; tfasted for possible blood collection from study day 1-2 

150200250300350

-12 -8 -2 0 2 

STUDY DAY

BODY WEIGHT (GRAMS)

0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM

a

44 of 435
TABLES 1 - 27

45 of 435
 TABLE 1 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF SURVIVAL AND DISPOSITION 

 

 MALES 

 GROUP : 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY LIVE FD EE SE LIVE FD EE SE LIVE FD EE SE LIVE FD EE SE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 0 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 1 5 0 0 0 5 0 0 0 5 0 0 0 4 1 0 0 

 2 5 0 0 0 5 0 0 0 5 0 0 0 4 0 0 0 

 3 5 0 0 0 5 0 0 0 5 0 0 0 4 0 0 0 

 4 5 0 0 0 5 0 0 0 5 0 0 0 4 0 0 0 

 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY = DAY OF STUDY FD = FOUND DEAD EE = EUTHANIZED IN EXTREMIS SE = SCHEDULED EUTHANASIA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

46 of 435
 TABLE 1 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF SURVIVAL AND DISPOSITION 

 

 FEMALES 

 GROUP : 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY LIVE FD EE SE LIVE FD EE SE LIVE FD EE SE LIVE FD EE SE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 0 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 1 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 2 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 3 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 4 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 

 5 0 0 0 5 0 0 0 5 0 0 0 5 0 0 0 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY = DAY OF STUDY FD = FOUND DEAD EE = EUTHANIZED IN EXTREMIS SE = SCHEDULED EUTHANASIA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PSURVv4.09 

 03/19/2008 

47 of 435
 TABLE 2 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF SURVIVAL AND DISPOSITION 

 

 MALES 

 GROUP : 5 

 DAY LIVE FD EE SE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 0 5 0 0 0 

 1 5 0 0 0 

 2 5 0 0 0 

 3 5 0 0 0 

 4 5 0 0 0 

 5 0 0 0 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY = DAY OF STUDY FD = FOUND DEAD EE = EUTHANIZED IN EXTREMIS SE = SCHEDULED EUTHANASIA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 

48 of 435
 TABLE 2 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF SURVIVAL AND DISPOSITION 

 

 FEMALES 

 GROUP : 5 

 DAY LIVE FD EE SE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 0 5 0 0 0 

 1 5 0 0 0 

 2 5 0 0 0 

 3 5 0 0 0 

 4 5 0 0 0 

 5 0 0 0 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY = DAY OF STUDY FD = FOUND DEAD EE = EUTHANIZED IN EXTREMIS SE = SCHEDULED EUTHANASIA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 PSURVv4.09 

 03/19/2008 

 R:03/24/2008 

49 of 435
 TABLE 3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 005 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 9/ 5 10/ 5 10/ 5 8/ 5 

 

 DISPOSITION 

 -FOUND DEAD 0/ 0 0/ 0 0/ 0 1/ 1 

 -PRIMARY NECROPSY (DAY 5) 5/ 5 5/ 5 5/ 5 4/ 4 

 

 EXCRETA 

 -SOFT FECES 1/ 1 0/ 0 0/ 0 0/ 0 

 

 ORAL/DENTAL 

 -UPPER INCISOR(S) MALALIGNED 0/ 0 0/ 0 0/ 0 1/ 1 

 

 BODY/INTEG III 

 -DRIED RED MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

50 of 435
 TABLE 3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 005 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 10/ 5 10/ 5 9/ 5 9/ 5 

 

 DISPOSITION 

 -PRIMARY NECROPSY (DAY 5) 5/ 5 5/ 5 5/ 5 5/ 5 

 

 BODY/INTEGUMENT 

 -HAIR LOSS FORELIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 -HAIR LOSS HINDLIMB(S) 0/ 0 0/ 0 1/ 1 0/ 0 

 -HAIR LOSS VENTRAL NECK 0/ 0 0/ 0 0/ 0 1/ 1 

 -HAIR LOSS UROGENITAL AREA 0/ 0 0/ 0 1/ 1 0/ 0 

 

 BODY/INTEG II 

 -SCABBING FORELIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 -SCABBING VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 

 BODY/INTEG III 

 -DRIED YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PCSUv4.07 

 03/19/2008 

 R:03/19/2008 

51 of 435
 TABLE 4 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 005 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 10/ 5 

 

 DISPOSITION 

 -PRIMARY NECROPSY (DAY 5) 5/ 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 

52 of 435
 TABLE 4 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 005 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 6/ 4 

 

 DISPOSITION 

 -PRIMARY NECROPSY (DAY 5) 5/ 5 

 

 BODY/INTEGUMENT 

 -HAIR LOSS FORELIMB(S) 2/ 1 

 -HAIR LOSS VENTRAL TRUNK 2/ 2 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 PCSUv4.07 

 03/19/2008 

53

 R:03/24/2008 

 of 435
 TABLE 5 (AT TIME OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 EYES/EARS/NOSE 

 -DRIED RED MATERIAL AROUND RIGHT EYE 0/ 0 0/ 0 0/ 0 3/ 1 

 -DRIED RED MATERIAL AROUND NOSE 0/ 0 0/ 0 0/ 0 3/ 1 

 

 EXCRETA 

 -RED PENILE DISCHARGE 0/ 0 1/ 1 0/ 0 0/ 0 

 

 ORAL/DENTAL 

 -DRIED RED MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 3/ 1 

 -DRIED RED MATERIAL VENTRAL NECK 0/ 0 0/ 0 0/ 0 1/ 1 

 

 SPECIAL 

 -SWOLLEN FACIAL AREA 0/ 0 0/ 0 0/ 0 2/ 1 

 

 BODY/INTEG III 

 -WET YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -WET YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 3/ 1 

 -DRIED YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 2/ 1 

 -DRIED RED MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL FORELIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

54 of 435
 TABLE 5 (AT TIME OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 EYES/EARS/NOSE 

 -DRIED RED MATERIAL AROUND NOSE 0/ 0 0/ 0 0/ 0 7/ 3 

 

 ORAL/DENTAL 

 -DRIED RED MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 5/ 3 

 -DRIED RED MATERIAL VENTRAL NECK 0/ 0 0/ 0 0/ 0 2/ 1 

 

 BODY/INTEG III 

 -WET YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -WET YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 4/ 2 

 -DRIED YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 4/ 2 

 -DRIED RED MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 3/ 2 

 -DRIED RED MATERIAL HINDLIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL FORELIMB(S) 0/ 0 0/ 0 0/ 0 4/ 2 

 -DRIED BROWN MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PCSUv4.07 

 03/19/2008 

 R:03/19/2008 

55 of 435
 TABLE 6 (AT TIME OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 

56 of 435
 TABLE 6 (AT TIME OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 PCSUv4.07 

 03/19/2008 

 R:03/24/2008 

57 of 435
 TABLE 7 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 BEHAVIOR/CNS 

 -TREMORS, INTERMITTENT 0/ 0 0/ 0 0/ 0 2/ 2 

 -CONVULSIONS, INTERMITTENT 0/ 0 0/ 0 3/ 1 2/ 2 

 -CONVULSIONS, CONTINUOUS 0/ 0 0/ 0 0/ 0 2/ 2 

 

 ORAL/DENTAL 

 -WET CLEAR MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 3/ 2 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

58 of 435
 TABLE 7 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 BEHAVIOR/CNS 

 -TREMORS, INTERMITTENT 0/ 0 0/ 0 0/ 0 1/ 1 

 -CONVULSIONS, INTERMITTENT 0/ 0 0/ 0 2/ 1 2/ 2 

 -CONVULSIONS, CONTINUOUS 0/ 0 0/ 0 0/ 0 2/ 2 

 

 ORAL/DENTAL 

 -WET CLEAR MATERIAL AROUND MOUTH 0/ 0 0/ 0 1/ 1 0/ 0 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PCSUv4.07 

 04/16/2008 

 R:04/16/2008 

59 of 435
 TABLE 8 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ORAL/DENTAL 

 -WET CLEAR MATERIAL AROUND MOUTH 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 1800 PPM 

 

60 of 435
 TABLE 8 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 1800 PPM 

 PCSUv4.07 

 04/16/2008 

 R:04/16/2008 

61 of 435
 TABLE 9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 EYES/EARS/NOSE 

 -DRIED RED MATERIAL AROUND LEFT EYE 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL AROUND RIGHT EYE 0/ 0 0/ 0 0/ 0 3/ 1 

 -DRIED RED MATERIAL AROUND NOSE 0/ 0 0/ 0 1/ 1 2/ 1 

 

 ORAL/DENTAL 

 -WET CLEAR MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 1/ 1 

 -WET YELLOW MATERIAL VENTRAL NECK 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 4/ 2 

 -DRIED RED MATERIAL VENTRAL NECK 0/ 0 0/ 0 0/ 0 1/ 1 

 

 SPECIAL 

 -SWOLLEN FACIAL AREA 0/ 0 0/ 0 0/ 0 2/ 1 

 

 BODY/INTEG III 

 -WET YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 1/ 1 2/ 2 

 -WET YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 2/ 2 

 -WET YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 2/ 2 2/ 2 

 -WET YELLOW MATERIAL FORELIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 1/ 1 6/ 4 

 -DRIED YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 2/ 2 

 -DRIED YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 4/ 3 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

62 of 435
 TABLE 9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 BODY/INTEG III 

 -DRIED RED MATERIAL FORELIMB(S) 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED BROWN MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED BROWN MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED BROWN MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

63 of 435
 TABLE 9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 BEHAVIOR/CNS 

 -HYPOACTIVITY 0/ 0 0/ 0 0/ 0 2/ 1 

 

 EYES/EARS/NOSE 

 -DRIED RED MATERIAL AROUND NOSE 0/ 0 0/ 0 2/ 1 5/ 2 

 

 ORAL/DENTAL 

 -WET RED MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 1/ 1 

 -DRIED RED MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 6/ 3 

 -DRIED RED MATERIAL VENTRAL NECK 0/ 0 0/ 0 0/ 0 4/ 2 

 

 SPECIAL 

 -SWOLLEN FACIAL AREA 0/ 0 0/ 0 0/ 0 4/ 3 

 -SWOLLEN LEFT FORELIMB 0/ 0 0/ 0 0/ 0 1/ 1 

 -SWOLLEN RIGHT FORELIMB 0/ 0 0/ 0 0/ 0 1/ 1 

 -REDDENED LEFT FORELIMB 0/ 0 0/ 0 0/ 0 1/ 1 

 -REDDENED RIGHT FORELIMB 0/ 0 0/ 0 0/ 0 1/ 1 

 

 BODY/INTEG III 

 -WET YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 8/ 5 

 -WET YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 2/ 2 

 -WET YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 6/ 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

64 of 435
 TABLE 9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 BODY/INTEG III 

 -DRIED YELLOW MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 5/ 2 

 -DRIED YELLOW MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 2/ 2 

 -DRIED YELLOW MATERIAL ANOGENITAL AREA 0/ 0 0/ 0 0/ 0 4/ 2 

 -DRIED YELLOW MATERIAL HINDLIMB(S) 0/ 0 0/ 0 0/ 0 2/ 1 

 -DRIED RED MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 2/ 2 

 -DRIED RED MATERIAL FORELIMB(S) 0/ 0 0/ 0 0/ 0 5/ 2 

 -DRIED BROWN MATERIAL VENTRAL TRUNK 0/ 0 0/ 0 0/ 0 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PCSUv4.07 

 03/19/2008 

 R:03/19/2008 

65 of 435
 TABLE 10 (END OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 

66 of 435
 TABLE 10 (END OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: DAY 000 TO DAY 004 

 GROUP: 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ORAL/DENTAL 

 -DRIED RED MATERIAL AROUND MOUTH 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 5- 1800 PPM 

 PCSUv4.07 

 03/19/2008 

 R:03/24/2008 

67 of 435
 TABLE 11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -12 

 MEAN 211. 217. 215. 214. 

 % DIFFERENCE 2.8 1.9 1.4 

 S.D. 12.5 11.5 9.7 7.7 

 S.E. 5.6 5.2 4.3 3.4 

 N 5 5 5 5 

 

 -8 

 MEAN 252. 255. 253. 253. 

 % DIFFERENCE 1.2 0.4 0.4 

 S.D. 12.3 13.8 11.6 12.9 

 S.E. 5.5 6.2 5.2 5.8 

 N 5 5 5 5 

 

 -2 

 MEAN 309. 306. 307. 309. 

 % DIFFERENCE -1.0 -0.6 0.0 

 S.D. 18.2 16.9 15.3 20.7 

 S.E. 8.1 7.5 6.8 9.3 

 N 5 5 5 5 

 

 0 

 MEAN 330. 321. 327. 327. 

 % DIFFERENCE -2.7 -0.9 -0.9 

 S.D. 21.6 19.5 13.5 26.2 

 S.E. 9.7 8.7 6.0 11.7 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

68 of 435
 TABLE 11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 2 

 MEAN 338. 321. 320. 275.** 

 % DIFFERENCE -5.0 -5.3 -18.6 

 S.D. 23.0 22.3 16.6 20.2 

 S.E. 10.3 10.0 7.4 10.1 

 N 5 5 5 4 

 

 4 

 MEAN 344. 325. 321. 317. 

 % DIFFERENCE -5.5 -6.7 -7.8 

 S.D. 25.8 22.1 18.3 22.9 

 S.E. 11.6 9.9 8.2 11.5 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 

 

69 of 435
 TABLE 11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -12 

 MEAN 169. 172. 170. 170. 

 % DIFFERENCE 1.8 0.6 0.6 

 S.D. 7.0 6.7 11.0 5.2 

 S.E. 3.1 3.0 4.9 2.3 

 N 5 5 5 5 

 

 -8 

 MEAN 186. 188. 187. 186. 

 % DIFFERENCE 1.1 0.5 0.0 

 S.D. 8.3 6.1 13.2 6.6 

 S.E. 3.7 2.7 5.9 2.9 

 N 5 5 5 5 

 

 -2 

 MEAN 209. 208. 211. 210. 

 % DIFFERENCE -0.5 1.0 0.5 

 S.D. 9.7 6.7 14.0 11.1 

 S.E. 4.3 3.0 6.2 5.0 

 N 5 5 5 5 

 

 0 

 MEAN 219. 214. 215. 217. 

 % DIFFERENCE -2.3 -1.8 -0.9 

 S.D. 9.9 8.5 14.5 15.8 

 S.E. 4.4 3.8 6.5 7.0 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

70 of 435
 TABLE 11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 2 

 MEAN 219. 215. 215. 192.** 

 % DIFFERENCE -1.8 -1.8 -12.3 

 S.D. 11.5 8.4 16.0 10.3 

 S.E. 5.2 3.8 7.2 4.6 

 N 5 5 5 5 

 

 4 

 MEAN 224. 220. 219. 215. 

 % DIFFERENCE -1.8 -2.2 -4.0 

 S.D. 9.6 6.5 13.9 11.1 

 S.E. 4.3 2.9 6.2 5.0 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 PBFSTv5.28 

 03/19/2008 

 R:05/08/2008 

71 of 435
 TABLE 12 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 

 MEAN 346. 

 S.D. 20.6 

 S.E. 9.2 

 N 5 

 

 2 

 MEAN 341. 

 S.D. 20.5 

 S.E. 9.2 

 N 5 

 

 4 

 MEAN 346. 

 S.D. 19.3 

 S.E. 8.6 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

72 of 435
 TABLE 12 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF BODY WEIGHTS [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 

 MEAN 213. 

 S.D. 18.9 

 S.E. 8.5 

 N 5 

 

 2 

 MEAN 214. 

 S.D. 15.2 

 S.E. 6.8 

 N 5 

 

 4 

 MEAN 216. 

 S.D. 15.3 

 S.E. 6.8 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PBFSTv5.28 

 03/25/2008 

73 of 435
 TABLE 13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -12 TO -8 

 MEAN 40. 38. 38. 39. 

 S.D. 1.5 3.9 2.8 5.8 

 S.E. 0.7 1.7 1.2 2.6 

 N 5 5 5 5 

 

 -8 TO -2 

 MEAN 57. 51. 54. 56. 

 S.D. 7.9 5.1 3.9 7.9 

 S.E. 3.5 2.3 1.7 3.5 

 N 5 5 5 5 

 

 -2 TO 0 

 MEAN 22. 15. 20. 18. 

 S.D. 4.9 4.8 2.9 6.2 

 S.E. 2.2 2.2 1.3 2.8 

 N 5 5 5 5 

 

 0 TO 2 

 MEAN 8. 0. -7.** -44.** 

 S.D. 1.5 5.8 5.7 11.6 

 S.E. 0.7 2.6 2.5 5.8 

 N 5 5 5 4 

 

 2 TO 4 

 MEAN 7. 4. 1. 42.** 

 S.D. 3.4 1.6 4.5 3.6 

 S.E. 1.5 0.7 2.0 1.8 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 

 

74 of 435
 TABLE 13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -12 TO -8 

 MEAN 17. 16. 17. 16. 

 S.D. 1.6 4.1 3.1 2.6 

 S.E. 0.7 1.8 1.4 1.2 

 N 5 5 5 5 

 

 -8 TO -2 

 MEAN 22. 19. 24. 23. 

 S.D. 3.8 4.7 5.5 7.4 

 S.E. 1.7 2.1 2.5 3.3 

 N 5 5 5 5 

 

 -2 TO 0 

 MEAN 10. 6. 4. 8. 

 S.D. 6.2 3.8 5.9 6.1 

 S.E. 2.8 1.7 2.6 2.7 

 N 5 5 5 5 

 

 0 TO 2 

 MEAN 0. 1. 0. -26.** 

 S.D. 8.3 5.1 3.8 14.9 

 S.E. 3.7 2.3 1.7 6.7 

 N 5 5 5 5 

 

 2 TO 4 

 MEAN 5. 4. 4. 24.** 

 S.D. 5.0 3.4 3.7 7.4 

 S.E. 2.2 1.5 1.7 3.3 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 PBFSTv5.28 

 03/19/2008 

 R:05/08/2008 

75 of 435
 TABLE 14 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN -5. 

 S.D. 3.3 

 S.E. 1.5 

 N 5 

 

 2 TO 4 

 MEAN 6. 

 S.D. 4.2 

 S.E. 1.9 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

76 of 435
 TABLE 14 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN 1. 

 S.D. 5.5 

 S.E. 2.5 

 N 5 

 

 2 TO 4 

 MEAN 2. 

 S.D. 4.7 

 S.E. 2.1 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PBFSTv5.28 

 03/19/2008 

77 of 435
 TABLE 15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN 8. 0. -7.** -44.** 

 S.D. 1.5 5.8 5.7 11.6 

 S.E. 0.7 2.6 2.5 5.8 

 N 5 5 5 4 

 

 0 TO 4 

 MEAN 14. 4. -6.** -2.* 

 S.D. 4.8 6.2 9.9 13.1 

 S.E. 2.2 2.8 4.4 6.5 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 

 

78 of 435
 TABLE 15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM-A 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN 0. 1. 0. -26.** 

 S.D. 8.3 5.1 3.8 14.9 

 S.E. 3.7 2.3 1.7 6.7 

 N 5 5 5 5 

 

 0 TO 4 

 MEAN 5. 6. 4. -2. 

 S.D. 3.6 3.4 3.7 7.6 

 S.E. 1.6 1.5 1.7 3.4 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 A = 5000 ppm group animals were fasted from study day 1-2 for possible blood collection 

 PBFSTv5.28 

 03/19/2008 

 R:05/08/2008 

79 of 435
 TABLE 16 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN -5. 

 S.D. 3.3 

 S.E. 1.5 

 N 5 

 

 0 TO 4 

 MEAN 1. 

 S.D. 3.2 

 S.E. 1.4 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

80 of 435
 TABLE 16 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 2 

 MEAN 1. 

 S.D. 5.5 

 S.E. 2.5 

 N 5 

 

 0 TO 4 

 MEAN 3. 

 S.D. 6.0 

 S.E. 2.7 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PBFSTv5.28 

 03/19/2008 

81 of 435
 TABLE 17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -8 TO -2 

 MEAN 27. 27. 27. 27. 

 S.D. 1.6 3.0 1.1 2.4 

 S.E. 0.7 1.3 0.5 1.1 

 N 5 5 5 5 

 

 0 TO 4 

 MEAN 26. 23. 20.** NA 

 S.D. 1.6 2.2 2.6 

 S.E. 0.7 1.0 1.2 

 N 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 NA = NOT APPLICABLE 

82

 

 of 435
 TABLE 17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY -8 TO -2 

 MEAN 19. 19. 20. 19. 

 S.D. 1.0 2.7 1.2 1.9 

 S.E. 0.4 1.2 0.6 0.9 

 N 5 5 4 5 

 

 0 TO 4 

 MEAN 17. 16. 15.* NA 

 S.D. 1.1 0.8 1.9 

 S.E. 0.5 0.4 0.8 

 N 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 NA = NOT APPLICABLE 

 PBFSTv5.28 

 03/19/2008 

83 of 435
 TABLE 18 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 4 

 MEAN 23. 

 S.D. 1.5 

 S.E. 0.7 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

84 of 435
 TABLE 18 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DAY 0 TO 4 

 MEAN 16. 

 S.D. 1.2 

 S.E. 0.5 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PBFSTv5.28 

 03/19/2008 

85 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE CELLS (thous/uL) 

 DAY 5 MEAN 9.91 11.26 9.44 11.11 

 % DIFFERENCE 13.6 -4.7 12.1 

 S.D. 1.463 2.808 2.487 2.580 

 S.E. 0.654 1.256 1.112 1.290 

 N 5 5 5 4 

 

 RED CELLS (mil/uL) 

 DAY 5 MEAN 7.85 8.11 8.13 7.87 

 % DIFFERENCE 3.3 3.6 0.3 

 S.D. 0.320 0.418 0.261 0.298 

 S.E. 0.143 0.187 0.117 0.149 

 N 5 5 5 4 

 

 HEMOGLOBIN (g/dL) 

 DAY 5 MEAN 16.1 16.3 16.6 15.8 

 % DIFFERENCE 1.2 3.1 -1.9 

 S.D. 0.44 0.51 0.60 0.45 

 S.E. 0.20 0.23 0.27 0.23 

 N 5 5 5 4 

 

 HEMATOCRIT (%) 

 DAY 5 MEAN 45.7 45.8 46.8 44.5 

 % DIFFERENCE 0.2 2.4 -2.6 

 S.D. 1.77 1.30 1.83 1.37 

 S.E. 0.79 0.58 0.82 0.68 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

86 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MCV (fL) 

 DAY 5 MEAN 58.3 56.5 57.5 56.5 

 % DIFFERENCE -3.1 -1.4 -3.1 

 S.D. 1.65 1.58 1.88 0.70 

 S.E. 0.74 0.71 0.84 0.35 

 N 5 5 5 4 

 

 MCH (pg) 

 DAY 5 MEAN 20.5 20.1 20.4 20.1 

 % DIFFERENCE -2.0 -0.5 -2.0 

 S.D. 0.71 0.73 0.61 0.45 

 S.E. 0.32 0.33 0.27 0.23 

 N 5 5 5 4 

 

 MCHC (g/dL) 

 DAY 5 MEAN 35.2 35.6 35.4 35.6 

 % DIFFERENCE 1.1 0.6 1.1 

 S.D. 0.50 0.54 0.38 0.36 

 S.E. 0.22 0.24 0.17 0.18 

 N 5 5 5 4 

 

 PLATELET (thous/uL) 

 DAY 5 MEAN 1510. 1269. 1312. 1501. 

 % DIFFERENCE -16.0 -13.1 -0.6 

 S.D. 145.9 210.0 363.1 147.6 

 S.E. 65.2 93.9 162.4 73.8 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

87 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PROTIME (seconds) 

 DAY 5 MEAN 13.8 13.3 13.3 13.0 

 % DIFFERENCE -3.6 -3.6 -5.8 

 S.D. 0.88 0.41 0.89 0.67 

 S.E. 0.44 0.18 0.40 0.33 

 N 4 5 5 4 

 

 APTT (seconds) 

 DAY 5 MEAN 19.7 18.4 18.4 19.0 

 % DIFFERENCE -6.6 -6.6 -3.6 

 S.D. 0.75 1.34 0.95 0.75 

 S.E. 0.37 0.60 0.42 0.38 

 N 4 5 5 4 

 

 RETICULOCYTE (%) 

 DAY 5 MEAN 2.8 2.3 2.0** 2.8 

 % DIFFERENCE -17.9 -28.6 0.0 

 S.D. 0.38 0.33 0.47 0.16 

 S.E. 0.17 0.15 0.21 0.08 

 N 5 5 5 4 

 

 RETIC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 226.4 186.6 167.0* 223.0 

 % DIFFERENCE -17.6 -26.2 -1.5 

 S.D. 37.39 21.12 34.00 21.08 

 S.E. 16.72 9.44 15.21 10.54 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 

88 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEUTROPHIL (%) 

 DAY 5 MEAN 11.8 11.5 10.5 14.7 

 % DIFFERENCE -2.5 -11.0 24.6 

 S.D. 2.03 5.42 3.91 4.29 

 S.E. 0.91 2.42 1.75 2.14 

 N 5 5 5 4 

 

 LYMPHOCYTE (%) 

 DAY 5 MEAN 84.3 85.0 85.9 81.6 

 % DIFFERENCE 0.8 1.9 -3.2 

 S.D. 1.88 6.05 4.49 4.31 

 S.E. 0.84 2.70 2.01 2.15 

 N 5 5 5 4 

 

 MONOCYTE (%) 

 DAY 5 MEAN 1.8 1.6 2.0 2.0 

 % DIFFERENCE -11.1 11.1 11.1 

 S.D. 0.25 0.36 0.66 0.34 

 S.E. 0.11 0.16 0.30 0.17 

 N 5 5 5 4 

 

 EOSINOPHIL (%) 

 DAY 5 MEAN 1.1 0.8 0.6 0.8 

 % DIFFERENCE -27.3 -45.5 -27.3 

 S.D. 0.34 0.37 0.16 0.44 

 S.E. 0.15 0.17 0.07 0.22 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

89 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BASOPHIL (%) 

 DAY 5 MEAN 0.3 0.4** 0.3 0.3 

 % DIFFERENCE 33.3 0.0 0.0 

 S.D. 0.05 0.07 0.07 0.05 

 S.E. 0.02 0.03 0.03 0.02 

 N 5 5 5 4 

 

 LG UNSTAIN CELL (%) 

 DAY 5 MEAN 0.7 0.7 0.7 0.7 

 % DIFFERENCE 0.0 0.0 0.0 

 S.D. 0.19 0.11 0.16 0.22 

 S.E. 0.09 0.05 0.07 0.11 

 N 5 5 5 4 

 

 NEU ABSOLUTE (thous/uL) 

 DAY 5 MEAN 1.16 1.20 0.96 1.70 

 % DIFFERENCE 3.4 -17.2 46.6 

 S.D. 0.189 0.288 0.295 0.882 

 S.E. 0.084 0.129 0.132 0.441 

 N 5 5 5 4 

 

 LYMPH ABSOLUTE (thous/uL) 

 DAY 5 MEAN 8.37 9.69 8.15 9.00 

 % DIFFERENCE 15.8 -2.6 7.5 

 S.D. 1.352 2.944 2.420 1.670 

 S.E. 0.605 1.317 1.082 0.835 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 

90 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MONO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.18 0.18 0.18 0.22 

 % DIFFERENCE 0.0 0.0 22.2 

 S.D. 0.028 0.056 0.050 0.021 

 S.E. 0.012 0.025 0.022 0.010 

 N 5 5 5 4 

 

 EOS ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.11 0.08 0.05 0.09 

 % DIFFERENCE -27.3 -54.5 -18.2 

 S.D. 0.044 0.028 0.015 0.067 

 S.E. 0.020 0.013 0.007 0.033 

 N 5 5 5 4 

 

 BASO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.03 0.04 0.03 0.03 

 % DIFFERENCE 33.3 0.0 0.0 

 S.D. 0.008 0.011 0.009 0.013 

 S.E. 0.004 0.005 0.004 0.006 

 N 5 5 5 4 

 

 LUC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.07 0.07 0.06 0.08 

 % DIFFERENCE 0.0 -14.3 14.3 

 S.D. 0.018 0.013 0.015 0.024 

 S.E. 0.008 0.006 0.007 0.012 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

91 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE CELLS (thous/uL) 

 DAY 5 MEAN 7.56 7.11 7.02 6.82 

 % DIFFERENCE -6.0 -7.1 -9.8 

 S.D. 2.568 2.286 0.585 1.137 

 S.E. 1.148 1.022 0.262 0.509 

 N 5 5 5 5 

 

 RED CELLS (mil/uL) 

 DAY 5 MEAN 8.02 7.98 7.76 7.70 

 % DIFFERENCE -0.5 -3.2 -4.0 

 S.D. 0.229 0.381 0.210 0.398 

 S.E. 0.102 0.170 0.094 0.178 

 N 5 5 5 5 

 

 HEMOGLOBIN (g/dL) 

 DAY 5 MEAN 16.1 15.8 16.0 15.4 

 % DIFFERENCE -1.9 -0.6 -4.3 

 S.D. 0.56 0.36 0.45 0.61 

 S.E. 0.25 0.16 0.20 0.27 

 N 5 5 5 5 

 

 HEMATOCRIT (%) 

 DAY 5 MEAN 43.7 42.9 43.3 42.2 

 % DIFFERENCE -1.8 -0.9 -3.4 

 S.D. 1.52 1.78 0.92 1.99 

 S.E. 0.68 0.80 0.41 0.89 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

92 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MCV (fL) 

 DAY 5 MEAN 54.5 53.8 55.8 54.9 

 % DIFFERENCE -1.3 2.4 0.7 

 S.D. 1.33 1.29 1.26 0.43 

 S.E. 0.59 0.58 0.56 0.19 

 N 5 5 5 5 

 

 MCH (pg) 

 DAY 5 MEAN 20.1 19.8 20.6 20.0 

 % DIFFERENCE -1.5 2.5 -0.5 

 S.D. 0.35 0.72 0.71 0.44 

 S.E. 0.16 0.32 0.32 0.20 

 N 5 5 5 5 

 

 MCHC (g/dL) 

 DAY 5 MEAN 36.9 36.8 36.8 36.5 

 % DIFFERENCE -0.3 -0.3 -1.1 

 S.D. 0.41 0.74 0.78 0.60 

 S.E. 0.18 0.33 0.35 0.27 

 N 5 5 5 5 

 

 PLATELET (thous/uL) 

 DAY 5 MEAN 1391. 1363. 1496. 1423. 

 % DIFFERENCE -2.0 7.5 2.3 

 S.D. 116.8 148.5 189.5 250.3 

 S.E. 52.2 66.4 84.7 111.9 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

93 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PROTIME (seconds) 

 DAY 5 MEAN 11.8 12.2 12.5 12.1 

 % DIFFERENCE 3.4 5.9 2.5 

 S.D. 0.79 0.43 0.71 0.71 

 S.E. 0.35 0.19 0.32 0.32 

 N 5 5 5 5 

 

 APTT (seconds) 

 DAY 5 MEAN 15.2 17.4 17.1 16.2 

 % DIFFERENCE 14.5 12.5 6.6 

 S.D. 3.47 0.82 1.47 0.80 

 S.E. 1.55 0.37 0.66 0.36 

 N 5 5 5 5 

 

 RETICULOCYTE (%) 

 DAY 5 MEAN 2.3 1.9 2.1 2.7 

 % DIFFERENCE -17.4 -8.7 17.4 

 S.D. 0.25 0.35 0.19 0.24 

 S.E. 0.11 0.16 0.08 0.11 

 N 5 5 5 5 

 

 RETIC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 185.7 150.5* 162.9 202.7 

 % DIFFERENCE -19.0 -12.3 9.2 

 S.D. 18.14 23.45 10.56 18.84 

 S.E. 8.11 10.49 4.72 8.43 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 

94 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEUTROPHIL (%) 

 DAY 5 MEAN 15.4 10.4 10.9 15.8 

 % DIFFERENCE -32.5 -29.2 2.6 

 S.D. 9.06 2.13 2.61 1.82 

 S.E. 4.05 0.95 1.17 0.81 

 N 5 5 5 5 

 

 LYMPHOCYTE (%) 

 DAY 5 MEAN 79.1 86.6 85.8 80.9 

 % DIFFERENCE 9.5 8.5 2.3 

 S.D. 12.54 2.47 2.72 1.87 

 S.E. 5.61 1.10 1.22 0.84 

 N 5 5 5 5 

 

 MONOCYTE (%) 

 DAY 5 MEAN 3.7 1.2 1.4 1.8 

 % DIFFERENCE -67.6 -62.2 -51.4 

 S.D. 4.36 0.46 0.26 0.24 

 S.E. 1.95 0.21 0.12 0.11 

 N 5 5 5 5 

 

 EOSINOPHIL (%) 

 DAY 5 MEAN 0.8 0.9 1.2 0.9 

 % DIFFERENCE 12.5 50.0 12.5 

 S.D. 0.31 0.19 0.48 0.27 

 S.E. 0.14 0.08 0.22 0.12 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

95 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 11 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BASOPHIL (%) 

 DAY 5 MEAN 0.3 0.3 0.2 0.2 

 % DIFFERENCE 0.0 -33.3 -33.3 

 S.D. 0.08 0.09 0.08 0.08 

 S.E. 0.04 0.04 0.04 0.04 

 N 5 5 5 5 

 

 LG UNSTAIN CELL (%) 

 DAY 5 MEAN 0.7 0.6 0.5 0.5 

 % DIFFERENCE -14.3 -28.6 -28.6 

 S.D. 0.12 0.18 0.24 0.07 

 S.E. 0.05 0.08 0.11 0.03 

 N 5 5 5 5 

 

 NEU ABSOLUTE (thous/uL) 

 DAY 5 MEAN 1.01 0.75 0.75 1.07 

 % DIFFERENCE -25.7 -25.7 5.9 

 S.D. 0.364 0.330 0.150 0.208 

 S.E. 0.163 0.148 0.067 0.093 

 N 5 5 5 5 

 

 LYMPH ABSOLUTE (thous/uL) 

 DAY 5 MEAN 6.21 6.14 6.03 5.52 

 % DIFFERENCE -1.1 -2.9 -11.1 

 S.D. 2.671 1.890 0.651 0.942 

 S.E. 1.195 0.845 0.291 0.421 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

96 of 435
 TABLE 19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 12 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MONO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.20 0.09 0.10 0.12 

 % DIFFERENCE -55.0 -50.0 -40.0 

 S.D. 0.134 0.064 0.023 0.029 

 S.E. 0.060 0.029 0.010 0.013 

 N 5 5 5 5 

 

 EOS ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.06 0.06 0.08 0.06 

 % DIFFERENCE 0.0 33.3 0.0 

 S.D. 0.031 0.021 0.031 0.021 

 S.E. 0.014 0.009 0.014 0.009 

 N 5 5 5 5 

 

 BASO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.03 0.02 0.01 0.01 

 % DIFFERENCE -33.3 -66.7 -66.7 

 S.D. 0.011 0.008 0.005 0.011 

 S.E. 0.005 0.004 0.002 0.005 

 N 5 5 5 5 

 

 LUC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.05 0.04 0.04 0.03 

 % DIFFERENCE -20.0 -20.0 -40.0 

 S.D. 0.024 0.029 0.019 0.005 

 S.E. 0.011 0.013 0.008 0.002 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 PCPSv5.24 

 03/24/2008 

97 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE CELLS (thous/uL) 

 DAY 5 MEAN 9.67 

 S.D. 1.649 

 S.E. 0.825 

 N 4 

 

 RED CELLS (mil/uL) 

 DAY 5 MEAN 8.12 

 S.D. 0.192 

 S.E. 0.096 

 N 4 

 

 HEMOGLOBIN (g/dL) 

 DAY 5 MEAN 16.9 

 S.D. 0.32 

 S.E. 0.16 

 N 4 

 

 HEMATOCRIT (%) 

 DAY 5 MEAN 47.4 

 S.D. 0.94 

 S.E. 0.47 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

98 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MCV (fL) 

 DAY 5 MEAN 58.4 

 S.D. 0.61 

 S.E. 0.31 

 N 4 

 

 MCH (pg) 

 DAY 5 MEAN 20.8 

 S.D. 0.43 

 S.E. 0.22 

 N 4 

 

 MCHC (g/dL) 

 DAY 5 MEAN 35.7 

 S.D. 0.50 

 S.E. 0.25 

 N 4 

 

 PLATELET (thous/uL) 

 DAY 5 MEAN 1235. 

 S.D. 257.4 

 S.E. 128.7 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

99 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PROTIME (seconds) 

 DAY 5 MEAN 13.3 

 S.D. 1.06 

 S.E. 0.48 

 N 5 

 

 APTT (seconds) 

 DAY 5 MEAN 18.1 

 S.D. 1.78 

 S.E. 0.80 

 N 5 

 

 RETICULOCYTE (%) 

 DAY 5 MEAN 1.9 

 S.D. 0.50 

 S.E. 0.25 

 N 4 

 

 RETIC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 156.9 

 S.D. 38.72 

 S.E. 19.36 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

100 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEUTROPHIL (%) 

 DAY 5 MEAN 10.0 

 S.D. 1.90 

 S.E. 0.95 

 N 4 

 

 LYMPHOCYTE (%) 

 DAY 5 MEAN 85.6 

 S.D. 1.68 

 S.E. 0.84 

 N 4 

 

 MONOCYTE (%) 

 DAY 5 MEAN 2.3 

 S.D. 0.42 

 S.E. 0.21 

 N 4 

 

 EOSINOPHIL (%) 

 DAY 5 MEAN 1.2 

 S.D. 0.58 

 S.E. 0.29 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

101 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BASOPHIL (%) 

 DAY 5 MEAN 0.4 

 S.D. 0.13 

 S.E. 0.06 

 N 4 

 

 LG UNSTAIN CELL (%) 

 DAY 5 MEAN 0.8 

 S.D. 0.24 

 S.E. 0.12 

 N 4 

 

 NEU ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.94 

 S.D. 0.068 

 S.E. 0.034 

 N 4 

 

 LYMPH ABSOLUTE (thous/uL) 

 DAY 5 MEAN 8.29 

 S.D. 1.534 

 S.E. 0.767 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

102 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MONO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.22 

 S.D. 0.075 

 S.E. 0.038 

 N 4 

 

 EOS ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.11 

 S.D. 0.055 

 S.E. 0.027 

 N 4 

 

 BASO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.04 

 S.D. 0.017 

 S.E. 0.009 

 N 4 

 

 LUC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.07 

 S.D. 0.032 

 S.E. 0.016 

 N 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

103 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE CELLS (thous/uL) 

 DAY 5 MEAN 8.45 

 S.D. 0.335 

 S.E. 0.150 

 N 5 

 

 RED CELLS (mil/uL) 

 DAY 5 MEAN 8.12 

 S.D. 0.251 

 S.E. 0.112 

 N 5 

 

 HEMOGLOBIN (g/dL) 

 DAY 5 MEAN 16.3 

 S.D. 0.59 

 S.E. 0.27 

 N 5 

 

 HEMATOCRIT (%) 

 DAY 5 MEAN 44.7 

 S.D. 2.23 

 S.E. 1.00 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

104 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MCV (fL) 

 DAY 5 MEAN 55.0 

 S.D. 1.88 

 S.E. 0.84 

 N 5 

 

 MCH (pg) 

 DAY 5 MEAN 20.1 

 S.D. 0.57 

 S.E. 0.26 

 N 5 

 

 MCHC (g/dL) 

 DAY 5 MEAN 36.6 

 S.D. 0.63 

 S.E. 0.28 

 N 5 

 

 PLATELET (thous/uL) 

 DAY 5 MEAN 1413. 

 S.D. 187.1 

 S.E. 83.7 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

105 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PROTIME (seconds) 

 DAY 5 MEAN 12.3 

 S.D. 0.44 

 S.E. 0.22 

 N 4 

 

 APTT (seconds) 

 DAY 5 MEAN 17.2 

 S.D. 0.46 

 S.E. 0.23 

 N 4 

 

 RETICULOCYTE (%) 

 DAY 5 MEAN 1.9 

 S.D. 0.40 

 S.E. 0.18 

 N 5 

 

 RETIC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 151.9 

 S.D. 35.13 

 S.E. 15.71 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

106 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEUTROPHIL (%) 

 DAY 5 MEAN 9.8 

 S.D. 4.10 

 S.E. 1.83 

 N 5 

 

 LYMPHOCYTE (%) 

 DAY 5 MEAN 86.3 

 S.D. 4.88 

 S.E. 2.18 

 N 5 

 

 MONOCYTE (%) 

 DAY 5 MEAN 2.1 

 S.D. 0.53 

 S.E. 0.24 

 N 5 

 

 EOSINOPHIL (%) 

 DAY 5 MEAN 1.0 

 S.D. 0.42 

 S.E. 0.19 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

107 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 11 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BASOPHIL (%) 

 DAY 5 MEAN 0.2 

 S.D. 0.08 

 S.E. 0.04 

 N 5 

 

 LG UNSTAIN CELL (%) 

 DAY 5 MEAN 0.5 

 S.D. 0.11 

 S.E. 0.05 

 N 5 

 

 NEU ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.84 

 S.D. 0.386 

 S.E. 0.173 

 N 5 

 

 LYMPH ABSOLUTE (thous/uL) 

 DAY 5 MEAN 7.28 

 S.D. 0.235 

 S.E. 0.105 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

108 of 435
 TABLE 20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 12 

 SUMMARY OF HEMATOLOGY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MONO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.18 

 S.D. 0.054 

 S.E. 0.024 

 N 5 

 

 EOS ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.09 

 S.D. 0.035 

 S.E. 0.016 

 N 5 

 

 BASO ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.02 

 S.D. 0.008 

 S.E. 0.004 

 N 5 

 

 LUC ABSOLUTE (thous/uL) 

 DAY 5 MEAN 0.05 

 S.D. 0.009 

 S.E. 0.004 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PCPSv5.24 

 03/25/2008 

109 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALBUMIN (g/dL) 

 DAY 5 MEAN 4.3 4.3 4.4 4.3 

 % DIFFERENCE 0.0 2.3 0.0 

 S.D. 0.05 0.10 0.19 0.37 

 S.E. 0.02 0.04 0.09 0.18 

 N 5 5 5 4 

 

 TOTAL PROTEIN (g/dL) 

 DAY 5 MEAN 6.3 6.3 6.5 6.3 

 % DIFFERENCE 0.0 3.2 0.0 

 S.D. 0.22 0.17 0.25 0.30 

 S.E. 0.10 0.07 0.11 0.15 

 N 5 5 5 4 

 

 GLOBULIN (g/dL) 

 DAY 5 MEAN 2.0 2.0 2.0 2.1 

 % DIFFERENCE 0.0 0.0 5.0 

 S.D. 0.29 0.15 0.18 0.17 

 S.E. 0.13 0.07 0.08 0.09 

 N 5 5 5 4 

 

 A/G RATIO 

 DAY 5 MEAN 2.22 2.18 2.23 2.08 

 % DIFFERENCE -1.8 0.5 -6.3 

 S.D. 0.388 0.186 0.209 0.261 

 S.E. 0.173 0.083 0.093 0.130 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

110 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL BILI (mg/dL) 

 DAY 5 MEAN 0.09 0.09 0.09 0.11 

 % DIFFERENCE 0.0 0.0 22.2 

 S.D. 0.019 0.021 0.013 0.036 

 S.E. 0.009 0.009 0.006 0.018 

 N 5 5 5 4 

 

 UREA NITROGEN (mg/dL) 

 DAY 5 MEAN 11.2 11.8 11.2 10.0 

 % DIFFERENCE 5.4 0.0 -10.7 

 S.D. 1.80 1.10 1.06 1.17 

 S.E. 0.81 0.49 0.47 0.58 

 N 5 5 5 4 

 

 CREATININE (mg/dL) 

 DAY 5 MEAN 0.2 0.2 0.2 0.2 

 % DIFFERENCE 0.0 0.0 0.0 

 S.D. 0.05 0.05 0.04 0.05 

 S.E. 0.02 0.02 0.02 0.03 

 N 5 5 5 4 

 

 ALKALINEPHOS’TSE (U/L) 

 DAY 5 MEAN 260. 222. 219. 231. 

 % DIFFERENCE -14.6 -15.8 -11.2 

 S.D. 61.8 82.5 38.0 45.4 

 S.E. 27.6 36.9 17.0 22.7 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

111 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALANINE TRANSFER (U/L) 

 DAY 5 MEAN 34. 35. 50. 38. 

 % DIFFERENCE 2.9 47.1 11.8 

 S.D. 5.9 4.8 20.3 5.9 

 S.E. 2.6 2.1 9.1 2.9 

 N 5 5 5 4 

 

 ASPARTATTRANSFER (U/L) 

 DAY 5 MEAN 87. 94. 100. 88. 

 % DIFFERENCE 8.0 14.9 1.1 

 S.D. 9.9 6.0 45.4 21.0 

 S.E. 4.4 2.7 20.3 10.5 

 N 5 5 5 4 

 

 GLUCOSE (mg/dL) 

 DAY 5 MEAN 123. 105.* 118. 108. 

 % DIFFERENCE -14.6 -4.1 -12.2 

 S.D. 8.9 9.9 12.5 5.0 

 S.E. 4.0 4.4 5.6 2.5 

 N 5 5 5 4 

 

 CHOLESTEROL (mg/dL) 

 DAY 5 MEAN 54. 63. 68. 62. 

 % DIFFERENCE 16.7 25.9 14.8 

 S.D. 7.0 13.1 15.8 9.4 

 S.E. 3.2 5.9 7.1 4.7 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 

112 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CALCIUM (mg/dL) 

 DAY 5 MEAN 10.8 11.0 11.0 10.8 

 % DIFFERENCE 1.9 1.9 0.0 

 S.D. 0.12 0.18 0.23 0.24 

 S.E. 0.05 0.08 0.10 0.12 

 N 5 5 5 4 

 

 CHLORIDE (mEq/L) 

 DAY 5 MEAN 103. 103. 104. 103. 

 % DIFFERENCE 0.0 1.0 0.0 

 S.D. 1.1 0.8 1.1 0.8 

 S.E. 0.5 0.4 0.5 0.4 

 N 5 5 5 4 

 

 PHOSPHORUS (mg/dL) 

 DAY 5 MEAN 9.4 9.1 9.0 9.0 

 % DIFFERENCE -3.2 -4.3 -4.3 

 S.D. 0.46 0.47 0.18 0.38 

 S.E. 0.20 0.21 0.08 0.19 

 N 5 5 5 4 

 

 POTASSIUM (mEq/L) 

 DAY 5 MEAN 4.71 4.77 4.91 4.69 

 % DIFFERENCE 1.3 4.2 -0.4 

 S.D. 0.325 0.269 0.320 0.110 

 S.E. 0.145 0.120 0.143 0.055 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

113 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 SODIUM (mEq/L) 

 DAY 5 MEAN 146. 146. 146. 146. 

 % DIFFERENCE 0.0 0.0 0.0 

 S.D. 0.4 0.8 1.3 0.6 

 S.E. 0.2 0.4 0.6 0.3 

 N 5 5 5 4 

 

 TRIGLYCERIDE (mg/dL) 

 DAY 5 MEAN 60. 47. 54. 42. 

 % DIFFERENCE -21.7 -10.0 -30.0 

 S.D. 26.6 5.5 17.9 5.9 

 S.E. 11.9 2.5 8.0 3.0 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

114 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALBUMIN (g/dL) 

 DAY 5 MEAN 4.6 4.6 4.6 4.3 

 % DIFFERENCE 0.0 0.0 -6.5 

 S.D. 0.16 0.28 0.15 0.21 

 S.E. 0.07 0.12 0.07 0.09 

 N 5 5 5 5 

 

 TOTAL PROTEIN (g/dL) 

 DAY 5 MEAN 6.9 6.8 6.7 6.4** 

 % DIFFERENCE -1.4 -2.9 -7.2 

 S.D. 0.28 0.18 0.10 0.38 

 S.E. 0.12 0.08 0.04 0.17 

 N 5 5 5 5 

 

 GLOBULIN (g/dL) 

 DAY 5 MEAN 2.3 2.3 2.1 2.1 

 % DIFFERENCE 0.0 -8.7 -8.7 

 S.D. 0.25 0.17 0.08 0.22 

 S.E. 0.11 0.07 0.04 0.10 

 N 5 5 5 5 

 

 A/G RATIO 

 DAY 5 MEAN 2.01 2.03 2.16 2.04 

 % DIFFERENCE 1.0 7.5 1.5 

 S.D. 0.228 0.293 0.162 0.147 

 S.E. 0.102 0.131 0.073 0.066 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ** = Significantly different from the control group at 0.01 using Dunnett’s test 

 

115 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL BILI (mg/dL) 

 DAY 5 MEAN 0.09 0.08 0.10 0.09 

 % DIFFERENCE -11.1 11.1 0.0 

 S.D. 0.030 0.019 0.023 0.030 

 S.E. 0.013 0.009 0.010 0.014 

 N 5 5 5 5 

 

 UREA NITROGEN (mg/dL) 

 DAY 5 MEAN 13.6 13.9 10.8* 13.8 

 % DIFFERENCE 2.2 -20.6 1.5 

 S.D. 0.75 0.84 2.12 1.70 

 S.E. 0.33 0.37 0.95 0.76 

 N 5 5 5 5 

 

 CREATININE (mg/dL) 

 DAY 5 MEAN 0.3 0.3 0.2 0.2 

 % DIFFERENCE 0.0 -33.3 -33.3 

 S.D. 0.04 0.05 0.05 0.04 

 S.E. 0.02 0.02 0.02 0.02 

 N 5 5 5 5 

 

 ALKALINEPHOS’TSE (U/L) 

 DAY 5 MEAN 117. 119. 143. 107. 

 % DIFFERENCE 1.7 22.2 -8.5 

 S.D. 28.9 9.7 17.5 16.2 

 S.E. 12.9 4.3 7.8 7.2 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 * = Significantly different from the control group at 0.05 using Dunnett’s test 

 

116 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALANINE TRANSFER (U/L) 

 DAY 5 MEAN 32. 30. 41. 33. 

 % DIFFERENCE -6.3 28.1 3.1 

 S.D. 6.5 3.6 15.3 8.1 

 S.E. 2.9 1.6 6.8 3.6 

 N 5 5 5 5 

 

 ASPARTATTRANSFER (U/L) 

 DAY 5 MEAN 84. 81. 84. 92. 

 % DIFFERENCE -3.6 0.0 9.5 

 S.D. 11.8 10.2 12.5 18.8 

 S.E. 5.3 4.5 5.6 8.4 

 N 5 5 5 5 

 

 GLUCOSE (mg/dL) 

 DAY 5 MEAN 112. 113. 121. 110. 

 % DIFFERENCE 0.9 8.0 -1.8 

 S.D. 6.5 8.9 12.7 3.7 

 S.E. 2.9 4.0 5.7 1.7 

 N 5 5 5 5 

 

 CHOLESTEROL (mg/dL) 

 DAY 5 MEAN 78. 88. 78. 70. 

 % DIFFERENCE 12.8 0.0 -10.3 

 S.D. 17.1 26.1 10.8 10.8 

 S.E. 7.7 11.7 4.8 4.8 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

117 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CALCIUM (mg/dL) 

 DAY 5 MEAN 11.0 11.0 11.0 10.6 

 % DIFFERENCE 0.0 0.0 -3.6 

 S.D. 0.44 0.13 0.40 0.29 

 S.E. 0.20 0.06 0.18 0.13 

 N 5 5 5 5 

 

 CHLORIDE (mEq/L) 

 DAY 5 MEAN 102. 104. 103. 103. 

 % DIFFERENCE 2.0 1.0 1.0 

 S.D. 1.9 1.1 1.8 1.1 

 S.E. 0.9 0.5 0.8 0.5 

 N 5 5 5 5 

 

 PHOSPHORUS (mg/dL) 

 DAY 5 MEAN 8.0 7.9 8.2 8.5 

 % DIFFERENCE -1.3 2.5 6.3 

 S.D. 1.03 0.30 0.65 0.39 

 S.E. 0.46 0.14 0.29 0.17 

 N 5 5 5 5 

 

 POTASSIUM (mEq/L) 

 DAY 5 MEAN 4.76 4.69 5.00 4.88 

 % DIFFERENCE -1.5 5.0 2.5 

 S.D. 0.419 0.264 0.137 0.346 

 S.E. 0.187 0.118 0.061 0.155 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

118 of 435
 TABLE 21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 SODIUM (mEq/L) 

 DAY 5 MEAN 146. 145. 145. 145. 

 % DIFFERENCE -0.7 -0.7 -0.7 

 S.D. 1.1 1.1 2.3 1.5 

 S.E. 0.5 0.5 1.0 0.7 

 N 5 5 5 5 

 

 TRIGLYCERIDE (mg/dL) 

 DAY 5 MEAN 43. 43. 37. 43. 

 % DIFFERENCE 0.0 -14.0 0.0 

 S.D. 11.2 15.8 4.3 6.7 

 S.E. 5.0 7.1 1.9 3.0 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 PCPSv5.24 

 03/24/2008 

119 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALBUMIN (g/dL) 

 DAY 5 MEAN 4.4 

 S.D. 0.11 

 S.E. 0.05 

 N 5 

 

 TOTAL PROTEIN (g/dL) 

 DAY 5 MEAN 6.6 

 S.D. 0.22 

 S.E. 0.10 

 N 5 

 

 GLOBULIN (g/dL) 

 DAY 5 MEAN 2.2 

 S.D. 0.10 

 S.E. 0.04 

 N 5 

 

 A/G RATIO 

 DAY 5 MEAN 2.02 

 S.D. 0.068 

 S.E. 0.031 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

120 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL BILI (mg/dL) 

 DAY 5 MEAN 0.10 

 S.D. 0.022 

 S.E. 0.010 

 N 5 

 

 UREA NITROGEN (mg/dL) 

 DAY 5 MEAN 11.7 

 S.D. 1.70 

 S.E. 0.76 

 N 5 

 

 CREATININE (mg/dL) 

 DAY 5 MEAN 0.2 

 S.D. 0.08 

 S.E. 0.04 

 N 5 

 

 ALKALINEPHOS’TSE (U/L) 

 DAY 5 MEAN 184. 

 S.D. 26.7 

 S.E. 11.9 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

121 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALANINE TRANSFER (U/L) 

 DAY 5 MEAN 40. 

 S.D. 11.6 

 S.E. 5.2 

 N 5 

 

 ASPARTATTRANSFER (U/L) 

 DAY 5 MEAN 92. 

 S.D. 17.1 

 S.E. 7.6 

 N 5 

 

 GLUCOSE (mg/dL) 

 DAY 5 MEAN 132. 

 S.D. 16.8 

 S.E. 7.5 

 N 5 

 

 CHOLESTEROL (mg/dL) 

 DAY 5 MEAN 72. 

 S.D. 7.6 

 S.E. 3.4 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

122 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CALCIUM (mg/dL) 

 DAY 5 MEAN 11.2 

 S.D. 0.44 

 S.E. 0.20 

 N 5 

 

 CHLORIDE (mEq/L) 

 DAY 5 MEAN 100. 

 S.D. 1.6 

 S.E. 0.7 

 N 5 

 

 PHOSPHORUS (mg/dL) 

 DAY 5 MEAN 9.9 

 S.D. 0.79 

 S.E. 0.35 

 N 5 

 

 POTASSIUM (mEq/L) 

 DAY 5 MEAN 5.40 

 S.D. 0.728 

 S.E. 0.326 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

123 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 SODIUM (mEq/L) 

 DAY 5 MEAN 145. 

 S.D. 2.3 

 S.E. 1.0 

 N 5 

 

 TRIGLYCERIDE (mg/dL) 

 DAY 5 MEAN 52. 

 S.D. 13.4 

 S.E. 6.0 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

124

 

 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALBUMIN (g/dL) 

 DAY 5 MEAN 4.5 

 S.D. 0.13 

 S.E. 0.06 

 N 5 

 

 TOTAL PROTEIN (g/dL) 

 DAY 5 MEAN 6.4 

 S.D. 0.22 

 S.E. 0.10 

 N 5 

 

 GLOBULIN (g/dL) 

 DAY 5 MEAN 1.9 

 S.D. 0.09 

 S.E. 0.04 

 N 5 

 

 A/G RATIO 

 DAY 5 MEAN 2.37 

 S.D. 0.065 

 S.E. 0.029 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

125 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL BILI (mg/dL) 

 DAY 5 MEAN 0.12 

 S.D. 0.029 

 S.E. 0.013 

 N 5 

 

 UREA NITROGEN (mg/dL) 

 DAY 5 MEAN 12.9 

 S.D. 1.50 

 S.E. 0.67 

 N 5 

 

 CREATININE (mg/dL) 

 DAY 5 MEAN 0.2 

 S.D. 0.04 

 S.E. 0.02 

 N 5 

 

 ALKALINEPHOS’TSE (U/L) 

 DAY 5 MEAN 115. 

 S.D. 35.9 

 S.E. 16.0 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

126 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ALANINE TRANSFER (U/L) 

 DAY 5 MEAN 38. 

 S.D. 10.6 

 S.E. 4.7 

 N 5 

 

 ASPARTATTRANSFER (U/L) 

 DAY 5 MEAN 89. 

 S.D. 13.3 

 S.E. 5.9 

 N 5 

 

 GLUCOSE (mg/dL) 

 DAY 5 MEAN 117. 

 S.D. 16.0 

 S.E. 7.2 

 N 5 

 

 CHOLESTEROL (mg/dL) 

 DAY 5 MEAN 72. 

 S.D. 20.0 

 S.E. 9.0 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

127 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CALCIUM (mg/dL) 

 DAY 5 MEAN 10.7 

 S.D. 0.27 

 S.E. 0.12 

 N 5 

 

 CHLORIDE (mEq/L) 

 DAY 5 MEAN 100. 

 S.D. 1.7 

 S.E. 0.8 

 N 5 

 

 PHOSPHORUS (mg/dL) 

 DAY 5 MEAN 8.6 

 S.D. 0.59 

 S.E. 0.26 

 N 5 

 

 POTASSIUM (mEq/L) 

 DAY 5 MEAN 4.80 

 S.D. 0.191 

 S.E. 0.085 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

128 of 435
 TABLE 22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 SUMMARY OF SERUM CHEMISTRY VALUES 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 ANALYSIS GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 SODIUM (mEq/L) 

 DAY 5 MEAN 143. 

 S.D. 0.8 

 S.E. 0.4 

 N 5 

 

 TRIGLYCERIDE (mg/dL) 

 DAY 5 MEAN 36. 

 S.D. 12.0 

 S.E. 5.4 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 PCPSv5.24 

 03/25/2008 

129 of 435
 TABLE 23 (UNSCHEDULED DEATH) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF MACROSCOPIC FINDINGS 

 

 FOUND DEAD OR EUTHANIZED MORIBUND OR IN EXTREMIS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ----- M A L E ----- 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NUMBER OF ANIMALS IN DOSE GROUP 5 5 5 5 

 NUMBER OF ANIMALS EXAMINED 0 0 0 1 

 

 

 LUNGS 

 -NOT FULLY COLLAPSED 0 0 0 1 

 

 SKIN 

 -MATTING, RED 0 0 0 1 

 

 SPLEEN 

 -AREA(S), WHITE 0 0 0 1 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 0 0 0 0 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PGRSI2v4.07 

 03/19/2008 

 R:04/04/2008 

130 of 435
 TABLE 24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF MACROSCOPIC FINDINGS 

 

 SCHEDULED NECROPSY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ----- M A L E ----- 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NUMBER OF ANIMALS IN DOSE GROUP 5 5 5 5 

 NUMBER OF ANIMALS EXAMINED 5 5 5 4 

 

 

 KIDNEYS 

 -AREA(S), DEPRESSED 1 1 0 0 

 

 LUNGS 

 -AREA(S), DARK RED 1 0 0 0 

 

 STOMACH 

 -CYST(S) 0 0 1 0 

 

 TEETH 

 -MALALIGNED 0 0 0 1 

 

 THYMUS 

 -AREA(S), DARK RED 0 1 0 0 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 4 3 4 3 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 

131 of 435
 TABLE 24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF MACROSCOPIC FINDINGS 

 

 SCHEDULED NECROPSY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ----- F E M A L E ----- 

 GROUP: 1 2 3 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NUMBER OF ANIMALS IN DOSE GROUP 5 5 5 5 

 NUMBER OF ANIMALS EXAMINED 5 5 5 5 

 

 

 SKIN 

 -SCABBING 0 0 0 1 

 

 STOMACH 

 -CONTENTS, YELLOW 0 0 0 1 

 

 UTERUS 

 -CONTENTS, CLEAR FLUID 3 1 0 0 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 2 4 5 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 0 PPM 2- 1250 PPM 3- 2500 PPM 4- 5000 PPM 

 PGRSI2v4.07 

 03/19/2008 

 

132 of 435
 TABLE 25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF MACROSCOPIC FINDINGS 

 

 SCHEDULED NECROPSY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ----- M A L E ----- 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NUMBER OF ANIMALS IN DOSE GROUP 5 

 NUMBER OF ANIMALS EXAMINED 5 

 

 

 DUODENUM 

 -CONTENTS, DARK RED 1 

 

 ILEUM 

 -CONTENTS, DARK RED 1 

 

 PANCREAS 

 -PALE 1 

 

 STOMACH 

 -CONTENTS, DARK RED 1 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 1800 PPM 

 

133 of 435
 TABLE 25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF MACROSCOPIC FINDINGS 

 

 SCHEDULED NECROPSY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ----- F E M A L E ----- 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NUMBER OF ANIMALS IN DOSE GROUP 5 

 NUMBER OF ANIMALS EXAMINED 5 

 

 

 UTERUS 

 -CONTENTS, CLEAR FLUID 1 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- 1800 PPM 

 PGRSI2v4.07 

 03/19/2008 

 

134 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FINAL BODY WT (G) 

 MEAN 309. 294. 289. 286. 

 % DIFFERENCE -4.9 -6.5 -7.4 

 S.D. 21.9 18.6 16.3 20.8 

 S.E. 9.8 8.3 7.3 10.4 

 N 5 5 5 4 

 

 BRAIN (G) 

 MEAN 2.00 1.96 1.93 1.97 

 % DIFFERENCE -2.0 -3.5 -1.5 

 S.D. 0.089 0.026 0.093 0.039 

 S.E. 0.040 0.012 0.041 0.020 

 N 5 5 5 4 

 

 BRAIN (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.648 0.668 0.670 0.693 

 % DIFFERENCE 3.1 3.4 6.9 

 S.D. 0.0250 0.0367 0.0359 0.0567 

 S.E. 0.0112 0.0164 0.0161 0.0284 

 N 5 5 5 4 

 

 KIDNEYS (G) 

 MEAN 2.40 2.30 2.23 2.27 

 % DIFFERENCE -4.2 -7.1 -5.4 

 S.D. 0.248 0.211 0.050 0.182 

 S.E. 0.111 0.094 0.022 0.091 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

135 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 KIDNEYS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.775 0.782 0.775 0.793 

 % DIFFERENCE 0.9 0.0 2.3 

 S.D. 0.0382 0.0373 0.0471 0.0266 

 S.E. 0.0171 0.0167 0.0211 0.0133 

 N 5 5 5 4 

 

 KIDNEYS (G/100 G BRAIN) 

 MEAN 119.783 117.460 115.848 115.090 

 % DIFFERENCE -1.9 -3.3 -3.9 

 S.D. 7.3943 9.3517 6.1710 10.8478 

 S.E. 3.3069 4.1822 2.7598 5.4239 

 N 5 5 5 4 

 

 LIVER (G) 

 MEAN 9.60 8.69 8.40 8.32 

 % DIFFERENCE -9.5 -12.5 -13.3 

 S.D. 1.074 1.107 0.691 0.866 

 S.E. 0.480 0.495 0.309 0.433 

 N 5 5 5 4 

 

 LIVER (G/100 G FINAL BODY WEIGHT) 

 MEAN 3.100 2.943 2.907 2.908 

 % DIFFERENCE -5.1 -6.2 -6.2 

 S.D. 0.1655 0.2150 0.1662 0.0954 

 S.E. 0.0740 0.0961 0.0743 0.0477 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

136 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 LIVER (G/100 G BRAIN) 

 MEAN 479.883 443.089 435.640 423.003 

 % DIFFERENCE -7.7 -9.2 -11.9 

 S.D. 42.5966 51.9746 41.7697 50.5074 

 S.E. 19.0498 23.2437 18.6800 25.2537 

 N 5 5 5 4 

 

 LUNGS (G) 

 MEAN 1.27 1.21 1.16 1.25 

 % DIFFERENCE -4.7 -8.7 -1.6 

 S.D. 0.084 0.104 0.073 0.172 

 S.E. 0.038 0.046 0.033 0.086 

 N 5 5 5 4 

 

 LUNGS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.411 0.412 0.402 0.436 

 % DIFFERENCE 0.2 -2.2 6.1 

 S.D. 0.0237 0.0249 0.0167 0.0417 

 S.E. 0.0106 0.0111 0.0075 0.0208 

 N 5 5 5 4 

 

 LUNGS (G/100 G BRAIN) 

 MEAN 63.500 61.916 60.059 63.375 

 % DIFFERENCE -2.5 -5.4 -0.2 

 S.D. 3.8135 4.8528 2.9720 9.1579 

 S.E. 1.7054 2.1702 1.3291 4.5789 

 N 5 5 5 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

137 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FINAL BODY WT (G) 

 MEAN 198. 195. 196. 193. 

 % DIFFERENCE -1.5 -1.0 -2.5 

 S.D. 10.7 6.6 13.9 9.9 

 S.E. 4.8 3.0 6.2 4.4 

 N 5 5 5 5 

 

 BRAIN (G) 

 MEAN 1.86 1.82 1.82 1.85 

 % DIFFERENCE -2.2 -2.2 -0.5 

 S.D. 0.108 0.083 0.103 0.081 

 S.E. 0.048 0.037 0.046 0.036 

 N 5 5 5 5 

 

 BRAIN (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.942 0.935 0.932 0.957 

 % DIFFERENCE -0.7 -1.1 1.6 

 S.D. 0.0868 0.0371 0.0629 0.0329 

 S.E. 0.0388 0.0166 0.0281 0.0147 

 N 5 5 5 5 

 

 KIDNEYS (G) 

 MEAN 1.43 1.46 1.43 1.39 

 % DIFFERENCE 2.1 0.0 -2.8 

 S.D. 0.103 0.075 0.149 0.074 

 S.E. 0.046 0.034 0.067 0.033 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

138 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 KIDNEYS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.722 0.747 0.732 0.718 

 % DIFFERENCE 3.5 1.4 -0.6 

 S.D. 0.0411 0.0277 0.0535 0.0406 

 S.E. 0.0184 0.0124 0.0239 0.0181 

 N 5 5 5 5 

 

 KIDNEYS (G/100 G BRAIN) 

 MEAN 76.887 80.030 78.756 75.141 

 % DIFFERENCE 4.1 2.4 -2.3 

 S.D. 5.2959 5.2666 6.3120 5.6593 

 S.E. 2.3684 2.3553 2.8228 2.5309 

 N 5 5 5 5 

 

 LIVER (G) 

 MEAN 6.08 6.08 5.94 5.71 

 % DIFFERENCE 0.0 -2.3 -6.1 

 S.D. 0.522 0.292 0.554 0.461 

 S.E. 0.234 0.130 0.248 0.206 

 N 5 5 5 5 

 

 LIVER (G/100 G FINAL BODY WEIGHT) 

 MEAN 3.063 3.117 3.033 2.953 

 % DIFFERENCE 1.8 -1.0 -3.6 

 S.D. 0.1296 0.1030 0.1815 0.1091 

 S.E. 0.0580 0.0461 0.0812 0.0488 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 

139 of 435
 TABLE 26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 LIVER (G/100 G BRAIN) 

 MEAN 327.709 334.124 326.021 309.014 

 % DIFFERENCE 2.0 -0.5 -5.7 

 S.D. 37.5578 21.5431 19.7120 19.9120 

 S.E. 16.7964 9.6344 8.8155 8.9049 

 N 5 5 5 5 

 

 LUNGS (G) 

 MEAN 1.04 1.05 0.93 1.01 

 % DIFFERENCE 1.0 -10.6 -2.9 

 S.D. 0.064 0.109 0.114 0.060 

 S.E. 0.029 0.049 0.051 0.027 

 N 5 5 5 5 

 

 LUNGS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.527 0.535 0.476 0.526 

 % DIFFERENCE 1.5 -9.7 -0.2 

 S.D. 0.0296 0.0417 0.0505 0.0416 

 S.E. 0.0132 0.0186 0.0226 0.0186 

 N 5 5 5 5 

 

 LUNGS (G/100 G BRAIN) 

 MEAN 56.203 57.405 50.956 55.018 

 % DIFFERENCE 2.1 -9.3 -2.1 

 S.D. 4.4167 5.4744 3.2086 4.9709 

 S.E. 1.9752 2.4482 1.4349 2.2231 

 N 5 5 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 None significantly different from control group 

 POFBSTv5.11 

 03/19/2008 

 

140 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FINAL BODY WT (G) 

 MEAN 319. 

 S.D. 16.2 

 S.E. 7.2 

 N 5 

 

 BRAIN (G) 

 MEAN 2.07 

 S.D. 0.075 

 S.E. 0.034 

 N 5 

 

 BRAIN (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.649 

 S.D. 0.0304 

 S.E. 0.0136 

 N 5 

 

 KIDNEYS (G) 

 MEAN 2.59 

 S.D. 0.114 

 S.E. 0.051 

 N 5 

 

 KIDNEYS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.814 

 S.D. 0.0535 

 S.E. 0.0239 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

141 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 KIDNEYS (G/100 G BRAIN) 

 MEAN 125.427 

 S.D. 7.8017 

 S.E. 3.4890 

 N 5 

 

 LIVER (G) 

 MEAN 9.83 

 S.D. 0.585 

 S.E. 0.262 

 N 5 

 

 LIVER (G/100 G FINAL BODY WEIGHT) 

 MEAN 3.087 

 S.D. 0.1226 

 S.E. 0.0548 

 N 5 

 

 LIVER (G/100 G BRAIN) 

 MEAN 475.824 

 S.D. 21.3577 

 S.E. 9.5514 

 N 5 

 

 LUNGS (G) 

 MEAN 1.34 

 S.D. 0.058 

 S.E. 0.026 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

142 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 MALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 LUNGS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.421 

 S.D. 0.0327 

 S.E. 0.0146 

 N 5 

 

 LUNGS (G/100 G BRAIN) 

 MEAN 64.809 

 S.D. 3.1640 

 S.E. 1.4150 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

143 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FINAL BODY WT (G) 

 MEAN 194. 

 S.D. 16.3 

 S.E. 7.3 

 N 5 

 

 BRAIN (G) 

 MEAN 1.83 

 S.D. 0.045 

 S.E. 0.020 

 N 5 

 

 BRAIN (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.945 

 S.D. 0.0716 

 S.E. 0.0320 

 N 5 

 

 KIDNEYS (G) 

 MEAN 1.58 

 S.D. 0.131 

 S.E. 0.059 

 N 5 

 

 KIDNEYS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.816 

 S.D. 0.0455 

 S.E. 0.0203 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

144 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 KIDNEYS (G/100 G BRAIN) 

 MEAN 86.642 

 S.D. 6.8673 

 S.E. 3.0711 

 N 5 

 

 LIVER (G) 

 MEAN 6.03 

 S.D. 0.547 

 S.E. 0.245 

 N 5 

 

 LIVER (G/100 G FINAL BODY WEIGHT) 

 MEAN 3.106 

 S.D. 0.0610 

 S.E. 0.0273 

 N 5 

 

 LIVER (G/100 G BRAIN) 

 MEAN 330.258 

 S.D. 25.8708 

 S.E. 11.5698 

 N 5 

 

 LUNGS (G) 

 MEAN 1.04 

 S.D. 0.068 

 S.E. 0.031 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

145 of 435
 TABLE 27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 SUMMARY OF ORGAN WEIGHTS AND RELATIVE ORGAN WEIGHTS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 FEMALES 

 GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 LUNGS (G/100 G FINAL BODY WEIGHT) 

 MEAN 0.537 

 S.D. 0.0460 

 S.E. 0.0206 

 N 5 

 

 LUNGS (G/100 G BRAIN) 

 MEAN 56.855 

 S.D. 3.6102 

 S.E. 1.6145 

 N 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 POFBSTv5.11 

 03/25/2008 

146

 

 of 435
APPENDIX A

Individual Animal Data

147 of 435
 TABLE A1 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL SURVIVAL AND DISPOSITION 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TYPE OF AGE IN DATE OF DAYS ON 

 ANIMAL SEX GROUP DEATH WEEKS A DEATH STUDY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95555 M 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95556 M 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95558 M 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95574 M 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95577 M 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95559 M 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95561 M 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95566 M 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95573 M 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95576 M 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95560 M 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95564 M 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95565 M 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95569 M 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95578 M 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95554 M 5000 PPM FOUND DEAD 9 07-FEB-08 1 

 95563 M 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95568 M 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95570 M 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95572 M 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 A = CALCULATED TO THE NEAREST WHOLE WEEK USING THE MEAN AGE IN WEEKS AT INITIATION OF DOSING (9) 

 

148 of 435
 TABLE A1 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL SURVIVAL AND DISPOSITION 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TYPE OF AGE IN DATE OF DAYS ON 

 ANIMAL SEX GROUP DEATH WEEKS A DEATH STUDY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95587 F 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95591 F 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95594 F 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95599 F 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95600 F 0 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95579 F 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95586 F 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95588 F 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95595 F 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95603 F 1250 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95580 F 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95589 F 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95593 F 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95597 F 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95598 F 2500 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 

 95581 F 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95583 F 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95590 F 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95592 F 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 95601 F 5000 PPM SCHEDULED EUTHANASIA 9 11-FEB-08 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 A = CALCULATED TO THE NEAREST WHOLE WEEK USING THE MEAN AGE IN WEEKS AT INITIATION OF DOSING (9) 

 PDEADv4.05 

 03/20/2008 

149 of 435
 TABLE A2 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL SURVIVAL AND DISPOSITION 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TYPE OF AGE IN DATE OF DAYS ON 

 ANIMAL SEX GROUP DEATH WEEKS A DEATH STUDY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 M 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 95562 M 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 95567 M 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 95571 M 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 95575 M 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 A = CALCULATED TO THE NEAREST WHOLE WEEK USING THE MEAN AGE IN WEEKS AT INITIATION OF DOSING (9) 

 

150 of 435
 TABLE A2 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL SURVIVAL AND DISPOSITION 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TYPE OF AGE IN DATE OF DAYS ON 

 ANIMAL SEX GROUP DEATH WEEKS A DEATH STUDY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6664 F 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 6674 F 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 6686 F 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 6712 F 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 6717 F 1800 PPM SCHEDULED EUTHANASIA 9 14-FEB-08 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 A = CALCULATED TO THE NEAREST WHOLE WEEK USING THE MEAN AGE IN WEEKS AT INITIATION OF DOSING (9) 

 PDEADv4.05 

 03/20/2008 

151 of 435
 TABLE A3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95555 M 0 PPM NORMAL 0 6:21 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:38 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95555 M 0 PPM DISPOSITION 5 9:06 P PRIMARY NECROPSY (DAY 5) 

 95556 M 0 PPM NORMAL 0 6:22 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:38 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95556 M 0 PPM DISPOSITION 5 9:06 P PRIMARY NECROPSY (DAY 5) 

 95558 M 0 PPM NORMAL 0 6:22 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95558 M 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95558 M 0 PPM EXCRETA 5 7:39 P SOFT FECES 

 95574 M 0 PPM NORMAL 0 6:22 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95574 M 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95577 M 0 PPM NORMAL 0 6:23 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95577 M 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95559 M 1250 PPM NORMAL 0 6:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95559 M 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95561 M 1250 PPM NORMAL 0 6:26 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95561 M 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95566 M 1250 PPM NORMAL 0 6:26 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95566 M 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95573 M 1250 PPM NORMAL 0 6:26 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95573 M 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95576 M 1250 PPM NORMAL 0 6:27 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

152 of 435
 TABLE A3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95576 M 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95560 M 2500 PPM NORMAL 0 6:29 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95560 M 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95564 M 2500 PPM NORMAL 0 6:29 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95564 M 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95565 M 2500 PPM NORMAL 0 6:30 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95565 M 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95569 M 2500 PPM NORMAL 0 6:30 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95569 M 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95578 M 2500 PPM NORMAL 0 6:31 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95578 M 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95554 M 5000 PPM NORMAL 0 6:33 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95554 M 5000 PPM DISPOSITION 1 8:37 P FOUND DEAD 

 95563 M 5000 PPM NORMAL 0 6:33 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:43 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95563 M 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95568 M 5000 PPM NORMAL 0 6:33 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:43 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95568 M 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95570 M 5000 PPM NORMAL 0 6:34 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95570 M 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95570 M 5000 PPM ORAL/DENTAL 5 7:43 P UPPER INCISOR(S) MALALIGNED 

 95570 M 5000 PPM BODY/INTEG III 5 7:43 P DRIED RED MATERIAL UROGENITAL AREA 

 95572 M 5000 PPM NORMAL 0 6:34 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

153 of 435
 TABLE A3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95572 M 5000 PPM NORMAL 5 7:43 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95572 M 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95587 F 0 PPM NORMAL 0 6:23 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95587 F 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95591 F 0 PPM NORMAL 0 6:24 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95591 F 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95594 F 0 PPM NORMAL 0 6:24 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95594 F 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95599 F 0 PPM NORMAL 0 6:24 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95599 F 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95600 F 0 PPM NORMAL 0 6:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:39 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95600 F 0 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95579 F 1250 PPM NORMAL 0 6:27 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95579 F 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95586 F 1250 PPM NORMAL 0 6:27 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95586 F 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95588 F 1250 PPM NORMAL 0 6:28 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:40 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95588 F 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95595 F 1250 PPM NORMAL 0 6:28 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95595 F 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

154 of 435
 TABLE A3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95603 F 1250 PPM NORMAL 0 6:29 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:41 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95603 F 1250 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95580 F 2500 PPM NORMAL 0 6:31 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:42 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95580 F 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95589 F 2500 PPM NORMAL 0 6:31 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95589 F 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95589 F 2500 PPM BODY/INTEGUMENT 5 7:42 P HAIR LOSS UROGENITAL AREA 

 5 7:42 P HAIR LOSS HINDLIMB(S) 

 95593 F 2500 PPM NORMAL 0 6:32 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:42 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95593 F 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95597 F 2500 PPM NORMAL 0 6:32 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:42 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95597 F 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95598 F 2500 PPM NORMAL 0 6:32 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:42 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95598 F 2500 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95581 F 5000 PPM NORMAL 0 6:35 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:43 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95581 F 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95583 F 5000 PPM NORMAL 0 6:35 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:44 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95583 F 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95590 F 5000 PPM NORMAL 0 6:35 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:44 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95590 F 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95592 F 5000 PPM NORMAL 0 6:36 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

155 of 435
 TABLE A3 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95592 F 5000 PPM NORMAL 5 7:44 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95592 F 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95601 F 5000 PPM NORMAL 0 6:36 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95601 F 5000 PPM DISPOSITION 5 9:07 P PRIMARY NECROPSY (DAY 5) 

 95601 F 5000 PPM BODY/INTEGUMENT 5 7:44 P HAIR LOSS FORELIMB(S) 

 5 7:44 P HAIR LOSS VENTRAL NECK 

 95601 F 5000 PPM BODY/INTEG II 5 7:44 P SCABBING FORELIMB(S) 

 5 7:45 P SCABBING VENTRAL TRUNK 

 95601 F 5000 PPM BODY/INTEG III 5 7:44 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

 R:03/24/2008 

156 of 435
 TABLE A4 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 M 1800 PPM NORMAL 0 6:17 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:24 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95557 M 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 95562 M 1800 PPM NORMAL 0 6:17 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95562 M 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 95567 M 1800 PPM NORMAL 0 6:18 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95567 M 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 95571 M 1800 PPM NORMAL 0 6:19 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95571 M 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 95575 M 1800 PPM NORMAL 0 6:19 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:25 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 95575 M 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 6664 F 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 6664 F 1800 PPM BODY/INTEGUMENT 0 6:20 P HAIR LOSS FORELIMB(S) 

 5 7:26 P HAIR LOSS FORELIMB(S) 

 6674 F 1800 PPM NORMAL 0 6:21 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:26 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 6674 F 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 6686 F 1800 PPM NORMAL 0 6:21 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 6686 F 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 6686 F 1800 PPM BODY/INTEGUMENT 5 7:26 P HAIR LOSS VENTRAL TRUNK 

 6712 F 1800 PPM NORMAL 0 6:22 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 5 7:27 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 6712 F 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 6717 F 1800 PPM NORMAL 0 6:23 P NO SIGNIFICANT CLINICAL OBSERVATIONS 

 6717 F 1800 PPM DISPOSITION 5 7:53 P PRIMARY NECROPSY (DAY 5) 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

157 of 435
 TABLE A4 (DETAILED PHYSICAL EXAMINATIONS/DISPOSITIONS - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6717 F 1800 PPM BODY/INTEGUMENT 5 7:27 P HAIR LOSS VENTRAL TRUNK 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

158 of 435
 TABLE A5 (AT TIME OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95561 M 1250 PPM EXCRETA 1 7:30 P RED PENILE DISCHARGE 

 95570 M 5000 PPM EYES/EARS/NOSE 1 7:45 P DRIED RED MATERIAL AROUND NOSE 

 2 7:34 P DRIED RED MATERIAL AROUND NOSE 

 2 7:35 P DRIED RED MATERIAL AROUND RIGHT EYE 

 3 6:35 P DRIED RED MATERIAL AROUND RIGHT EYE 

 4 6:21 P DRIED RED MATERIAL AROUND RIGHT EYE 

 4 6:21 P DRIED RED MATERIAL AROUND NOSE 

 95570 M 5000 PPM ORAL/DENTAL 1 7:45 P DRIED RED MATERIAL AROUND MOUTH 

 1 7:45 P DRIED RED MATERIAL VENTRAL NECK 

 2 7:35 P DRIED RED MATERIAL AROUND MOUTH 

 3 6:35 P DRIED RED MATERIAL AROUND MOUTH 

 95570 M 5000 PPM SPECIAL 1 7:45 P SWOLLEN FACIAL AREA 

 2 7:34 P SWOLLEN FACIAL AREA 

 95570 M 5000 PPM BODY/INTEG III 1 7:45 P DRIED RED MATERIAL FORELIMB(S) 

 1 7:45 P DRIED RED MATERIAL VENTRAL TRUNK 

 1 7:45 P WET YELLOW MATERIAL UROGENITAL AREA 

 1 7:45 P WET YELLOW MATERIAL ANOGENITAL AREA 

 2 7:35 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 7:35 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 2 7:35 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 3 6:36 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 4 6:22 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 4 6:22 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 95590 F 5000 PPM EYES/EARS/NOSE 1 7:47 P DRIED RED MATERIAL AROUND NOSE 

 2 7:36 P DRIED RED MATERIAL AROUND NOSE 

 95590 F 5000 PPM ORAL/DENTAL 1 7:47 P DRIED RED MATERIAL AROUND MOUTH 

 95590 F 5000 PPM BODY/INTEG III 1 7:47 P DRIED RED MATERIAL FORELIMB(S) 

 1 7:47 P DRIED RED MATERIAL VENTRAL TRUNK 

 1 7:47 P DRIED RED MATERIAL UROGENITAL AREA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

159 of 435
 TABLE A5 (AT TIME OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95590 F 5000 PPM BODY/INTEG III 2 7:35 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 7:36 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 2 7:36 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 3 6:38 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 4 6:24 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 95592 F 5000 PPM EYES/EARS/NOSE 2 7:36 P DRIED RED MATERIAL AROUND NOSE 

 95592 F 5000 PPM ORAL/DENTAL 1 7:48 P DRIED RED MATERIAL AROUND MOUTH 

 95601 F 5000 PPM EYES/EARS/NOSE 1 7:48 P DRIED RED MATERIAL AROUND NOSE 

 2 7:37 P DRIED RED MATERIAL AROUND NOSE 

 3 6:39 P DRIED RED MATERIAL AROUND NOSE 

 4 6:26 P DRIED RED MATERIAL AROUND NOSE 

 95601 F 5000 PPM ORAL/DENTAL 1 7:48 P DRIED RED MATERIAL AROUND MOUTH 

 1 7:48 P DRIED RED MATERIAL VENTRAL NECK 

 2 7:37 P DRIED RED MATERIAL VENTRAL NECK 

 2 7:38 P DRIED RED MATERIAL AROUND MOUTH 

 3 6:40 P DRIED RED MATERIAL AROUND MOUTH 

 95601 F 5000 PPM BODY/INTEG III 1 7:48 P DRIED RED MATERIAL FORELIMB(S) 

 1 7:48 P DRIED RED MATERIAL VENTRAL TRUNK 

 1 7:48 P WET YELLOW MATERIAL UROGENITAL AREA 

 1 7:48 P WET YELLOW MATERIAL ANOGENITAL AREA 

 2 7:37 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 7:37 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 2 7:37 P DRIED RED MATERIAL VENTRAL TRUNK 

 2 7:37 P DRIED RED MATERIAL FORELIMB(S) 

 3 6:40 P DRIED RED MATERIAL HINDLIMB(S) 

 3 6:40 P DRIED RED MATERIAL FORELIMB(S) 

 3 6:44 P DRIED BROWN MATERIAL ANOGENITAL AREA 

 4 6:27 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 4 6:28 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

 R:03/24/2008 

160 of 435
 TABLE A6 (AT TIME OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

 R:03/24/2008 

161 of 435
 TABLE A7 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95564 M 2500 PPM BEHAVIOR/CNS 2 8:13 P CONVULSIONS, INTERMITTENT 

 3 7:35 P CONVULSIONS, INTERMITTENT 

 4 7:22 P CONVULSIONS, INTERMITTENT 

 95554 M 5000 PPM BEHAVIOR/CNS 0 8:16 P TREMORS, INTERMITTENT 

 1 8:09 P CONVULSIONS, INTERMITTENT 

 1 8:13 P CONVULSIONS, CONTINUOUS 

 95554 M 5000 PPM ORAL/DENTAL 1 8:11 P WET CLEAR MATERIAL AROUND MOUTH 

 95563 M 5000 PPM BEHAVIOR/CNS 1 8:12 P CONVULSIONS, INTERMITTENT 

 95563 M 5000 PPM ORAL/DENTAL 0 8:17 P WET CLEAR MATERIAL AROUND MOUTH 

 1 8:12 P WET CLEAR MATERIAL AROUND MOUTH 

 95572 M 5000 PPM BEHAVIOR/CNS 0 8:18 P TREMORS, INTERMITTENT 

 1 8:16 P CONVULSIONS, CONTINUOUS 

 95597 F 2500 PPM BEHAVIOR/CNS 2 8:18 P CONVULSIONS, INTERMITTENT 

 4 7:29 P CONVULSIONS, INTERMITTENT 

 95597 F 2500 PPM ORAL/DENTAL 4 7:23 P WET CLEAR MATERIAL AROUND MOUTH 

 95581 F 5000 PPM BEHAVIOR/CNS 1 8:17 P CONVULSIONS, CONTINUOUS 

 95583 F 5000 PPM BEHAVIOR/CNS 1 8:24 P CONVULSIONS, CONTINUOUS 

 95590 F 5000 PPM BEHAVIOR/CNS 0 8:17 P TREMORS, INTERMITTENT 

 1 8:18 P CONVULSIONS, INTERMITTENT 

 95592 F 5000 PPM BEHAVIOR/CNS 1 8:10 P CONVULSIONS, INTERMITTENT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 04/16/2008 

 R:04/16/2008 

162 of 435
 TABLE A8 (APPROXIMATELY 15-30 MINUTES INTO EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 M 1800 PPM ORAL/DENTAL 4 8:02 P WET CLEAR MATERIAL AROUND MOUTH 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 04/16/2008 

163 of 435
 TABLE A9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95560 M 2500 PPM EYES/EARS/NOSE 1 14:38 P DRIED RED MATERIAL AROUND NOSE 

 95565 M 2500 PPM BODY/INTEG III 0 14:25 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:25 P WET YELLOW MATERIAL ANOGENITAL AREA 

 2 14:28 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 95578 M 2500 PPM BODY/INTEG III 0 14:26 P WET YELLOW MATERIAL ANOGENITAL AREA 

 95554 M 5000 PPM ORAL/DENTAL 0 14:41 P DRIED RED MATERIAL AROUND MOUTH 

 95554 M 5000 PPM BODY/INTEG III 0 14:41 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:41 P WET YELLOW MATERIAL VENTRAL TRUNK 

 0 14:41 P WET YELLOW MATERIAL ANOGENITAL AREA 

 95563 M 5000 PPM BODY/INTEG III 0 14:41 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 0 14:41 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 0 14:41 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 95568 M 5000 PPM BODY/INTEG III 0 14:42 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 0 14:42 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 95570 M 5000 PPM EYES/EARS/NOSE 1 14:51 P DRIED RED MATERIAL AROUND LEFT EYE 

 1 14:51 P DRIED RED MATERIAL AROUND RIGHT EYE 

 1 14:51 P DRIED RED MATERIAL AROUND NOSE 

 3 13:51 P DRIED RED MATERIAL AROUND RIGHT EYE 

 3 13:52 P DRIED RED MATERIAL AROUND NOSE 

 4 13:17 P DRIED RED MATERIAL AROUND RIGHT EYE 

 95570 M 5000 PPM ORAL/DENTAL 0 14:43 P WET CLEAR MATERIAL AROUND MOUTH 

 0 14:43 P WET YELLOW MATERIAL VENTRAL NECK 

 1 14:52 P DRIED RED MATERIAL AROUND MOUTH 

 1 14:52 P DRIED RED MATERIAL VENTRAL NECK 

 2 14:31 P DRIED RED MATERIAL AROUND MOUTH 

 3 13:52 P DRIED RED MATERIAL AROUND MOUTH 

 95570 M 5000 PPM SPECIAL 0 14:43 P SWOLLEN FACIAL AREA 

 1 14:50 P SWOLLEN FACIAL AREA 

 95570 M 5000 PPM BODY/INTEG III 0 14:44 P WET YELLOW MATERIAL FORELIMB(S) 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

164 of 435
 TABLE A9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95570 M 5000 PPM BODY/INTEG III 0 14:44 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:44 P WET YELLOW MATERIAL VENTRAL TRUNK 

 0 14:44 P WET YELLOW MATERIAL ANOGENITAL AREA 

 1 14:51 P DRIED BROWN MATERIAL UROGENITAL AREA 

 1 14:51 P DRIED BROWN MATERIAL VENTRAL TRUNK 

 1 14:51 P DRIED BROWN MATERIAL ANOGENITAL AREA 

 1 14:51 P DRIED RED MATERIAL FORELIMB(S) 

 2 14:30 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 14:30 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 2 14:30 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 3 13:50 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 3 13:51 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 4 13:17 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 95572 M 5000 PPM BODY/INTEG III 0 14:45 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 95597 F 2500 PPM EYES/EARS/NOSE 3 13:44 P DRIED RED MATERIAL AROUND NOSE 

 4 13:37 P DRIED RED MATERIAL AROUND NOSE 

 95581 F 5000 PPM BODY/INTEG III 0 14:37 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:37 P WET YELLOW MATERIAL VENTRAL TRUNK 

 0 14:37 P WET YELLOW MATERIAL ANOGENITAL AREA 

 95583 F 5000 PPM BODY/INTEG III 0 14:38 P WET YELLOW MATERIAL UROGENITAL AREA 

 95590 F 5000 PPM EYES/EARS/NOSE 0 14:38 P DRIED RED MATERIAL AROUND NOSE 

 95590 F 5000 PPM ORAL/DENTAL 0 14:39 P DRIED RED MATERIAL AROUND MOUTH 

 1 14:58 P DRIED RED MATERIAL AROUND MOUTH 

 1 14:58 P DRIED RED MATERIAL VENTRAL NECK 

 95590 F 5000 PPM SPECIAL 1 14:58 P SWOLLEN FACIAL AREA 

 95590 F 5000 PPM BODY/INTEG III 0 14:39 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:39 P WET YELLOW MATERIAL VENTRAL TRUNK 

 0 14:39 P DRIED RED MATERIAL FORELIMB(S) 

 1 14:57 P WET YELLOW MATERIAL UROGENITAL AREA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

165 of 435
 TABLE A9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95590 F 5000 PPM BODY/INTEG III 1 14:57 P WET YELLOW MATERIAL ANOGENITAL AREA 

 1 14:57 P DRIED RED MATERIAL FORELIMB(S) 

 1 14:57 P DRIED RED MATERIAL VENTRAL TRUNK 

 2 14:32 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 14:32 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 2 14:32 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 3 13:57 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 95592 F 5000 PPM ORAL/DENTAL 0 14:40 P WET RED MATERIAL AROUND MOUTH 

 1 14:59 P DRIED RED MATERIAL AROUND MOUTH 

 95592 F 5000 PPM SPECIAL 0 14:40 P SWOLLEN FACIAL AREA 

 1 14:59 P SWOLLEN FACIAL AREA 

 95592 F 5000 PPM BODY/INTEG III 0 14:39 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:39 P WET YELLOW MATERIAL ANOGENITAL AREA 

 1 14:59 P WET YELLOW MATERIAL UROGENITAL AREA 

 1 14:59 P WET YELLOW MATERIAL ANOGENITAL AREA 

 95601 F 5000 PPM BEHAVIOR/CNS 0 14:45 P HYPOACTIVITY 

 1 15:00 P HYPOACTIVITY 

 95601 F 5000 PPM EYES/EARS/NOSE 0 14:35 P DRIED RED MATERIAL AROUND NOSE 

 1 15:02 P DRIED RED MATERIAL AROUND NOSE 

 3 13:58 P DRIED RED MATERIAL AROUND NOSE 

 4 13:20 P DRIED RED MATERIAL AROUND NOSE 

 95601 F 5000 PPM ORAL/DENTAL 0 14:36 P DRIED RED MATERIAL AROUND MOUTH 

 0 14:36 P DRIED RED MATERIAL VENTRAL NECK 

 1 15:01 P DRIED RED MATERIAL AROUND MOUTH 

 1 15:01 P DRIED RED MATERIAL VENTRAL NECK 

 2 14:33 P DRIED RED MATERIAL AROUND MOUTH 

 2 14:33 P DRIED RED MATERIAL VENTRAL NECK 

 95601 F 5000 PPM SPECIAL 0 14:34 P SWOLLEN LEFT FORELIMB 

 0 14:34 P SWOLLEN RIGHT FORELIMB 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

166 of 435
 TABLE A9 (END OF EXPOSURE - GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95601 F 5000 PPM SPECIAL 0 14:35 P REDDENED LEFT FORELIMB 

 0 14:35 P REDDENED RIGHT FORELIMB 

 1 15:02 P SWOLLEN FACIAL AREA 

 95601 F 5000 PPM BODY/INTEG III 0 14:35 P DRIED RED MATERIAL VENTRAL TRUNK 

 0 14:35 P DRIED RED MATERIAL FORELIMB(S) 

 0 14:36 P WET YELLOW MATERIAL UROGENITAL AREA 

 0 14:36 P WET YELLOW MATERIAL ANOGENITAL AREA 

 1 15:00 P WET YELLOW MATERIAL UROGENITAL AREA 

 1 15:01 P WET YELLOW MATERIAL ANOGENITAL AREA 

 1 15:01 P DRIED BROWN MATERIAL VENTRAL TRUNK 

 1 15:01 P DRIED RED MATERIAL FORELIMB(S) 

 2 14:33 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 2 14:33 P DRIED YELLOW MATERIAL VENTRAL TRUNK 

 2 14:33 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 2 14:33 P DRIED YELLOW MATERIAL HINDLIMB(S) 

 2 14:33 P DRIED RED MATERIAL FORELIMB(S) 

 3 13:58 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 3 13:58 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 3 13:58 P DRIED YELLOW MATERIAL HINDLIMB(S) 

 4 13:20 P DRIED YELLOW MATERIAL UROGENITAL AREA 

 4 13:21 P DRIED YELLOW MATERIAL ANOGENITAL AREA 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

167 of 435
 TABLE A10 (END OF EXPOSURE - GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6712 F 1800 PPM ORAL/DENTAL 2 14:21 P DRIED RED MATERIAL AROUND MOUTH 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 03/24/2008 

168 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 MALE GROUP: 0 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95555 205. 248. 313. 338. 347. 358. 

 95556 210. 250. 307. 331. 339. 345. 

 95558 205. 245. 291. 304. 310. 313. 

 95574 203. 242. 295. 317. 323. 327. 

 95577 233. 273. 337. 361. 370. 379. 

 

 

 MEAN 211. 252. 309. 330. 338. 344. 

 S.D. 12.5 12.3 18.2 21.6 23.0 25.8 

 S.E. 5.6 5.5 8.1 9.7 10.3 11.6 

 N 5 5 5 5 5 5 

 

169 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 MALE GROUP: 1250 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95559 216. 256. 308. 327. 324. 329. 

 95561 220. 260. 305. 325. 332. 338. 

 95566 202. 233. 280. 288. 286. 290. 

 95573 214. 254. 310. 325. 319. 322. 

 95576 234. 271. 327. 340. 346. 348. 

 

 

 MEAN 217. 255. 306. 321. 321. 325. 

 S.D. 11.5 13.8 16.9 19.5 22.3 22.1 

 S.E. 5.2 6.2 7.5 8.7 10.0 9.9 

 N 5 5 5 5 5 5 

 

170 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 MALE GROUP: 2500 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95560 205. 241. 293. 316. 302. 298. 

 95564 215. 254. 310. 332. 333. 340. 

 95565 230. 272. 332. 348. 341. 339. 

 95569 217. 252. 305. 323. 312. 312. 

 95578 208. 247. 297. 316. 310. 314. 

 

 

 MEAN 215. 253. 307. 327. 320. 321. 

 S.D. 9.7 11.6 15.3 13.5 16.6 18.3 

 S.E. 4.3 5.2 6.8 6.0 7.4 8.2 

 N 5 5 5 5 5 5 

 

171 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 MALE GROUP: 5000 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95554 226. 272. 338. 360. 

 95563 215. 259. 320. 343. 303. 350. 

 95568 211. 247. 298. 314. 276. 315. 

 95570 215. 250. 306. 327. 266. 306. 

 95572 205. 238. 284. 292. 256. 298. 

 

 

 MEAN 214. 253. 309. 327. 275. 317. 

 S.D. 7.7 12.9 20.7 26.2 20.2 22.9 

 S.E. 3.4 5.8 9.3 11.7 10.1 11.5 

 N 5 5 5 5 4 4 

 

172 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 FEMALE GROUP: 0 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95587 158. 173. 196. 207. 206. 213. 

 95591 175. 193. 221. 227. 237. 236. 

 95594 174. 191. 214. 230. 220. 232. 

 95599 167. 183. 203. 219. 213. 220. 

 95600 172. 191. 209. 211. 217. 219. 

 

 

 MEAN 169. 186. 209. 219. 219. 224. 

 S.D. 7.0 8.3 9.7 9.9 11.5 9.6 

 S.E. 3.1 3.7 4.3 4.4 5.2 4.3 

 N 5 5 5 5 5 5 

 

173 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 FEMALE GROUP: 1250 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95579 169. 184. 200. 207. 207. 213. 

 95586 180. 192. 216. 220. 228. 227. 

 95588 179. 194. 207. 215. 214. 222. 

 95595 169. 192. 213. 224. 219. 224. 

 95603 165. 180. 203. 204. 209. 213. 

 

 

 MEAN 172. 188. 208. 214. 215. 220. 

 S.D. 6.7 6.1 6.7 8.5 8.4 6.5 

 S.E. 3.0 2.7 3.0 3.8 3.8 2.9 

 N 5 5 5 5 5 5 

 

174 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 FEMALE GROUP: 2500 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95580 170. 190. 210. 213. 217. 222. 

 95589 166. 181. 209. 210. 209. 217. 

 95593 174. 188. 204. 218. 213. 218. 

 95597 186. 206. 234. 236. 240. 238. 

 95598 156. 170. 197. 196. 196. 199. 

 

 

 MEAN 170. 187. 211. 215. 215. 219. 

 S.D. 11.0 13.2 14.0 14.5 16.0 13.9 

 S.E. 4.9 5.9 6.2 6.5 7.2 6.2 

 N 5 5 5 5 5 5 

 

175 of 435
 TABLE A11 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 FEMALE GROUP: 5000 PPM 

 DAY -12 -8 -2 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95581 163. 176. 195. 196. 178. 198. 

 95583 171. 191. 208. 213. 198. 215. 

 95590 168. 184. 206. 219. 187. 214. 

 95592 177. 192. 215. 219. 205. 224. 

 95601 172. 189. 225. 240. 191. 226. 

 

 

 MEAN 170. 186. 210. 217. 192. 215. 

 S.D. 5.2 6.6 11.1 15.8 10.3 11.1 

 S.E. 2.3 2.9 5.0 7.0 4.6 5.0 

 N 5 5 5 5 5 5 

 PBFTSv4.44 

 03/24/2008 

176 of 435
 TABLE A12 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 MALE GROUP: 1800 PPM 

 DAY 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95557 324. 321. 329. 

 95562 367. 360. 364. 

 95567 325. 317. 325. 

 95571 348. 348. 347. 

 95575 364. 358. 367. 

 

 

 MEAN 346. 341. 346. 

 S.D. 20.6 20.5 19.3 

 S.E. 9.2 9.2 8.6 

 N 5 5 5 

 

177 of 435
 TABLE A12 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL BODY WEIGHTS [G] 

 

 FEMALE GROUP: 1800 PPM 

 DAY 0 2 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 6664 209. 214. 216. 

 6674 234. 232. 228. 

 6686 208. 204. 208. 

 6712 186. 194. 195. 

 6717 228. 224. 233. 

 

 

 MEAN 213. 214. 216. 

 S.D. 18.9 15.2 15.3 

 S.E. 8.5 6.8 6.8 

 N 5 5 5 

 PBFTSv4.44 

 03/24/2008 

178 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 0 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95555 43. 65. 25. 9. 11. 

 95556 40. 57. 24. 8. 6. 

 95558 40. 46. 13. 6. 3. 

 95574 39. 53. 22. 6. 4. 

 95577 40. 64. 24. 9. 9. 

 

 

 MEAN 40. 57. 22. 8. 7. 

 S.D. 1.5 7.9 4.9 1.5 3.4 

 S.E. 0.7 3.5 2.2 0.7 1.5 

 N 5 5 5 5 5 

 

179 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 1250 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95559 40. 52. 19. -3. 5. 

 95561 40. 45. 20. 7. 6. 

 95566 31. 47. 8. -2. 4. 

 95573 40. 56. 15. -6. 3. 

 95576 37. 56. 13. 6. 2. 

 

 

 MEAN 38. 51. 15. 0. 4. 

 S.D. 3.9 5.1 4.8 5.8 1.6 

 S.E. 1.7 2.3 2.2 2.6 0.7 

 N 5 5 5 5 5 

 

180 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 2500 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95560 36. 52. 23. -14. -4. 

 95564 39. 56. 22. 1. 7. 

 95565 42. 60. 16. -7. -2. 

 95569 35. 53. 18. -11. 0. 

 95578 39. 50. 19. -6. 4. 

 

 

 MEAN 38. 54. 20. -7. 1. 

 S.D. 2.8 3.9 2.9 5.7 4.5 

 S.E. 1.2 1.7 1.3 2.5 2.0 

 N 5 5 5 5 5 

 

181 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 5000 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95554 46. 66. 22. 

 95563 44. 61. 23. -40. 47. 

 95568 36. 51. 16. -38. 39. 

 95570 35. 56. 21. -61. 40. 

 95572 33. 46. 8. -36. 42. 

 

 

 MEAN 39. 56. 18. -44. 42. 

 S.D. 5.8 7.9 6.2 11.6 3.6 

 S.E. 2.6 3.5 2.8 5.8 1.8 

 N 5 5 5 4 4 

 

182 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 0 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95587 15. 23. 11. -1. 7. 

 95591 18. 28. 6. 10. -1. 

 95594 17. 23. 16. -10. 12. 

 95599 16. 20. 16. -6. 7. 

 95600 19. 18. 2. 6. 2. 

 

 

 MEAN 17. 22. 10. 0. 5. 

 S.D. 1.6 3.8 6.2 8.3 5.0 

 S.E. 0.7 1.7 2.8 3.7 2.2 

 N 5 5 5 5 5 

 

183 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 1250 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95579 15. 16. 7. 0. 6. 

 95586 12. 24. 4. 8. -1. 

 95588 15. 13. 8. -1. 8. 

 95595 23. 21. 11. -5. 5. 

 95603 15. 23. 1. 5. 4. 

 

 

 MEAN 16. 19. 6. 1. 4. 

 S.D. 4.1 4.7 3.8 5.1 3.4 

 S.E. 1.8 2.1 1.7 2.3 1.5 

 N 5 5 5 5 5 

 

184 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 2500 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95580 20. 20. 3. 4. 5. 

 95589 15. 28. 1. -1. 8. 

 95593 14. 16. 14. -5. 5. 

 95597 20. 28. 2. 4. -2. 

 95598 14. 27. -1. 0. 3. 

 

 

 MEAN 17. 24. 4. 0. 4. 

 S.D. 3.1 5.5 5.9 3.8 3.7 

 S.E. 1.4 2.5 2.6 1.7 1.7 

 N 5 5 5 5 5 

 

185 of 435
 TABLE A13 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 5000 PPM 

 DAY -12 TO -8 -8 TO -2 -2 TO 0 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95581 13. 19. 1. -18. 20. 

 95583 20. 17. 5. -15. 17. 

 95590 16. 22. 13. -32. 27. 

 95592 15. 23. 4. -14. 19. 

 95601 17. 36. 15. -49. 35. 

 

 

 MEAN 16. 23. 8. -26. 24. 

 S.D. 2.6 7.4 6.1 14.9 7.4 

 S.E. 1.2 3.3 2.7 6.7 3.3 

 N 5 5 5 5 5 

 PBFTSv4.44 

 03/24/2008 

186 of 435
 TABLE A14 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 1800 PPM 

 DAY 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95557 -3. 8. 

 95562 -7. 4. 

 95567 -8. 8. 

 95571 0. -1. 

 95575 -6. 9. 

 

 

 MEAN -5. 6. 

 S.D. 3.3 4.2 

 S.E. 1.5 1.9 

 N 5 5 

 

187 of 435
 TABLE A14 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 1800 PPM 

 DAY 0 TO 2 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 6664 5. 2. 

 6674 -2. -4. 

 6686 -4. 4. 

 6712 8. 1. 

 6717 -4. 9. 

 

 

 MEAN 1. 2. 

 S.D. 5.5 4.7 

 S.E. 2.5 2.1 

 N 5 5 

 PBFTSv4.44 

 03/24/2008 

188 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 0 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95555 9. 20. 

 95556 8. 14. 

 95558 6. 9. 

 95574 6. 10. 

 95577 9. 18. 

 

 

 MEAN 8. 14. 

 S.D. 1.5 4.8 

 S.E. 0.7 2.2 

 N 5 5 

 

189 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 1250 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95559 -3. 2. 

 95561 7. 13. 

 95566 -2. 2. 

 95573 -6. -3. 

 95576 6. 8. 

 

 

 MEAN 0. 4. 

 S.D. 5.8 6.2 

 S.E. 2.6 2.8 

 N 5 5 

 

190 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 2500 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95560 -14. -18. 

 95564 1. 8. 

 95565 -7. -9. 

 95569 -11. -11. 

 95578 -6. -2. 

 

 

 MEAN -7. -6. 

 S.D. 5.7 9.9 

 S.E. 2.5 4.4 

 N 5 5 

 

191 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 5000 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95554 

 95563 -40. 7. 

 95568 -38. 1. 

 95570 -61. -21. 

 95572 -36. 6. 

 

 

 MEAN -44. -2. 

 S.D. 11.6 13.1 

 S.E. 5.8 6.5 

 N 4 4 

 

192 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 0 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95587 -1. 6. 

 95591 10. 9. 

 95594 -10. 2. 

 95599 -6. 1. 

 95600 6. 8. 

 

 

 MEAN 0. 5. 

 S.D. 8.3 3.6 

 S.E. 3.7 1.6 

 N 5 5 

 

193 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 1250 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95579 0. 6. 

 95586 8. 7. 

 95588 -1. 7. 

 95595 -5. 0. 

 95603 5. 9. 

 

 

 MEAN 1. 6. 

 S.D. 5.1 3.4 

 S.E. 2.3 1.5 

 N 5 5 

 

194 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 2500 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95580 4. 9. 

 95589 -1. 7. 

 95593 -5. 0. 

 95597 4. 2. 

 95598 0. 3. 

 

 

 MEAN 0. 4. 

 S.D. 3.8 3.7 

 S.E. 1.7 1.7 

 N 5 5 

 

195 of 435
 TABLE A15 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 5000 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95581 -18. 2. 

 95583 -15. 2. 

 95590 -32. -5. 

 95592 -14. 5. 

 95601 -49. -14. 

 

 

 MEAN -26. -2. 

 S.D. 14.9 7.6 

 S.E. 6.7 3.4 

 N 5 5 

 PBFTSv4.44 

 03/24/2008 

196 of 435
 TABLE A16 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 MALE GROUP: 1800 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95557 -3. 5. 

 95562 -7. -3. 

 95567 -8. 0. 

 95571 0. -1. 

 95575 -6. 3. 

 

 

 MEAN -5. 1. 

 S.D. 3.3 3.2 

 S.E. 1.5 1.4 

 N 5 5 

 

197 of 435
 TABLE A16 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CUMULATIVE BODY WEIGHT CHANGES [G] 

 

 FEMALE GROUP: 1800 PPM 

 DAY 0 TO 2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 6664 5. 7. 

 6674 -2. -6. 

 6686 -4. 0. 

 6712 8. 9. 

 6717 -4. 5. 

 

 

 MEAN 1. 3. 

 S.D. 5.5 6.0 

 S.E. 2.5 2.7 

 N 5 5 

 PBFTSv4.44 

 03/24/2008 

198 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 0 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95555 28. 28. 

 95556 26. 25. 

 95558 26. 24. 

 95574 25. 25. 

 95577 29. 27. 

 

 

 MEAN 27. 26. 

 S.D. 1.6 1.6 

 S.E. 0.7 0.7 

 N 5 5 

 

199 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 1250 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95559 27. 22. 

 95561 26. 23. 

 95566 22. 20. 

 95573 30. 23. 

 95576 28. 26. 

 

 

 MEAN 27. 23. 

 S.D. 3.0 2.2 

 S.E. 1.3 1.0 

 N 5 5 

 

200 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 2500 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95560 25. 17. 

 95564 27. 24. 

 95565 28. 21. 

 95569 26. 19. 

 95578 27. 19. 

 

 

 MEAN 27. 20. 

 S.D. 1.1 2.6 

 S.E. 0.5 1.2 

 N 5 5 

 

201 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 5000 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95554 30. 

 95563 29. NA 

 95568 26. NA 

 95570 26. NA 

 95572 24. NA 

 

 

 MEAN 27. NA 

 S.D. 2.4 

 S.E. 1.1 

 N 5 

 

 NA = NOT APPLICABLE 

 

202 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 0 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95587 18. 16. 

 95591 20. 19. 

 95594 20. 17. 

 95599 19. 17. 

 95600 18. 18. 

 

 

 MEAN 19. 17. 

 S.D. 1.0 1.1 

 S.E. 0.4 0.5 

 N 5 5 

 

203 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 1250 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95579 17. 16. 

 95586 21. 17. 

 95588 18. 16. 

 95595 17. 15. 

 95603 23. 17. 

 

 

 MEAN 19. 16. 

 S.D. 2.7 0.8 

 S.E. 1.2 0.4 

 N 5 5 

 

204 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 2500 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95580 NA 17. 

 95589 19. 15. 

 95593 21. 12. 

 95597 21. 16. 

 95598 19. 15. 

 

 

 MEAN 20. 15. 

 S.D. 1.2 1.9 

 S.E. 0.6 0.8 

 N 4 5 

 

 NA = NOT APPLICABLE 

 

205 of 435
 TABLE A17 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 5000 PPM 

 DAY -8 TO -2 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95581 18. NA 

 95583 17. NA 

 95590 18. NA 

 95592 18. NA 

 95601 22. NA 

 

 

 MEAN 19. NA 

 S.D. 1.9 

 S.E. 0.9 

 N 5 

 

 NA = NOT APPLICABLE 

 PBFTSv4.44 

 03/24/2008 

206 of 435
 TABLE A18 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 1800 PPM 

 DAY 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95557 23. 

 95562 25. 

 95567 21. 

 95571 22. 

 95575 23. 

 

 

 MEAN 23. 

 S.D. 1.5 

 S.E. 0.7 

 N 5 

 

207 of 435
 TABLE A18 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 1800 PPM 

 DAY 0 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 6664 16. 

 6674 15. 

 6686 15. 

 6712 16. 

 6717 18. 

 

 

 MEAN 16. 

 S.D. 1.2 

 S.E. 0.5 

 N 5 

 PBFTSv4.44 

 03/24/2008 

208 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM MALES 

 

 95555 11.79 8.03 16.8 48.5 60.3 20.9 34.7 1623. 14.8 19.8 

 95556 8.89 8.08 15.9 45.8 56.7 19.7 34.7 1426. 12.7 19.5 

 95558 10.85 7.31 15.7 43.7 59.8 21.5 35.9 1471. CLT CLT 

 95574 8.15 7.79 15.8 44.9 57.7 20.3 35.2 1336. 13.5 18.8 

 95577 9.87 8.02 16.2 45.7 57.0 20.1 35.3 1693. 14.0 20.6 

 

 MEAN 9.91 7.85 16.1 45.7 58.3 20.5 35.2 1510. 13.8 19.7 

 S.D. 1.463 0.320 0.44 1.77 1.65 0.71 0.50 145.9 0.88 0.75 

 S.E. 0.654 0.143 0.20 0.79 0.74 0.32 0.22 65.2 0.44 0.37 

 N 5 5 5 5 5 5 5 5 4 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CLT = CLOTTED 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

209 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM MALES 

 

 95555 3.3 269.0 9.7 86.3 1.6 1.5 0.3 0.6 

 95556 3.1 250.4 13.1 83.2 1.6 0.7 0.3 1.0 

 95558 2.4 178.7 10.3 85.7 2.0 0.8 0.3 0.9 

 95574 2.5 197.6 11.2 84.8 2.1 1.2 0.2 0.6 

 95577 2.9 236.2 14.6 81.7 1.6 1.3 0.2 0.6 

 

 MEAN 2.8 226.4 11.8 84.3 1.8 1.1 0.3 0.7 

 S.D. 0.38 37.39 2.03 1.88 0.25 0.34 0.05 0.19 

 S.E. 0.17 16.72 0.91 0.84 0.11 0.15 0.02 0.09 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

210 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM MALES 

 

 95555 1.15 10.18 0.19 0.18 0.03 0.07 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95556 1.17 7.40 0.15 0.07 0.03 0.09 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95558 1.12 9.30 0.22 0.09 0.04 0.09 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95574 0.91 6.91 0.17 0.09 0.02 0.05 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95577 1.44 8.06 0.16 0.13 0.02 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 1.16 8.37 0.18 0.11 0.03 0.07 

 S.D. 0.189 1.352 0.028 0.044 0.008 0.018 

 S.E. 0.084 0.605 0.012 0.020 0.004 0.008 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

211 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM MALES 

 

 95559 12.36 7.50 15.9 44.1 58.8 21.2 36.1 1076. 13.3 18.6 

 95561 9.25 7.94 15.7 44.7 56.3 19.8 35.2 1006. 12.8 18.0 

 95566 11.52 8.50 16.9 46.7 54.9 19.9 36.1 1412. 13.0 16.8 

 95573 7.99 8.14 16.7 46.6 57.3 20.5 35.8 1446. 13.6 18.3 

 95576 15.20 8.49 16.4 46.9 55.3 19.3 34.9 1404. 13.8 20.5 

 

 MEAN 11.26 8.11 16.3 45.8 56.5 20.1 35.6 1269. 13.3 18.4 

 S.D. 2.808 0.418 0.51 1.30 1.58 0.73 0.54 210.0 0.41 1.34 

 S.E. 1.256 0.187 0.23 0.58 0.71 0.33 0.24 93.9 0.18 0.60 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

212 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM MALES 

 

 95559 2.5 185.4 6.3 91.2 1.1 0.4 0.4 0.5 

 95561 2.8 221.2 13.5 82.3 2.1 1.0 0.5 0.7 

 95566 2.1 177.7 10.3 86.6 1.5 0.5 0.4 0.7 

 95573 2.0 164.2 19.9 75.9 1.6 1.3 0.4 0.8 

 95576 2.2 184.5 7.7 88.9 1.7 0.7 0.3 0.6 

 

 MEAN 2.3 186.6 11.5 85.0 1.6 0.8 0.4 0.7 

 S.D. 0.33 21.12 5.42 6.05 0.36 0.37 0.07 0.11 

 S.E. 0.15 9.44 2.42 2.70 0.16 0.17 0.03 0.05 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

213 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM MALES 

 

 95559 0.78 11.27 0.14 0.05 0.06 0.07 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95561 1.25 7.61 0.19 0.09 0.04 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95566 1.19 9.98 0.17 0.05 0.04 0.08 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95573 1.59 6.07 0.13 0.10 0.03 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95576 1.17 13.52 0.27 0.11 0.05 0.09 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 1.20 9.69 0.18 0.08 0.04 0.07 

 S.D. 0.288 2.944 0.056 0.028 0.011 0.013 

 S.E. 0.129 1.317 0.025 0.013 0.005 0.006 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

214 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM MALES 

 

 95560 8.17 8.13 17.2 47.9 59.0 21.1 35.8 990. 14.5 17.7 

 95564 13.74 7.70 15.9 45.2 58.6 20.7 35.3 1245. 12.7 18.9 

 95565 8.94 8.30 16.3 46.2 55.6 19.7 35.4 1378. 14.0 17.9 

 95569 7.40 8.37 17.2 49.4 59.0 20.6 34.9 1049. 12.7 19.8 

 95578 8.96 8.17 16.2 45.2 55.3 19.8 35.8 1900. 12.6 17.6 

 

 MEAN 9.44 8.13 16.6 46.8 57.5 20.4 35.4 1312. 13.3 18.4 

 S.D. 2.487 0.261 0.60 1.83 1.88 0.61 0.38 363.1 0.89 0.95 

 S.E. 1.112 0.117 0.27 0.82 0.84 0.27 0.17 162.4 0.40 0.42 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

215 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM MALES 

 

 95560 1.7 142.0 17.2 78.1 2.8 0.8 0.4 0.8 

 95564 2.8 218.4 8.0 89.4 1.2 0.5 0.3 0.5 

 95565 1.6 130.9 7.8 88.2 2.2 0.6 0.3 0.9 

 95569 2.0 170.2 10.7 86.6 1.4 0.4 0.3 0.6 

 95578 2.1 173.6 8.9 87.2 2.3 0.7 0.2 0.7 

 

 MEAN 2.0 167.0 10.5 85.9 2.0 0.6 0.3 0.7 

 S.D. 0.47 34.00 3.91 4.49 0.66 0.16 0.07 0.16 

 S.E. 0.21 15.21 1.75 2.01 0.30 0.07 0.03 0.07 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

216 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM MALES 

 

 95560 1.41 6.38 0.23 0.06 0.03 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95564 1.11 12.28 0.17 0.07 0.04 0.07 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95565 0.70 7.89 0.19 0.05 0.02 0.08 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95569 0.79 6.40 0.10 0.03 0.02 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95578 0.80 7.82 0.21 0.06 0.02 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 0.96 8.15 0.18 0.05 0.03 0.06 

 S.D. 0.295 2.420 0.050 0.015 0.009 0.015 

 S.E. 0.132 1.082 0.022 0.007 0.004 0.007 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

217 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM MALES 

 

 95563 9.55 7.85 15.5 44.0 56.1 19.8 35.3 1705. 12.6 18.3 

 95568 9.78 8.07 15.9 45.0 55.7 19.7 35.4 1359. 13.0 19.6 

 95570 14.96 7.46 15.4 42.8 57.3 20.7 36.1 1497. 13.9 18.4 

 95572 10.14 8.11 16.4 46.0 56.7 20.2 35.6 1441. 12.4 19.7 

 

 MEAN 11.11 7.87 15.8 44.5 56.5 20.1 35.6 1501. 13.0 19.0 

 S.D. 2.580 0.298 0.45 1.37 0.70 0.45 0.36 147.6 0.67 0.75 

 S.E. 1.290 0.149 0.23 0.68 0.35 0.23 0.18 73.8 0.33 0.38 

 N 4 4 4 4 4 4 4 4 4 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

218

 

 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 11 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM MALES 

 

 95563 2.8 223.5 16.5 79.7 2.1 1.1 0.2 0.5 

 95568 3.0 243.9 10.8 85.6 2.4 0.3 0.3 0.6 

 95570 2.6 194.0 19.9 76.4 1.6 1.2 0.3 0.6 

 95572 2.8 230.4 11.6 84.6 1.9 0.5 0.3 1.0 

 

 MEAN 2.8 223.0 14.7 81.6 2.0 0.8 0.3 0.7 

 S.D. 0.16 21.08 4.29 4.31 0.34 0.44 0.05 0.22 

 S.E. 0.08 10.54 2.14 2.15 0.17 0.22 0.02 0.11 

 N 4 4 4 4 4 4 4 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

219

 

 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 12 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM MALES 

 

 95563 1.57 7.61 0.20 0.10 0.02 0.05 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95568 1.06 8.37 0.23 0.03 0.03 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95570 2.98 11.42 0.24 0.18 0.05 0.09 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95572 1.18 8.58 0.20 0.05 0.03 0.10 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 1.70 9.00 0.22 0.09 0.03 0.08 

 S.D. 0.882 1.670 0.021 0.067 0.013 0.024 

 S.E. 0.441 0.835 0.010 0.033 0.006 0.012 

 N 4 4 4 4 4 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

220

 

 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 13 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM FEMALES 

 

 95587 6.60 8.27 16.3 43.5 52.7 19.7 37.3 1575. 12.1 18.4 

 95591 7.80 8.11 16.6 45.7 56.4 20.5 36.4 1333. 11.1 11.7 

 95594 10.46 7.76 15.6 42.3 54.5 20.1 36.9 1320. 12.0 16.4 

 95599 9.18 8.17 16.7 44.7 54.7 20.4 37.3 1437. 11.0 11.3 

 95600 3.77 7.80 15.5 42.2 54.1 19.8 36.6 1290. 12.9 18.2 

 

 MEAN 7.56 8.02 16.1 43.7 54.5 20.1 36.9 1391. 11.8 15.2 

 S.D. 2.568 0.229 0.56 1.52 1.33 0.35 0.41 116.8 0.79 3.47 

 S.E. 1.148 0.102 0.25 0.68 0.59 0.16 0.18 52.2 0.35 1.55 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

221 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 14 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM FEMALES 

 

 95587 1.9 154.9 19.9 76.5 2.0 0.6 0.4 0.5 

 95591 2.4 195.6 8.9 86.4 2.2 1.3 0.4 0.8 

 95594 2.5 197.4 13.3 84.0 0.9 0.7 0.3 0.8 

 95599 2.2 183.6 6.2 90.1 1.8 0.8 0.3 0.7 

 95600 2.5 197.0 28.7 58.5 11.4 0.5 0.2 0.7 

 

 MEAN 2.3 185.7 15.4 79.1 3.7 0.8 0.3 0.7 

 S.D. 0.25 18.14 9.06 12.54 4.36 0.31 0.08 0.12 

 S.E. 0.11 8.11 4.05 5.61 1.95 0.14 0.04 0.05 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

222 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 15 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM FEMALES 

 

 95587 1.31 5.05 0.13 0.04 0.03 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95591 0.70 6.75 0.17 0.10 0.03 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95594 1.39 8.79 0.09 0.07 0.04 0.08 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95599 0.57 8.27 0.17 0.07 0.03 0.07 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95600 1.08 2.21 0.43 0.02 0.01 0.02 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 1.01 6.21 0.20 0.06 0.03 0.05 

 S.D. 0.364 2.671 0.134 0.031 0.011 0.024 

 S.E. 0.163 1.195 0.060 0.014 0.005 0.011 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

223 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 16 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM FEMALES 

 

 95579 7.77 8.33 16.4 45.6 54.7 19.7 36.0 1205. 12.6 17.9 

 95586 10.62 7.93 15.6 42.1 53.2 19.7 37.0 1368. 12.4 16.0 

 95588 5.38 7.84 15.6 41.7 53.2 19.9 37.4 1243. 12.2 17.7 

 95595 6.91 7.44 15.5 41.3 55.5 20.9 37.6 1575. 12.4 18.0 

 95603 4.85 8.36 15.8 43.8 52.3 18.9 36.1 1425. 11.5 17.3 

 

 MEAN 7.11 7.98 15.8 42.9 53.8 19.8 36.8 1363. 12.2 17.4 

 S.D. 2.286 0.381 0.36 1.78 1.29 0.72 0.74 148.5 0.43 0.82 

 S.E. 1.022 0.170 0.16 0.80 0.58 0.32 0.33 66.4 0.19 0.37 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

224 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 17 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM FEMALES 

 

 95579 2.0 164.4 10.4 86.5 1.6 0.6 0.4 0.5 

 95586 1.9 152.0 12.2 84.0 1.8 0.9 0.2 0.8 

 95588 2.2 169.2 9.9 86.9 1.2 1.1 0.2 0.7 

 95595 2.1 156.7 7.2 90.5 0.9 0.9 0.2 0.4 

 95603 1.3 110.3 12.5 85.1 0.7 1.0 0.3 0.4 

 

 MEAN 1.9 150.5 10.4 86.6 1.2 0.9 0.3 0.6 

 S.D. 0.35 23.45 2.13 2.47 0.46 0.19 0.09 0.18 

 S.E. 0.16 10.49 0.95 1.10 0.21 0.08 0.04 0.08 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

225 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 18 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM FEMALES 

 

 95579 0.81 6.72 0.12 0.05 0.03 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95586 1.30 8.92 0.19 0.10 0.02 0.09 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95588 0.53 4.68 0.06 0.06 0.01 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95595 0.50 6.25 0.06 0.06 0.01 0.02 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95603 0.61 4.12 0.03 0.05 0.02 0.02 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 0.75 6.14 0.09 0.06 0.02 0.04 

 S.D. 0.330 1.890 0.064 0.021 0.008 0.029 

 S.E. 0.148 0.845 0.029 0.009 0.004 0.013 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

226 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 19 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM FEMALES 

 

 95580 6.38 7.68 16.0 44.1 57.4 20.8 36.2 1272. 12.2 15.1 

 95589 7.92 7.77 15.2 42.2 54.4 19.6 36.0 1430. 12.3 16.1 

 95593 7.06 8.11 16.3 44.4 54.7 20.1 36.8 1644. 13.0 18.1 

 95597 7.08 7.65 16.3 43.0 56.2 21.3 37.9 1736. 13.4 18.5 

 95598 6.64 7.57 16.0 42.8 56.5 21.1 37.3 1398. 11.6 17.9 

 

 MEAN 7.02 7.76 16.0 43.3 55.8 20.6 36.8 1496. 12.5 17.1 

 S.D. 0.585 0.210 0.45 0.92 1.26 0.71 0.78 189.5 0.71 1.47 

 S.E. 0.262 0.094 0.20 0.41 0.56 0.32 0.35 84.7 0.32 0.66 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

227 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 20 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM FEMALES 

 

 95580 2.1 163.2 10.5 86.3 1.3 1.4 0.1 0.3 

 95589 2.2 174.7 7.8 88.9 1.5 0.8 0.2 0.8 

 95593 1.8 148.5 10.9 86.2 1.8 0.6 0.1 0.4 

 95597 2.1 157.1 10.1 86.2 1.4 1.3 0.2 0.8 

 95598 2.3 171.0 15.0 81.4 1.1 1.8 0.3 0.4 

 

 MEAN 2.1 162.9 10.9 85.8 1.4 1.2 0.2 0.5 

 S.D. 0.19 10.56 2.61 2.72 0.26 0.48 0.08 0.24 

 S.E. 0.08 4.72 1.17 1.22 0.12 0.22 0.04 0.11 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

228 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 21 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM FEMALES 

 

 95580 0.67 5.50 0.08 0.09 0.01 0.02 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95589 0.61 7.04 0.12 0.06 0.02 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95593 0.77 6.08 0.12 0.04 0.01 0.03 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95597 0.72 6.10 0.10 0.09 0.01 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95598 1.00 5.41 0.07 0.12 0.02 0.03 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 0.75 6.03 0.10 0.08 0.01 0.04 

 S.D. 0.150 0.651 0.023 0.031 0.005 0.019 

 S.E. 0.067 0.291 0.010 0.014 0.002 0.008 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

229 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 22 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM FEMALES 

 

 95581 6.45 7.50 15.5 41.5 55.4 20.7 37.4 1389. 11.9 15.9 

 95583 6.49 8.24 16.2 45.1 54.7 19.6 35.9 1458. 12.7 17.2 

 95590 5.33 7.77 15.3 42.4 54.7 19.7 36.0 1492. 12.5 16.9 

 95592 7.54 7.83 15.6 42.6 54.4 19.9 36.6 1734. 12.3 15.8 

 95601 8.30 7.17 14.5 39.6 55.3 20.2 36.5 1040. 10.9 15.3 

 

 MEAN 6.82 7.70 15.4 42.2 54.9 20.0 36.5 1423. 12.1 16.2 

 S.D. 1.137 0.398 0.61 1.99 0.43 0.44 0.60 250.3 0.71 0.80 

 S.E. 0.509 0.178 0.27 0.89 0.19 0.20 0.27 111.9 0.32 0.36 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

230 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 23 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM FEMALES 

 

 95581 2.4 176.4 15.7 80.7 1.7 1.3 0.2 0.4 

 95583 2.4 198.1 15.0 82.0 1.6 0.8 0.1 0.5 

 95590 2.8 218.2 17.6 79.1 1.9 0.7 0.1 0.6 

 95592 2.9 223.6 13.2 83.4 1.5 1.1 0.3 0.5 

 95601 2.8 197.2 17.4 79.1 2.1 0.7 0.2 0.5 

 

 MEAN 2.7 202.7 15.8 80.9 1.8 0.9 0.2 0.5 

 S.D. 0.24 18.84 1.82 1.87 0.24 0.27 0.08 0.07 

 S.E. 0.11 8.43 0.81 0.84 0.11 0.12 0.04 0.03 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

231 of 435
 TABLE A19 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 24 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM FEMALES 

 

 95581 1.01 5.21 0.11 0.09 0.01 0.03 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95583 0.97 5.32 0.10 0.05 0.01 0.03 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95590 0.94 4.21 0.10 0.04 0.00 0.03 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95592 0.99 6.29 0.11 0.08 0.03 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95601 1.44 6.57 0.17 0.06 0.01 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 1.07 5.52 0.12 0.06 0.01 0.03 

 S.D. 0.208 0.942 0.029 0.021 0.011 0.005 

 S.E. 0.093 0.421 0.013 0.009 0.005 0.002 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 PHEMAv1.34 

 03/24/2008 

232 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM MALES 

 

 95557 11.63 8.18 17.2 48.3 59.0 21.0 35.6 1394. 13.9 17.7 

 95562 8.20 8.20 17.2 47.5 57.9 20.9 36.1 955. 14.4 17.2 

 95567 8.42 7.84 16.6 46.1 58.8 21.2 36.0 1086. 13.9 19.9 

 95571 10.44 8.27 16.7 47.8 57.8 20.2 35.0 1505. 11.8 15.9 

 95575 CLT CLT CLT CLT CLT CLT CLT CLT 12.7 20.0 

 

 MEAN 9.67 8.12 16.9 47.4 58.4 20.8 35.7 1235. 13.3 18.1 

 S.D. 1.649 0.192 0.32 0.94 0.61 0.43 0.50 257.4 1.06 1.78 

 S.E. 0.825 0.096 0.16 0.47 0.31 0.22 0.25 128.7 0.48 0.80 

 N 4 4 4 4 4 4 4 4 5 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CLT = CLOTTED 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

233 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM MALES 

 

 95557 2.6 211.5 8.5 86.2 2.7 1.3 0.5 0.9 

 95562 1.5 125.1 12.4 83.6 1.7 1.4 0.4 0.6 

 95567 2.0 156.5 10.5 84.9 2.2 1.6 0.2 0.5 

 95571 1.6 134.4 8.4 87.5 2.4 0.3 0.3 1.0 

 95575 CLT CLT CLT CLT CLT CLT CLT CLT 

 

 MEAN 1.9 156.9 10.0 85.6 2.3 1.2 0.4 0.8 

 S.D. 0.50 38.72 1.90 1.68 0.42 0.58 0.13 0.24 

 S.E. 0.25 19.36 0.95 0.84 0.21 0.29 0.06 0.12 

 N 4 4 4 4 4 4 4 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CLT = CLOTTED 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

234 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM MALES 

 

 95557 0.98 10.02 0.31 0.15 0.06 0.10 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95562 1.01 6.86 0.14 0.12 0.03 0.05 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95567 0.88 7.15 0.18 0.14 0.02 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95571 0.88 9.14 0.25 0.03 0.03 0.10 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 95575 CLT CLT CLT CLT CLT CLT PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 0.94 8.29 0.22 0.11 0.04 0.07 

 S.D. 0.068 1.534 0.075 0.055 0.017 0.032 

 S.E. 0.034 0.767 0.038 0.027 0.009 0.016 

 N 4 4 4 4 4 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CLT = CLOTTED 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

235 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 WHITE RED HEMO- HEMATO- 

 ANIMAL CELLS CELLS GLOBIN CRIT MCV MCH MCHC PLATELET PROTIME APTT 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL mil/uL g/dL % fL pg g/dL thous/uL seconds seconds 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM FEMALES 

 

 6664 8.64 8.18 16.6 44.9 54.9 20.3 37.0 1608. 12.4 17.0 

 6674 8.06 8.11 17.0 47.2 58.2 21.0 36.1 1220. 12.8 16.7 

 6686 8.19 7.82 15.6 41.9 53.5 20.0 37.3 1584. CLT CLT 

 6712 8.89 8.50 16.6 46.4 54.6 19.5 35.8 1225. 11.8 17.7 

 6717 8.46 8.00 15.8 43.0 53.8 19.8 36.8 1426. 12.0 17.5 

 

 MEAN 8.45 8.12 16.3 44.7 55.0 20.1 36.6 1413. 12.3 17.2 

 S.D. 0.335 0.251 0.59 2.23 1.88 0.57 0.63 187.1 0.44 0.46 

 S.E. 0.150 0.112 0.27 1.00 0.84 0.26 0.28 83.7 0.22 0.23 

 N 5 5 5 5 5 5 5 5 4 4 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CLT = CLOTTED 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER, mil/uL = MILLIONS/MICROLITER, fL = FEMTOLITERS, pg = PICOGRAMS, g/dL = GRAMS/DECILITER 

 

236 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 RETIC- RETIC NEUTRO- LYMPH- EOSIN- LG UNST- 

 ANIMAL ULOCYTE ABSOLUTE PHIL OCYTE MONOCYTE OPHIL BASOPHIL AIN CELL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 % thous/uL % % % % % % 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM FEMALES 

 

 6664 2.2 177.8 9.0 87.8 1.9 0.5 0.3 0.5 

 6674 2.0 163.2 7.1 89.5 1.8 0.9 0.2 0.6 

 6686 1.2 95.1 6.4 90.2 1.7 0.8 0.1 0.7 

 6712 2.1 180.7 16.7 78.1 3.0 1.4 0.3 0.5 

 6717 1.8 142.9 9.7 85.9 2.2 1.5 0.2 0.4 

 

 MEAN 1.9 151.9 9.8 86.3 2.1 1.0 0.2 0.5 

 S.D. 0.40 35.13 4.10 4.88 0.53 0.42 0.08 0.11 

 S.E. 0.18 15.71 1.83 2.18 0.24 0.19 0.04 0.05 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 

237 of 435
 TABLE A20 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL HEMATOLOGY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 NEU LYMPH MONO EOS BASO LUC PLATELET RBC 

 ANIMAL ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ABSOLUTE ESTIMATE MORPHOLOGY 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL thous/uL thous/uL thous/uL thous/uL thous/uL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM FEMALES 

 

 6664 0.78 7.59 0.16 0.05 0.02 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 6674 0.57 7.22 0.14 0.07 0.01 0.05 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 6686 0.53 7.39 0.14 0.07 0.01 0.06 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 6712 1.49 6.95 0.27 0.12 0.03 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 6717 0.82 7.27 0.19 0.13 0.02 0.04 PLATELET ESTIMATE AND MORPHOLOGY NOT REVIEWED 

 

 MEAN 0.84 7.28 0.18 0.09 0.02 0.05 

 S.D. 0.386 0.235 0.054 0.035 0.008 0.009 

 S.E. 0.173 0.105 0.024 0.016 0.004 0.004 

 N 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 thous/uL = THOUSANDS/MICROLITER 

 PHEMAv1.34 

 03/24/2008 

238 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM MALES 

 

 95555 4.3 6.4 2.1 2.06 0.09 13.0 0.2 320. 40. 89. 

 95556 4.3 6.5 2.2 1.92 0.10 10.2 0.2 276. 37. 88. 

 95558 4.4 6.0 1.5 2.86 0.11 12.9 0.2 297. 37. 101. 

 95574 4.4 6.2 1.9 2.31 0.08 10.9 0.1 244. 27. 80. 

 95577 4.3 6.5 2.2 1.96 0.06 8.8 0.1 161. 28. 75. 

 

 MEAN 4.3 6.3 2.0 2.22 0.09 11.2 0.2 260. 34. 87. 

 S.D. 0.05 0.22 0.29 0.388 0.019 1.80 0.05 61.8 5.9 9.9 

 S.E. 0.02 0.10 0.13 0.173 0.009 0.81 0.02 27.6 2.6 4.4 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

239 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM MALES 

 

 95555 127. 57. 10.8 101. 9.8 4.93 145. 104. 

 95556 132. 64. 10.6 102. 9.5 5.00 146. 60. 

 95558 109. 49. 10.9 103. 9.7 4.92 146. 35. 

 95574 126. 46. 10.9 103. 8.7 4.34 146. 45. 

 95577 119. 55. 10.8 104. 9.1 4.38 146. 54. 

 

 MEAN 123. 54. 10.8 103. 9.4 4.71 146. 60. 

 S.D. 8.9 7.0 0.12 1.1 0.46 0.325 0.4 26.6 

 S.E. 4.0 3.2 0.05 0.5 0.20 0.145 0.2 11.9 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

240 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM MALES 

 

 95559 4.2 6.3 2.1 2.02 0.12 12.9 0.2 114. 40. 104. 

 95561 4.2 6.0 1.8 2.29 0.11 10.9 0.2 206. 34. 93. 

 95566 4.4 6.2 1.8 2.44 0.09 13.0 0.1 290. 35. 89. 

 95573 4.3 6.4 2.1 2.00 0.08 10.7 0.1 184. 39. 91. 

 95576 4.4 6.4 2.0 2.16 0.07 11.4 0.2 318. 28. 91. 

 

 MEAN 4.3 6.3 2.0 2.18 0.09 11.8 0.2 222. 35. 94. 

 S.D. 0.10 0.17 0.15 0.186 0.021 1.10 0.05 82.5 4.8 6.0 

 S.E. 0.04 0.07 0.07 0.083 0.009 0.49 0.02 36.9 2.1 2.7 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

241 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM MALES 

 

 95559 106. 69. 10.8 102. 8.7 4.61 145. 40. 

 95561 117. 77. 11.1 103. 8.8 4.81 146. 51. 

 95566 90. 53. 11.0 104. 9.0 4.97 147. 52. 

 95573 103. 69. 11.2 103. 9.1 4.39 146. 51. 

 95576 109. 45. 10.8 104. 9.9 5.05 147. 43. 

 

 MEAN 105. 63. 11.0 103. 9.1 4.77 146. 47. 

 S.D. 9.9 13.1 0.18 0.8 0.47 0.269 0.8 5.5 

 S.E. 4.4 5.9 0.08 0.4 0.21 0.120 0.4 2.5 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

242 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM MALES 

 

 95560 4.5 6.4 1.9 2.42 0.10 11.4 0.1 184. 57. 89. 

 95564 4.2 6.4 2.2 1.94 0.07 10.5 0.2 174. 28. 66. 

 95565 4.4 6.3 1.8 2.43 0.10 13.0 0.2 261. 71. 180. 

 95569 4.7 6.9 2.2 2.11 0.10 10.6 0.2 237. 28. 80. 

 95578 4.3 6.3 2.0 2.23 0.10 10.6 0.2 240. 64. 87. 

 

 MEAN 4.4 6.5 2.0 2.23 0.09 11.2 0.2 219. 50. 100. 

 S.D. 0.19 0.25 0.18 0.209 0.013 1.06 0.04 38.0 20.3 45.4 

 S.E. 0.09 0.11 0.08 0.093 0.006 0.47 0.02 17.0 9.1 20.3 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

243 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM MALES 

 

 95560 110. 55. 10.9 104. 8.9 4.89 145. 45. 

 95564 131. 95. 11.4 103. 9.0 4.38 147. 82. 

 95565 108. 59. 11.0 106. 9.2 4.97 146. 62. 

 95569 132. 64. 11.1 104. 8.8 5.16 148. 44. 

 95578 108. 69. 10.8 104. 9.2 5.16 145. 38. 

 

 MEAN 118. 68. 11.0 104. 9.0 4.91 146. 54. 

 S.D. 12.5 15.8 0.23 1.1 0.18 0.320 1.3 17.9 

 S.E. 5.6 7.1 0.10 0.5 0.08 0.143 0.6 8.0 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

244 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM MALES 

 

 95563 4.4 6.2 1.8 2.36 0.08 8.5 0.2 187. 45. 113. 

 95568 4.4 6.4 2.1 2.12 0.09 11.2 0.2 285. 40. 79. 

 95570 3.7 5.9 2.2 1.73 0.16 9.6 0.2 201. 31. 64. 

 95572 4.5 6.6 2.1 2.12 0.12 10.5 0.1 252. 37. 94. 

 

 MEAN 4.3 6.3 2.1 2.08 0.11 10.0 0.2 231. 38. 88. 

 S.D. 0.37 0.30 0.17 0.261 0.036 1.17 0.05 45.4 5.9 21.0 

 S.E. 0.18 0.15 0.09 0.130 0.018 0.58 0.03 22.7 2.9 10.5 

 N 4 4 4 4 4 4 4 4 4 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

245

 

 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM MALES 

 

 95563 105. 63. 10.4 103. 8.5 4.70 145. 50. 

 95568 103. 58. 10.9 104. 9.1 4.84 146. 38. 

 95570 110. 53. 10.8 103. 9.4 4.59 145. 37. 

 95572 114. 75. 10.9 102. 9.1 4.63 146. 41. 

 

 MEAN 108. 62. 10.8 103. 9.0 4.69 146. 42. 

 S.D. 5.0 9.4 0.24 0.8 0.38 0.110 0.6 5.9 

 S.E. 2.5 4.7 0.12 0.4 0.19 0.055 0.3 3.0 

 N 4 4 4 4 4 4 4 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

246

 

 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM FEMALES 

 

 95587 4.5 6.8 2.3 1.95 0.06 13.9 0.2 143. 37. 103. 

 95591 4.7 7.1 2.5 1.89 0.10 13.4 0.3 116. 37. 74. 

 95594 4.8 7.3 2.5 1.92 0.08 13.3 0.3 72. 35. 83. 

 95599 4.4 6.8 2.4 1.89 0.09 12.7 0.3 112. 25. 74. 

 95600 4.7 6.6 1.9 2.42 0.14 14.7 0.3 142. 24. 84. 

 

 MEAN 4.6 6.9 2.3 2.01 0.09 13.6 0.3 117. 32. 84. 

 S.D. 0.16 0.28 0.25 0.228 0.030 0.75 0.04 28.9 6.5 11.8 

 S.E. 0.07 0.12 0.11 0.102 0.013 0.33 0.02 12.9 2.9 5.3 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

247 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM FEMALES 

 

 95587 119. 89. 11.1 103. 8.3 5.26 146. 50. 

 95591 107. 82. 11.3 103. 8.6 5.15 146. 39. 

 95594 104. 92. 11.1 99. 7.7 4.42 144. 59. 

 95599 116. 79. 11.2 104. 8.9 4.63 147. 33. 

 95600 116. 49. 10.2 103. 6.3 4.35 146. 34. 

 

 MEAN 112. 78. 11.0 102. 8.0 4.76 146. 43. 

 S.D. 6.5 17.1 0.44 1.9 1.03 0.419 1.1 11.2 

 S.E. 2.9 7.7 0.20 0.9 0.46 0.187 0.5 5.0 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

248 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 11 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM FEMALES 

 

 95579 4.4 6.8 2.4 1.81 0.07 14.3 0.3 135. 26. 78. 

 95586 4.5 6.9 2.4 1.85 0.11 13.0 0.3 120. 33. 68. 

 95588 4.3 6.6 2.3 1.84 0.06 15.1 0.2 113. 31. 84. 

 95595 4.7 6.8 2.2 2.15 0.08 13.3 0.2 115. 34. 96. 

 95603 5.0 7.1 2.0 2.49 0.09 13.7 0.3 111. 27. 80. 

 

 MEAN 4.6 6.8 2.3 2.03 0.08 13.9 0.3 119. 30. 81. 

 S.D. 0.28 0.18 0.17 0.293 0.019 0.84 0.05 9.7 3.6 10.2 

 S.E. 0.12 0.08 0.07 0.131 0.009 0.37 0.02 4.3 1.6 4.5 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

249 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 12 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1250 PPM FEMALES 

 

 95579 106. 115. 11.0 104. 8.2 4.84 147. 56. 

 95586 104. 109. 11.1 102. 7.7 4.32 145. 63. 

 95588 126. 94. 10.9 105. 7.6 4.95 144. 26. 

 95595 113. 61. 11.1 104. 7.9 4.84 145. 38. 

 95603 117. 60. 10.8 104. 8.3 4.52 146. 32. 

 

 MEAN 113. 88. 11.0 104. 7.9 4.69 145. 43. 

 S.D. 8.9 26.1 0.13 1.1 0.30 0.264 1.1 15.8 

 S.E. 4.0 11.7 0.06 0.5 0.14 0.118 0.5 7.1 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

250 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 13 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM FEMALES 

 

 95580 4.4 6.7 2.2 1.98 0.11 11.7 0.3 124. 42. 87. 

 95589 4.7 6.8 2.1 2.24 0.13 9.3 0.3 153. 66. 84. 

 95593 4.4 6.6 2.2 2.00 0.11 14.1 0.2 150. 34. 65. 

 95597 4.6 6.6 2.1 2.23 0.07 10.1 0.2 124. 40. 84. 

 95598 4.7 6.8 2.0 2.35 0.09 8.9 0.2 162. 25. 100. 

 

 MEAN 4.6 6.7 2.1 2.16 0.10 10.8 0.2 143. 41. 84. 

 S.D. 0.15 0.10 0.08 0.162 0.023 2.12 0.05 17.5 15.3 12.5 

 S.E. 0.07 0.04 0.04 0.073 0.010 0.95 0.02 7.8 6.8 5.6 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

251 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 14 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 2500 PPM FEMALES 

 

 95580 139. 77. 11.3 102. 8.3 4.95 146. 37. 

 95589 130. 95. 11.1 100. 7.3 5.22 141. 43. 

 95593 114. 82. 11.2 104. 9.1 5.04 147. 37. 

 95597 114. 68. 11.0 104. 8.2 4.91 145. 39. 

 95598 109. 70. 10.3 104. 8.0 4.88 144. 31. 

 

 MEAN 121. 78. 11.0 103. 8.2 5.00 145. 37. 

 S.D. 12.7 10.8 0.40 1.8 0.65 0.137 2.3 4.3 

 S.E. 5.7 4.8 0.18 0.8 0.29 0.061 1.0 1.9 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

252 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 15 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM FEMALES 

 

 95581 4.3 6.4 2.1 2.01 0.09 14.4 0.2 110. 43. 94. 

 95583 4.3 6.7 2.4 1.80 0.13 15.8 0.3 128. 30. 91. 

 95590 4.4 6.5 2.1 2.08 0.08 12.2 0.2 87. 22. 66. 

 95592 4.4 6.5 2.0 2.17 0.11 14.6 0.2 116. 33. 119. 

 95601 3.9 5.7 1.8 2.14 0.05 11.8 0.2 96. 39. 91. 

 

 MEAN 4.3 6.4 2.1 2.04 0.09 13.8 0.2 107. 33. 92. 

 S.D. 0.21 0.38 0.22 0.147 0.030 1.70 0.04 16.2 8.1 18.8 

 S.E. 0.09 0.17 0.10 0.066 0.014 0.76 0.02 7.2 3.6 8.4 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

253 of 435
 TABLE A21 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 16 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 5000 PPM FEMALES 

 

 95581 109. 63. 10.8 103. 7.8 4.69 145. 40. 

 95583 114. 75. 10.9 103. 8.8 5.45 146. 37. 

 95590 111. 57. 10.5 105. 8.6 4.91 146. 38. 

 95592 104. 85. 10.8 102. 8.6 4.83 143. 53. 

 95601 111. 70. 10.2 103. 8.6 4.54 143. 46. 

 

 MEAN 110. 70. 10.6 103. 8.5 4.88 145. 43. 

 S.D. 3.7 10.8 0.29 1.1 0.39 0.346 1.5 6.7 

 S.E. 1.7 4.8 0.13 0.5 0.17 0.155 0.7 3.0 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 PCHEv4.03 

 03/24/2008 

254 of 435
 TABLE A22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM MALES 

 

 95557 4.4 6.5 2.2 1.99 0.14 12.0 0.3 220. 44. 100. 

 95562 4.3 6.3 2.1 2.06 0.10 13.4 0.1 163. 36. 118. 

 95567 4.4 6.5 2.1 2.11 0.10 10.7 0.2 169. 32. 79. 

 95571 4.5 6.8 2.3 1.93 0.10 13.2 0.2 164. 59. 86. 

 95575 4.6 6.8 2.3 2.02 0.08 9.4 0.3 206. 31. 77. 

 

 MEAN 4.4 6.6 2.2 2.02 0.10 11.7 0.2 184. 40. 92. 

 S.D. 0.11 0.22 0.10 0.068 0.022 1.70 0.08 26.7 11.6 17.1 

 S.E. 0.05 0.10 0.04 0.031 0.010 0.76 0.04 11.9 5.2 7.6 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

255 of 435
 TABLE A22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM MALES 

 

 95557 155. 65. 11.0 98. 10.4 5.17 143. 35. 

 95562 125. 77. 10.7 101. 8.7 4.60 144. 67. 

 95567 111. 66. 11.2 100. 9.6 4.91 145. 41. 

 95571 142. 83. 11.3 99. 10.4 6.15 145. 56. 

 95575 129. 71. 11.9 102. 10.6 6.19 149. 60. 

 

 MEAN 132. 72. 11.2 100. 9.9 5.40 145. 52. 

 S.D. 16.8 7.6 0.44 1.6 0.79 0.728 2.3 13.4 

 S.E. 7.5 3.4 0.20 0.7 0.35 0.326 1.0 6.0 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 

256 of 435
 TABLE A22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TOTAL A/G TOTAL UREA CREAT- ALKALINE ALANINE ASPARTAT 

 ANIMAL ALBUMIN PROTEIN GLOBULIN RATIO BILI NITROGEN ININE PHOS’TSE TRANSFER TRANSFER 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 g/dL g/dL g/dL mg/dL mg/dL mg/dL U/L U/L U/L 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM FEMALES 

 

 6664 4.7 6.6 2.0 2.37 0.12 15.5 0.2 76. 33. 105. 

 6674 4.6 6.5 2.0 2.35 0.15 12.0 0.3 170. 31. 73. 

 6686 4.4 6.1 1.8 2.47 0.14 12.4 0.2 106. 43. 101. 

 6712 4.5 6.5 2.0 2.29 0.08 12.5 0.2 126. 30. 85. 

 6717 4.4 6.2 1.9 2.35 0.10 11.9 0.2 95. 55. 83. 

 

 MEAN 4.5 6.4 1.9 2.37 0.12 12.9 0.2 115. 38. 89. 

 S.D. 0.13 0.22 0.09 0.065 0.029 1.50 0.04 35.9 10.6 13.3 

 S.E. 0.06 0.10 0.04 0.029 0.013 0.67 0.02 16.0 4.7 5.9 

 N 5 5 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, U/L = INTERNATIONAL UNIT/LITER, g/dL = GRAMS/DECILITER 

 

257 of 435
 TABLE A22 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL SERUM CHEMISTRY VALUES DAY 5 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHOL- PHOS- POTAS- TRIGLY- 

 ANIMAL GLUCOSE ESTEROL CALCIUM CHLORIDE PHORUS SIUM SODIUM CERIDE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL mg/dL mg/dL mEq/L mg/dL mEq/L mEq/L mg/dL 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 1800 PPM FEMALES 

 

 6664 144. 91. 10.5 97. 7.9 4.77 143. 32. 

 6674 109. 95. 10.9 100. 9.1 5.00 144. 57. 

 6686 119. 69. 10.6 101. 8.1 4.94 142. 30. 

 6712 109. 57. 10.5 101. 9.0 4.77 143. 34. 

 6717 104. 50. 11.1 101. 9.1 4.51 142. 27. 

 

 MEAN 117. 72. 10.7 100. 8.6 4.80 143. 36. 

 S.D. 16.0 20.0 0.27 1.7 0.59 0.191 0.8 12.0 

 S.E. 7.2 9.0 0.12 0.8 0.26 0.085 0.4 5.4 

 N 5 5 5 5 5 5 5 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 mg/dL = MILLIGRAMS/DECILITER, mEq/L = MILLIEQUIVALENTS/LITER 

 PCHEv4.03 

 03/24/2008 

258 of 435
 TABLE A23 (UNSCHEDULED DEATH) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95554 GROUP 4: 5000 PPM MALE FOUND DEAD 02/07/08 DATE OF DEATH: 02/07/08 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GENERAL COMMENT GROSS: NOT POSITIVELY IDENTIFIED P 

 FINAL BODY WT(G) 336. BRONCHIAL LYMPH NODES 

 LUNGS GROSS: NOT FULLY COLLAPSED P 

 ALL LOBES 

 SKIN GROSS: MATTING, RED P 

 NASAL; BUCCAL 

 SPLEEN GROSS: AREA(S), WHITE P 

 MULTIPLE, IRREGULARLY SHAPED 

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 JOINT BRAIN CECUM COLON 

 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LARYNX NERVE, SCIATIC PANCREAS 

 PHARYNX PITUITARY PROSTATE RECTUM 

 SPINAL CORD SAL. GLAND MAND STOMACH SKELETAL MUSCLE 

 SEMINAL VESICLES TESTES THYROID GLANDS THYMUS 

 TRACHEA URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 PGRHv4.59 

 03/24/2008 

259 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95555 GROUP 1: 0 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.02 0.633 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 10.55 3.307 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.39 0.749 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.26 0.395 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 319. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

260

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95556 GROUP 1: 0 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. KIDNEYS GROSS: AREA(S), DEPRESSED P 

 BRAIN 2.08 0.665 FEW, IRREGULARLY SHAPED, IN CORTEX, RIGHT 

 LIVER 9.20 2.939 LUNGS GROSS: AREA(S), DARK RED P 

 KIDNEYS 2.56 0.818 FEW, IRREGULARLY SHAPED, ALL LOBES 

 LUNGS 1.20 0.383 NO SIGNIFICANT 

 FINAL BODY WT(G) 313. CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 JOINT BRAIN CECUM COLON 

 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LARYNX NERVE, SCIATIC PANCREAS PHARYNX 

 PITUITARY PROSTATE RECTUM SPINAL CORD 

 SAL. GLAND MAND STOMACH SKELETAL MUSCLE SKIN 

 SPLEEN SEMINAL VESICLES TESTES THYROID GLANDS 

 THYMUS TRACHEA URINARY BLADDER PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

261 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95558 GROUP 1: 0 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.92 0.678 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 8.30 2.933 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.20 0.777 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.26 0.445 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 283. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

262

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95574 GROUP 1: 0 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.89 0.647 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 9.08 3.110 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.12 0.726 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.21 0.414 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 292. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

263

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95577 GROUP 1: 0 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.08 0.615 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 10.86 3.213 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.72 0.805 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.41 0.417 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 338. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

264

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95559 GROUP 2: 1250 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.97 0.659 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 8.91 2.980 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.24 0.749 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.10 0.368 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 299. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

265

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95561 GROUP 2: 1250 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. THYMUS GROSS: AREA(S), DARK RED P 

 BRAIN 1.95 0.644 MULTIPLE, PINPOINT 

 LIVER 9.16 3.023 NO SIGNIFICANT 

 KIDNEYS 2.28 0.752 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.28 0.422 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 303. DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS TRACHEA URINARY BLADDER 

 PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

266 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95566 GROUP 2: 1250 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.92 0.730 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.75 2.567 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.01 0.764 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.11 0.422 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 263. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

267

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95573 GROUP 2: 1250 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.97 0.668 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 9.15 3.102 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.41 0.817 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.25 0.424 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 295. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

268

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95576 GROUP 2: 1250 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. KIDNEYS GROSS: AREA(S), DEPRESSED P 

 BRAIN 1.99 0.638 FEW, PINPOINT, IN CORTEX, LEFT 

 LIVER 9.50 3.045 NO SIGNIFICANT 

 KIDNEYS 2.58 0.827 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.33 0.426 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 312. DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX NERVE, SCIATIC PANCREAS 

 PHARYNX PITUITARY PROSTATE RECTUM 

 SPINAL CORD SAL. GLAND MAND STOMACH SKELETAL MUSCLE 

 SKIN SPLEEN SEMINAL VESICLES TESTES 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

269 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 11 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95560 GROUP 3: 2500 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.78 0.667 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 7.98 2.989 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.23 0.835 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.05 0.393 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 267. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

270

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 12 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95564 GROUP 3: 2500 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.92 0.636 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 9.55 3.162 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.22 0.735 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.25 0.414 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 302. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

271

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 13 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95565 GROUP 3: 2500 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.95 0.633 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 8.55 2.776 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.24 0.727 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.16 0.377 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 308. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

272

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 14 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95569 GROUP 3: 2500 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. STOMACH GROSS: CYST(S) P 

 BRAIN 2.00 0.702 FEW, IRREGULARLY SHAPED, NONGLANDULAR PORTION 

 LIVER 7.99 2.804 NO SIGNIFICANT 

 KIDNEYS 2.31 0.811 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.19 0.418 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 285. DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND SKELETAL MUSCLE 

 SKIN SPLEEN SEMINAL VESICLES TESTES 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

273 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 15 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95578 GROUP 3: 2500 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.01 0.710 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 7.93 2.802 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.17 0.767 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.15 0.406 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 283. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

274

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 16 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95563 GROUP 4: 5000 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.92 0.610 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 9.54 3.029 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.48 0.787 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.39 0.441 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 315. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

275

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 17 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95568 GROUP 4: 5000 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.99 0.703 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 8.05 2.845 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.35 0.830 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.38 0.488 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 283. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

276

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 18 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95570 GROUP 4: 5000 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. TEETH GROSS: MALALIGNED P 

 BRAIN 2.01 0.720 UPPER INCISOR, BILATERAL; CEO MALALIGNED 

 LIVER 8.20 2.939 NO SIGNIFICANT 

 KIDNEYS 2.14 0.767 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.19 0.427 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 279. DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

277 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 19 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95572 GROUP 4: 5000 PPM MALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.96 0.737 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 7.50 2.820 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.09 0.786 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.03 0.387 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 266. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

278

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 20 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95587 GROUP 1: 0 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.00 1.087 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.46 2.967 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.43 0.777 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.01 0.549 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 184. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

279

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 21 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95591 GROUP 1: 0 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.85 0.881 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.89 3.281 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.57 0.748 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.14 0.543 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 210. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

280

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 22 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95594 GROUP 1: 0 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BRAIN 1.86 0.899 BOTH HORNS 

 LIVER 6.17 2.981 NO SIGNIFICANT 

 KIDNEYS 1.47 0.710 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 0.99 0.478 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 207. DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 VAGINA CERVIX PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

281 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 23 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95599 GROUP 1: 0 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BRAIN 1.70 0.885 BOTH HORNS 

 LIVER 5.92 3.083 NO SIGNIFICANT 

 KIDNEYS 1.29 0.672 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.00 0.521 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 192. DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 VAGINA CERVIX PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

282 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 24 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95600 GROUP 1: 0 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BRAIN 1.90 0.960 BOTH HORNS 

 LIVER 5.95 3.005 NO SIGNIFICANT 

 KIDNEYS 1.39 0.702 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.08 0.545 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 198. DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 VAGINA CERVIX PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

283 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 25 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95579 GROUP 2: 1250 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.78 0.942 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.12 3.238 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.34 0.709 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.01 0.534 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 189. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

284

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 26 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95586 GROUP 2: 1250 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.81 0.887 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.52 3.196 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.55 0.760 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.16 0.569 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 204. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

285

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 27 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95588 GROUP 2: 1250 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BRAIN 1.82 0.929 BOTH HORNS 

 LIVER 6.10 3.112 NO SIGNIFICANT 

 KIDNEYS 1.47 0.750 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.12 0.571 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 196. DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 VAGINA CERVIX PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

286 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 28 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95595 GROUP 2: 1250 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.96 0.990 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.91 2.985 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.45 0.732 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.06 0.535 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 198. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

287

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 29 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95603 GROUP 2: 1250 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.74 0.926 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.74 3.053 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.47 0.782 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.88 0.468 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 188. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

288

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 30 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95580 GROUP 3: 2500 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.77 0.908 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.74 2.944 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.55 0.795 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.88 0.451 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 195. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

289

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 31 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95589 GROUP 3: 2500 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.77 0.868 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.26 3.069 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.34 0.657 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.86 0.422 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 204. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

290

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 32 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95593 GROUP 3: 2500 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.75 0.907 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.34 2.767 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.37 0.710 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.86 0.446 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 193. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

291

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 33 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95597 GROUP 3: 2500 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.00 0.943 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.73 3.175 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.63 0.769 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.13 0.533 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 212. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

292

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 34 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95598 GROUP 3: 2500 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.81 1.034 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.62 3.211 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.28 0.731 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.92 0.526 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 175. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

293

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 35 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95581 GROUP 4: 5000 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.73 0.961 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.08 2.822 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.41 0.783 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.02 0.567 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 180. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

294

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 36 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95583 GROUP 4: 5000 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.89 0.969 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.59 2.867 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.34 0.687 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.03 0.528 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 195. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

295

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 37 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95590 GROUP 4: 5000 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.87 1.000 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.56 2.973 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.28 0.684 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.98 0.524 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 187. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

296

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 38 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95592 GROUP 4: 5000 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.94 0.946 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.18 3.015 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.45 0.707 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.94 0.459 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 205. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

297

 

 of 435
 TABLE A24 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 39 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95601 GROUP 4: 5000 PPM FEMALE SCHEDULED EUTH 02/11/08 DATE OF DEATH: 02/11/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. STOMACH GROSS: CONTENTS, YELLOW P 

 BRAIN 1.81 0.910 SKIN GROSS: SCABBING P 

 LIVER 6.15 3.090 VENTRAL THORACIC; CEO SCABBING 

 KIDNEYS 1.45 0.729 NO SIGNIFICANT 

 LUNGS 1.10 0.553 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 FINAL BODY WT(G) 199. JOINT BRAIN CECUM COLON 

 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 SKELETAL MUSCLE SPLEEN THYROID GLANDS THYMUS 

 TRACHEA URINARY BLADDER UTERUS VAGINA 

 CERVIX PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 PGRHv4.59 

 03/24/2008 

298 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95557 GROUP 1: 1800 PPM MALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.12 0.697 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 9.90 3.257 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.49 0.819 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.39 0.457 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 304. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

299

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95562 GROUP 1: 1800 PPM MALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. GENERAL COMMENT GROSS: ORGAN DAMAGED AT NECROPSY P 

 BRAIN 2.05 0.623 THYROID GLANDS, BILATERAL 

 LIVER 9.89 3.006 NO SIGNIFICANT 

 KIDNEYS 2.44 0.742 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.37 0.416 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 329. DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

300 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95567 GROUP 1: 1800 PPM MALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.97 0.659 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 8.84 2.957 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.66 0.890 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.35 0.452 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 299. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

301

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95571 GROUP 1: 1800 PPM MALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. DUODENUM GROSS: CONTENTS, DARK RED P 

 BRAIN 2.03 0.625 ILEUM GROSS: CONTENTS, DARK RED P 

 LIVER 10.29 3.166 PANCREAS GROSS: PALE P 

 KIDNEYS 2.68 0.825 STOMACH GROSS: CONTENTS, DARK RED P 

 LUNGS 1.24 0.382 NO SIGNIFICANT 

 FINAL BODY WT(G) 325. CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 JOINT BRAIN CECUM COLON 

 EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS JEJUNUM KIDNEYS LYMPH NODE, MAND 

 LAC. GLAND EXOR LIVER LYMPH NODE, MES LUNGS 

 LARYNX NERVE, SCIATIC PHARYNX PITUITARY 

 PROSTATE RECTUM SPINAL CORD SAL. GLAND MAND 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

302 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 95575 GROUP 1: 1800 PPM MALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 2.16 0.643 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 10.24 3.048 JOINT BRAIN CECUM COLON 

 KIDNEYS 2.67 0.795 DUODENUM EPIDIDYMIDES ESOPHAGUS EYES/OPTIC N. 

 LUNGS 1.34 0.399 HEART HARDERIAN GLANDS ILEUM JEJUNUM 

 FINAL BODY WT(G) 336. KIDNEYS LYMPH NODE, MAND LAC. GLAND EXOR LIVER 

 LYMPH NODE, MES LUNGS LARYNX NERVE, SCIATIC 

 PANCREAS PHARYNX PITUITARY PROSTATE 

 RECTUM SPINAL CORD SAL. GLAND MAND STOMACH 

 SKELETAL MUSCLE SKIN SPLEEN SEMINAL VESICLES 

 TESTES THYROID GLANDS THYMUS TRACHEA 

 URINARY BLADDER PEYER’S PATCHES LYMPH NODE, MED LYMPH NODE, BRON 

 NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

303

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 6664 GROUP 1: 1800 PPM FEMALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BRAIN 1.79 0.923 BOTH HORNS 

 LIVER 6.14 3.165 NO SIGNIFICANT 

 KIDNEYS 1.51 0.778 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LUNGS 1.02 0.526 JOINT BRAIN CECUM COLON 

 FINAL BODY WT(G) 194. DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 VAGINA CERVIX PEYER’S PATCHES LYMPH NODE, MED 

 LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

304 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 6674 GROUP 1: 1800 PPM FEMALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.89 0.922 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.52 3.180 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.55 0.756 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.99 0.483 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 205. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

305

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 6686 GROUP 1: 1800 PPM FEMALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.78 0.957 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.70 3.065 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.59 0.855 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 0.98 0.527 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 186. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

306

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 9 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 6712 GROUP 1: 1800 PPM FEMALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.82 1.058 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 5.27 3.064 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.46 0.849 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.05 0.610 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 172. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

307

 

 of 435
 TABLE A25 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 10 

 INDIVIDUAL MACROSCOPIC FINDINGS 

 

 

 ANIMAL NO. 6717 GROUP 1: 1800 PPM FEMALE SCHEDULED EUTH 02/14/08 DATE OF DEATH: 02/14/08 STUDY DAY: 5 

 GRADE 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ORGAN WEIGHT ABS.(G) REL. NO SIGNIFICANT 

 BRAIN 1.85 0.864 CHANGES OBSERVED GROSS:ADRENAL GLANDS AORTA STERNEBRAE FEMUR 

 LIVER 6.54 3.056 JOINT BRAIN CECUM COLON 

 KIDNEYS 1.80 0.841 DUODENUM ESOPHAGUS EYES/OPTIC N. HEART 

 LUNGS 1.15 0.537 HARDERIAN GLANDS ILEUM JEJUNUM KIDNEYS 

 FINAL BODY WT(G) 214. LYMPH NODE, MAND LAC. GLAND EXOR LIVER LYMPH NODE, MES 

 LUNGS LARYNX MAMMARY GLAND NERVE, SCIATIC 

 OVIDUCTS OVARIES PANCREAS PHARYNX 

 PITUITARY RECTUM SPINAL CORD SAL. GLAND MAND 

 STOMACH SKELETAL MUSCLE SKIN SPLEEN 

 THYROID GLANDS THYMUS TRACHEA URINARY BLADDER 

 UTERUS VAGINA CERVIX PEYER’S PATCHES 

 LYMPH NODE, MED LYMPH NODE, BRON NASAL CAVITY 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 PGRHv4.59 

 03/24/2008 

308 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 MALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95555 319. 2.02 10.55 2.39 1.26 

 95556 313. 2.08 9.20 2.56 1.20 

 95558 283. 1.92 8.30 2.20 1.26 

 95574 292. 1.89 9.08 2.12 1.21 

 95577 338. 2.08 10.86 2.72 1.41 

 

 MEAN 309. 2.00 9.60 2.40 1.27 

 S.D. 21.9 0.089 1.074 0.248 0.084 

 S.E. 9.8 0.040 0.480 0.111 0.038 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

309 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 MALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95559 299. 1.97 8.91 2.24 1.10 

 95561 303. 1.95 9.16 2.28 1.28 

 95566 263. 1.92 6.75 2.01 1.11 

 95573 295. 1.97 9.15 2.41 1.25 

 95576 312. 1.99 9.50 2.58 1.33 

 

 MEAN 294. 1.96 8.69 2.30 1.21 

 S.D. 18.6 0.026 1.107 0.211 0.104 

 S.E. 8.3 0.012 0.495 0.094 0.046 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

310 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 MALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95560 267. 1.78 7.98 2.23 1.05 

 95564 302. 1.92 9.55 2.22 1.25 

 95565 308. 1.95 8.55 2.24 1.16 

 95569 285. 2.00 7.99 2.31 1.19 

 95578 283. 2.01 7.93 2.17 1.15 

 

 MEAN 289. 1.93 8.40 2.23 1.16 

 S.D. 16.3 0.093 0.691 0.050 0.073 

 S.E. 7.3 0.041 0.309 0.022 0.033 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

311 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 MALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95563 315. 1.92 9.54 2.48 1.39 

 95568 283. 1.99 8.05 2.35 1.38 

 95570 279. 2.01 8.20 2.14 1.19 

 95572 266. 1.96 7.50 2.09 1.03 

 

 MEAN 286. 1.97 8.32 2.27 1.25 

 S.D. 20.8 0.039 0.866 0.182 0.172 

 S.E. 10.4 0.020 0.433 0.091 0.086 

 N 4 4 4 4 4 

 

 FBW = FINAL BODY WEIGHT 

 

312 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 FEMALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95587 184. 2.00 5.46 1.43 1.01 

 95591 210. 1.85 6.89 1.57 1.14 

 95594 207. 1.86 6.17 1.47 0.99 

 95599 192. 1.70 5.92 1.29 1.00 

 95600 198. 1.90 5.95 1.39 1.08 

 

 MEAN 198. 1.86 6.08 1.43 1.04 

 S.D. 10.7 0.108 0.522 0.103 0.064 

 S.E. 4.8 0.048 0.234 0.046 0.029 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

313 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 FEMALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95579 189. 1.78 6.12 1.34 1.01 

 95586 204. 1.81 6.52 1.55 1.16 

 95588 196. 1.82 6.10 1.47 1.12 

 95595 198. 1.96 5.91 1.45 1.06 

 95603 188. 1.74 5.74 1.47 0.88 

 

 MEAN 195. 1.82 6.08 1.46 1.05 

 S.D. 6.6 0.083 0.292 0.075 0.109 

 S.E. 3.0 0.037 0.130 0.034 0.049 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

314 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 FEMALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95580 195. 1.77 5.74 1.55 0.88 

 95589 204. 1.77 6.26 1.34 0.86 

 95593 193. 1.75 5.34 1.37 0.86 

 95597 212. 2.00 6.73 1.63 1.13 

 95598 175. 1.81 5.62 1.28 0.92 

 

 MEAN 196. 1.82 5.94 1.43 0.93 

 S.D. 13.9 0.103 0.554 0.149 0.114 

 S.E. 6.2 0.046 0.248 0.067 0.051 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

315 of 435
 TABLE A26 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 FEMALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95581 180. 1.73 5.08 1.41 1.02 

 95583 195. 1.89 5.59 1.34 1.03 

 95590 187. 1.87 5.56 1.28 0.98 

 95592 205. 1.94 6.18 1.45 0.94 

 95601 199. 1.81 6.15 1.45 1.10 

 

 MEAN 193. 1.85 5.71 1.39 1.01 

 S.D. 9.9 0.081 0.461 0.074 0.060 

 S.E. 4.4 0.036 0.206 0.033 0.027 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

316

 03/24/2008 

 of 435
 TABLE A27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 MALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 304. 2.12 9.90 2.49 1.39 

 95562 329. 2.05 9.89 2.44 1.37 

 95567 299. 1.97 8.84 2.66 1.35 

 95571 325. 2.03 10.29 2.68 1.24 

 95575 336. 2.16 10.24 2.67 1.34 

 

 MEAN 319. 2.07 9.83 2.59 1.34 

 S.D. 16.2 0.075 0.585 0.114 0.058 

 S.E. 7.2 0.034 0.262 0.051 0.026 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

317 of 435
 TABLE A27 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL ORGAN WEIGHTS AND FINAL BODY WEIGHTS [G] DAY 5 

 

 FEMALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6664 194. 1.79 6.14 1.51 1.02 

 6674 205. 1.89 6.52 1.55 0.99 

 6686 186. 1.78 5.70 1.59 0.98 

 6712 172. 1.82 5.27 1.46 1.05 

 6717 214. 1.85 6.54 1.80 1.15 

 

 MEAN 194. 1.83 6.03 1.58 1.04 

 S.D. 16.3 0.045 0.547 0.131 0.068 

 S.E. 7.3 0.020 0.245 0.059 0.031 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

318

 03/24/2008 

 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 1 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 MALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95555 319. 0.633 3.307 0.749 0.395 

 95556 313. 0.665 2.939 0.818 0.383 

 95558 283. 0.678 2.933 0.777 0.445 

 95574 292. 0.647 3.110 0.726 0.414 

 95577 338. 0.615 3.213 0.805 0.417 

 

 MEAN 309. 0.648 3.100 0.775 0.411 

 S.D. 21.9 0.0250 0.1655 0.0382 0.0237 

 S.E. 9.8 0.0112 0.0740 0.0171 0.0106 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

319 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 2 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 MALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95559 299. 0.659 2.980 0.749 0.368 

 95561 303. 0.644 3.023 0.752 0.422 

 95566 263. 0.730 2.567 0.764 0.422 

 95573 295. 0.668 3.102 0.817 0.424 

 95576 312. 0.638 3.045 0.827 0.426 

 

 MEAN 294. 0.668 2.943 0.782 0.412 

 S.D. 18.6 0.0367 0.2150 0.0373 0.0249 

 S.E. 8.3 0.0164 0.0961 0.0167 0.0111 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

320 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 3 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 MALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95560 267. 0.667 2.989 0.835 0.393 

 95564 302. 0.636 3.162 0.735 0.414 

 95565 308. 0.633 2.776 0.727 0.377 

 95569 285. 0.702 2.804 0.811 0.418 

 95578 283. 0.710 2.802 0.767 0.406 

 

 MEAN 289. 0.670 2.907 0.775 0.402 

 S.D. 16.3 0.0359 0.1662 0.0471 0.0167 

 S.E. 7.3 0.0161 0.0743 0.0211 0.0075 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

321 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 4 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 MALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95563 315. 0.610 3.029 0.787 0.441 

 95568 283. 0.703 2.845 0.830 0.488 

 95570 279. 0.720 2.939 0.767 0.427 

 95572 266. 0.737 2.820 0.786 0.387 

 

 MEAN 286. 0.693 2.908 0.793 0.436 

 S.D. 20.8 0.0567 0.0954 0.0266 0.0417 

 S.E. 10.4 0.0284 0.0477 0.0133 0.0208 

 N 4 4 4 4 4 

 

 FBW = FINAL BODY WEIGHT 

 

322 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 5 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 FEMALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95587 184. 1.087 2.967 0.777 0.549 

 95591 210. 0.881 3.281 0.748 0.543 

 95594 207. 0.899 2.981 0.710 0.478 

 95599 192. 0.885 3.083 0.672 0.521 

 95600 198. 0.960 3.005 0.702 0.545 

 

 MEAN 198. 0.942 3.063 0.722 0.527 

 S.D. 10.7 0.0868 0.1296 0.0411 0.0296 

 S.E. 4.8 0.0388 0.0580 0.0184 0.0132 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

323 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 6 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 FEMALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95579 189. 0.942 3.238 0.709 0.534 

 95586 204. 0.887 3.196 0.760 0.569 

 95588 196. 0.929 3.112 0.750 0.571 

 95595 198. 0.990 2.985 0.732 0.535 

 95603 188. 0.926 3.053 0.782 0.468 

 

 MEAN 195. 0.935 3.117 0.747 0.535 

 S.D. 6.6 0.0371 0.1030 0.0277 0.0417 

 S.E. 3.0 0.0166 0.0461 0.0124 0.0186 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

324 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 7 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 FEMALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95580 195. 0.908 2.944 0.795 0.451 

 95589 204. 0.868 3.069 0.657 0.422 

 95593 193. 0.907 2.767 0.710 0.446 

 95597 212. 0.943 3.175 0.769 0.533 

 95598 175. 1.034 3.211 0.731 0.526 

 

 MEAN 196. 0.932 3.033 0.732 0.476 

 S.D. 13.9 0.0629 0.1815 0.0535 0.0505 

 S.E. 6.2 0.0281 0.0812 0.0239 0.0226 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

325 of 435
 TABLE A28 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS 10:14 24-MAR-08 PAGE 8 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 FEMALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95581 180. 0.961 2.822 0.783 0.567 

 95583 195. 0.969 2.867 0.687 0.528 

 95590 187. 1.000 2.973 0.684 0.524 

 95592 205. 0.946 3.015 0.707 0.459 

 95601 199. 0.910 3.090 0.729 0.553 

 

 MEAN 193. 0.957 2.953 0.718 0.526 

 S.D. 9.9 0.0329 0.1091 0.0406 0.0416 

 S.E. 4.4 0.0147 0.0488 0.0181 0.0186 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

326

 03/24/2008 

 of 435
 TABLE A29 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 MALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 304. 0.697 3.257 0.819 0.457 

 95562 329. 0.623 3.006 0.742 0.416 

 95567 299. 0.659 2.957 0.890 0.452 

 95571 325. 0.625 3.166 0.825 0.382 

 95575 336. 0.643 3.048 0.795 0.399 

 

 MEAN 319. 0.649 3.087 0.814 0.421 

 S.D. 16.2 0.0304 0.1226 0.0535 0.0327 

 S.E. 7.2 0.0136 0.0548 0.0239 0.0146 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

327 of 435
 TABLE A29 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL ORGAN WTS. RELATIVE TO FINAL BODY WTS. [G/100 G] DAY 5 

 

 FEMALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 ANIMAL FBW(G) BRAIN LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6664 194. 0.923 3.165 0.778 0.526 

 6674 205. 0.922 3.180 0.756 0.483 

 6686 186. 0.957 3.065 0.855 0.527 

 6712 172. 1.058 3.064 0.849 0.610 

 6717 214. 0.864 3.056 0.841 0.537 

 

 MEAN 194. 0.945 3.106 0.816 0.537 

 S.D. 16.3 0.0716 0.0610 0.0455 0.0460 

 S.E. 7.3 0.0320 0.0273 0.0203 0.0206 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

328

 03/24/2008 

 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 MALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95555 319. 2.02 522.277 118.317 62.376 

 95556 313. 2.08 442.308 123.077 57.692 

 95558 283. 1.92 432.292 114.583 65.625 

 95574 292. 1.89 480.423 112.169 64.021 

 95577 338. 2.08 522.115 130.769 67.788 

 

 MEAN 309. 2.00 479.883 119.783 63.500 

 S.D. 21.9 0.089 42.5966 7.3943 3.8135 

 S.E. 9.8 0.040 19.0498 3.3069 1.7054 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

329 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 MALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95559 299. 1.97 452.284 113.706 55.838 

 95561 303. 1.95 469.744 116.923 65.641 

 95566 263. 1.92 351.563 104.688 57.813 

 95573 295. 1.97 464.467 122.335 63.452 

 95576 312. 1.99 477.387 129.648 66.834 

 

 MEAN 294. 1.96 443.089 117.460 61.916 

 S.D. 18.6 0.026 51.9746 9.3517 4.8528 

 S.E. 8.3 0.012 23.2437 4.1822 2.1702 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

330 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 MALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95560 267. 1.78 448.315 125.281 58.989 

 95564 302. 1.92 497.396 115.625 65.104 

 95565 308. 1.95 438.462 114.872 59.487 

 95569 285. 2.00 399.500 115.500 59.500 

 95578 283. 2.01 394.527 107.960 57.214 

 

 MEAN 289. 1.93 435.640 115.848 60.059 

 S.D. 16.3 0.093 41.7697 6.1710 2.9720 

 S.E. 7.3 0.041 18.6800 2.7598 1.3291 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

331 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 4 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 MALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95563 315. 1.92 496.875 129.167 72.396 

 95568 283. 1.99 404.523 118.090 69.347 

 95570 279. 2.01 407.960 106.468 59.204 

 95572 266. 1.96 382.653 106.633 52.551 

 

 MEAN 286. 1.97 423.003 115.090 63.375 

 S.D. 20.8 0.039 50.5074 10.8478 9.1579 

 S.E. 10.4 0.020 25.2537 5.4239 4.5789 

 N 4 4 4 4 4 

 

 FBW = FINAL BODY WEIGHT 

 

332 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 5 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 FEMALE GROUP: 0 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95587 184. 2.00 273.000 71.500 50.500 

 95591 210. 1.85 372.432 84.865 61.622 

 95594 207. 1.86 331.720 79.032 53.226 

 95599 192. 1.70 348.235 75.882 58.824 

 95600 198. 1.90 313.158 73.158 56.842 

 

 MEAN 198. 1.86 327.709 76.887 56.203 

 S.D. 10.7 0.108 37.5578 5.2959 4.4167 

 S.E. 4.8 0.048 16.7964 2.3684 1.9752 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

333 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 6 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 FEMALE GROUP: 1250 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95579 189. 1.78 343.820 75.281 56.742 

 95586 204. 1.81 360.221 85.635 64.088 

 95588 196. 1.82 335.165 80.769 61.538 

 95595 198. 1.96 301.531 73.980 54.082 

 95603 188. 1.74 329.885 84.483 50.575 

 

 MEAN 195. 1.82 334.124 80.030 57.405 

 S.D. 6.6 0.083 21.5431 5.2666 5.4744 

 S.E. 3.0 0.037 9.6344 2.3553 2.4482 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

334 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 7 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 FEMALE GROUP: 2500 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95580 195. 1.77 324.294 87.571 49.718 

 95589 204. 1.77 353.672 75.706 48.588 

 95593 193. 1.75 305.143 78.286 49.143 

 95597 212. 2.00 336.500 81.500 56.500 

 95598 175. 1.81 310.497 70.718 50.829 

 

 MEAN 196. 1.82 326.021 78.756 50.956 

 S.D. 13.9 0.103 19.7120 6.3120 3.2086 

 S.E. 6.2 0.046 8.8155 2.8228 1.4349 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

335 of 435
 TABLE A30 (GROUPS 1-4) 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 8 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 FEMALE GROUP: 5000 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95581 180. 1.73 293.642 81.503 58.960 

 95583 195. 1.89 295.767 70.899 54.497 

 95590 187. 1.87 297.326 68.449 52.406 

 95592 205. 1.94 318.557 74.742 48.454 

 95601 199. 1.81 339.779 80.111 60.773 

 

 MEAN 193. 1.85 309.014 75.141 55.018 

 S.D. 9.9 0.081 19.9120 5.6593 4.9709 

 S.E. 4.4 0.036 8.9049 2.5309 2.2231 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

336

 03/24/2008 

 of 435
 TABLE A31 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 MALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95557 304. 2.12 466.981 117.453 65.566 

 95562 329. 2.05 482.439 119.024 66.829 

 95567 299. 1.97 448.731 135.025 68.528 

 95571 325. 2.03 506.897 132.020 61.084 

 95575 336. 2.16 474.074 123.611 62.037 

 

 MEAN 319. 2.07 475.824 125.427 64.809 

 S.D. 16.2 0.075 21.3577 7.8017 3.1640 

 S.E. 7.2 0.034 9.5514 3.4890 1.4150 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

337 of 435
 TABLE A31 (GROUP 5) 

 PROJECT NO.: 534011A A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL ORGAN WEIGHTS RELATIVE TO BRAIN WEIGHTS [G/100 G] DAY 5 

 

 FEMALE GROUP: 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 BRAIN WT 

 ANIMAL FBW(G) (GRAMS) LIVER KIDNEYS LUNGS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 6664 194. 1.79 343.017 84.358 56.983 

 6674 205. 1.89 344.974 82.011 52.381 

 6686 186. 1.78 320.225 89.326 55.056 

 6712 172. 1.82 289.560 80.220 57.692 

 6717 214. 1.85 353.514 97.297 62.162 

 

 MEAN 194. 1.83 330.258 86.642 56.855 

 S.D. 16.3 0.045 25.8708 6.8673 3.6102 

 S.E. 7.3 0.020 11.5698 3.0711 1.6145 

 N 5 5 5 5 5 

 

 FBW = FINAL BODY WEIGHT 

 

 POFBWv4.14 

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 03/24/2008 

 of 435
FINAL REPORT

Volume 2 of 2

(Appendices B through I)

STUDY TITLE

A 5-DAY REPEATED-DOSE INHALATION TOXICITY

STUDY OF IN SPRAGUE-DAWLEY RATS

STUDY NUMBER

STUDY DIRECTOR

STUDY INITIATION DATE

9 January 2008

STUDY COMPLETION DATE

14 May 2008

PERFORMING LABORATORY

SPONSOR

339 of 435
APPENDIX B

Certificate Of Analysis (Sponsor-Provided Data)

340 of 435
CERTIFICATE OF ANALYSIS 

jttn: 

- r 

. 

341 of 435
APPENDIX C

Exposure Atmosphere Generation Report (

342 of 435
A 5-DAY REPEATED-DOSE INHALATION TOXICITY

STUDY OF IN SPRAGUE-DAWLEY RATS

Exposure Atmosphere Generation Report

Inhalation Department

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TABLE OF CONTENTS

Page

Table Of Contents......................................................................................2

Index Of Figures ........................................................................................3

Index Of Tables..........................................................................................3

1. Exposure Methods .....................................................................................4

1.1. Exposure Regimen.......................................................................................4

1.2. Inhalation Exposure System Description.....................................................4

1.3. Animal Transport And Placement ...............................................................5

1.4. Exposure Environmental Conditions ...........................................................5

2. Test Atmosphere Generation Methods ....................................................6

3. Methods Of Characterization Of Exposure Atmospheres.....................8

3.1. Nominal Exposure Concentrations ..............................................................8

3.2. Analyzed Exposure Concentrations.............................................................8

3.2.1. Analytical Methods......................................................................................8

3.2.2. Gas Chromatograph Calibration ..................................................................9

3.3. Determination Of Homogeneity Of Exposure Atmospheres.....................11

4. Results Of Characterization Of Actual Exposure

Concentrations .........................................................................................12

4.1. Nominal Exposure Concentrations ............................................................12

4.2. Analyzed Exposure Concentrations...........................................................13

5. Key Study Personnel And Report Submission......................................14

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INDEX OF FIGURES

Page

1. Atmosphere Generation And Exposure System ........................................................16

INDEX OF TABLES

1. Daily Mean Chamber Temperature [Degrees Celsius]..............................................18

2. Daily Mean Chamber Relative Humidity [%] ...........................................................19

3. Daily Mean Chamber Ventilation Rate [SLPM] .......................................................20

4. Test Atmosphere Homogeneity Determination .........................................................21

5. Daily Nominal Concentrations [PPM].......................................................................24

6. Daily Mean Test Atmosphere Concentrations...........................................................25

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1. EXPOSURE METHODS

1.1. EXPOSURE REGIMEN

The test substance or filtered air (control group) was administered as a daily 6-hour

whole-body inhalation exposure. Exposures were conducted for 5 consecutive days for

Groups 1, 2, 3 and 5 and 2 consecutive days for Group 4. A detailed description of the

study design and exposure schedule is presented in the main report. The following table

presents the overall schedule for inhalation exposures:

Study Day Date

First Exposure (Groups 1-4) 0 6 February 2008

Last Exposure (Group 4) 1 7 February 2008

Last Exposure (Groups 1-3) 4 10 February 2008

First Exposure (Group 5) 3 9 February 2008

Last Exposure (Group 5) 7 13 February 2008

1.2. INHALATION EXPOSURE SYSTEM DESCRIPTION

Exposures were conducted in four 500-L stainless steel and glass whole-body inhalation

exposure chambers. One chamber was dedicated for each group with the exception of

Chamber 4. Following the termination of Group 4, an additional group (Group 5) was

added to the study and was exposed in Chamber 4. The following table presents the

chambers use for each group:

Group Number 1 2 3 4 5

Chamber Number 1 2 3 4 4

Target Exposure Concentration (ppm) 0 1250 2500 5000 1800

Chamber supply air was provided from a HEPA- and charcoal-filtered, temperature- and

humidity-controlled source. All test atmosphere chamber exhaust passed through carbon

scrubbers (Environtrol, Inc., Sewickley, PA) prior to the facility exhaust system, which

consisted of charcoal and HEPA filtration.

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1.3. ANIMAL TRANSPORT AND PLACEMENT

Animals were individually housed in stainless steel wire-mesh caging during the

exposures. Food and water were withheld during the exposure periods. Animals were

housed in a normal animal colony room during non-exposure hours. For the exposure

each day, the animals were transferred to exposure caging, transported to the exposure

chamber room, exposed for the requisite duration and returned to their home cages in the

animal colony room.

The cage batteries were rotated on a daily basis between 2 battery positions in the

chambers to help ensure a similar exposure for all animals within each group over the

duration of the exposure period.

1.4. EXPOSURE ENVIRONMENTAL CONDITIONS

Chamber temperature, relative humidity, ventilation rate and negative pressure within

each chamber were continually monitored and manually recorded at approximately

35-minute intervals. For each 6-hour exposure period, at least 10 data points were

collected per chamber. Chamber temperature and relative humidity were monitored with

an Omega Model No. HX94C Humidity and Temperature transmitter probe

(Omega Engineering, Inc., Stamford, CT). The mean temperature and mean relative

humidity were to be between 20°C to 24°C and 30% to 70%, respectively.

All chambers were operated under dynamic conditions, at least 12 to 15 air changes per

hour (100 to 125 liters per minute [LPM]) at a slight negative pressure. Chamber airflow

was monitored by a sharp-edge orifice plate and Dwyer Magnehelic® Indicating

Transmitter pressure gauge (Michigan City, IN). Each gauge was calibrated under the

conditions of exposure for conversion from pressure to airflow in standard liters per

minute (SLPM) through the use of a Fox Gas Mass Flowmeter Transmitter (Model FT2,

Fox Thermal Instruments, Marina, CA). Daily means for chamber temperature, relative

humidity and ventilation rate over the study period are presented in Tables 1 through 3 of

 -5- 

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this appendix. The following table summarizes the grand mean environmental conditions

for all groups:

Group 1 Group 2 Group 3 Group 4 Group 5

Temperature (oC): 21 21 20 21 21

Standard Deviation: 0.4 0.0 0.0 0.0 0.0

Relative Humidity (%): 56 58 53 56 51

Standard Deviation: 1.4 1.1 1.9 2.8 2.1

Chamber Ventilation Rate (SLPM): 113 111 111 113 112

Standard Deviation: 0.9 0.4 1.1 2.1 1.5

Exposure Days: 5 5 5 2 5

Oxygen content was measured during the method development phase for Groups 1

through 4 and during animal exposure for Group 5 using a Drager Pac III equipped with a

calibrated oxygen sensor (Draeger Safety, Pittsburgh, PA). Oxygen content was at least

19% for all groups.

The high concentration chamber was monitored for aerosol formation on 31 January 2008

during the method development phase of the study using an MIE High Pressure Industrial

Particulates Monitor (Model HPM-1000, Thermo Fisher Scientific, Franklin, MA) and an

Omega RD6110 chart recorder. No aerosol formation was observed.

2. TEST ATMOSPHERE GENERATION METHODS

A test substance atmosphere generation and exposure system is shown in Figure 1.

Vapors of the test substance were generated using a glass-bead column-type vaporization

system operated as follows: Liquid test substance was metered using a calibrated FMI

Lab Pump (Fluid Metering Inc., Syosset, NY) to the top of the vaporization column filled

with various sized glass beads. The following table summarizes the specifications for the

test substance delivery:

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Group

FMI Pump

Model No.

FMI Pump

Piston Head Size

Test Substance

Flowrate (mL/minute)

2 QG-20 1/8-inch 0.8

3 QG-6 1/4-inch 1.7

4 QG-20 1/4-inch 3.4

5 QG-20 1/4-inch 1.3

The vaporization column was wrapped with an electric heating tape (Omega Engineering

Co., Stamford, CT) controlled using a J-type thermocouple and digital temperature

controller. Using a Coilhose Pneumatics Regulator (model no. 8802K, East

Brunswick, NJ) and calibrated rotameter-type flowmeters (serial no. 115010-2,

Cole-Parmer, Vernon Hills, IL for Group 2 and model no. GF-4542-1225, Barnant

Co./Gilmont Instruments, Barrington, IL for Groups 3, 4 and 5), nitrogen was metered to

the bottom of each vaporization column. Vaporization occurred as the liquid test

substance coated the surface of the heated beads and nitrogen flowed up through the

column. The concentrated vapors were piped to the chamber inlet and diluted to the

desired concentration by mixing with the chamber supply air. For Group 1, nitrogen was

supplied to the chamber inlet using the aforementioned Coilhose Pneumatics Regulator

(model no. 8802K) and a calibrated Gilmont rotameter-type flowmeter and diluted with

chamber supply air. The parameters used for this study are summarized in the following

table:

Group

Column Dimensions

(ID × height) (cm)

Column

Temperature (°C)

Nitrogen

Flowrate (LPM)

1 NA NA 5.5

2 2.4 × 20 55 2.5

3 2.4 × 35 65 4.7

4 2.4 × 35 69 4.5

5 2.4 × 35 69 4.5

NA = Not Applicable

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3. METHODS OF CHARACTERIZATION OF EXPOSURE ATMOSPHERES

3.1. NOMINAL EXPOSURE CONCENTRATIONS

A nominal exposure concentration was calculated daily for each test substance group

from the total amount of test substance used during the exposure and the total volume of

air passed through the chamber during that day’s exposure. The amount of test substance

used was obtained by weighing the test substance reservoir prior to and after each day’s

exposure. The total volume of air passed through each chamber was calculated from the

daily average chamber ventilation flowrate in LPM and the exposure duration. The

nominal concentration was calculated as follows.

WT × MV × 106

Concentration (ppm) = GMW × CVR × DUR

Where:

WT = Weight of test substance used, grams

MV = Molar volume at 730 mmHg and 21oC, 25.11 L/mole

106 = ppm conversion factor

GMW = Test substance gram molecular weight, 200.05 g/mole

CVR = Daily mean chamber ventilation rate for a given day, LPM

DUR = Duration of the daily exposure, minutes

3.2. ANALYZED EXPOSURE CONCENTRATIONS

3.2.1. ANALYTICAL METHODS

Analyzed exposure concentrations were determined at approximately 30-minute intervals

using a gas chromatograph (GC). Samples were collected from the approximate

animal-breathing zone of the inhalation exposure chambers via 1/8-inch Teflon® tubing.

Samples were collected manually using an external multi-position valve (Model E16,

Valco Instruments Co., Inc., Houston, TX) and a Hewlett Packard Model 3396 Series II

integrator (with BASIC program). Gas sample injection onto the chromatography

column occurred via an internal gas-sampling valve with a sample loop. The

chromatograph was displayed and the area under the sample peak was calculated and

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stored. The concentration in parts per million (ppm) was calculated using an ln-quadratic

equation based on the GC calibration curve. The following table summarizes the

operational parameters for the gas chromatography methods:

Instrument: Hewlett Packard 5890 Series II

Detector: Flame Ionization (FID)

Column: J&W Scientific, DB-5, 30m × 0.530mm ID, 0.5-micron film thickness

Gases Pressure (psig) Flow Rate (mL/minute)

Carrier - Helium: 14 10

Fuel - Hydrogen: 18 31

Air: 35 294

Temperatures (oC)

Column: 100

Detector: 250

Injector: 100

Auxiliary: 100

Integrator: Hewlett Packard Model 3396 Series II

Run Parameters

Chart Zero Offset: 0

Chart Attenuation: 8

Chart Speed: 2.0 cm/minute

Peak Area Rejection Value: 0

Peak Threshold: 4

Peak Width: 0.04

Retention Time (minutes): Approximately 0.757

3.2.2. GAS CHROMATOGRAPH CALIBRATION

The GC was calibrated using gas-phase standards prepared to contain a known vapor

concentrations of the test substance in 5- and 10-L Tedlar® gas bags (SKC, Inc., Eighty

Four, PA). Standard bags were prepared by metering a known volume of air into the bag

using a dry test meter (Model DTM-200A, Elster American Meter Co., Nebraska

 -9- 

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City, NE) and then injecting a known volume of test substance into the bag. Using a

hand-held heated blower, the bag was warmed until total volatilization of the test

substance was visually observed. Concentrations of the gas-phase standards are

calculated as follows:

VOL × R × T × D × 10-3 × 106

Concentration (ppm) = L × GMW × P

Where:

VOL = Volume of test substance vaporized into bag, μL

R = Universal constant, 62.36 L mmHg/mole K

T = Nominal laboratory temperature in K (273 + 21°C = 294 K)

D = Density of the test substance, 1.487 g/mL

L = Volume of air used to prepare bag, 30 L

GMW = Gram molecular weight, 200.05 g/mole

P = Nominal laboratory barometric pressure, 730 mmHg

10-3 = μL to mL conversion factor

106 = Conversion factor to ppm

Prior to initiation of animal exposures, the GC was calibrated with standards prepared

and analyzed in triplicate. The calibration curve was defined using standards prepared at

5 vapor concentrations spanning an appropriate range relative to the target exposure

concentrations for the study. The prime calibration curve was prepared using the

quadratic formula and was used to calculate exposure concentrations for all groups. The

peak area (y) and the theoretical concentrations of the calibration standards (x) were fit

with least-squares regression analysis to the ln-quadratic function:

ln (y) = a × [ln (x)]2 + b × ln (x) + c

Each day, prior to the initiation of exposure, 1 of the 5 standards was prepared and

analyzed, and the prime calibration curve was used to perform a calibration check of the

GC. The GC was considered to be within normal calibration limits if the analyzed

concentration of the prepared standard was within ± 10% of the known concentration.

The following table summarizes the standard parameters:

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Standard

(ppm)

Volume of Test

Substance (μL)

Total Dilution

Air Volume (L)

933 40 8

2240 60 5

3360 90 5

4978 80 3

6223 100 3

3.3. DETERMINATION OF HOMOGENEITY OF EXPOSURE ATMOSPHERES

Homogeneity of exposure concentrations was evaluated during the method development

phase of the study. Four test locations and a reference location were used for these

determinations. The test locations were Lower Front, Lower Rear, Upper Front and

Upper Rear. Samples were collected and analyzed on the GC as rapidly as possible by

alternating from the reference location and then to a test location. The measured

concentration was calculated as a percent difference for each position from the reference

location. Homogeneity was performed in triplicate for each test substance exposure

chamber. The results are presented in Table 4 of this appendix. The following table

summarizes the mean data of the replicates for each test substance chamber:

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Chamber Number Test Location Mean % From Reference

2 Lower Front -2.1

Lower Rear 0.9

Upper Front 0.1

Upper Rear -2.0

3 Lower Front -0.7

Lower Rear 0.2

Upper Front -0.7

Upper Rear -0.4

4 Lower Front 1.2

Lower Rear 0.9

Upper Front 1.2

Upper Rear -0.7

These data indicate that the homogeneity of each exposure chamber atmosphere was

adequate for the purpose of this study.

4. RESULTS OF CHARACTERIZATION OF ACTUAL EXPOSURE

CONCENTRATIONS

4.1. NOMINAL EXPOSURE CONCENTRATIONS

Daily nominal concentrations for each test substance group are presented in Table 5 of

this appendix. The following table summarizes the overall mean nominal concentrations

for each test substance group:

Group 2 Group 3 Group 4 Group 5

Mean Concentration (ppm): 1303 2700 5323 2186

Standard Deviation: 7.7 38.1 78.5 16.9

N: 5 5 2 5

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4.2. ANALYZED EXPOSURE CONCENTRATIONS

Daily mean analyzed concentrations for each group are presented in Table 6 of this

appendix. The following table summarizes the overall mean analyzed concentrations for

each group:

Group 1 Group 2 Group 3 Group 4 Group 5

Mean Concentration (ppm): 0 1247 2536 5039 1793

Standard Deviation: 0.0 5.8 32.4 14.8 7.2

N: 5 5 5 2 5

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53401 1 

5. KEY STUDY PERSONNEL AND REPORT SUBMISSION 

Report Prepared By:-, 

Report Reviewed By: 

Study Personnel: 

-14- 

356 of 435
FIGURE 1

 -15- 

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FIGURE 1: ATMOSPHERE GENERATION AND EXPOSURE SYSTEM

500-Liter Chamber

Supply Air

Rotameter and

Regulator

Glass Bead

Column

Nitrogen

Source

Test Article

Temp. Reservoir

Controller

123

Inlet

FMI

Pump

To Exhaust

Activated

Carbon Scrubber

Orifice Meter

 -16- 

358 of 435
TABLES 1-6

 -17- 

359 of 435
 INHALATION TABLE 1 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 DAILY MEAN CHAMBER TEMPERATURE [DEGREES CELSIUS] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DATE GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ---------------------------------------------------------------------------------------------------------------------------------- 

 02/06/08 21. 21. 20. 21. NA 

 02/07/08 21. 21. 20. 21. NA 

 02/08/08 21. 21. 20. NA NA 

 02/09/08 20. 21. 20. NA 21. 

 02/10/08 21. 21. 20. NA 21. 

 02/11/08 NA NA NA NA 21. 

 02/12/08 NA NA NA NA 21. 

 02/13/08 NA NA NA NA 21. 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRAND MEAN 21. 21. 20. 21. 21. 

 S.D. 0.4 0.0 0.0 0.0 0.0 

 C.V.(%) 1.90 0.00 0.00 0.00 0.00 

 N 5 5 5 2 5 

 

 NA = NOT APPLICABLE 

 

 MANUALv1.0 

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360 of 435
 INHALATION TABLE 2 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 DAILY MEAN CHAMBER RELATIVE HUMIDITY [%] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DATE GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ---------------------------------------------------------------------------------------------------------------------------------- 

 02/06/08 57. 60. 53. 58. NA 

 02/07/08 57. 58. 53. 54. NA 

 02/08/08 55. 57. 52. NA NA 

 02/09/08 57. 59. 56. NA 55. 

 02/10/08 54. 58. 51. NA 51. 

 02/11/08 NA NA NA NA 51. 

 02/12/08 NA NA NA NA 50. 

 02/13/08 NA NA NA NA 50. 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRAND MEAN 56. 58. 53. 56. 51. 

 S.D. 1.4 1.1 1.9 2.8 2.1 

 C.V.(%) 2.50 1.90 3.58 5.00 4.12 

 N 5 5 5 2 5 

 

 NA = NOT APPLICABLE 

 

 MANUALv1.0 

 03/17/2008 

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361 of 435
 INHALATION TABLE 3 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 DAILY MEAN CHAMBER VENTILATION RATE [SLPM] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DATE GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ---------------------------------------------------------------------------------------------------------------------------------- 

 02/06/08 111. 112. 110. 114. NA 

 02/07/08 113. 111. 110. 111. NA 

 02/08/08 113. 111. 110. NA NA 

 02/09/08 113. 111. 112. NA 113. 

 02/10/08 113. 111. 112. NA 113. 

 02/11/08 NA NA NA NA 112. 

 02/12/08 NA NA NA NA 110. 

 02/13/08 NA NA NA NA 110. 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRAND MEAN 113. 111. 111. 113. 112. 

 S.D. 0.9 0.4 1.1 2.1 1.5 

 C.V.(%) 0.80 0.36 0.99 1.86 1.34 

 N 5 5 5 2 5 

 

 NA = NOT APPLICABLE 

 

 MANUALv1.0 

 03/17/2008 

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362 of 435
 INHALATION TABLE 4 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 TEST ATMOSPHERE HOMOGENEITY DETERMINATION 

 

 --------------------------------------------------------------------------------------------------------------------------------- 

 TARGET: 1250 PPM CHAMBER #2 

 --------------------------------------------------------------------------------------------------------------------------------- 

 DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN % 

 --------------------------------------------------------------------------------------------------------------------------------- 

 01/30/08 REFERENCE PORT 1244 

 LOWER FRONT 1229 -1.2 

 

 REFERENCE PORT 1235 

 LOWER FRONT 1217 -1.5 

 

 REFERENCE PORT 1234 

 LOWER FRONT 1189 -3.6 -2.1 

 

 REFERENCE PORT 1180 

 LOWER REAR 1221 3.5 

 

 REFERENCE PORT 1227 

 LOWER REAR 1220 -0.6 

 

 REFERENCE PORT 1230 

 LOWER REAR 1227 -0.2 0.9 

 

 REFERENCE PORT 1242 

 UPPER FRONT 1221 -1.7 

 

 REFERENCE PORT 1170 

 UPPER FRONT 1202 2.7 

 

 REFERENCE PORT 1220 

 UPPER FRONT 1211 -0.7 0.1 

 

 REFERENCE PORT 1240 

 UPPER REAR 1213 -2.2 

 

 REFERENCE PORT 1227 

 UPPER REAR 1179 -3.9 

 

 REFERENCE PORT 1214 

 UPPER REAR 1216 0.2 -2.0 

 -------------------------------------------------------------------------------------------------------------------------------- 

 PPM = PARTS PER MILLION 

 

 

 

-21- 

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 INHALATION TABLE 4 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 TEST ATMOSPHERE HOMOGENEITY DETERMINATION 

 

 --------------------------------------------------------------------------------------------------------------------------------- 

 TARGET: 2500 PPM CHAMBER #3 

 --------------------------------------------------------------------------------------------------------------------------------- 

 DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN % 

 --------------------------------------------------------------------------------------------------------------------------------- 

 01/30/08 REFERENCE PORT 2591 

 LOWER FRONT 2585 -0.2 

 

 REFERENCE PORT 2516 

 LOWER FRONT 2470 -1.8 

 

 REFERENCE PORT 2474 

 LOWER FRONT 2473 0.0 -0.7 

 

 REFERENCE PORT 2599 

 LOWER REAR 2609 0.4 

 

 REFERENCE PORT 2489 

 LOWER REAR 2470 -0.8 

 

 REFERENCE PORT 2484 

 LOWER REAR 2511 1.1 0.2 

 

 REFERENCE PORT 2596 

 UPPER FRONT 2584 -0.5 

 

 REFERENCE PORT 2477 

 UPPER FRONT 2479 0.1 

 

 REFERENCE PORT 2517 

 UPPER FRONT 2471 -1.8 -0.7 

 

 REFERENCE PORT 2596 

 UPPER REAR 2564 -1.2 

 

 REFERENCE PORT 2478 

 UPPER REAR 2466 -0.5 

 

 REFERENCE PORT 2463 

 UPPER REAR 2473 0.4 -0.4 

 --------------------------------------------------------------------------------------------------------------------------------- 

 PPM = PARTS PER MILLION 

 

 

 

-22- 

364 of 435
 INHALATION TABLE 4 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 3 

 TEST ATMOSPHERE HOMOGENEITY DETERMINATION 

 

 --------------------------------------------------------------------------------------------------------------------------------- 

 TARGET: 5000 PPM CHAMBER #4 

 --------------------------------------------------------------------------------------------------------------------------------- 

 DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN % 

 --------------------------------------------------------------------------------------------------------------------------------- 

 01/29/08 REFERENCE PORT 5107 

 LOWER FRONT 5204 1.9 

 

 REFERENCE PORT 5103 

 LOWER FRONT 5205 2.0 

 

 REFERENCE PORT 5132 

 LOWER FRONT 5119 -0.3 1.2 

 

 REFERENCE PORT 5117 

 LOWER REAR 5201 1.6 

 

 REFERENCE PORT 5122 

 LOWER REAR 5202 1.6 

 

 REFERENCE PORT 5126 

 LOWER REAR 5093 -0.6 0.9 

 

 REFERENCE PORT 5170 

 UPPER FRONT 5203 0.6 

 

 REFERENCE PORT 5075 

 UPPER FRONT 5108 0.7 

 

 REFERENCE PORT 5111 

 UPPER FRONT 5226 2.3 1.2 

 

 REFERENCE PORT 5166 

 UPPER REAR 5119 -0.9 

 

 REFERENCE PORT 5204 

 UPPER REAR 5140 -1.2 

 

 REFERENCE PORT 5222 

 UPPER REAR 5219 -0.1 -0.7 

 --------------------------------------------------------------------------------------------------------------------------------- 

 PPM = PARTS PER MILLION 

 MANUALv1.0 

 03/17/2008 

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 INHALATION TABLE 5 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 DAILY NOMINAL CONCENTRATIONS [PPM] 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 DATE GROUP: 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ---------------------------------------------------------------------------------------------------------------------------------- 

 02/06/08 1292 2735 5267 NA 

 02/07/08 1307 2710 5378 NA 

 02/08/08 1297 2735 NA NA 

 02/09/08 1310 2655 NA 2175 

 02/10/08 1307 2665 NA 2169 

 02/11/08 NA NA NA 2179 

 02/12/08 NA NA NA 2206 

 02/13/08 NA NA NA 2203 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRAND MEAN 1303 2700 5323 2186 

 S.D. 7.7 38.1 78.5 16.9 

 C.V.(%) 0.59 1.41 1.47 0.77 

 N 5 5 2 5 

 

 NA = NOT APPLICABLE 

 

 MANUALv1.0 

 03/17/2008 

 R:05/14/2008 -24- 

366 of 435
 INHALATION TABLE 6 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHAMBER 1 (0.5M3) CHAMBER 2 (0.5M3) CHAMBER 3 (0.5M3) CHAMBER 4 (0.5M3) CHAMBER 4 (0.5M3) 

 CONCENTRATION CONCENTRATION CONCENTRATION CONCENTRATION CONCENTRATION 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 STUDY DAY: 0 

 MEAN 0. 1244. 2560. 5049. NA 

 SD 0.0 27.3 35.2 94.0 

 CV(%) 0.00 2.19 1.37 1.86 

 N 10 10 10 10 

 

 STUDY DAY: 1 

 MEAN 0. 1243. 2555. 5028. NA 

 SD 0.0 11.6 46.8 71.6 

 CV(%) 0.00 0.93 1.83 1.42 

 N 10 10 10 10 

 

 STUDY DAY: 2 

 MEAN 0. 1242. 2557. NA NA 

 SD 0.0 15.6 23.3 

 CV(%) 0.00 1.26 0.91 

 N 10 10 10 

 

 STUDY DAY: 3 

 MEAN 0. 1254. 2521. NA 1784. 

 SD 0.0 17.2 24.2 26.4 

 CV(%) 0.00 1.37 0.96 1.48 

 N 10 10 10 10 

 

 STUDY DAY: 4 

 MEAN 0. 1253. 2485. NA 1797. 

 SD 0.0 12.8 28.0 21.0 

 CV(%) 0.00 1.02 1.13 1.17 

 N 10 10 10 10 

 

 CV (%) = COEFFICIENT OF VARIATION, NA = NOT APPLICABLE 

 CONCENTRATION IN: PPM 

 

-25- 

367 of 435
 INHALATION TABLE 6 

 PROJECT NO.: A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS 

 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GROUP: 0 PPM 1250 PPM 2500 PPM 5000 PPM 1800 PPM 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 CHAMBER 1 (0.5M3) CHAMBER 2 (0.5M3) CHAMBER 3 (0.5M3) CHAMBER 4 (0.5M3) CHAMBER 4 (0.5M3) 

 CONCENTRATION CONCENTRATION CONCENTRATION CONCENTRATION CONCENTRATION 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 STUDY DAY: 5 

 MEAN NA NA NA NA 1792. 

 SD 22.6 

 CV(%) 1.26 

 N 10 

 

 STUDY DAY: 6 

 MEAN NA NA NA NA 1790. 

 SD 25.0 

 CV(%) 1.40 

 N 10 

 

 STUDY DAY: 7 

 MEAN NA NA NA NA 1803. 

 SD 14.2 

 CV(%) 0.79 

 N 10 

 

 ALL STUDY DAYS COMBINED 

 MEAN 0. 1247. 2536. 5039. 1793. 

 SD 0.0 5.8 32.4 14.8 7.2 

 CV(%) 0.00 0.47 1.28 0.29 0.40 

 N 5 5 5 2 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 CV (%) = COEFFICIENT OF VARIATION, NA = NOT APPLICABLE 

 CONCENTRATION IN: PPM 

 PCHCSUv4.06 

 03/17/2008 

 R:05/14/2008 

-26- 

368 of 435
APPENDIX D

Pretest Clinical Observations

369 of 435
 PRETEST CLINICAL OBSERVATIONS (GROUPS 1-4) 

 PROJECT NO.: 534011P A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: 01-25-08 TO 02-04-08 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 72/25 

 

 BODY/INTEG II 

 -SCABBING DORSAL HEAD 2/ 2 

 -SCABBING VENTRAL NECK 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- PRETEST 

 

370 of 435
 PRETEST CLINICAL OBSERVATIONS (GROUPS 1-4) 

 PROJECT NO.: 534011P A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 

 ----- F E M A L E ----- 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 TABLE RANGE: 01-25-08 TO 02-04-08 

 GROUP: 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 74/25 

 

 BODY/INTEGUMENT 

 -HAIR LOSS FORELIMB(S) 1/ 1 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 1- PRETEST 

 PCSUv4.07 

 03/24/2008 

371 of 435
APPENDIX E

Animal Room Environmental Conditions

372 of 435
TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

A 5-DAY INHALATION STUDY IN RATS

PROJECT NO.:

01/22/08 02/14/08 

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 44RAT

LOW TEMPERATURE oF: 66.0 HIGH TEMPERATURE oF: 76.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

DATE MEAN (oF) MEAN (%RH)

LOW TEMPERATURE oC: 18.9 HIGH TEMPERATURE oC: 24.4

MEAN (oC)

22-Jan-08 22.1 71.7 36.8

23-Jan-08 21.6 71.0 36.8

24-Jan-08 21.2 70.1 36.9

25-Jan-08 21.6 70.8 37.0

26-Jan-08 21.6 70.8 36.6

27-Jan-08 22.1 71.8 36.1

28-Jan-08 21.8 71.2 37.1

29-Jan-08 22.0 71.6 37.1

30-Jan-08 21.1 70.0 36.8

31-Jan-08 21.3 70.3 36.2

01-Feb-08 21.5 70.7 37.2

02-Feb-08 21.3 70.3 37.1

03-Feb-08 21.6 70.9 37.1

04-Feb-08 21.8 71.3 38.2

05-Feb-08 22.1 71.7 41.6

06-Feb-08 21.5 70.6 38.2

07-Feb-08 21.6 70.8 37.6

08-Feb-08 22.0 71.6 37.4

09-Feb-08 21.8 71.3 37.8

10-Feb-08 21.7 71.0 36.1

11-Feb-08 22.2 72.0 37.4

12-Feb-08 21.6 70.9 36.3

13-Feb-08 22.0 71.5 37.0

5

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

373 of 435
TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

A 5-DAY INHALATION STUDY IN RATS

PROJECT NO.:

01/22/08 02/14/08 

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 44RAT

LOW TEMPERATURE oF: 66.0 HIGH TEMPERATURE oF: 76.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

DATE MEAN (oF) MEAN (%RH)

LOW TEMPERATURE oC: 18.9 HIGH TEMPERATURE oC: 24.4

MEAN (oC)

14-Feb-08 22.1 71.8 40.9

71.1TEMPERATURE oF 70.0 72.0

41.636.137.4

24MEAN MIN MAX

TEMPERATURE oC 21.7 21.1 22.2

HUMIDITY (%RH)GRAND STATSN DAYS

5

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

374 of 435
TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

A 5-DAY INHALATION STUDY IN RATS

PROJECT NO.: 16:35 14-May-

B ROOM 44RAT

LOW TEMPERATURE: 66.0HIGH TEMPERATURE: 76.0LOW HUMIDITY: 30.0HIGH HUMIDITY: 70.0ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

01/22/087:0016:0002/14/08

DATE IN:TIME IN:DATE OUT:TIME OUT:

ROOM B ROOM 44 SUMMARY

MEANMINMAX

71.168.573.6

37.4

8.1

68.2

SD 1.56 2.78N SAMPLES 561 560N DAYSFIRST DAYLAST DAY

01/22/0802/14/08

24

5

NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY UNITS = % RELATIVE HUMIDITYNOTE: MEANS REPRESENT THE MEAN OF ALL VALUES

375 of 435
TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

A 5-DAY INHALATION STUDY IN RATS

PROJECT NO.: 16:35 14-May-

STUDY SUMMARY

MEANMINMAX

71.168.573.6

37.4

8.1

68.2

SD 1.56 2.78N SAMPLES 561 560FIRST DAYLAST DAY

01/22/0802/14/08

N DAYS 24

5

NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY UNITS = % RELATIVE HUMIDITYNOTE: MEANS REPRESENT THE MEAN OF ALL VALUES

376 of 435
APPENDIX F

Unscheduled Clinical Observations

377 of 435
 UNSCHEDULED CLINICAL OBSERVATIONS 

 PROJECT NO.: 534011U A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95563 M 5000 PPM SPECIAL II 2 7:55 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95568 M 5000 PPM BEHAVIOR/CNS 1 8:35 P CONVULSIONS, CONTINUOUS 

 95568 M 5000 PPM SPECIAL II 2 7:55 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95570 M 5000 PPM BEHAVIOR/CNS 0 8:31 P TREMORS, INTERMITTENT 

 0 8:33 P CONVULSIONS, INTERMITTENT 

 1 8:34 P CONVULSIONS, CONTINUOUS 

 95570 M 5000 PPM ORAL/DENTAL 0 8:33 P WET CLEAR MATERIAL AROUND MOUTH 

 0 8:33 P WET CLEAR MATERIAL VENTRAL NECK 

 0 8:33 P WET CLEAR MATERIAL FORELIMB(S) 

 1 8:35 P WET CLEAR MATERIAL AROUND MOUTH 

 1 8:35 P WET CLEAR MATERIAL VENTRAL NECK 

 3 6:35 P UPPER INCISOR(S) MALALIGNED 

 95570 M 5000 PPM SPECIAL II 2 7:55 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95572 M 5000 PPM SPECIAL II 2 7:55 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95581 F 5000 PPM SPECIAL II 2 7:56 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95583 F 5000 PPM SPECIAL II 2 7:56 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95590 F 5000 PPM BEHAVIOR/CNS 0 8:29 P TREMORS, INTERMITTENT 

 1 8:47 P CONVULSIONS, CONTINUOUS 

 95590 F 5000 PPM EYES/EARS/NOSE 0 9:07 P WET RED MATERIAL AROUND NOSE 

 95590 F 5000 PPM ORAL/DENTAL 0 8:30 P WET RED MATERIAL AROUND MOUTH 

 95590 F 5000 PPM SPECIAL II 2 7:56 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95592 F 5000 PPM BEHAVIOR/CNS 0 8:29 P CONVULSIONS, INTERMITTENT 

 95592 F 5000 PPM SPECIAL II 2 7:56 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 95601 F 5000 PPM BODY/INTEG II 3 6:45 P SCABBING VENTRAL NECK 

 3 6:45 P SCABBING FORELIMB(S) 

 4 6:27 P SCABBING VENTRAL NECK 

 4 6:27 P SCABBING FORELIMB(S) 

 4 13:20 P SCABBING VENTRAL NECK 

 4 13:20 P SCABBING FORELIMB(S) 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 

378 of 435
 UNSCHEDULED CLINICAL OBSERVATIONS 

 PROJECT NO.: 534011U A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL CLINICAL OBSERVATIONS 

 

 STUDY DAYS: 0 THROUGH 5 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 STUDY 

 ANIMAL SEX GROUP CATEGORY DAY TIME GRADE OBSERVATIONS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 95601 F 5000 PPM SPECIAL II 0 14:57 P WATER BOTTLE ADDED - POOR BODY CONDITION 

 2 7:56 P WATER BOTTLE ADDED-BODY WEIGHT LOSS 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT 

 PCRDv4.11 

 04/16/2008 

379 of 435
 UNSCHEDULED DATA (GROUP 4) 

 PROJECT NO.: 534011U A 5-DAY INHALATION STUDY IN RATS PAGE 1 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 MALE GROUP: 5000 PPM 

 DAY 0 TO 1 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95554 NA NA 

 95563 24. 31. 

 95568 20. 30. 

 95570 1. 23. 

 95572 12. 26. 

 

 

 MEAN 14. 28. 

 S.D. 10.1 3.7 

 N 4 4 

 

 NA = NOT APPLICABLE 

 

 

380 of 435
 UNSCHEDULED DATA (GROUP 4) 

 PROJECT NO.: 534011U A 5-DAY INHALATION STUDY IN RATS PAGE 2 

 INDIVIDUAL FOOD CONSUMPTION [G/ANIMAL/DAY] 

 

 FEMALE GROUP: 5000 PPM 

 DAY 0 TO 1 2 TO 4 

 ----------------------------------------------------------------------------------------------------------------------------------- 

 ANIMAL 

 95581 16. 32. 

 95583 16. 19. 

 95590 2. 17. 

 95592 19. 22. 

 95601 1. 22. 

 

 

 MEAN 11. 22. 

 S.D. 8.6 5.8 

 N 5 5 

 PBFTSv4.44 

 05/08/2008 

 R:05/08/2008 

381 of 435
APPENDIX G

Clinical Pathology Methods, Procedures And References

382 of 435
CLINICAL PATHOLOGY METHODS, PROCEDURES AND REFERENCES

Serum Chemistry - Hitachi 912

Albumin - Bromcresol Green (BCG) Method, Modification of the Doumas reaction.

Default unit: g/dL. Hitachi 912 Application Code 413. Roche Reagent, catalog number

11970569.

A/G Ratio - Calculated from Albumin and Globulin Results. Default unit: %.

Alkaline Phosphatase - based on the International Federation of Clinical Chemistry (IFCC)

Method (Tietz et al. J Clin Chem Clin Biochem 1983; 21:731-748). Default unit: U/L.

Hitachi 912 Application Code 158. Roche Reagent, catalog number 2172933.

Alanine Aminotransferase - Modification of the International Federation of Clinical

Chemistry (IFCC) recommended method. Default unit: U/L. Hitachi 912 Application

Code 706. Roche Reagent, catalog number 450065.

Aspartate Aminotransferase - Kinetic method based on the International Federation of

Clinical Chemistry (IFCC) recommendations. Default unit: U/L. Hitachi 912 Application

Code 713. Roche Reagent, catalog number 450064.

Bilirubin (Total) - Diazo method developed by Wahlefeld et al. Scand J Clin Lab Invest

1972; 29: Supplement 126. Default unit: mg/dL. Hitachi 912 Application Code 018. Roche

Reagent, catalog number 1822730.

Blood Urea Nitrogen (BUN) - A urease-triggered methodology based upon the method of

Talke and Schubert Klin Wschr, 1965; 43:174. Default unit: mg/dL. Hitachi 912

Application Code 427. Roche Reagent, catalog number 1489321.

Calcium - Modified method using a gamma-amino-butyric acid (GABA) buffer. Default

unit: mg/dL. Hitachi 912 Application Code 180. Roche Reagent, catalog number 1125621.

Chloride - An ion-selective electrode that measures the electrical potential of the ions

present in solution. Default unit: mEq/L. Hitachi 912 Application. Roche Reagent, catalog

numbers 450043,450042, and 450041.

Cholesterol - Enzymatic reaction as described by Trinder. Ann Clin Biochem 1974; 12:266.

Default unit: mg/dL. Hitachi 912 Application Code 722. Roche Reagent, catalog number

450061.

383 of 435
Creatinine - Modified Jaffe reaction based on the work of Poper et al. Biochem Z 1937;

291:354, and Seelig and Wuest. Aerztl Labor 1969; 15:34. Default unit: mg/dL. Hitachi

912 Application Code 727. Roche Reagent, catalog number 450019.

Globulin - Calculation obtained by subtracting Albumin from Total Protein. Default unit:

g/dL.

Glucose - Glucose hexokinase method based on the work of Schmidt, Peterson and Young.

Klin Wschr 1961; 39:1244. Methods of Enzymatic Analysis, 2nd Eng ed. New York,

Academic Press, 1974; 1196. Anal Biochemistry 1958; 23:301. Default unit: mg/dL.

Hitachi 912 Application Code 767. Roche Reagent, catalog number 450058.

Phosphorus - Method involves the formation of ammonium phosphomolybdate. Default

unit: mg/dL. Hitachi 912 Application Code 714. Roche Reagent, catalog number 1040898.

Potassium - An ion-selective electrode that measures the electrical potential of the ions

present in solution. Default unit: mEq/L. Hitachi 912 Application. Roche Reagent, catalog

numbers 450043,450042, and 450041.

Sodium - An ion-selective electrode that measures the electrical potential of the ions present

in solution. Default unit: mEq/L. Hitachi 912 Application. Roche Reagent, catalog number

450043,450042, and 450041.

Total Protein - Endpoint biuret method that utilizes a sample blank. Default unit: g/dL.

Hitachi 912 Application Code 756. Roche Reagent, catalog number 1040901.

Triglycerides - Method that utilizes lipase from a microorganism to promote rapid and

complete hydrolysis of triglycerides to glycerol. Default unit: mg/dL. Hitachi 912

Application Code 781. Roche Reagent, catalog number 1488899.

Hematology - Manual Methods

White Cell Differential - Manual method of counting 100 white cells stained with Wright

Giemsa and entered on-line into the data files.

Reticulocyte Count - Manual method of counting the reticulocytes present in 1000 red

blood cells stained with New Methylene Blue and entered on-line into the data files.

Red Blood Cell Morphology - Manual method of evaluating red blood cells on a Wright

Giemsa-stained slide and entered on-line into the data files.

384 of 435
Platelet Estimate- Manual method of evaluating platelets on a Wright Giemsa-stained slide.

Platelet estimation is evaluated and entered on-line into the data files as decreased, adequate

or increased. Platelet clumps present on the slide will be reported as part of the RBC

morphology.

AMAX Destiny Amelung Coagulation

Mechanical (Ball Method) Measurement – Mechanical measurement methods depend on

the physical formation of fibrin strands that attach to a moving mechanical device that either

completes or opens an electrical circuit. The elapsed time from the addition of the starting

reagent, up to the beginning of fibrin formation is measured.

Prothrombin Time (Protime-PT)/(PTM)- mechanical clot detection is used to measure and

record the time required for plasma specimens to clot by adding an excess of thromboplastin

reagent and an optional amount of calcium to citrated plasma. The PT measures from factor

VII through fibrin formation (extrinsic and common pathways of coagulation). Default unit:

sec.

Activated Partial Thromboplastin Time (APTT)/(PTTM)- mechanical clot detection is used

to measure and record clotting time in a one-stage procedure which consists of recalcifying

plasma in the presence of an excess of platelet-like reagent (cephalin) containing a plasma

activator. The APTT measures the clotting time from factor XII through fibrin formation

(intrinsic and common pathways of coagulation) Default unit: sec.

Hematology-Bayer Advia® 120-Siemens Healthcare Diagnostics/(Formerly: Bayer

Advia®120)

WBC Count - The whole blood sample is mixed with ADVIA® 120 BASO reagent that

contains acid and surfactant. The red cells are hemolyzed, and the white blood cells are then

analyzed using two angle laser light scatter signals. Default unit: x 103 cells/μL

RBC / Platelet Count - Both red blood cells and platelets are analyzed by a single optical

cytometer after appropriate dilution of the blood sample with ADVIA®

 120 RBC/PLT

reagent. The red blood cells are isovolumetrically sphered and lightly fixed with

glutaraldehyde to preserve the spherical shape. Red cells and platelets are counted from the

signals from a common detector with 2 different gain settings. Default unit

RBC: x 106cells/μL. Default unit PLT: x 103 cells/μL

385 of 435
Hgb - Hemoglobin: The hemoglobin method is a modification of the manual

cyanmethemoglobin method developed by the International Committee for

standardization in Hematology (ICSH). Default unit: g/dL.

Hematocrit - The percentage of blood volume that is occupied by red blood cells. Also

referred to as the packed red cell volume. On the ADVIA®

 120 Hematology System this

parameter is derived from the measured red cell volume (MCV) and the red cell count

(RBC). Default unit: %.

MCH - Mean Corpuscular Hemoglobin: the average weight of hemoglobin in the red

blood cells, calculated from the RBC and Hgb measurements. Default unit: pg.

MCHC - Mean Corpuscular Hemoglobin Concentration: the average concentration of

hemoglobin in the red blood cells. This parameter is computed from the measured

hemoglobin and the computed hematocrit. Default unit: g/dL.

MCV - Mean Corpuscular Volume: the average volume of the red blood cells. Default

unit: fL

White blood cell differential - The ADVIA® 120 Hematology System White Blood Cell

Differential (WBC DIFF) methods, consists of both the Peroxidase method and the

Basophil/Lobularity method. The ADVIA® 120 Hematology System performs a six-part

differential that consists of basophils, eosinophils, large unstained cells, lymphocytes,

monocytes, and neutrophils. The white blood cell differential count is reported in percent

and the actual number of each type of cell per microliter of blood.

Reticulocyte - This method uses a nucleic acid dye (oxazine 750) to stain cellular RNA.

The ADVIA® 120 autoRETIC reagent isovolumetrically spheres the erythroid cells and

stains cellular RNA. Low-angle laser light scatter, high-angle laser light scatter, and

absorption characteristics of all cells are counted and measured. The absorption data are

used to classify each cell as a reticulocyte or mature red blood cell based on its RNA

content. The reticulocyte is reported in percent and actual number x 109

cells/Liter =

thous/μl.

References:

ADVIA® 120 Hematology System Operator's Guide: Copyright© 1997, 1998. Siemens

Healthcare Diagnostics/ (Formerly: Bayer Corporation Diagnostics Division).

AMAX Destiny Operation Manual SW V 1.1.4, 31/08/05. Trinity Biotech Plc.

386 of 435
APPENDIX H

Historical Control Data (

387 of 435
Sex:

Species:

Strain:

- Historical Control Summary of Clinical Pathology Values Page 1 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 52

12/02 02/07 -

M

9 12 - Weeks

/ 52

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Serum Chemistry Values

Mean Reference Range

1.98 1.56 2.47

N

411

S.D.

0.208

A/G Ratio

/

Mean Reference Range

40 25 60

N

411

S.D.

7.3

Alanine Aminotransferase (U/L)

/

Mean Reference Range

4.3 3.9 4.7

N

411

S.D.

0.19

Albumin (g/dL)

/

Mean Reference Range

203 122 322

N

411

S.D.

44.3

Alkaline Phosphatase (U/L)

/

Mean Reference Range

95 67 154

N

411

S.D.

17.1

Aspartate Aminotransferase (UL)

/

Mean Reference Range

11.1 10.3 12.7

N

411

S.D.

0.50

Calcium (mg/dL)

/

Mean Reference Range

102 99 106

N

411

S.D.

1.6

Chloride (mEq/L)

/

Mean Reference Range

50 30 74

N

393

S.D.

9.8

Cholesterol (mg/dL)

/

Mean Reference Range

471 136 1562

N

106

S.D.

280.3

Creatine Kinase (U/L)

/

Mean Reference Range

0.2 0.1 0.3

N

412

S.D.

0.06

Creatinine (mg/dL)

/

388 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 2 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 52

12/02 02/07 -

M

9 12 - Weeks

/ 52

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

0.5 0.1 1.4

N

60

S.D.

0.36

GGT (U/L)

/

Mean Reference Range

2.2 1.7 2.6

N

411

S.D.

0.21

Globulin (g/dL)

/

Mean Reference Range

116 81 181

N

822

S.D.

20.9

Glucose (mg/dL)

/

Mean Reference Range

9.8 7.8 13.7

N

411

S.D.

1.30

Phosphorus (mg/dL)

/

Mean Reference Range

5.36 4.17 8.46

N

411

S.D.

0.905

Potassium (mEq/L)

/

Mean Reference Range

145 142 151

N

411

S.D.

1.8

Sodium (mEq/L)

/

Mean Reference Range

0.1 0.1 0.2

N

393

S.D.

0.04

Total Bilirubin (mg/dL)

/

Mean Reference Range

6.4 5.8 7.1

N

411

S.D.

0.29

Total Protein (g/dL)

/

Mean Reference Range

48 18 97

N

355

S.D.

17.3

Triglyceride (mg/dL)

/

Mean Reference Range

14.1 9.8 19.7

N

411

S.D.

2.17

Urea Nitrogen (mg/dL)

/

389 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 3 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 52

12/02 02/07 -

M

9 12 - Weeks

/ 52

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

26-Sep-07

Version 2.5

390 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 1 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 53

12/02 02/07 -

F

9 12 - Weeks

/ 53

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Serum Chemistry Values

Mean Reference Range

2.10 1.64 2.66

N

422

S.D.

0.227

A/G Ratio

/

Mean Reference Range

34 21 67

N

424

S.D.

8.4

Alanine Aminotransferase (U/L)

/

Mean Reference Range

4.6 4.1 5.2

N

423

S.D.

0.26

Albumin (g/dL)

/

Mean Reference Range

125 67 191

N

424

S.D.

29.0

Alkaline Phosphatase (U/L)

/

Mean Reference Range

96 66 160

N

424

S.D.

19.0

Aspartate Aminotransferase (UL)

/

Mean Reference Range

11.1 10.0 12.8

N

423

S.D.

0.60

Calcium (mg/dL)

/

Mean Reference Range

103 99 107

N

424

S.D.

1.6

Chloride (mEq/L)

/

Mean Reference Range

64 39 97

N

403

S.D.

12.5

Cholesterol (mg/dL)

/

Mean Reference Range

452 137 1441

N

103

S.D.

275.2

Creatine Kinase (U/L)

/

Mean Reference Range

0.3 0.2 0.4

N

423

S.D.

0.07

Creatinine (mg/dL)

/

391 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 2 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 53

12/02 02/07 -

F

9 12 - Weeks

/ 53

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

0.7 0.2 2.3

N

90

S.D.

0.45

GGT (U/L)

/

Mean Reference Range

2.2 1.7 2.7

N

422

S.D.

0.22

Globulin (g/dL)

/

Mean Reference Range

112 79 165

N

846

S.D.

15.1

Glucose (mg/dL)

/

Mean Reference Range

9.2 6.2 14.8

N

424

S.D.

1.76

Phosphorus (mg/dL)

/

Mean Reference Range

5.35 4.07 8.94

N

424

S.D.

1.070

Potassium (mEq/L)

/

Mean Reference Range

144 140 150

N

424

S.D.

1.9

Sodium (mEq/L)

/

Mean Reference Range

0.1 0.1 0.3

N

403

S.D.

0.06

Total Bilirubin (mg/dL)

/

Mean Reference Range

6.8 6.0 7.7

N

423

S.D.

0.37

Total Protein (g/dL)

/

Mean Reference Range

42 19 75

N

365

S.D.

12.4

Triglyceride (mg/dL)

/

Mean Reference Range

15.8 11.3 22.4

N

423

S.D.

2.25

Urea Nitrogen (mg/dL)

/

392 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 3 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 53

12/02 02/07 -

F

9 12 - Weeks

/ 53

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

26-Sep-07

Version 2.5

393 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 1 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 35

06/04 02/07 -

M

9 12 - Weeks

/ 35

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Hematology Values

Mean Reference Range

0.04 0.01 0.14

N

273

S.D.

0.025

Basophil - Abs (thous/uL)

/

Mean Reference Range

0.4 0.1 1.1

N

273

S.D.

0.18

Basophil (%)

/

Mean Reference Range

1.1 0.3 3.7

N

273

S.D.

0.69

Eosiniphil (%)

/

Mean Reference Range

0.11 0.03 0.43

N

273

S.D.

0.063

Eosinophil - Abs (thous/uL)

/

Mean Reference Range

46.6 39.8 53.4

N

273

S.D.

2.88

Hematocrit (%)

/

Mean Reference Range

15.6 13.5 17.1

N

273

S.D.

0.72

Hemoglobin (g/dL)

/

Mean Reference Range

0.8 0.2 1.5

N

273

S.D.

0.28

LG Unstain Cell

/

Mean Reference Range

0.08 0.02 0.22

N

273

S.D.

0.041

Luc Absolute (thous/uL)

/

Mean Reference Range

8.07 4.19 14.33

N

273

S.D.

2.233

Lymphocyte - Abs (thous/uL)

/

Mean Reference Range

82.8 69.9 89.8

N

273

S.D.

4.19

Lymphocyte (%)

/

394 of 435
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Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 2 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 35

06/04 02/07 -

M

9 12 - Weeks

/ 35

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

19.6 18.3 21.3

N

273

S.D.

0.68

MCH (pg)

/

Mean Reference Range

33.5 30.1 36.6

N

273

S.D.

1.48

MCHC (g/dL)

/

Mean Reference Range

58.7 52.5 66.2

N

273

S.D.

3.13

MCV (fL)

/

Mean Reference Range

0.18 0.07 0.42

N

273

S.D.

0.074

Monocyte - Abs (thous/uL)

/

Mean Reference Range

1.8 0.8 3.4

N

273

S.D.

0.59

Monocyte (%)

/

Mean Reference Range

1.25 0.57 2.50

N

273

S.D.

0.429

Neutrophil - Abs (thous/uL)

/

Mean Reference Range

12.9 6.8 26.0

N

273

S.D.

3.68

Neutrophil (%)

/

Mean Reference Range

1102 653 1502

N

273

S.D.

174.8

Platelet (thous/uL)

/

Mean Reference Range

11.2 11.0 12.0

N

5

S.D.

0.45

Red Cell Width (%)

/

395 of 435
Sex:

Species:

Strain:

- Historical Control Summary of Clinical Pathology Values Page 3 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 35

06/04 02/07 -

M

9 12 - Weeks

/ 35

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

7.96 6.77 9.04

N

273

S.D.

0.494

Red Cells (mil/uL)

/

Mean Reference Range

0.184 0.106 0.283

N

179

S.D.

0.0423

Reticulocyte - Abs (mil/uL)

/

Mean Reference Range

69.5 0.1 312.7

N

273

S.D.

101.78

Reticulocyte - Abs (thous/uL)

/

Mean Reference Range

2.5 1.3 4.5

N

273

S.D.

0.66

Reticulocyte (%)

/

Mean Reference Range

9.7 5.2 17.1

N

273

S.D.

2.56

White Cells (thous/uL)

/

25-Sep-07

Version 2.5

396 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 1 of 1

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 21

10/05 02/07 -

M

9 12 - Weeks

/ 21

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Hematology Values

Mean Reference Range

20.3 16.4 26.6

N

151

S.D.

2.16

APTT (seconds)

/

Mean Reference Range

246.40 211.00 287.00

N

10

S.D.

20.178

Fibrinogen (mg/dL)

/

Mean Reference Range

16.4 13.2 20.1

N

151

S.D.

1.83

Prothrombin Time (seconds)

/

24-Sep-07

Version 2.5

397 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 1 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 37

06/04 02/07 -

F

9 12 - Weeks

/ 37

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Hematology Values

Mean Reference Range

0.03 0.00 0.14

N

282

S.D.

0.020

Basophil - Abs (thous/uL)

/

Mean Reference Range

0.3 0.0 1.2

N

282

S.D.

0.18

Basophil (%)

/

Mean Reference Range

1.3 0.4 4.2

N

282

S.D.

0.72

Eosiniphil (%)

/

Mean Reference Range

0.10 0.03 0.34

N

282

S.D.

0.055

Eosinophil - Abs (thous/uL)

/

Mean Reference Range

44.3 38.4 51.1

N

282

S.D.

2.99

Hematocrit (%)

/

Mean Reference Range

15.1 13.1 16.7

N

282

S.D.

0.77

Hemoglobin (g/dL)

/

Mean Reference Range

0.7 0.0 1.6

N

282

S.D.

0.30

LG Unstain Cell

/

Mean Reference Range

0.06 0.00 0.16

N

282

S.D.

0.034

Luc Absolute (thous/uL)

/

Mean Reference Range

6.41 3.05 12.93

N

282

S.D.

2.079

Lymphocyte - Abs (thous/uL)

/

Mean Reference Range

83.0 65.1 90.7

N

282

S.D.

5.25

Lymphocyte (%)

/

398 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 2 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 37

06/04 02/07 -

F

9 12 - Weeks

/ 37

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

19.6 18.3 21.2

N

282

S.D.

0.67

MCH (pg)

/

Mean Reference Range

34.2 30.4 37.6

N

282

S.D.

1.70

MCHC (g/dL)

/

Mean Reference Range

57.4 51.7 63.9

N

282

S.D.

2.85

MCV (fL)

/

Mean Reference Range

0.13 0.04 0.34

N

282

S.D.

0.063

Monocyte - Abs (thous/uL)

/

Mean Reference Range

1.6 0.7 3.9

N

282

S.D.

0.61

Monocyte (%)

/

Mean Reference Range

0.95 0.38 2.30

N

282

S.D.

0.373

Neutrophil - Abs (thous/uL)

/

Mean Reference Range

12.9 5.7 29.7

N

282

S.D.

4.95

Neutrophil (%)

/

Mean Reference Range

1144 734 1531

N

282

S.D.

167.3

Platelet (thous/uL)

/

Mean Reference Range

10.4 10.0 11.0

N

5

S.D.

0.55

Red Cell Width (%)

/

399 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 3 of 3

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 37

06/04 02/07 -

F

9 12 - Weeks

/ 37

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Mean Reference Range

7.72 6.61 8.55

N

282

S.D.

0.461

Red Cells (mil/uL)

/

Mean Reference Range

0.144 0.088 0.225

N

175

S.D.

0.0321

Reticulocyte - Abs (mil/uL)

/

Mean Reference Range

62.1 0.1 289.4

N

282

S.D.

84.74

Reticulocyte - Abs (thous/uL)

/

Mean Reference Range

2.0 1.1 4.0

N

282

S.D.

0.52

Reticulocyte (%)

/

Mean Reference Range

7.7 3.8 15.1

N

282

S.D.

2.33

White Cells (thous/uL)

/

25-Sep-07

Version 2.5

400 of 435
Sex:

Species:

Strain:

 - Historical Control Summary of Clinical Pathology Values Page 1 of 1

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RAT Age:

Crl:CD(SD)

SUBCHRONIC 24

10/05 02/07 -

F

9 12 - Weeks

/ 24

Serum/Hematology/Coagulation Instrument: 912/ADVIA/AMAX

Hematology Values

Mean Reference Range

19.0 15.0 24.8

N

176

S.D.

2.14

APTT (seconds)

/

Mean Reference Range

197.40 169.00 228.00

N

10

S.D.

18.846

Fibrinogen (mg/dL)

/

Mean Reference Range

14.3 11.9 17.1

N

176

S.D.

1.62

Prothrombin Time (seconds)

/

24-Sep-07

Version 2.5

401 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 48

06/03 03/07 -

M / 48

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

ADRENAL GLANDS

Mean Observed Low/High Value0.0608 0.04 0.10

N318

S.D.0.00995

Mean +/- 2 S.D.

Absolute OW: 0.0409 0.0807 0.0310 0.0907OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.019 0.0031 318 0.012 0.025 0.009 0.028 0.01 0.03

3.117 0.4807 308 2.156 4.078 1.675 4.559 2.06 4.83

///

///

///

BRAIN

Mean Observed Low/High Value1.95 1.61 2.26

N324

S.D.0.105

Mean +/- 2 S.D.

Absolute OW: 1.74 2.16 1.63 2.26OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.599 0.0714 324 0.456 0.741 0.384 0.813 0.45 0.84

NA 0.00 0.00

//

//

//

EPIDIDYMIDES

Mean Observed Low/High Value0.88 0.49 1.21

N259

S.D.0.166

Mean +/- 2 S.D.

Absolute OW: 0.55 1.21 0.38 1.38OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.264 0.0354 259 0.193 0.334 0.157 0.370 0.17 0.36

44.848 7.9601 259 28.928 60.769 20.968 68.729 25.51 64.74

///

///

///

402 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 48

06/03 03/07 -

M / 48

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

HEART

Mean Observed Low/High Value1.30 0.89 1.93

N300

S.D.0.177

Mean +/- 2 S.D.

Absolute OW: 0.95 1.66 0.77 1.83OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.399 0.0452 300 0.308 0.489 0.263 0.535 0.30 0.59

66.938 8.3091 300 50.320 83.556 42.011 91.865 48.90 96.02

///

///

///

KIDNEYS

Mean Observed Low/High Value2.84 2.00 4.14

N329

S.D.0.440

Mean +/- 2 S.D.

Absolute OW: 1.96 3.71 1.52 4.15OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.868 0.0848 329 0.698 1.038 0.614 1.122 0.63 1.14

146.455 19.6824 319 107.091 185.820 87.408 205.503 103.50 196.67

///

///

///

LIVER

Mean Observed Low/High Value10.8 6.95 20.27

N329

S.D.2.03

Mean +/- 2 S.D.

Absolute OW: 6.7 14.9 4.7 16.9OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

3.299 0.3734 329 2.552 4.045 2.179 4.419 2.61 4.73

557.885 94.2772 319 369.331 746.440 275.054 840.717 376.50 1018.59

///

///

///

403 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 48

06/03 03/07 -

M / 48

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

LUNGS

Mean Observed Low/High Value1.32 1.07 1.62

N30

S.D.0.121

Mean +/- 2 S.D.

Absolute OW: 1.08 1.57 0.96 1.69OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.465 0.0394 30 0.386 0.544 0.347 0.583 0.37 0.58

69.840 4.8037 20 60.233 79.448 55.429 84.251 60.00 78.06

///

///

///

PITUITARY

Mean Observed Low/High Value0.0117 0.01 0.02

N171

S.D.0.00200

Mean +/- 2 S.D.

Absolute OW: 0.0077 0.0157 0.0057 0.0177OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.004 0.0006 171 0.002 0.005 0.002 0.005 0.00 0.00

0.599 0.0955 171 0.408 0.790 0.313 0.886 0.27 0.88

///

///

///

PROSTATE

Mean Observed Low/High Value0.66 0.35 1.31

N111

S.D.0.169

Mean +/- 2 S.D.

Absolute OW: 0.32 1.00 0.16 1.17OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.204 0.0471 111 0.110 0.299 0.063 0.346 0.12 0.43

34.066 8.9111 111 16.244 51.888 7.333 60.799 17.50 75.29

///

///

///

404 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 48

06/03 03/07 -

M / 48

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

SEM VES/COAG GL.

Mean Observed Low/High Value1.3108 0.81 1.97

N13

S.D.0.33555

Mean +/- 2 S.D.

Absolute OW: 0.6397 1.9819 0.3041 2.3174OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.391 0.0741 13 0.242 0.539 0.168 0.613 0.28 0.50

66.726 16.6936 13 33.339 100.113 16.646 116.807 42.86 104.23

///

///

///

SPLEEN

Mean Observed Low/High Value0.67 0.38 1.15

N281

S.D.0.122

Mean +/- 2 S.D.

Absolute OW: 0.43 0.92 0.31 1.04OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.206 0.0310 281 0.144 0.268 0.113 0.299 0.14 0.30

34.577 5.8388 281 22.899 46.255 17.060 52.093 20.99 59.58

///

///

///

TESTES

Mean Observed Low/High Value3.16 2.05 3.88

N327

S.D.0.281

Mean +/- 2 S.D.

Absolute OW: 2.60 3.72 2.32 4.00OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.977 0.1159 327 0.746 1.209 0.630 1.325 0.70 1.41

162.749 13.5416 317 135.666 189.832 122.124 203.374 112.02 211.54

///

///

///

405 of 435
Sex:

Species:

- Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 48

06/03 03/07 -

M / 48

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

THYMUS GLAND

Mean Observed Low/High Value0.5323 0.28 1.03

N261

S.D.0.12763

Mean +/- 2 S.D.

Absolute OW: 0.2771 0.7876 0.1494 0.9152OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.163 0.0435 261 0.076 0.250 0.033 0.294 0.07 0.31

27.396 6.6917 261 14.012 40.779 7.321 47.471 13.35 52.62

///

///

///

THYROID/PARATHYROID

Mean Observed Low/High Value0.0208 0.01 0.04

N267

S.D.0.00511

Mean +/- 2 S.D.

Absolute OW: 0.0106 0.0310 0.0055 0.0361OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.006 0.0015 267 0.003 0.009 0.002 0.011 0.00 0.01

1.067 0.2665 267 0.534 1.600 0.267 1.866 0.50 2.01

///

///

///

13-Aug-07Version 2.4

406 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 50

06/03 03/07 -

F / 50

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

ADRENAL GLANDS

Mean Observed Low/High Value0.0705 0.05 0.11

N334

S.D.0.01056

Mean +/- 2 S.D.

Absolute OW: 0.0494 0.0916 0.0388 0.1022OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.034 0.0051 334 0.024 0.044 0.018 0.049 0.02 0.05

3.854 0.5569 324 2.740 4.967 2.183 5.524 2.51 5.73

///

///

///

BRAIN

Mean Observed Low/High Value1.83 1.54 2.03

N339

S.D.0.087

Mean +/- 2 S.D.

Absolute OW: 1.65 2.00 1.57 2.09OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.878 0.0931 339 0.692 1.065 0.599 1.158 0.64 1.30

NA 0.00 0.00

//

//

//

HEART

Mean Observed Low/High Value0.90 0.57 1.29

N316

S.D.0.110

Mean +/- 2 S.D.

Absolute OW: 0.68 1.12 0.57 1.23OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.429 0.0396 316 0.349 0.508 0.310 0.548 0.34 0.57

49.042 5.4861 316 38.070 60.014 32.584 65.500 33.93 65.82

///

///

///

407 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 50

06/03 03/07 -

F / 50

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

KIDNEYS

Mean Observed Low/High Value1.82 1.24 2.58

N344

S.D.0.232

Mean +/- 2 S.D.

Absolute OW: 1.36 2.29 1.12 2.52OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.871 0.0857 344 0.699 1.042 0.613 1.128 0.61 1.12

99.796 11.4811 334 76.834 122.758 65.353 134.240 72.38 137.71

///

///

///

LIVER

Mean Observed Low/High Value7.2 4.51 12.02

N344

S.D.1.08

Mean +/- 2 S.D.

Absolute OW: 5.1 9.4 4.0 10.5OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

3.445 0.3532 344 2.739 4.151 2.385 4.504 2.62 4.73

395.963 57.4247 334 281.114 510.812 223.689 568.237 265.56 656.83

///

///

///

LUNGS

Mean Observed Low/High Value1.16 0.94 1.53

N40

S.D.0.126

Mean +/- 2 S.D.

Absolute OW: 0.91 1.42 0.79 1.54OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.575 0.0510 40 0.473 0.677 0.422 0.728 0.50 0.69

62.225 6.2047 30 49.816 74.635 43.611 80.840 50.81 75.74

///

///

///

408 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 50

06/03 03/07 -

F / 50

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

OVARIES

Mean Observed Low/High Value0.1303 0.10 0.18

N25

S.D.0.01917

Mean +/- 2 S.D.

Absolute OW: 0.0919 0.1686 0.0728 0.1878OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.061 0.0083 25 0.044 0.077 0.036 0.086 0.04 0.08

7.111 1.1043 25 4.903 9.320 3.798 10.424 5.39 9.60

///

///

///

OVARIES/OVIDUCTS

Mean Observed Low/High Value0.1308 0.08 0.21

N281

S.D.0.02028

Mean +/- 2 S.D.

Absolute OW: 0.0903 0.1714 0.0700 0.1917OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.063 0.0090 281 0.045 0.081 0.036 0.090 0.04 0.09

7.166 1.0647 281 5.037 9.296 3.972 10.360 4.93 11.13

///

///

///

PITUITARY

Mean Observed Low/High Value0.0145 0.01 0.02

N182

S.D.0.00269

Mean +/- 2 S.D.

Absolute OW: 0.0091 0.0198 0.0064 0.0225OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.007 0.0011 182 0.005 0.009 0.004 0.010 0.00 0.01

0.788 0.1374 182 0.513 1.063 0.376 1.200 0.51 1.31

///

///

///

409 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 50

06/03 03/07 -

F / 50

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

SPLEEN

Mean Observed Low/High Value0.48 0.30 0.79

N296

S.D.0.086

Mean +/- 2 S.D.

Absolute OW: 0.31 0.65 0.23 0.74OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.231 0.0351 296 0.161 0.302 0.126 0.337 0.16 0.36

26.369 4.4409 296 17.487 35.251 13.046 39.692 17.10 44.25

///

///

///

THYMUS GLAND

Mean Observed Low/High Value0.4491 0.15 0.75

N276

S.D.0.09537

Mean +/- 2 S.D.

Absolute OW: 0.2583 0.6398 0.1630 0.7352OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.215 0.0454 276 0.124 0.305 0.079 0.351 0.08 0.35

24.590 5.1679 276 14.254 34.926 9.087 40.094 8.26 40.30

///

///

///

THYROID/PARATHYROID

Mean Observed Low/High Value0.0182 0.01 0.03

N275

S.D.0.00447

Mean +/- 2 S.D.

Absolute OW: 0.0093 0.0272 0.0048 0.0316OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.009 0.0021 275 0.005 0.013 0.003 0.015 0.00 0.01

0.999 0.2436 275 0.512 1.486 0.268 1.730 0.51 1.88

///

///

///

410 of 435
Sex:

Species:

 - Historical Control Summary of Organ Weights

Range of Study Dates:

Study Type: Number of Studies/Control Groups:

RATCrl:CD(SD)

SUBCHRONIC 50

06/03 03/07 -

F / 50

Age: 9 12 -

Strain: Report Type: Excluding +/- 5 S.D.

Weeks

UTERUS

Mean Observed Low/High Value0.52 0.28 1.06

N229

S.D.0.167

Mean +/- 2 S.D.

Absolute OW: 0.19 0.86 0.02 1.02OW relative to brain:OW relative to FBW:

Mean +/- 3 S.D.

0.249 0.0798 229 0.089 0.408 0.009 0.488 0.14 0.51

28.519 8.8932 229 10.732 46.305 1.839 55.198 14.81 56.25

///

///

///

13-Aug-07Version 2.4

411 of 435
APPENDIX I

Study Protocol

412 of 435
Study Number: 

PROTOCOL AMENDMENT KKI 

Sponsor: 

A. Title of Study: 

A S-Day Repeated-Dose Inhalation Toxicity Study of in 

Sprague-Dawley Rats 

B. Protocol Modification: 

1) The Sponsor Name is corrected to ,

2) 3 STUDY SCHEDULE: 

The following information adds to that currently in the protocol. 

Proposed Experimental 

TerminatiodCompletion Date: February 14,2008 

Proposed Audited Draft Report Date: May 14,2008 

3) 9 STATISTICAL METHODS: 

The following information clarifies to that currently in the protocol. 

For the 1800 ppm group (Group S), statistical analysis will not be 

performed by comparison to the study control group (Group I) since 

endpoint evaluations for Group 5 were separated from those for a11 ather 

groups by 3 days. historical coritrol information wil1 be 

used to aid in interpretation of the 1800 ppm group results, as needed. 

C. Reason for Protocol Modification: 

1) To correct the Sponsor Name. 

2) To add study schedule information. 

Improving human health and pmtectlng nment thmugh sclent fflc research services,@ 

413 of 435
ndmcnt I11 

Page 2 

3) To clarify that statistical analysis will not be performed for Group 5. 

Approved By: 

,

Sponsor Representative 

Prepared By: 

414 of 435
Study Number: 

PROTOCOL AMENDMENT II

Sponsor: 

A. Title of Study: 

 A 5-Day Repeated-Dose Inhalation Toxicity Study of in 

Sprague-Dawley Rats 

B. Protocol Modification: 

 1) 5.4 Number of Animals:

 In accordance with the study director notification dated January 30, 2008, 

animals ordered for this study but not selected for use on this study will be 

transferred for use on other studies or euthanized via CO2 inhalation. 

 2) 7.4.1 Organization of Test Groups:

 In accordance with the study director notification dated February 8, 2008, an 

additional group of five animals/sex will be added to the study and exposed 

at a target concentration of 1800 ppm. 

 

 7.4.3 Treatment Regimen:

 3) In accordance with the study director notification dated February 7, 2008, 

exposures for the 5000 ppm group (Group 4) will be terminated effective at 

the end of exposure on February 7, 2008. 

 4) In accordance with the study director notification dated February 8, 2008, 

exposures for the additional (1800 ppm) group will be initiated on Saturday, 

February 9, 2008 and will end on Wednesday, February 13, 2008. All 

protocol-defined observations will be performed for this group. Necropsy 

will take place on February 14, 2008. 

 5) 8.2 Clinical Observations:

 In accordance with the study director notification dated February 7, 2008, a 

scheduled clinical observation session will be added to the study for Groups 

1, 2 and 3 and any additional groups, if needed. Animals will be observed in 

the exposure chambers near the beginning of each day’s exposure 

(approximately 15-30 minutes into the exposure. Only clinical signs that can 

415 of 435
Protocol Amendment 11 

Page 2 

be observed clearly through the chamber windows will be recorded (in those 

animals that are visible through the chamber windows). 

C. Reason for Protocol Modification: 

1) Clarification of disposition of animals ordered but not selected for study. 

2) Addition of exposure group. 

3) Termination of exposure for 5000 ppm group (Group 4). 

4) Addition of treatment regimen for added group. 

5) Addition of clinical observation during exposure period. 

Approved By: 

Prepared By: 

416 of 435
Study Number: 

PROTOCOL AMENDMENT I 

Sponsor: 

A. Title of Study: 

A 5-Day Repeated-Dose Inhalation Toxicity Study of in 

Sprague-Dawley Rats 

B. Protocol Modification: 

1) 4.1 Identification: 

Trade name:

Chemical name: 

2) 4.2 Lot Number: 

3) 4.3 Puritv: 

99.99% (as shown in the Certificate of Analysis) 

4) 4.4 Stability: 

Stable for one year when stored at room temperature. 

C. Reason for Protocol Modification: 

1) Correction of test article identification. 

2) Addition of lot number. 

3) Addition of purity information. 

Tmnrnvin~ human health and nrntecti nment through scientjfjc research services.@ 

417 of 435
Protocol Amendment I 

Page 2 

4) Addition of stability information. 

Approved By: 

Prepared By: 

418 of 435
Page 1 of17 January 8,2008 

PROTOCOL 

A 5-DAY REPEATED-DOSE INHALATION TOXICITY 

STUDY OF IN SPRAGUE-DAWLEY RATS 

Submitted To: 

Testing Facility: 

Improving human health and protecting the environment through scientific research services.@ 

419 of 435
Page 2 of 17 January 8,2008 

1 OBJECTIVE: 

The objective of this dose range-finding study is to evaluate potential toxic effects of 

the test article when administered via whole-body inhalation to rats for 5 consecutive 

days. Standard hematology and serum chemistry evaluations will be performed at the 

time of scheduled necropsy. Standard tissues will be harvested from all animals at 

necropsy and preserved, but will not be examined microscopically. 

This study will be conducted in compliance with the following Good Laboratory 

Practice Regulations: 

Organisation for Economic Cooperation and Development: [C(97) 186lFinall 

U.S. Environmental Protection Agency - TSCA: 40 CFR Part 792 

Japan MAFF Good Laboratory Practice Standards 1 1 Nousan No. 6283, October 1, 

1999. 

2 PERSONNEL INVOLVED IN THE STUDY: 

2.1 Sponsor Representative: 

2.2 Studv Director: 

2.3 Deputv Director: 

420 of 435
Page 3 of 17 January 8,2008 

2.4 Departmental Responsibilities: 

3 STUDY SCHEDULE: 

421 of 435
Paae 4 of 17 January 8,2008 

Proposed Audited Report Date: To be added by protocol amendment. 

4 TEST ARTICLE DATA: 

4.1 Identification: 

(

4.2 Lot Number: 

To be provided by the Sponsor. 

4.3 Puritv: 

To be provided by the Sponsor in Certificate of Analysis. 

4.4 Stabilitv: 

Stable under conditions of storage. Expiration date: to be added by protocol 

amendment. 

4.5 Physical Description: 

To be documented by 

4.6 Storage Conditions: 

Ambient conditions in Inhalation Department test article storage area. 

4.7 Reserve Samples: 

A reserve sample of each lot of the test article will be taken in accordance with 

Standard Operating Procedures and stored in the Archives at 

 indefinitely, unless otherwise specified. 

4.8 Personnel Safety Information: 

To be provided by the Sponsor, preferably in the form of a Material Safety Data 

Sheet (MSDS). 

At a minimum, technical staff will wear safety glasses, appropriate gloves, and 

facility clothing when handling or working with the test article. Additional 

personal protective equipment, such as a respirator, protective coveralls or 

sleeve covers, may be required. Specific equipment and its use will be defined 

by study management and communicated to technical staff, as appropriate. 

422 of 435
Page 5 of 17 January 8,2008 

5 TEST SYSTEM: 

5.1 Species: 

Rat 

5.2 Strain: 

Sprague-Dawley c~~:cD@(sD). 

5.3 Source: 

Charles River Laboratories 

(Facility to be documented in study records) 

5.4 Number on Studv: 

Five males and 5 females per exposure level (40 animals on study). 

Twenty-five animalslsex will be purchased. 

The n er of animals used will be the minim eded to meet the 

objectives of the study. 

5.5 Approximate Weight: 

250 to 350 grams for males and 170 to 300 grams for females at initiation of 

exposure, + 20% of the mean for each sex. 

5.6 Approximate Ape: 

8-12 weeks at the time of exposure 

5.7 Identification Svstem: 

mals will be uniquely identified by a metal ear tag displaying the animal 

number. Individual cage cards will be affixed to each cage and will display the 

study number, animal number and group (exposure level). 

5.8 Justification for Selection: 

This species and strain is generally recognized to be appropriate for inhalation 

studies. The Crl:CD(SD) rat will be utilized because it is a widely-used strain 

for which significant historical control data are available. The number of 

423 of 435
Page 6 of 17 January 8,2008 

animals selected is the minimum needed to yield statistically valid and 

scientifically meaningful data. 

6 SPECIFIC WON-EXPOSURE PERIOD) MAINTENANCE SCHEDULE: 

6.1 Animal Housing: 

The animals will be individually housed in suspended wire-mesh cages in an 

environmentally controlled room. The cages will be elevated above cage-board 

or other suitable material. The cages will be subject to routine cleaning at a 

frequency consistent with maintaining good animal health. The facilities at 

 are fully accredited by the Association for 

Assessment and Accreditation of Laboratory Animal Care International 

(AAALAC International). 

6.2 Environmental Conditions: 

Controls will be set to maintain an average daily temperature of 71 * 5°F 

(approximately 22 + 3°C) and an average daily relative humidity of 50 * 20%. 

Temperature and relative humidity will be monitored continuously. Data for 

these two parameters will be scheduled for automatic collection on an hourly 

basis. Fluorescent lighting will provide illumination for a 12 hour lighvdark 

photoperiod. Temporary adjustments to the lighvdark cycles may be made to 

accommodate protocol-specified activities. The ventilation rate will be set at a 

minimum of 10 room air changes per hour, 1'00% fresh air.

6.3 Drinkinp Water: 

Reverse osmosis-treated tap water will be available ad libitum via an automatic 

watering system throughout the study, except during exposure periods. Filters 

servicing the automatic watering system are changed regularly according to 

Standard Operating Procedures. Water supplying the laboratory is 

analyzed for contaminants according to Standard Operating Procedures to 

ascertain that none are present at concentrations that would be expected to affect 

the outcome of the study. 

6.4 Basal Diet: 

PMI Nutition International, LLC Certified Rodent ~ab~iet@ 5002 will be 

offered ad libitum throughout the study, except during exposure periods or any 

scheduled period of fasting. Each lot utilized will be identified and recorded. 

Standard Operating Procedures provide specifications for acceptable levels of 

heavy metals and pesticides that are reasonably expected to be present in the 

diet without interfering with the purpose or conduct of the study. Each lot of 

feed has been analyzed to assure specifications are met. Feeders will be 

424 of 435
Page 7 of 17 

WnJanuary 8,2008 

changed and sanitized once per week. Copies of the appropriate analyses will 

be maintained on file at

.7 EXPERIMENTAL DESIGN: 

7.1 Animal Recei~t and Acclimation ' 

Each animal will be inspected by a qualified technician upon receipt. Animals 

judged to be in good health and suitable as test subjects will be acclimated for a 

minimum of seven days. All animals will be weighed and permanently 

identified with an ear tag. 

During the acclimation period, each animal will be observed twice daily for 

changes in general appearance and behavior. The animals will be allowed a 

pretreatment week (as part of the acclimation period) during which body 

weights and food consumption will be recorded and general health will be 

monitored, but they will not receive the test article. All animals will receive a 

detailed physical examination approximately one week prior to initiation of 

dosing and at the time of animal selection for randomization. 

7.2 Randomization: 

Near the end of the acclimation period, animals judged to be suitable for testing 

will be assigned to groups at random based on body weight stratification into a 

block design using a computer program. A printout containing the animal 

numbers and individual group assignments will be generated. Animals will then 

be arranged into groups according to the printout. Body weights at 

randomization will be within A 20% of the mean for each sex. If, after 

randomization, significant differences between groups exist, new 

randomizations will be generated until group mean body weights are not 

statistically different between groups by sex. 

7.3 Route and Rationale of Test Article Administration: 

The route of administration will be inhalation exposure since this is a potential 

route of human exposure. 

425 of 435
Page 8 of 17 January 8,2008 

7.4 Organization of Test Groups, Exposure Levels and Treatment Regimen: 

7.4.1 Organization of Test Groups: 

The following table presents the study group arrangement. 

7.4.2 Exposure Levels: 

Group 

Number 

1 

2 

3 

4 

The three test article exposure concentrations were selected by the 

Sponsor based on the results of previous inhalation toxicity studies. 

7.4.3 Treatment Regimen: 

Test 

Article 

Filtered Air 

Filtered-air and test article vapor atmospheres will be administered as 

six-hour, whole-body exposures for 5 consecutive days. On the day 

following the fifth exposure, all animals will be euthanized and 

necropsied. The first day of exposure is defined as exposure day zero. 

7.5 Exposure Methods: 

Exposures will be conducted in 500-L stainless-steel and glass whole-body 

exposure chambers. The exposure systems will be operated under dynamic

conditions from a HEPA- and charcoal-filtered air source or breathing quality

in-house compressed air source. Air flow rate through the chamber will be such

that there will be 12-15 air changes per hour. Mean chamber temperature and

relative humidity will be 22 * 2°C and 30-70%, respectively. These parameters

will be monitored continuously and recorded approximately every 30-40 minutes

throughout the exposure. Readings outside the average range will be documented.

Oxygen content of the exposure atmosphere will be measured during the methods

development phase of the study, while operating at the above targeted conditions, 

and will be at least 19%. 

Target Exposure 

Level (ppm) 

0 

1250" 

2500 

5000 

All animals will be housed in a normal animal colony room during 

non-exposure hours. For each day's exposure, the animals will be placed in 

exposure batteries, transported to the exposure room, exposed for the requisite 

duration, and returned to their home cages. Food and water will not be 

availa ng the exposures. 

Number of Animals 

Males 

5 

5 

5 

5 

Females 

5 

5 

5 

5 

426 of 435
5340 1 1 

Page 9 of 17 January 8,2008 

7.6 Test Material Generation Methods: 

Vapors of the test article will be generated using a bead-filled vaporization 

column or a gas-washing bottle, or other appropriate generation system. Prior 

to entering the test chambers, the vapors will be mixed with dilution air to 

achieve desired exposure levels. Further details of generation systems and 

methodologies, including specific types andlor models and operating conditions 

for the system, will be defined during pre-study method development and included 

in a description of exposure, test atmosphere generation and monitoring methods, 

which will be approved by the Study Director. 

7.7 Methods of Characterization of Exposure Atmospheres: 

7.7.1 Nominal Concentrations: 

Nominal exposure concentrations will be calculated for each day's 

exposure using the following formula: 

PPm - Wt. Mol. Vol. lo6 

MW Ch. Flow Exp. Dur. 

Where: 

Wt. = the weight of test article used during a given day's 

exposure, grams 

Mol. Vol. = molar volume of test article at 730 mrn Hg and 21°C 

1 o6 = ppm conversion factor 

MW = molecular weight of test article 

Ch. Flow = daily average chamber flow rate for a given day, in 

L/min 

Exp. Dur. = duration of a given days' exposure, in minutes 

Given the physical characteristics of the test article, it is expected that 

the nominal concentration will be within *lo% of the measured chamber 

concentration. Variation outside this range will be investigated as 

potential system performance problems. 

7.7.2 Analyzed Exposure Concentrations: 

Analyzed concentrations of the test article(s) in the exposure chamber 

will be determined by a specific on-line gas chromatographic method 

and will be measured approximately every 30-40 minutes throughout the 

exposure period. Details concerning these specific methods to be used 

will be defined during pre-study method development and included in a 

427 of 435
Page 10 of 17 January 8,2008 

description of exposure, test atmosphere generation and monitoring 

methods, which will be approved by the Study Director. 

The calibration of the gas chromatograph will be considered acceptable if 

the r2 value is > 0.98 and the individual points of the calibration are within 

10% of their target concentrations. Daily mean analyzed concentrations 

of test article will be maintained within * 10% get exposure 

concentrations. 

8 EXPERIMENTAL OBSERVATIONS: 

8.1 Viability Observations: 

All animals will be observed for mortalitylmoribundity twice daily, once in the 

morning and once in the afternoon, except on the day of scheduled necropsy. 

Moribund animals will be euthanized to ensure that tissues will not be lost due 

to autolysis. 

8.2 Clinical Observations: 

Clinical observations will be conducted prior to exposure and 0-1 hour 

following the exposure on exposure days. The clinical observations prior to 

exposure will not be performed on the days of detailed physical examinations.

Observations will include, but are not limited to, changes in the skin, fur, eyes 

and mucous membranes, respiratory, circulatory and autonomic and central 

nervous system functions, somatomotor activity and behavior patterns. 

Findings noted at the clinical examination will be recorded for individual 

animals; the condition of animals without signs will be documented as a general 

comment. 

8.3 Detailed Physical Examination: 

All animals will receive a detailed physical examination prior to test article 

administration for randomization and group assignment and twice during the 

exposufe phase (including prior to scheduled necropsy). Animals to be 

euthanized prior to scheduled necropsy will undergo an additional detailed 

physical examination prior to euthanasia to issist in determination of the cause 

of death. 

The animals will be removed fiom their home cages and placed in a standard 

arena for observation. Observations will be detailed and carefully noted. When 

appropriate, explicitly defined scoring systems will be used if, in the opinion of 

the Study Director, doing so increases the utility of the data. Signs noted shall 

include, but are not limited to, changes in skin, fur, eyes, mucous membranes, 

occurrence of secretions and excretions, and autonomic activity (e.g., 

428 of 435
Page 11 of 17 January 8,2008 

lacrimation, piloerection, pupil size, unusual respiratory pattern). Changes in 

gait, posture and response to handling, as well as the presence of clonic or tonic 

movements, stereotypes (e.g., excessive grooming, repetitive circling) or bizarre 

behavior (e.g., self-mutilation, walking backwards) will be recorded. The 

absence or presence of findings will be recorded for individual animals. 

8.4 Individual Bodv Weights: 

Individual body weights will be recorded during the pretest phase for 

randomization and group assignment and prior to the first, third and fifth 

exposures. The animals will be fasted overnight prior to scheduled necropsy. A 

final body weight will be determined prior to necropsy. 

8.5 Individual Food Consum~tion: 

Individual food consumption will be recorded weekly for all animals, beginning 

at least one week prior to test article administration. 

8.6 Clinical Patholow: 

Hematology, serum chemistry and coagulation parameters will be evaluated 

fiom all surviving animals on the day of the scheduled necropsy. The animals 

will be fasted overnight before blood collection and necropsy. For hematology 

(except clotting parameters) and standard serum chemistry evaluations, blood 

samples will be collected fiom the retro-orbital sinus fiom animals anesthetized 

using isoflurane. Blood samples for clotting evaluations will be collected via 

the vena cava at necropsy (animals anesthetized using isoflurane). EDTA will 

be used for the anticoagulant on samples collected for hematology, and sodium 

citrate will be used for samples collected for clotting determinations. Serum 

collection tubes will be used for blood samples collected for serum chemistry. 

8.6.1 Hematology: 

Differential leukocyte counta Mean corpuscular hemoglobin 

Erythrocyte count Concentration 

Hematocrit Mean corpuscular volume 

Hemoglobin Platelet Count 

Mean corpuscular hemoglobin Reticulocyte count 

Total leukocyte count a - If performed manually, results will include platelet estimates and RBC 

morphology. 

8.6.2 Coagulation Parameters: 

Activated partial thromboplastin time Prothrombin time 

429 of 435
Page 12 of 17 January 8,2008 

8.6.3 Serum Chemistry: 

A/G ratio 

Alanine aminotransferase 

Albumin 

Alkaline phosphatase 

Aspartate aminotransferase 

Calcium 

Chloride 

CreatinineGlobulin 

Glucose 

Phosphorus 

Potassium 

Sodium 

Total bilirubin 

Total cholesterol 

Total protein 

Triglycerides 

Urea nitrogen 

8.7 Anatomic Pathology: 

8.7.1 Macroscopic Examination: 

A complete necropsy will be conducted on all animals dying 

spontaneously, euthanized in extremis or at the scheduled necropsy. 

Animals euthanized in extremis or at the scheduled necropsy will be 

anesthetized with isoflurane and exsanguinated. Necropsy will include 

examination of the external surface; all orifices; and the cranial, 

thoracic, abdominal and pelvic cavities including viscera. The following 

tissues will be collected and placed in 10% neutral-buffered formalin: 

430 of 435
Page 13 of 17 January 8,2008 

Adrenal glands (2) 

Aorta 

Bone with marrow (sternebrae) 

Bone with marrow (femur with joint) 

Bone marrow smear (taken fiom femur") 

Brain 

Cerebrum Level 1 

Cerebrum Level 2 

Cerebellum with ponslmedulla 

Cervix 

Epididymides (21b 

Eyes with optic nerves (2)' 

Gastrointestinal tract 

Esophagus 

Stomach 

Duodenum 

Jejunum 

Ileum Peyer's patches 

Cecum 

Colon 

Rectum 

Harderian glands (2) 

Heart 

Kidneys (2) 

Lacrimal glands [exorbital (2)] 

Larynx 

Liver (sections of two lobes) 

Lungs (including bronchi, fixed by 

inflation with fixative) 

Lymph node 

Mediastinal and bronchial (if visible) 

Mesenteric and mandibular (2) 

~a'krnar~ gland (females only) 

Nasal cavityd 

Ovaries/oviducts (2)" 

Pancreas 

Peripheral nerve (sciatic) 

Peyer's patches 

Pharynx 

Pituitary 

Prostate 

Salivary glands [mandibular (2)] 

Seminal vesicles (2) 

Skeletal muscle (rectus femoris) 

Skin 

Spinal cord 

Cervical 

Thoracic 

Lumbar 

Spleen 

Testes (2)b 

Thymus 

Thyroid gland [with parathyroids (2)Ie 

Trachea 

Urinary bladder 

Uterus 

Vagina 

All gross lesions 

a - Bone marrow smears will be obtained at scheduled necropsy and fiom all anirilals euthanized in 

extrernis (not placed in formalin). To be examined only if scientifically warranted. 

b - Placed in Bouin's solution. 

c - Placed in Davidson's solution. 

d - Following collection of the appropriate protocol-specified tissues, the entire head will be removed 

and preserved. 

e - Parathyroids and oviducts will be examined microscopically if in the plane of section and in all cases 

when a gross lesion of the organ is present. 

431 of 435
Page 14 of 17 January 8,2008 

8.7.2 Organ Weights: 

The following organs fiom all animals at the scheduled necropsy will be 

weighed: 

Liver Kidneys 

Lungs (prior to inflation with fixative) Brain 

Paired organs will be weighed together. Organ-to-body-weight and 

organ-to-brain-weight ratios will be calculated fiom animals euthanized 

at the scheduled necropsy. 

8.7.3 Microscopic Examination: 

Microscopic examination of hematoxylin-eosin stained tissue sections 

will not be conducted, but may be performed at a later date at additional 

cost. 

9 STATISTICAL METHODS: 

All statistical tests for experi ata will be performed using appropriate 

cpmputing devices or programs as referenced below. All analyses will be two-tailed 

for significance levels of 5% and 1%. Mean values will be presented with standard 

deviations. Body weights, body weight changes and food consumption as well as 

clinical pathology values and absolute and relative organ weights will be subjected to 

a one-way analysis of variance (Snedecor and Cochran, 1980). If a statistically 

significant difference (pC0.05) is present in this ANOVA, a comparison of the control 

group to each treated group by Dunnett's test (Dunnett, 1964) will be performed. 

Statistical analysis will not be performed on groups with an N of two (2) or less. 

10 REPORT: 

The Final Report will contain a summary, test material data, methods and procedures, 

appropriate individual animal and summary data tables, methods and results of test 

atmosphere generation and characterization, a copy of the protocol and amendments 

(if any) and an interpretation and discussion of the study results. The report will be 

comprehensive and shall attempt to define toxicity and the no-observed-effect level(s) 

under the conditions of this investigation. 

will submit one copy of an audited draft report in a 

timely manner upon completion of data collection prior to issuance of the final report. 

One revision will be permitted as part of the cost of the study, fiom which the 

Sponsor's reasonable revisions and suggestions will be incorporated into the final 

report, as appropriate. Additional changes or revisions may be made, at an extra cost. 

It is expected that the Sponsor will review the draft report and provide comments to 

432 of 435
Pace 15 of 17 January 8,2008 

within a two-month time frame following submission. will submit the final 

report within one month following receipt of comments. If the Sponsor's comments 

and/or authorization to finalize the report have not been received at within one 

year following submission of the draft report, may elect to finalize the report 

following appropriate written notification to the Sponsor. The original paper final 

report (containing original signatures) and two electronic copies (one in PDF and one 

in MS Word format) of the final report on CD-R will be provided. Requests for 

additional paper copies of the final report may result in additional charges. 

11 QUALITY ASSURANCE: 

The study will be audited by the Quality Assurance Unit while in progress to 

assure complisince with Good Laboratory Practice Regulations, adherence to the 

protocol and to Standard Operating Procedures. The raw data and draft report 

will be audited by the Quality Assurance Unit prior to submission to the Sponsor 

to assure that the final report accurately describes the conduct and the findings of the 

study. 

12 RECORDS TO BE MAINTAINED: 

All original raw data, as defined by SOPs and the applicable GLPs, will be 

maintained in permanently bound notebooks or in loose-leaf notebooks and at study 

completion will be stored in the Archives at

13 WORK PRODUCT: 

Sponsor will have title to all documentation records, raw data, slides, specimens, or 

other work product generated during the performance of the study. All work product 

including raw paper data and pertinent electronic storage media will be retained for a 

period of ten (10) years following issuance of the final report in the archives at 

Thereafter, will 

charge a monthly archiving fee for retention of all work product. All work product 

will be stored in compliance with regulatory requirements. 

Any work product, including documents, specimens, and samples, that are required 

by this protocol, its amendments, or other written instructions of the Sponsor, to be 

shipped by to another location will be appropriately 

packaged and labeled as defined by SOPs and delivered to a common carrier for 

shipment. will not be responsible for shipment 

following delivery to the common carrier. 

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Paae 16 of 17 

14 ANIMAL WELFARE ACT COMPLIANCE: 

This study will comply with all applicable sections of the Final Rules of the Animal 

Welfare ~ct regulations (9 CFR). The Sponsor should make particular note of the 

following: 

The Sponsor signature on this protocol documents for the Study Director the 

Sponsor's assurance that the study described in this protocol does not unnecessarily 

duplicate previous experiments. 

Whenever possible, procedures used in this study have been designed to avoid or 

minimize discomfort, distress or pain to animals. All methods are described in this 

study protocol or in written laboratory Standard Operating Procedures. 

Animals that experience severe or chronic pain or distress that cannot be relieved 

will be painlessly euthanized as deemed appropriate by the veterinary staff and 

Study Director. The Sponsor will be advised by the Study Director of all 

circumstances which could lead to this action in as timely a manner as possible. 

Methods of euthanasia used during this study are in conformance with the above 

referenced regulation. 

The SponsorIStudy Director has considered alternatives to procedures that may 

cause more than momentary or slight pain or distress to the animals and has 

provided a written narrative description (AWA covered species) of the methods and 

sources used to determine that alternatives are not available. 

15 REFERENCES: 

Dunnett, C.W. New tables for multiple comparisons with a control. Biometries 1964, 

20, pp. 482-491. 

434 of 435
Page 17 of 17 January 8,2008 

Snedecor, G.W. and Cochran, W.G. One Way Classifications; Analysis of Variance. In 

Statistical Methods, 7th ed.; The Iowa State University Press: Arnes, IA, 1980; pp. 

21 5-237. 

16 PROTOCOL APPROVAL: 

Sponsor approval received via email on 08 January 2008. 

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