# Page 1 of 640 

# REPORT

BENZOFLEX 1046:

Oral (Gavage) Combined Repeat Dose Toxicity Study with

Reproduction/Developmental To xicity Screening Test in the

Rat (OECD 422 with Recovery Groups)

Study Director: J Dunster

Test Facility: Harlan Laboratories Ltd.

Shardlow Business Park

Shardlow

Derbyshire

DE72 2GD

UK



# Sponsor: Eastman Chemical Company

100 North Eastman Road

P.O. Box 511

Kingsport

TN 37662-5054

USA

Harlan Study Number: 41204605

Study Completion Date: 13 November 2013

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# CONTENTS

CONTENTS ...................................................................................................................... .............. 3

STUDY DIRECTOR STATEMENT OF GLP COMPLIANCE .................................................... 9

QUALITY ASSURANCE STATEMENT.................................................................................... 11

SIGNATURE OF MANAGEMENT ............................................................................................ 13

SUMMARY ....................................................................................................................... ........... 15

Introduction .................................................................................................................. ........ 15

Methods....... .................................................................................................................... .. 15

Results....... .................................................................................................................... ..... 16

Adult Responses ............................................................................................................... ... 16

Mortality ..................................................................................................................... ......... 16

Clinical Observations ......................................................................................................... .. 16

Behavioural Assessment ...................................................................................................... 1 6

Functional Performance Tests ............................................................................................. 16

Sensory Reactivity Assessments .......................................................................................... 16

Body Weight ................................................................................................................... ..... 16

Food Consumption .............................................................................................................. . 17

Water Consumption ............................................................................................................. 17

Reproductive Performance .................................................................................................. 17

Mating ....................................................................................................................... ........ 17

Fertility .................................................................................................................... ........... 17

Gestation Lengths ............................................................................................................. ... 17

Litter Responses .............................................................................................................. ..... 17

Offspring Litter Size, Sex Ratio and Viability .................................................................... 17

Offspring Growth and Development ................................................................................... 18

Laboratory Investigations .................................................................................................... 18

Haematology ................................................................................................................... ..... 18

Blood Chemistry ............................................................................................................... ... 18

Urinalysis .................................................................................................................... ......... 18

Pathology ..................................................................................................................... ........ 18

Necropsy ...................................................................................................................... ........ 18

Organ Weights ................................................................................................................. .... 18

Histopathology ................................................................................................................ ..... 19

Conclusion .................................................................................................................... ....... 19

GENERAL INFORMATION ....................................................................................................... 20

Schedule ...................................................................................................................... ......... 20

Animal Welfare ................................................................................................................ .... 20

Multi – Site Study Details .................................................................................................... 20

Additional Responsibilities .................................................................................................. 21

Deviations from Study Plan ................................................................................................. 21

Archiving ..................................................................................................................... ........ 22

1 INTRODUCTION AND PURPOSE ................................................................................... 23

1.1 Guidelines / Regulations ........................................................................................ 23

2 TEST ITEM ..................................................................................................................... .... 24

2.1 Test Item ................................................................................................................ 24

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# 3 MATERIALS AND METHODS ........................................................................................ 24

3.1 Test System ........................................................................................................... 24

3.1.1 Animals and Animal Husbandry ............................................................. 24

3.1.2 Justification ............................................................................................. 25

3.2 Test Item Preparation ............................................................................................ 25

3.3 Procedure ............................................................................................................... 26

3.3.1 Chronological Sequence of Study ........................................................... 26

3.3.1.1 Non-Recovery Dose Groups ................................................................... 26

3.3.1.2 Recovery Dose Groups ........................................................................... 27

3.4 Observations .......................................................................................................... 27

3.4.1 Clinical Observations .............................................................................. 27

3.4.2 Functional Observations .......................................................................... 27

3.4.2.1 Behavioural Assessments ........................................................................ 27

3.4.2.2 Functional Performance Tests ................................................................. 28

3.4.2.3 Sensory Reactivity .................................................................................. 28

3.4.3 Body Weight ........................................................................................... 29

3.4.4 Food Consumption .................................................................................. 29

3.4.5 Water Consumption ................................................................................ 29

3.4.6 Reproductive Performance ...................................................................... 29

3.4.6.1 Mating ..................................................................................................... 30

3.4.6.2 Pregnancy and Parturition ....................................................................... 30

3.4.6.3 Litter Data ............................................................................................... 30

3.4.6.4 Physical Development ............................................................................. 30

3.4.7 Laboratory Investigations ........................................................................ 31

3.4.7.1 Haematology ........................................................................................... 31

3.4.7.2 Blood Chemistry ..................................................................................... 32

3.4.7.3 Urinalysis ................................................................................................ 32

3.4.8 Pathology ................................................................................................. 32

3.4.8.1 Necropsy ................................................................................................. 32

3.4.8.2 Organ Weights ........................................................................................ 33

3.4.8.3 Histopathology ........................................................................................ 33

3.4.9 Evaluation of Data ................................................................................... 35

3.4.9.1 Treatment of Data ................................................................................... 35

3.4.9.2 Reproductive Indices ............................................................................... 35

3.4.9.3 Litter Responses ...................................................................................... 36

3.4.9.4 Statistical Analysis .................................................................................. 37

4 RESULTS AND DISCUSSI ON ............................ .............................................................. 39

4.1 Results ................................................................................................................... 39

4.1.1 Adult Reponses ....................................................................................... 39

4.1.1.1 Mortality .................................................................................................. 39

4.1.1.2 Clinical Observations .............................................................................. 39

4.1.1.3 Functional Observations .......................................................................... 39

4.1.1.4 Body Weight ........................................................................................... 40

4.1.1.5 Food Consumption .................................................................................. 41

4.1.1.6 Water Consumption ................................................................................ 41

4.1.2 Reproductive Performance ...................................................................... 41

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# 4.1.2.1 Mating ..................................................................................................... 41

4.1.2.2 Fertility .................................................................................................... 41

4.1.2.3 Gestation Length ..................................................................................... 42

4.1.3 Litter Responses ...................................................................................... 42

4.1.3.1 Offspring Litter Size, Sex Ratio and Viability ........................................ 42

4.1.3.2 Offspring Growth and Development ....................................................... 42

4.1.4 Laboratory Investigations ........................................................................ 43

4.1.4.1 Haematology............................................................................................ 43

4.1.4.2 Blood Chemistry ...................................................................................... 43

4.1.4.3 Urinalysis ................................................................................................. 44

4.1.5 Pathology ................................................................................................. 44

4.1.5.1 Necropsy .................................................................................................. 44

4.1.5.2 Organ Weights ......................................................................................... 45

4.1.5.3 Histopathology ........................................................................................ 45

4.2 Discussion .............................................................................................................. 46

5 CONCLUSION .................................................................................................................... 47

6 REFERENCES .................................................................................................................... 48

TABULAR SUMMARY REPORT OF EFFECTS OF

REPRODUCTION/DEVELOPMENT ................................................................................ 49

KEY TO TABLES AND APPENDICES ..................................................................................... 50

KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS AND SENSORY REACTIVITY TESTS ............................................... 51

TABLES ........................................................................................................................ ................ 57

FIGURES ....................................................................................................................... ............. 153

APPENDICES .................................................................................................................... ......... 163



# LIST OF TABLES

Table 1 Summary of Reproductive Performance - Groups Values .................................... 58

Table 2 Summary Incidence of Daily Clinical Observations ............................................. 59

Table 3 Summary Incidence of Behavioural Assessments (Observations) ........................ 61

Table 4 Summary Incidence of Behavioural Assessments (Scores) .................................. 65

Table 5 Group Mean Functional Test Values and Standard Deviations ............................ 79

Table 6 Summary Incidence of Sensory Reactivity Assessments (Scores) ........................ 81

Table 7 Group Mean Body Weight Values ........................................................................ 83

Table 8 Group Mean Body Weight Gains .......................................................................... 88

Table 9 Group Mean Food Consumptions .......................................................................... 93

Table 10 Food Efficiency ..................................................................................................... 98

Table 11 Group Mean Daily Water Consumptions ............................................................ 102

Table 12 Summary Incidence of Mating Performance, Fertility and Gestation

Lengths ................................................................................................................ 117

Table 13 Group Mean Litter Size and Litter Weights ........................................................ 118

Table 14 Group Mean Implantation Losses and Survival Indices Values .......................... 119

Table 15 Group Mean Sex Ratio Values ............................................................................ 120

Table 16 Summary Incidence of Clinical Signs for Offspring ........................................... 121

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# Table 17 Group Mean Reflexological Responses for Offspring ........................................ 122

Table 18 Group Mean Haematological Values .................................................................. 123

Table 19 Group Mean Blood Chemical Values ................................................................. 127

Table 20 Summary Incidence of Urinalytical Findings ..................................................... 135

Table 21 Summary Incidence of Offspring Necropsy Findings ......................................... 137

Table 22 Summary Incidence of Necropsy Findings ......................................................... 138

Table 23 Group Mean Organ Weights with Corresponding Relative (% of

Body Weight) Organ Weights ............................................................................. 140



# LIST OF FIGURES

Figure 1 Group Mean Body Weights - Males .................................................................... 154

Figure 2 Group Mean Body Weights - Females ................................................................ 156

Figure 3 Group Mean Food Consumption - Males ............................................................ 159

Figure 4 Group Mean Food Consumption – Females ........................................................ 160



# LIST OF APPENDICES

Appendix 1 Individual Daily Clinical Observations ............................................................... 164

Appendix 2 Individual Behavioural Assessments (Observations) .......................................... 196

Appendix 3 Individual Behavioural Assessments (Scores) .................................................... 204

Appendix 4 Individual and Group Mean Functional Test Values (Grip Strength) ................. 260

Appendix 5 Individual and Group Mean Functional Test Values (Motor

Activity) ............................................................................................................... 268

Appendix 6 Individual Sensory Reactivity Assessments ........................................................ 276

Appendix 7 Individual and Group Mean Body Weights ........................................................ 284

Appendix 8 Individual and Group Mean Body Weight Gains ................................................ 300

Appendix 9 Individual and Group Mean Food Consumption Values for Females

Following Mating and During Lactation ............................................................. 316

Appendix 10 Individual and Group Mean Water Consumption Values for

Females Following Mating and Lactation ........................................................... 320

Appendix 11 Individual Mating Performance, Fertility and Gestation Lengths ....................... 324

Appendix 12 Individual and Group Mean Litter Size and Litter Weights ................................ 328

Appendix 13 Individual and Group Mean Implantation Losses and Survival

Indices ................................................................................................................. 332

Appendix 14 Individual and Group Mean Sex Ratio Values for Offspring ............................. 336

Appendix 15 Individual Clinical Signs for Offspring ............................................................... 340

Appendix 16 Individual and Group Mean Re flexological Responses for

Offspring ............................................................................................................. 344

Appendix 17 Individual Haematological Values ...................................................................... 348

Appendix 18 Individual Coagulation Values ............................................................................ 360

Appendix 19 Individual Blood Chemical Values ..................................................................... 372

Appendix 20 Individual Bile Acid Values ................................................................................ 384

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# Appendix 21 Individual and Group Mean Urinalytical Findings .............................................. 396

Appendix 22 Individual Necropsy Findings for Offspring ....................................................... 402

Appendix 23 Individual Necropsy Findings ............................................................................. 406

Appendix 24 Individual Organ Weights ................................................................................... 414

Appendix 25 Individual Relative Organ Weights ..................................................................... 426

Appendix 26 Histopathology Phase Report .............................................................................. 444

Appendix 27 Analytical Investigations ..................................................................................... 583

Appendix 28 Study Plan ............................................................................................................ 594

Appendix 29 Histology Processing Phase Test Site Quality Assurance Statement .................. 623

Appendix 30 Histology Processing Phase Test Site Statement of Compliance ........................ 624

Appendix 31 Histology Processing Phase Test Site Statement of GLP

Compliance .......................................................................................................... 625

Appendix 32 Certificates of Analysis of Diet Used .................................................................. 626

Appendix 33 Laboratory Methods ............................................................................................ 630

Appendix 34 Normal Ranges for Reproductive Parameters in the Pregnant and

Lactating Female Wistar HanTM:RccHanTM:WIST Strain Rat ............................ 633

Appendix 35 Normal Ranges for Offspring Pa rameters in the Wistar HanTM:

RccHanTM:WIST Strain Rat ................................................................................ 634

Appendix 36 Normal Ranges for Haematological and Blood Chemical Values in

the Wistar HanTM:RccHanTM:WIST Strain Rat ................................................... 635

Appendix 37 Normal Ranges for Absolute and Body Weight-Relative Organ

Weight Values in the Wistar HanTM:RccHanTM:WIST Strain Rat ...................... 637

Appendix 38 Certificate of Analysis of the Test Item ............................................................... 639

Appendix 39 Monitoring Authority Statement of GLP Compliance ........................................ 640

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# SUMMARY

Introduction

The study was designed to investigate the systemic toxicity and potential adverse effects of the

test item on reproduction (including offspring development) and is designed to be compatible

with the requirements of the OECD Guidelines for Testing of Chemicals No. 422 “Combined

Repeated Dose Toxicity Study with the Reproduc tion/ Developmental Toxicity Screening Test”

(adopted 22 March 1996).



# Methods

.......

The test item was administered by gavage to three groups, each of twelve male and twelve

female Wistar HanTM:Rcc HanTM:WIST strain rats, for up to eight weeks (including a two week

pre-pairing phase, pairing, gestation and early lact ation for females), at dose levels of 30, 60 and

120 mg/kg bw/day. A control group of twelve males and twelve females was dosed with vehicle

alone (Arachis oil BP). Two recovery groups, each of five males and five females, were treated

with the high dose (120 mg/kg bw/day) or the vehicle alone for forty-two consecutive days and

then maintained without treatment for a further fourteen days.

Clinical signs, behavioural assessments, body we ight change and food and water consumption

were monitored during the study.

Pairing of non-recovery animals within each dose group was undertaken on a one male: one

female basis within each treatment group on Day 15 of the study, with females subsequently

being allowed to litter and rear their offspring to Day 5 of lactation.

During the lactation phase, daily clinical observa tions were performed on all surviving offspring,

together with litter size and offspring wei ghts and assessment of surface righting reflex.

Extensive functional observations were perform ed on five selected non-recovery males from

each dose group after the completion of the pairi ng phase, and for five selected parental females

from each dose group on Day 4 post partum . Urinalysis was performed on five non-recovery

males per dose group during the final week of treatment and five non-recovery males and

females from each dose group were selected fo r haematology and blood chemistry assessments

prior to termination.

Adult non-recovery males were terminated on Day 43, followed by the termination of all females

and offspring on Day 5 post partum . Any female which did not produce a pregnancy was

terminated on or after Day 25 post coitum . All animals were subjected to a gross necropsy

examination and histopathological evaluation of selected tissues was performed.

Following forty-two days of treatment, recovery group animals were maintained without

treatment for a further fourteen days. Urinal ysis was performed on all recovery group males

during the final week of the treatment period. In addition, haematological and blood chemical

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# assessments were performed on all recovery group animals at the end of the treatment-free

period. These animals were then subjected to a gross necropsy.



# Results

.......

Adult Responses

Mortality

There were no unscheduled deaths.



# Clinical Observations

There were no clinically observable signs of toxicity detected during the study.



# Behavioural Assessment

No treatment-related e ffects were detected.



# Functional Performance Tests

No treatment-related e ffects were detected.



# Sensory Reactivity Assessments

There were no treatment-related changes in sensory reactivity.



# Body Weight

Actual body weight losses and reduced body weight gains were evident for some animals of

either sex treated with 120 mg/kg bw/day when compared to controls. Reduced body weight

gains were also evident during the first two weeks of treatment for animals of either sex treated

with 60 mg/kg bw/day.

Reduced body weight gains were evident for females treated with 120 and 60 mg/kg bw/day

throughout the gestation phase, when compared to controls.

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# Actual body weights were lower for treated females during the study when compared to controls.

For recovery animals, high dose males showed a reduction in body weight gains and actual body

weight losses when compared to controls during the first three weeks of treatment, with recovery

thereafter.



# Food Consumption

Reduced dietary intake was evident for males treated with 120 and 60 mg/kg bw/day. Females at

all dose levels showed a reduction in dietary inta ke during the pre-pairing phase when compared

to controls. Reductions in dietary intake at all dose levels were also evident during gestation

when compared to controls.



# Water Consumption

Daily measurements of water bottles did not reveal any significant intergroup differences.



# Reproductive Performance

Mating

No treatment-related effects were detected in mating performance.



# Fertility

There were no treatment-related changes detected in fertility.



# Gestation Lengths

No treatment-related effects were detected in the length of gestation between control and treated

groups.



# Litter Responses

Offspring Litter Size, Sex Ratio and Viability

One female treated with 120 mg/kg bw/day showed both corpora lutea and implantation sites,

but did not produce a litter. Furthermore, there were two total litter losses observed at 120 mg/kg

bw/day.

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# No differences in sex ratio or litter size were evident for offspring from treated litters when

compared to those from the controls. No significant differences in the number or corpora lutea

or implantation sites were noted for treated female s when compared to controls. The percentages

of pre- and post-implantation loss for treate d females were compar able to controls.



# Offspring Growth and Development

No significant differences in litter weights or offspring weights were evident in the treated

groups when compared to controls. There were no clinically observable signs of toxicity

observed in offspring, or any macroscopic abnormalities detected at terminal kill.



# Laboratory Investigations

Haematology

There were no toxicologically significant cha nges detected in the haematology parameters

investigated.



# Blood Chemistry

There were no toxicologically significant cha nges detected in the blood chemical parameter

investigated.



# Urinalysis

There were no treatment-rela ted changes detected.



# Pathology

Necropsy

There were no treatment-related macroscopic abnormalities detected.



# Organ Weights

There were no toxicologically significant organ weight changes detected.

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# Histopathology

Histopathological examinations did not reveal any treatment-related changes.



# Conclusion

The oral administration of Benzoflex 1046 to rats by gavage, at dose levels of 120, 60 and

30 mg/kg bw/day, resulted in treatment-related changes at all dose levels. The effects detected at

60 and 30 mg/kg bw/day were considered not to represent an adverse effect. Therefore a ‘No

Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was considered to be 60 mg/kg

bw/day.

The presence of two females which showed a total litter loss and one female which was pregnant

but did not produce a litter at the high dose level cannot be completely discounted as a treatment

effect upon reproduction even though other parame ters such as fertility and histopathology of

reproductive organs showed no treatment effect s. This effect upon reproduction can only be

classified as equivocal on the basis of only limited toxicological findings on reproduction and

that these findings were only observed at dose le vels where other evidence of general toxicity

could be observed in the adult female (redu ced body weight gain and food consumption).

Therefore, it must be concluded that the ‘No Observed Effect Level’ (NOEL) for reproductive

toxicity was considered to be 60 mg/kg bw/day.

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# GENERAL INFORMATION

Schedule

Experimental Starting Date: 02 January 2013

Experimental Completion Date: 11 November 2013



# Animal Welfare

The study was designed and conducted to cause th e minimum suffering or distress to the animals

consistent with the scientific objectives and in accordance with the Harlan Laboratories Ltd,

Shardlow, UK policy on animal welfare and the requirements of the United Kingdom’s Animals

(Scientific Procedure) Act 1986. The conduct of the study may be reviewed, as part of the

Harlan Laboratories Ltd, Shardlow, UK Ethical Review Process.

The study was conducted in accordance with the UK Home Office Guidance document on

Regulatory Toxicology and Safety Evaluation Studies and the OECD guidance document on

recognition, assessment and use of clinical signs as humane endpoints for experimental animals

used in safety evaluation.



# Multi – Site Study Details

Lead Quality Assurance: J Riley

Harlan Laboratories Ltd.

Study Phase: Histology Processing

Test Site: TUPI Manufacturing

PO Box 305

Diss

Norfolk

IP22 4XL

UK

Principal Investigator: R Trindall

Test Site Quality Assurance: S Needham

TUPI Manufacturing

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# Study Phase: Histopathology Examination

Test Site: Peter Millar Associates Ltd.

3 Queen Charlotte Street

Edinburgh

SCOTLAND

EH6 6AY

Principal Investigator: P Millar

Test Site Quality Assurance: J Lawrence

Peter Millar Associate Ltd.



# Additional Responsibilities

Analytical Investigations: P Watson

Harlan Laboratories Ltd., Shardlow, UK

Animal Health: P Highton

Harlan Laboratories Ltd., Shardlow, UK

Clinical Pathology: J Kemp

Harlan Laboratories Ltd., Shardlow, UK



# Deviations from Study Plan

Deviation No. 1 (22 August 2013)

Urinalysis

During the collection of urine for the recovery male urinalytical investigations, the recovery

females were also housed in metabolism cages overnight and urine samples were collected.

These samples were also examined and data was recorded. This was not required by the Study

Plan and no data was collected for non-recovery fe males therefore this data will be kept in the

Study file but will not be reported.

Organ weights

The ovaries and uterus for female No. 89 were not recorded due to a technician error.

These deviations were considered not to a ffect the purpose or integrity of the study.

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# Archiving

Unless instructed otherwise by the Sponsor, the study plan, all raw data (paper and electronic)

generated at the test facility, all original data including tissue blocks and tissue slides generated

at the histology processing Test Site, the final report and the histopathology examination phase

report and any raw data will be retained in the Harlan Laboratories Ltd, Shardlow, UK archives

for five years after which instructions will be sought as to further retention or disposal.

Unprocessed wet tissue samples will be retained for two years prior to disposal. Further

retention or return of the data will be chargeable to the Sponsor.

No data will be discarded without contacting the Sponsor to obtain their written consent.

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# 1 INTRODUCTION AND PURPOSE

The study was performed according to the study plan presented in Appendix 28 and was

designed to screen for potential adverse effects on reproduction, including offspring

development, by repeated oral administration to the Wistar HanTM:RccHanTM:WIST strain rat for

up to eight weeks at dose levels of 30, 60 and 120 mg/kg bw/day. A control group was dosed

with vehicle alone (Arachis oil BP). Two recovery groups were treated with the high dose level

of 120 mg/kg bw/day or the vehicle alone (Arachis oil BP) for forty-two days and then

maintained without treatment for a further fourteen days.

The dose levels were chosen based on the results of previous toxicity work (Harlan Laboratories

Ltd., Study Numbers 41204604 and 41300243). The oral route was selected as the most

appropriate route of exposure, based on the physical properties of the test item, and the results of

the study are believed to be of value in predicting the likely toxicity of the test item to man.

The study was performed between 02 January 2013 and 11 November 2013 (date of final

histopathology report). The in-life phase of the study was conducted between 27 March 2013

(first day of treatment) and 22 May 2013 (final day of necropsy).



# 1.1 Guidelines / Regulations

The study was designed to be compatible with the requirements of OECD Guidelines for Testing

of Chemicals, No.422: “Combined Repeated Dose Toxicity Study with the Reproduction/

Developmental Toxicity Screening Test” (adopted 22 March 1996).

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# 2 TEST ITEM

2.1 Test Item

Information as provided by the Sponsor.

Identification : Benzoflex 1046

Description : Clear colourless liquid

Purity : not supplied

Batch Number : V046212201

Label : Benzoflex (TM) 1046 Plasticiser Batch V046212201

Date Received : 21 May 2012

Storage Conditions : room temperature in the dark

Expiry Date : 30 April 2014

No correction for purity was made.

The integrity of supplied data relating to the identity, purity and stability of the test item is the

responsibility of the Sponsor.

A Certificate of Analysis of Test Item is included as Appendix 38.



# 3 MATERIALS AND METHODS

3.1 Test System

3.1.1 Animals and Animal Husbandry

A sufficient number of male and female Wistar HanTM:RccHanTM:WIST strain rats were

obtained from Harlan Laboratories U.K. Ltd., Blackthorn, Bicester, Oxon, UK. On receipt the

animals were examined for signs of ill-health or injury. The animals were acclimatised for six

days during which time their health status wa s assessed. A total of one hundred and sixteen

animals (fifty eight males and fifty eight females) were accepted into the study. At the start of

treatment the males weighed 295 to 346g, th e females weighed 182 to 212g, and were

approximately twelve weeks old.

Initially, all animals were housed in groups of f our or five in solid floor polypropylene cages

with stainless steel mesh lids and softwood flake bedding (Datesand Ltd., Cheshire, UK).

During the pairing phase, the non-recovery animals were transferred to polypropylene grid floor

cages suspended over trays lined with absorbent paper on a one male: one female basis within

each dose group. Following evidence of successf ul mating, the males were returned to their

original cages. Mated females were housed indi vidually during gestation and lactation in solid

floor polypropylene cages with stainless steel mesh lids and softwood flakes. Recovery group

animals were housed in groups of five in solid floor polypropylene cages with stainless steel

mesh lids and furnished with softwood flake bedding.

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# The animals were allowed free access to food and water. A pelleted diet (Rodent 2018C Teklad

Global Certified Diet, Harlan Laboratories U.K. Ltd., Oxon, UK.) was used. Certificates of

analysis of the batches of diet used are given in Appendix 32. Mains drinking water was

supplied from polycarbonate bottles attached to the cage. The diet and drinking water were

considered not to contain any contaminant at a level that might have affected the purpose or

integrity of the study. Environmental enrichment was provided in the form of wooden chew

blocks and cardboard fun tunnels (Datesand Ltd ., Cheshire, UK) except for paired animals and

mated females during gestation and lactation. Mated females were also given softwood flakes,

as bedding, throughout gestation and lactation.

The animals were housed in a single air-conditioned room within the Harlan Laboratories Ltd.,

Shardlow, UK Barrier Maintained Rodent Facility. The rate of air exchange was at least fifteen

air changes per hour and the low intensity fluorescent lighting was controlled to give twelve

hours continuous light and twelve hours darkness. Environmental conditions were continuously

monitored by a computerised system, and print- outs of hourly temperatures and humidities are

included in the study records. The temperature and relative humidity controls were set to

achieve target values of 21 ± 2 °C and 55 ± 15% respectively. Short term deviations from these

targets were considered not to have affected the purpose or integrity of the study.

The animals were randomly allocated to treatment groups using a stratified body weight

randomisation procedure and the group mean body weights were then determined to ensure

similarity between the treatment groups. The cage distribution within the holding rack was also

randomised. The animals were uniquely identified within the study by an ear punching system

routinely used in these laboratories.

3.1.2 Justification

The rat was selected for this study as it is a readily available rodent species historically used in

safety evaluation studies and is acceptable to appropriate regulatory authorities.



# 3.2 Test Item Preparation

For the purpose of this study the test item was pr epared at the appropriate concentrations as a

solution in Arachis oil BP. The stability and homogeneity of the test item formulations were

determined by Harlan Laboratories Ltd., Shardlow , UK, Analytical Services. Results show the

formulations to be stable for at least sixteen da ys. Formulations were therefore prepared twice

monthly and stored at approximately +4 °C in the dark.

Samples of the test item formulation were take n and analysed for concentration of Benzoflex

1046 at Harlan Laboratories Ltd., Shardlow, UK, Analytical Services. The method used for

analysis of formulations and the results obtaine d are given in Appendix 27. The results indicate

that the prepared formulations were within ± 4% of the nominal concentration.

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# 3.3 Procedure

Animals were allocated to treatment groups as follows:

Treatment Group Dose Level

(mg/kg bw/day) Treatment

Volume (mL/kg) Concentration

(mg/mL) Animal Numbers

Male Female

Control 0 4 0 12 (1-12) 12 (13-24)

Recovery Control 0 4 0 5 (97-101) 5 (102-106)

Low 30 4 7.5 12 (25-36) 12 (37-48)

Intermediate 60 4 15 12 (49-60) 12 (61-72)

High 120 4 30 12 (73-84) 12 (85-96)

Recovery High 120 4 30 5 (107-111) 5 (112-116)



# The numbers in parentheses ( ) show the individual animal numbers allocated to each treatment

group.

The test item was administered daily by gavage using a stainless steel cannula attached to a

disposable plastic syringe. Control animals were treated in an identical manner with 4 ml/kg of

Arachis oil BP.

The volume of test and control item administered to each animal was based on the most recent

scheduled body weight and was adjusted at weekly intervals.

3.3.1 Chronological Sequence of Study

3.3.1.1 Non-Recovery Dose Groups

i. Groups of twelve male and twelve female an imals were treated daily at the appropriate

dose level throughout the study (except for females during parturition where applicable).

The first day of dosing was designated as Day 1 of the study.

ii. Prior to the start of treatment and once week ly thereafter, all animals were observed for

signs of functional/behavioural toxicity.

iii. On Day 15, animals were paired on a 1 male: 1 female basis within each dose group for a

maximum of fourteen days.

iv. Following evidence of mating (designated as Day 0 post coitum ) the males were returned

to their original cages and females were transferred to individual cages.

v. On completion of the pairing phase (during Week 6), five selected males per dose group

were evaluated for functional/sensor y responses to various stimuli.

vi. Pregnant females were allowed to give birt h and maintain their offspring until Day 5 post

partum. Litter size, offspring weight and sex, surface righting and clinical signs were

also recorded during this period.

vii. At Day 4 post partum , five selected females per dose group were evaluated for

functional/sensory responses to various stimuli.

# Harlan Study Number: 41204605 Report Page 27



# viii. Blood samples were taken from five males from each dose group for hematological and

blood chemical assessments on Day 42. The male dose groups were killed and examined

macroscopically on Day 43.

ix. Blood samples were taken from five randomly selected females from each dose group for

haematological and blood chemical assessment on Day 4 post partum . At Day 5 post

partum , all females and surviving offspring were killed and examined macroscopically.

Any female which did not produce a pregnancy was also killed and examined

macroscopically.

3.3.1.2 Recovery Dose Groups

i. Groups of five male and five female rats were dosed according to dose group

continuously up to the point of sacrifice of non-recovery males at which time treatment

was discontinued.

ii. The males and females were maintained wit hout treatment for a further fourteen days.

iii. Urinalysis was performed for all males during the final week of recovery.

iv. Blood samples were taken for haematologica l and blood chemical assessment on Day 56.

v. After fourteen days of recovery, male s and females were killed and examined

macroscopically.



# 3.4 Observations

3.4.1 Clinical Observations

All animals were examined for overt signs of toxicity, ill-health and behavioural change

immediately before dosing, up to thirty minutes after dosing, and one and five hours after dosing,

during the working week. Animals were observed immediately before dosing, soon after dosing,

and one hour after dosing at weekends and public holidays (except for females during parturition

where applicable). During the treatment-free peri od, recovery animals were observed daily. All

observations were recorded.

3.4.2 Functional Observations

Prior to the start of treatment and at weekly in tervals thereafter, all non-recovery animals were

observed for signs of functional/behavioural toxi city. Functional performance tests were also

performed on five selected males and female s from each non-recovery dose level, prior to

termination, together with an assessment of sensory reactivity to various stimuli.

3.4.2.1 Behavioural Assessments

Detailed individual clinical observations were performed for each animal using a purpose built

arena. The following parameters were observed:

# Harlan Study Number: 41204605 Report Page 28



# Gait Hyper/Hypothermia

Tremors Skin colour

Twitches Respiration

Convulsions Palpebral closure

Bizarre/Abnormal/Stereotypic behavior Urination

Salivation Defecation

Pilo-erection Transfer arousal

Exophthalmia Tail elevation

Lachrymation

This test was developed from the methods used by Irwin (1968) and Moser et al (1988). The

scoring system used is outlined in The Key to Scoring System and Explanation for Behavioral

Assessments and Sensory Reactivity Tests.

3.4.2.2 Functional Performance Tests

Motor Activity. Purpose-built 44 infra-red beam automated activity monitors were used to assess

motor activity. Animals were randomly allocated to the activity monitors. The tests were

performed at approximately the same time on eac h occasion (at least two hours after dosing),

under similar laboratory conditions. The evaluation period was thirty minutes for each animal.

The percentage of time each animal was active and mobile was recorded for the overall thirty

minute period and also during the final 20% of the period (considered to be the asymptotic

period, Reiter and Macphail, 1979).

Forelimb/Hindlimb Grip Strength. An automated meter was used. Each animal was allowed to

grip the proximal metal bar of the meter with its forepaws. The animal was pulled by the base of

the tail until its grip was broken. The animal was drawn along the trough of the meter by the tail

until its hind paws gripped the distal metal bar. The animal was pulled by the base of the tail

until its grip was broken. A record of the for ce required to break the grip for each animal was

made. Three consecutive trials were performed for each animal. The assessment was developed

from the method employed by Meyer et al (1979).

3.4.2.3 Sensory Reactivity

Each animal was individually assessed for sensory reactivity to auditory, visual and

proprioceptive stimuli. This assessment was developed from the methods employed by Irwin

(1968) and Moser et al (1988).

The following parameters were observed:

Grasp response Touch escape

Vocalisation Pupil reflex

# Harlan Study Number: 41204605 Report Page 29



# Toe pinch Blink reflex

Tail pinch Startle reflex

Finger approach

3.4.3 Body Weight

Individual body weights were recorded on Day 1 (prior to dosing) and then weekly for males

until termination and weekly for females until mating was evident. Body weights were then

recorded for females on Days 0, 7, 14 and 20 post coitum , and on Days 1 and 4 post partum

. Recovery animals were weighed on Day 1 (prior to dosing) and then weekly until termination.

Normal range data for body weight changes in pregnant and lactating females are shown in

Appendix 34.

3.4.4 Food Consumption

During the pre-pairing period, weekly food consum ption was recorded for each cage of adults.

This was continued for males after the mating phase. For females showing evidence of mating,

food consumption was recorded for the periods covering post coitum Days 0-7, 7-14 and 14-20.

For females with live litters, food consumption was recorded on Days 1 and 4 post partum.

Weekly food consumptions were performed for each cage of recovery group animals throughout

the study period.

Food efficiency (the ratio of body weight change /dietary intake) was calculated retrospectively

for non-recovery males (except during the mating phase) and recovery group animals throughout

the study period and for non-recovery females during the pre-pairing phase. Due to offspring

growth and milk production, food efficiency could not be accurately calculated for females,

during gestation and lactation.

Normal range data for pregnant and lacta ting females are presented in Appendix 34.

3.4.5 Water Consumption

Water intake was measured daily throughout the study (with the exception of the pairing phase).

3.4.6 Reproductive Performance

Normal range data for reproductive parameters and offspring are presented in Appendix 34 and

Appendix 35.

# Harlan Study Number: 41204605 Report Page 30



# 3.4.6.1 Mating

Non-recovery animals were paired on a 1 male: 1 female basis within each dose group, for a

period of up to fourteen days. Cage tray-liners were checked each morning for the presence of

ejected copulation plugs and each female was ex amined for the presence of a copulation plug in

the vagina. A vaginal smear was prepared for each female and the stage of oestrus or the

presence of sperm was recorded. The presence of sperm within the vaginal smear and/or vaginal

plug in situ was taken as positive evidence of mating (Day 0 of gestation) and the males were

subsequently returned to their original holdin g cages (unless required for additional pairing).

Mated females were housed individually duri ng the period of gestation and lactation.

3.4.6.2 Pregnancy and Parturition

Each pregnant female was observed at approximately 0830, 1230 and 1630 hours and around the

period of expected parturition. Observations were carried out at approximately 0830 and

1230 hours at weekends and public holidays. The following was recorded for each female:

i. Date of pairing

ii. Date of mating

iii. Date and time of observe d start of parturition

iv. Date and time of observed completion of parturition

3.4.6.3 Litter Data

On completion of parturition (Day 0 post partum ), the number of live and dead offspring was

recorded. Offspring were individually identified within each litter by tattoo on Day 1 post

partum.

For each litter the following was recorded:

i. Number of offspring born

ii. Number of offspring alive recorded daily and reported on Days 1 and 4 post partum

iii. Sex of offspring on Days 1 and 4 post partum

iv. Clinical condition of offspring from birth to Day 5 post partum

v. Individual offspring weights on Days 1 and 4 post partum (litter weights were calculated

retrospectively from this data)

3.4.6.4 Physical Development

All live offspring were assessed for surface righting reflex on Day 1 post partum.

# Harlan Study Number: 41204605 Report Page 31



# 3.4.7 Laboratory Investigations

Haematological and blood chemical investigat ions were performed on five males and five

females selected from each non-recovery test and control group prior to termination (Day 42 for

males and Day 4 post partum for females). In addition haematological and blood chemical

investigations were performed on all recovery group animals after the fourteen day treatmentfree period at termination (Day 56). Blood samp les were obtained from the lateral tail vein.

Where necessary repeat samples were taken by ca rdiac puncture at termination. Animals were

not fasted prior to sampling.

Urinalytical investigations were performed on fi ve non-recovery males from the control and each

test group during the final week of treatment an d on all recovery males during the final week of

the recovery period. Urine samples were collect ed overnight by housing the rats in metabolism

cages. Animals were maintained under conditi ons of normal hydration during collection but

without access to food.

The methods used for haematological, blood ch emical and urinalytical investigations are

presented in Appendix 33.

3.4.7.1 Haematology

The following parameters were measured on bl ood collected into tubes containing potassium

EDTA anti-coagulant:

Haemoglobin (Hb)

Erythrocyte count (RBC)

Haematocrit (Hct)

Erythrocyte indices - mean corpuscular haemoglobin (MCH)

- mean corpuscular volume (MCV)

- mean corpuscular haemoglobin concentration (MCHC)

Total leucocyte count (WBC)

Differential leucocyte count - neutrophils (Neut)

- lymphocytes (Lymph)

- monocytes (Mono)

- eosinophils (Eos)

- basophils (Bas)

Platelet count (PLT)

Reticulocyte count (Retic) - Methylene blue st ained slides were prepared but reticulocytes

were not assessed

# Harlan Study Number: 41204605 Report Page 32



# Prothrombin time (CT) was assessed by ‘Innovin’ and Activated partial thromboplastin time

(APTT) was assessed by ‘Actin FS’ using samples collected into sodium citrate solution

(0.11 mol/l).

3.4.7.2 Blood Chemistry

The following parameters were measured on plasma from blood collected into tubes containing

lithium heparin anti-coagulant:

Urea Calcium (Ca++)

Glucose Inorganic phosphorus (P)

Total protein (Tot.Prot.) Aspart ate aminotransferase (ASAT)

Albumin Alanine aminot ransferase (ALAT)

Albumin/Globulin (A/G) ratio (by calcul ation) Alkaline phosphatase (AP)

Sodium (Na+) Creatinine (Creat)

Potassium (K+) Total cholesterol (Chol)

Chloride (Cl-) Total bilirubin (Bili)

Bile acids

3.4.7.3 Urinalysis

The following parameters were measured on collected urine:

Volume Ketones

Specific Gravity Bilirubin

pH Urobilinogen

Protein Blood

Glucose Appearance

3.4.8 Pathology

3.4.8.1 Necropsy

Adult non-recovery males were killed by intravenous overdose of a suitable barbiturate agent

followed by exsanguination on Day 43. Adult non -recovery females were killed by intravenous

overdose of a suitable barbiturate agent followed by exsanguination on Day 5 post partum

. Surviving offspring were terminated via intracardiac overdose of sodium pentobarbitone. Any

females which failed to achieve pregnancy or pr oduce a litter were killed on or after Day 25 post

coitum.

# Harlan Study Number: 41204605 Report Page 33



# For all non-recovery females, the uterus was examined for signs of implantation and the number

of uterine implantations in each horn was record ed. This procedure was enhanced; as necessary,

by staining the uteri with a 0.5% ammonium polysulphide solution (Salewski 1964). The

corpora lutea were also counted.

Recovery group animals were killed by intrave nous overdose of a suitable barbiturate agent

followed by exsanguination on Day 57.

All adult animals and offspring, including those dying during the study, were subjected to a full

external and internal examination, and any macroscopic abnormalities were recorded.

3.4.8.2 Organ Weights

The following organs were di ssected free from fat and weighe d before fixation from five

selected males and five selected females from each non-recovery dose group and from all

recovery group animals. Tissues shown in bold were weighed from all remaining animals:

Adrenals Prostate

Brain Seminal vesicles

Epididymides Spleen

Heart Testes

Kidneys Thymus

Liver Thyroid (weighed post-fixation with Parathyroid)

Ovaries Uterus (weighed with Cervix)

Pituitary (post fixation)

Normal ranges for organ weights are given in Appendix 37.

3.4.8.3 Histopathology

Samples of the following tissues were removed from five selected males and five selected

females from each dose group and preserved in buffered 10% formalin, except where stated.

Tissues shown in bold were preserved from all remaining animals:

Adrenals Ovaries

Aorta (thoracic) Pancreas

Bone & bone marrow (femur including stifle joint) Pituitary

Bone & bone marrow (sternum) Prostate

Brain (including cerebrum, cerebellum and pons) Oesophagus

Caecum Rectum

Coagulating gland Salivary glands (submaxillary)

Colon Sciatic nerve

# Harlan Study Number: 41204605 Report Page 34



# Duodenum Seminal vesicles

Epididymides  Skin (hind limb)

Eyes * 

# Spinal cord (cervical, mid-thoracic and

Gross lesions lumbar)

Heart Spleen

Ileum (including peyer’s patches) Stomach

Jejunum Thyroid/parathyroid

Kidneys Trachea

Liver Testes 



# Lungs (with bronchi) # 

# Thymus

Lymph nodes (mandibular and mesenteric) Urinary bladder

Mammary gland Uterus/Cervix

Muscle (skeletal) Vagina

Tissues were despatched to the Test Site (T UPI Manufacturing) for processing (Principal

Investigator: R Trindall). The tissues from five selected non-recovery control and 1000 mg/kg

bw/day dose group animals, any animals dying during the study, and any animals which failed to

mate or did not achieve a pregnancy were prepar ed as paraffin blocks, sectioned at a nominal

thickness of 5 μ m and stained with haematoxylin and eosin for subsequent microscopic

examination. The tissues shown in bold from the remaining control and 120 mg/kg bw/day

animals and animals which did not achieve a pregnancy were also processed. In addition,

sections of testes and epididymides from all control and 120 mg/kg bw/day males were also

stained with Periodic Acid-Schiff (PAS) stain and examined.

Detailed qualitative examination of the testes wa s undertaken, taking into account the tubular

stages of the spermatogenic cycle. The examination was conducted in order to identify

treatment-related effects such as missing germ cell layers or types, retained spermatids,

multinucleated or apoptotic germ cells and sloughing of spermatogenic cells into the lumen.

Any cell-or stage-specificity of testicular findings was noted.

Microscopic examination was conducted by the St udy Pathologist (Peter Millar at Peter Millar

Associates Ltd). A complete histopathology phase report is presented in Appendix 26.

* 

# = eyes fixed in Davidson’s fluid

 

# = preserved in Bouin’s fluid then transferred to 70% Industrial Methylated Spirits (IMS) approximately

forty-eight hours later

# 

# = lungs were inflated to approximately normal inspiratory volume with buffered 10% formalin before

immersion in fixative

# Harlan Study Number: 41204605 Report Page 35



# 3.4.9 Evaluation of Data

3.4.9.1 Treatment of Data

Data were processed to give summary incidence or group mean values and standard deviations

where appropriate. All data were summarised in tabular form.

Data shown in the appendices are frequently rounded values for presentation purposes. Group

mean values are generally calculated using non -rounded values therefore is it not always possible

to calculate the exact group values from the individual values presented in the appendices.

For body weights and food consumptions during ge station, group mean values were calculated

using data from females which were observed to give birth to offspring.

For body weights and food consumptions during lactation, group mean values were calculated

using data from females with live young at Day 5 of lactation.

3.4.9.2 Reproductive Indices

Mating Performance and Fertility

The following parameters were ca lculated from the individual data during the mating period of

the parental generation:

i. Pre-coital Interval

Calculated as the time elapsing between initial pairing and the observation of positive

evidence of mating.

ii. Fertility Indices

For each group the following were calculated:

Mating Index (%) = paired animals of Number mated animals of Number x 100

Pregnancy Index (%) =



# mate d animals of Number females pregnant of Number x 100

Gestation and Parturition Data

The following parameters were calculated from individual data during the gestation and

parturition period of the parental generation:

i. Gestation Length

# Harlan Study Number: 41204605 Report Page 36



# Calculated as the number of days of gestation including the day for observation of mating

and the start of parturition.

ii. Parturition Index

The following was calculated for each group:

Parturition Index (%) =

females pregnant of Number offspring live delivering females of Number x 100

3.4.9.3 Litter Responses

The standard unit of assessment was considered to be the litter, therefore values were first

calculated for each litter and the group mean was calculated using their individual litter values.

Group mean values included all litters reared to termination (Day 5 of age).

i. Implantation Losses (%)

Group mean percentile pre-implantation and po st-implantation loss were calculated for

each female/litter as follows:

% pre–implantation loss =

lutea corpora of Number sites on implantati of Number

- lutea corpora of Number 

# x100

% post–implantation loss =

sites on implantati of Number born offspring of number Total

- sites on implantati of Number 

# x 100

ii. Live Birth and Viability Indices

The following indices were calcul ated for each litter as follows:

Live Birth Index (%) =

born offspring of Number 1 Day on alive offspring of Number 

# x 100

Viability Index (%) =

1 Day on alive offspring of Number 4 Day on alive offspring of Number x 100

iii. Sex Ratio (% males)

Sex ratio was calculated for each litter value on Days 1 and 4 post partum 

# , using the

following formula:

# Harlan Study Number: 41204605 Report Page 37



# pring er of offs Total numb ring male offsp Number of 

# x 100

3.4.9.4 Statistical Analysis

Where considered appropriate, quantitative data was subjected to statistical analysis to detect the

significance of intergroup differences from cont rol; statistical significance was achieved at a

level of p<0.05. Statistical analysis was performed on the following parameters:

Grip Strength, Motor Activity, Body Weight, Body Weight Change, Food Consumption during

gestation and lactation, Water Consumption during gestation and lactation, Pre-Coital Interval,

Gestation Length, Litter Size, Litter Weight, Se x Ratio, Corpora Lutea, Implantation Sites,

Implantation Losses, Viability Indices, Offspri ng Body Weight, Offspring Body Weight Change,

Offspring Surface Righting, Haematology, Blood Chemistry, Absolute Organ Weights, Body

Weight-Relative Organ Weights.

Data were analysed using the decision tree from the Provantis TM 

# Tables and Statistics Module as

detailed as follows:

Where appropriate, data transformations were performed using the most suitable method. The

homogeneity of variance from mean values was analysed using Bartlett’s test. Intergroup

variance were assessed using suitable ANOVA, or if required, ANCOVA with appropriate

covarities. Any transformed data were analysed to find the lowest treatment level that showed a

significant effect using the Williams Test fo r parametric data or the Shirley Test for nonparametric data. If no dose re sponse was found but the data shows non-homogeneity of means,

the data were analysed by a stepwise Dunnett’s (parametric) or Steel (non-parametric) test to

determine significant difference from the control group. Where the data were unsuitable for

these analyses, pair-wise tests was performed usi ng the Student t-test (parametric) or the MannWhitney U test (non-parametric).

Data not analysed by the Provantis data capture system were assessed separately using the SPSS

statistical package. Initially, the homogeneity of the data was assessed using Levene’s test.

Where Levene’s test was shown to be non-significant (p ≥ 0.05), parametric analysis of the data

was applied, incorporating analysis of vari ance (ANOVA). If this data was shown to be

significant, this analysis was followed by pair-wise comparisons using Dunnett’s test. Where

Levene’s test was significant, non-parametric anal ysis of the data was analysed incorporating the

Kruskal-Wallis test which if significant, was followed by the Mann-Whitney U test. Dose

response relationship was also be investigated by linear regression. Where the data was

unsuitable for these analyses, then pair-wise tests were performed using the Student t-test

(parametric) or the Mann-Whitne y U test (non-parametric).

Due to the preponderance of non-normally di stributed data, reproductive parameters

(implantation losses, offspring sex ratio and offs pring surface righting) were analysed using nonparametric analyses.

# Harlan Study Number: 41204605 Report Page 38



# Probability values (p) are presented as follows:

p<0.01 **

p<0.05 *

p> 0.05 (not significant)

# Harlan Study Number: 41204605 Report Page 39



# 4 RESULTS AND DISCUSSION

4.1 Results

4.1.1 Adult Reponses



# 4.1.1.1 Mortality

There were no unscheduled deaths detected during the study.

4.1.1.2 Clinical Observations

A summary incidence of daily clinical observations is given in Table 2. Individual data is

presented in Appendix 1.

There were no clinically observable signs of toxicity detected during the study.

Clinical signs were confined to the presence of post-dose increased salivation for animals of

either sex treated with 120 mg/kg bw/day. Isolat ed instances of increased salivation following

dosing were also evident at 60 mg/kg bw/day. Increased salivation is often recorded following

the oral administration of an unpleasant tasting and/ or locally irritant test item formulation and,

in isolation, is considered not to be indicative of systemic toxicity.

4.1.1.3 Functional Observations

Summary incidence of behavioural assessment observations are given in Table 3 and group mean

behavioural assessment scores are given in Ta ble 4. Group mean functional performance test

values and standard deviations are given in Ta ble 5 (statistically significant differences are

indicated). Individual values are given in Appe ndices 2 to 5. Group mean sensory reactivity

assessment scores are given in Table 6. Individual responses are given in Appendix 6.

Behavioural Assessments

No treatment-related effects were detected in the behavioural assessment parameters

investigated.

All inter and intra group differences in urination and defecation scores were considered to be a

result of normal variation for rats of the stra in and age used and were of no toxicological

importance.

Functional Performance Tests

No treatment-related effects were detected in the functional performance parameters

investigated.

# Harlan Study Number: 41204605 Report Page 40



# Females from all treatment groups showed a statis tically significant increase in forelimb grip

strength when compared to controls. The significance achieved was minimal (p<0.05) and only

occurred during one out of three tests. In the absence of a dose-related response, these increases

were considered to be unrelated to treatment.

Females treated with 120 mg/kg bw/day showed an increase in hind limb grip strength when

compared to controls. This was only observed in one out of three tests performed, and as such,

was considered not to represent a true effect of treatment.

Sensory Reactivity Assessments

There were no treatment-related changes in sensory reactivity.

All inter and intra group differences in sensory reacti vity scores were considered to be a result of

normal variation for rats of the strain and age used and were of no toxicological importance.

4.1.1.4 Body Weight

Group mean weekly body weights and standard deviations are given in Table 7 and are presented

graphically in Figure 1 and Figure 2. Group me an weekly body weight gains and standard

deviations are given in Table 8 (statistically si gnificant differences are indicated). Individual

data are given in Appendix 7 and Appendix 8.

Actual body weight losses and reduced body weight gains were evident for some animals of

either sex treated with 120 mg/kg bw/day when compared to controls, with statistically

significant reductions evident for females from Day 1 to Day 15 (p<0.01).

Reduced body weight gains were also evident during the first two weeks of treatment for animals

of either sex treated with 60 mg/kg bw/day, with statistically significant reductions observed for

females (p<0.01) when compared to controls. Recovery was evident in males thereafter.

Reduced body weight gains were evident for females treated with 120 and 60 mg/kg bw/day

throughout the gestation phase, when compared to control females (p<0.05 – p<0.01).

Furthermore, actual body weights were lower for treated females during the study when

compared to controls, with statistical signifi cance achieved for females during gestation and

lactation for all treated females when compared to controls.

For recovery animals, high dose males showed a reduction in body weight gains and actual body

weight losses when compared to controls during the first three weeks of treatment, with recovery

thereafter.

# Harlan Study Number: 41204605 Report Page 41



# 4.1.1.5 Food Consumption

Group mean food consumptions are given in Table 9 (statistically significant differences are

indicated) and are presented graphi cally in Figure 3 and Figure 4. Individual values for females

during gestation and lactation are presented in Appendix 9. Food efficiency for males and for

females during the pre-mating phase is given in Table 10.

Reduced dietary intake was evident for males treated with 120 mg/kg bw/day during the first two

weeks of treatment. Females treated with 120 mg/kg bw/day showed a reduction in dietary

intake during the pre-pairing phase when compared to controls. Statistically significant

reductions in dietary intake at all dose levels were evident during gestation when compared to

controls. No such effects were detected during lactation.

4.1.1.6 Water Consumption

Group mean daily water consumptions are given in Table 11. Individual and group mean daily

water consumptions for females following mating and lactat ion are presented in Appendix 10.

Daily measurements of water bottles did not re veal any significant intergroup differences for

males or for females during the pre-pairing, gestation and lactation phases of the study.

Females treated with 30 mg/kg bw/day showed a statistically significant reduction in water

consumption during the final week of gestation. In the absence of a true dose related response

the intergroup difference was considered not to be of toxicological importance.

4.1.2 Reproductive Performance



# 4.1.2.1 Mating

A summary of adult performance is presented in Table 1. A summary incidence for mating

performance is presented in Table 12. Individual data are given in Appendix 11.

No treatment-related effects were detected in mating performance. All animals mated within

five days of pairing.

4.1.2.2 Fertility

A summary of adult performance is presented in Ta ble 1. Group values for fertility, litter data

and implantation losses are given in Tables 12, 13 and 14. Individual data are given in

Appendices 11 to 13.

There were no treatment-related changes detected in fertility.

# Harlan Study Number: 41204605 Report Page 42



# There were two non-pregnant females at the high dose. One non-pregnant female was present in

the intermediate dose level and two non-pregnant females were present in the low dose. Nonpregnancies are low incidence findings in reproducti ve studies of this type and considered not to

represent an effect of treatment.

4.1.2.3 Gestation Length

A summary of gestation lengths is presented in Table 12. Individual lengths are given in

Appendix 11.

No treatment-related effects were detected in the length of gestation between control and treated

groups. Gestation lengths were spread over 21 to 24 1⁄2 days.

4.1.3 Litter Responses



# In total, twelve females from the control group, nine females treated with 30 mg/kg bw/day,

eleven females treated with 60 mg/kg bw/day and seven females treated with 120 mg/kg bw/day

gave birth to a live litter and successfully reared young to Day 5 of age. The following

assessment of litter response is based on all litters reared to termination on Day 5 of

lactation/age.

4.1.3.1 Offspring Litter Size, Sex Ratio and Viability

Group mean corpora lutea and implantation counts, litter size, implantation losses, survival

indices and sex ratio are given in Tables 13 to 15 . Individual data are given in Appendices 12 to

14.

One female treated with 120 mg/kg bw/day showed both corpora lutea and implantation sites,

but did not produce a litter. Furthermore, there were two total litter losses observed at 120 mg/kg

bw/day and one total litter loss observed at 30 mg/kg bw/day.

No differences in sex ratio or litter size were evident for offspring from treated litters when

compared to those from the controls. No significant differences in the number of corpora lutea

or implantation sites were noted for treated female s when compared to controls. The percentages

of pre- and post-implantation losses for treated fe males were comparable to controls. Statistical

analysis of the data did not reveal any significant intergroup differences.

4.1.3.2 Offspring Growth and Development

Group mean values for total litter weights, offspring body weights and body weight changes,

surface righting reflex and a summary incidence of clinical signs are given in Tables 13, 16 and

17. Individual values and observations are given in Appendices 12, 15 and 16.

# Harlan Study Number: 41204605 Report Page 43



# No significant differences in litter weights or offspring weights were evident in the treated

groups when compared to controls. Statistical analysis of the data did not reveal any significant

intergroup differences.

There were no clinically observable signs of toxicity observed in offspring.

4.1.4 Laboratory Investigations



# 4.1.4.1 Haematology

Group mean values and standard deviations for test and control group animals are given in Table

18 (statistically significant differences are indicated). Individual data are given in Appendix 17

and Appendix 18.

There were no toxicologically significant cha nges detected in the haematology parameters

investigated.

Non-recovery and recovery females treated w ith 120 mg/kg bw/day showed a statistically

significant increase in platelet counts when compared to the concurrent controls. In the absence

of any associated histopathology correlates the intergroup differences were considered to have

arisen incidentally and were consider ed of no toxicological significance.

4.1.4.2 Blood Chemistry

Group mean values and standard deviations for test and control group animals are given in Table

19 (statistically significant diffe rences are indicated). Individual data are given in Appendices

19 and 20.

There were no toxicologically significant changes detected in the blood chemical parameters

investigated.

Non-recovery females treated with 120 mg/kg bw/day showed a statistically significant increase

in bilirubin and a statistically significant reduction in bile acids. In the absence of any associated

histopathological correlates the intergroup differences were considered not to be of toxicological

importance.

Non-recovery males treated with 120 mg/kg bw/day showed a slight but statistically significant

reduction in albumin/globulin ratio and urea when compared to controls. The significance

achieved was minimal (p<0.05) and the majority of individual values were within the normally

expected ranges. As such, these reductions were considered to have arisen incidentally.

Non-recovery males treated with 30 mg/kg bw/day showed a statistically significant increase in

alkaline phosphatase values when compared to controls, with one value outside of the normally

expected ranges. In the absence of a dose-related response, this increase was considered to have

arisen incidentally and was of no toxicologi cal importance. Recovery males treated with

# Harlan Study Number: 41204605 Report Page 44



# 120 mg/kg bw/day showed a statistically significant increase in alkaline phosphatase levels when

compared to the recovery controls. All individual values were within the normally expected

ranges, and as such, this increase was considered not to represent systemic toxicity.

Recovery females treated with 120 mg/kg bw/day showed a statistically significant reduction in

albumin/globulin ratio and alkaline phosphatase. In the absence of similar findings detected

following the treatment period, the intergroup differences were considered to have arisen

incidentally and were considered unrelated to test item toxicity.

Finally, aspartate aminotransfera se levels were lower for recovery males when compared to

recovery controls. This reduction was attributable to four higher than expected control values

and was considered not to represent an effect of treatment.

4.1.4.3 Urinalysis

A summary of urinalytical findings is given in Table 20. Individual data are given in

Appendix 21.

There were no treatment-related cha nges detected in the urinalytical parameters investigated.

Statistical analysis of the quantitative data did not reveal any significant intergroup differences.

4.1.5 Pathology



# 4.1.5.1 Necropsy

A summary incidence of necropsy findings for offspr ing and adults is given in Tables 21 and 22.

Individual data are given in Appendices 22 and 23.

Offspring

No treatment-related macroscopic abnormalities were detected in interim death or terminal kill

offspring. The incidental findings observed were those occasionally observed in reproductive

studies of this type and were considered to be unrelated to toxicity of the test item.

Adults

There were no treatment-related macroscopic abnormalities detected.

One male treated with 30 mg/kg bw/day displayed a fibrous mass on the mammary gland. One

female treated with 30 mg/kg bw/day displayed a distended left horn of the uterus and a cream

coloured fluid was present in the vagina. One male treated with 120 mg/kg bw/day displayed

small seminal vesicles. Another male treated with 120 mg/kg bw/day showed a yellow fluidfilled mass attached to the left cauda of the epididymis. One female treated with 120 mg/kg

# Harlan Study Number: 41204605 Report Page 45



# bw/day showed reddened eyes. These macroscopic changes were considered to be low incidence

findings in rats of the age and strain employed, and considered not to represent systemic toxicity.

4.1.5.2 Organ Weights

Group mean absolute and body weight-relative organ weights and standard deviations for test

and control group animals are presented in Tabl e 23 (statistically signifi cant differences are

indicated). Individual data are given in Appendix 24 and Appendix 25.

There were no toxicologically significant organ weight changes detected for treated animals

when compared to controls.

Non-recovery males treated at all dose levels showed a statistically significant increase in kidney

weights, both absolute and relative to terminal body weights, when compared to controls. In the

absence of a dose-related response and no histopa thological correlates, these increases were

considered to be of minimal toxicological importance.

Non-recovery males treated with 120 mg/kg bw/day showed a statistically significant increase in

liver weights when compared to controls. All individual values were within the normally

expected ranges, and in the absence of any tr eatment-related histopathological changes in the

liver, this increase was considered to represent an adaptive response to treatment with a

xenobiotic and considered not to represent systemic toxicity.

Non-recovery males treated with 120 mg/kg bw/day also showed a reduction in prostate weights

when compared to controls. The significance achieved was minimal and although there were

two lower than expected values in the treated groups, there were also two higher than expected

values in the control group. Furthermore, ther e were no histopathological correlates; therefore

this reduction was without toxicological importance.

Finally, non-recovery females treated with 120 and 60 mg/kg bw/day showed a reduction in

thymus weights and females treated with 120 mg/kg bw/day showed a reduction in pituitary

weight when compared to controls. There were no histopathological correlates, therefore the

toxicological significance of these reductions were considered to be of minimal importance.

No organ weight changes were noted in the recovery group animals after the fourteen day

treatment-free period.

4.1.5.3 Histopathology

A complete histopathology phase report is presented in Appendix 26.

Histopathological examinations did not reveal any treatment-related changes in the tissues

examined.

All of the histopathological findings encount ered were considered to have occurred

spontaneously or at post mortem



# .

# Harlan Study Number: 41204605 Report Page 46



# 4.2 Discussion

The oral administration of Benzoflex 1046 to rats for a period of up to eight weeks (including

two weeks pre-pairing, gestation and early lactati on period for females) at dose levels of 120, 60

and 30 mg/kg bw/day resulted in treatment-related changes at all dose levels employed.

There were no clinical signs considered to be rela ted to systemic toxicity. Actual body weight

losses and reduced body weight gains were evident at 120 mg/kg bw/day. Reduced body weight

gains were also evident during the first two weeks of treatment for animals of either sex treated

with 60 mg/kg bw/day. Recovery was evident in males thereafter. Reduced body weight gains

were evident for females treated with 120 mg/kg bw/day throughout the gestation phase, when

compared to control females. Reduced body weight gain was also evident at 60 mg/kg bw/day

during gestation albeit to a much lesser extent. Reduced dietary intake was evident for males

treated with 120 mg/kg bw/day. Females treated with 120 mg/kg bw/day showed a reduction in

dietary intake during the pre-pairing phase when compared to controls. Reductions in dietary

intake at all dose levels were evident during gest ation when compared to controls. The effects at

60 and 30 mg/kg bw/day were at a lesser extent than at 120 mg/kg bw/day.

There were no toxicologically important haemat ology, blood chemical or organ weight changes

detected.

No treatment-related macroscopic or microscopic were detected.

Due to the changes detected in this study, a ‘No Observed Adverse Effect Level’ (NOAEL) was

considered to be 60 mg/kg bw/day for systemic toxicity.

There were two total litter losses at 120 mg/kg bw/day and one total litter loss at 30 mg/kg

bw/day. These females all had a small number of offspring born (1 or 2 pups). The female

treated with 30 mg/kg bw/day had a greater number of corpora lutea and implantation sites

therefore resulting in a high post implantation loss. The females treated with 120 mg/kg bw/day

had a much lower number of corpora lutea and implantation sites and consequently a lower post

implantation loss. A true treatment related effect on embryo lethality has therefore not been

established and the total litter losses between the tw o groups are considered not to be related. It

is not unusual for dams with low litter size not to maintain the litter during lactation especially if

their health is compromised and as there was no effect on post natal survival in the remaining

litters a true treatment related effect on offspri ng development can not be confirmed. The female

that did not produce a litter in the high dose group may represent an atypical finding because no

other treatment related effects on embryo survival were evident. Although these results may

represent normal biological variation the findings are equivocal therefore the ‘No Observed

Effect level’ (NOEL) for reproductive toxicity was considered to be 60 mg/kg bw/day.

# Harlan Study Number: 41204605 Report Page 47



# 5 CONCLUSION

The oral administration of Benzoflex 1046 to rats by gavage, at dose levels of 120, 60 and

30 mg/kg bw/day, resulted in treatment-related changes at all dose levels. The effects detected at

60 and 30 mg/kg bw/day were considered not to represent an adverse effect. Therefore a ‘No

Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was considered to be 60 mg/kg

bw/day.

The presence of two females which showed a total litter loss and one female which was pregnant

but did not produce a litter at the high dose level cannot be completely discounted as a treatment

effect upon reproduction even though other parame ters such as fertility and histopathology of

reproductive organs showed no treatment effect s. This effect upon reproduction can only be

classified as equivocal on the basis of only limited toxicological findings on reproduction and

that these findings were only observed at dose le vels where other evidence of general toxicity

could be observed in the adult female (redu ced body weight gain and food consumption).

Therefore, it must be concluded that the ‘No Observed Effect Level’ (NOEL) for reproductive

toxicity was considered to be 60 mg/kg bw/day.

# Harlan Study Number: 41204605 Report Page 48



# 6 REFERENCES

Irwin, S. (1968). Comprehensive Observational Assessment: la. A Systematic, Quantitative

Procedure for Assessing the Behavioral and Physiologic State of the Mouse.

Psychopharmacologia 13, 

# 222-257.

Meyer, O.A., et al 

# (1979). A Method for the Routine Assessment of Fore- and Hindlimb Grip

Strength of Rats and Mice. Neurobehavioral Toxicology 1, 

# 233-236.

Moser, V.C., et al 

# (1988). Comparison of Chlordimeform and Carbaryl using a Functional

Observational Battery. Fundamental and Applied Toxicology 11, 

# 189-206.

Reiter, L.W., and MacPhail, R.C. (1979). Motor Activity: A Survey of Methods with Potential

Use in Toxicology Testing. Neurobehavioral Toxicology 1 (1), 

# 53-66.

Salewski, E. (1964). Färbemethode zum makr oskopischen Nachweis von Implantationsstellen

am Uterus der Ratte. Naunyn - Schmiedebergs Arch Exp Path Pharmakol



# . 247, 

# 367.

# Harlan Study Number: 41204605 Report Page 49



# TABULAR SUMMARY REPORT OF EFFECTS OF

REPRODUCTION/DEVELOPMENT

Observations Dose Level (mg/kg bw/day)

0 (Control) 30 60 120

Paired animals n 12 12 12 12

Females showing evidence of copulation n 12 12 12 12

Pregnant females n 12 10 11 9

Conception Days 1-5 n 12 12 12 12

Gestation = 21 Days n 1 0 0 1

Gestation = 22 Days n 1 3 3 0

Gestation = 22 1⁄2 Days n 5 5 3 1

Gestation = 23 Days n 3 1 2 3

Gestation = 23 1⁄2 Days n 2 0 2 4

Gestation = 24 Days n 0 0 1 0

Gestation = 24 1⁄2 Days n 0 1 0 0

Dams with live young born n 12 10 11 9

Dams with live young at Day 4 p ost partum n 12 9 11 7

Corpora lutea/dam 13.3 13.2 11.5 11.3

Implants/dam 12.3 12.2 10.8 10.3

Live offspring/dam at Day 1 p ost partum 11.4 11.7 9.1 8.7

Live offspring/dam at Day 4 p ost partum 11.3 11.7 9.1 8.7

Sex ratio: % males at Day 1 p ost partum 43.0 38.9 50.6 54.9

Sex ratio: % males at Day 4 p ost partum 43.2 38.9 50.6 54.9

Litter weight (g) at Day 1 p ost partum 69.37 68.03 56.51 55.76

Litter weight (g) at Day 4 p ost partum 97.43 96.48 80.46 79.90

Male offspring weight (g) at Day 1 p ost partum 6.40 6.06 6.63 6.50

Male offspring weight (g) at Day 4 p ost partum 8.99 8.57 9.56 9.19

Female offspring weight (g) at Day 1 p ost partum 6.07 5.85 6.21 6.19

Female offspring weight (g) at Day 4 p ost partum 8.77 8.37 9.13 9.02

LOSS OF OFFSPRING/DAM

Pre-implantation (corpora lutea minus implantations)

0 n 4 4 7 4

1 n 6 4 2 2

2 n 1 1 1 3

3 n 0 0 1 1

4 n 0 1 0 0

5 n 1 0 0 0

Pre-natal (implantations minus live births)

0 n 5 3 5 1

1 n 5 5 2 0

2 n 1 1 1 4

3 n 1 0 1 2

4 n 0 0 1 1

5 n 0 0 0 1

8 n 0 1 1 0

10 n 0 0 0 1

Post natal (live births minus offspring alive on Day 4 p ost p artum)

0 n 11 9 11 7

1 n 1 0 0 0



# n = Number



# x = Mean x

x

x

x

x

x



# x

x

x x

x

x

# Harlan Study Number: 41204605 Report Page 50



# KEY TO TABLES AND APPENDICES

M Male

F Female

S.D. Standard deviation

N Number of animals/litters

. No data available

1+ Occasional spermatozoa present

2+ Continuous few spermatozoa in all fields

3+ Many spermatozoa in all fields

H Haemorrhage

PT Plug detected on tray liner

PV Vaginal plug

P Pregnant

NP Not pregnant (values excluded from mean and sd)

NL Evidence of pregnancy but no litter detected (values excluded from mean

and sd, where applicable)

TLL Total litter loss (values excluded from mean and sd, where applicable)

N/A Not applicable

U Sex not determined; prior to within litter identification

% Food Efficiency

x100 days of number x ) (g/rat/day n consumptio food mean Group iod) (g/rat/per gain bodyweight mean Group  

 

 

 



# Statistical Footnotes:

* Significantly different from control group p<0.05

** Significantly different from control group p<0.01

*** Significantly different from control group p<0.001

n Data not appropriate for statistical analysis

Organ Weight Footnotes:

Epididys Epididymides

Bodywt Body weight

Thyroid Thyroid/Parathyroid

Uterus Uterus with Cervix

Sem Ves Seminal vesicles

# Harlan Study Number: 41204605 Report Page 51



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSESSMENTS AND SENSORY REACTIVITY

TESTS

1. NEUROLOGIC

These parameters are the first to be evaluated when the animal is placed in the arena:



# 1.1 Transfer Arousal (Time to Movement) and Locomotion

-2 = animal stays in one place

-1 = slow, deliberate movement

0 = moderate, undisturbed investigation of environment

1 = active progression around arena

2 = darting movements



# 1.2 Tail Elevation

0 = flattened

1 = rigidly horizontally extended

2 = rigidly diagonally elevated

3 = rigidly vertical

4 = diagonally retrograde (past vertical)



# 2. GAIT AND CO-ORDINATION

Tiptoe Hindlimbs raised on tiptoe during movement

High stepping Forelimbs lifted high during movement

Spastic Shuffling of limbs

Waddling Lateral movements

Dysmetric Unco-ordinated movement with tremors

Splayed Thighs splayed outwards, animal appears crouched

Scissor Forelimbs cross over when extended

Ataxic Lack of co-ordinated movement of trunk, pelvis and limbs.

Observation graded: Slight

Moderate (does not fall)

Extreme (falls repeatedly)

# Harlan Study Number: 41204605 Report Page 52



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSE SSMENTS AND SENSORY REACTIVITY

TESTS (CONTINUED)

3. CNS EXCITATION

3.1 Tremors

These are general involuntary movements of the muscles

Exertion only occurs during movement

Rest only occurs when animal is resting

Whole body

Head only

Body only

Tail only

When present, any observation is also graded:

Slight

Moderate

Extreme



# 3.2 Twitches

Identified as brief, coarse jerks of body or limbs - observation graded:

Slight

Moderate

Extreme



# 3.3 Convulsions

Clonic Convulsions with alternate contraction and relaxation of muscles

Running excitement Often accompanied by clonic convulsions

Champing Clonus of the paws only

Hopping Animal repeatedly “hops” into the air

Asphyxeal Terminal convulsion, results in death from respiratory failure

Tonic Seizure in which the head, body and limbs are arched backwards

Emprosthotonus Seizure where the head, body and limbs are arched forwards



# 3.4 Bizarre Behaviour

Any bizarre behavior is recorded using a unique code.

# Harlan Study Number: 41204605 Report Page 53



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSE SSMENTS AND SENSORY REACTIVITY

TESTS (CONTINUED)

4. AUTONOMIC

Salivation* Excessive visi ble wetness around the mouth

Pilo-erection* Fur stands up - marked cases are described as “puff ball”

appearance

Exophthalmia Bulging eyes

Lachrymation Tear staining (clear fluid)

Chromodacryorrhea (red/pink fluid)

Hyperthermia

Hypothermia

Skin colour** Blue (cyanotic)

Redness of extremities

Skin pallor

Respiration Decreased respiratory rate

Gasping

Increased rate

Laboured

Noisy

Palpebral closure Degree of eyelid closur e e.g. ptosis - observation is graded:

Slight

Moderate

Severe

Urination and defecation During the study this can only be observed as urogenital

wetness and/or diarrhoea. In the open arena, the number of

occasions that the animal defecates/urinates is recorded

* 

# When present, observation is graded slight or extreme.

** 

# When present, observation is graded slight, moderate, or extreme.

# Harlan Study Number: 41204605 Report Page 54



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSE SSMENTS AND SENSORY REACTIVITY

TESTS (CONTINUED)

5. MANIPULATIVE TESTS

Performed in the open arena:



# 5.1 Grasp Response

The animal is grasped around the body and its reaction is scored:

0 = no response

1 = animal struggles slightly but becomes passive

2 = animal repeatedly struggles with/without vocalisation

3 = animal struggles violently with/without vocalisation

4 = animal attempts to bite operator



# 5.2 Vocalisation

The number of vocalisations exhib ited by the animal during handling.



# 5.3 Toe Pinch

On handling one toe of a hindfoot is lightly pressed with a pair of forceps:

-3 = no response

-2 = animal shows awareness of actions

-1 = withdrawal

0 = rapid withdrawal with single vocalisation

1 = rapid withdrawal with multiple vocalisations



# 5.4 Tail Pinch

Whilst animal is in the arena, the end of the tail is lightly pressed with forceps:

-2 = no response

-1 = animal freezes/shows awareness of grasping

0 = animal attempts to escape/struggles with none or single vocalisation

1 = animal struggles violently with multiple vocalisations

# Harlan Study Number: 41204605 Report Page 55



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSE SSMENTS AND SENSORY REACTIVITY

TESTS (CONTINUED)

5.5 Finger Approach

Whilst animal is in the arena the operator moves one finger towards the animal:

-1 = animal is oblivious to approach

0 = animal is aware of finger but is unmoved

1 = head sways from side to side

2 = moves towards finger

3 = investigates finger by moving onto it



# 5.6 Touch Escape

Whilst animal is in the arena the operator runs his finger down the body of the animal:

-2 = no response

-1 = animal twitches ears, investigates finger

0 = animal crouches

1 = animal moves away but is unhurried

2 = animal moves away as if startled



# 5.7 Pupil Reflex

The animal is placed in a darkened area to allow the pupils to dilate. A light beam is shone into

each eye separately and the pupil is observed for immediate constriction.

The response recorded:

-2 = no response

-1 = sluggish

0 = normal

# Harlan Study Number: 41204605 Report Page 56



# KEY TO SCORING SYSTEM AND EXPLANATION FOR

BEHAVIOURAL ASSE SSMENTS AND SENSORY REACTIVITY

TESTS (CONTINUED)

5.8 Blink Reflex (Palpebral Closure)

The operator attempts to touch the eye of the rat, the response is recorded:

-2 = no response

-1 = sluggish

0 = normal blink reflex

1 = rapid or repeated eye blink



# 5.9 Startle Reflex

A sharp sudden noise is produced by a noise generato r or finger snap or similar. Each animal is

held lightly but firmly facing the origin of the noise. The response is recorded:

-1 = no response

0 = normal

1 = hyper-responsive

# Harlan Study Number: 41204605 Report Page 57



# TABLESHarlan Study Number:41204605Report Page 58Table 1 Summary of Reproductive Performance - Groups ValuesDose Group (mg/kg bw/day)0 (Control) 30 60 120



# MalesInitial group size12 12 12 12Paired12 12 12 12Failed to induce pregnancy in female partner 0 2 1 3Induced pregnancy in female partner 12 10 11 9Surviving to terminal necropsy 12 12 12 12



# FemalesInitial group size12 12 12 12Paired12 12 12 12Non-pregnant0 2 1 2Pregnant12 10 11 10No litter observed0 0 0 1Total litter loss0 1 0 2Rearing young to Day 5 of age 12 9 11 7Harlan Study Number:41204605Report Page 59Table 2 Summary Incidence of Daily Clinical ObservationsDay Numbers Relative to Start DateSex: MaleGroup 1 Group 2 Group 3 Group 40 (Control) 30 60 120mg/kg bw/dayScheduled killNumber of Observations 17 12 12 17Number of Animals 17 12 12 17Days from ƒ to 43 57 43 43 43 43 43 57Increased salivationNumber of Observations 1 . 8 108Number of Animals 1 . 5 17Days from ƒ to 3 3 . 36 42 3 42Harlan Study Number:41204605Report Page 60Table 2 (continued) Summary Incidence of Daily Clinical ObservationsDay Numbers Relative to Start DateSex: FemaleGroup 1 Group 2 Group 3 Group 40 (Control) 30 60 120mg/kg bw/dayLitteringNumber of Observations 2 . 2 1Number of Animals 2 . 2 1Days from ƒ to 38 38 . 38 38 40 40Not Observed Due to LitteringNumber of Observations . . 2 .Number of Animals . . 2 .Days from ƒ to . . 38 38 .Scheduled killNumber of Observations 17 12 12 17Number of Animals 17 12 12 17Days from ƒ to 42 57 42 46 42 46 42 57Increased salivationNumber of Observations . . 2 88Number of Animals . . 2 17Days from ƒ to . . 41 41 3 43Harlan Study Number:41204605Report Page 61Table 3 Summary Incidence of Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign ƒ1 7 14 21 28 35 38/4 

# post partum1(M) ANIMALS ALIVE 17 17 17 17 17 17 17ANIMALS NORMAL 12 12 12 12 12 12 121(F) ANIMALS ALIVE 17 17 17 17 17 17 17ANIMALS NORMAL 12 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 62Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign ƒ1 7 14 21 28 35 38/4 

# post partum #2(M) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 122(F) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 12# = Day 25 

# post coitumfor female Numbers 43 and 48Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 63Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign ƒ1 7 14 21 28 35 38/4 

# post partum #3(M) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 123(F) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 12# = Day 25 

# post coitumfor female Number 62Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 64Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign ƒ1 7 14 21 28 35 38/4 

# post partum #4(M) ANIMALS ALIVE 17 17 17 17 17 17 17ANIMALS NORMAL 12 12 12 12 12 12 124(F) ANIMALS ALIVE 17 17 17 17 17 17 17ANIMALS NORMAL 12 12 12 12 12 12 12# = Day 25 

# post coitumfor female Numbers 85, 87 and 88Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 65Table 4 Summary Incidence of Behavioural Assessments (Scores)Day: ƒ1 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.5 0.1 0.0S.D. 0.0 1.0 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.6 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 66Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: ƒ1 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.4 0.0 0.0S.D. 0.0 0.8 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 67Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 7 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 68Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 7 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 69Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 14 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 70Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 14 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 71Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 21 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.4 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 72Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 21 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 73Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 28 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.4 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 74Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 28 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 75Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 35 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 76Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 35 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.6 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.6 0.2 0.0S.D. 0.0 0.5 0.4 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 77Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 38 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(M) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 78Table 4 (continued) Summary Incidenceof Behavioural Assessments (Scores)Day: 4 

# post partum#Transfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(F) Mean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.0 0.3 0.2 0.0S.D. 0.0 0.5 0.4 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumfor female Numbers 43, 48, 62, 85, 87 and 88Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 79Table 5 Group Mean Functional TestValues and Standard DeviationsTest 1 Test 1 Test 2 Test 2 Test 3 Test 3 Overall Overall Last 20%Last 20%Group Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb activity mobile activitymobile(Sex) g g g g g g1(M) Mean 1065.0 408.0 1168.0 333.4 961.4 422.8 431.6 0.6 8.00.0nS.D. 147.1 170.5 226.6 154.1 530.9 205.2 82.7 0.9 7.70.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ2(M) Mean 1001.4 318.2 904.6 306.0 1014.8 337.2 253.4 0.8 6.80.0nS.D. 260.1 125.4 335.0 131.3 311.3 145.3 121.0 1.8 8.80.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ3(M) Mean 902.2 363.6 983.6 383.6 915.8 334.4 434.0 0.8 13.60.0nS.D. 418.2 87.9 450.0 112.8 373.4 79.7 109.8 1.3 20.40.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ4(M) Mean 953.8 320.6 1215.2 535.0 1132.0 450.8 328.2 1.0 1.60.0nS.D. 296.4 101.8 478.8 278.0 308.5 108.2 179.6 1.4 1.80.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒGeneral Footnote: Unit = Time (seconds) for Motor Activity AssessmentsDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 80Table 5 (continued) Group Mean FunctionalTest Values and Standard DeviationsTest 1 Test 1 Test 2 Test 2 Test 3 Test 3 Overall Overall Last 20%Last 20%Group Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb activity mobile activitymobile(Sex) g g g g g g1(F) Mean 553.8 238.8 951.2 194.2 851.2 190.8 556.6 4.8 47.80.0nS.D. 145.4 104.4 230.5 73.3 280.4 55.1 122.8 4.5 49.30.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ2(F) Mean 983.0* 274.0 730.0 240.4 758.6 254.0 573.2 1.2 78.00.0nS.D. 88.7 30.9 296.3 88.2 226.3 19.6 130.2 1.3 57.60.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ3(F) Mean 876.0* 274.4 939.8 241.2 957.0 192.2 571.2 1.8 70.60.4nS.D. 226.2 110.2 137.9 41.9 241.9 45.6 221.6 0.8 74.10.5N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ4(F) Mean 773.0* 273.0 845.6 374.4 797.6 341.6** 555.4 0.6 61.80.4nS.D. 233.2 90.2 114.3 265.5 139.6 108.0 241.5 0.9 53.10.9N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒGeneral Footnote: Unit = Time (seconds) for Motor Activity AssessmentsDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 81Table 6 Summary Incidence of Sensory Reactivity Assessments (Scores)Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink StartleGroup response isation pinch pinch approach escape reflex reflex reflex(Sex)1(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(M) Mean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(M) Mean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 82Table 6 (continued) Summary Incidence of Sensory Reactivity Assessments (Scores)Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink StartleGroup response isation pinch pinch approach escape reflex reflex reflex(Sex)1(F) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(F) Mean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(F) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(F) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 83Table 7 Group Mean Body Weight ValuesBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 15 22 29 36 431(M) Mean 316.4 329.5 343.0 347.8 359.3 369.3 368.8S.D. 9.2 11.0 12.5 14.2 17.6 20.0 19.3N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(M) Mean 324.9 335.2 351.3 360.2 371.3 381.7 386.5S.D. 16.5 20.1 25.7 26.7 29.1 29.7 35.1N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(M) Mean 318.4 324.5 333.1 342.5 350.0 359.6 364.7S.D. 11.2 15.3 20.8 17.8 20.5 22.1 21.3N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 319.3 321.2 328.1 338.0 343.0 350.2 359.9S.D. 12.9 17.2 24.7 22.6 25.4 26.2 23.4N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 84Table 7 (continued) Group Mean Body Weight ValuesPre-PairingBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 151(F) Mean 204.8 211.3 223.5S.D. 5.0 8.0 8.8N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(F) Mean 197.6 200.6 205.3S.D. 7.0 11.2 9.9N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(F) Mean 199.7 197.8 205.1S.D. 6.2 10.2 11.1N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 200.3 198.8 201.9S.D. 5.8 7.3 7.9N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 85Table 7 (continued) Group Mean Body Weight ValuesGroup(Sex)Body Weight (g)Day NumbersGestationLactation071420141(F)Mean224.1 251.8 283.5 348.3258.9 269.9S.D.8.9 8.9 10.1 15.615.7 13.1N1212121212122(F)Mean205.4** 228.8***257.1***314.2**235.2** 244.6**S.D.13.1 9.9 14.2 28.310.2 10.4N10101010993(F)Mean206.2***226.8***251.3***300.4***226.5***239.0***S.D.8.9 10.5 17.1 24.014.8 14.8N11 11 11 1111 114(F)Mean205.9***223.3***240.3***287.6***227.0***237.3**S.D.6.4 9.5 11.9 22.98.5 10.4N9 9 9 97 7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 86Table 7 (continued) Group Mean Body Weight ValuesRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 15 22 29 36 43 50 571(M) Mean 322.0 335.0 350.0 359.6 372.4 381.6 384.2 394.6 397.8S.D. 9.9 13.7 15.0 17.9 20.9 23.6 24.4 25.6 25.9N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 317.6 318.8 328.2 326.2 342.8 348.6 356.4 371.0 369.8S.D. 12.5 16.1 18.8 14.9 25.9 26.8 26.6 28.9 29.3N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 87Table 7 (continued) Group Mean Body Weight ValuesRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 15 22 29 36 43 50 571(F) Mean 189.4 194.2 200.6 206.0 206.6 209.8 212.2 220.8 218.4S.D. 6.5 7.7 7.8 10.0 10.6 12.1 13.1 12.1 11.5N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 198.2 195.8 200.0 205.2 208.6 210.6 215.4 221.8 220.8S.D. 5.2 5.4 7.0 9.7 9.4 8.4 10.6 13.2 10.1N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 88Table 8 Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateAbs %Gain GainGroup From: 1 8 15 22 29 36 1 1(Sex) To: 8 15 22 29 36 43 43 431(M) Mean 13.1 13.5 4.8 11.6 10.0 ƒ0.5 52.4 16.5S.D. 4.1 5.8 5.6 4.8 4.2 4.5 14.8 4.6N 12 12 12 12 12 12 12 122(M) Mean 10.3 16.1 8.9 11.1 10.4 4.8 61.6 18.8S.D. 6.3 6.6 3.1 4.1 3.0 7.8 21.3 5.9N 12 12 12 12 12 12 12 123(M) Mean 6.1 8.6 9.4 7.5 9.6 5.1 46.3 14.5S.D. 8.0 9.6 8.1 7.3 4.2 7.1 18.6 5.9N 12 12 12 12 12 12 12 124(M) Mean 1.9 6.9 9.9 5.0 7.2 9.8 40.7 12.7S.D. 7.4 10.6 6.6 7.8 6.4 9.7 15.5 4.8N 12 12 12 12 12 12 12 12Dose Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 89Table 8 (continued) Group Mean Body Weight GainsPre-PairingIncrease in Body Weight (g)Day Numbers Relative to Start DateAbs %Gain GainGroup From: 1 8 1 1(Sex) To: 8 15 15 151(F) Mean 6.5 12.3 18.8 9.2S.D. 7.2 3.7 8.8 4.4N 12 12 12 122(F) Mean 3.0 4.8** 7.8 3.9S.D. 5.7 5.4 7.0 3.5N 12 12 12 123(F) Mean ƒ1.8** 7.3** 5.4 2.7S.D. 8.6 6.7 8.7 4.4N 12 12 12 124(F) Mean ƒ1.4** 3.1** 1.7 0.9S.D. 5.6 4.8 8.0 4.0N 12 12 12 12Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 90Table 8 (continued) Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysGestationLactationGestationGroup(sex)From: 0 714100To: 7 1420414201(F) Mean27.8 31.7 64.811.059.4 124.2S.D.6.1 4.3 10.78.55.8 13.3N12 12 121212 122(F) Mean23.4 28.3 57.19.351.7 108.8S.D.8.2 7.1 15.29.011.6 22.1N10 1010910103(F) Mean20.6** 24.5* 49.1**12.545.1** 94.2**S.D.5.1 8.3 12.86.212.4 20.1N11 11 111111 114(F) Mean17.4** 17.0** 47.2*10.334.4*** 81.7***S.D.8.8 9.2 19.48.314.2 25.4N9 99799Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 91Table 8 (continued) Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateAbs %Gain GainGroup From: 1 8 15 22 29 36 43 50 1 1(Sex) To: 8 15 22 29 36 43 50 57 57 571(M) Mean 13.0 15.0 9.6 12.8 9.2 2.6 10.4 3.2 75.8 23.5S.D. 4.0 3.0 3.2 3.4 3.5 1.7 4.0 0.4 17.3 4.9N 5 5 5 5 5 5 5 5 5 54(M) Mean 1.2** 9.4* ƒ2.0 16.6 5.8 7.8** 14.6 ƒ1.2** 52.2 16.3S.D. 6.7 3.8 21.1 26.3 2.9 1.5 3.0 2.0 19.4 5.7N 5 5 5 5 5 5 5 5 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 92Table 8 (continued) Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateAbs %Gain GainGroup From: 1 8 15 22 29 36 43 50 1 1(Sex) To: 8 15 22 29 36 43 50 57 57 571(F) Mean 4.8 6.4 5.4 0.6 3.2 2.4 8.6 ƒ2.4 29.0 15.3S.D. 4.0 4.7 7.2 4.2 7.9 6.8 4.4 4.2 8.5 4.4N 5 5 5 5 5 5 5 5 5 54(F) Mean ƒ2.4* 4.2 5.2 3.4 2.0 4.8 6.4 ƒ1.0 22.6 11.4S.D. 5.3 4.3 7.0 2.9 2.4 5.7 4.9 4.6 8.2 4.2N 5 5 5 5 5 5 5 5 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 93Table 9 Group Mean Food ConsumptionsDay Numbers Relative to Start DateGroup From: 1 8 22 29 36(Sex) To: 8 15 29 36 431(M) Mean 18.3 18.3 18.6 19.5 20.0N 12 12 12 12 122(M) Mean 18.7 18.7 20.0 21.1 21.8N 12 12 12 12 123(M) Mean 16.2 16.5 17.8 19.4 21.2N 12 12 12 12 124(M) Mean 15.2 15.1 17.7 18.4 20.7N 12 12 12 12 12Food Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 94Table 9 (continued) Group Mean Food ConsumptionsPre-PairingDay Numbers Relative to Start DateGroup From: 1 8(Sex) To: 8 151(F) Mean 15.0 14.6N 12 122(F) Mean 13.4 13.3N 12 123(F) Mean 11.1 13.2N 12 124(F) Mean 11.0 11.5N 12 12Food Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 95Table 9 (continued) Group Mean Food ConsumptionsDay NumbersGestation LactationGroup(Sex)From: 0 7 14 1To: 7 14 20 41(F)Mean19.1 22.6 26.3 26.8S.D.1.4 1.8 2.0 4.8N11 11 12 122(F)Mean16.8* 19.9* 23.1* 23.6S.D.1.9 2.7 3.0 5.4N10 10 10 93(F)Mean15.3***18.3** 22.0** 24.4S.D.1.6 3.0 2.9 4.7N11 11 11 94(F)Mean14.5***17.0** 21.4** 22.9S.D.2.5 3.2 3.4 8.5N9 9 9 6Food Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 96Table 9 (continued) Group Mean Food ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 1 8 15 22 29 36 43 50(Sex) To: 8 15 22 29 36 43 50 571(M) Mean 17.7 18.1 19.7 19.2 19.8 20.1 22.5 20.1N 5 5 5 5 5 5 5 54(M) Mean 15.2 15.8 19.1 16.5 17.7 20.5 22.1 19.8N 5 5 5 5 5 5 5 5Food Consumption = g/animal/day.Dose Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 97Table 9 (continued) Group Mean Food ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 1 8 15 22 29 36 43 50(Sex) To: 8 15 22 29 36 43 50 571(F) Mean 12.8 12.9 15.0 13.7 14.3 14.9 17.3 14.9N 5 5 5 5 5 5 5 54(F) Mean 11.2 11.6 16.0 12.9 13.8 15.3 17.4 15.7N 5 5 5 5 5 5 5 5Food Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 98Table 10 Food EfficiencyDay Numbers Relative to Start DateGroup From: 1 8 22 29 36(Sex) To: 8 15 29 36 431(M) Mean 10.2 10.5 8.8 7.3 ƒ0.4N 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ2(M) Mean 7.8 12.3 7.9 7.1 2.8N 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ3(M) Mean 5.4 7.6 6.1 7.1 3.3N 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4(M) Mean 1.8 6.4 4.0 5.5 6.3N 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 99Table 10 (continued) Food EfficiencyPre-PairingDay Numbers Relative to Start DateGroup From: 1 8(Sex) To: 8 151(F) Mean 6.2 12.1N 12 12ƒƒƒƒƒ ƒƒƒƒƒ2(F) Mean 3.2 5.2N 12 12ƒƒƒƒƒ ƒƒƒƒƒ3(F) Mean ƒ2.5 7.6N 12 12ƒƒƒƒƒ ƒƒƒƒƒ4(F) Mean ƒ1.9 3.7N 12 12ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 100Table 10 (continued) Food EfficiencyRecovery GroupsDay Numbers Relative to Start DateGroup From: 1 8 15 22 29 36 43 50(Sex) To: 8 15 22 29 36 43 50 571(M) Mean 10.5 11.9 7.0 9.5 6.6 1.8 6.6 2.2N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4(M) Mean 1.1 8.5 ƒ1.5 14.3 4.7 5.5 9.4 ƒ0.9N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 101Table 10 (continued) Food EfficiencyRecovery GroupsDay Numbers Relative to Start DateGroup From: 1 8 15 22 29 36 43 50(Sex) To: 8 15 22 29 36 43 50 571(F) Mean 5.3 7.0 5.2 0.6 3.2 2.3 7.1 ƒ2.3N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4(F) Mean ƒ3.1 5.2 4.6 3.7 2.1 4.5 5.3 ƒ0.9N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 102Table 11 Group Mean Daily Water ConsumptionsDay Numbers Relative to Start DateGroup From: 3 4 5 6 7 8 9 10 11 12 13(Sex) To: 4 5 6 7 8 9 10 11 12 13 141(M) Mean 26 26.3 26.3 29 24 30 29.7 26.3 25.7 30.3 28.7N 12 12 12 12 12 12 12 12 12 12 122(M) Mean 30.3 26.7 28.7 32 27 30.3 31.3 26.3 29.7 31 28N 12 12 12 12 12 12 12 12 12 12 123(M) Mean 28.7 29.7 29 33.3 25 29.3 34 27.7 28.7 31 30N 12 12 12 12 12 12 12 12 12 12 124(M) Mean 30.3 31 29 35 27 26.3 36 31.3 30.3 28.3 32.3N 12 12 12 12 12 12 12 12 12 12 12Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 103Table 11 (continued) Group Mean Daily Water ConsumptionsDay Numbers Relative to Start DateGroup From: 14 22 23 24 25 26 27 28 29 30 31(Sex) To: 15 23 24 25 26 27 28 29 30 31 321(M) Mean 29.7 27 31 27.7 26 27.7 29.3 33.7 29.7 32 29.7N 12 12 12 12 12 12 12 12 12 12 122(M) Mean 30.3 25 30.7 28.7 25.7 29.3 31.7 33.3 33 35 33.3N 12 12 12 12 12 12 12 12 12 12 123(M) Mean 29.3 26 32.3 30.3 30.3 34.7 33.7 36 31 34.7 35.3N 12 12 12 12 12 12 12 12 12 12 124(M) Mean 31 27.7 32.7 35.3 32.7 36 32 36 35 34.7 31.7N 12 12 12 12 12 12 12 12 12 12 12Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 104Table 11 (continued) Group Mean Daily Water ConsumptionsDay Numbers Relative to Start DateGroup From: 32 33 34 35 36 37 38 39 40 41 42(Sex) To: 33 34 35 36 37 38 39 40 41 42 431(M) Mean 29.3 32.3 32.7 32.3 28.7 29.7 30 27.7 18.7 31 24.7N 12 12 12 12 12 12 12 12 12 12 122(M) Mean 33.7 33 33.7 30.7 30 31.3 30.3 30.7 20 33 28N 12 12 12 12 12 12 12 12 12 12 123(M) Mean 36.7 34.3 37 34 30.7 33 30.3 28.7 21.7 34 26.3N 12 12 12 12 12 12 12 12 12 12 124(M) Mean 35.3 33 38 33 32 33.7 29.7 28.3 18 32.7 26.7N 12 12 12 12 12 12 12 12 12 12 12Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 105Table 11 (continued) Group Mean Daily Water ConsumptionsPre-PairingDay Numbers Relative to Start DateGroup From: 3 4 5 6 7 8 9 10 11 12 13 14(Sex) To: 4 5 6 7 8 9 10 11 12 13 14 151(F) Mean 25.7 24.7 24 27.3 21 22.3 26 22.3 23.3 27.7 25 24.7N 12 12 12 12 12 12 12 12 12 12 12 122(F) Mean 25.7 22.7 21.3 26.3 21.3 22 25.7 21.3 27 26.7 25.7 23N 12 12 12 12 12 12 12 12 12 12 12 123(F) Mean 28.3 24.7 24 31 26 21.7 31.3 27.7 29 28.7 31.3 27.3N 12 12 12 12 12 12 12 12 12 12 12 124(F) Mean 28 23.7 24 30.3 28.7 24.7 28 25.3 29.7 27.3 27.7 26N 12 12 12 12 12 12 12 12 12 12 12 12Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 106Table 11 (continued) Group Mean Water ConsumptionsDay NumbersGestation LactationGroup(Sex)From: 0 7 14 1To: 7 14 20 41(F)Mean31.8 35.6 42.8 41.0S.D.8.2 10.3 10.2 10.1N12 12 12 122(F)Mean29.4 35.7 38.1* 37.1S.D.9.2 14.6 10.9 11.5N10 10 10 93(F)Mean32.9 36.5 38.5 38.0S.D.13.7 16.5 13.4 15.0N11 11 11 114(F)Mean34.1 35.4 41.6 38.8S.D.12.5 12.3 11.3 12.2N9 9 9 7Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 107Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 3 4 5 6 7 8 9 10 11 12 13(Sex) To: 4 5 6 7 8 9 10 11 12 13 141(M) Mean 35 31 18 48 32 32 33 30 33 34 31N 5 5 5 5 5 5 5 5 5 5 54(M) Mean 41 37 32 35 30 32 35 31 39 36 33N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 108Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 14 15 16 17 18 19 20 21 22 23 24(Sex) To: 15 16 17 18 19 20 21 22 23 24 251(M) Mean 31 31 33 26 30 30 36 30 28 31 28N 5 5 5 5 5 5 5 5 5 5 54(M) Mean 32 37 37 39 35 34 55 39 30 40 36N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 109Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 25 26 27 28 29 30 31 32 33 34 35(Sex) To: 26 27 28 29 30 31 32 33 34 35 361(M) Mean 29 34 29 31 34 35 30 28 34 36 32N 5 5 5 5 5 5 5 5 5 5 54(M) Mean 33 43 42 46 35 38 39 36 41 46 49N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 110Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 36 37 38 39 40 41 42 43 44 45 46(Sex) To: 37 38 39 40 41 42 43 44 45 46 471(M) Mean 29 31 33 28 18 32 29 31 33 32 26N 5 5 5 5 5 5 5 5 5 5 54(M) Mean 42 50 39 40 36 48 32 31 33 34 36N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 111Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 47 48 49 50 51 52 53 54 55 56(Sex) To: 48 49 50 51 52 53 54 55 56 571(M) Mean 30 34 33 31 3 33 25 25 28 24N 5 5 5 5 5 5 5 5 5 54(M) Mean 32 34 33 38 4 39 28 30 32 26N 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 112Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 3 4 5 6 7 8 9 10 11 12 13(Sex) To: 4 5 6 7 8 9 10 11 12 13 141(F) Mean 19 17 32 4 18 20 26 18 22 21 24N 5 5 5 5 5 5 5 5 5 5 54(F) Mean 28 30 25 28 20 21 22 22 24 23 25N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 113Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 14 15 16 17 18 19 20 21 22 23 24(Sex) To: 15 16 17 18 19 20 21 22 23 24 251(F) Mean 18 22 21 30 21 22 26 24 18 22 19N 5 5 5 5 5 5 5 5 5 5 54(F) Mean 23 27 26 28 20 19 34 24 24 26 26N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 114Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 25 26 27 28 29 30 31 32 33 34 35(Sex) To: 26 27 28 29 30 31 32 33 34 35 361(F) Mean 21 22 23 19 26 21 19 19 20 17 22N 5 5 5 5 5 5 5 5 5 5 54(F) Mean 25 28 26 27 25 30 26 28 26 33 27N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 115Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 36 37 38 39 40 41 42 43 44 45 46(Sex) To: 37 38 39 40 41 42 43 44 45 46 471(F) Mean 18 25 22 22 26 27 20 24 25 26 22N 5 5 5 5 5 5 5 5 5 5 54(F) Mean 25 34 29 24 28 33 29 33 30 25 28N 5 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 116Table 11 (continued) Group Mean Daily Water ConsumptionsRecovery GroupsDay Numbers Relative to Start DateGroup From: 47 48 49 50 51 52 53 54 55 56(Sex) To: 48 49 50 51 52 53 54 55 56 571(F) Mean 25 25 26 19 7 27 24 21 24 19N 5 5 5 5 5 5 5 5 5 54(F) Mean 29 30 26 25 4 29 26 27 25 18N 5 5 5 5 5 5 5 5 5 5Water Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 117Table 12 Summary Incidence of Mating Performance, Fertility and Gestation LengthsGroupNumberof MalesPairedNumber of Females Pre-Coital Interval (Days) MatingIndex(%)PregnancyIndex(%)Gestation Length (Days) Femaleswith liveOffspringParturitionIndex (%)Paired Mated Pregnant1 2 3 4 5 2122221⁄223231⁄224241⁄21 1212 12 12 4 1 5 2 0 100 100 1 1 5 3 2 0 0 12 1002 1212 12 10 3 4 3 1 1 100 83 0 3 5 1 0 0 1 10 1003 1212 12 11 4 5 2 1 0 100 92 0 3 3 2 2 1 0 11 1004 1212 12 10 1 2 5 2 2 100 83 1 0 1 3 4 0 0 9 90Harlan Study Number:41204605Report Page 118Table 13 Group Mean Litter Size and Litter WeightsGroupNumberofCorporaLuteaNumber ofImplantationSitesTotalNumber ofOffspringBornNumber of LiveOffspringLitter Weight(g)Offspring Weight (g)OffspringBody Weight Change(g)Day 1 Day 4 Days 1-4Day 1 Day 4 Day 1 Day 4 Males FemalesMales FemalesMales Females1 Mean 13.3 12.311.611.411.369.3797.43 6.406.078.998.772.592.70S.D. 1.7 2.6 2.5 2.4 2.5 12.03 16.10 0.64 0.81 1.33 1.63 0.82 0.90N 12 12 12 12 12 12 12 12 12 12 12 12 122 Mean 13.2 12.2 11.7 11.7 11.7 68.03 96.48 6.06 5.85 8.57 8.37 2.51 2.52S.D. 2.1 2.72.92.92.914.7820.20 0.630.471.060.850.580.47N 10 10 9 9 9 9 9 9 9 9 9 9 93 Mean 11.5 10.8 9.1 9.1 9.1 56.51 80.46 6.63 6.21 9.56 9.13 2.94 2.92S.D. 2.8 2.9 3.5 3.5 3.5 19.63 23.88 0.66 0.69 1.39 1.49 0.80 0.90N 11 11 11 11 11 11 11 11 11 11 11 11 114 Mean 11.3 10.38.18.78.755.7679.90 6.506.199.199.022.702.83S.D. 3.0 2.9 3.2 2.1 2.1 17.12 24.79 0.73 0.42 1.08 0.78 0.39 0.41N 9 9 7 7 7 7 7 7 7 7 7 7 7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 119Table 14 Group Mean Implantation Losses and Survival Indices ValuesGroupPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex(%)ViabilityIndex (%)1Mean8.9 5.2 98.7 99.2S.D.13.6 6.5 3.0 2.6N12 12 12 122Mean8.3 14.2 100.0 100.0S.D.12.0 23.8 0.0 0.0N10 10 10 93Mean6.4 15.6 100.0 100.0S.D.12.8 22.3 0.0 0.0N11 11 11 114Mean8.3 28.1 95.8 100.0S.D.9.1 22.4 12.5 0.0N9 9 9 7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 120Table 15 Group Mean Sex Ratio ValuesGroupSex Ratio (% Males) 

# Post PartumDay:At birth 1 41Mean43.9 43.0 43.2S.D.17.1 17.8 17.6N12 12 122Mean38.9 38.9 38.9S.D.10.3 10.3 10.3N9 9 93Mean50.6 50.6 50.6S.D.16.1 16.1 16.1N11 11 114Mean54.9 54.9 54.9S.D.24.9 24.9 24.9N7 7 7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 121Table 16 Summary Incidence of Clinical Signs for OffspringDose Level (mg/kg bw/day)0 (Control) 30 60 120Number of litters 1210 119Small.. .3M 1F (3)Cold. . . 1M 3F (3)Weak. 2M (1) . 2F (2)Pale1F (1). .1F (1)No milk in stomach 1F (1) 2M (1) . 1M 3F (3)Bruised head 1F (1) . . .Scab on dorsal region 1F (1). ..Swollen left hind limb 1F (1) . . .Open wound on right hind limb . . 1F (1) .Missing 2F (2) 2M (1) . 1M 2F 1U (3)Found dead 2M (2) . . 2M 1F (2)() = Number of littersHarlan Study Number:41204605Report Page 122Table 17 Group Mean Reflexological Responses for OffspringGroupSurface Righting (%passed)1Mean96.0S.D.8.0N122Mean95.1S.D.9.8N93Mean81.5S.D.18.6N114Mean83.7S.D.17.0N7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 123Table 18 Group Mean Haematological ValuesGroup Hb RBC Hct MCH MCV MCHC WBC Neut Lymph Mono Eos Bas CTPLT APTT(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(M) Mean 16.24 9.140 50.32 17.78 55.10 32.24 6.50 0.940 5.536 0.000n 0.028 0.000n 9.30 603.6 15.04S.D. 0.68 0.321 1.57 0.85 1.99 0.55 0.35 0.383 0.437 0.000 0.038 0.000 0.35 50.5 0.58N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(M) Mean 16.62 9.424 51.08 17.66 54.20 32.52 7.20 1.412 5.738 0.000n 0.058 0.000n 9.58 577.6 15.92S.D. 0.35 0.344 1.61 0.47 1.26 0.41 1.21 0.366 1.179 0.000 0.066 0.000 0.43 44.5 1.18N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(M) Mean 16.12 9.140 49.78 17.64 54.44 32.40 7.46 1.130 6.256 0.000n 0.078 0.000n 9.48 609.6 17.08S.D. 0.75 0.276 2.04 0.83 1.68 0.68 0.57 0.379 0.435 0.000 0.078 0.000 0.52 106.0 1.61N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(M) Mean 16.04 8.828 48.82 18.20 55.38 32.86 6.26 0.866 5.348 0.000n 0.048 0.000n 9.44 602.6 15.52S.D. 0.90 0.633 2.33 0.44 2.02 0.81 0.55 0.529 0.804 0.000 0.054 0.000 0.71 134.2 1.58N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 124Table 18 (continued) Group Mean Haematological ValuesGroup Hb RBC Hct MCH MCV MCHC WBC Neut Lymph Mono Eos Bas CTPLT APTT(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(F) Mean 13.74 7.298 42.38 18.90 58.26 32.46 5.40 1.778 3.600 0.014n 0.010n 0.000n 9.00 875.0 16.18S.D. 0.53 0.581 1.81 0.89 2.48 0.30 0.94 0.676 0.654 0.031 0.022 0.000 0.43 80.4 1.98N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(F) Mean 13.48 7.394 42.12 18.26 57.06 31.98 4.76 1.456 3.304 0.000n 0.000n 0.000n 9.08 1033.0 17.30S.D. 1.19 0.767 3.86 0.65 1.38 0.30 1.03 0.475 1.193 0.000 0.000 0.000 0.65 147.5 1.01N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(F) Mean 13.04 7.102 40.98 18.36 57.74 31.80 5.30 2.138 3.162 0.000n 0.000n 0.000n 8.70 946.8 16.60S.D. 0.62 0.448 2.37 0.76 2.45 0.58 1.37 0.913 1.071 0.000 0.000 0.000 0.34 64.0 1.45N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(F) Mean 13.54 7.096 42.48 19.06 59.86 31.88 4.92 1.594 3.302 0.000n 0.026n 0.000n 9.00 1021.2* 16.26S.D. 0.45 0.184 1.86 0.61 1.77 0.75 1.47 0.740 0.983 0.000 0.036 0.000 0.36 94.1 1.84N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 125Table 18 (continued) Group Mean Haematological ValuesRecovery GroupsGroup Hb RBC Hct MCH MCV MCHC WBC Neut Lymph Mono Eos Bas CTPLT APTT(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(M) Mean 16.02 8.800 49.10 18.30 56.00 32.66 8.40 1.184 7.110 0.000n 0.106 0.000n 9.58 643.2 15.56S.D. 0.59 0.760 2.25 1.47 3.43 0.88 1.90 0.300 2.068 0.000 0.070 0.000 0.65 89.7 0.88N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(M) Mean 15.52 9.050 48.24 17.14 53.32 32.14 6.56 1.434 5.088 0.000n 0.038 0.000n 9.68 689.0 15.52S.D. 0.23 0.089 0.67 0.40 1.09 0.11 0.71 0.182 0.735 0.000 0.058 0.000 0.62 112.8 1.55N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 126Table 18 (continued) Group Mean Haematological ValuesRecovery GroupsGroup Hb RBC Hct MCH MCV MCHC WBC Neut Lymph Mono Eos Bas CTPLT APTT(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(F) Mean 14.28 7.774 43.32 18.38 55.74 32.96 3.22 0.588 2.592 0.000n 0.040 0.000n 9.24 515.8 15.22S.D. 1.96 1.123 5.96 0.34 0.87 0.35 2.04 0.433 1.622 0.000 0.032 0.000 0.40 291.6 1.69N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(F) Mean 15.18 8.392 46.12 18.10 54.98 32.94 3.52 0.614 2.890 0.000n 0.016 0.000n 8.98 714.0* 16.22S.D. 0.42 0.342 1.20 0.46 1.24 0.27 0.43 0.047 0.397 0.000 0.022 0.000 0.33 35.7 0.70N 5 5 5 5 5 5 5 5 5 5 5 5 55 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 127Table 19 Group Mean Blood Chemical ValuesTot.Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l1(M) Mean 43.2 142.8 6.974 3.94 1.294 147.0 4.492 103.0 2.752S.D. 4.4 16.1 0.284 0.15 0.035 2.2 0.428 3.2 0.082N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(M) Mean 43.0 149.2 6.954 3.86 1.268 146.8 4.584 103.2 2.750S.D. 3.2 25.1 0.464 0.22 0.171 2.5 0.980 1.6 0.094N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(M) Mean 41.4 148.0 7.168 3.88 1.182 146.6 4.778 103.8 2.750S.D. 2.9 13.5 0.437 0.19 0.066 4.2 0.372 2.5 0.178N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 38.2* 145.4 7.296 3.92 1.142* 146.2 4.940 102.8 2.770S.D. 3.3 10.5 0.562 0.25 0.067 2.2 0.779 2.2 0.195N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 128Table 19 (continued) Group Mean Blood Chemical ValuesGroup P ASAT ALAT AP Creat Chol Bili Bile Acid(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dlμmol/l1(M) Mean 1.76 108.0 62.0 173.6 0.720 82.6 0.094 7.96S.D. 0.40 30.8 8.4 34.0 0.030 9.6 0.021 4.82N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 1.74 93.2 64.8 243.2* 0.730 80.0 0.086 6.44S.D. 0.64 16.3 7.3 45.0 0.046 17.5 0.065 4.13N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 1.72 90.8 65.0 181.8 0.720 78.0 0.124 7.30S.D. 0.33 11.9 8.0 38.4 0.058 15.5 0.041 4.04N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 2.14 91.4 54.0 170.8 0.712 72.6 0.124 7.44S.D. 0.53 16.9 7.8 28.7 0.059 7.9 0.038 3.07N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 129Table 19 (continued) Group Mean Blood Chemical ValuesTot.Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l1(F) Mean 48.6 135.2 6.420 3.62 1.308 145.2 4.328 102.6 2.624S.D. 11.3 13.7 0.486 0.23 0.098 2.2 0.329 2.6 0.128N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(F) Mean 51.0 122.2 6.454 3.70 1.350 147.8 4.710 104.6 2.750S.D. 4.7 12.1 0.386 0.12 0.089 2.2 0.604 3.2 0.164N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(F) Mean 55.0 131.0 6.472 3.72 1.344 145.0 4.280 104.2 2.590S.D. 10.1 16.6 0.248 0.13 0.076 2.5 0.519 1.3 0.078N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 57.4 125.4 6.764 3.82 1.296 147.2 5.046 102.8 2.728S.D. 6.0 10.6 0.257 0.13 0.096 1.8 0.718 2.4 0.080N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 130Table 19 (continued) Group Mean Blood Chemical ValuesGroup P ASAT ALAT AP Creat Chol Bili Bile Acid(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dlμmol/l1(F) Mean 1.00 88.0 82.0 128.6 0.848 82.2 0.084 10.84S.D. 0.19 23.8 8.2 36.8 0.319 13.1 0.015 4.65N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 0.96 99.2 75.8 147.2 0.758 69.8 0.076 6.06S.D. 0.55 23.8 18.8 24.7 0.053 15.9 0.005 1.41N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 0.86 83.0 72.0 138.0 0.710 64.4 0.086 7.34S.D. 0.68 16.2 14.9 31.4 0.046 8.7 0.011 4.90N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 1.00 79.6 62.6 169.2 0.848 71.0 0.112* 4.68*S.D. 0.29 14.9 17.4 73.3 0.235 32.1 0.028 1.13N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 131Table 19 (continued) Group Mean Blood Chemical ValuesRecovery GroupsTot.Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l1(M) Mean 52.0 197.6 6.322 3.48 1.228 147.2 4.516 102.0 2.582S.D. 6.6 39.5 0.654 0.31 0.096 2.5 0.667 2.0 0.136N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 50.6 170.0 6.688 3.66 1.216 145.6 4.566 103.2 2.634S.D. 3.8 19.3 0.161 0.17 0.055 1.5 0.234 0.8 0.058N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 132Table 19 (continued) Group Mean Blood Chemical ValuesRecovery GroupsGroup P ASAT ALAT AP Creat Chol Bili Bile Acid(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dlμmol/l1(M) Mean 1.50 123.6 83.6 116.6 0.628 89.6 0.080 9.64S.D. 0.52 39.4 45.5 9.9 0.049 24.0 0.036 12.80N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 1.62 68.0** 56.0 157.4* 0.668 92.2 0.106 8.30S.D. 0.19 6.8 9.4 39.0 0.045 9.4 0.015 3.00N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 133Table 19 (continued) Group Mean Blood Chemical ValuesRecovery GroupsTot.Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l1(F) Mean 53.2 150.4 7.364 4.44 1.520 149.4 4.942 104.2 2.786S.D. 5.4 41.3 0.732 0.44 0.053 3.6 0.711 3.3 0.124N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 51.0 152.0 7.406 4.14 1.276** 147.4 4.682 104.0 2.766S.D. 4.9 8.5 0.237 0.11 0.107 1.3 0.276 1.0 0.051N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 134Table 19 (continued) Group Mean Blood Chemical ValuesRecovery GroupsGroup P ASAT ALAT AP Creat Chol Bili Bile Acid(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dlμmol/l1(F) Mean 1.42 115.2 58.0 103.0 0.704 83.0 0.078 4.86S.D. 0.35 88.3 6.0 23.6 0.046 12.1 0.013 0.51N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 1.50 77.8 63.8 75.6* 0.682 83.0 0.072 7.20S.D. 0.20 17.4 11.0 8.2 0.022 17.7 0.019 6.46N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 135Table 20 Summary Incidence of Urinalytical FindingsMALESDOSE LEVEL: 0 30 60 120 0 120(Control) (mg/kg bw/day) (mg/kg bw/day)(mg/kg bw/day)(Control) (mg/kg bw/day)GROUP:123456Volume Mean (ml) 23.75 17.40 22.40 22.80 21.60 20.80S.D. 6.24 5.94 7.44 9.04 6.80 1.92N 455555Specific Gravity Mean 1.0128 1.0138 1.0122 1.0124 1.0106 1.0134S.D. 0.0043 0.0040 0.0032 0.0049 0.0011 0.0025N 4 5 5 5 5 5pH Examined 5 5 5 5 5 5(Incidence) 5 0 0 0 0 1 16 2 2 4 4 4 47 3 3 1 1 0 0Protein Examined555555(Incidence) 1+ 5 5 5 5 5 5Glucose Examined 5 5 5 5 5 5(Incidence) Normal555555Ketones Examined 5 5 5 5 5 5(Incidence) Neg. 5 5 5 5 5 5Harlan Study Number:41204605Report Page 136Table 20 (continued) Summary Incidence of Urinalytical FindingsMALESDOSE LEVEL: 0 30 60 120 0 120(Control) (mg/kg bw/day) (mg/kg bw/day)(mg/kg bw/day)(Control) (mg/kg bw/day)GROUP:123456UrobilinogenExamined5 5 5 5 5 5(Incidence) Normal5 5 5 5 5 5BilirubinExamined555555(Incidence) Neg.5 5 5 5 5 5Blood - ErythrocytesExamined5 5 5 5 5 5(Incidence) Neg.5 5 5 5 5 5Blood - HaemoglobinExamined5 5 5 5 5 5(Incidence) Neg.5 5 5 5 5 5AppearanceExamined555555Clear5 5 5 5 5 5Harlan Study Number:41204605Report Page 137Table 21 Summary Incidence of Offspring Necropsy FindingsInterim DeathsTerminal Kill (Day 5 

# Post Partu m)Group 

# Post-PartumDayof TerminationNumber ofaffectedLittersNumber ofoffspringMacroscopic FindingsNumberofLittersNumber ofOffspringMacroscopic Findings1 Pre Day 1 1 1MAutolytic changes detected1 1F Scab on dorsal region1 1M No abnormalities detected 1 1F Swollen left hind limb10 . No abnormalities detected2 9 . No abnormalities detected31 1FOpen wound on right hindlimb10 . No abnormalities detected4 Pre Day 1 1 1M 1F Autolytic changes detected 1 1M Small5 1 1M No abnormalities detected 6 . No abnormalities detectedDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 138Table 22 Summary Incidence of Necropsy Findings------------ MALES ------------Removal Reason: SCHEDULED KILL ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60120(Control) mg/kg bw/dayNumber of Animals Examined : 17 12 1217Group : (1) (2) (3)(4)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒEpididymides;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 12 1216Mass; left ...................................................................................... 0 0 01Mammary Gland;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 11 1217Mass ............................................................................................ 0 1 00Seminal Vesicles;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 12 1216Small ........................................................................................... 0 0 01Harlan Study Number:41204605Report Page 139Table 22 (continued) Summary Incidence of Necropsy Findings----------- FEMALES -----------Removal Reason: SCHEDULED KILL ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60120(Control) mg/kg bw/dayNumber of Animals Examined : 17 12 1217Group : (1) (2) (3)(4)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒEyes;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 12 1216Reddened; right ................................................................................. 0 0 01Uterus & Cervix;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 11 1217Distended; left horn ............................................................................ 0 1 00Vagina;Submitted........................................................................................ (17) (12) (12)(17)No Visible Lesions............................................................................... 17 11 1217Fluid Filled .................................................................................... 0 1 00Harlan Study Number:41204605Report Page 140Table 23 Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒTerminal Bodyweight ........... Mean (g) 368.8 386.5 364.7 359.9S.D. 19.3 35.1 21.3 23.4N 12 12 12 12Adrenals ...................... Mean (g) 0.07054 0.06724 0.06116 0.06958S.D. 0.00993 0.01276 0.00784 0.00459N 5 5 5 5Mean (%) 0.018 0.018 0.017 0.019S.D. 0.003 0.004 0.002 0.002N 5 5 5 5Brain (Including Cerebrum,Cerebellum And Pons) .......... Mean (g) 2.05486 2.11214 2.05006 2.02022S.D. 0.08179 0.04234 0.11192 0.05576N 5 5 5 5Mean (%) 0.538 0.571 0.566 0.562S.D. 0.030 0.055 0.034 0.049N 5 5 5 5Epididymides .................. Mean (g) 1.46903 1.46486 1.39471 1.42588S.D. 0.16359 0.20559 0.09263 0.16008N 12 12 12 12Mean (%) 0.398 0.380 0.384 0.396S.D. 0.039 0.050 0.033 0.031N 12 12 12 12Heart ......................... Mean (g) 1.09622 1.12728 1.04006 1.04942S.D. 0.08287 0.12438 0.15560 0.24704N 5 5 5 5Mean (%) 0.287 0.305 0.285 0.288S.D. 0.023 0.050 0.026 0.053N 5 5 5 5Harlan Study Number:41204605Report Page 141Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒKidneys ....................... Mean (g) 2.09492 2.34530* 2.28052* 2.50644**S.D. 0.26027 0.20846 0.11630 0.49391N 5 5 5 5Mean (%) 0.548 0.631* 0.629* 0.689**S.D. 0.057 0.037 0.023 0.092N 5 5 5 5Liver ......................... Mean (g) 11.4692 11.4094 11.1958 12.1312**S.D. 0.72540 1.41625 1.14413 1.89008N 5 5 5 5Mean (%) 3.004 3.056 3.082 3.343**S.D. 0.191 0.085 0.180 0.310N 5 5 5 5Pituitary ..................... Mean (g) 0.01188 0.01317 0.01328 0.01343S.D. 0.00210 0.00318 0.00403 0.00390N 12 12 12 12Mean (%) 0.003 0.003 0.004 0.004S.D. 0.001 0.001 0.001 0.001N 12 12 12 12Prostate ...................... Mean (g) 0.58791 0.56530 0.54142 0.49996*S.D. 0.12897 0.07772 0.07102 0.10906N 12 12 12 12Mean (%) 0.160 0.147 0.149 0.139*S.D. 0.036 0.025 0.019 0.028N 12 12 12 12Harlan Study Number:41204605Report Page 142Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒSeminal Vesicles .............. Mean (g) 1.98853 2.09621 1.85843 1.65654S.D. 0.35281 0.32206 0.24142 0.56221N 12 12 12 12Mean (%) 0.540 0.542 0.511 0.456S.D. 0.103 0.070 0.071 0.144N 12 12 12 12Spleen ........................ Mean (g) 0.67532 0.68622 0.70070 0.68724S.D. 0.07424 0.11915 0.09007 0.06466N 5 5 5 5Mean (%) 0.176 0.183 0.193 0.191S.D. 0.014 0.021 0.024 0.022N 5 5 5 5Testes ........................ Mean (g) 3.54083 3.67949 3.57387 3.44931S.D. 0.27102 0.22075 0.26153 0.44585N 12 12 12 12Mean (%) 0.962 0.957 0.982 0.959S.D. 0.080 0.081 0.081 0.111N 12 12 12 12Thymus ........................ Mean (g) 0.44996 0.37970 0.39078 0.36374S.D. 0.06312 0.06863 0.10430 0.05655N 5 5 5 5Mean (%) 0.119 0.102 0.107 0.101S.D. 0.022 0.015 0.026 0.016N 5 5 5 5Harlan Study Number:41204605Report Page 143Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒThyroid/Parathyroid ........... Mean (g) 0.02086 0.02310 0.02042 0.02392S.D. 0.00499 0.00269 0.00407 0.00534N 5 5 5 5Mean (%) 0.005 0.006 0.006 0.007S.D. 0.001 0.001 0.001 0.001N 5 5 5 5Harlan Study Number:41204605Report Page 144Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒTerminal Bodyweight ........... Mean (g) 274.0 240.2 236.4 233.2S.D. 13.1 33.3 18.1 18.5N 12 12 12 12Adrenals ...................... Mean (g) 0.09412 0.09080 0.08688 0.08354S.D. 0.01057 0.01118 0.01306 0.01381N 5 5 5 5Mean (%) 0.034 0.042 0.037 0.036S.D. 0.004 0.007 0.007 0.004N 5 5 5 5Brain (Including Cerebrum,Cerebellum And Pons) .......... Mean (g) 1.82766 1.80580 1.81458 1.79434S.D. 0.05221 0.04933 0.04234 0.08993N 5 5 5 5Mean (%) 0.663 0.853 0.771 0.769S.D. 0.042 0.234 0.059 0.058N 5 5 5 5Heart ......................... Mean (g) 0.96620 0.83188 0.79450 0.76636S.D. 0.16500 0.12342 0.06622 0.14537N 5 5 5 5Mean (%) 0.349 0.390 0.337 0.328S.D. 0.050 0.104 0.036 0.064N 5 5 5 5Kidneys ....................... Mean (g) 1.59194 1.48776 1.51298 1.41826S.D. 0.09496 0.07908 0.17224 0.10175N 5 5 5 5Mean (%) 0.577 0.704 0.640 0.606S.D. 0.046 0.208 0.050 0.032N 5 5 5 5Harlan Study Number:41204605Report Page 145Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒLiver ......................... Mean (g) 11.5588 9.80792 10.3356 10.2245S.D. 1.15216 0.96526 1.07891 1.08438N 5 5 5 5Mean (%) 4.188 4.617 4.370 4.370S.D. 0.427 1.259 0.234 0.411N 5 5 5 5Ovaries ....................... Mean (g) 0.10820 0.11041 0.10215 0.09284S.D. 0.01302 0.01068 0.01532 0.01224N 12 9 11 7Mean (%) 0.040 0.048 0.043 0.039S.D. 0.005 0.010 0.007 0.006N 12 9 11 7Pituitary ..................... Mean (g) 0.01720 0.01874 0.01733 0.01409*S.D. 0.00219 0.00470 0.00209 0.00202N 12 8 10 7Mean (%) 0.006 0.008 0.007 0.006*S.D. 0.001 0.002 0.001 0.001N 12 8 10 7Spleen ........................ Mean (g) 0.61280 0.53334 0.52158 0.54270S.D. 0.07238 0.05712 0.09310 0.02346N 5 5 5 5Mean (%) 0.222 0.251 0.222 0.232S.D. 0.031 0.066 0.043 0.015N 5 5 5 5Harlan Study Number:41204605Report Page 146Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 60 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒThymus ........................ Mean (g) 0.26878 0.23310 0.22170* 0.18640*S.D. 0.04921 0.04087 0.05661 0.03448N 5 5 5 5Mean (%) 0.097 0.113 0.095* 0.080*S.D. 0.014 0.047 0.028 0.016N 5 5 5 5Thyroid/Parathyroid ........... Mean (g) 0.01898 0.02260 0.02160 0.02118S.D. 0.00299 0.00499 0.00367 0.00201N 5 5 5 5Mean (%) 0.007 0.011 0.009 0.009S.D. 0.001 0.004 0.002 0.001N 5 5 5 5Uterus & Cervix ............... Mean (g) 0.68538 0.65874 0.62923 0.61047S.D. 0.13143 0.09946 0.13848 0.05708N 12 9 11 7Mean (%) 0.252 0.289 0.264 0.257S.D. 0.058 0.092 0.057 0.035N 12 9 11 7Harlan Study Number:41204605Report Page 147Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒKidneys ....................... Mean (g) 2.11860 2.30742S.D. 0.06606 0.47074N 5 5Mean (%) 0.534 0.620S.D. 0.034 0.089N 5 5Liver ......................... Mean (g) 12.0344 11.3880S.D. 1.30935 0.91637N 5 5Mean (%) 3.019 3.085S.D. 0.162 0.214N 5 5Pituitary ..................... Mean (g) 0.01082 0.01100S.D. 0.00101 0.00210N 5 5Mean (%) 0.003 0.003S.D. 0.000 0.001N 5 5Prostate ...................... Mean (g) 0.60260 0.48336S.D. 0.10012 0.09687N 5 5Mean (%) 0.151 0.131S.D. 0.016 0.028N 5 5Harlan Study Number:41204605Report Page 148Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒSeminal Vesicles .............. Mean (g) 2.11602 2.07198S.D. 0.23668 0.35038N 5 5Mean (%) 0.534 0.558S.D. 0.077 0.062N 5 5Spleen ........................ Mean (g) 0.64076 0.60758S.D. 0.04745 0.10857N 5 5Mean (%) 0.162 0.164S.D. 0.021 0.027N 5 5Testes ........................ Mean (g) 3.57770 3.40932S.D. 0.23303 0.25097N 5 5Mean (%) 0.903 0.925S.D. 0.095 0.076N 5 5Thymus ........................ Mean (g) 0.42268 0.32344S.D. 0.06598 0.05761N 5 5Mean (%) 0.106 0.088S.D. 0.011 0.019N 5 5Harlan Study Number:41204605Report Page 149Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒThyroid/Parathyroid ........... Mean (g) 0.02258 0.02162S.D. 0.00117 0.00274N 5 5Mean (%) 0.006 0.006S.D. 0.000 0.001N 5 5Harlan Study Number:41204605Report Page 150Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒTerminal Bodyweight ........... Mean (g) 218.4 220.8S.D. 11.5 10.1N 5 5Adrenals ...................... Mean (g) 0.07984 0.08284S.D. 0.01130 0.01186N 5 5Mean (%) 0.036 0.038S.D. 0.004 0.006N 5 5Brain (Including Cerebrum,Cerebellum And Pons) .......... Mean (g) 1.78686 1.84922S.D. 0.09015 0.13123N 5 5Mean (%) 0.819 0.839S.D. 0.049 0.075N 5 5Heart ......................... Mean (g) 0.76796 0.70458S.D. 0.10617 0.02719N 5 5Mean (%) 0.351 0.320S.D. 0.039 0.020N 5 5Kidneys ....................... Mean (g) 1.36402 1.36676S.D. 0.13965 0.08392N 5 5Mean (%) 0.626 0.621S.D. 0.067 0.056N 5 5Harlan Study Number:41204605Report Page 151Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒLiver ......................... Mean (g) 7.27868 7.73596S.D. 0.90210 0.39415N 5 5Mean (%) 3.324 3.505S.D. 0.247 0.143N 5 5Ovaries ....................... Mean (g) 0.10370 0.09744S.D. 0.02236 0.01659N 5 5Mean (%) 0.047 0.044S.D. 0.010 0.009N 5 5Pituitary ..................... Mean (g) 0.01666 0.01988S.D. 0.00235 0.00392N 5 5Mean (%) 0.008 0.009S.D. 0.001 0.002N 5 5Spleen ........................ Mean (g) 0.51454 0.45104S.D. 0.10796 0.03879N 5 5Mean (%) 0.235 0.205S.D. 0.043 0.024N 5 5Harlan Study Number:41204605Report Page 152Table 23 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ WeightsRecovery Groupsƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 120Control mg/kg bw/dayƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒThymus ........................ Mean (g) 0.28620 0.29462S.D. 0.03899 0.04860N 5 5Mean (%) 0.131 0.134S.D. 0.014 0.023N 5 5Thyroid/Parathyroid ........... Mean (g) 0.01988 0.01704S.D. 0.00421 0.00470N 5 5Mean (%) 0.009 0.008S.D. 0.002 0.002N 5 5Uterus & Cervix ............... Mean (g) 0.62746 0.77958S.D. 0.13815 0.27845N 5 5Mean (%) 0.287 0.357S.D. 0.058 0.144N 5 5

# Harlan Study Number: 41204605 Report Page 153



# FIGURESHarlan Study Number:41204605Report Page 154Figure 1 Group Mean Body Weights - MalesNon-Recovery GroupsHarlan Study Number:41204605Report Page 155Figure 1 (continued) Group Mean Body Weights - MalesRecovery GroupsHarlan Study Number:41204605Report Page 156Figure 2 Group Mean Body Weights - FemalesPre-PairingHarlan Study Number:41204605Report Page 157Figure 2 (continued) Group Mean Body Weights - FemalesGestationHarlan Study Number:41204605Report Page 158Figure 2 (continued) Group Mean Body Weights - FemalesRecovery GroupsHarlan Study Number:41204605Report Page 159Figure 3 Group Mean Food Consumption - MalesHarlan Study Number:41204605Report Page 160Figure 4 Group Mean Food Consumption – FemalesNon-Recovery GroupsHarlan Study Number:41204605Report Page 161Figure 4 (continued) Group Mean Food Consumption – FemalesRecovery Groups

# Harlan Study Number: 41204605 Report Page 162



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# Harlan Study Number: 41204605 Report Page 163



# APPENDICESHarlan Study Number:41204605Report Page 164Appendix 1 Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 221(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .2 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .3 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .4 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .5 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .6 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .7 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .8 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .9 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .10 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .11 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .12 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 165Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 431(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X2 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X3 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X4 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X5 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X6 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X7 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X8 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X9 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X10 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X11 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X12 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 166Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 222(M) 25 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .26 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .27 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .28 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .29 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .30 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .31 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .32 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .33 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .34 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .35 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .36 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 167Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 432(M) 25 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X26 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X27 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X28 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X29 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X30 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X31 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X32 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X33 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X34 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X35 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X36 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 168Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 223(M) 49 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .50 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .54 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .55 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .59 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 169Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 433(M) 49 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X50 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X51 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X52 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . . . . . X . .53 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . X X . . . X X .54 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X55 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X56 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . X . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . X58 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . . . . . . X .59 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . . . . . X . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 170Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 223(M) 60 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 171Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 433(M) 60 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 172Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 224(M) 73 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . .74 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . .78 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . X . . . . . . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . X . . .80 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . .81 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 173Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 434(M) 73 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . X . . . . . . . . . . . . . . . X . .74 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation X . . . . . . . . . . X . . . . X . X . .75 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X . . . . . . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation X X X X . . . X . X . . X . X . . X X X .77 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . . . X X . X .78 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X X X . X . . X . . . X . X X . . X . .79 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation X . . X . . . X . X . X X . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . X X . X . . X . . . . . . . . X . . .81 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X . . . X . . X . . . . . . . . . X . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 174Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 224(M) 82 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . .84 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 175Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 434(M) 82 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . X X . . . X X X . . X . . X X . . . .83 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation X . . X . . . . . . . . . . . X . X X X .84 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . X . . . . . . . X . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 176Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 241(F) 13 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .14 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .15 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .16 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XLittering . . . . . . . . . . . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . . . . .17 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .18 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .19 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XLittering . . . . . . . . . . . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . . . . .20 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .21 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .22 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .23 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .24 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 177Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 471(F) 13 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .14 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .15 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .16 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Littering . . . . . . . . . . . . . X . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .17 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .18 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . . . . . . . . . X .19 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Littering . . . . . . . . . . . . . X . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .20 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .21 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .22 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .23 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .24 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 178Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 242(F) 37 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .38 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .39 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .40 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .41 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .42 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .43 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .44 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .45 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .46 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .47 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .48 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 179Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 472(F) 37 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .38 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .39 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .40 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .41 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .42 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .43 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . . . . . . . . . X .44 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .45 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .46 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .47 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .48 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 180Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 243(F) 61 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .62 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .63 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .64 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .65 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .66 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .67 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XLittering . . . . . . . . . . . . . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . . . . .68 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XLittering . . . . . . . . . . . . . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . . . . .69 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .70 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .71 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 181Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 473(F) 61 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .62 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .Increased salivation . . . . . . . . . . . . . . . . X . . . . . .63 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .Increased salivation . . . . . . . . . . . . . . . . X . . . . . .64 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .65 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .66 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .67 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Littering . . . . . . . . . . . . . X . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . . . X . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .68 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Littering . . . . . . . . . . . . . X . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . . . X . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .69 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . . . . . . . . . X .70 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .71 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 182Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 243(F) 72 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 183Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 473(F) 72 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 184Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 244(F) 85 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .86 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .87 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . . . X88 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . X . . . . .89 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . . . .90 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . X . . . . X91 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XLittering . . . . . . . . . . . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . . . .92 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . X . . . . . . . . . . . . . . . . . . . . .93 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 185Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 474(F) 85 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .Increased salivation . . . . . . . . . . . . . . . . X . . . . . .86 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .Increased salivation X X . . . X . . . . . . . . . . . . . . . . .87 No Abnormalities Detected X X X X X X X X X X X X X X X X X X . . . . .Scheduled kill . . . . . . . . . . . . . . . . . X . . . . .Increased salivation X . . . . . X X . . . . . . X X . . . . . . .88 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .Increased salivation . X . . . . X . . . . . . . . . . . . . . . .89 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X X . X . X . . . . . . . . . . X . . . . . .90 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .Increased salivation . X . X . . . X . . . . . . X X . . . . . . .91 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Littering . . . . . . . . . . . . . . . X . . . . . . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .Increased salivation . . . . . X X . . . . . . . . . X . . . . . .92 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . . . . . . X . . . .Increased salivation . X . X . . . . . . . . . . . . . . . . . . .93 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . . . . . . . . X . .Increased salivation X . . . . X X X . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 186Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 244(F) 94 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . . X .95 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . X96 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 187Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 474(F) 94 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . . . . . . . . . X .Increased salivation . . . . . . . . . . . . . . . X . . X . . . .95 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X . . .Scheduled kill . . . . . . . . . . . . . . . . . . . X . . .Increased salivation X X . . . . . . . . . . . . . . . . . . . . .96 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . . . . . . . . . X .Increased salivation . . . . . . X X . . . . . . . . X . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 188Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 291(M) 97 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . X . . . . . . . . . . . . . . . . . . . . . . . . . .100 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 189Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 571(M) 97 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X98 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X99 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . . . . . . . . . . . . . . . . . . . . . .100 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X101 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 190Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 294(M) 107 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . X . . . . . . X X . . X108 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . X . . . X X X109 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . X . . . X X . . X X X110 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . X . . . . . . . . . . . . . . . . . . . X . X . X . .111 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . X . . X . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 191Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 574(M) 107 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . . . . . . . X . . . X X . . . . . . . . . . . . . . .108 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X . . . X . X . . . . X . . . . . . . . . . . . . . .109 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X . X . . . . . X X X X . . . . . . . . . . . . . . . .110 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X X X . . . . . . . X . . . . . . . . . . . . . . . . .111 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X . . . . . . . X . X X . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 192Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 291(F) 102 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .104 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 193Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 571(F) 102 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X103 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X104 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X105 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . X106 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 194Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 294(F) 112 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . X . . . . . X . . . .113 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . X . . X . . .114 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . X . . . . . . . . . . . . . . X . . . . X X X . X X .115 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . X . . . X . X116 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Increased salivation . . . . . . . . . . . . . . . . . . . . . . . X . . X . XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 195Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal(Sex) Number Clinical Sign 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 574(F) 112 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X . . . . . . . . . . X . . . . . . . . . . . . . . . .113 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X . . . X X . . . . X X . . . . . . . . . . . . . . .114 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X X X . . . X X . . X . . . . . . . . . . . . . . . . .115 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation . X X . . . . . . X . X X . . . . . . . . . . . . . . .116 No Abnormalities Detected X X X X X X X X X X X X X X X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . . . . . . . . . . . . . . . XIncreased salivation X X X . . . . . . . . X X . . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 196Appendix 2 Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 381(M) 1 No Abnormalities Detected X X X X X X X2 No Abnormalities Detected X X X X X X X3 No Abnormalities Detected X X X X X X X4 No Abnormalities Detected X X X X X X X5 No Abnormalities Detected X X X X X X X6 No Abnormalities Detected X X X X X X X7 No Abnormalities Detected X X X X X X X8 No Abnormalities Detected X X X X X X X9 No Abnormalities Detected X X X X X X X10 No Abnormalities Detected X X X X X X X11 No Abnormalities Detected X X X X X X X12 No Abnormalities Detected X X X X X X XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 197Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 Day 4 

# post partum1(F) 13 No Abnormalities Detected X X X X X X X14 No Abnormalities Detected X X X X X X X15 No Abnormalities Detected X X X X X X X16 No Abnormalities Detected X X X X X X X17 No Abnormalities Detected X X X X X X X18 No Abnormalities Detected X X X X X X X19 No Abnormalities Detected X X X X X X X20 No Abnormalities Detected X X X X X X X21 No Abnormalities Detected X X X X X X X22 No Abnormalities Detected X X X X X X X23 No Abnormalities Detected X X X X X X X24 No Abnormalities Detected X X X X X X XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 198Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 382(M) 25 No Abnormalities Detected X X X X X X X26 No Abnormalities Detected X X X X X X X27 No Abnormalities Detected X X X X X X X28 No Abnormalities Detected X X X X X X X29 No Abnormalities Detected X X X X X X X30 No Abnormalities Detected X X X X X X X31 No Abnormalities Detected X X X X X X X32 No Abnormalities Detected X X X X X X X33 No Abnormalities Detected X X X X X X X34 No Abnormalities Detected X X X X X X X35 No Abnormalities Detected X X X X X X X36 No Abnormalities Detected X X X X X X XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 199Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 Day 4 

# post partum #2(F) 37 No Abnormalities Detected X X X X X X X38 No Abnormalities Detected X X X X X X X39 No Abnormalities Detected X X X X X X X40 No Abnormalities Detected X X X X X X X41 No Abnormalities Detected X X X X X X X42 No Abnormalities Detected X X X X X X X43 No Abnormalities Detected X X X X X X X44 No Abnormalities Detected X X X X X X X45 No Abnormalities Detected X X X X X X X46 No Abnormalities Detected X X X X X X X47 No Abnormalities Detected X X X X X X X48 No Abnormalities Detected X X X X X X X# = Day 25 

# post coitumfor female Numbers 43 and 48X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 200Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 383(M) 49 No Abnormalities Detected X X X X X X X50 No Abnormalities Detected X X X X X X X51 No Abnormalities Detected X X X X X X X52 No Abnormalities Detected X X X X X X X53 No Abnormalities Detected X X X X X X X54 No Abnormalities Detected X X X X X X X55 No Abnormalities Detected X X X X X X X56 No Abnormalities Detected X X X X X X X57 No Abnormalities Detected X X X X X X X58 No Abnormalities Detected X X X X X X X59 No Abnormalities Detected X X X X X X X60 No Abnormalities Detected X X X X X X XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 201Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 Day 4 

# post partum #3(F) 61 No Abnormalities Detected X X X X X X X62 No Abnormalities Detected X X X X X X X63 No Abnormalities Detected X X X X X X X64 No Abnormalities Detected X X X X X X X65 No Abnormalities Detected X X X X X X X66 No Abnormalities Detected X X X X X X X67 No Abnormalities Detected X X X X X X X68 No Abnormalities Detected X X X X X X X69 No Abnormalities Detected X X X X X X X70 No Abnormalities Detected X X X X X X X71 No Abnormalities Detected X X X X X X X72 No Abnormalities Detected X X X X X X X# = Day 25 

# post coitumfor female Number 62X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 202Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 384(M) 73 No Abnormalities Detected X X X X X X X74 No Abnormalities Detected X X X X X X X75 No Abnormalities Detected X X X X X X X76 No Abnormalities Detected X X X X X X X77 No Abnormalities Detected X X X X X X X78 No Abnormalities Detected X X X X X X X79 No Abnormalities Detected X X X X X X X80 No Abnormalities Detected X X X X X X X81 No Abnormalities Detected X X X X X X X82 No Abnormalities Detected X X X X X X X83 No Abnormalities Detected X X X X X X X84 No Abnormalities Detected X X X X X X XX = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 203Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign ƒ1 7 14 21 28 35 Day 4 

# post partum #4(F) 85 No Abnormalities Detected X X X X X X X86 No Abnormalities Detected X X X X X X X87 No Abnormalities Detected X X X X X X X88 No Abnormalities Detected X X X X X X X89 No Abnormalities Detected X X X X X X X90 No Abnormalities Detected X X X X X X X91 No Abnormalities Detected X X X X X X X92 No Abnormalities Detected X X X X X X X93 No Abnormalities Detected X X X X X X X94 No Abnormalities Detected X X X X X X X95 No Abnormalities Detected X X X X X X X96 No Abnormalities Detected X X X X X X X# = Day 25 

# post coitumfor female Numbers 85, 87 and 88X = PresentDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 204Appendix 3 Individual Behavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 1 0 03 0 1 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 0 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 205Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 1 0 015 0 0 0 016 0 1 0 017 0 0 0 018 0 0 0 019 0 0 0 020 0 0 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 206Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 0 0 027 0 0 0 028 0 0 0 029 0 1 1 030 0 3 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 2 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.5 0.1 0.0S.D. 0.0 1.0 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 207Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 2 0 038 0 0 0 039 0 0 0 040 0 2 0 041 0 0 0 042 0 0 0 043 0 1 0 044 0 0 0 045 0 0 0 046 0 0 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.4 0.0 0.0S.D. 0.0 0.8 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 208Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 0 0 051 0 0 0 052 0 1 0 053 0 0 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 0 0 058 0 2 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.6 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 209Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 0 0 063 0 1 0 064 0 0 0 065 0 0 0 066 0 0 0 067 0 0 0 068 0 0 0 069 0 0 0 070 0 0 0 071 0 0 0 072 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 210Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 1 0 075 0 0 0 076 0 0 0 077 0 0 0 078 0 0 0 079 0 1 0 080 0 0 0 081 0 0 0 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 211Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: ƒ1 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 0 0 090 0 0 0 091 0 1 0 092 0 0 0 093 0 0 0 094 0 0 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 212Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 0 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 1 1 08 0 0 0 09 0 0 0 010 0 0 0 011 0 0 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 213Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 0 0 015 0 0 0 016 0 0 0 017 0 0 0 018 0 0 0 019 0 0 0 020 0 0 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 214Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 0 0 027 0 0 0 028 0 1 0 029 0 0 0 030 0 0 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 0 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 215Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 1 0 038 0 0 0 039 0 0 0 040 0 0 0 041 0 0 0 042 0 0 0 043 0 0 0 044 0 0 1 045 0 0 0 046 0 0 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 216Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 0 0 051 0 0 0 052 0 0 0 053 0 0 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 0 0 058 0 0 0 059 0 1 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 217Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 0 0 063 0 0 0 064 0 0 0 065 0 0 0 066 0 0 0 067 0 0 0 068 0 0 0 069 0 0 0 070 0 1 1 071 0 0 0 072 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.1 0.0S.D. 0.0 0.3 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 218Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 0 0 075 0 0 0 076 0 0 0 077 0 0 0 078 0 1 0 079 0 0 0 080 0 0 0 081 0 0 0 082 0 1 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 219Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 7 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 0 0 090 0 0 0 091 0 0 0 092 0 0 0 093 0 0 0 094 0 0 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 220Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 1 0 04 0 0 0 05 0 0 0 06 0 1 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 0 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 221Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 0 0 015 0 0 0 016 0 0 0 017 0 0 0 018 0 0 0 019 0 0 0 020 0 0 0 021 0 1 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 222Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 0 0 027 0 1 0 028 0 0 0 029 0 0 0 030 0 0 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 0 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 223Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 1 1 038 0 1 0 039 0 0 0 040 0 0 0 041 0 0 0 042 0 0 0 043 0 0 0 044 0 0 0 045 0 0 0 046 0 1 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 224Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 1 0 051 0 0 0 052 0 0 0 053 0 1 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 1 0 058 0 0 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 225Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 0 0 063 0 0 0 064 0 0 0 065 0 1 0 066 0 0 0 067 0 0 0 068 0 1 0 069 0 0 0 070 0 0 0 071 0 0 0 072 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 226Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 0 0 075 0 0 0 076 0 0 0 077 0 0 0 078 0 0 0 079 0 0 0 080 0 1 0 081 0 1 1 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 227Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 1 0 090 0 0 0 091 0 1 0 092 0 0 0 093 0 1 0 094 0 0 0 095 0 1 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 228Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 1 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 1 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 229Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 1 0 014 0 0 0 015 0 1 0 016 0 0 0 017 0 0 0 018 0 0 0 019 0 0 0 020 0 0 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 230Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 1 0 027 0 1 0 028 0 1 0 029 0 0 0 030 0 1 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 1 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.4 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 231Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 0 0 038 0 0 0 039 0 0 0 040 0 0 0 041 0 0 0 042 0 0 0 043 0 1 0 044 0 0 0 045 0 0 0 046 0 1 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 232Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 0 0 051 0 1 0 052 0 0 0 053 0 1 1 054 0 0 0 055 0 0 0 056 0 0 0 057 0 0 0 058 0 0 0 059 0 1 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 233Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 0 0 063 0 0 0 064 0 0 0 065 0 1 0 066 0 1 0 067 0 0 0 068 0 0 0 069 0 0 0 070 0 0 0 071 0 0 0 072 0 1 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 234Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 1 0 074 0 0 0 075 0 0 0 076 0 0 0 077 0 0 0 078 0 0 0 079 0 0 0 080 0 0 0 081 0 1 0 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 235Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 21 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 1 0 089 0 0 0 090 0 1 0 091 0 0 0 092 0 0 0 093 0 0 0 094 0 0 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 236Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 0 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 0 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 237Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 0 0 015 0 0 0 016 0 0 0 017 0 0 0 018 0 1 0 019 0 0 0 020 0 0 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 238Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 0 0 027 0 1 0 028 0 1 0 029 0 0 0 030 0 1 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 1 0 035 0 0 0 036 0 1 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.4 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 239Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 0 0 038 0 0 0 039 0 0 0 040 0 0 0 041 0 0 0 042 0 0 0 043 0 0 0 044 0 0 0 045 0 1 0 046 0 0 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 240Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 1 0 051 0 0 0 052 0 0 0 053 0 0 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 1 0 058 0 1 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 241Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 1 0 063 0 0 0 064 0 0 0 065 0 0 0 066 0 0 0 067 0 0 0 068 0 1 0 069 0 0 0 070 0 1 1 071 0 0 0 072 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 242Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 0 0 075 0 1 0 076 0 0 0 077 0 0 1 078 0 0 0 079 0 0 0 080 0 1 0 081 0 1 0 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 243Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 28 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 0 0 090 0 0 0 091 0 0 0 092 0 1 0 093 0 0 0 094 0 1 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 244Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 0 0 04 0 0 0 05 0 1 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 1 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 245Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 1 0 014 0 0 0 015 0 1 0 016 0 1 0 017 0 1 0 018 0 0 0 019 0 1 0 020 0 1 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 1 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.6 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 246Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 1 0 026 0 0 0 027 0 0 0 028 0 0 0 029 0 0 0 030 0 0 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 0 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 247Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 0 0 038 0 0 0 039 0 0 0 040 0 0 0 041 0 0 0 042 0 0 0 043 0 1 0 044 0 1 0 045 0 0 0 046 0 0 0 047 0 1 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 248Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 1 0 050 0 0 0 051 0 0 0 052 0 0 0 053 0 0 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 0 0 058 0 0 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 0.0 0.0S.D. 0.0 0.3 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 249Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 1 0 062 0 0 0 063 0 1 1 064 0 0 0 065 0 1 0 066 0 0 0 067 0 1 0 068 0 1 0 069 0 1 1 070 0 0 0 071 0 0 0 072 0 1 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.6 0.2 0.0S.D. 0.0 0.5 0.4 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 250Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 0 0 075 0 0 0 076 0 0 0 077 0 0 0 078 0 0 0 079 0 0 0 080 0 0 0 081 0 0 0 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 251Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 1 0 090 0 0 0 091 0 1 0 092 0 1 0 093 0 0 0 094 0 0 0 095 0 1 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 252Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 38 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 0 0 02 0 0 0 03 0 0 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 0 0 010 0 0 0 011 0 0 0 012 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 253Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 4 

# post partumGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 0 0 015 0 0 0 016 0 0 0 017 0 0 0 018 0 0 0 019 0 1 0 020 0 0 0 021 0 1 0 022 0 1 0 023 0 1 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.0 0.0S.D. 0.0 0.5 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 254Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 38 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 1 0 026 0 0 0 027 0 0 0 028 0 1 1 029 0 0 0 030 0 0 0 031 0 0 0 032 0 0 0 033 0 0 0 034 0 0 0 035 0 0 0 036 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 255Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 4 

# post partum #Group Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 1 0 038 0 0 0 039 0 1 0 040 0 0 0 041 0 1 1 042 0 0 0 043 0 0 0 044 0 0 0 045 0 0 0 046 0 0 1 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 0.2 0.0S.D. 0.0 0.5 0.4 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumfor female Numbers 43 and 48Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 256Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 38 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 0 0 050 0 0 0 051 0 0 0 052 0 0 0 053 0 0 0 054 0 0 0 055 0 0 0 056 0 0 0 057 0 0 0 058 0 0 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 257Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 4 

# post partum #Group Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 0 0 062 0 0 0 063 0 0 0 064 0 1 0 065 0 0 0 066 0 0 0 067 0 0 0 068 0 1 1 069 0 0 0 070 0 0 0 071 0 0 0 072 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.1 0.0S.D. 0.0 0.4 0.3 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumfor female Number 62Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 258Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 38 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(M) 73 0 0 0 074 0 0 0 075 0 0 0 076 0 1 0 077 0 0 0 078 0 0 0 079 0 0 0 080 0 0 0 081 0 1 0 082 0 0 0 083 0 0 0 084 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0S.D. 0.0 0.4 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 259Appendix 3 (continued) IndividualBehavioural Assessments (Scores)Day: 4 

# post partum #Group Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 0 0 088 0 0 0 089 0 0 0 090 0 0 0 091 0 0 0 092 0 0 0 093 0 0 0 094 0 0 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumfor female Numbers 85, 87 and 88Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 260Appendix 4 Individual and Group Mean Functional Test Values (Grip Strength)Day: 38 Relative to Start DateGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g1(M) 1 879 267 1458 279 845 3012 1125 556 1146 499 1877 6673 942 272 1245 222 899 6254 1156 318 829 495 579 2465 1223 627 1162 172 607 275ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 1065.0 408.0 1168.0 333.4 961.4 422.8S.D. 147.1 170.5 226.6 154.1 530.9 205.2N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 261Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 4 

# post partumGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g1(F) 13 707 181 680 145 985 22416 544 282 948 136 1173 23819 344 175 1129 146 529 16920 501 153 773 297 584 10422 673 403 1226 247 985 219ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 553.8 238.8 951.2 194.2 851.2 190.8S.D. 145.4 104.4 230.5 73.3 280.4 55.1N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 262Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 38 Relative to Start DateGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g2(M) 25 811 238 836 267 651 33526 688 540 797 537 866 58527 1352 265 537 221 1362 21828 1050 257 903 229 875 29429 1106 291 1450 276 1320 254ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 1001.4 318.2 904.6 306.0 1014.8 337.2S.D. 260.1 125.4 335.0 131.3 311.3 145.3N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 263Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 4 

# post partumGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g2(F) 37 1002 221 1081 310 954 23939 916 282 416 236 499 25342 1105 300 1010 171 531 23145 1013 290 590 346 855 27746 879 277 553 139 954 270ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 983.0 274.0 730.0 240.4 758.6 254.0S.D. 88.7 30.9 296.3 88.2 226.3 19.6N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 264Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 38 Relative to Start DateGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g3(M) 49 1523 359 1602 546 602 31450 610 335 554 249 475 31151 683 262 1312 376 954 28952 1143 504 753 429 1333 47553 552 358 697 318 1215 283ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 902.2 363.6 983.6 383.6 915.8 334.4S.D. 418.2 87.9 450.0 112.8 373.4 79.7N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 265Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 4 

# post partumGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g3(F) 66 1045 229 887 198 1011 13767 1067 152 941 240 566 16068 504 352 761 245 1227 24171 857 423 969 308 951 18872 907 216 1141 215 1030 235ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 876.0 274.4 939.8 241.2 957.0 192.2S.D. 226.2 110.2 137.9 41.9 241.9 45.6N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 266Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 38 Relative to Start DateGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g4(M) 73 1327 440 1775 392 1382 56874 635 260 637 340 1263 42475 775 273 1062 926 1291 47076 828 212 1641 289 607 28277 1204 418 961 728 1117 510ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 953.8 320.6 1215.2 535.0 1132.0 450.8S.D. 296.4 101.8 478.8 278.0 308.5 108.2N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 267Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 4 

# post partumGroup Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimbg g g g g g4(F) 86 991 269 1004 831 779 42790 605 412 771 321 932 44191 474 297 708 311 584 37892 794 196 848 138 779 27495 1001 191 897 271 914 188ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 773.0 273.0 845.6 374.4 797.6 341.6S.D. 233.2 90.2 114.3 265.5 139.6 108.0N 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 268Appendix 5 Individual and Group Mean Functional Test Values (Motor Activity)Day: 38 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile1(M) 1 520 0 13 02 325 0 0 03 442 2 18 04 499 1 1 05 372 0 8 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 431.6 0.6 8.0 0.0S.D. 82.7 0.9 7.7 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 269Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 4 

# post partumGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile1(F) 13 720 3 121 016 392 0 77 019 528 8 15 020 520 2 9 022 623 11 17 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 556.6 4.8 47.8 0.0S.D. 122.8 4.5 49.3 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 270Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 38 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile2(M) 25 284 0 0 026 433 4 4 027 265 0 9 028 125 0 21 029 160 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 253.4 0.8 6.8 0.0S.D. 121.0 1.8 8.8 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 271Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 4 

# post partumGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile2(F) 37 546 3 32 039 771 0 135 042 527 0 107 045 606 1 114 046 416 2 2 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 573.2 1.2 78.0 0.0S.D. 130.2 1.3 57.6 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 272Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 38 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile3(M) 49 301 0 5 050 550 3 50 051 512 1 6 052 336 0 4 053 471 0 3 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 434.0 0.8 13.6 0.0S.D. 109.8 1.3 20.4 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 273Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 4 

# post partumGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile3(F) 66 650 2 56 067 750 2 62 168 302 1 19 071 370 1 18 072 784 3 198 1ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 571.2 1.8 70.6 0.4S.D. 221.6 0.8 74.1 0.5N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 274Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 38 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile4(M) 73 43 0 0 074 343 0 1 075 328 3 0 076 537 2 3 077 390 0 4 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 328.2 1.0 1.6 0.0S.D. 179.6 1.4 1.8 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 275Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 4 

# post partumGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile4(F) 86 756 2 92 290 644 1 107 091 739 0 102 092 178 0 0 095 460 0 8 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 555.4 0.6 61.8 0.4S.D. 241.5 0.9 53.1 0.9N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒUnit = Time (seconds)Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 276Appendix 6 Individual Sensory Reactivity AssessmentsDay: 38 Relative to Start DateGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex1(M) 1 0 0 0 0 0 0 0 0 02 0 0 0 0 0 0 0 0 03 0 0 0 0 0 0 0 0 04 0 0 0 0 0 0 0 0 05 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 277Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 4 

# post partumGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex1(F) 13 0 0 0 0 0 0 0 0 016 0 0 0 0 0 0 0 0 019 0 0 0 0 0 0 0 0 020 0 0 0 0 0 0 0 0 022 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 278Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 38 Relative to Start DateGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex2(M) 25 0 0 0 0 0 0 0 0 026 0 0 0 0 0 0 0 0 027 0 0 0 0 0 0 0 0 028 0 1 0 0 0 0 0 0 029 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 279Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 4 

# post partumGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex2(F) 37 0 0 0 0 0 0 0 0 039 0 1 0 0 0 0 0 0 042 0 0 0 0 0 0 0 0 045 0 0 0 0 0 0 0 0 046 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 280Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 38 Relative to Start DateGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex3(M) 49 0 0 0 0 0 0 0 0 050 0 0 0 0 0 0 0 0 051 0 0 0 0 0 0 0 0 052 0 1 0 0 0 0 0 0 053 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 281Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 4 

# post partumGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex3(F) 66 0 0 0 0 0 0 0 0 067 0 0 0 0 0 0 0 0 068 0 0 0 0 0 0 0 0 071 0 0 0 0 0 0 0 0 072 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 282Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 38 Relative to Start DateGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex4(M) 73 0 0 0 0 0 0 0 0 074 0 0 0 0 0 0 0 0 075 0 0 0 0 0 0 0 0 076 0 0 0 0 0 0 0 0 077 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 283Appendix 6 (continued) IndividualSensory Reactivity AssessmentsDay: 4 

# post partumGroup Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle(Sex) Number response isation pinch pinch approach escape reflex reflex reflex4(F) 86 0 0 0 0 0 0 0 0 090 0 0 0 0 0 0 0 0 091 0 0 0 0 0 0 0 0 092 0 0 0 0 0 0 0 0 095 0 0 0 0 0 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒMean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 284Appendix 7 Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 431(M) 1 325 344 360 361 376 388 3872 330 345 362 373 392 412 4083 310 325 348 359 377 389 3864 310 322 344 355 365 375 3735 317 324 335 341 358 365 3576 309 322 340 334 343 357 3577 318 328 338 343 349 354 3508 307 314 318 325 336 345 3439 331 345 355 363 376 382 38510 320 339 347 344 349 358 36711 302 318 331 337 343 349 35212 318 328 338 338 348 358 361ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 316.4 329.5 343.0 347.8 359.3 369.3 368.8S.D. 9.2 11.0 12.5 14.2 17.6 20.0 19.3N 12 12 12 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 285Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 432(M) 25 303 306 321 330 337 344 33826 335 353 373 385 399 410 41227 327 332 352 358 372 384 37928 302 305 312 322 330 339 33229 338 352 367 379 384 397 40230 302 311 316 322 330 341 34931 336 359 383 393 409 418 43432 346 359 385 396 413 422 43833 325 337 355 365 380 398 40534 329 335 345 358 369 377 38135 311 323 335 339 350 360 36736 345 350 371 375 382 390 401ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 324.9 335.2 351.3 360.2 371.3 381.7 386.5S.D. 16.5 20.1 25.7 26.7 29.1 29.7 35.1N 12 12 12 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 286Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 433(M) 49 325 341 363 372 382 394 38750 339 349 358 364 372 382 38651 316 319 317 317 321 324 32852 307 307 317 337 355 361 35853 303 310 322 332 347 357 35654 322 331 339 354 368 378 39355 334 339 341 348 344 350 36756 325 333 337 351 349 355 36257 318 330 344 342 348 360 36858 311 326 354 353 369 385 38859 316 302 298 322 322 339 35060 305 307 307 318 323 330 333ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 318.4 324.5 333.1 342.5 350.0 359.6 364.7S.D. 11.2 15.3 20.8 17.8 20.5 22.1 21.3N 12 12 12 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 287Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 434(M) 73 318 327 341 352 355 364 35474 306 307 322 330 335 345 34075 334 343 349 361 364 369 37576 338 345 359 372 389 393 40177 312 302 290 309 317 328 33778 330 330 347 358 356 365 37679 321 328 343 352 360 361 37480 331 328 345 338 332 354 36381 295 284 279 293 290 290 31182 307 319 331 334 351 361 37583 324 326 321 332 329 327 35184 315 315 310 325 338 345 362ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 319.3 321.2 328.1 338.0 343.0 350.2 359.9S.D. 12.9 17.2 24.7 22.6 25.4 26.2 23.4N 12 12 12 12 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 288Appendix 7 (continued) Individual and Group Mean Body WeightsPre-PairingBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 151(F) 13 209 215 23014 196 198 20815 210 217 22516 200 200 21717 204 208 22118 203 209 21519 205 206 22020 202 219 23221 201 211 22922 203 225 23923 212 208 21624 212 219 230ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 204.8 211.3 223.5S.D. 5.0 8.0 8.8N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 289Appendix 7 (continued) Individual and Group Mean Body WeightsPre-PairingBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 152(F) 37 195 196 20338 194 189 19639 185 185 19840 211 215 21241 198 205 20242 194 202 21043 199 202 20544 195 192 20145 197 201 21246 192 188 18647 206 212 21748 205 220 222ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 197.6 200.6 205.3S.D. 7.0 11.2 9.9N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 290Appendix 7 (continued) Individual and Group Mean Body WeightsPre-PairingBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 153(F) 61 192 193 19962 199 180 17863 201 209 20864 207 206 21765 204 207 21266 193 193 19667 197 180 20168 206 205 21669 206 208 21270 204 196 21271 199 202 21172 188 195 199ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 199.7 197.8 205.1S.D. 6.2 10.2 11.1N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 291Appendix 7 (continued) Individual and Group Mean Body WeightsPre-PairingBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 154(F) 85 211 203 19786 203 211 21087 207 204 21588 196 188 18989 205 204 20590 197 191 19591 199 193 19292 192 198 20693 197 201 20694 192 190 19695 201 196 20496 203 207 208ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 200.3 198.8 201.9S.D. 5.8 7.3 7.9N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 292Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 41(F) 13 229 251 279 336 254 26014 208 234 265 338 239 25015 231 262 290 354 258 27916216253283359 23726117 223 249 283 347 253 26818 222 261 289 331 280 28619216242269320 23826120 235 251 291 365 276 29121 226 252 285 352 262 26322239267304375 28228923 217 247 283 360 263 26624 227 253 281 342 265 265Mean 224.1 251.8 283.5 348.3 258.9 269.9S.D.8.98.910.115.6 15.713.1N 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 293Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 42(F) 37 208 236 263 323 235 24238 197 231 262 329 240 25139 199 235 272 340 243 24440225241280350 24326641 202 220 238 267 240 23742 210 231 258 316 237 2454321522523423644 200 225 242 299 215 23845 210 231 257 321 227 23946180206237267 22922847 223 232 262 330 248 24848 210 248 254 246Mean 205.4 228.8 257.1 314.2 235.2 244.6S.D.13.19.914.228.3 10.210.4N 10 10 10 10 9 9Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 294Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 43(F) 61 199 217 241 272 218 22962 183 186 188 20463 212 220 227 268 219 22864213235269321 23525965 211 232 256 315 223 23766 195 217 236 276 222 23767193214231279 20822068 216 245 273 344 230 25269 218 239 275 304 262 26470207226248305 21522471 208 233 264 317 239 24972 196 217 244 303 220 230Mean 206.2 226.8 251.3 300.4 226.5 239.0S.D.8.910.517.124.0 14.814.8N 11 11 11 11 11 11Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 295Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 44(F) 85 196 205 215 21986 210 222 245 292 232 23287 208 232 246 2758819019319620189 214 232 230 254 215 23190 202 209 228 288 233 23591198215237294 21923192 203 228 258 324 235 25293 207 234 248 256 229 23194196221241285 23324195 212 214 223 282 213 22296 211 235 253 313 224 248Mean 205.9 223.3 240.3 287.6 227.0 237.3S.D.6.49.511.922.9 8.510.4N 9 9 9 9 7 7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 296Appendix 7 (continued) Individual and Group Mean Body WeightsRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 43 50 571(M) 97 327 341 361 371 385 392 396 406 40998 315 325 340 350 364 373 377 394 39799 321 336 350 359 370 381 384 393 396100 336 354 368 382 399 413 415 425 429101 311 319 331 336 344 349 349 355 358ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 322.0 335.0 350.0 359.6 372.4 381.6 384.2 394.6 397.8S.D. 9.9 13.7 15.0 17.9 20.9 23.6 24.4 25.6 25.9N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 297Appendix 7 (continued) Individual and Group Mean Body WeightsRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 43 50 574(M) 107 308 317 329 332 335 345 352 367 368108 323 323 336 350 359 366 376 392 393109 308 305 309 316 315 317 325 339 336110 312 305 312 317 326 331 339 349 347111 337 344 355 316 379 384 390 408 405ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 317.6 318.8 328.2 326.2 342.8 348.6 356.4 371.0 369.8S.D. 12.5 16.1 18.8 14.9 25.9 26.8 26.6 28.9 29.3N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 298Appendix 7 (continued) Individual and Group Mean Body WeightsRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 43 50 571(F) 102 196 196 199 211 215 211 207 217 218103 189 196 197 211 213 218 213 228 228104 196 205 213 216 215 221 232 235 231105 182 189 202 201 195 209 213 221 212106 184 185 192 191 195 190 196 203 203ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 189.4 194.2 200.6 206.0 206.6 209.8 212.2 220.8 218.4S.D. 6.5 7.7 7.8 10.0 10.6 12.1 13.1 12.1 11.5N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 299Appendix 7 (continued) Individual and Group Mean Body WeightsRecovery GroupsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 15 22 29 36 43 50 574(F) 112 197 192 203 209 210 210 219 227 221113 202 205 211 214 221 220 229 233 233114 193 195 196 210 211 216 212 223 222115 194 192 194 189 195 198 200 199 205116 205 195 196 204 206 209 217 227 223ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 198.2 195.8 200.0 205.2 208.6 210.6 215.4 221.8 220.8S.D. 5.2 5.4 7.0 9.7 9.4 8.4 10.6 13.2 10.1N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 300Appendix 8 Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36(Sex) Number To: 8 15 22 29 36 431(M) 1 19 16 1 15 12 ƒ12 15 17 11 19 20 ƒ43 15 23 11 18 12 ƒ34 12 22 11 10 10 ƒ25 7 11 6 17 7 ƒ86 13 18 ƒ6 9 14 07 10 10 5 6 5 ƒ48 7 4 7 11 9 ƒ29 14 10 8 13 6 310 19 8 ƒ3 5 9 911 16 13 6 6 6 312 10 10 0 10 10 3ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 13.1 13.5 4.8 11.6 10.0 ƒ0.5S.D. 4.1 5.8 5.6 4.8 4.2 4.5N 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 301Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36(Sex) Number To: 8 15 22 29 36 432(M) 25 3 15 9 7 7 ƒ626 18 20 12 14 11 227 5 20 6 14 12 ƒ528 3 7 10 8 9 ƒ729 14 15 12 5 13 530 9 5 6 8 11 831 23 24 10 16 9 1632 13 26 11 17 9 1633 12 18 10 15 18 734 6 10 13 11 8 435 12 12 4 11 10 736 5 21 4 7 8 11ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 10.3 16.1 8.9 11.1 10.4 4.8S.D. 6.3 6.6 3.1 4.1 3.0 7.8N 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 302Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36(Sex) Number To: 8 15 22 29 36 433(M) 49 16 22 9 10 12 ƒ750 10 9 6 8 10 451 3 ƒ2 0 4 3 452 0 10 20 18 6 ƒ353 7 12 10 15 10 ƒ154 9 8 15 14 10 1555 5 2 7 ƒ4 6 1756 8 4 14 ƒ2 6 757 12 14 ƒ2 6 12 858 15 28 ƒ1 16 16 359 ƒ14 ƒ4 24 0 17 1160 2 0 11 5 7 3ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 6.1 8.6 9.4 7.5 9.6 5.1S.D. 8.0 9.6 8.1 7.3 4.2 7.1N 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 303Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36(Sex) Number To: 8 15 22 29 36 434(M) 73 9 14 11 3 9 ƒ1074 1 15 8 5 10 ƒ575 9 6 12 3 5 676 7 14 13 17 4 877 ƒ10 ƒ12 19 8 11 978 0 17 11 ƒ2 9 1179 7 15 9 8 1 1380 ƒ3 17 ƒ7 ƒ6 22 981 ƒ11 ƒ5 14 ƒ3 0 2182 12 12 3 17 10 1483 2 ƒ5 11 ƒ3 ƒ2 2484 0 ƒ5 15 13 7 17ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 1.9 6.9 9.9 5.0 7.2 9.8S.D. 7.4 10.6 6.6 7.8 6.4 9.7N 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 304Appendix 8 (continued) Individual and Group Mean Body Weight GainsPre-PairingIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 151(F) 13 6 1514 2 1015 7 816 0 1717 4 1318 6 619 1 1420 17 1321 10 1822 22 1423 ƒ4 824 7 11ƒƒƒƒƒ ƒƒƒƒƒMean 6.5 12.3S.D. 7.2 3.7N 12 12ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 305Appendix 8 (continued) Individual and Group Mean Body Weight GainsPre-PairingIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 152(F) 37 1 738 ƒ5 739 0 1340 4 ƒ341 7 ƒ342 8 843 3 344 ƒ3 945 4 1146 ƒ4 ƒ247 6 548 15 2ƒƒƒƒƒ ƒƒƒƒƒMean 3.0 4.8S.D. 5.7 5.4N 12 12ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 306Appendix 8 (continued) Individual and Group Mean Body Weight GainsPre-PairingIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 153(F) 61 1 662 ƒ19 ƒ263 8 ƒ164 ƒ1 1165 3 566 0 367 ƒ17 2168 ƒ1 1169 2 470 ƒ8 1671 3 972 7 4ƒƒƒƒƒ ƒƒƒƒƒMean ƒ1.8 7.3S.D. 8.6 6.7N 12 12ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 307Appendix 8 (continued) Individual and Group Mean Body Weight GainsPre-PairingIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 154(F) 85 ƒ8 ƒ686 8 ƒ187 ƒ3 1188 ƒ8 189 ƒ1 190 ƒ6 491 ƒ6 ƒ192 6 893 4 594 ƒ2 695 ƒ5 896 4 1ƒƒƒƒƒ ƒƒƒƒƒMean ƒ1.4 3.1S.D. 5.6 4.8N 12 12ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 308Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter MatingLactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 201(F)1322 28 57 6 50 1071426 31 73 11 57 1301531 28 64 21 59 1231637 30 76 24 67 1431726 34 64 15 60 1241839 28 42 6 67 1091926 27 51 23 53 1042016 40 74 15 56 1302126 33 67 1 59 1262228 37 71 7 65 1362330 36 77 3 66 1432426 28 61 0 54 115Mean27.8 31.7 64.8 11.0 59 124S.D.6.1 4.3 10.7 8.5 6 13N12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 309Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter MatingLactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 202(F)3728 27 60 7 55 1153834 31 67 11 65 1323936 37 68 1 73 1414016 39 70 23 55 12541 TLL18 18 29 -3 36 654221 27 58 8 48 10643 NP10 9 2 19 214425 17 57 23 42 994521 26 64 12 47 1114626 31 30 -1 57 87479 30 68 0 39 10748 NP38 6 -8 44 36Mean23.4 28.3 57.1 9.3 52 109S.D.8.2 7.1 15.2 9.0 12 22N10 10 10 9 10 10Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 310Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter MatingLactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 203(F)6118 24 31 11 42 7362 NP3 2 16 5 21638 7 41 9 15 566422 34 52 24 56 1086521 24 59 14 45 1046622 19 40 15 41 816721 17 48 12 38 866829 28 71 22 57 1286921 36 29 2 57 867019 22 57 9 41 987125 31 53 10 56 1097221 27 59 10 48 107Mean20.6 24.5 49.1 12.5 45 94S.D.5.1 8.3 12.8 6.2 12 20N11 11 11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 311Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter MatingLactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 204(F) 85 NP9 10 4 19 238612 23 47 0 35 8287 NL24 14 29 38 6788 NP3 3 5 6 1189 TLL18 -2 24 16 16 40907 19 60 2 26 869117 22 57 12 39 969225 30 66 17 55 12193 TLL27 14 8 2 41 499425 20 44 8 45 89952 9 59 9 11 709624 18 60 24 42 102Mean17.4 17.0 47.2 10.3 34 82S.D.8.8 9.2 19.4 8.3 14 25N9 9 9 7 9 9Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 312Appendix 8 (continued) Individual and Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36 43 50(Sex) Number To: 8 15 22 29 36 43 50 571(M) 97 14 20 10 14 7 4 10 398 10 15 10 14 9 4 17 399 15 14 9 11 11 3 9 3100 18 14 14 17 14 2 10 4101 8 12 5 8 5 0 6 3ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 13.0 15.0 9.6 12.8 9.2 2.6 10.4 3.2S.D. 4.0 3.0 3.2 3.4 3.5 1.7 4.0 0.4N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 313Appendix 8 (continued) Individual and Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36 43 50(Sex) Number To: 8 15 22 29 36 43 50 574(M) 107 9 12 3 3 10 7 15 1108 0 13 14 9 7 10 16 1109 ƒ3 4 7 ƒ1 2 8 14 ƒ3110 ƒ7 7 5 9 5 8 10 ƒ2111 7 11 ƒ39 63 5 6 18 ƒ3ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 1.2 9.4 ƒ2.0 16.6 5.8 7.8 14.6 ƒ1.2S.D. 6.7 3.8 21.1 26.3 2.9 1.5 3.0 2.0N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 314Appendix 8 (continued) Individual and Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36 43 50(Sex) Number To: 8 15 22 29 36 43 50 571(F) 102 0 3 12 4 ƒ4 ƒ4 10 1103 7 1 14 2 5 ƒ5 15 0104 9 8 3 ƒ1 6 11 3 ƒ4105 7 13 ƒ1 ƒ6 14 4 8 ƒ9106 1 7 ƒ1 4 ƒ5 6 7 0ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 4.8 6.4 5.4 0.6 3.2 2.4 8.6 ƒ2.4S.D. 4.0 4.7 7.2 4.2 7.9 6.8 4.4 4.2N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 315Appendix 8 (continued) Individual and Group Mean Body Weight GainsRecovery GroupsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8 15 22 29 36 43 50(Sex) Number To: 8 15 22 29 36 43 50 574(F) 112 ƒ5 11 6 1 0 9 8 ƒ6113 3 6 3 7 ƒ1 9 4 0114 2 1 14 1 5 ƒ4 11 ƒ1115 ƒ2 2 ƒ5 6 3 2 ƒ1 6116 ƒ10 1 8 2 3 8 10 ƒ4ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean ƒ2.4 4.2 5.2 3.4 2.0 4.8 6.4 ƒ1.0S.D. 5.3 4.3 7.0 2.9 2.4 5.7 4.9 4.6N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 316Appendix 9 Individual and Group Mean Food Consumption Values for Females Following Mating and During LactationMean Food Consumption (g/rat/day)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142041(F)13202225321418 20 25291520 23 252916192428331718 22 252118* * 29221917 20 23292020 25 292821202326252221 25 29302320 24 27172417202626Mean19.1 22.6 26.3 26.8S.D.1.4 1.8 2.0 4.8N11 11 12 12* = data unavailableDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 317Appendix 9 (continued) Individual and Group Mean Food Consumption Values for Females Following Mating and DuringLactationMean Food Consumption (g/rat/day)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142042(F)3718 22 262238192328283920 23 26204018 23 263541TLL141622154215 18 212343 NP16 19 194417 16 19264517 21 25194615 18 20184715 18 212148 NP19 20 18Mean16.8 19.9 23.1 23.6S.D.1.9 2.7 3.0 5.4N10 10 10 9Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 318Appendix 9 (continued) Individual and Group Mean Food Consumption Values for Females Following Mating and DuringLactationMean Food Consumption (g/rat/day)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142043(F)6113 17 21*62 NP810136315 13 23326414 17 19316517182388■6614 16 19236713 15 19206817 23 25256915 21 27207017 19 26207116 20 19267216 22 2223Mean15.3 18.3 22.0 24.4S.D.1.6 3.0 2.9 4.7N11 11 11 9* = data unavailable■= food scattered in cage, value excluded from mean and S.D.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 319Appendix 9 (continued) Individual and Group Mean Food Consumption Values for Females Following Mating and DuringLactationMean Food Consumption (g/rat/day)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142044(F)85 NP11 13 13861315241187 NL16 17 2388 NP10 11 1389TLL161819499013 17 25269115 17 20339215 18 222593 TLL17 21 19179413 17 24299510 10 15159618 20 2697■Mean14.5 17.0 21.4 22.9S.D.2.5 3.2 3.4 8.5N9 9 96■= food scattered in cage, value excluded from mean and S.D.Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 320Appendix 10 Individual and Group Mean Water ConsumptionValues for Females Following Mating and LactationWaterConsumption (g)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142041(F)13263137371428 29 36421530 34 434916293241461726 30 38331849 58 60431931 31 41432046 53 644921303140392231 35 40432328 35 39292426283639Mean31.8 35.6 42.8 41.0S.D.8.2 10.3 10.2 10.1N12 12 12 12Water consumption = g/animal/dayDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 321Appendix 10 (continued) Individual and Group Mean Water Consumption Values for Females Following Mating andLactationWaterConsumption (g)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142042(F)3743 64 494038283235393935 43 47414027 31 344841 TLL262634254223 25 303743 NP32 30 344426 28 31414525 31 37284624 25 29254737 57 583748 NP42 35 35Mean29.4 35.7 38.1 37.1S.D.9.2 14.6 10.9 11.5N10 10 10 9Water consumption = g/animal/dayDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 322Appendix 10 (continued) Individual and Group Mean Water Consumption Values for Females Following Mating andLactationWaterConsumption (g)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142043(F)6128 38 452862 NP2327246339 41 40316430 29 304165313536366621 26 29306732 31 39526824 32 36446926 30 38337035 38 39317167 58 68507238 37 4544Mean32.9 36.5 38.5 38.0S.D.13.7 16.5 13.4 15.0N11 11 11 11Water consumption = g/animal/dayDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 323Appendix 10 (continued) Individual and Group Mean Water Consumption Values for Females Following Mating andLactationWaterConsumption (g)After MatingLactationGroup(Sex)AnimalNumberFrom:07141To:7142044(F)85 NP37 45 36862626473087 NL33 30 3788 NP28 26 3289 TLL485760379030 30 40399125 31 36419225 31 343693 TLL50 43 37329443 41 43459527 23 37289632 36 4152Mean34.1 35.4 41.6 38.8S.D.12.5 12.3 11.3 12.2N9 9 97Water consumption = g/animal/dayDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 324Appendix 11 Individual Mating Performance, Fertility and Gestation LengthsGroup: 1 Dose Level: 0 (Control)Paired Animal NumberPre-Coital Interval(Days)Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)13 F 1 M23 PT 2+ P2314 F 2 M35 PT H 3+ P231⁄215 F 3 M48 PT H 3+ P221⁄216 F 4 M15 PT H 1+ P2317 F 5 M13 PT H 1+ P2218 F 6 M43 PT PV 3+ P231⁄219 F 7 M15 PT 2+ P2320 F 8 M3PV 3+ P2121 F 9 M14 PT 2+ P221⁄222 F 10 M33 PT 3+ P221⁄223 F 11 M34 PT 3+ P221⁄224 F 12 M34 PT H 3+ P221⁄2Harlan Study Number:41204605Report Page 325Appendix 11 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 2 Dose Level: 30 mg/kg bw/dayPaired Animal NumberPre-Coital Interval(Days)Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)37 F 25 M34 PT H 2+ P221⁄238 F 26 M32 PT H 2+ P221⁄239 F 27 M25 PT H 2+ P2240 F 28 M46 PT 3+ P2241 F 29 M22 PT H 3+ P241⁄242 F 30 M23 PT 1+ P221⁄243 F 31 M55 PT H 3+ NP.44 F 32 M15 PT 2+ P2245 F 33 M27 PT H 3+ P221⁄246 F 34 M14 PT H 1+ P2347 F 35 M33 PT H 3+ P221⁄248 F 36 M12 PT H 2+ NP.Harlan Study Number:41204605Report Page 326Appendix 11 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 3 Dose Level: 60 mg/kg bw/dayPaired Animal NumberPre-Coital Interval(Days)Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)61 F 49 M22 PT 2+ P231⁄262 F 50 M34 PT H 3+ NP.63 F 51 M24 PT 2+ P2464 F 52 M15 PT H 3+ P2265 F 53 M34 PT 3+ P221⁄266 F 54 M24 PT 3+ P2267 F 55 M14 PT 3+ P2368 F 56 M14 PT 3+ P2369 F 57 M43 PT H 2+ P231⁄270 F 58 M13 PT 2+ P221⁄271 F 59 M23 PT H 3+ P2272 F 60 M25 PT 3+ P221⁄2Harlan Study Number:41204605Report Page 327Appendix 11 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 4 Dose Level: 120 mg/kg bw/dayPaired Animal NumberPre-Coital Interval(Days)Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)85 F 73 M34 PT H 3+ NP.86 F 74 M33 PT 3+ P2387 F 75 M14 PT H 3+ NL.88 F 76 M32 PT H 2+ NP.89 F 77 M55 PT 3+ P231⁄290 F 78 M34 PT H 3+ P2391 F 79 M34 PT 3+ P2392 F 80 M21 PT 3+ P221⁄293 F 81 M56 PT 3+ P2194 F 82 M46 PT H 3+ P231⁄295 F 83 M23 PT H 3+ P231⁄296 F 84 M43 PT H 3+ P231⁄2Harlan Study Number:41204605Report Page 328Appendix 12 Individual and Group Mean Litter Size and Litter WeightsGroup: 1 Dose Level: 0(Control)Animal/LitterNumberNumberofCorporaLuteaNumber ofImplantationSitesTotalNumber ofOffspringBornNumber of LiveOffspringLitter Weight(g)Mean Offspring Weight(g)Mean OffspringBody Weight Change(g)Day 1 Day 4 Day 1 Day 4Day 1 Day 4 Days 1-4Males Females Males Females Males Females1312 12 11 11 10 75.2 99.2 7.2 6.7 10.1 9.8 2.9 3.11415 14 11 11 11 63.7 98.6 6.0 5.6 9.2 8.7 3.2 3.11514 13 12 12 12 69.5 103.9 5.9 5.7 8.7 8.7 2.7 2.91614 14 14 14 14 88.3 120.1 6.6 6.1 8.8 8.4 2.3 2.31714 14 13 12 12 65.3 86.5 5.9 5.2 7.7 7.0 1.8 1.81810 5 5 5 5 39.4 60.6 7.8 8.1 11.9 12.9 4.1 4.81912 11 10 10 10 68.3 104.3 6.9 6.8 10.6 10.2 3.7 3.52012 12 11 11 11 68.1 93.5 6.6 6.1 9.0 8.4 2.4 2.32116 14 14 14 14 75.9 103.4 5.6 5.2 7.6 7.1 2.0 1.92215 14 14 14 14 82.8 121.3 6.0 5.8 8.8 8.5 2.8 2.72314 13 13 12 12 71.3 88.2 6.2 5.8 7.5 7.3 1.3 1.52412 11 11 11 11 64.6 89.6 6.0 5.8 7.9 8.3 1.9 2.5Mean13.3 12.3 11.6 11.4 11.3 69.37 97.43 6.40 6.07 8.99 8.77 2.59 2.70S.D.1.7 2.6 2.5 2.4 2.5 12.03 16.10 0.64 0.81 1.33 1.63 0.82 0.90N12 12 12 12 12 12 12 12 12 12 12 12 12Harlan Study Number:41204605Report Page 329Appendix 12 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 2 Dose Level: 30 mg/kg bw/dayAnimal/LitterNumberNumberofCorporaLuteaNumber ofImplantationSitesTotalNumber ofOffspringBornNumber of LiveOffspringLitter Weight(g)Mean Offspring Weight(g)Mean OffspringBody Weight Change(g)Day 1 Day 4 Day 1 Day 4Day 1 Day 4 Days 1-4Males Females Males Females Males Females3713 13 12 12 12 69.6 96.5 5.9 5.8 8.3 7.9 2.4 2.23816 14 12 12 12 71.9 105.7 6.0 6.0 8.8 8.9 2.8 2.93913 13 13 13 13 77.6 110.4 6.2 5.8 8.7 8.3 2.5 2.54017 16 16 16 16 87.9 127.3 5.5 5.5 8.2 7.8 2.6 2.441 TLL11 10 2 2 11.2 5.64213 12 11 11 11 64.6 96.1 5.8 5.9 8.6 8.8 2.8 2.943 NP4413 12 12 12 12 62.1 90.4 5.2 5.2 7.5 7.5 2.3 2.44512 12 11 11 11 63.7 87.1 6.2 5.6 8.4 7.8 2.1 2.14610 6 5 5 5 35.6 53.1 7.5 6.9 11.2 10.3 3.7 3.44714 14 13 13 13 79.3 101.7 6.2 6.1 7.7 8.0 1.5 1.948 NPMean13.2 12.2 11.7 11.7 11.7 68.03 96.48 6.06 5.85 8.57 8.37 2.51 2.52S.D.2.1 2.7 2.9 2.9 2.9 14.78 20.20 0.63 0.47 1.06 0.85 0.58 0.47N10 10 9 9 9 9 9 9 9 9 9 9 9Harlan Study Number:41204605Report Page 330Appendix 12 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 3 Dose Level: 60 mg/kg bw/dayAnimal/LitterNumberNumberofCorporaLuteaNumber ofImplantationSitesTotalNumber ofOffspringBornNumber of LiveOffspringLitter Weight(g)Mean Offspring Weight(g)Mean OffspringBody Weight Change(g)Day 1 Day 4 Day 1 Day 4Day 1 Day 4 Days 1-4Males Females Males Females Males Females619 9 5 5 5 35.7 53.3 7.3 7.0 10.9 10.3 3.7 3.362 NP637 4 4 4 4 27.8 45.6 7.3 6.7 11.6 11.3 4.3 4.66412 12 12 12 12 69.5 94.5 5.8 5.7 7.9 7.8 2.1 2.16513 13 12 12 12 69.6 96.7 6.1 5.6 8.4 7.7 2.4 2.26610 10 7 7 7 45.4 69.7 6.8 6.4 10.1 9.9 3.3 3.66710 10 9 9 9 58.1 81.8 6.5 6.3 9.1 9.1 2.6 2.86818 16 14 14 14 91.8 119.4 6.8 6.3 8.8 8.3 1.9 2.06912 12 4 4 4 30.9 47.3 7.8 7.5 11.9 11.7 4.1 4.27011 11 11 11 11 58.7 82.7 5.6 5.0 7.9 7.1 2.3 2.17112 11 11 11 11 66.7 96.6 6.7 5.9 9.7 8.6 3.0 2.77212 11 11 11 11 67.4 97.5 6.3 6.0 9.0 8.7 2.8 2.7Mean11.5 10.8 9.1 9.1 9.1 56.51 80.46 6.63 6.21 9.56 9.13 2.94 2.92S.D.2.8 2.9 3.5 3.5 3.5 19.63 23.88 0.66 0.69 1.39 1.49 0.80 0.90N11 11 11 11 11 11 11 11 11 11 11 11 11Harlan Study Number:41204605Report Page 331Appendix 12 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 4 Dose Level: 120 mg/kg bw/dayAnimal/LitterNumberNumberofCorporaLuteaNumber ofImplantationSitesTotalNumber ofOffspringBornNumber of LiveOffspringLitter Weight(g)Mean Offspring Weight(g)Mean OffspringBody Weight Change(g)Day 1 Day 4 Day 1 Day 4Day 1 Day 4 Days 1-4Males Females Males Females Males Females85 NP8611 10 8 5 5 27.7 40.5 5.4 6.1 7.9 9.0 2.5 2.987 NL12 1088 NP89 TLL6 4 2 2 11.4 5.8 5.69010 8 8 8 8 54.0 78.4 6.9 6.3 9.9 9.6 3.0 3.39113 13 11 11 11 71.0 103.7 6.8 6.1 9.9 9.1 3.0 2.99212 12 10 10 10 63.0 87.3 6.6 6.2 9.0 8.7 2.4 2.493 TLL4 4 1 1 5.2 5.29413 12 8 8 8 51.3 74.9 6.9 6.3 9.7 9.3 2.8 3.09514 11 8 8 8 44.4 61.0 5.6 5.5 7.7 7.6 2.1 2.19613 13 11 11 11 78.9 113.5 7.3 6.9 10.5 10.1 3.1 3.2Mean11.3 10.3 8.1 8.7 8.7 55.76 79.90 6.50 6.19 9.19 9.02 2.70 2.83S.D.3.0 2.9 3.2 2.1 2.1 17.12 24.79 0.73 0.42 1.08 0.78 0.39 0.41N9 9 7 7 7 7 7 7 7 7 7 7 7Harlan Study Number:41204605Report Page 332Appendix 13 Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex(%)ViabilityIndex (%)1(F)130 8 100 91147 21 100 100157 8 100 100160 0 100 100170 7 92 1001850 0 100 100198 9 100 100200 8 100 1002113 0 100 100227 0 100 100237 0 92 100248 0 100 100Mean8.9 5.2 98.7 99.2S.D.13.6 6.5 3.0 2.6N12 12 12 12Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 333Appendix 13 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex(%)ViabilityIndex (%)2(F) 37 0 8 100 10038 13 14 100 10039 0 0 100 10040 6 0 100 10041 TLL 9 80 100 042 8 8 100 10043 NP44 8 0 100 10045 0 8 100 10046 40 17 100 10047 0 7 100 10048 NPMean8.3 14.2 100.0 100.0S.D.12.0 23.8 0.0 0.0N10 10 10 9Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 334Appendix 13 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex(%)ViabilityIndex (%)3(F)610 44 100 10062 NP6343 0 100 100640 0 100 100650 8 100 100660 30 100 100670 10 100 1006811 13 100 100690 67 100 100700 0 100 100718 0 100 100728 0 100 100Mean6.4 15.6 100.0 100.0S.D.12.8 22.3 0.0 0.0N11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 335Appendix 13 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex(%)ViabilityIndex (%)4(F)85 NP869 20 63 10087 NL17 10088 NP89 TLL33 50 100 09020 0 100 100910 15 100 100920 17 100 10093 TLL0 75 100 0948 33 100 1009521 27 100 100960 15 100 100Mean10.2 28.1 95.8 100.0S.D.12.1 22.4 12.5 0.0N9 9 9 7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 336Appendix 14 Individual and Group MeanSex Ratio Values for OffspringGroup: 1 Dose Level: 0 (Control)Litter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male13 3 8 27 3 8 27 3 7 3014 5 6 45 5 6 45 5 6 4515 4 8 334833483316 6 8 43 6 8 43 6 8 4317 5 8 38 4 8 33 4 8 3318 4 1 804180418019 6 4 60 6 4 60 6 4 6020 2 9 18 2 9 18 2 9 1821 8 6 57 8 6 57 8 6 5722 8 6 57 8 6 57 8 6 5723 4 9 31 3 9 25 3 9 2524 4 7 36 4 7 36 4 7 36Mean 43.943.043.2S.D. 17.1 17.8 17.6N 12 12 12Harlan Study Number:41204605Report Page 337Appendix 14 (continued) Individual and Group Mean Sex Ratio Values for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male37 4 8 33 4 8 33 4 8 3338 7 5 58 7 5 58 7 5 5839 6 7 466746674640 6 10 38 6 10 38 6 10 3841 TLL 2 0 100 2 0 10042 4 7 364736473643 NP44 3 9 25 3 9 25 3 9 2545 3 8 273827382746 2 3 40 2 3 40 2 3 4047 6 7 46 6 7 46 6 7 4648 NPMean 38.938.938.9S.D. 10.3 10.3 10.3N 9 9 9Harlan Study Number:41204605Report Page 338Appendix 14 (continued) Individual and Group Mean Sex Ratio Values for OffspringGroup: 3 Dose Level: 60 mg/kg bw/dayLitter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male61 3 2 60 3 2 60 3 2 6062 NP63 2 2 502250225064 7 5 58 7 5 58 7 5 5865 6 6 50 6 6 50 6 6 5066 2 5 292529252967 6 3 67 6 3 67 6 3 6768 7 7 50 7 7 50 7 7 5069 3 1 753175317570 6 5 55 6 5 55 6 5 5571 2 9 18 2 9 18 2 9 1872 5 6 45 5 6 45 5 6 45Mean 50.650.650.6S.D. 16.1 16.1 16.1N 50.6 11 11Harlan Study Number:41204605Report Page 339Appendix 14 (continued) Individual and Group Mean Sex Ratio Values for OffspringGroup: 4 Dose Level: 120 mg/kg bw/dayLitter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male85 NP86 4 1 80 4 1 80 4 1 8087 NL88 NP89 TLL 1 1 50 1 1 5090 6 2 75 6 2 75 6 2 7591 5 6 45 5 6 45 5 6 4592 2 8 20 2 8 20 2 8 2093 TLL 0 1 001094 2 6 25 2 6 25 2 6 2595 6 2 75 6 2 75 6 2 7596 7 4 64 7 4 64 7 4 64Mean 54.954.954.9S.D. 24.9 24.9 24.9N 7 7 7Harlan Study Number:41204605Report Page 340Appendix 15 Individual Clinical Signs for OffspringGroup: 1 Dose Level: 0 (Control)Litter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum13 F5 Missing 314 No Abnormalities Detected15 No Abnormalities Detected16 No Abnormalities Detected17 1M Found dead Pre Day 1F12 Scab on dorsal region 4-518 No Abnormalities Detected19 No Abnormalities Detected20 No Abnormalities Detected21 No Abnormalities Detected22 F13 Swollen left hind limb 4-523 1M Found dead Pre Day 1F9 Bruised head 1-224 F4 No milk in stomach, Pale 3-4Missing 5Harlan Study Number:41204605Report Page 341Appendix 15 (continued) Individual Clinical Signs for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum37 No Abnormalities Detected38 No Abnormalities Detected39 No Abnormalities Detected40 No Abnormalities Detected41 TLL M1 M2 No milk in stomach, Weak Pre Day 1 - 1Missing 242 No Abnormalities Detected43 NP .44 No Abnormalities Detected45 No Abnormalities Detected46 No Abnormalities Detected47 No Abnormalities Detected48 NP .Harlan Study Number:41204605Report Page 342Appendix 15 (continued) Individual Clinical Signs for OffspringGroup: 3 Dose Level: 60 mg/kg bw/dayLitter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum61No Abnormalities Detected62 NP.63No Abnormalities Detected64No Abnormalities Detected65No Abnormalities Detected66No Abnormalities Detected67No Abnormalities Detected68No Abnormalities Detected69No Abnormalities Detected70No Abnormalities Detected71F5 Open wound on right hind limb 1-572No Abnormalities DetectedHarlan Study Number:41204605Report Page 343Appendix 15 (continued) Individual Clinical Signs for OffspringGroup: 4 Dose Level: 120 mg/kg bw/dayLitter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum85 NP.861F Cold, Weak, No milk in stomach Pre Day 11M, 1F Found dead Pre Day 11U Missing 1M4 Small 1-5M1 Found dead 587 NL.88 NP.89 TLLM1, F2 (Whole litter) Small, Cold, No milk in stomach 2Missing 390No Abnormalities Detected91No Abnormalities Detected92No Abnormalities Detected93 TLLF1 No milk in stomach Pre Day 1 - 1Cold, Pale, Weak 1Missing 294No Abnormalities Detected95M4 Small 1-596No Abnormalities DetectedHarlan Study Number:41204605Report Page 344Appendix 16 Individual and Group Mean Reflexological Responses for OffspringGroup: 1 Dose Level: 0 (Control)LitterNumberSurface righting(Day 1 

# Post Partum)Number of offspring% passedexamined passed1311 11 100.01411 11 100.01512 11 91.71614 14 100.01712 9 75.0185 5 100.01910 10 100.02011 11 100.02114 12 85.72214 14 100.02312 12 100.02411 11 100.0Mean96.0S.D.8.0N12Harlan Study Number:41204605Report Page 345Appendix 16 (continued) Individual and Group Mean Reflexological Responses for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Partu m)Number of offspring% passedexamined passed37 12 12 100.038 12 12 100.039 13 13 100.040 16 13 81.341 TLL 2 0 0.042 11 11 100.043 NP44 12 9 75.045 11 11 100.046 5 5 100.047 13 13 100.048 NPMean95.1S.D.9.8N9Harlan Study Number:41204605Report Page 346Appendix 16 (continued) Individual and Group Mean Reflexological Responses for OffspringGroup: 3 Dose Level: 60 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Partu m)Number of offspring% passedexamined passed615 5 100.062 NP634 4 100.06412 10 83.36512 12 100.0667 6 85.7679 7 77.86814 14 100.0694 2 50.07011 7 63.67111 6 54.57211 9 81.8Mean81.5S.D.18.6N11Harlan Study Number:41204605Report Page 347Appendix 16 (continued) Individual and Group Mean Reflexological Responses for OffspringGroup: 4 Dose Level: 120 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Partu m)Number of offspring% passedexamined passed85 NP865 3 60.087 NL88 NP89 TLL2 2 100.0908 8 100.09111 11 100.09210 6 60.093 TLL1 0 0.0948 7 87.5958 7 87.59611 10 90.9Mean83.7S.D.17.0N7Harlan Study Number:41204605Report Page 348Appendix 17 Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l1(M) 1 42 17.1 8.89 51.6 19.2 58.1 33.1 6.7 16 1.07 84 5.63 0 0.00 0 0.00 0 0.00643ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2 42 15.9 8.88 49.7 17.9 55.9 32.0 6.5 19 1.24 80 5.20 0 0.00 1 0.07 0 0.00537ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3 42 16.8 9.66 51.9 17.4 53.8 32.3 5.9 10 0.59 90 5.31 0 0.00 0 0.00 0 0.00584ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4 42 15.9 9.21 50.4 17.3 54.7 31.6 6.6 20 1.32 80 5.28 0 0.00 0 0.00 0 0.00664ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ5 42 15.5 9.06 48.0 17.1 53.0 32.2 6.8 7 0.48 92 6.26 0 0.00 1 0.07 0 0.00590Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 349Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l2(M) 25 42 17.2 9.82 53.8 17.5 54.8 31.9 7.0 18 1.26 82 5.74 0 0.00 0 0.00 0 0.00622ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ26 42 16.3 9.38 49.8 17.4 53.1 32.7 8.9 15 1.34 85 7.57 0 0.00 0 0.00 0 0.00535ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ27 42 16.4 9.05 50.1 18.1 55.3 32.6 7.8 26 2.03 72 5.62 0 0.00 2 0.16 0 0.00626ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ28 42 16.6 9.73 51.2 17.1 52.6 32.4 5.7 24 1.37 75 4.28 0 0.00 1 0.06 0 0.00569ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ29 42 16.6 9.14 50.5 18.2 55.2 33.0 6.6 16 1.06 83 5.48 0 0.00 1 0.07 0 0.00536Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 350Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l3(M) 49 42 17.0 8.92 51.1 19.0 57.2 33.3 7.3 12 0.88 88 6.42 0 0.00 0 0.00 0 0.00453ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ50 42 16.3 9.15 49.6 17.8 54.2 32.9 6.6 14 0.92 86 5.68 0 0.00 0 0.00 0 0.00665ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ51 42 15.4 8.98 47.8 17.2 53.2 32.2 8.1 16 1.30 83 6.72 0 0.00 1 0.08 0 0.00733ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ52 42 15.3 9.04 47.9 16.9 53.0 31.9 7.8 22 1.72 76 5.93 0 0.00 2 0.16 0 0.00629ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ53 42 16.6 9.61 52.5 17.3 54.6 31.7 7.5 11 0.83 87 6.53 0 0.00 2 0.15 0 0.00568Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 351Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l4(M) 73 42 17.4 9.65 51.1 18.1 52.9 34.2 6.3 7 0.44 92 5.80 0 0.00 1 0.06 0 0.00532ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ74 42 15.9 9.03 48.7 17.6 53.9 32.7 6.6 5 0.33 95 6.27 0 0.00 0 0.00 0 0.00712ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ75 42 16.4 9.08 51.2 18.1 56.4 32.1 6.5 13 0.85 85 5.53 0 0.00 2 0.13 0 0.00401ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ76 42 15.2 8.25 46.0 18.4 55.7 32.9 6.6 25 1.65 75 4.95 0 0.00 0 0.00 0 0.00708ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ77 42 15.3 8.13 47.1 18.8 58.0 32.4 5.3 20 1.06 79 4.19 0 0.00 1 0.05 0 0.00660Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 352Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l1(F) 13 43 14.4 7.64 44.2 18.9 57.9 32.6 4.7 26 1.22 73 3.43 0 0.00 1 0.05 0 0.00819ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ16 42 13.0 6.46 39.9 20.1 61.8 32.6 6.2 29 1.80 71 4.40 0 0.00 0 0.00 0 0.00950ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ19 42 13.5 6.99 41.1 19.3 58.9 32.8 6.5 36 2.34 63 4.10 1 0.07 0 0.00 0 0.00814ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ20 42 14.0 7.94 43.6 17.7 54.9 32.2 4.3 23 0.99 77 3.31 0 0.00 0 0.00 0 0.00817ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ22 43 13.8 7.46 43.1 18.5 57.8 32.1 5.3 48 2.54 52 2.76 0 0.00 0 0.00 0 0.00975Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 353Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l2(F) 37 43 14.0 7.53 43.2 18.6 57.5 32.3 6.2 30 1.86 70 4.34 0 0.00 0 0.00 0 0.00 1050ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ39 42 12.5 6.93 39.3 18.1 56.7 31.9 4.1 40 1.64 60 2.46 0 0.00 0 0.00 0 0.00 1261ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ42 42 12.5 6.51 38.5 19.2 59.2 32.3 4.0 35 1.40 65 2.60 0 0.00 0 0.00 0 0.00952ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ45 42 13.1 7.45 41.4 17.6 55.6 31.7 4.0 43 1.72 57 2.28 0 0.00 0 0.00 0 0.00 1037ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ46 42 15.3 8.55 48.2 17.8 56.3 31.7 5.5 12 0.66 88 4.84 0 0.00 0 0.00 0 0.00865Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 354Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l3(F) 66 42 13.0 6.58 40.4 19.7 61.4 32.2 5.6 60 3.36 40 2.24 0 0.00 0 0.00 0 0.00930ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ67 42 13.0 7.27 40.6 17.9 55.8 32.0 3.7 39 1.44 61 2.26 0 0.00 0 0.00 0 0.00 1021ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ68 42 12.1 6.71 37.5 18.0 55.8 32.2 5.5 24 1.32 76 4.18 0 0.00 0 0.00 0 0.00936ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ71 42 13.3 7.29 43.1 18.2 59.1 30.8 4.4 39 1.72 61 2.68 0 0.00 0 0.00 0 0.00855ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ72 42 13.8 7.66 43.3 18.0 56.6 31.8 7.3 39 2.85 61 4.45 0 0.00 0 0.00 0 0.00992Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 355Appendix 17 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l4(F) 86 44 14.3 7.26 45.5 19.7 62.7 31.4 2.9 20 0.58 78 2.26 0 0.00 2 0.06 0 0.00915ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ90 44 13.2 7.18 42.8 18.4 59.6 30.9 5.8 33 1.91 67 3.89 0 0.00 0 0.00 0 0.00 1129ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ91 44 13.5 7.23 42.1 18.6 58.2 32.0 5.3 22 1.17 78 4.13 0 0.00 0 0.00 0 0.00 1050ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ92 42 13.5 6.83 41.1 19.7 60.2 32.8 6.6 38 2.51 61 4.03 0 0.00 1 0.07 0 0.00 1081ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ95 43 13.2 6.98 40.9 18.9 58.6 32.3 4.0 45 1.80 55 2.20 0 0.00 0 0.00 0 0.00931Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 356Appendix 17 (continued) Individual Haematological ValuesRecovery GroupsGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l1(M) 97 56 15.8 7.56 46.7 20.8 61.8 33.8 7.5 15 1.13 84 6.30 0 0.00 1 0.08 0 0.00647ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ98 56 16.0 9.23 51.1 17.4 55.3 31.4 11.5 6 0.69 92 10.58 0 0.00 2 0.23 0 0.00741ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ99 56 16.3 9.49 50.3 17.2 53.0 32.4 8.4 17 1.43 82 6.89 0 0.00 1 0.08 0 0.00702ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ100 56 16.8 9.09 50.8 18.4 55.9 33.0 8.2 17 1.39 82 6.72 0 0.00 1 0.08 0 0.00619ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ101 56 15.2 8.63 46.6 17.7 54.0 32.7 6.4 20 1.28 79 5.06 0 0.00 1 0.06 0 0.00507Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 357Appendix 17 (continued) Individual Haematological ValuesRecovery GroupsGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l4(M) 107 56 15.2 9.12 47.3 16.6 51.9 32.0 5.9 22 1.30 78 4.60 0 0.00 0 0.00 0 0.00638ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ108 56 15.4 9.04 47.8 17.0 52.9 32.2 6.4 27 1.73 71 4.54 0 0.00 2 0.13 0 0.00678ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ109 56 15.8 8.90 48.9 17.7 54.9 32.3 6.7 22 1.47 78 5.23 0 0.00 0 0.00 0 0.00872ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ110 56 15.6 9.09 48.5 17.2 53.4 32.1 7.7 18 1.39 82 6.31 0 0.00 0 0.00 0 0.00568ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ111 56 15.6 9.10 48.7 17.2 53.5 32.1 6.1 21 1.28 78 4.76 0 0.00 1 0.06 0 0.00689Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 358Appendix 17 (continued) Individual Haematological ValuesRecovery GroupsGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l1(F) 102 56 10.8 5.81 32.8 18.6 56.4 32.9 0.6 6 0.04 92 0.55 0 0.00 2 0.01 0 0.002ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ103 56 15.4 8.42 46.3 18.3 55.0 33.2 4.0 23 0.92 77 3.08 0 0.00 0 0.00 0 0.00641ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ104 56 14.8 7.86 44.4 18.8 56.4 33.4 5.9 19 1.12 80 4.72 0 0.00 1 0.06 0 0.00688ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ105 56 15.3 8.36 47.1 18.3 56.3 32.5 3.7 13 0.48 85 3.15 0 0.00 2 0.07 0 0.00685ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ106 56 15.1 8.42 46.0 17.9 54.6 32.8 1.9 20 0.38 77 1.46 0 0.00 3 0.06 0 0.00563Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 359Appendix 17 (continued) Individual Haematological ValuesRecovery GroupsGroup Animal(Sex) Number Day Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% BasPLTNumber g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l4(F) 112 56 14.9 8.25 45.1 18.1 54.7 33.1 3.5 18 0.63 82 2.87 0 0.00 0 0.00 0 0.00729ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ113 56 15.2 8.74 46.8 17.4 53.6 32.5 3.5 16 0.56 84 2.94 0 0.00 0 0.00 0 0.00758ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ114 56 15.0 8.30 45.5 18.1 54.8 33.0 4.1 15 0.62 84 3.44 0 0.00 1 0.04 0 0.00700ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ115 56 15.9 8.73 47.9 18.2 54.8 33.2 3.6 19 0.68 80 2.88 0 0.00 1 0.04 0 0.00721ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ116 56 14.9 7.94 45.3 18.7 57.0 32.9 2.9 20 0.58 80 2.32 0 0.00 0 0.00 0 0.00662Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 360Appendix 18 Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds1(M) 1 42 9.8 15.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2 42 8.8 14.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3 42 9.3 15.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4 42 9.3 14.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ5 42 9.3 14.9Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 361Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds2(M) 25 42 10.1 15.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ26 42 9.9 17.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ27 42 9.1 15.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ28 42 9.6 14.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ29 42 9.2 16.0Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 362Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds3(M) 49 42 9.6 18.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ50 42 10.1 18.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ51 42 9.0 14.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ52 42 8.9 15.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ53 42 9.8 18.1Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 363Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds4(M) 73 42 10.6 17.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ74 42 9.2 14.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ75 42 9.6 17.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ76 42 8.9 14.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ77 42 8.9 14.3Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 364Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds1(F) 13 43 9.2 18.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ16 42 9.3 13.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ19 42 8.4 15.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ20 42 8.7 15.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ22 43 9.4 18.0Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 365Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds2(F) 37 43 8.6 15.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ39 42 9.1 18.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ42 42 8.7 18.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ45 42 8.8 17.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ46 42 10.2 16.6Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 366Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds3(F) 66 42 8.9 14.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ67 42 8.5 15.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ68 42 8.5 17.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ71 42 9.2 17.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ72 42 8.4 17.7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 367Appendix 18 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds4(F) 86 44 9.5 15.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ90 44 9.1 13.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ91 44 8.5 16.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ92 42 8.9 18.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ95 43 9.0 16.7Dose Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 368Appendix 18 (continued) Individual Coagulation ValuesRecovery GroupsGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds1(M) 97 56 9.1 15.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ98 56 9.8 14.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ99 56 9.4 15.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ100 56 10.6 16.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ101 56 9.0 16.6Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 369Appendix 18 (continued) Individual Coagulation ValuesRecovery GroupsGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds4(M) 107 56 9.6 16.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ108 56 9.3 16.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ109 56 9.1 13.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ110 56 10.7 16.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ111 56 9.7 15.1Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 370Appendix 18 (continued) Individual Coagulation ValuesRecovery GroupsGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds1(F) 102 56 9.1 12.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ103 56 8.6 15.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ104 56 9.6 15.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ105 56 9.4 17.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ106 56 9.5 16.1Dose Levels: Group 1 ƒ 0 (Control) Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 371Appendix 18 (continued) Individual Coagulation ValuesRecovery GroupsGroup Animal(Sex) Number Day CT APTTNumber Seconds Seconds4(F) 112 56 9.5 17.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ113 56 8.7 15.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ114 56 9.1 15.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ115 56 8.9 16.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ116 56 8.7 15.9Dose Levels: Group 1 ƒ 0 (Control) Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 372Appendix 19 Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl1(M) 1 42 41 124 7.20 4.1 1.31 146 5.16 99 2.69 1.9 100 73 178 0.69 88 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ2 42 39 154 6.93 3.9 1.27 147 4.26 105 2.82 1.8 83 51 181 0.75 83 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ3 42 41 139 7.30 4.1 1.30 148 4.44 101 2.86 2.3 156 67 224 0.75 90 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4 42 50 133 6.85 3.8 1.25 150 4.58 107 2.69 1.6 82 58 149 0.72 66 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ5 42 45 164 6.59 3.8 1.34 144 4.02 103 2.70 1.2 119 61 136 0.69 86 0.10Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 373Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl2(M) 25 42 44 117 7.60 4.2 1.24 151 6.10 101 2.90 2.8 120 72 209 0.80 97 0.05ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ26 42 38 140 6.88 3.6 1.13 145 4.74 104 2.73 1.8 80 60 265 0.67 68 0.17ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ27 42 42 155 6.69 3.8 1.31 145 3.69 104 2.69 1.2 84 66 265 0.72 82 0.00ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ28 42 46 186 6.40 3.9 1.54 146 3.74 105 2.66 1.3 97 71 293 0.73 57 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ29 42 45 148 7.20 3.8 1.12 147 4.65 102 2.77 1.6 85 55 184 0.73 96 0.12Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 374Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl3(M) 49 42 45 141 7.41 3.9 1.11 153 4.78 108 2.87 1.6 100 59 198 0.74 99 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ50 42 42 160 7.17 3.8 1.15 144 4.57 102 2.50 1.7 83 62 140 0.67 57 0.19ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ51 42 38 138 7.11 4.0 1.27 146 5.00 103 2.92 2.2 84 74 155 0.67 74 0.13ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ52 42 39 165 6.49 3.6 1.23 142 4.29 104 2.63 1.3 80 57 178 0.71 75 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ53 42 43 136 7.66 4.1 1.15 148 5.25 102 2.83 1.8 107 73 238 0.81 85 0.08Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 375Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl4(M) 73 42 41 146 7.81 4.0 1.05 146 5.60 102 2.51 2.8 97 53 128 0.69 78 0.18ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ74 42 38 159 6.85 3.7 1.14 145 4.39 100 2.77 1.9 114 47 163 0.75 69 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ75 42 38 130 8.00 4.3 1.14 150 5.95 102 3.03 2.4 95 62 201 0.73 70 0.12ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ76 42 33 149 6.86 3.7 1.14 145 4.24 105 2.68 2.2 69 46 193 0.62 83 0.14ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ77 42 41 143 6.96 3.9 1.24 145 4.52 105 2.86 1.4 82 62 169 0.77 63 0.09Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 376Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl1(F) 13 43 66 116 6.34 3.5 1.27 147 4.51 102 2.72 1.2 77 72 139 1.41 89 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ16 42 43 139 5.82 3.4 1.40 144 4.47 104 2.40 1.0 79 77 95 0.76 68 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ19 42 37 131 6.20 3.6 1.42 142 3.99 102 2.67 1.1 82 93 124 0.62 68 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ20 42 53 154 6.62 3.6 1.19 147 3.97 106 2.65 1.0 130 87 99 0.75 94 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ22 43 44 136 7.12 4.0 1.26 146 4.70 99 2.68 0.7 72 81 186 0.70 92 0.08Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 377Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl2(F) 37 43 49 141 6.21 3.7 1.43 147 5.12 99 2.96 1.4 128 96 167 0.80 74 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ39 42 51 113 6.57 3.6 1.25 150 4.51 106 2.75 0.6 94 94 159 0.76 85 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ42 42 45 120 6.42 3.7 1.34 145 4.46 105 2.52 0.5 71 67 120 0.67 76 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ45 42 52 126 6.03 3.6 1.45 147 3.96 106 2.69 0.6 119 70 121 0.76 71 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ46 42 58 111 7.04 3.9 1.28 150 5.50 107 2.83 1.7 84 52 169 0.80 43 0.07Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 378Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl3(F) 66 42 46 129 6.33 3.6 1.28 142 4.16 105 2.51 0.5 108 60 155 0.72 68 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ67 42 65 114 6.29 3.7 1.47 145 4.12 103 2.64 1.0 71 71 142 0.68 59 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ68 42 67 147 6.58 3.8 1.34 149 5.17 106 2.70 2.0 91 88 175 0.77 78 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ71 42 49 116 6.86 3.9 1.34 145 4.15 103 2.56 0.4 73 86 126 0.65 60 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ72 42 48 149 6.30 3.6 1.29 144 3.80 104 2.54 0.4 72 55 92 0.73 57 0.08Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 379Appendix 19 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl4(F) 86 44 66 128 6.66 3.9 1.37 149 6.18 103 2.86 1.2 99 35 111 1.20 34 0.16ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ90 44 54 134 7.00 3.8 1.16 145 4.90 101 2.74 1.4 68 68 155 0.69 113 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ91 44 61 107 7.03 3.9 1.24 146 5.25 104 2.70 0.7 88 78 114 0.63 90 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ92 42 55 128 6.72 3.9 1.39 149 4.48 106 2.69 0.8 81 75 291 0.97 72 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ95 43 51 130 6.41 3.6 1.32 147 4.42 100 2.65 0.9 62 57 175 0.75 46 0.10Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 380Appendix 19 (continued) Individual Blood Chemical ValuesRecovery GroupsGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl1(M) 97 56 57 153 6.56 3.5 1.18 149 4.55 105 2.63 2.0 185 163 115 0.57 101 0.13ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ98 56 43 220 5.84 3.2 1.18 143 4.12 101 2.47 1.2 123 78 112 0.64 55 0.03ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ99 56 58 160 7.32 4.0 1.19 147 5.66 100 2.79 2.1 75 67 122 0.70 120 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ100 56 55 244 6.21 3.4 1.19 148 4.18 101 2.56 1.3 117 60 104 0.63 89 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ101 56 47 211 5.68 3.3 1.40 149 4.07 103 2.46 0.9 118 50 130 0.60 83 0.07Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 381Appendix 19 (continued) Individual Blood Chemical ValuesRecovery GroupsGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl4(M) 107 56 49 173 6.76 3.8 1.26 145 4.37 103 2.66 1.8 72 67 135 0.66 98 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ108 56 48 141 6.62 3.7 1.24 146 4.55 104 2.62 1.6 72 55 218 0.61 77 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ109 56 48 195 6.65 3.6 1.22 144 4.31 102 2.57 1.3 56 43 122 0.69 99 0.13ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ110 56 57 173 6.49 3.4 1.12 145 4.75 104 2.60 1.7 69 63 138 0.73 89 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ111 56 51 168 6.92 3.8 1.24 148 4.85 103 2.72 1.7 71 52 174 0.65 98 0.10Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 382Appendix 19 (continued) Individual Blood Chemical ValuesRecovery GroupsGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl1(F) 102 56 53 185 6.35 3.8 1.52 147 4.61 103 2.62 1.0 272 65 86 0.64 69 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ103 56 54 104 7.47 4.6 1.59 148 5.28 103 2.82 1.9 73 56 91 0.68 73 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ104 56 46 202 6.99 4.2 1.53 146 3.93 102 2.70 1.4 64 50 144 0.76 83 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ105 56 52 133 8.27 4.9 1.44 151 5.08 103 2.92 1.6 73 63 92 0.72 96 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ106 56 61 128 7.74 4.7 1.52 155 5.81 110 2.87 1.2 94 56 102 0.72 94 0.07Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 383Appendix 19 (continued) Individual Blood Chemical ValuesRecovery GroupsGroup Animal Tot.(Sex) Number Day Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol BiliNumber mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl4(F) 112 56 58 138 7.66 4.0 1.09 146 5.14 104 2.83 1.7 60 49 70 0.69 101 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ113 56 52 160 7.13 4.1 1.35 149 4.67 105 2.69 1.2 72 63 81 0.71 64 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ114 56 45 152 7.62 4.3 1.32 148 4.67 103 2.78 1.6 106 73 80 0.68 69 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ115 56 48 153 7.41 4.2 1.28 148 4.45 103 2.78 1.6 81 76 83 0.65 79 0.05ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ116 56 52 157 7.21 4.1 1.34 146 4.48 105 2.75 1.4 70 58 64 0.68 102 0.07Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 384Appendix 20 Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l1(M) 1 42 5.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ2 42 6.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ3 42 16.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ4 42 7.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ5 42 4.6Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 385Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l2(M) 25 42 3.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ26 42 3.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ27 42 3.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ28 42 10.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ29 42 11.2Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 386Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l3(M) 49 42 6.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ50 42 3.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ51 42 13.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ52 42 8.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ53 42 4.4Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 387Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l4(M) 73 42 2.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ74 42 9.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ75 42 7.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ76 42 10.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ77 42 6.2Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 388Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l1(F) 13 43 11.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ16 42 14.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ19 42 3.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ20 42 15.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ22 43 9.2Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 389Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l2(F) 37 43 7.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ39 42 6.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ42 42 4.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ45 42 5.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ46 42 6.8Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 390Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l3(F) 66 42 3.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ67 42 4.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ68 42 8.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ71 42 15.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ72 42 4.2Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 391Appendix 20 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Day Bile AcidNumberμmol/l4(F) 86 44 4.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ90 44 6.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ91 44 4.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ92 42 3.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ95 43 5.4Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 392Appendix 20 (continued) Individual Bile Acid ValuesRecovery GroupsGroup Animal(Sex) Number Day Bile AcidNumberμmol/l1(M) 97 56 5.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ98 56 3.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ99 56 32.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ100 56 3.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ101 56 3.6Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 393Appendix 20 (continued) Individual Bile Acid ValuesRecovery GroupsGroup Animal(Sex) Number Day Bile AcidNumberμmol/l4(M) 107 56 4.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ108 56 6.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ109 56 10.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ110 56 11.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ111 56 8.1Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 394Appendix 20 (continued) Individual Bile Acid ValuesRecovery GroupsGroup Animal(Sex) Number Day Bile AcidNumberμmol/l1(F) 102 56 4.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ103 56 4.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ104 56 5.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ105 56 4.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ106 56 4.8Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 395Appendix 20 (continued) Individual Bile Acid ValuesRecovery GroupsGroup Animal(Sex) Number Day Bile AcidNumberμmol/l4(F) 112 56 3.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ113 56 4.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ114 56 4.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ115 56 5.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ116 56 18.7Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 396Appendix 21 Individual and Group Mean Urinalytical FindingsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)1(M) 1 17.0 1.019 6 1+ Normal Negative Normal Negative Negative Negative Clear2 24.0 1.010 6 1+ Normal Negative Normal Negative Negative Negative Clear3 22.0 1.012 7 1+ Normal Negative Normal Negative Negative Negative Clear4 . . 7 1+ Normal Negative Normal Negative Negative Negative Clear5 32.0 1.010 7 1+ Normal Negative Normal Negative Negative Negative ClearMean 23.8 1.013S.D. 6.2 0.004N 4 4. = data unavailable; water bottle leakedDose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 397Appendix 21 (continued) Individual and Group Mean Urinalytical FindingsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)2(M) 25 15.0 1.016 7 1+ Normal Negative Normal Negative Negative Negative Clear26 27.0 1.009 71+NormalNegativeNormalNegativeNegativeNegativeClear27 19.0 1.010 6 1+ Normal Negative Normal Negative Negative Negative Clear28 12.0 1.016 7 1+ Normal Negative Normal Negative Negative Negative Clear29 14.0 1.018 6 1+ Normal Negative Normal Negative Negative Negative ClearMean 17.4 1.014S.D. 5.9 0.004N 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 398Appendix 21 (continued) Individual and Group Mean Urinalytical FindingsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)3(M) 49 15.0 1.016 6 1+ Normal Negative Normal Negative Negative Negative Clear50 28.0 1.010 61+NormalNegativeNormalNegativeNegativeNegativeClear51 16.0 1.014 6 1+ Normal Negative Normal Negative Negative Negative Clear52 32.0 1.008 6 1+ Normal Negative Normal Negative Negative Negative Clear53 21.0 1.013 7 1+ Normal Negative Normal Negative Negative Negative ClearMean 22.4 1.012S.D. 7.4 0.003N 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 399Appendix 21 (continued) Individual and Group Mean Urinalytical FindingsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)4(M) 73 8.0 1.021 6 1+ Normal Negative Normal Negative Negative Negative Clear74 24.0 1.010 61+NormalNegativeNormalNegativeNegativeNegativeClear75 31.0 1.009 7 1+ Normal Negative Normal Negative Negative Negative Clear76 22.0 1.011 6 1+ Normal Negative Normal Negative Negative Negative Clear77 29.0 1.011 6 1+ Normal Negative Normal Negative Negative Negative ClearMean 22.8 1.012S.D. 9.0 0.005N 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 400Appendix 21 (continued) Individual and Group Mean Urinalytical FindingsRecovery GroupsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)1(M) 97 28.0 1.010 6 1+ Normal Negative Normal Negative Negative Negative Clear98 27.0 1.009 6 1+ Normal Negative Normal Negative Negative Negative Clear99 20.0 1.011 61+NormalNegativeNormalNegativeNegativeNegativeClear100 22.0 1.012 5 1+ Normal Negative Normal Negative Negative Negative Clear101 11.0 1.011 6 1+ Normal Negative Normal Negative Negative Negative ClearMean 21.6 1.011S.D. 6.8 0.001N 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 401Appendix 21 (continued) Individual and Group Mean Urinalytical FindingsRecovery GroupsGroupAnimalNumberVolume(ml)SpecificGravity pH Protein Glucose Ketones Urobilinogen BilirubinBlood -ErythrocytesBlood -Haemoglobin Appearance(Sex)4(M) 107 18.0 1.016 5 1+ Normal Negative Normal Negative Negative Negative Clear108 22.0 1.011 6 1+ Normal Negative Normal Negative Negative Negative Clear109 21.0 1.013 61+NormalNegativeNormalNegativeNegativeNegativeClear110 20.0 1.016 6 1+ Normal Negative Normal Negative Negative Negative Clear111 23.0 1.011 6 1+ Normal Negative Normal Negative Negative Negative ClearMean 20.8 1.013S.D. 1.9 0.003N 5 5Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 402Appendix 22 Individual Necropsy Findings for OffspringGroup: 1 Dose Level: 0 (Control)Litter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partu m)Offspring Sex &NumberMacroscopic ObservationTotal Numberof OffspringMacroscopic Observation13 3M 7F No abnormalities detected14 5M 6F No abnormalities detected15 4M 8F No abnormalities detected16 6M 8F No abnormalities detected17 Pre Day 1 1M Autolytic changes detected F12 Scab on dorsal region4M 7F No abnormalities detected184M 1F No abnormalities detected19 6M 4F No abnormalities detected20 2M 9F No abnormalities detected21 8M 6F No abnormalities detected22 F13 Swollen left hind limb8M 5F No abnormalities detected23 Pre Day 1 1M No abnormalities detected 3M 9F No abnormalities detected24 3M 7F No abnormalities detectedHarlan Study Number:41204605Report Page 403Appendix 22 (continued) IndividualNecropsy Findings for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partu m)Offspring Sex &NumberMacroscopic ObservationTotal Numberof OffspringMacroscopic Observation37 4M 8F No abnormalities detected38 7M 5F No abnormalities detected39 6M 7F No abnormalities detected40 6M 10F No abnormalities detected41 TLL . .424M 7F No abnormalities detected43 NP . .44 3M 9F No abnormalities detected45 3M 8F No abnormalities detected46 2M 3F No abnormalities detected47 6M 7F No abnormalities detected48 NP . .Harlan Study Number:41204605Report Page 404Appendix 22 (continued) Individual Necropsy Findings for OffspringGroup: 3 Dose Level: 60 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partu m)Offspring Sex &NumberMacroscopic ObservationTotal Numberof OffspringMacroscopic Observation61 3M 2F No abnormalities detected62 NP . .63 2M 2F No abnormalities detected64 7M 5F No abnormalities detected65 6M 6F No abnormalities detected662M 5F No abnormalities detected67 6M 3F No abnormalities detected68 7M 7F No abnormalities detected69 3M 1F No abnormalities detected70 6M 5F No abnormalities detected71 F5 Open wound on right hind limb2M 8F No abnormalities detected72 5M 6F No abnormalities detectedHarlan Study Number:41204605Report Page 405Appendix 22 (continued) Individual Necropsy Findings for OffspringGroup: 4 Dose Level: 120 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partu m)Offspring Sex &NumberMacroscopic ObservationTotal Numberof OffspringMacroscopic Observation85 NP . .86 Pre Day 1 1M 1F Autolytic changes detected M4 Small5 1M No abnormalities detected 1M 2F No abnormalities detected87 NL . .88 NP . .89 TLL . .906M 2F No abnormalities detected91 5M 6F No abnormalities detected92 2M 8F No abnormalities detected93 TLL . .94 2M 8F No abnormalities detected95 6M 2F No abnormalities detected96 7M 4F No abnormalities detectedHarlan Study Number:41204605Report Page 406Appendix 23 Individual Necropsy FindingsGroup: 1 Dose Level: 0 (Control) Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ1 SCHEDULED KILL 43 (7) No abnormalities detected2 SCHEDULED KILL 43 (7) No abnormalities detected3 SCHEDULED KILL 43 (7) No abnormalities detected4 SCHEDULED KILL 43 (7) No abnormalities detected5 SCHEDULED KILL 43 (7) No abnormalities detected6 SCHEDULED KILL 43 (7) No abnormalities detected7 SCHEDULED KILL 43 (7) No abnormalities detected8 SCHEDULED KILL 43 (7) No abnormalities detected9 SCHEDULED KILL 43 (7) No abnormalities detected10 SCHEDULED KILL 43 (7) No abnormalities detected11 SCHEDULED KILL 43 (7) No abnormalities detected12 SCHEDULED KILL 43 (7) No abnormalities detected97 SCHEDULED KILL 57 (9) No abnormalities detected98 SCHEDULED KILL 57 (9) No abnormalities detected99 SCHEDULED KILL 57 (9) No abnormalities detected100 SCHEDULED KILL 57 (9) No abnormalities detected101 SCHEDULED KILL 57 (9) No abnormalities detectedHarlan Study Number:41204605Report Page 407Appendix 23 (continued) Individual Necropsy FindingsGroup: 1 Dose Level: 0 (Control) Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ13 SCHEDULED KILL 44 (7) No abnormalities detected14 SCHEDULED KILL 45 (7) No abnormalities detected15 SCHEDULED KILL 45 (7) No abnormalities detected16 SCHEDULED KILL 43 (7) No abnormalities detected17 SCHEDULED KILL 42 (6) No abnormalities detected18 SCHEDULED KILL 46 (7) No abnormalities detected19 SCHEDULED KILL 43 (7) No abnormalities detected20 SCHEDULED KILL 43 (7) No abnormalities detected21 SCHEDULED KILL 42 (6) No abnormalities detected22 SCHEDULED KILL 44 (7) No abnormalities detected23 SCHEDULED KILL 44 (7) No abnormalities detected24 SCHEDULED KILL 44 (7) No abnormalities detected102 SCHEDULED KILL 57 (9) No abnormalities detected103 SCHEDULED KILL 57 (9) No abnormalities detected104 SCHEDULED KILL 57 (9) No abnormalities detected105 SCHEDULED KILL 57 (9) No abnormalities detected106 SCHEDULED KILL 57 (9) No abnormalities detectedHarlan Study Number:41204605Report Page 408Appendix 23 (continued) Individual Necropsy FindingsGroup: 2 Dose Level: 30 mg/kg bw/day Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ25 SCHEDULED KILL 43 (7) No abnormalities detected26 SCHEDULED KILL 43 (7) No abnormalities detected27 SCHEDULED KILL 43 (7) Mammary Gland; Mass: Soft fibrous mass approximately 40mm x 32mm x 22mm.All remaining tissues had no abnormalities detected28 SCHEDULED KILL 43 (7) No abnormalities detected29 SCHEDULED KILL 43 (7) No abnormalities detected30 SCHEDULED KILL 43 (7) No abnormalities detected31 SCHEDULED KILL 43 (7) No abnormalities detected32 SCHEDULED KILL 43 (7) No abnormalities detected33 SCHEDULED KILL 43 (7) No abnormalities detected34 SCHEDULED KILL 43 (7) No abnormalities detected35 SCHEDULED KILL 43 (7) No abnormalities detected36 SCHEDULED KILL 43 (7) No abnormalities detectedHarlan Study Number:41204605Report Page 409Appendix 23 (continued) Individual Necropsy FindingsGroup: 2 Dose Level: 30 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ37 SCHEDULED KILL 44 (7) No abnormalities detected38 SCHEDULED KILL 44 (7) No abnormalities detected39 SCHEDULED KILL 43 (7) No abnormalities detected40 SCHEDULED KILL 45 (7) No abnormalities detected41 SCHEDULED KILL 45 (7) No abnormalities detected42 SCHEDULED KILL 43 (7) No abnormalities detected43 SCHEDULED KILL 46 (7) No abnormalities detected44 SCHEDULED KILL 42 (6) No abnormalities detected45 SCHEDULED KILL 43 (7) No abnormalities detected46 SCHEDULED KILL 43 (7) No abnormalities detected47 SCHEDULED KILL 44 (7) No abnormalities detected48 SCHEDULED KILL 42 (6) Uterus & Cervix; left horn; DistendedVagina; Fluid Filled: vagina filled with a viscous cream coloured fluidAll remaining tissues had no abnormalities detectedHarlan Study Number:41204605Report Page 410Appendix 23 (continued) Individual Necropsy FindingsGroup: 3 Dose Level: 60 mg/kg bw/day Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ49 SCHEDULED KILL 43 (7) No abnormalities detected50 SCHEDULED KILL 43 (7) No abnormalities detected51 SCHEDULED KILL 43 (7) No abnormalities detected52 SCHEDULED KILL 43 (7) No abnormalities detected53 SCHEDULED KILL 43 (7) No abnormalities detected54 SCHEDULED KILL 43 (7) No abnormalities detected55 SCHEDULED KILL 43 (7) No abnormalities detected56 SCHEDULED KILL 43 (7) No abnormalities detected57 SCHEDULED KILL 43 (7) No abnormalities detected58 SCHEDULED KILL 43 (7) No abnormalities detected59 SCHEDULED KILL 43 (7) No abnormalities detected60 SCHEDULED KILL 43 (7) No abnormalities detectedHarlan Study Number:41204605Report Page 411Appendix 23 (continued) Individual Necropsy FindingsGroup: 3 Dose Level: 60 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ61 SCHEDULED KILL 44 (7) No abnormalities detected62 SCHEDULED KILL 44 (7) No abnormalities detected63 SCHEDULED KILL 45 (7) No abnormalities detected64 SCHEDULED KILL 42 (6) No abnormalities detected65 SCHEDULED KILL 44 (7) No abnormalities detected66 SCHEDULED KILL 43 (7) No abnormalities detected67 SCHEDULED KILL 43 (7) No abnormalities detected68 SCHEDULED KILL 43 (7) No abnormalities detected69 SCHEDULED KILL 46 (7) No abnormalities detected70 SCHEDULED KILL 42 (6) No abnormalities detected71 SCHEDULED KILL 43 (7) No abnormalities detected72 SCHEDULED KILL 43 (7) No abnormalities detectedHarlan Study Number:41204605Report Page 412Appendix 23 (continued) Individual Necropsy FindingsGroup: 4 Dose Level: 120 mg/kg bw/day Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ73 SCHEDULED KILL 43 (7) No abnormalities detected74 SCHEDULED KILL 43 (7) No abnormalities detected75 SCHEDULED KILL 43 (7) No abnormalities detected76 SCHEDULED KILL 43 (7) No abnormalities detected77 SCHEDULED KILL 43 (7) No abnormalities detected78 SCHEDULED KILL 43 (7) No abnormalities detected79 SCHEDULED KILL 43 (7) No abnormalities detected80 SCHEDULED KILL 43 (7) No abnormalities detected81 SCHEDULED KILL 43 (7) Seminal Vesicles; SmallAll remaining tissues had no abnormalities detected82 SCHEDULED KILL 43 (7) No abnormalities detected83 SCHEDULED KILL 43 (7) Epididymides; left; Mass: Yellow fluid filled mass attached to left caudaapproximately 12mm x 5mm x 3mmAll remaining tissues had no abnormalities detected84 SCHEDULED KILL 43 (7) No abnormalities detected107 SCHEDULED KILL 57 (9) No abnormalities detected108 SCHEDULED KILL 57 (9) No abnormalities detected109 SCHEDULED KILL 57 (9) No abnormalities detected110 SCHEDULED KILL 57 (9) No abnormalities detected111 SCHEDULED KILL 57 (9) No abnormalities detectedHarlan Study Number:41204605Report Page 413Appendix 23 (continued) Individual Necropsy FindingsGroup: 4 Dose Level: 120 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ85 SCHEDULED KILL 44 (7) No abnormalities detected86 SCHEDULED KILL 45 (7) No abnormalities detected87 SCHEDULED KILL 42 (6) No abnormalities detected88 SCHEDULED KILL 44 (7) No abnormalities detected89 SCHEDULED KILL 47 (7) No abnormalities detected90 SCHEDULED KILL 45 (7) No abnormalities detected91 SCHEDULED KILL 45 (7) No abnormalities detected92 SCHEDULED KILL 43 (7) Eyes; right; ReddenedAll remaining tissues had no abnormalities detected93 SCHEDULED KILL 45 (7) No abnormalities detected94 SCHEDULED KILL 46 (7) No abnormalities detected95 SCHEDULED KILL 44 (7) No abnormalities detected96 SCHEDULED KILL 46 (7) No abnormalities detected112 SCHEDULED KILL 57 (9) No abnormalities detected113 SCHEDULED KILL 57 (9) No abnormalities detected114 SCHEDULED KILL 57 (9) No abnormalities detected115 SCHEDULED KILL 57 (9) No abnormalities detected116 SCHEDULED KILL 57 (9) No abnormalities detectedHarlan Study Number:41204605Report Page 414Appendix 24 Individual Organ WeightsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g1(M) 1 43 0.0581 2.0822 1.5987 0.9971 2.4687 11.5575 0.0099 0.4667 1.9006 0.7467 3.7905 0.4097 0.0221ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 0.0702 2.0747 1.7685 1.1389 2.0907 11.2223 0.0116 0.6168 2.1267 0.7086 3.5050 0.3666 0.0224ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 0.0800 1.9760 1.4845 1.1247 2.1392 12.1917 0.0147 0.7261 2.1056 0.7302 3.4192 0.4711 0.0121ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 0.0807 2.1679 1.4767 1.1957 2.0357 12.0105 0.0097 0.7637 2.1446 0.6028 4.1733 0.4723 0.0246ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 0.0637 1.9735 1.4990 1.0247 1.7403 10.3642 0.0129 0.5305 1.5048 0.5883 3.8388 0.5301 0.0231ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 1.4727 0.0085 0.5505 2.5415 3.5059ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 1.5903 0.0138 0.6420 2.6145 3.4840ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 1.2074 0.0133 0.7711 1.7422 3.3825ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 1.2312 0.0145 0.6204 1.7531 3.3719ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 1.3602 0.0104 0.5350 1.9416 3.5372ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 1.3371 0.0101 0.4977 2.0028 3.2770ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 1.6021 0.0131 0.3344 1.4843 3.2046Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 415Appendix 24 (continued) Individual Organ WeightsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g2(M) 25 43 0.0770 2.1372 1.5198 1.1696 2.1160 10.1829 0.0093 0.6037 1.8288 0.5382 3.8787 0.4073 0.0215ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 0.0567 2.0927 1.5777 1.1603 2.6201 12.9691 0.0114 0.5351 2.3914 0.7391 3.7004 0.4313 0.0246ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 0.0766 2.1649 1.4901 0.9074 2.2130 11.5656 0.0100 0.4496 2.0913 0.8204 3.5200 0.4029 0.0192ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 0.0503 2.0540 1.2894 1.2097 2.2781 9.7607 0.0105 0.5503 1.6608 0.5851 3.5151 0.2591 0.0244ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 0.0756 2.1119 1.5380 1.1894 2.4993 12.5685 0.0145 0.4790 2.2428 0.7483 3.5709 0.3979 0.0258ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 1.1684 0.0127 0.4837 1.4604 3.4274ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 1.3905 0.0202 0.5578 2.2572 3.7541ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 1.4268 0.0118 0.5769 1.9099 3.9447ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 2.0040 0.0168 0.6039 2.3568 3.9830ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 1.3297 0.0160 0.6901 2.0812 3.5668ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 1.3723 0.0127 0.7027 2.4918 3.3421ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 1.4716 0.0121 0.5508 2.3821 3.9507Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 416Appendix 24 (continued) Individual Organ WeightsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g3(M) 49 43 0.0650 2.1442 1.5270 1.1145 2.2945 11.7335 0.0118 0.5468 1.8117 0.8223 3.3389 0.3730 0.0240ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 0.0634 2.1021 1.4456 1.2587 2.4639 12.9700 0.0117 0.5096 1.8957 0.7253 3.8168 0.5490 0.0213ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 0.0483 1.9788 1.4209 0.8485 2.1485 10.3283 0.0093 0.4782 1.6541 0.7303 3.8069 0.3860 0.0218ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 0.0602 1.8888 1.3618 1.0180 2.2668 10.4300 0.0095 0.6354 1.6759 0.5937 3.4527 0.2561 0.0216ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 0.0689 2.1364 1.2331 0.9606 2.2289 10.5174 0.0251 0.3992 1.6450 0.6319 3.1444 0.3898 0.0134ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 1.3350 0.0121 0.5411 1.4608 4.1205ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 1.4606 0.0120 0.5393 1.7287 3.3939ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 1.2274 0.0135 0.4708 2.1486 3.5594ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 1.3815 0.0134 0.6128 1.9654 3.6626ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 1.4531 0.0134 0.6437 2.3075 3.6690ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 1.4152 0.0133 0.5514 1.9694 3.3873ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 1.4753 0.0142 0.5687 2.0383 3.5340Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 417Appendix 24 (continued) Individual Organ WeightsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g4(M) 73 43 0.0706 2.0865 1.5167 1.2403 2.5906 11.0026 0.0110 0.6003 2.2712 0.5761 3.8236 0.4114 0.0268ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 0.0686 2.0673 1.3831 0.8235 2.3176 10.9380 0.0111 0.4942 1.7587 0.7363 3.3153 0.3554 0.0182ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 0.0622 2.0115 1.5424 1.0267 2.4837 14.2434 0.0192 0.4779 2.1295 0.6908 4.5289 0.4317 0.0234ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 0.0739 1.9561 1.5100 1.3562 3.2500 14.1214 0.0117 0.4704 2.3240 0.7274 3.2993 0.3163 0.0314ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 0.0726 1.9797 1.1414 0.8004 1.8903 10.3508 0.0090 0.4956 1.1099 0.7056 3.0299 0.3039 0.0198ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 1.6729 0.0174 0.7242 1.2244 3.4350ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 1.4283 0.0107 0.5826 1.9512 3.5184ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 1.4141 0.0110 0.3381 0.8787 3.4750ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 1.1353 0.0213 0.3264 0.6662 2.7805ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 1.5408 0.0150 0.4939 1.8223 3.0862ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 1.4871 0.0129 0.4437 1.6051 3.7225ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 1.3384 0.0109 0.5522 2.1373 3.3771Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 418Appendix 24 (continued) Individual and Group Mean Organ WeightsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g1(F) 13 44 0.0780 1.7754 0.7426 1.5757 10.4316 0.1039 0.0173 0.5223 0.2388 0.6201 0.0160ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ14 45 0.1117 0.0149 0.9791ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ15 45 0.0970 0.0185 0.4851ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ16 43 0.0990 1.7971 1.0950 1.7195 12.9887 0.1001 0.0177 0.7082 0.2205 0.8279 0.0189ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ17 42 0.0960 0.0143 0.6275ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ18 46 0.1048 0.0142 0.6166ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ19 43 0.1021 1.8869 0.8399 1.4535 10.4310 0.1220 0.0179 0.6167 0.2636 0.7567 0.0187ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ20 43 0.1026 1.8810 1.0458 1.6062 12.4086 0.1170 0.0173 0.6509 0.3489 0.6045 0.0239ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ21 42 0.1394 0.0164 0.7806ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ22 44 0.0889 1.7979 1.1077 1.6048 11.5342 0.1112 0.0167 0.5659 0.2721 0.6212 0.0174ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ23 44 0.0999 0.0193 0.6079ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ24 44 0.0954 0.0219 0.6974Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 419Appendix 24 (continued) Individual and Group Mean Organ WeightsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g2(F) 37 44 0.0873 1.7358 0.8392 1.5533 11.1502 0.0990 0.0177 0.5225 0.1934 0.7999 0.0274ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ38 44 0.1198 0.0248 0.5871ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ39 43 0.0916 1.8015 1.0030 1.5194 10.2572 0.1231 0.0156 0.5322 0.1949 0.6283 0.0185ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ40 45 0.1182 0.6445ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ41 45 0.1175 0.0134 0.6505ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ42 43 0.0766 1.8347 0.8018 1.5593 9.8442 0.1034 0.0170 0.5259 0.2780 0.7484 0.0233ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ43 46 0.1213 0.0173 0.5024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ44 42 0.1043 0.0275 0.5827ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ45 43 0.1077 1.7901 0.6585 1.3899 8.7335 0.0938 0.0153 0.6227 0.2263 0.6787 0.0165ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ46 43 0.0908 1.8669 0.8569 1.4169 9.0545 0.1112 0.0163 0.4634 0.2729 0.4935 0.0273ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ47 44 0.1209 0.0157 0.7656ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ48 42 0.0614 0.0161 1.1611Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 420Appendix 24 (continued) Individual and Group Mean Organ WeightsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g3(F) 61 44 0.0999 0.0185 0.5030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ62 44 0.0729 0.0131 0.9181ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ63 45 0.0809 0.0204 0.6160ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ64 42 0.1030 0.0174 0.5227ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ65 44 0.0995 0.7605ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ66 43 0.1056 1.7515 0.7917 1.3373 9.4765 0.0895 0.0205 0.6843 0.2788 0.8072 0.0188ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ67 43 0.0856 1.8602 0.7191 1.5060 9.6079 0.1008 0.0166 0.4756 0.2149 0.5571 0.0230ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ68 43 0.0690 1.8356 0.8064 1.7576 12.1130 0.1305 0.0181 0.5086 0.1436 0.7466 0.0212ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ69 46 0.0836 0.0160 0.4464ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ70 42 0.1077 0.0149 0.5092ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ71 43 0.0848 1.7946 0.7587 1.5960 10.5654 0.1029 0.0166 0.4535 0.1967 0.8483 0.0179ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ72 43 0.0894 1.8310 0.8966 1.3680 9.9153 0.1254 0.0143 0.4859 0.2745 0.6045 0.0271Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 421Appendix 24 (continued) Individual and Group Mean Organ WeightsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g4(F) 85 44 0.1017 0.0103 1.5485ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ86 45 0.0888 1.7854 1.0071 1.3644 9.0150 0.0832 0.0145 0.5141 0.1413 0.6532 0.0203ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ87 42 0.0882 0.0092 0.8556ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ88 44 0.0662 0.0127 1.4173ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ89 47 0.0185ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ90 45 0.0741 1.8717 0.6783 1.5150 11.5112 0.0837 0.0134 0.5356 0.1717 0.5285 0.0209ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ91 45 0.0870 1.6482 0.7977 1.5231 11.1669 0.0798 0.0126 0.5316 0.1768 0.5656 0.0202ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ92 43 0.1017 1.8641 0.6956 1.4046 10.0126 0.1040 0.0140 0.5737 0.2228 0.6354 0.0198ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ93 45 0.1054 0.0174 0.7370ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ94 46 0.1018 0.0175 0.5832ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ95 44 0.0661 1.8023 0.6531 1.2842 9.4170 0.1105 0.0112 0.5585 0.2194 0.6978 0.0247ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ96 46 0.0869 0.0154 0.6096Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 422Appendix 24 (continued) Individual Organ WeightsRecovery GroupsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g1(M) 97 57 0.0608 1.9700 1.5098 1.0489 2.0859 12.3281 0.0117 0.5926 1.7827 0.6225 3.2232 0.4801 0.0240ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ98 57 0.0554 1.9682 1.5134 1.0201 2.1867 11.4149 0.0113 0.6099 2.0251 0.6932 3.7925 0.4361 0.0234ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ99 57 0.0834 2.1806 1.5696 0.9110 2.0341 12.6113 0.0105 0.5531 2.0866 0.6420 3.4634 0.3878 0.0214ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ100 57 0.0711 2.1512 1.4384 1.0801 2.1844 13.6442 0.0114 0.7631 2.3645 0.5716 3.6981 0.4824 0.0227ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ101 57 0.0681 2.0919 1.5864 0.9064 2.1019 10.1734 0.0092 0.4943 2.3212 0.6745 3.7113 0.3270 0.0214Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 423Appendix 24 (continued) Individual Organ WeightsRecovery GroupsGroup Animal Epididyƒ Seminal(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus ThyroidNumber g g g g g g g g g g g g g4(M) 107 57 0.0658 1.9515 1.5934 1.2918 2.3302 12.2472 0.0115 0.5029 2.2599 0.7708 3.1249 0.2525 0.0241ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ108 57 0.0896 2.1700 1.5912 0.9008 2.4416 10.8199 0.0122 0.5496 2.4607 0.6149 3.7864 0.3428 0.0238ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ109 57 0.0457 1.8899 1.2985 0.8557 1.5978 10.3209 0.0099 0.3494 1.7025 0.4703 3.2571 0.3189 0.0222ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ110 57 0.0692 1.8959 1.5481 1.0223 2.2585 11.1208 0.0134 0.5901 1.6976 0.5680 3.4834 0.4075 0.0174ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ111 57 0.0613 1.9703 1.5401 1.0616 2.9090 12.4310 0.0080 0.4248 2.2392 0.6139 3.3948 0.2955 0.0206Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 424Appendix 24 (continued) Individual Organ WeightsRecovery GroupsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g1(F) 102 57 0.0835 1.6439 0.7834 1.1600 7.0625 0.0697 0.0153 0.3876 0.2690 0.4636 0.0171ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ103 57 0.0808 1.8065 0.7103 1.3251 7.6694 0.1189 0.0170 0.5741 0.3042 0.5652 0.0259ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ104 57 0.0903 1.8855 0.9450 1.5139 8.6135 0.1237 0.0198 0.6573 0.3159 0.8382 0.0224ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ105 57 0.0840 1.8279 0.6772 1.4741 6.7837 0.0928 0.0176 0.4336 0.3163 0.6584 0.0184ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ106 57 0.0606 1.7705 0.7239 1.3470 6.2643 0.1134 0.0136 0.5201 0.2256 0.6119 0.0156Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 425Appendix 24 (continued) Individual Organ WeightsRecovery GroupsGroup Animal(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Uterus ThyroidNumber g g g g g g g g g g g4(F) 112 57 0.0766 1.7284 0.7293 1.2428 7.8026 0.0847 0.0208 0.4092 0.3352 0.8694 0.0187ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ113 57 0.0936 1.7160 0.6661 1.3160 7.8622 0.0748 0.0199 0.4098 0.2320 0.7530 0.0152ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ114 57 0.0838 1.9468 0.7260 1.4308 7.4768 0.1068 0.0163 0.4896 0.2873 0.5201 0.0211ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ115 57 0.0941 1.8415 0.6870 1.4223 7.2535 0.1104 0.0165 0.4800 0.2681 1.2054 0.0205ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ116 57 0.0661 2.0134 0.7145 1.4219 8.2847 0.1105 0.0259 0.4666 0.3505 0.5500 0.0097Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 426Appendix 25 Individual Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %1(M) 1 43 387 0.0150 0.5380 0.4131 0.2576 0.6379 2.9864 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 408 0.0172 0.5085 0.4335 0.2791 0.5124 2.7506 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 386 0.0207 0.5119 0.3846 0.2914 0.5542 3.1585 0.0038ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 373 0.0216 0.5812 0.3959 0.3206 0.5458 3.2200 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 357 0.0178 0.5528 0.4199 0.2870 0.4875 2.9031 0.0036ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 357 0.4125 0.0024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 350 0.4544 0.0039ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 343 0.3520 0.0039ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 385 0.3198 0.0038ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 367 0.3706 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 352 0.3799 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 361 0.4438 0.0036Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 427Appendix 25 (continued) Individual Relative Organ Weights(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %1(M) 1 43 0.1206 0.4911 0.1929 0.9795 0.1059 0.0057ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 0.1512 0.5213 0.1737 0.8591 0.0899 0.0055ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 0.1881 0.5455 0.1892 0.8858 0.1220 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 0.2047 0.5750 0.1616 1.1188 0.1266 0.0066ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 0.1486 0.4215 0.1648 1.0753 0.1485 0.0065ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 0.1542 0.7119 0.9820ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 0.1834 0.7470 0.9954ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 0.2248 0.5079 0.9862ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 0.1611 0.4554 0.8758ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 0.1458 0.5290 0.9638ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 0.1414 0.5690 0.9310ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 0.0926 0.4112 0.8877Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 428Appendix 25 (continued) Individual Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %2(M) 25 43 338 0.0228 0.6323 0.4496 0.3460 0.6260 3.0127 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 412 0.0138 0.5079 0.3829 0.2816 0.6359 3.1478 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 379 0.0202 0.5712 0.3932 0.2394 0.5839 3.0516 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 332 0.0152 0.6187 0.3884 0.3644 0.6862 2.9400 0.0032ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 402 0.0188 0.5253 0.3826 0.2959 0.6217 3.1265 0.0036ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 349 0.3348 0.0036ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 434 0.3204 0.0047ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 438 0.3258 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 405 0.4948 0.0041ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 381 0.3490 0.0042ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 367 0.3739 0.0035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 401 0.3670 0.0030Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 429Appendix 25 (continued) Individual Relative Organ Weights(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %2(M) 25 43 0.1786 0.5411 0.1592 1.1475 0.1205 0.0064ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 0.1299 0.5804 0.1794 0.8982 0.1047 0.0060ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 0.1186 0.5518 0.2165 0.9288 0.1063 0.0051ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 0.1658 0.5002 0.1762 1.0588 0.0780 0.0073ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 0.1192 0.5579 0.1861 0.8883 0.0990 0.0064ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 0.1386 0.4185 0.9821ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 0.1285 0.5201 0.8650ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 0.1317 0.4361 0.9006ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 0.1491 0.5819 0.9835ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 0.1811 0.5462 0.9362ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 0.1915 0.6790 0.9107ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 0.1374 0.5940 0.9852Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 430Appendix 25 (continued) Individual Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %3(M) 49 43 387 0.0168 0.5541 0.3946 0.2880 0.5929 3.0319 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 386 0.0164 0.5446 0.3745 0.3261 0.6383 3.3601 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 328 0.0147 0.6033 0.4332 0.2587 0.6550 3.1489 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 358 0.0168 0.5276 0.3804 0.2844 0.6332 2.9134 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 356 0.0194 0.6001 0.3464 0.2698 0.6261 2.9543 0.0071ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 393 0.3397 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 367 0.3980 0.0033ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 362 0.3391 0.0037ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 368 0.3754 0.0036ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 388 0.3745 0.0035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 350 0.4043 0.0038ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 333 0.4430 0.0043Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 431Appendix 25 (continued) Individual Relative Organ Weights(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %3(M) 49 43 0.1413 0.4681 0.2125 0.8628 0.0964 0.0062ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 0.1320 0.4911 0.1879 0.9888 0.1422 0.0055ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 0.1458 0.5043 0.2227 1.1606 0.1177 0.0066ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 0.1775 0.4681 0.1658 0.9644 0.0715 0.0060ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 0.1121 0.4621 0.1775 0.8833 0.1095 0.0038ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 0.1377 0.3717 1.0485ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 0.1469 0.4710 0.9248ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 0.1301 0.5935 0.9833ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 0.1665 0.5341 0.9953ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 0.1659 0.5947 0.9456ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 0.1575 0.5627 0.9678ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 0.1708 0.6121 1.0613Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 432Appendix 25 (continued) Individual Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %4(M) 73 43 354 0.0199 0.5894 0.4284 0.3504 0.7318 3.1081 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 340 0.0202 0.6080 0.4068 0.2422 0.6816 3.2171 0.0033ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 375 0.0166 0.5364 0.4113 0.2738 0.6623 3.7982 0.0051ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 401 0.0184 0.4878 0.3766 0.3382 0.8105 3.5215 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 337 0.0215 0.5874 0.3387 0.2375 0.5609 3.0715 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 376 0.4449 0.0046ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 374 0.3819 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 363 0.3896 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 311 0.3650 0.0068ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 375 0.4109 0.0040ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 351 0.4237 0.0037ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 362 0.3697 0.0030Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 433Appendix 25 (continued) Individual Relative Organ Weights(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %4(M) 73 43 0.1696 0.6416 0.1627 1.0801 0.1162 0.0076ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 0.1454 0.5173 0.2166 0.9751 0.1045 0.0054ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 0.1274 0.5679 0.1842 1.2077 0.1151 0.0062ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 0.1173 0.5796 0.1814 0.8228 0.0789 0.0078ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 0.1471 0.3293 0.2094 0.8991 0.0902 0.0059ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 0.1926 0.3256 0.9136ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 0.1558 0.5217 0.9407ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 0.0931 0.2421 0.9573ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 0.1050 0.2142 0.8941ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 0.1317 0.4859 0.8230ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 0.1264 0.4573 1.0605ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 0.1525 0.5904 0.9329Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 434Appendix 25 (continued) Individual and Group Mean Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %1(F) 13 44 263 0.0297 0.6751 0.2824 0.5991 3.9664 0.0395 0.0066 0.1986 0.0908 0.0061 0.2358ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ14 45 255 0.0438 0.0058 0.3840ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ15 45 281 0.0345 0.0066 0.1726ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ16 43 265 0.0374 0.6782 0.4132 0.6489 4.9014 0.0378 0.0067 0.2672 0.0832 0.0071 0.3124ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ17 42 268 0.0358 0.0053 0.2341ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ18 46 286 0.0366 0.0050 0.2156ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ19 43 264 0.0387 0.7147 0.3181 0.5506 3.9511 0.0462 0.0068 0.2336 0.0998 0.0071 0.2866ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ20 43 291 0.0353 0.6464 0.3594 0.5520 4.2641 0.0402 0.0059 0.2237 0.1199 0.0082 0.2077ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ21 42 269 0.0518 0.0061 0.2902ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ22 44 299 0.0297 0.6013 0.3705 0.5367 3.8576 0.0372 0.0056 0.1893 0.0910 0.0058 0.2078ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ23 44 268 0.0373 0.0072 0.2268ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ24 44 279 0.0342 0.0078 0.2500Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 435Appendix 25 (continued) Individual and Group Mean Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %2(F) 37 44 246 0.0355 0.7056 0.3411 0.6314 4.5326 0.0402 0.0072 0.2124 0.0786 0.0111 0.3252ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ38 44 256 0.0468 0.0097 0.2293ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ39 43 244 0.0375 0.7383 0.4111 0.6227 4.2038 0.0505 0.0064 0.2181 0.0799 0.0076 0.2575ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ40 45 274 0.0431 0.2352ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ41 45 234 0.0502 0.0057 0.2780ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ42 43 145 0.0528 1.2653 0.5530 1.0754 6.7891 0.0713 0.0117 0.3627 0.1917 0.0161 0.5161ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ43 46 241 0.0503 0.0072 0.2085ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ44 42 241 0.0433 0.0114 0.2418ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ45 43 241 0.0447 0.7428 0.2732 0.5767 3.6239 0.0389 0.0063 0.2584 0.0939 0.0068 0.2816ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ46 43 230 0.0395 0.8117 0.3726 0.6160 3.9367 0.0483 0.0071 0.2015 0.1187 0.0119 0.2146ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ47 44 252 0.0480 0.0062 0.3038ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ48 42 278 0.0221 0.0058 0.4177Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 436Appendix 25 (continued) Individual and Group Mean Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %3(F) 61 44 224 0.0446 0.0083 0.2246ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ62 44 209 0.0349 0.0063 0.4393ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ63 45 222 0.0364 0.0092 0.2775ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ64 42 261 0.0395 0.0067 0.2003ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ65 44 244 0.0408 0.3117ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ66 43 233 0.0453 0.7517 0.3398 0.5739 4.0672 0.0384 0.0088 0.2937 0.1197 0.0081 0.3464ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ67 43 218 0.0393 0.8533 0.3299 0.6908 4.4073 0.0462 0.0076 0.2182 0.0986 0.0106 0.2556ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ68 43 257 0.0268 0.7142 0.3138 0.6839 4.7132 0.0508 0.0070 0.1979 0.0559 0.0082 0.2905ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ69 46 265 0.0315 0.0060 0.1685ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ70 42 231 0.0466 0.0065 0.2204ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ71 43 247 0.0343 0.7266 0.3072 0.6462 4.2775 0.0417 0.0067 0.1836 0.0796 0.0072 0.3434ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ72 43 226 0.0396 0.8102 0.3967 0.6053 4.3873 0.0555 0.0063 0.2150 0.1215 0.0120 0.2675Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 437Appendix 25 (continued) Individual and Group Mean Relative Organ WeightsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %4(F) 85 44 216 0.0471 0.0048 0.7169ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ86 45 230 0.0386 0.7763 0.4379 0.5932 3.9196 0.0362 0.0063 0.2235 0.0614 0.0088 0.2840ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ87 42 258 0.0342 0.0036 0.3316ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ88 44 194 0.0341 0.0065 0.7306ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ89 47 232 0.0080ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ90 45 234 0.0317 0.7999 0.2899 0.6474 4.9193 0.0358 0.0057 0.2289 0.0734 0.0089 0.2259ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ91 45 242 0.0360 0.6811 0.3296 0.6294 4.6144 0.0330 0.0052 0.2197 0.0731 0.0083 0.2337ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ92 43 248 0.0410 0.7517 0.2805 0.5664 4.0373 0.0419 0.0056 0.2313 0.0898 0.0080 0.2562ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ93 45 229 0.0460 0.0076 0.3218ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ94 46 241 0.0422 0.0073 0.2420ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ95 44 216 0.0306 0.8344 0.3024 0.5945 4.3597 0.0512 0.0052 0.2586 0.1016 0.0114 0.3231ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ96 46 258 0.0337 0.0060 0.2363Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 438Appendix 25 (continued) Individual Relative Organ WeightsRecovery GroupsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %1(M) 97 57 409 0.0149 0.4817 0.3691 0.2565 0.5100 3.0142 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ98 57 397 0.0140 0.4958 0.3812 0.2570 0.5508 2.8753 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ99 57 396 0.0211 0.5507 0.3964 0.2301 0.5137 3.1847 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ100 57 429 0.0166 0.5014 0.3353 0.2518 0.5092 3.1805 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ101 57 358 0.0190 0.5843 0.4431 0.2532 0.5871 2.8417 0.0026Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 439Appendix 25 (continued) Individual Relative Organ WeightsRecovery Groups(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %1(M) 97 57 0.1449 0.4359 0.1522 0.7881 0.1174 0.0059ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ98 57 0.1536 0.5101 0.1746 0.9553 0.1098 0.0059ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ99 57 0.1397 0.5269 0.1621 0.8746 0.0979 0.0054ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ100 57 0.1779 0.5512 0.1332 0.8620 0.1124 0.0053ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ101 57 0.1381 0.6484 0.1884 1.0367 0.0913 0.0060Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 440Appendix 25 (continued) Individual Relative Organ WeightsRecovery GroupsGroup Animal Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver PituitaryNumber g % % % % % % %4(M) 107 57 368 0.0179 0.5303 0.4330 0.3510 0.6332 3.3280 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ108 57 393 0.0228 0.5522 0.4049 0.2292 0.6213 2.7532 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ109 57 336 0.0136 0.5625 0.3865 0.2547 0.4755 3.0717 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ110 57 347 0.0199 0.5464 0.4461 0.2946 0.6509 3.2048 0.0039ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ111 57 405 0.0151 0.4865 0.3803 0.2621 0.7183 3.0694 0.0020Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 441Appendix 25 (continued) Individual Relative Organ WeightsRecovery Groups(continued)Group Animal Relative Relative Relative Relative Relative Relative(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus ThyroidNumber % % % % % %4(M) 107 57 0.1367 0.6141 0.2095 0.8492 0.0686 0.0065ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ108 57 0.1398 0.6261 0.1565 0.9635 0.0872 0.0061ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ109 57 0.1040 0.5067 0.1400 0.9694 0.0949 0.0066ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ110 57 0.1701 0.4892 0.1637 1.0039 0.1174 0.0050ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ111 57 0.1049 0.5529 0.1516 0.8382 0.0730 0.0051Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 442Appendix 25 (continued) Individual Relative Organ WeightsRecovery GroupsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %1(F) 102 57 218 0.0383 0.7541 0.3594 0.5321 3.2397 0.0320 0.0070 0.1778 0.1234 0.0078 0.2127ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ103 57 228 0.0354 0.7923 0.3115 0.5812 3.3638 0.0521 0.0075 0.2518 0.1334 0.0114 0.2479ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ104 57 231 0.0391 0.8162 0.4091 0.6554 3.7288 0.0535 0.0086 0.2845 0.1368 0.0097 0.3629ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ105 57 212 0.0396 0.8622 0.3194 0.6953 3.1999 0.0438 0.0083 0.2045 0.1492 0.0087 0.3106ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ106 57 203 0.0299 0.8722 0.3566 0.6635 3.0859 0.0559 0.0067 0.2562 0.1111 0.0077 0.3014Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/dayHarlan Study Number:41204605Report Page 443Appendix 25 (continued) Individual Relative Organ WeightsRecovery GroupsGroup Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid UterusNumber g % % % % % % % % % % %4(F) 112 57 221 0.0347 0.7821 0.3300 0.5624 3.5306 0.0383 0.0094 0.1852 0.1517 0.0085 0.3934ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ113 57 233 0.0402 0.7365 0.2859 0.5648 3.3743 0.0321 0.0085 0.1759 0.0996 0.0065 0.3232ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ114 57 222 0.0377 0.8769 0.3270 0.6445 3.3679 0.0481 0.0073 0.2205 0.1294 0.0095 0.2343ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ115 57 205 0.0459 0.8983 0.3351 0.6938 3.5383 0.0539 0.0080 0.2341 0.1308 0.0100 0.5880ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ116 57 223 0.0296 0.9029 0.3204 0.6376 3.7151 0.0496 0.0116 0.2092 0.1572 0.0043 0.2466Dose Levels: Group 1 ƒ 0 (Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 60 mg/kg bw/day Group 4 ƒ 120 mg/kg bw/day

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# Appendix 26 Histopathology Phase Report

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# Appendix 26 (continued) Histopathology Phase Report

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# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 572



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 573



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 574



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 575



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 576



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 577



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 578



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 579



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 580



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 581



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 582



# Appendix 26 (continued) Histopathology Phase Report

# Harlan Study Number: 41204605 Report Page 583



# Appendix 27 Analytical Investigations



# 1 MATERIALS AND METHODS

1.1 Introduction

The test item concentration in the test samples was determined by high performance liquid

chromatography with UV detection (HPLC/UV) using an external standard technique. The test

item gave a chromatographic prof ile consisting of a single peak.



# 1.2 Test Item

The test item described in the main part of this study was also used as the analytical standard.



# 1.3 Analytical Procedure

1.3.1 Preparation of Standard Solutions



# Stock solutions of test item in acetonitrile were prepared for external standard calibration. An

aliquot, 100 mg (nominal) of test item was accurately weighed into a 100 mL volumetric flask

and brought to volume with acetonitrile to yiel d a solution with a concentration of 1 mg/mL.

Aliquots of this stock standard solution were used to prepare working standard solutions in

acetonitrile with a concentration of 0.1 mg/mL.

On each occasion standard solutions derived fro m two stock standard solutions were used for

calculation.

1.3.2 Analysis of Samples



# The formulations received were extracted with ace tonitrile. An aliquot of test item formulation

was accurately weighed into a volumetric flask and brought to volume with acetonitrile, this was

then ultra-sonicated for 15 minutes and centrifuged at 4500 rpm for 10 minutes. Where

necessary, sample solutions were further dilu ted with acetonitrile to achieve the working

concentration.

1.3.3 Preparation of Accuracy Samples



# Samples of Arachis Oil BP were accurately fortif ied with known amounts of test item equivalent

to the lowest and highest anticipated dose concentrations. These samples were then prepared for

analysis as the test samples in section 1.3.2.

# Harlan Study Number: 41204605 Report Page 584



# Appendix 27 (conti nued) Analytical Investigations

1.3.4 Preparation of Linearity Standards



# A range of standard solutions were prepared in acetonitrile from a stock solution of 1 mg/mL by

serial dilution covering the concentration range 0 to 0.1511 mg/mL.

1.3.5 Instrumental Setup



# HPLC : Agilent Technologies 1200, incorporating autosampler

and workstation

Column : Luna 5μ C8 (250 x 4.6 mm id) at 40 oC

Flow-rate : 1 mL/min

UV detector wavelength : 231 nm

Injection volume : 10  

# L

Retention time : ~ 12 mins



# 1.4 Study Samples and Storage

Representative samples were dispatched to the analytical laboratories internally (under ambient

conditions) and stored at room temperature until analysis.

# Harlan Study Number: 41204605 Report Page 585



# Appendix 27 (conti nued) Analytical Investigations



# 2 RESULTS

2.1 Validation of Analytical Method

2.1.1 Specificity



# The control dose samples and a solvent blank did not significantly affect the chromatogram at

the retention time of the test item whose area changed accordingly with known concentration.

2.1.2 Linearity



# The linearity of the analytical system used for sample analyses was demonstrated to have a good

relationship between peak areas measured and wo rking standard concentrations. The regression

coefficient calculated was found to be 1.000. The linearity is presented in Figure 5.

2.1.3 Accuracy



# The fortified samples of Arachis Oil BP were f ound to have a recovery value of ± 10% of the

fortification. The results are presented in Table 24.

2.1.4 Test Item Formulations



# The formulations investigated during the study were found to comprise test item in the range of

98% to 104% and, thus, the required content limit of ±10% with reference to the nominal content

was met.

In addition, the test item was found to be stable in the formulations when kept for 16 days in a

refrigerator (4  

# C) due to results which met the variation limit of 10% from the time-zero mean.

In conclusion, the results indicate the accurate use of the test item and Arachis Oil BP as vehicle

during this study. The formulations were found to be homogeneously prepared and sufficient

formulation stability under storage conditions was approved. Results are presented in Table 25

to Table 26.

The test item peak was assigned in sample chromatograms by comparison to that of working

standards. In blank sample chromatograms no peak appeared at the retention time of test item

and, therefore, the absence of the test item in the vehicle control samples was confirmed.

Examples of chromatograms are shown in Figure 6 to Figure 9.

# Harlan Study Number: 41204605 Report Page 586



# Appendix 27 (conti nued) Analytical Investigations



# 3 DISCUSSION

The detection system was found to have acceptable linearity. The analytical procedure had

acceptable recoveries of test item in the vehicle. The method of analysis was validated and

proven to be suitable for use.

# Harlan Study Number: 41204605 Report Page 587



# Appendix 27 (conti nued) Analytical Investigations



# TABLES

Table 24 Results of Accuracy Analysis

(Rounded results presented are based on calculations with exact data)

Fortification

(mg/g) Concentration

Found (mg/g) Recovered

(%) Mean Recovery

(%)



# 3.51 3.50 100 99

3.78 3.75 99

249 256 103 103

247 257 104

Table 25 Results of Formulation Analysis

(Rounded results presented are based on calculations with exact data)

Week Number Nominal Concentration

(mg/mL) Concentration Found

(mg/mL) (expressed as % of

nominal)



# 1 0 ND -

7.5 7.51 100

15 15.3 102

30 30.8 103

2 0 ND -

7.5 7.63 102

15 15.6 104

30 31.3 104

3 0 ND -

7.5 7.34 98

15 15.0 100

30 30.2 101

4 0 ND -

7.5 7.37 98

15 14.9 99

30 30.3 101

ND = none detected

- = not applicable

# Harlan Study Number: 41204605 Report Page 588



# Appendix 27 (conti nued) Analytical Investigations

Table 25 (continued) Results of Formulation Analysis



# 5 0 ND -

7.5 7.53 100

15 15.1 101

30 30.6 102

6 0 ND -

7.5 7.51 100

15 15.2 101

30 30.6 102

7 0 ND -

7.5 7.41 99

15 15.2 101

30 30.5 102

Table 26 Results of Formulation Stability Analysis

(Rounded results presented are based on calculations with exact data)

Nominal

Concentration

(mg/mL) Concentration Found

Initially (mg/mL) Concentration Found After Storage for 16

Days

(mg/mL) (expressed as % of

initial)



# 3.75 3.88 3.86 99

250 258 258 100

Results of Formulation Homogeneity Analysis



# The test item formulations were deem ed homogeneous by visual inspection.

ND = none detected

- = not applicable

# Harlan Study Number: 41204605 Report Page 589



# Appendix 27 (conti nued) Analytical Investigations



# FIGURES

Figure 5 Linearity

# Harlan Study Number: 41204605 Report Page 590



# Appendix 27 (conti nued) Analytical Investigations

Figure 6 Chromatogram of Calibration Solution

Minutes 0 2 4 6 8 10 12 14mAU



# 0 50 100 150 200 250 300mAU



# 0 50 100 150 200 250 30011.725 

# VWD: Signal A, 231 nm

Standard B



# Retention Time

# Harlan Study Number: 41204605 Report Page 591



# Appendix 27 (conti nued) Analytical Investigations

Figure 7 Chromatogram of Control Sample

Minutes 0 2 4 6 8 10 12 14mAU



# 0 50 100 150 200 250 300mAU



# 0 50 100 150 200 250 300 VWD: Signal A, 231 nm

Control



# Retention Time

# Harlan Study Number: 41204605 Report Page 592

Minutes 0 2 4 6 8 10 12 14mAU



# 0 50 100 150 200 250 300mAU



# 0 50 100 150 200 250 30011.803 

# VWD: Signal A, 231 nm

7.5mg_ml



# Retention Time 

# Appendix 27 (conti nued) Analytical Investigations

Figure 8 Chromatogram of Test Sample (low level)

# Harlan Study Number: 41204605 Report Page 593



# Appendix 27 (conti nued) Analytical Investigations

Figure 9 Chromatogram of Test Sample (high level)

Minutes 0 2 4 6 8 10 12 14mAU



# 0 50 100 150 200 250 300mAU



# 0 50 100 150 200 250 30011.730 

# VWD: Signal A, 231 nm

30mg_ml



# Retention Time

# Harlan Study Number: 41204605 Report Page 594



# Appendix 28 Study Plan

# Harlan Study Number: 41204605 Report Page 595



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 596



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 597



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 598



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 599



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 600



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 601



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 602



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 603



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 604



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 605



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 606



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 607



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 608



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 609



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 610



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 611



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 612



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 613



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 614



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 615



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 616



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 617



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 618



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 619



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 620



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 621



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 622



# Appendix 28 (continued) Study Plan

# Harlan Study Number: 41204605 Report Page 623



# Appendix 29 Histology Processing Phase Test Site Quality Assurance Statement

# Harlan Study Number: 41204605 Report Page 624



# Appendix 30 Histology Processing Phase Test Site Statement of Compliance

# Harlan Study Number: 41204605 Report Page 625



# Appendix 31 Histology Processing Phase Test Site Statement of GLP Compliance

# Harlan Study Number: 41204605 Report Page 626



# Appendix 32 Certificates of Analysis of Diet Used

# Harlan Study Number: 41204605 Report Page 627



# Appendix 32 (continued) Certificates of Analysis of Diet Used

# Harlan Study Number: 41204605 Report Page 628



# Appendix 32 (continued) Certificates of Analysis of Diet Used

# Harlan Study Number: 41204605 Report Page 629



# Appendix 32 (continued) Certificates of Analysis of Diet Used

# Harlan Study Number: 41204605 Report Page 630



# Appendix 33 Laboratory Methods

UNITS

HAEMATOLOGY

Parameters measured on potassium EDTA - treated blood:

Haemoglobin (Hb) - estimated by measurem ent of cyanmethaemoglobin using the

A c 

# .T5 Diff analyser g/dl

Total erythrocyte count (RBC) - estimated by the A c 

# .T5 Diff analyser 10 12 

# /l

Haematocrit (Hct) - derived from MCV and RBC by the A c 

# .T5 Diff analyser %

Mean Corpuscular Haemoglobin (MCH) - derived from the Hb concentration and RBC by the

A c 

# .T5 Diff analyser pg

Mean Corpuscular Volume (MCV) - estimated by the A c 

# .T5 Diff analyser fl

Mean Corpuscular Haemoglobin Concentration (MCHC) - derived from Hb concentration, RBC

and MCV by the A c 

# .T5 Diff analyser g/dl

Total leucocyte count (WBC) - estimated by the A c 

# .T5 Diff analyser 10 9 

# /l

Differential leucocyte count - determined by vi sual assessment of May-Grünwald-Giemsa

stained blood film: 10 9 

# /l

Neutrophils (Neut)

Lymphocytes (Lymph)

Monocytes (Mono)

Eosinophils (Eos)

Basophils (Bas)

Platelet count (PLT) - estimated by the A c 

# .T5 Diff analyser 10 9 

# /l

Reticulocyte count (Retics) - Methylene Blue stained blood film prepared but count not performed %

Parameters measured on citrate-treated blood:

Prothrombin time (CT) - estimated by ‘Innovin’ Dade Siemens reagent kit No. B4212-50 and Bio

Mérieux Option 4 coagulometer secs

Activated partial thromboplastin time (APTT) - estimated by ‘Actin FS’ Dade Siemens reagent kit

No. B4218-20 and Bio Mérieux Option 4 coagulometer secs

# Harlan Study Number: 41204605 Report Page 631



# Appendix 33 (continued) Laboratory Methods

UNITS

BLOOD CHEMISTRY

Parameters measured on lithium heparin treated blood:

Urea - estimated by ILab reagent kit No. 00182554400 and

ILab 600 auto-analyser mg/dl

Glucose - estimated by ILab reagent kit No. 0018250840 and

ILab 600 auto-analyser mg/dl

Total protein (Tot.Prot.) - estimated by ILab reagent kit No. 0018251440

and ILab 600 auto-analyser g/dl

Albumin - estimated by ILab reagent kit No. 0018250040 and ILab 600 auto-analyser g/dl

Albumin/Globulin (A/G) ratio =



# albumin protein total albumin



Sodium (Na+) - estimated by ISE electrode No. 0018262400 and ILab 600 auto-analyser mmol/l

Potassium (K+) - estimated by ISE electrode No. 0018263500 and ILab 600 auto-analyser mmol/l

Chloride (Cl-) - estimated by ISE electrode No. 0018263600 and ILab 600 auto-analyser mmol/l

Calcium (Ca++) - estimated by ILab reagent kit No. 0018250340

and ILab 600 auto-analyser mmol/l

Inorganic phosphorus (P) - estimated by ILab reagent kit No. 0018251240

and ILab 600 auto-analyser mmol/l

Aspartate aminotransferase (ASAT) - estimated by ILab reagent kit No. 0018257540 and ILab

600 auto-analyser IU/l

Alanine aminotransferase (ALAT) - estimated by ILab reagent kit No. 0018257440

and ILab 600 auto-analyser IU/l

Alkaline phosphatase (AP) - estimated by ILab reagent kit No. 0018259640

and ILab 600 auto-analyser IU/l

Creatinine (Creat) - estimated by ILab reagent kit No. 0018255540

and ILab 600 auto-analyser mg/dl

Total cholesterol (Chol) - estimated by ILab reagent kit No. 0018250540

and ILab 600 auto-analyser mg/dl

Total bilirubin (Bili) - estimated by ILab reagent k it No. 0018258340

and ILab 600 auto-analyser mg/dl

Bile acids (Bile) - estimated by Randox Kit No. B13863 and ILab 600 auto-analyser μ mol/l

# Harlan Study Number: 41204605 Report Page 632



# Appendix 33 (continued) Laboratory Methods

URINALYSIS

Specific gravity – measured directly by Refractometer (Atago Co., Tokyo, Japan)

pH, protein, glucose, ketones, urobilinogen, bilirubin and blood – estimated by Cobas, Roche Combur 9 

# Test

Strips

# Harlan Study Number: 41204605 Report Page 633



# Appendix 34 Normal Ranges fo r Reproductive Parameters in the Pregnant and Lactating

Female Wistar HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. APPROXIMATE AGE: Fourteen to Nineteen weeks

UPDATED: November 2011

Range * No. of Animals

MATING & GESTATION

Pre-Coital Interval (Days) 1 - 5 209

( 2 ) ( 1 )

Gestation Lengths (Days) 21.8 - 23.5 213

( 22 .7) (0. 4 )

FOOD CONSUMPTIONS (g/rat/day)

Gestation Days 0 - 7 15 - 23 208

( 1 9) ( 2 )

Gestation Days 7 - 14 17 - 25 208

( 21 ) ( 2 )

Gestation Days 14 - 20 19 - 27 206

( 2 3) ( 2 )

Lactation Days 1 - 4 18 - 36 196

( 2 7) ( 4 )

BODY WEIGHT CHANGE (g)

Gestation Days 0 - 7 13 - 35 208

( 24 ) ( 5 )

Gestation Days 7 - 14 16 - 36 180

( 26 ) ( 5 )

Gestation Days 14 - 20 44 - 81 179

( 63 ) (9)

Lactation Days 1 - 4 -3 - 24 209

( 10 ) (7)

CORPORA LUTEA &

IMPLANTATIONS

Corpora Lutea (Number) 10 - 19 208

( 15 ) ( 2 )

Implantations (Number) 9 - 18 208

( 13 ) ( 2 )

Pre-Implantation loss (%) 0 - 27 200

( 8 ) ( 10 )

Post-Implantation loss (%) 0 - 24 207

(7) (8)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 634



# Appendix 35 Normal Ranges for Offspr ing Parameters in the Wistar HanTM:

RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. AGE: 0 – 4 Days

UPDATED: November 2011

OFFSPRING DATA Range * No. of Animals

SURVIVAL INDICES (%)

Live Birth Indices 97 - 100 214

(100) (1)

Viability on Day 4 92 - 100 214

(99) (4)

LITTER SIZE

Litter size at birth 7 - 17 213

(12) (3)

Litter size at Day 1 8 - 17 210

(12) (2)

Litter size at Day 4 7 - 17 209

(12) (2)

LITTER WEIGHT (g)

Litter weight at Day 1 48.2 - 93.1 209

(70.6) (11.2)

Litter weight at Day 4 71.0 - 131.7 208

(101.3) (15.2)

SEX RATIOS

% Males at Day 1 24 - 76 203

(50) (13)

% Males at Day 4 24 - 76 203

(50) (13)

OFFSPRING BODY WEIGHTS (g)

Male body Weights at Day 1 4.8 - 7.0 208

(5.9) (0.5)

Male body Weights at Day 4 6.6 - 10.8 209

(8.7) (1.0)

Female body Weights at Day 1 4.6 - 6.7 206

(5.7) (0.5)

Female body Weight at Day 4 6.5 - 10.1 200

(8.3) (0.9)

DEVELOPMENTAL & REFLEX

MARKERS

Surface Righting (%) 61.9 - 100.0 213

(87.5) (12.8)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 635



# Appendix 36 Normal Ranges for Haematological and Blood Chemical Values in the Wistar

HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd.

UPDATED: November 2011 APPROXIMATE AGE: Eighteen weeks

PHASE: Prior to Termination

HAEMATOLOGY Male Female

Range* No. of

Animals Range* No. of

Animals

Hb (g/dl) 15.4 - 17.2 70 11.7 - 14.7 71

(16.3) (0.4) (13.2) (0.8)

RBC (10 12 

# /l) 8.52 - 9.54 62 6.25 - 7.70 67

(9.03) (0.25) (6.98) (0.36)

Hct (%) 44.9 - 50.4 69 35.2 - 43.3 71

(47.6) (1.4) (39.2) (2.0)

MCH (pg) 17.0 - 19.3 67 17.7 - 20.1 69

(18.1) (0.6) (18.9) (0.6)

MCV (fl) 50.5 - 55.5 66 53.1 - 59.2 66

(53.0) (1.2) (56.1) (1.5)

MCHC (g/dl) 32.2 - 35.9 70 32.1 - 35.0 69

(34.0) (0.9) (33.6) (0.7)

WBC (10 9 

# /l) 4.8 - 9.8 72 2.3 - 8.7 70

(7.3) (1.2) (5.5) (1.6)

Neut (10 9 

# /l) 0.29 - 1.26 62 0.45 - 2.84 67

(0.78) (0.24) (1.64) (0.60)

Lymph (10 9 

# /l) 3.97 - 8.70 73 1.49 - 6.28 71

(6.33) (1.18) (3.88) (1.20)

Mono (10 9 

# /l) 0.00 - 0.00 75 0.00 - 0.00 70

(0.00) (0.00) (0.00) (0.00)

Eos (10 9 

# /l) 0.00 - 0.13 65 0.00 - 0.02 66

(0.05) (0.04) (0.00) (0.01)

Bas (10 9 

# /l) 0.00 75 0.00 75

CT (secs) 8.7 - 10.8 60 8.0 - 10.1 68

(9.8) (0.5) (9.1) (0.5)

APTT (secs) 12.8 - 18.6 70 10.9 - 19.7 69

(15.7) (1.4) (15.3) (2.2)

PLT (10 9 

# /l) 464 - 660 68 570 - 1043 73

(562) (49) (807) (118)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 636



# Appendix 36 (continued) Normal Ranges for Haematological and Blood Chemical

Values in the Wistar HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. APPROXIMATE AGE: Eighteen weeks

UPDATED: N ovember 2011 PHASE: Prior to Termination

BLOOD CHEMISTRY Male Female

Range* No. of

Animals Range* No. of

Animals

Urea ( m g /dl ) 35 - 58 71 37 - 63 67

( 46 ) ( 6 ) ( 50 ) ( 7 )

Glucose ( m g /dl ) 118 - 169 64 97 - 149 66

( 143 ) ( 13 ) ( 123 ) ( 13 )

Tot.Prot. (g /dl ) 6.38 - 7.54 65 5.65 - 6.90 67

( 6.96 ) ( 0.29 ) ( 6.27 ) ( 0.31 )

Albumin (g /dl ) 3.4 - 4.2 73 3.2 - 4.0 71

( 3.8 ) ( 0.2 ) ( 3.6 ) ( 0.2 )

A/G Ratio 1.04 - 1.35 66 1.11 - 1.65 72

( 1.20 ) ( 0.08 ) ( 1.38 ) ( 0.14 )

N a+ ( mmol/l ) 145 - 155 68 144 - 152 68

( 150 ) ( 2 ) ( 148 ) ( 2 )

K+ ( mmol/l ) 3.90 - 4.92 59 3.70 - 4.90 70

( 4.41 ) ( 0.25 ) ( 4.30 ) ( 0.30 )

Cl- ( mmol/l ) 98 - 107 72 100 - 108 74

( 102 ) ( 2 ) ( 104 ) ( 2 )

Ca++ ( mmol/l ) 2.32 - 3.00 70 2.34 - 2.85 67

( 2.66 ) ( 0.17 ) ( 2.60 ) ( 0.13 )

P ( mmol/l ) 1.2 - 2.7 70 0.2 - 1.7 75

( 1.9 ) ( 0.4 ) ( 0.9 ) ( 0.4 )

ASAT ( IU/l ) 56 - 91 65 55 - 92 64

( 73 ) ( 9 ) ( 73 ) ( 9 )

ALAT ( IU/l ) 36 - 67 61 31 - 87 66

( 52 ) ( 8 ) ( 59 ) ( 14 )

AP ( IU/l ) 80 - 289 68 84 - 240 42

( 184 ) ( 52 ) ( 162 ) ( 39 )

Creat ( m g /dl ) 0.56 - 0.87 71 0.59 - 0.81 65

( 0.71 ) ( 0.08 ) ( 0.70 ) ( 0.06 )

Chol ( m g /dl ) 56 - 102 68 51 - 78 58

( 79 ) ( 12 ) ( 64 ) ( 7 )

Bili ( m g /dl ) 0.00 - 0.16 65 0.00 - 0.11 75

( 0.08 ) ( 0.04 ) ( 0.06 ) ( 0.03 )

Bile Acids (μ mol/l ) 0.0 - 13.9 33 4.6 - 21.0 31

( 6.9 ) ( 3.5 ) ( 12.8 ) ( 4.1 )

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 637



# Appendix 37 Normal Ranges for Absolute and Body Weight-Relative Organ Weight

Values in the Wistar HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. APPROXIMATE AGE: Eighteen to Twenty Weeks

UPDATED: November 2011

MALE ORGAN WEIGHTS ABSOLUTE WEIGHT (g) RELATIVE TO TERMINAL BODY

WEIGHT (%)

Range (g)* No. of

Animals Range (%)* No. of

Animals

Adrenals 0.0420 - 0.0809 140 0.0104 - 0.0210 150

(0.0614) (0.0097) (0.0157) (0.0027)

Brain 1.8435 - 2.1774 150 0.4340 - 0.5724 151

(2.0105) (0.0835) (0.5032) (0.0346)

Epididymides 1.1566 - 1.6432 222 0.2896 - 0.4105 210

(1.3999) (0.1216) (0.3501) (0.0302)

Heart 1.0013 - 1.4852 139 0.2562 - 0.3723 143

(1.2433) (0.1210) (0.3142) (0.0290)

Kidneys 1.8425 - 2.7070 162 0.4519 - 0.6867 174

(2.2747) (0.2161) (0.5693) (0.0587)

Liver 10.0646 - 15.2853 163 2.7634 - 3.5536 163

(12.6750) (1.3052) (3.1585) (0.1975)

Pituitary 0.0074 - 0.0120 78 0.0020 - 0.0029 73

(0.0097) (0.0012) (0.0025) (0.0002)

Prostate 0.3731 - 0.7418 85 0.0925 - 0.1918 89

(0.5575) (0.0922) (0.1421) (0.0248)

Seminal vesicles 1.5821 - 2.7187 87 0.3940 - 0.6642 84

(2.1504) (0.2841) (0.5291) (0.0676)

Spleen 0.5302 - 0.8397 150 0.1361 - 0.2054 151

(0.6850) (0.0774) (0.1708) (0.0173)

Testes 3.0354 - 4.2231 224 0.7534 - 1.0558 213

(3.6292) (0.2969) (0.9046) (0.0756)

Thymus 0.2866 - 0.6494 149 0.0749 - 0.1634 151

(0.4680) (0.0907) (0.1191) (0.0221)

Thyroid/Parathyroid 0.0107 - 0.0286 159 0.0029 - 0.0070 157

(0.0196) (0.0045) (0.0049) (0.0010)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 638



# Appendix 37 (continued) Normal Ranges for Absolute and Body Weight-Relative Organ

Weight Values in the Wistar HanTM:RccHanTM: WIST Strain

Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. APPROXIMATE AGE: Eighteen Weeks

UPDATED: November 2011

LACTATING FEMALE ORGAN

WEIGHTS ABSOLUTE WEIGHT (g) RELATIVE TO TERMINAL

BODY WEIGHT (%)

Range (g)* No. of

Animals Range (%)* No. of

Animals

Adrenals 0.0654 - 0.1085 132 0.0259 - 0.0407 133

(0.0870) (0.0108) (0.0333) (0.0037)

Brain 1.7469 - 1.9906 130 0.6378 - 0.7871 137

(1.8687) (0.0609) (0.7125) (0.0373)

Heart 0.7786 - 1.1823 128 0.3065 - 0.4480 127

(0.9805) (0.1009) (0.3772) (0.0354)

Kidneys 1.2887 - 1.7435 139 0.4980 - 0.6713 150

(1.5161) (0.1137) (0.5846) (0.0433)

Liver 8.5995 - 12.9085 147 3.5429 - 4.6890 145

(10.7540) (1.0772) (4.1159) (0.2865)

Ovaries 0.0822 - 0.1410 134 0.0336 - 0.0519 131

(0.1116) (0.0147) (0.0427) (0.0046)

Pituitary 0.0109 - 0.0171 69 0.0042 - 0.0066 71

(0.0140) (0.0015) (0.0054) (0.0006)

Spleen 0.4475 - 0.7611 124 0.1797 - 0.2755 121

(0.6043) (0.0784) (0.2276) (0.0240)

Thymus 0.1497 - 0.3320 134 0.0607 - 0.1201 128

(0.2409) (0.0456) (0.0904) (0.0148)

Thyroid/Parathyroid 0.0095 - 0.0226 136 0.0037 - 0.0085 134

(0.0160) (0.0033) (0.0061) (0.0012)

Uterus 0.4968 - 0.8480 126 0.2005 - 0.3144 114

(0.6724) (0.0878) (0.2575) (0.0285)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# Harlan Study Number: 41204605 Report Page 639



# Appendix 38 Certificate of Analysis of the Test Item

# Harlan Study Number: 41204605 Report Page 640



# Appendix 39 Monitoring Authorit y Statement of GLP Compliance