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# SODIUM GLUCOHEPTONATE (EC 250-480-2)

ORAL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH

REPRODUCTION/DEVELOPMENTAL TOXICITY

SCREENING TEST IN THE RAT (OECD 422)

RE-ISSUED REPORT

PROJECT NUMBER: 41104692R

AUTHORS: L A McRae

P Watson

STUDY SPONSOR: TEST FACILITY:

Harcros Chemicals Inc.

3452 Corporate Drive

Dalton GA 30720

UNITED STATES OF AMERICA Harlan Laboratories Ltd.

Shardlow Business Park

Shardlow

Derbyshire

DE72 2GD

UK

Telephone: +44 (0) 1332 792896

Facsimile: +44 (0) 1332 799018

TEST SITES:

Histology Processing:

Propath UK Ltd

Willow Court

Netherwood Road

Rotherwas

Hereford

HR2 6JU

Histopathology Examination:

Peter Millar Associates

3 Queen Charlotte Lane

Edinburgh

SCOTLAND

EH6 6AY

United Kingdom

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# RESPONSIBLE PERSONNEL

The following scientific and supervisory personnel were involved in the study:

ANALYTICAL CHEMISTRY

P Watson

Harlan Laboratories Ltd., Shardlow, UK

CLINICAL PATHOLOGY

J Kemp

Harlan Laboratories Ltd., Shardlow, UK

ANIMAL HEALTH

P Highton

Harlan Laboratories Ltd., Shardlow, UK

HISTOLOGY PROCESSING

Principal Investigator: N Fower

Propath UK Ltd., Hereford, UK

HISTOPATHOLOGY EXAMINATION

Principal Investigator: P Millar

Peter Millar Associates Ltd., Edinburgh, UK

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# CONTENTS

QUALITY ASSURANCE REPORT 3

GLP COMPLIANCE STATEMENT 5

AUTHENTICATION 7

RESPONSIBLE PERSONNEL 9

CONTENTS 11

SUMMARY 15

1. INTRODUCTION 19

2. TEST ITEM AND EXPERIMENTAL PREPARATION 20

2.1 Description, Identification and Storage Conditions 20

2.2 Preparation of Test Item 20

3. METHODS 20

3.1 Animals and Animal Husbandry 20

3.2 Procedure 22

3.3 Observations 23

3.4 Evaluation of Data 30

4. DEVIATIONS FROM STUDY PLAN 33

5. ARCHIVES 33

6. RESULTS 35

6.1 Adult Responses 35

6.2 Reproductive Performance 37

6.3 Litter Responses 38

6.4 Laboratory Investigations 40

6.5 Pathology 41

7. DISCUSSION 43

8. CONCLUSION 43

9. REFERENCES 44

TABULAR SUMMARY REPORT OF EFFECTS ON REPRODUCTION/

DEVELOPMENT 45

KEY TO TABLES AND APPENDICES 46

KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS AND SENSORY REACTIVITY TESTS 47

TABLES 53

Table 1 Summary of Reproductive Performance - Group Values 54

Table 2 Summary Incidence of Daily Clinical Observations 55

Table 3 Summary Incidence of Behavioural Assessments (Observations) 58

Table 4 Group Mean Behavioural Assessments (Scores) 62

Table 5 Group Mean Functional Test Values and Standard Deviations 76

Table 6 Group Mean Sensory Reactivity Assessments (Scores) 78

Table 7 Group Mean Body Weight Values 80

Table 8 Group Mean Body Weight Gains 83

Table 9 Group Mean Food Consumptions 86

Table 10 Food Efficiency 89

Table 11 Group Mean Daily Water Consumptions 91

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# Table 12 Summary Incidence of Mating Performance, Fertility and Gestation

Lengths 93

Table 13 Group Mean Litter Size and Litter Weights 94

Table 14 Group Mean Implantation Losses and Survival Indices Values 95

Table 15 Group Mean Sex Ratio Values 96

Table 16 Summary Incidence of Clinical Signs for Offspring 97

Table 17 Group Mean Reflexological Responses for Offspring 98

Table 18 Group Mean Haematological Values 99

Table 19 Group Mean Blood Chemical Values 103

Table 20 Summary Incidence of Offspring Necropsy Findings 107

Table 21 Summary Incidence of Necropsy Findings 108

Table 22 Group Mean Organ Weights with Corresponding Relative

(% of Body Weight) Organ Weights 110

FIGURES 115

Figure 1 Group Mean Body Weights - Males 116

Figure 2 Group Mean Body Weights - Females 117

Figure 3 Group Mean Food Consumption - Males 119

Figure 4 Group Mean Food Consumption - Females 120

APPENDICES 121

Appendix 1 Individual Daily Clinical Observations 122

Appendix 2 Individual Behavioural Assessments (Observations) 268

Appendix 3 Individual and Group Mean Behavioural Assessments (Scores) 276

Appendix 4 Individual and Group Mean Functional Test Values (Grip Strength) 332

Appendix 5 Individual and Group Mean Functional Test Values (Motor Activity) 340

Appendix 6 Individual and Group Mean Sensory Reactivity Assessments 348

Appendix 7 Individual and Group Mean Body Weights 356

Appendix 8 Individual and Group Mean Body Weight Gains 368

Appendix 9 Individual and Group Mean Food Consumption Values for Females

Following Mating and During Lactation 380

Appendix 10 Individual Mating Performance, Fertility and Gestation Lengths 384

Appendix 11 Individual and Group Mean Litter Size and Litter Weights 388

Appendix 12 Individual and Group Mean Implantation Losses and Survival Indices 392

Appendix 13 Individual and Group Mean Sex Ratio Values for Offspring 396

Appendix 14 Individual Clinical Signs for Offspring 400

Appendix 15 Individual and Group Mean Reflexological Responses for Offspring 404

Appendix 16 Individual Haematological Values 408

Appendix 17 Individual Coagulation Values 416

Appendix 18 Individual Blood Chemical Values 424

Appendix 19 Individual Bile Acid Values 432

Appendix 20 Individual Necropsy Findings for Offspring 440

Appendix 21 Individual Necropsy Findings 444

Appendix 22 Individual Organ Weights 452

Appendix 23 Individual Relative Organ Weights 460

Appendix 24 Histopathology Phase Report 472

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# Appendix 25 Chemical Analysis of Test Item Formulations, Methods and Results 591

Appendix 26 Study Plan 596

Appendix 27 Histology Processing Phase Test Site Quality Assurance Statement 618

Appendix 28 Histology Processing Phase Test Site Statement of Compliance 619

Appendix 29 Histology Processing Phase Test Site Statement of GLP Compliance 620

Appendix 30 Statement of GLP Compliance in Accordance with

Directive 2004/9/EC 621

Appendix 31 Certificates of Analysis of Diet Used 622

Appendix 32 Laboratory Methods 625

Appendix 33 Normal Ranges for Reproductive Parameters in the Pregnant and

Lactating Female Wistar Han TM:RccHanTM:WIST Strain Rat 627

Appendix 34 Normal Ranges for Offspring Parameters in the Wistar HanTM:

RccHanTM:WIST Strain Rat 628

Appendix 35 Normal Ranges for Haematological and Blood Chemical Values

in the Wistar HanTM:RccHanTM:WIST Strain Rat 629

Appendix 36 Normal Ranges for Functional Performance Assessments

in the Wistar HanTM:RccHanTM:WIST Strain Rat 631

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

Values in the Wistar HanTM:RccHanTM:WIST Strain Rat 632

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# Sodium Glucoheptonate (EC 250-480-2):

ORAL (GAVAGE) COMBINED REPEAT DOSE TOXICITY STUDY WITH

REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT

(OECD 422)



# 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 Reproduction/

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

This study was also designed to be compatible with the Commission Regulation (EC) No.

440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No.

1907/2006 of the European Parliament and of the Council on the Registration,

Evaluation, Authorisation and Restriction of Chemicals (REACH).

Methods. The test item was administered by gavage to three groups, each of twelve

male and twelve female Wist ar HanTM:RccHanTM:WIST strain rats, for up to eight weeks

(including a two week pre-pairing phase, pairing, gestation and early lactation for

females), at dose levels of 30, 300 and 1000 mg/kg bw/day (incorporating a test item

correction factor for 50.5% w/w purity minus 49.5% w/w test item water content). A

control group of twelve males and twelve females was dosed with vehicle alone (Distilled

water).

Clinical signs, behavioural assessments, body weight change and food and water

consumption were monitored during the study.

Pairing of 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 observations were performed on all surviving

offspring, together with litter size and offspring weights and assessment of surface

righting reflex.

Extensive functional observations were performed on five selected males from each

dose group after the completion of the pairing phase, and for five selected parental

females from each dose group on Day 4 post partum . Haematology and blood chemistry

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# were evaluated prior to termination on five selected males and females from each dose

group.

Adult 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.

Results.

Adult Responses:

Mortality. There were no unscheduled deaths in this study.

Clinical Observations. No toxicologically significant clinical observations were detected.

Behavioural Assessment. There were no treatment-related changes in the behavioural

parameters measured.

Functional Performance Tests. There were no treatment-related changes in functional

performance.

Sensory Reactivity Assessments. There were no treatment-related changes in

sensory reactivity.

Body Weight. There were no convincing treatment-related adverse findings.

Food Consumption. No adverse effects on food consumption or food efficiency were

detected in test animals in comparison with controls.

Water Consumption. No intergroup differences were detected.

Reproductive Performance:

Mating. There were no treatment-related effects on mating.

Fertility. No treatment-related effects on conception rates were identified.

Gestation Lengths. There were no differences in gestation lengths between treated

females when compared to controls. The distribution for treated females was comparable

to that of the controls.

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# Litter Responses:

Offspring Litter Size, Sex Ratio and Viability. Of the litters born, litter size at birth and

over subsequent days post partum was comparable to controls.

Sex ratio were also comparable to controls.

Offspring Growth and Development. There were no significant differences in litter

weights or mean offspring body weights between control and treated animals. Statistical

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

Laboratory Investigations:

Haematology. No toxicologically significant effects were detected in the haematological

parameters examined.

Blood Chemistry. No toxicologically significant effects were detected in the blood

chemical parameters examined.

Pathology:

Necropsy. No treatment-related macroscopic abnormalities were observed in any animal

at study termination.

Organ Weights. There were no convincing treatment-related organ weight changes

detected in test animals in comparison with controls.

Histopathology. No treatment-related histopathological changes in the tissues

examined were detected.

Conclusion. The oral administration of Sodium Glucoheptonate (EC 250-480-2)

(incorporating a test item correction factor for 50.5% w/w purity minus 49.5% w/w test

item water content) to rats by gavage, at dose levels of 30, 300 and 1000 mg/kg bw/day

did not produce any convincing adverse effects of treatment and on this basis the ‘No

Observed Adverse Effect Level’ (NOAEL) and possible ‘No Observed Effect Level’

(NOEL) for systemic toxicity for either sex was considered to be 1000 mg/kg bw/day.

No treatment-related effects were observed for reproduction, the ‘No Observed Effect

Level’ (NOEL) for reproductive toxicity was therefore considered to be 1000 mg/kg

bw/day.

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# Sodium Glucoheptonate (EC 250-480-2):

ORAL (GAVAGE) COMBINED REPEAT DOSE TOXICITY STUDY WITH

REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT

(OECD 422)

1. INTRODUCTION

The study was performed according to the Study Plan presented in Appendix 26 and was

designed to screen for potential adverse effects of the test item on reproduction,

including offspring development, following repeated oral administration to the Wistar

HanTM:RccHanTM:WIST strain rat for up to eight weeks (including a two week pre-pairing

phase, pairing, gestation and early lactation), at dose levels of 30, 300 and 1000 mg/kg

bw/day (incorporating a test item correction factor for 50.5% w/w purity minus 49.5% w/w

test item water content). A control group was dosed with vehicle alone (Distilled water).

The study was designed to be compatible wi th the requirements of the OECD Guidelines

for Testing of Chemicals, No.422: “Combined Repeated Dose Toxicity Study with the

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

This study was also designed to be compatible with the Commission Regulation (EC) No.

440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No.

1907/2006 of the European Parliament and of the Council on the Registration,

Evaluation, Authorisation and Restriction of Chemicals (REACH).

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.

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

Laboratories Project Number: 41104691). The oral route was selected as the most

appropriate route of exposure, based on the physical properties of the test item. The

results of the study are believed to be of value in predicting the likely toxicity of the test

item to man and to screen for potential adverse effects on reproduction.

Shortly after the final report was issued a number of pages were discovered to incorrectly

reference the test item. As this error could be misleading it is considered appropriate

that the report be re-issued in its entirety and the original version be withdrawn.

The study was performed between 03 December 2012 and 09 August 2013 (date of final

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

05 December 2012 (first day of treatment) and 15 January 2013 (final necropsy).

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# 2. TEST ITEM AND EXPERIMENTAL PREPARATION

2.1 Description, Identification and Storage Conditions

Sponsor's identification : Sodium Glucoheptonate (EC 250-480-2)

Description : Dark brown liquid

Purity : 50.5% (solids)

Batch number : 921000100

Label : SGH Intermediate Lot 921000100

Date received : 09 February 2012

Storage conditions : Room temperature in the dark

Expiry date : 09 February 2015

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

the responsibility of the sponsor.

2.2 Preparation of Test Item

For the purpose of this study the test item was prepared at the appropriate

concentrations as a solution in Distilled water. 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 seven days.

Formulations were therefore prepared week ly and stored at approximately 4oC in the

dark.

Samples of each test item formulation were taken and analysed for concentration of

Sodium Glucoheptonate (EC 250-480-2) at Harlan Laboratories Ltd., Shardlow, UK,

Analytical Services. The method used for analysis of formulations and the results

obtained are given in Appendix 25. The results indicate that the prepared formulations

were within acceptable ranges for the purpose of this study.

3. METHODS

3.1 Animals and Animal Husbandry

A sufficient number of male and female Wi star 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 was assessed. A total of

ninety six animals (forty eight males and forty eight females) were accepted into the

study. At the start of treatment the males weighed 302 to 346g, the females weighed

191 to 217g, and were approximately twelve weeks old.

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# Initially, all animals were housed in groups of four in solid floor polypropylene cages with

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

During the pairing phase, 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 successful mating, the males were returned to

their original cages. Mated females were housed individually during gestation and

lactation in solid floor polypropylene cages with stainless steel mesh lids and softwood

flakes.

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 31. Mains

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

and drinking water were considered not to c ontain 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.

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 temperatures

and relative humidity controls were set to achieve target values of 21 ± 2°C and 55 ±

15% respectively. There were no deviations from these targets.

The animals were allocated to dose groups using a randomisation procedure based on

stratified body weights, group mean body weights were then determined to ensure

similarity between the dose groups. The animals were uniquely identified within the

study by an ear punching system rout inely used in these laboratories.

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# 3.2 Procedure

Animals were allocated to tr eatment groups as follows:

Treatment

Group Dose Level #

(mg/kg bw/day) Dose level of

Test Item (as

supplied)

(mg/kg bw/day) Treatment

Volume

(ml/kg) Concentration #

(mg/ml) Animal Numbers

Male Female

Control 0 0 5 0 12 (1-12) 12 (13-24)

Low 30 59.4 5 6 12 (25-36) 12 (37-48)

Intermediate 300 594 5 60 12 (49-60) 12 (61-72)

High 1000 1980 5 200 12 (73-84) 12 (85-96)

# = Including a correction factor of 50.5% w/w (i.e. concentration of test item minus test item water content

(49.5% w/w))



# 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

5 ml/kg of Distilled water.

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

recent scheduled body weight and was adjusted at regular intervals.

Chronological Sequence of Study

i) Groups of twelve male and twelve female animals 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 weekly 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/sensory responses to various stimuli.

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# vi) Pregnant females were allowed to give birth 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.

viii) Blood samples were taken from five males from each dose group for

haematological 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 (Day 25 post coitum ).

3.3 Observations

3.3.1 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). All observations were recorded.

3.3.2 Functional Observations

Prior to the start of treatment and at weekly intervals thereafter, all animals were

observed for signs of functional/behavioural toxicity. Functional performance tests were

also performed on five selected males and females from each dose level, prior to

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

3.3.2.1 Behavioural Assessments

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

built arena. The following parameters were observed:

Gait Hyper/Hypothermia

Tremors Skin colour

Twitches Respiration

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# Convulsions Palpebral closure

Bizarre/Abnormal/Stereotypic behaviour 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

Behavioural Assessments and Sensory Reactivity Tests.

3.3.2.2 Functional Performance Tests

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

to assess motor activity. Animals were random ly allocated to the activity monitors. The

tests were performed at approximately the same time on each occasion, 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 force 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).

3.3.2.3 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

Toe pinch Blink reflex

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# Tail pinch Startle reflex

Finger approach

Normal range data for the functional performance test parameters are presented in

Appendix 36.

3.3.3 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 . Body weights were also recorded at terminal kill.

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

presented in Appendix 33.

3.3.4 Food Consumption

During the pre-pairing period, weekly food consumption 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.

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

retrospectively for males throughout the study period (with the exception of the mating

phase) and for 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 lactating females are presented in Appendix 33.

3.3.5 Water Consumption

Water intake was measured daily during the first two weeks of the study.

3.3.6 Reproduction Screening

Normal range data for reproductive parameters and offspring are presented in

Appendix 33 and Appendix 34.

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# 3.3.6.1 Mating

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 examined 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 holding cages

(unless required for additional pairing). Mated females were housed individually during

the period of gestation and lactation.

3.3.6.2 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 observed start of parturition

iv) Date and time of observed completion of parturition

3.3.6.3 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

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# v) Individual offspring weights on Days 1 and 4 post partum (litter weights were

calculated retrospectively from this data)

3.3.6.4 Physical Development

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

3.3.7 Laboratory Investigations

Haematological and blood chemical investigations were performed on five males and five

females selected from each test and control group prior to termination (Day 42 for males

and Day 4 post partum for females). Blood samples were obtained from the lateral tail

vein. Where necessary repeat samples were taken by cardiac puncture at termination.

Animals were not fasted prior to sampling.

The methods used for haematological and blood chemical investigations are given in

Appendix 32 and normal ranges are shown in Appendix 35.

3.3.7.1 Haematology

The following parameters were measured on blood 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 stained slides were prepared but

reticulocytes were not assessed

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).

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# 3.3.7.2 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.) Aspartate aminotransferase (ASAT)

Albumin Alanine aminotransferase (ALAT)

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

Sodium (Na+) Creatinine (Creat)

Potassium (K+) Total cholesterol (Chol)

Chloride (Cl-) Total bilirubin (Bili)

Bile acids

3.3.8 Pathology

Adult males were killed by intravenous overdose of a suitable barbiturate agent followed

by exsanguination on Day 43. Adult 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 produce a litter were killed on or after Day

25 post coitum.

For all females, the uterus was examined for signs of implantation and the number of

uterine implantations in each horn was recorded. 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.

All adult animals and offspring, including thos e dying during the study, were subjected to

a full external and internal examination, and any macroscopic abnormalities were

recorded.

3.3.8.1 Organ Weights

The following organs were dissected free from fat and weighed before fixation from five

selected males and five selected females from each dose group. Tissues shown in bold

were weighed from all remaining animals:

Adrenals Prostate

Brain Seminal vesicles

Epididymides Spleen

# PROJECT NUMBER: 41104692R PAGE 29



# Heart Testes

Kidneys Thymus

Liver Thyroid (weighed post-fixation with Parathyroid)

Ovaries Uterus (weighed with Cervix)

Pituitary (post fixation)

Normal ranges for these organ weights are given in Appendix 37.

3.3.8.2 Histopathology

Samples of the following ti ssues 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 anmals:

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

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

* = 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 insp iratory volume with buffered 10% formalin before

immersion in fixative

# PAGE 30 PROJECT NUMBER: 41104692R



# Tissues were despatched to the histology processing Test Site (Propath UK Ltd., Willow

Court, Netherwood Road, Hereford, HR2 6JU, UK) for processing (Principal Investigator:

N Fower). The tissues from five selected 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 prepared 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 1000 mg/kg

bw/day animals were also processed. In addition, sections of testes and epididymides

from all control and 1000 mg/kg bw/day males were also stained with Periodic AcidSchiff (PAS) stain and examined.

Microscopic examination was conducted by the Study Pathologist (Principal Investigator

Peter Millar at Peter Millar Associates Ltd., 3 Queen Charlott e Lane, Edinburgh,

Scotland, EH6 6AY). A complete histopathology phase report, including methods, is

presented in Appendix 24.

3.4 Evaluation of Data

3.4.1 Treatment of Data

Data were processed to give group mean values and standard deviations where

appropriate.

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

Group mean values are generally calculated using unrounded values, therefore, it is not

always possible to calculate the exact group values from the individual values presented

in the appendices.

For body weights and food consumptions during gestation, 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.

3.4.2 Reproductive Indices

3.4.2.1 Mating Performance and Fertility

The following parameters were calculated from the individual data during the mating

period of the parental generation:

i) Pre-coital Interval

# PROJECT NUMBER: 41104692R PAGE 31



# 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 (%) =

mated animals of Number females pregnant of Number x 100



# 3.4.2.2 Gestation and Parturition Data

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

parturition period of the parental generation.

i) Gestation Length

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



# 3.4.2.3 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 the 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 post-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

# PAGE 32 PROJECT NUMBER: 41104692R



# 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 calculated 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 on Days 1 and 4 

# post partum , using the following

formula: offspring of number Total offspring male of Number x 100



# 3.4.3 Statistical Analysis

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

detect the significance of intergroup differences from control; 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, Pre-Coital Interval, Gestation Length, Litter Size, Litter

Weight, Sex Ratio, Corpora Lutea, Implantation Sites, Implantation Losses, Viability

Indices, Offspring Body Weight, Offspring Body Weight Change, Offspring Surface

Righting, Haematology, Blood Chemistry, Absolute Organ Weights, Body WeightRelative Organ Weights.

Data were analysed using the decision tree from the Provantis TM 

# Tables and Statistics

Module as detailed below:

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 variances were assessed using suitable ANOVA, or if required, ANCOVA

with appropriate covariates. Any transformed data were analysed to find the lowest

treatment level that showed a significant effect, using the Williams Test for parametric

data or the Shirley Test for non-parametric da ta. If no dose response was found, but the

# PROJECT NUMBER: 41104692R PAGE 33



# data showed 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 using the Student t-test (parametric) or the Mann-Whitney U test

(non-parametric).

Data not analysed by the Provantis data capt ure 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 variance (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

analysis 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 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-Whitney U test (non-parametric).

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

(implantation losses, offspring sex ratio and offspring surface righting) were analysed

using non-parametric analyses.

Probability values (p) were calculated as follows:

p<0.001 ***

p<0.01 **

p<0.05 *

p 

#  0.05 (not significant)



# 4. DEVIATIONS FROM STUDY PLAN

There were no deviations to the Study Plan.



# 5. ARCHIVES

Unless instructed otherwise by the Sponsor, specimens (as long as the quality permits

evaluation), the study plan, raw data (paper and electronic) generated at the test facility,

all original data including tissue blocks an d tissue slides generated at the histology

processing Test Site, the original histopathology report and any raw data generated at

the histology examination test site, and the final report will be retained in the Harlan

Laboratories Ltd., Shardlow, UK archives for five years after which instructions will be

# PAGE 34 PROJECT NUMBER: 41104692R



# sought as to further retention or disposal. Further retention or return of the data will be

chargeable to the Sponsor.

# PROJECT NUMBER: 41104692R PAGE 35



# 6. RESULTS

6.1 Adult Responses

6.1.1 Mortality

There were no unscheduled deaths on the study.



# 6.1.2 Clinical Observations

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

given in Appendix 1.

No toxicologically significant adverse findings were detected.

Incidental findings involved noisy respiration which developed from Day 31 in one female

at 30 and 300 mg/kg bw/day and in one 1000 mg/kg bw/day male. This finding was

accompanied on Day 42 in the 30 mg/kg bw/day female by laboured respiration,

increased salivation, pilo-erection and hunched posture. Given the isolated nature of

these changes, they were considered attributable to the gavage procedure rather than a

direct effect of the test item (or vehicle).

Remaining findings involved the presence (from Day 31) of a small mass under the right

forelimb of one 1000 mg/kg bw/day female. While the aetiology of the swelling is

uncertain, there was no indication this swelling caused distress or impaired the animals

movement and microscopic evaluation concluded this finding not to be a consequence of

treatment.

Four males treated with 300 mg/kg bw/day had generalised scab formation from Day 19

onwards. Observations of this nature are commonly observed in group housed animals

and result from social interaction and are therefore considered unrelated to test item

toxicity.



# 6.1.3 Functional Observations

A summary incidence of behavioural assessment observations is given in Table 3 and

group mean behavioural assessment scores are given in Table 4. Group mean

functional test values and standard deviations are given in Table 5 (statistically

significant differences are indicated). Individual values are given in Appendices 2 to 5.

Group mean sensory reactivity assessment scores are given in Table 6. Individual

responses are given in Appendix 6.

# PAGE 36 PROJECT NUMBER: 41104692R



# 6.1.3.1 Behavioural Assessments

There were no treatment-related changes in behavioural assessments.

All inter and intra group differences in urinat ion, defecation and transfer arousal scores

were considered to be a result of normal variation for rats of the strain and age used and

were considered to be of no toxicological importance.



# 6.1.3.2 Functional Performance Tests

There were no treatment related changes detected in the functional performance

measurements.

Females treated with 300 and 1000 mg/kg bw/day showed a slight but statistically

significant increase (p<0.05) in one of three hind limb grip strength measurements. In

the absence of a dose dependent trend or other evidence to suggest an association with

test item toxicity it is reasonable to assume that the isolated nature of these observations

indicate this finding to be a result of biological variation rather than an association with

test item toxicity.



# 6.1.3.3 Sensory Reactivity Assessments

There were no treatment-related changes in sensory reactivity.

All inter and intra group differences in sensory reactivity scores were considered to be a

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

importance.



# 6.1.4 Body Weight

Group mean body weights, body weight changes and standard deviations are given in

Table 7 and Table 8 (statistically significant differences are indicated). Group mean body

weight data are presented graphically in Figure 1 and Figure 2. Individual data are given

in Appendix 7 and Appendix 8.

Group mean gains for males tested at 1000 mg/kg bw/day were slightly lower (p<0.05)

than that of the controls at Week 2 but showed recovery thereafter. Body weight gains in

one or more test groups at Week 4 and during the final week of treatment exceeded that

of the controls. However, as weight gains are seldom seen as an adverse effect of

treatment, under the conditions of this study they were considered attributable to natural

variability.

# PROJECT NUMBER: 41104692R PAGE 37



# Body weight development in females treated with 1000 mg/kg bw/day was generally

slightly lower than that of the concurrent controls. However, there was no supporting

evidence to support any significance to this trend and as individual values with few

exceptions were similar to the controls, this finding was considered to be fortuitous.



# 6.1.5 Food Consumption

Group mean food consumptions are given in Table 9 and are presented graphically in

Figure 3 and Figure 4. Individual and group mean food consumptions for females

following mating and during lactation are presented in Appendix 9.

Food efficiencies for males and females during the pre-mating phase are given in Table

10.

No adverse effect on food consumption or food efficiency was detected in treated

animals in comparison with controls throughout the study.



# 6.1.6 Water Consumption

Group mean daily water consumptions are given in Table 11.

Gravimetric measurement of water consumption undertaken during the pre-pairing phase

did not reveal any adverse effect.



# 6.2 Reproductive Performance

6.2.1 Mating

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

performance is presented in Table 12. Individual data are given in Appendix 10.

No treatment-related effects were detected in mating performance.

With the exception of one paired control male and female all females mated within the

first four days of pairing.

Statistical analysis of the pre-coital interval data did not reveal any significant intergroup

differences.

# PAGE 38 PROJECT NUMBER: 41104692R



# 6.2.2 Fertility

A summary of adult performance is given in Table 1. Group values for fertility, litter data

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

Appendices 10 to 12.

No treatment-related effects were detecte d on fertility for treated animals when

compared to controls.

One control female (No. 21) did not achieve pregnancy following evidence of mating. In

the absence of histopathological correlates this intergroup difference was considered to

be incidental. In addition, one 300 mg/kg bw/day female (No. 69) did not achieve

pregnancy following evidence of mating. However, there were no histopathological

correlates in the reproductive organs, the male partner was observed at necropsy to

have small epididymides (given the isolated nature this finding it was considered not to

be related to test item toxicity) with histopathological examination determining severe

bilateral hypospermia and severe bilateral germinal epithelial atrophy; thus accounting

for the probable absence of pregnancy in female No.69.



# 6.2.3 Gestation Length

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

lengths are given in Appendix 10.

No treatment-related effects were detected in the length of gestation for treated females

when compared to controls. All animals showed gestation lengths between 22 to 241⁄2

days.



# 6.3 Litter Responses

In total ten control females, all twelve females from the 30 mg/kg bw/day dose group,

eleven females from the 300 mg/kg bw/day dose group and all twelve females from the

1000 mg/kg bw/day dose group gave birth to a live litter and successfully reared young to

Day 5 age.

The following assessment of litter response is based on all litters reared to termination on

Day 5 of lactation/age.

# PROJECT NUMBER: 41104692R PAGE 39



# 6.3.1 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 11 to 13.

No treatment related effects were detected.

No significant differences were detected for corpora lutea, implantation counts or litter

viability for treated animals when compared to controls. A slight reduction (p<0.05) in

litter size for offspring born was identified in females treated with 1000 mg/kg bw/day in

comparison with controls. However, individual litter sizes at birth were for the most part

within historical background ranges, therefore in the absence of any supporting evidence

of reproductive toxicity this isolated intergroup difference was considered not to be

treatment-related.



# 6.3.2 Offspring Growth and Development

Group values for total litter weights, offspring body weight and body weight change,

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 11, 14 and 15.

There were no significant differences in litter weights or mean offspring body weights

between control and treated animals. Statistical analysis of the data did not reveal any

significant intergroup differences.

Litters from females treated with 1000 mg/kg bw/day showed a slight reduction in litter

weight compared to litters from control animals. This reduction is thought to be

attributable to two small litters within the 1000 mg/kg bw/day dose group. In the absence

of a statistically significant difference and as the majority of the litter weights were within

normal historical background ranges, the difference is considered not to represent a true

effect of treatment.

No overt clinical evidence of toxicity was detected for offspring from treated females

when compared to controls. The incidental clinical signs detected throughout the control

and treated groups, consisting of small size, offspring found dead or missing, bruising,

cold and physical injuries were considered to be low incidence findings observed in

offspring in studies of this type, and were unrelated to test item toxicity.

# PAGE 40 PROJECT NUMBER: 41104692R



# 6.4 Laboratory Investigations

6.4.1 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 16 and Appendix 17.

There were no toxicologically significant treatment-related effects detected in the

haematological parameters.

Males treated with 1000 mg/kg bw/day showed statistically significant reductions for

haemoglobin (p<0.05), erythrocyte count (p<0.05) and haematocrit (p<0.01) when

compared to control animals. However, the majority of individual vales remained similar

to that of the concurrent control and in the absence of any supporting indications of an

anaemia, the most plausible reason for these changes is a non-specific “stress

response” and not test item toxicity.

Females treated with 1000 mg/kg bw/day had a statistically significant reduction in total

leucocyte count and lymphocyte count and a statistically significant increase in

eosinophil count. The majority of individual values were within the normal range for rats

of strain and age used and in the absence of any supporting microscopic findings, the

intergroup differences were considered not to be of toxicological significance.

No such findings were apparent in animals of either sex treated with 300 or 30 mg/kg

bw/day.



# 6.4.2 Blood Chemistry

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

in Table 19 (statistically significant differences are indicated). Individual data are given in

Appendices 18 and 19.

Males treated with 1000 or 300 mg/kg bw/day had statistically significant reductions in

total protein (p<0.05) and creatinine (p<0.05) and a statistically significant increase in

albumin/globulin ratio (p<0.05 or p<0.01 respectively). In the absence of any convincing

trends among individual values or histopathological correlates these isolated changes

were considered not to be indicative of hepatic or renal impairment but more likely a

result of biological variability.

# PROJECT NUMBER: 41104692R PAGE 41



# A slight but statistically significant reduction in inorganic phosphate concentrations was

identified among females receiving 300 mg/kg bw/day (p<0.05) and 1000 mg/kg bw/day

p<0.01). Individual values were within the normal historical background ranges for rats

of the strain and age used and in the absence of associated changes, the toxicological

significance of this finding is considered to be highly dubious.

Females treated with 1000 mg/kg bw/day also showed a statistically significant reduction

in calcium. In the absence of any supporting biochemical or microscopic findings, this

intergroup difference was considered spurious.

Females treated with 30 mg/kg bw/day showed a slight increase (p<0.05) for plasma

glucose levels which in the absence of a dose-dependent trend was considered to have

arisen fortuitously.



# 6.5 Pathology

6.5.1 Necropsy

A summary incidence of necropsy findings is given in Tables 20 and 21. Individual data

are given in Appendices 20 and 21.

Offspring

No treatment-related macroscopic abnormalities were detected for 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

One male treated with 1000 mg/kg bw/day had a dark spleen and reddened lungs at

necropsy, both the lungs and spleen were found to be congested, the lungs were also

found to contain moderate peribronchiolar intra-alveolar pink fluid when analysed

microscopically.

This may have been a result of a partial mal-dose during the study. However, given the

isolated nature of this finding it was considered incidental and not to be related to test

item toxicity.

One male treated with 300 mg/kg bw/day had small epididymides and small, flaccid

testes. In addition, one female treated with 1000 mg/kg bw/day had a mass under the

right forelimb at necropsy. Upon histopathological evaluation this was confirmed to be

an adenocarcinoma. Furthermore, one control male was noted to have small seminal

# PAGE 42 PROJECT NUMBER: 41104692R



# vesicles and one control female an increased left renal pelvic space and mineral calculi

in the urinary bladder at necropsy. Such observations represent common sporadic

finding amongst rats of the strain and age used in the study and since there was neither

a dose-response relationship nor a similar finding amongst the remaining animals at any

dose level, these isolated findings were considered not to represent a treatment-related

effect.



# 6.5.2 Organ Weights

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

for test and control group animals are presented in Table 22 (statistically significant

differences are indicated). Individual data are given in Appendix 22 and Appendix 23.

There were no treatment-related changes detected in the organ weights of either sex of

test animals in comparison with controls.

Incidental findings involved males treated with 1000 mg/kg bw/day that showed a

statistically significant reduction (p<0.01) in absolute and relative pituitary weight

compared with controls. In addition, 1000 mg/kg bw/day females showed a slight but

statistically significant increase (p<0.05) in both absolute and relative thyroid/parathyroid.

However, the great majority of male individ ual values and all female values were within

the expected historical ranges for animals of this age and strain. Furthermore, there was

no evidence of microscopic pituitary changes or any other apparent changes which may

indicate endocrine imbalances and, consequently, these findings were considered

spurious and considered not to be indicative of test item toxicity.

An increase (p<0.05) for uterus/cervix weights was identified in the females treated at

1000 mg/kg bw/day. However, the majority of individual values were within the

anticipated historical ranges. Furthermore there was no histopatholigical indication of an

associated treatment related response and on this basis this finding was considered to

have arisen fortuitously.



# 6.5.3 Histopathology

A complete histopathology phase report is presented in Appendix 24.

No treatment-related histopathological changes in the tissues examined were detected.

All remaining morphological changes were those commonly observed in laboratory

maintained rats of the age and strain employed and there were no differences in

incidence or severity between control and treatment groups that were considered to be of

toxicological significance.

# PROJECT NUMBER: 41104692R PAGE 43



# 7. DISCUSSION

The oral administration to rats of Sodium Glucoheptonate (EC 250-480-2) for a period of

up to eight weeks (including two weeks pre-pairing, gestation and early lactation period

for females) at dose levels of 30, 300 and 1000 mg/kg bw/day (incorporating a test item

correction factor for 50.5% w/w purity minus 49. 5% w/w test item water content) resulted

in no toxicologically significant treatment-related findings.

The incidental findings identified in this study (slight impairment of bodyweight

development in either sex treated with 1000 mg/kg bw/day and minor haematological

changes in 1000 mg/kg bw/day males) were considered to be either low incidence

changes attributable to biological variabilit y and/or sporadic findings that lacked any

convincing supporting histopathological evidence to suggest they represented a

convincing treatment-related effect. Furthermore there were no differences on the

completeness of stages or cell populations of the testes recorded between controls and

1000 mg/kg bw/day animals and all but two mated females (control and 300 mg/kg

bw/day) gave birth to a live litter and successfully reared their young to Day 5 of age. In

relation to offspring, there were no notable significant differences in litter weights or

mean offspring body weights between control and treated animals. On this basis, the ‘No

Observed Adverse Effect Level’ (NOAEL) and possible ‘No Observed Effect Level’

(NOEL) for systemic toxicity for either sex was considered to be 1000 mg/kg bw/day.

No treatment-related effects were observed for reproduction and on this basis the ‘No

Observed Effect Level’ (NOEL) for reprod uctive toxicity was considered to be

1000 mg/kg bw/day.



# 8. CONCLUSION

The oral administration to rats of Sodium Glucoheptonate (EC 250-480-2) (incorporating

a test item correction factor for 50.5% w/ w purity minus 49.5% w/w test item water

content) to rats by gavage, at dose levels of 30, 300 and 1000 mg/kg bw/day did not

produce any convincing adverse effects of treatment and on this basis the ‘No Observed

Adverse Effect Level’ (NOAEL) and possible ‘No Observed Effect Level’ (NOEL) for

systemic toxicity for either sex was considered to be 1000 mg/kg bw/day.

No treatment-related effects were observed for reproduction, the ‘No Observed Effect

Level’ (NOEL) for reproductive toxicity was therefore considered to be 1000 mg/kg

bw/day.

# PAGE 44 PROJECT NUMBER: 41104692R



# 9. 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 makroskopischen Nachweis von

Implantationsstellen am Uterus der Ratte. Naunyn - Schmiedebergs 

# Arch Exp Path

Pharmakol

. 

# 247, 367.

# PROJECT NUMBER: 41104692R PAGE 45



# TABULAR SUMMARY REPORT OF EFFE CTS ON REPRODUCTION/DEVELOPMENT

Observations Dose Level (mg/kg bw/day)

0 (Control) 30 300 1000

Paired animals n 12 12 12 12

Females showing evidence of copulation n 12 12 12 12

Pregnant females n 11 12 11 12

Conception Days 1-5 n 10 12 11 12

Conception Day 11 n 1 0 0 0

Gestation = 22 Days n 0 1 0 3

Gestation = 22 1⁄2 Days n 1 3 1 1

Gestation = 23 Days n 3 3 2 2

Gestation = 23 1⁄2 Days n 7 5 6 6

Gestation = 24 1⁄2 Days 0 0 2 0

Dams with live young born n 11 12 11 12

Dams with live young at Day 4 post partum n 10 12 11 12

Corpora lutea/dam 15.0 14.5 14.9 13.3

Implants/dam 14.2 13.7 14.5 11.8

Live offspring/dam at Day 1 post partum 13.1 12.8 13.3 10.3

Live offspring/dam at Day 4 post partum 13.0 12.3 12.8 10.2

Sex ratio: % males at Day 1 post partum 54.9 53.4 53.7 50.9

Sex ratio: % males at Day 4 post partum 55.4 54.2 54.3 51.7

Litter weight (g) at Day 1 post partum 77.18 73.06 82.80 64.46

Litter weight (g) at Day 4 post partum 106.82 99.76 112.78 90.87

Male offspring weight (g) at Day 1 post partum 6.08 6.02 6.48 6.54

Male offspring weight (g) at Day 4 post partum 8.47 8.57 9.11 9.56

Female offspring weight (g) at Day 1 post partum 5.85 5.63 6.07 6.19

Female offspring weight (g) at Day 4 post partum 8.15 8.12 8.65 9.10

LOSS OF OFFSPRING/DAM

Pre-implantation (corpora lutea minus implantations)

0 n 7 8 8 4

1 n 1 2 0 4

2 n 1 1 1 2

3 n 0 0 1 0

5 n 1 0 0 1

6 n 0 1 0 1

Pre-natal (implantations minus live births)

0 n 3 5 1 4

1 n 5 5 7 4

2 n 2 2 3 2

3 n 0 0 0 1

4 n 1 0 0 0

5 n 0 0 0 1

Post natal (live births minus offspring alive on Day 4 post

p artum )

0 n 8 9 9 10

1 n 1 2 1 1

2 n 1 0 0 1

3 n 0 2 0 0

4 n 0 0 1 0

14 n 1 0 0 0



# n

= Number



# x = Mean x

x

x

x

x

x

x

x

x x

x

x

# PAGE 46 PROJECT NUMBER: 41104692R



# KEY TO TABLES AND APPENDICES

M Male

F Female

S.D. Standard deviation

N Number of animals/litters

. No data available

- Not applicable

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)

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

N/A Not applicable

% Food

Efficiency 

# 100 x f days x number o /rat/day) umption (g food cons Group mean d) /rat/perio ht gain (g body weig Group mean        

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

# PROJECT NUMBER: 41104692R PAGE 47



# 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)

# PAGE 48 PROJECT NUMBER: 41104692R



# KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS 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 behaviour is recorded using a unique code.

# PROJECT NUMBER: 41104692R PAGE 49



# KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)

4. AUTONOMIC



# Salivation* Excessive visible 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 closure eg 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, moderate or extreme.

# PAGE 50 PROJECT NUMBER: 41104692R



# KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS 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 exhibited 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

# PROJECT NUMBER: 41104692R PAGE 51



# KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS 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

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

# PAGE 52 PROJECT NUMBER: 41104692R



# KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIOURAL

ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)

5.9 Startle Reflex



# A sharp sudden noise is produced by a noise generator 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

# PROJECT NUMBER: 41104692R PAGE 53



# TABLESPROJECT NUMBER: 41104692RPAGE 54SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 1 Summary of ReproductivePerformance - Group ValuesDose Group (mg/kg bw/day)0 (Control) 30 300 1000



# MalesInitial group size12 12 12 12Paired12 12 12 12Failed to induce pregnancy in female partner 1 0 1 0Induced pregnancy in female partner 11 12 11 12Surviving to terminal necropsy12 12 12 12



# FemalesInitial group size12 12 12 12Paired12 12 12 12Non-pregnant1 0 1 0Pregnant11 12 11 12Rearing young to Day 5 of age10 12 11 12SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 55Table 2 Summary Incidence of Daily Clinical ObservationsDay Numbers Relative to Start DateSex: MaleGroup 1 Group 2 Group 3 Group 40(Control) 30 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/dayAbnormal GaitNumber of Animals . . 1 .Days from ƒ to . . 8 43 .ScabNumber of Animals . . 4 .Days from ƒ to . . 19 43 .Scheduled killNumber of Animals 12 12 12 12Days from ƒ to 43 43 43 43 43 43 43 43Noisy respirationNumber of Animals . . . 1Days from ƒ to . . . 35 35PROJECT NUMBER: 41104692RPAGE 56SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 2 (continued) Summary Incidence of Daily Clinical ObservationsDay Numbers Relative to Start DateSex: FemaleGroup 1 Group 2 Group 3 Group 40(Control) 30 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/dayLitteringNumber of Animals 1 . 2 2Days from ƒ to 38 38 . 40 40 40 40Not Observed Due to LitteringNumber of Animals 1 . 2 2Days from ƒ to 38 38 . 40 40 40 40MassNumber of Animals . . . 1Days from ƒ to . . . 31 44Respiration ƒ LabouredNumber of Animals . 1 . .Days from ƒ to . 42 42 . .Scheduled killNumber of Animals 12 12 12 12Days from ƒ to 42 52 42 46 42 45 42 46Increased salivationNumber of Animals . 1 . .Days from ƒ to . 42 42 . .Noisy respirationNumber of Animals . 1 1 .Days from ƒ to . 42 42 31 32 .SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 57Table 2 (continued) Summary Incidence of Daily Clinical ObservationsDay Numbers Relative to Start DateSex: FemaleGroup 1 Group 2 Group 3 Group 40(Control) 30 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/dayPiloƒerectionNumber of Animals . 1 . .Days from ƒ to . 42 42 . .Hunched postureNumber of Animals . 1 . .Days from ƒ to . 42 42 . .PROJECT NUMBER: 41104692RPAGE 58SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 3 Summary Incidence of Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign -1 7 14 20 27 35 41/4 

# post partum#1(M) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 121(F) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 12# = Day 25 

# post coitumDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 59Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign -1 7 14 20 27 35 41/4 

# post partum2(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 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 60SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign -1 7 14 20 27 35 41/4 

# 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 coitumDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 61Table 3 (continued) Summary Incidence ofBehavioural Assessments (Observations)Day Numbers Relative to Start DateGroup(Sex) Clinical Sign -1 7 14 20 27 35 41/4 

# post partum4(M) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS NORMAL 12 12 12 12 12 12 124(F) ANIMALS ALIVE 12 12 12 12 12 12 12ANIMALS 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 62SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 Group Mean Behavioural Assessments (Scores)Day: ƒ1 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 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 0.2 0.0 0.0S.D. 0.0 0.4 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 63Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: ƒ1 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 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 0.2 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 64SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 7 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 ƒƒƒƒƒƒƒƒ2(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 ƒƒƒƒƒƒƒƒ3(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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 65Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 7 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 0.1 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 0.0 0.1 0.0S.D. 0.0 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 66SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 14 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 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(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 ƒƒƒƒƒƒƒƒ4(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 ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 67Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 14 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 0.2 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 0.1 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 0.3 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 68SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 20 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 0.2 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 0.2 0.0 0.0S.D. 0.0 0.4 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 69Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 20 Relative to Start DateTransfer 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 0.1 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 0.1 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 70SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 27 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 0.0 0.0 0.0S.D. 0.0 0.0 0.0 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 0.0 0.0 0.1 0.0S.D. 0.0 0.0 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(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 ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 71Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 27 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 72SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 35 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 ƒƒƒƒƒƒƒƒ2(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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 73Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 35 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 74SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 4 (continued) Group Mean Behavioural Assessments (Scores)Day: 41 Relative to Start DateTransfer Urinƒ Defƒ Tail elƒGroup arousal ation ecation evation(Sex)1(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 ƒƒƒƒƒƒƒƒ2(M) Mean 0.0 0.0 0.3 0.0S.D. 0.0 0.0 0.9 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 75Table 4 (continued) Group Mean 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 0.2 0.2 0.0S.D. 0.0 0.4 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 0.3 0.1 0.0S.D. 0.0 0.5 0.3 0.0N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 76SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 5 Group Mean Functional Test 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(M) Mean 1081.2 395.6 1025.2 433.8 900.4 378.4 281.6 0.0n 25.00.0nS.D. 302.0 195.8 420.1 217.6 199.1 87.4 126.0 0.0 32.10.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ2(M) Mean 936.6 574.4 871.6 419.8 954.0 398.0 343.6 0.8n 44.20.0nS.D. 278.5 61.6 351.3 95.4 361.9 139.8 121.4 1.3 54.10.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ3(M) Mean 1128.0 424.8 835.4 355.2 1054.6 449.4 278.6 0.4n 15.00.0nS.D. 174.1 122.7 236.1 152.0 296.5 152.1 79.9 0.5 14.70.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ4(M) Mean 1062.4 489.4 969.0 445.0 1085.6 487.8 400.4 1.2n 38.40.2nS.D. 254.5 277.5 82.5 260.7 249.4 71.2 147.5 1.3 62.00.4N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 77Table 5 (continued) Group Mean Functional Test 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 801.4 231.4 728.8 243.0 828.4 359.8 466.6 2.0 40.40.2nS.D. 156.8 117.3 104.4 79.4 163.8 161.6 103.0 1.6 34.30.4N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ2(F) Mean 954.0 396.6 879.4 334.2 826.8 378.6 462.8 2.0 29.40.0nS.D. 364.1 171.7 369.2 136.6 228.8 122.2 128.6 1.2 49.40.0N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ3(F) Mean 848.2 380.6 1074.8 622.6* 845.0 345.6 309.4 1.6 62.60.4nS.D. 229.2 54.2 242.3 283.4 290.6 170.4 155.0 1.5 47.80.9N 5 5 5 5 5 5 5 5 55ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ4(F) Mean 953.4 429.2 1041.4 488.4* 882.0 379.4 387.0 3.8 67.81.0nS.D. 341.3 227.2 370.4 278.7 294.1 165.6 223.6 2.6 53.11.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 78SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 6 Group Mean 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 0.0 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 ƒƒƒƒƒƒƒ3(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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 79Table 6 (continued) Group Mean 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 0.0 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 ƒƒƒƒƒƒƒ3(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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 80SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 7 Group Mean Body Weight ValuesBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 15 22 29 36 431(M) Mean 326.0 346.1 362.8 370.2 377.3 389.8 387.8S.D. 9.0 10.9 12.6 13.5 13.2 13.6 19.8N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(M) Mean 324.9 342.8 359.0 365.8 374.8 386.9 391.2S.D. 6.9 8.1 11.0 12.2 13.3 14.3 15.2N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(M) Mean 321.3 336.9 355.8 356.9 369.5 386.3 392.7S.D. 10.9 13.2 13.7 20.5 25.0 19.8 17.9N 12 12 12 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 327.2 344.7 357.1 363.3 377.8 391.8 396.8S.D. 8.9 13.0 16.5 16.9 17.3 21.0 23.1N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 81Table 7 (continued) Group Mean Body Weight ValuesBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup(Sex) 1 8 151(F) Mean 206.2 218.9 227.7S.D. 5.1 12.3 13.4N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(F) Mean 202.5 213.2 223.3S.D. 6.6 7.8 7.8N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(F) Mean 207.4 217.4 227.3S.D. 5.7 6.6 7.6N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 201.5 210.4 218.3S.D. 6.8 11.0 13.6N 12 12 12ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 82SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 7 (continued) Group Mean Body Weight ValuesGroup(Sex)Body Weight (g)Day NumbersGestationLactation071420 141(F)Mean230.9258.1288.6358.5257.9271.2S.D.18.5 16.9 19.5 24.219.8 21.0N11 11 11 1110 102(F)Mean226.1254.9287.9351.0258.4271.5S.D.8.0 8.2 12.3 18.217.3 15.7N12 12 12 1212 123(F)Mean227.5259.5292.8361.6261.5275.5S.D.9.4 11.8 17.3 24.014.5 14.0N11 11 11 1111 114(F)Mean221.1249.5278.8336.0261.2271.7S.D.16.4 19.2 22.5 33.922.5 20.1N12 12 12 1212 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 83Table 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 20.1 16.7 7.4 7.1 12.5 ƒ1.9 61.8 18.9S.D. 4.0 4.3 6.5 7.3 4.8 8.2 14.6 4.3N 12 12 12 12 12 12 12 122(M) Mean 17.8 16.3 6.8 9.0 12.2 4.3* 66.3 20.4S.D. 5.1 5.8 3.5 6.3 4.1 4.4 11.4 3.4N 12 12 12 12 12 12 12 123(M) Mean 15.6 18.9 1.1 12.6* 16.8 6.4** 71.3 22.2S.D. 6.4 4.7 13.1 9.5 9.9 7.2 11.8 3.6N 12 12 12 12 12 12 12 124(M) Mean 17.5 12.4* 6.2 14.5* 14.0 5.0** 69.6 21.2S.D. 6.7 4.4 5.9 3.9 5.4 4.6 15.3 4.1N 12 12 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 84SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 8 (continued) Group Mean Body Weight GainsIncrease in Bodyweight (g)Day Numbers Relative to Start DateAbs %Gain GainGroup From: 1 8 1 1(Sex) To: 8 15 15 151(F) Mean 12.8 8.8 21.5 10.4S.D. 10.5 4.5 11.8 5.7N 12 12 12 122(F) Mean 10.7 10.2 20.8 10.3S.D. 4.9 4.8 6.9 3.6N 12 12 12 123(F) Mean 10.0 9.9 19.9 9.6S.D. 5.5 5.3 6.1 3.0N 12 12 12 124(F) Mean 8.9 7.8 16.8 8.2S.D. 4.9 4.4 7.7 3.6N 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 85Table 8 (continued) Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysGestationLactationGestationGroup(sex)From: 0 71410 0To: 7 1420414 201(F) Mean27.2 30.5 69.813.357.7 127.5S.D.4.8 5.0 8.56.36.1 11.8N11 11 111011 112(F) Mean28.8 33.063.113.161.8 124.9S.D.6.0 6.0 8.76.39.8 16.7N12 12 121212 123(F) Mean31.9 33.4 68.814.165.3 134.1S.D.6.1 6.4 9.78.211.4 18.7N11 11 111111 114(F) Mean28.4 29.357.310.557.7 114.9S.D.6.5 5.8 18.28.710.8 24.2N12 12 121212 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 86SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 9 Group Mean Food ConsumptionsDay Numbers Relative to Start DateGroup From: 1 8 29 36(Sex) To: 8 15 36 431(M) Mean 21.6 22.6 22.5 21.8N 12 12 12 122(M) Mean 21.1 22.1 23.0 22.7N 12 12 12 123(M) Mean 20.6 22.2 24.1 23.4N 12 12 12 124(M) Mean 20.6 21.1 20.4 22.4N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 87Table 9 (continued) Group Mean Food ConsumptionsDay Numbers Relative to Start DateGroup From: 1 8(Sex) To: 8 151(F) Mean 16.5 17.6N 12 122(F) Mean 15.8 17.1N 12 123(F) Mean 16.1 17.1N 12 124(F) Mean 15.5 17.0N 12 12Food Consumption = g/animal/day.Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 88SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 9 (continued) Group Mean Food ConsumptionsDay NumbersGestation LactationGroup(Sex)From: 0 7 14 1To: 7 14 20 41(F)Mean22.8 23.1 27.8 28.3S.D.2.1 3.4 3.3 4.2N11 11 11 102(F)Mean21.9 23.6 26.8 27.8S.D.2.1 4.0 2.9 6.3N12 12 12 123(F)Mean23.1 23.8 27.8 30.3S.D.2.2 3.8 2.6 4.6N11 11 11 114(F)Mean22.2 24.3 26.6 29.1S.D.3.4 2.8 3.3 5.5N12 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 89Table 10 Food EfficiencyDay Numbers Relative to Start DateGroup From: 1 8 29 36(Sex) To: 8 15 36 431(M) Mean 13.2 10.5 7.9 ƒ1.5N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ2(M) Mean 12.1 10.5 7.6 2.7N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ3(M) Mean 10.7 12.2 9.9 3.7N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4(M) Mean 12.2 8.4 9.9 3.2N 12 12 12 12ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 90SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 10 (continued) Food EfficiencyDay Numbers Relative to Start DateGroup From: 1 8(Sex) To: 8 151(F) Mean 11.0 7.1N 12 12ƒƒƒƒ ƒƒƒƒ2(F) Mean 9.6 8.6N 12 12ƒƒƒƒ ƒƒƒƒ3(F) Mean 8.9 8.2N 12 12ƒƒƒƒ ƒƒƒƒ4(F) Mean 8.3 6.6N 12 12ƒƒƒƒ ƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 91Table 11 Group Mean Daily Water ConsumptionsDay Numbers Relative to Start DateGroup From: 2 3 4 5 6 7 8 9 10 11 12 13 14(Sex) To: 3 4 5 6 7 8 9 10 11 12 13 14 151(M) Mean 26.7 33.3 29.3 34.3 30.3 33.3 32.3 31.7 31.3 36 34 31.7 32N 12 12 12 12 12 12 12 12 12 12 12 12 122(M) Mean 30 37.3 32.3 39.3 32 32.7 36.3 35 35.3 35.7 38 37.3 33.7N 12 12 12 12 12 12 12 12 12 12 12 12 123(M) Mean 31 36.3 29.3 35.7 30.7 33 32 37.3 33 38 41 34.7 33.3N 12 12 12 12 12 12 12 12 12 12 12 12 124(M) Mean 28.7 35.7 25 35 28.3 27.7 35 36.7 29 30 31.3 31.3 29.7N 12 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 92SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 11 (continued) Group Mean Daily Water ConsumptionsDay Numbers Relative to Start DateGroup From: 2 3 4 5 6 7 8 9 10 11 12 13 14(Sex) To: 3 4 5 6 7 8 9 10 11 12 13 14 151(F) Mean 23.3 28.7 21.7 27 26.3 25.3 27 26 27.3 26.3 25.3 24.7 27N 12 12 12 12 12 12 12 12 12 12 12 12 122(F) Mean 21 24 22.3 26.7 22.3 23 26 23.7 23.3 25.3 26.3 24 23.7N 12 12 12 12 12 12 12 12 12 12 12 12 123(F) Mean 23.7 27 22.3 26 24.7 25 28 27.7 25.3 25.7 28.3 24.3 27N 12 12 12 12 12 12 12 12 12 12 12 12 124(F) Mean 22 29.3 21 27.3 21.3 26.3 28 28 23 26.7 27.3 25 25.7N 8 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 93Table 12 Summary Incidence of Mating Performance, Fertility and Gestation LengthsGroupNumberofMalesPairedNumber of Females Pre-Coital Interval (Days)MatingIndex(%)PregnancyIndex(%)Gestation Length (Days)Femaleswith liveOffspringParturitionIndex (%)Paired Mated Pregnant1 2 3 4 1122 221⁄223 231⁄2241⁄21 1212 12 11 3 4 3 1 1 100 92 0 1 3 7 0 11 1002 1212 12 12 4 1 4 3 0 100 100 1 3 3 5 0 12 1003 1212 12 11 3 3 5 1 0 100 92 0 1 2 6 2 11 1004 1212 12 12 1 3 5 3 0 100 100 3 1 2 6 0 12 100Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 94SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 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 15.0 14.213.313.113.077.18106.82 6.085.858.478.152.392.30S.D. 2.4 2.1 2.3 2.3 2.4 9.92 11.98 0.51 0.43 0.96 0.92 0.49 0.50N 10 10 10 10 10 10 10 10 10 10 10 10 102 Mean 14.5 13.7 12.9 12.8 12.3 73.06 99.76 6.02 5.63 8.57 8.12 2.55 2.49S.D. 1.8 2.82.82.82.811.6415.36 0.540.651.201.270.700.68N 12 12 12 12 12 12 12 12 12 12 12 12 123 Mean 14.9 14.5 13.3 13.3 12.8 82.80 112.78 6.48 6.07 9.11 8.65 2.63 2.58S.D. 2.3 2.1 2.1 2.1 1.9 11.47 14.18 0.62 0.63 1.19 1.10 0.67 0.55N 11 111111111111 1111111111114 Mean 13.3 11.8 10.4* 10.3 10.2 64.46 90.87 6.54 6.19 9.56 9.10 3.02 2.91S.D. 2.5 3.3 3.8 3.7 3.7 21.55 26.23 0.60 0.76 1.48 1.51 0.97 0.88N 12 12 12 12 12 12 12 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 95Table 14 Group Mean Implantation Losses and Survival Indices ValuesGroupPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex (%)ViabilityIndex (%)1Mean4.7 6.4 98.6 99.1S.D.9.5 5.1 4.5 2.9N10 10 10 102Mean6.2 5.4 98.8 96.2S.D.14.3 5.2 2.9 7.4N12 12 12 123Mean2.7 8.3 100.0 97.0S.D.6.0 4.1 0.0 7.7N11 11 11 114Mean12.4 13.6 99.4 98.7S.D.16.2 17.5 2.1 3.1N12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 96SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 15 Group Mean Sex Ratio ValuesGroupSex Ratio (% Males) 

# Post PartumDay:At birth 1 41Mean55.6 54.9 55.4S.D.8.5 8.6 8.8N10 10 102Mean53.9 53.4 54.2S.D.13.2 13.1 13.1N12 12 123Mean53.7 53.7 54.3S.D.13.4 13.4 13.4N11 11 114Mean50.9 50.9 51.7S.D.15.3 15.3 16.1N12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 97Table 16 Summary Incidence of Clinical Signs for OffspringDose Level (mg/kg bw/day)0 (Control) 30 300 1000Number of litters 11 12 11 12Small. 1M 1F (2) . 3F (3)Cold.8M 6F (1) .1F (1)Bruising to neck region. 1F (1) . .Swollen abdomen. 1M (1) . .Swollen snout.. .1F (1)Missing 4M 11F (2) 3M 3F (3) 2M 3F (2) 2F (2)Found dead 2M (1) 2M (2) . 1M (1)() = Number of littersPROJECT NUMBER: 41104692RPAGE 98SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 17 Group Mean Reflexological Responses for OffspringGroup Surface Righting (% passed)1Mean94.6S.D.6.8N112Mean91.6S.D.7.2N123Mean94.7S.D.9.4N114Mean97.8S.D.5.6N12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 99Table 18 Group Mean Haematological ValuesGroup Hb RBC Hct MCH MCV MCHC WBC Neut(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l1(M) Mean 16.58 9.104 50.60 18.20 55.58 32.78 8.20 1.608S.D. 0.41 0.171 1.29 0.50 1.56 0.26 2.21 1.226N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(M) Mean 16.12 9.062 49.16 17.84 54.26 32.82 9.54 1.282S.D. 0.97 0.545 3.08 0.51 1.48 0.19 0.71 0.506N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(M) Mean 15.88 8.954 48.66 17.70 54.36 32.60 6.84 1.244S.D. 0.64 0.296 1.44 0.19 0.49 0.37 1.87 0.585N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 14.80* 8.280* 44.90** 17.88 54.26 32.92 6.00 0.870S.D. 1.47 0.875 4.70 0.19 0.42 0.23 1.18 0.382N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 100SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 18 (continued) Group Mean Haematological ValuesGroup Lymph Mono Eos Bas CT PLT APTT(Sex) 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(M) Mean 6.566 0.014n 0.014n 0.000n 9.72 529.2 15.34S.D. 1.390 0.031 0.031 0.000 0.66 41.4 3.39N 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(M) Mean 8.240 0.018n 0.000n 0.000n 9.72 625.0 15.88S.D. 1.018 0.040 0.000 0.000 0.41 71.8 1.50N 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(M) Mean 5.546 0.000n 0.050n 0.000n 9.72 600.4 15.04S.D. 1.739 0.000 0.062 0.000 0.59 108.7 1.67N 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(M) Mean 5.070 0.000n 0.058n 0.000n 9.60 531.0 13.32S.D. 1.237 0.000 0.058 0.000 0.49 47.2 1.88N 5 5 5 5 5 5 5ƒƒƒƒƒ 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 101Table 18 (continued) Group Mean Haematological ValuesGroup Hb RBC Hct MCH MCV MCHC WBC Neut(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l1(F) Mean 12.96 6.822 39.82 19.00 58.36 32.58 7.48 1.966S.D. 1.02 0.607 3.32 0.34 1.10 0.29 1.55 0.899N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(F) Mean 13.44 7.288 41.06 18.46 56.38 32.76 5.98 1.894S.D. 0.59 0.393 1.38 0.61 1.69 0.55 1.29 0.926N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(F) Mean 13.04 6.866 39.84 19.00 58.10 32.70 6.20 2.038S.D. 1.34 0.687 3.49 0.61 1.39 0.68 2.02 0.847N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 12.78 6.834 39.06 18.72 57.16 32.76 4.90* 1.526S.D. 3.04 1.652 9.42 0.57 1.62 0.33 1.35 0.598N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 102SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 18 (continued) Group Mean Haematological ValuesGroup Lymph Mono Eos Bas CT PLT APTT(Sex) 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds1(F) Mean 5.514 0.000n 0.000n 0.000n 9.76 912.2 15.88S.D. 1.497 0.000 0.000 0.000 1.01 33.4 2.85N 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2(F) Mean 4.086 0.000n 0.000n 0.000n 9.33 812.2 15.45S.D. 1.026 0.000 0.000 0.000 0.21 422.7 1.05N 5 5 5 5 4 5 4ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3(F) Mean 4.148 0.014n 0.000n 0.000n 9.76 891.4 14.58S.D. 1.451 0.031 0.000 0.000 0.77 104.7 2.39N 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4(F) Mean 3.350* 0.000n 0.028*,n 0.000n 9.74 658.6 16.10S.D. 0.976 0.000 0.048 0.000 0.62 375.2 1.45N 5 5 5 5 5 5 5ƒƒƒƒƒ 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 103Table 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 55.8 173.6 6.798 3.70 1.198 146.0 5.094 101.0 2.652S.D. 7.8 15.2 0.583 0.37 0.118 2.2 1.185 1.2 0.089N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(M) Mean 49.6 178.6 6.590 3.56 1.180 145.6 4.686 101.6 2.590S.D. 4.3 9.2 0.270 0.11 0.098 2.4 0.416 1.7 0.078N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(M) Mean 47.8 155.6 6.236* 3.60 1.368* 148.4 4.688 102.6 2.598S.D. 5.8 31.9 0.414 0.22 0.121 2.3 0.140 2.6 0.119N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(M) Mean 47.4 163.0 6.100* 3.56 1.432** 145.8 4.816 100.2 2.632S.D. 8.8 13.8 0.377 0.13 0.138 2.3 0.738 1.6 0.049N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 104SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 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 2.10 109.6 62.6 151.6 0.808 80.0 0.092 11.16S.D. 0.32 21.4 5.6 29.6 0.181 15.0 0.024 10.55N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(M) Mean 1.82 115.0 67.0 131.8 0.768 85.4 0.076 8.86S.D. 0.28 27.0 6.2 19.3 0.058 11.8 0.018 6.15N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(M) Mean 2.14 129.2 65.0 156.0 0.678* 81.2 0.064 9.52S.D. 0.27 18.2 11.7 61.3 0.039 5.9 0.015 9.53N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(M) Mean 2.02 141.0 73.6 147.6 0.630* 75.0 0.088 14.44S.D. 0.27 44.9 26.2 36.0 0.053 7.0 0.020 11.49N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 105Table 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 47.6 126.6 6.294 3.76 1.476 145.0 4.716 102.4 2.596S.D. 3.6 10.9 0.343 0.18 0.102 2.9 0.470 1.8 0.040N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ2(F) Mean 58.0 155.8* 5.916 3.54 1.496 145.8 4.718 104.0 2.550S.D. 11.0 22.6 0.352 0.27 0.236 1.8 0.694 1.4 0.118N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ3(F) Mean 49.8 130.2 6.050 3.60 1.470 145.0 4.246 103.2 2.478S.D. 3.1 11.0 0.524 0.29 0.096 1.9 0.330 1.9 0.128N 5 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ4(F) Mean 52.6 141.8 5.894 3.56 1.560 146.2 4.770 103.6 2.404*S.D. 7.7 14.6 0.680 0.29 0.217 3.8 0.691 2.4 0.201N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 106SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 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 1.66 85.6 80.4 113.6 0.664 77.8 0.084 11.36S.D. 0.31 15.0 15.9 29.1 0.032 28.4 0.011 8.71N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2(F) Mean 1.34 141.6 95.8 159.8 0.850 73.6 0.078 15.54S.D. 0.34 61.1 25.9 83.7 0.264 11.8 0.013 10.83N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3(F) Mean 1.14* 113.8 74.8 144.2 0.734 78.8 0.068 12.28S.D. 0.34 42.5 8.9 58.5 0.130 7.7 0.013 9.99N 5 5 5 5 5 5 5 5ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4(F) Mean 0.66** 117.2 80.2 179.6 0.696 78.4 0.080 11.56S.D. 0.34 46.5 8.1 93.2 0.129 15.2 0.020 4.87N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 107Table 20 Summary Incidence ofOffspring Necropsy FindingsInterim DeathsTerminal Kill (Day 5 

# Post Partu m)Group 

# Post-PartumDayof TerminationNumber ofaffectedLittersNumber ofoffspringMacroscopic FindingsNumberofLittersNumber ofOffspringMacroscopic Findings1 Pre Day 1 1 2MAutolytic changes detected10 . No abnormalities detected2 Pre Day 1 1 1M Autolytic changes detected 1 1F Small1 1 1M Autolytic changes detected 11 . No abnormalities detected3 1 1MEnlarged kidneys, leftkidney fluid filled10 . No abnormalities detected4 1 1 1M Autolytic changes detected 2 2F Small10 .No abnormalitiesdetectedDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 108SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 21 Summary Incidence of Necropsy Findings------------ MALES ------------Removal Reason: SCHEDULED KILL ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000(Control) mg/kg bw/dayNumber of Animals Examined : 12 12 1212Group : (1) (2) (3)(4)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒBrain (Including Cerebrum, Cerebellum And Pons);Submitted........................................................................................ (6) (6) (5)(5)No Visible Lesions............................................................................... 6 5 55Damaged On Removal .............................................................................. 0 1 00Epididymides;Submitted........................................................................................ (12) (12) (12)(12)No Visible Lesions............................................................................... 12 12 1112Small ........................................................................................... 0 0 10Lungs (With Bronchi);Submitted........................................................................................ (6) (6) (5)(5)No Visible Lesions............................................................................... 6 6 54Reddened ........................................................................................ 0 0 01Seminal Vesicles;Submitted........................................................................................ (12) (12) (12)(12)No Visible Lesions............................................................................... 11 12 1212Small; right horn ............................................................................... 1 0 00Spleen;Submitted........................................................................................ (6) (6) (5)(5)No Visible Lesions............................................................................... 6 6 54Dark ............................................................................................ 0 0 01Testes;Submitted........................................................................................ (12) (12) (12)(12)No Visible Lesions............................................................................... 12 12 1112Small ........................................................................................... 0 0 10Flaccid ......................................................................................... 0 0 10SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 109Table 21 (continued) Summary Incidence of Necropsy Findings----------- FEMALES -----------Removal Reason: SCHEDULED KILL ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000(Control) mg/kg bw/dayNumber of Animals Examined : 12 12 1212Group : (1) (2) (3)(4)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒGross Lesions;Submitted........................................................................................ (12) (12) (12)(12)No Visible Lesions............................................................................... 12 12 1211Mass; right fore limb ........................................................................... 0 0 01Kidneys;Submitted........................................................................................ (6) (5) (5)(5)No Visible Lesions............................................................................... 5 5 55Increased Pelvic Space; left .................................................................... 1 0 00Urinary Bladder;Submitted........................................................................................ (6) (5) (5)(5)No Visible Lesions............................................................................... 5 5 55Mineral Calculi ................................................................................. 1 0 00PROJECT NUMBER: 41104692RPAGE 110SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 22 Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000 0 30 300 1000Control mg/kg bw/day Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒTerminal Bodyweight ........... Mean (g) 387.8 391.2 392.7 396.8 271.8 270.7 278.3 273.2S.D. 19.8 15.2 17.9 23.1 19.8 16.6 17.7 21.0N 12 12 12 12 12 12 12 12Adrenals ...................... Mean (g) 0.06822 0.07550 0.08304 0.08130 0.10566 0.09568 0.09664 0.10288S.D. 0.01271 0.01836 0.01392 0.00665 0.01676 0.01249 0.01112 0.01068N 5 5 5 5 5 5 5 5Mean (%) 0.018 0.019 0.021 0.021 0.039 0.035 0.035 0.038S.D. 0.003 0.004 0.003 0.002 0.006 0.005 0.003 0.002N 5 5 5 5 5 5 5 5Brain (Including Cerebrum,Cerebellum And Pons) .......... Mean (g) 2.04764 2.08708 2.04328 2.04698 1.89254 1.86992 1.92750 1.86830S.D. 0.10479 0.07051 0.12760 0.05783 0.07104 0.05434 0.10713 0.06019N 5 5 5 5 5 5 5 5Mean (%) 0.532 0.518 0.517 0.522 0.696 0.674 0.707 0.689S.D. 0.019 0.011 0.027 0.012 0.052 0.039 0.051 0.065N 5 5 5 5 5 5 5 5Epididymides .................. Mean (g) 1.50231 1.48043 1.41907 1.47703S.D. 0.21300 0.23576 0.37600 0.12940N 12 12 12 12Mean (%) 0.387 0.378 0.362 0.374S.D. 0.051 0.058 0.097 0.042N 12 12 12 12Heart ......................... Mean (g) 0.99584 1.01492 1.08980 1.02040 0.88390 0.90178 0.87132 0.86090S.D. 0.03942 0.08959 0.11791 0.10876 0.10378 0.05219 0.06145 0.12236N 5 5 5 5 5 5 5 5Mean (%) 0.259 0.252 0.276 0.260 0.324 0.325 0.319 0.315S.D. 0.010 0.017 0.029 0.025 0.035 0.016 0.025 0.026N 5 5 5 5 5 5 5 5SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 111Table 22 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000 0 30 300 1000Control mg/kg bw/day Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒKidneys ....................... Mean (g) 2.37476 2.24916 2.33842 2.25434 1.72216 1.72392 1.66360 1.68630S.D. 0.19848 0.19924 0.23691 0.06681 0.11285 0.09355 0.19112 0.11478N 5 5 5 5 5 5 5 5Mean (%) 0.617 0.557 0.591 0.575 0.632 0.620 0.608 0.620S.D. 0.042 0.037 0.049 0.026 0.035 0.031 0.055 0.022N 5 5 5 5 5 5 5 5Liver ......................... Mean (g) 11.9881 12.2413 11.7700 11.5083 11.3415 11.2092 10.9708 10.9126S.D. 0.98753 1.27728 1.00921 1.25170 0.37037 0.52721 0.51282 1.44201N 5 5 5 5 5 5 5 5Mean (%) 3.117 3.033 2.978 2.932 4.169 4.038 4.016 3.993S.D. 0.239 0.255 0.265 0.253 0.281 0.256 0.120 0.292N 5 5 5 5 5 5 5 5Ovaries ....................... Mean (g) 0.12268 0.11463 0.11986 0.12328S.D. 0.02237 0.02122 0.01244 0.01441N 12 12 12 12Mean (%) 0.046 0.042 0.043 0.045S.D. 0.009 0.006 0.004 0.004N 12 12 12 12Pituitary ..................... Mean (g) 0.01053 0.01124 0.01071 0.00841** 0.01362 0.01458 0.01492 0.01438S.D. 0.00128 0.00214 0.00219 0.00137 0.00286 0.00282 0.00254 0.00285N 12 12 12 12 12 12 12 12Mean (%) 0.003 0.003 0.003 0.002** 0.005 0.005 0.005 0.005S.D. 0.000 0.001 0.001 0.000 0.001 0.001 0.001 0.001N 12 12 12 12 12 12 12 12PROJECT NUMBER: 41104692RPAGE 112SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Table 22 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000 0 30 300 1000Control mg/kg bw/day Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒProstate ...................... Mean (g) 0.65223 0.66563 0.60388 0.58856S.D. 0.07289 0.12843 0.11031 0.15725N 12 12 12 12Mean (%) 0.168 0.170 0.154 0.147S.D. 0.020 0.033 0.030 0.032N 12 12 12 12Seminal Vesicles .............. Mean (g) 2.33127 2.10186 2.26599 2.06461S.D. 0.19256 0.39853 0.40337 0.39151N 12 12 12 12Mean (%) 0.602 0.537 0.578 0.521S.D. 0.052 0.101 0.101 0.098N 12 12 12 12Spleen ........................ Mean (g) 0.72358 0.70430 0.72820 0.76134 0.64742 0.62800 0.68288 0.66776S.D. 0.11851 0.05583 0.07667 0.06513 0.06510 0.13053 0.07843 0.08914N 5 5 5 5 5 5 5 5Mean (%) 0.188 0.175 0.184 0.194 0.238 0.226 0.250 0.247S.D. 0.028 0.011 0.019 0.013 0.022 0.045 0.031 0.041N 5 5 5 5 5 5 5 5Testes ........................ Mean (g) 3.84450 3.72373 3.51740 3.82026S.D. 0.41833 0.25064 0.79151 0.33606N 12 12 12 12Mean (%) 0.993 0.952 0.898 0.966S.D. 0.113 0.061 0.203 0.102N 12 12 12 12SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 113Table 22 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weightsƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ0 30 300 1000 0 30 300 1000Control mg/kg bw/day Control mg/kg bw/dayƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒThymus ........................ Mean (g) 0.39198 0.47070 0.41596 0.42490 0.26990 0.27214 0.23954 0.25296S.D. 0.05982 0.09849 0.06967 0.09363 0.11311 0.08815 0.03036 0.06277N 5 5 5 5 5 5 5 5Mean (%) 0.102 0.117 0.105 0.108 0.098 0.098 0.088 0.093S.D. 0.015 0.023 0.018 0.021 0.038 0.032 0.013 0.022N 5 5 5 5 5 5 5 5Thyroid/Parathyroid ........... Mean (g) 0.01754 0.02020 0.01952 0.02070 0.01294 0.01728 0.01708 0.01872*S.D. 0.00512 0.00125 0.00411 0.00155 0.00186 0.00493 0.00409 0.00373N 5 5 5 5 5 5 5 5Mean (%) 0.005 0.005 0.005 0.005 0.005 0.006 0.006 0.007*S.D. 0.001 0.000 0.001 0.000 0.000 0.002 0.002 0.001N 5 5 5 5 5 5 5 5Uterus & Cervix ............... Mean (g) 0.74216 0.69504 0.67338 0.63584*S.D. 0.15435 0.08060 0.09863 0.13801N 12 12 12 12Mean (%) 0.274 0.257 0.243 0.232*S.D. 0.057 0.030 0.039 0.043N 12 12 12 12

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# FIGURESPROJECT NUMBER: 41104692RPAGE 116SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Figure 1 Group Mean Body Weights - MalesSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 117Figure 2 Group Mean Body Weights - FemalesPre-PairingPROJECT NUMBER: 41104692RPAGE 118SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Figure 2 (continued) Group Mean Body Weights - FemalesGestationSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 119Figure 3 Group Mean Food Consumption - MalesPROJECT NUMBER: 41104692RPAGE 120SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Figure 4 Group Mean Food Consumption - Females

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# APPENDICESPROJECT NUMBER: 41104692RPAGE 122SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 123Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 4 5 5 5 6 6 6 6 7 7 7 7 8 8(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 124SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 8 8 9 9 9 9 10 10 10 10 11 11 11 12(Sex) Number Clinical Sign 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 125Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 12 12 13 13 13 13 14 14 14 14 15 15 15 15(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 126SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 16 16 16 16 17 17 17 17 18 18 18 19 19 19(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 127Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 20 20 20 20 21 21 21 22 22 22 23 23 23 23(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 128SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 24 24 24 24 25 25 25 26 26 26 27 27 27 27(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 129Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 28 28 28 29 29 29 29 30 30 30 30 31 31 31(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 130SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 31 32 32 32 33 33 33 34 34 34 34 35 35 35(Sex) Number Clinical Sign 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 131Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 35 36 36 36 36 37 37 37 37 38 38 38 38 39(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 132SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 39 39 40 40 40 41 41 41 41 42 42 42 42 43(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h A.M.1(M) 1 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X3 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X5 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X7 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X9 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X11 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 133Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 134SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 4 5 5 5 6 6 6 6 7 7 7 7 8 8(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 135Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 8 8 9 9 9 9 10 10 10 10 11 11 11 12(Sex) Number Clinical Sign 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 136SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 12 12 13 13 13 13 14 14 14 14 15 15 15 15(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 137Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 16 16 16 16 17 17 17 17 18 18 18 19 19 19(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 138SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 20 20 20 20 21 21 21 22 22 22 23 23 23 23(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 139Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 24 24 24 24 25 25 25 26 26 26 27 27 27 27(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 140SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 28 28 28 29 29 29 29 30 30 30 30 31 31 31(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 141Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 31 32 32 32 33 33 33 34 34 34 34 35 35 35(Sex) Number Clinical Sign 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 142SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 35 36 36 36 36 37 37 37 37 38 38 38 38 39(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 143Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 39 39 40 40 40 41 41 41 41 42 42 42 42 43(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h A.M.2(M) 25 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X27 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X29 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X31 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X33 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X35 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . XX = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 144SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected X X X X X X X X X X X X X XAbnormal Gait . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 145Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 4 5 5 5 6 6 6 6 7 7 7 7 8 8(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected X X X X X X X X X X X X . .Abnormal Gait . . . . . . . . . . . . X XScheduled kill . . . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 146SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 8 8 9 9 9 9 10 10 10 10 11 11 11 12(Sex) Number Clinical Sign 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 147Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 12 12 13 13 13 13 14 14 14 14 15 15 15 15(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 148SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 16 16 16 16 17 17 17 17 18 18 18 19 19 19(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X . .Scab . . . . . . . . . . . . X XScheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X . .Scab . . . . . . . . . . . . X XScheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 149Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 20 20 20 20 21 21 21 22 22 22 23 23 23 23(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h3(M) 49 No Abnormalities Detected 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 XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected . . . . . . . . . . X X X XScab X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected . . . . . . . . . . X X X XScab X X X X X X X X X X . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 150SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 24 24 24 24 25 25 25 26 26 26 27 27 27 27(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h3(M) 49 No Abnormalities Detected 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 . . . .Scab . . . . . . . . . . X X X XScheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 151Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 28 28 28 29 29 29 29 30 30 30 30 31 31 31(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h3(M) 49 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .50 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected X X X . . . . . . . . . . .Scab . . . 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 XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected X X X . . . . . . . . . . .Scab . . . X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 152SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 31 32 32 32 33 33 33 34 34 34 34 35 35 35(Sex) Number Clinical Sign 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h3(M) 49 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .50 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected . . . . . . . . . . . . . .Scab 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 XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 153Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 35 36 36 36 36 37 37 37 37 38 38 38 38 39(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre3(M) 49 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .50 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .51 No Abnormalities Detected . . . . . . . . . . . . . .Scab 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 XScheduled kill . . . . . . . . . . . . . .53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . .56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . .58 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 154SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 39 39 40 40 40 41 41 41 41 42 42 42 42 43(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h A.M.3(M) 49 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X50 No Abnormalities Detected . . . . . . . . . . . . . XScab X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . X51 No Abnormalities Detected . . . . . . . . . . . . . XScab X X X X X X X X X X X X X .Scheduled kill . . . . . . . . . . . . . X52 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X53 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X54 No Abnormalities Detected 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 XScheduled kill . . . . . . . . . . . . . X56 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X57 No Abnormalities Detected X X X X X X X X X X X X X XScab . . . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . . . X58 No Abnormalities Detected . . . . . . . . . . . . . .Scab X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X59 No Abnormalities Detected . . . . . . . . . . . . . .Abnormal Gait 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 155Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 156SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 4 5 5 5 6 6 6 6 7 7 7 7 8 8(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 157Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 8 8 9 9 9 9 10 10 10 10 11 11 11 12(Sex) Number Clinical Sign 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 158SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 12 12 13 13 13 13 14 14 14 14 15 15 15 15(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 159Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 16 16 16 16 17 17 17 17 18 18 18 19 19 19(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 160SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 20 20 20 20 21 21 21 22 22 22 23 23 23 23(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 161Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 24 24 24 24 25 25 25 26 26 26 27 27 27 27(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 162SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 28 28 28 29 29 29 29 30 30 30 30 31 31 31(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 163Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 31 32 32 32 33 33 33 34 34 34 34 35 35 35(Sex) Number Clinical Sign 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 164SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 35 36 36 36 36 37 37 37 37 38 38 38 38 39(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 165Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 39 39 40 40 40 41 41 41 41 42 42 42 42 43(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h A.M.3(M) 60 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 166SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 167Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 4 5 5 5 6 6 6 6 7 7 7 7 8 8(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 168SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 8 8 9 9 9 9 10 10 10 10 11 11 11 12(Sex) Number Clinical Sign 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 169Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 12 12 13 13 13 13 14 14 14 14 15 15 15 15(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 170SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 16 16 16 16 17 17 17 17 18 18 18 19 19 19(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 171Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 20 20 20 20 21 21 21 22 22 22 23 23 23 23(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 172SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 24 24 24 24 25 25 25 26 26 26 27 27 27 27(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 173Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 28 28 28 29 29 29 29 30 30 30 30 31 31 31(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 174SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 31 32 32 32 33 33 33 34 34 34 34 35 35 35(Sex) Number Clinical Sign 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X . .Scheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . X X77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 175Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 35 36 36 36 36 37 37 37 37 38 38 38 38 39(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . .84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 176SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 39 39 40 40 40 41 41 41 41 42 42 42 42 43(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h A.M.4(M) 73 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X74 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X75 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X76 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . XNoisy respiration . . . . . . . . . . . . . .77 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X78 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X79 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X80 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X81 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X82 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X83 No Abnormalities Detected X X X X X X X X X X X X X XScheduled kill . . . . . . . . . . . . . X84 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 177Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 178SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 179Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 180SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 181Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 182SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 183Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 184SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 185Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 186SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.1(F) 13 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected . . . . X X X X X X X X X X.Littering X X X X . . . . . . . . . ..Not Observed Due to Littering . X X X . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . .X22 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 187Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.1(F) 13 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..14 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..15 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..16 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X17 No Abnormalities Detected X X X X . X X X X . X X X X.Scheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..19 No Abnormalities Detected X X X X X . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..20 No Abnormalities Detected X X X X . X X X X . X X X X.Scheduled kill . . . . . . . . . . . . . ..21 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X23 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..24 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 188SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre1(F) 13 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..14 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..15 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..16 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..17 No Abnormalities Detected X X X X . X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..18 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..19 No Abnormalities Detected . . . . . . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..20 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..21 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..22 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..23 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..24 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 189Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.1(F) 13 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .14 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .15 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .16 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .17 No Abnormalities Detected X X X X X X X X X X X XScheduled kill . . . . . . . . . . . X18 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .19 No Abnormalities Detected . . . . . . . . . . . .Littering . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .20 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .21 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .22 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .23 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .24 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 190SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 191Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 192SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 193Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 194SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 195Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 196SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 197Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 198SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 199Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.2(F) 37 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . .X42 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . .X47 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 200SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.2(F) 37 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..38 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X39 No Abnormalities Detected X X X X . X X X X . X X X X.Scheduled kill . . . . . . . . . . . . . ..40 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X41 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..43 No Abnormalities Detected X X X X . X X X X X . . . ..Scheduled kill . . . . . . . . . X . . . ..44 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..45 No Abnormalities Detected X X X X . X X X X X . . . ..Scheduled kill . . . . . . . . . X . . . ..46 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 201Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre2(F) 37 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..38 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..39 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..40 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..41 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..42 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..43 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..44 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..45 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..46 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..47 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 202SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.2(F) 37 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .38 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .39 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .40 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .41 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .42 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .43 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .44 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .45 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .46 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .47 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 203Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 204SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 205Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 206SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 207Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 208SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 209Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 210SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 211Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X XXRespiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 212SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.2(F) 48 No Abnormalities Detected X X X X X X X X X X X X X X.Respiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 213Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.2(F) 48 No Abnormalities Detected X . . . . X X X X . X X X XXRespiration ƒ Laboured . X . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . .XIncreased salivation . X . . . . . . . . . . . ..Noisy respiration . X . . . . . . . . . . . ..Piloƒerection . . X X . . . . . . . . . ..Hunched posture . X X X . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 214SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre2(F) 48 No Abnormalities Detected . . . . . . . . . . . . . ..Respiration ƒ Laboured . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Increased salivation . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..Piloƒerection . . . . . . . . . . . . . ..Hunched posture . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 215Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.2(F) 48 No Abnormalities Detected . . . . . . . . . . . .Respiration ƒ Laboured . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .Increased salivation . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . .Piloƒerection . . . . . . . . . . . .Hunched posture . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 216SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 217Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 218SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 219Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 220SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 221Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 222SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 223Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X . . . . . . . X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . X X X X X X X . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 224SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 225Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.3(F) 61 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected X X X X X X X . . . X X X X.Littering . . . . . . . X X X . . . ..Not Observed Due to Littering . . . . . . . . X X . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected X X X X X X X . . . X X X X.Littering . . . . . . . X X X . . . ..Not Observed Due to Littering . . . . . . . . X X . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . .X70 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 226SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.3(F) 61 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..62 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..63 No Abnormalities Detected X X X X . X X X X . X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . .XNoisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X65 No Abnormalities Detected 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 XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . .X67 No Abnormalities Detected X X X X . X X X X X . . . ..Scheduled kill . . . . . . . . . X . . . ..68 No Abnormalities Detected X X X X . X X X . X . . . ..Scheduled kill . . . . . . . . . X . . . ..69 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..71 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 227Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre3(F) 61 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..62 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..63 No Abnormalities Detected . . . . . . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..Noisy respiration . . . . . . . . . . . . . ..64 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..65 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..66 No Abnormalities Detected . . . . . . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..67 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..68 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..69 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..70 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..71 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 228SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.3(F) 61 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .62 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .63 No Abnormalities Detected . . . . . . . . . . . .Littering . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .Noisy respiration . . . . . . . . . . . .64 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .65 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .66 No Abnormalities Detected . . . . . . . . . . . .Littering . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .67 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .68 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .69 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .70 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .71 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 229Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 230SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 231Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 232SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 233Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 234SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 235Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 236SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 237Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 238SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.3(F) 72 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 239Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.3(F) 72 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .XX = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 240SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre3(F) 72 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 241Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.3(F) 72 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 242SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 243Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 244SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 245Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 246SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 247Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 248SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X X X X X X X X X X XXMass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 249Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected X X X X . . . . . . . . . ..Mass . . . . X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 250SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X X X X X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected . . . . . . . . . . . . . ..Mass X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 251Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.4(F) 85 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected X X X X X X X . . . X X X X.Littering . . . . . . . X X X . . . ..Not Observed Due to Littering . . . . . . . . X X . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected X X X X X X X . . . X X X X.Littering . . . . . . . X X X . . . ..Not Observed Due to Littering . . . . . . . . X X . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . .X91 No Abnormalities Detected . . . . . . . . . . . . . ..Mass X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 252SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.4(F) 85 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..86 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..87 No Abnormalities Detected X X X X . X X X X . X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . .X88 No Abnormalities Detected X X X X . X X X X . X X X XXLittering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . .X89 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X90 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected . . . . . . . . . . . . . ..Mass X X X X . X X X X X . . . ..Scheduled kill . . . . . . . . . X . . . ..92 No Abnormalities Detected X X X X . X X X X . X X X X.Scheduled kill . . . . . . . . . . . . . ..93 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X94 No Abnormalities Detected X X X X . X X X X . X X X XXScheduled kill . . . . . . . . . . . . . .X95 No Abnormalities Detected X X X X . X X X X . X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 253Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre4(F) 85 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..86 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..87 No Abnormalities Detected . . . . . . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..88 No Abnormalities Detected . . . . . . . . . . . . . ..Littering . . . . . . . . . . . . . ..Not Observed Due to Littering . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..89 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..90 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..91 No Abnormalities Detected . . . . . . . . . . . . . ..Mass . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..92 No Abnormalities Detected X X X X X . . . . . . . . ..Scheduled kill . . . . X . . . . . . . . ..93 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..94 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..95 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 254SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.4(F) 85 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .86 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .87 No Abnormalities Detected . . . . . . . . . . . .Littering . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .88 No Abnormalities Detected . . . . . . . . . . . .Littering . . . . . . . . . . . .Not Observed Due to Littering . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .89 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .90 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .91 No Abnormalities Detected . . . . . . . . . . . .Mass . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .92 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .93 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .94 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .95 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 255Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start DateGroup Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 44(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post1h4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 256SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 88(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 257Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 1213(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 258SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 1616(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 259Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 2021(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hPre4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 260SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 21 21 22 22 22 23 23 23 23 24 24 24 24 2525(Sex) Number Clinical Sign Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h PrePost4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 261Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 25 26 26 26 27 27 27 27 28 28 28 29 29 2929(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h Pre Post 1h5h4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day yPROJECT NUMBER: 41104692RPAGE 262SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 30 30 30 30 31 31 31 31 32 32 32 33 33 3334(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1hPre4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 263Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 34 34 34 35 35 35 35 36 36 36 36 37 37 3737(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h5h4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X XXScheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 264SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 38 38 38 38 39 39 39 40 40 40 41 41 41 4142(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5hA.M.4(F) 96 No Abnormalities Detected X X X X X X X X X X X X X X.Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 265Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 42 42 42 42 43 43 43 43 43 44 44 44 44 4445(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5hA.M.4(F) 96 No Abnormalities Detected 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 266SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 45 45 45 45 46 46 46 47 47 47 48 48 48 4849(Sex) Number Clinical Sign Pre Post 1h 5h A.M. Pre 1h Pre Post 1h Pre Post 1h 5hPre4(F) 96 No Abnormalities Detected . . . . . . . . . . . . . ..Scheduled kill . . . . . . . . . . . . . ..X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 267Appendix 1 (continued) Individual Daily Clinical ObservationsDay Numbers Relative to Start Date(continued)Group Animal 49 49 49 50 50 50 50 51 51 51 51 52(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h A.M.4(F) 96 No Abnormalities Detected . . . . . . . . . . . .Scheduled kill . . . . . . . . . . . .X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 268SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 2 Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 411(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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 269Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 4 

# post partum#1(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 X# = Day 25 

# post coitumfor Female 21X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 270SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 412(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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 271Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 4 

# post partum2(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 XX = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 272SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 413(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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 273Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 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 69X = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 274SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 414(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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 275Appendix 2 (continued) Individual Behavioural Assessments (Observations)Day Numbers Relative to Start DateGroup Animal(Sex) Number Clinical Sign -1 7 14 20 27 35 4 

# post partum4(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 XX = PresentDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 276SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 Individual and Group Mean 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 0 0 03 0 0 0 04 0 0 0 05 0 0 0 06 0 0 0 07 0 1 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 277Appendix 3 (continued) Individual and GroupMean Behavioural 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 0 0 015 0 0 0 016 0 1 0 017 0 1 1 018 0 0 0 019 0 0 0 020 0 1 0 021 0 0 0 022 0 0 0 023 0 0 0 024 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 278SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 279Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: ƒ1 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 280SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 0 0 053 0 0 0 054 0 1 0 055 0 1 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 0.2 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 281Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 282SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: ƒ1 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 283Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 1 089 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 284SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 05 0 0 0 06 0 0 0 07 0 1 0 08 0 0 0 09 0 1 0 010 0 1 0 011 0 1 0 012 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 285Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 021 0 0 0 022 0 0 0 023 0 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 286SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 027 0 0 0 028 0 0 0 029 0 1 0 030 0 0 0 031 0 1 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 0.3 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 287Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 041 0 0 0 042 0 0 0 043 0 0 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 0.2 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 288SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 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 0.2 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 289Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 290SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 076 0 0 1 077 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 291Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 091 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 0.1 0.0S.D. 0.0 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 292SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 293Appendix 3 (continued) Individual and GroupMean Behavioural 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 294SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 295Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(F) 37 0 0 0 038 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 0 0 047 0 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 296SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 14 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(M) 49 0 1 0 050 0 1 0 051 0 0 0 052 0 0 0 053 0 0 0 054 0 0 0 055 0 1 0 056 0 0 0 057 0 1 0 058 0 0 0 059 0 1 0 060 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 297Appendix 3 (continued) Individual and GroupMean Behavioural 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 0 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 298SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 077 0 0 0 078 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 299Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 1 087 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 300SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 301Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 0 0 016 0 0 0 017 0 0 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 302SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation2(M) 25 0 0 0 026 0 1 1 027 0 0 0 028 0 0 0 029 0 0 0 030 0 0 0 031 0 0 0 032 0 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 303Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 0 045 0 0 0 046 0 0 0 047 0 0 0 048 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 304SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 1 0 055 0 1 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 0.2 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 305Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 306SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 307Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 20 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 308SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 309Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 310SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 311Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 1 0 042 0 0 0 043 0 0 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 312SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 1 058 0 0 0 059 0 0 0 060 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.0 0.1 0.0S.D. 0.0 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 313Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 0 064 0 0 0 065 0 0 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 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 314SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 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 1 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 315Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 27 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 1 0 087 0 0 0 088 0 0 0 089 0 1 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 0.2 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 316SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 0 0 06 0 0 0 07 0 0 0 08 0 0 0 09 0 1 0 010 0 0 0 011 0 0 0 012 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 317Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 35 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 1 014 0 0 0 015 0 1 0 016 0 0 0 017 0 0 0 018 0 0 0 019 0 1 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 318SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 35 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 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 319Appendix 3 (continued) Individual and GroupMean Behavioural 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 1 0 043 0 0 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 320SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 35 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 321Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 35 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 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 322SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 323Appendix 3 (continued) Individual and GroupMean Behavioural 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 0 0 090 0 0 0 091 0 0 0 092 0 0 0 093 0 0 0 094 0 0 0 095 0 1 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 324SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 41 Relative to Start DateGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(M) 1 0 1 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 0.1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 325Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 4 

# post partum#Group Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation1(F) 13 0 0 0 014 0 0 0 015 0 1 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 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 ƒƒƒƒƒƒƒƒ# = Day 25 

# post coitumfor Female 21Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 326SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 41 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 3 028 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 0.0 0.3 0.0S.D. 0.0 0.0 0.9 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 327Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 4 

# post partumGroup 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 1 0 045 0 0 0 046 0 0 0 047 0 1 1 048 0 0 1 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.2 0.2 0.0S.D. 0.0 0.4 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 328SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 41 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 329Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 4 

# post partum#Group Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation3(F) 61 0 1 1 062 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 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 0.2 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 69Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 330SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 41 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 331Appendix 3 (continued) Individual and GroupMean Behavioural Assessments (Scores)Day: 4 

# post partumGroup Animal Transfer Urinƒ Defƒ Tail elƒ(Sex) Number arousal ation ecation evation4(F) 85 0 0 0 086 0 0 0 087 0 1 1 088 0 0 0 089 0 1 0 090 0 0 0 091 0 0 0 092 0 1 0 093 0 0 0 094 0 0 0 095 0 0 0 096 0 0 0 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 0.0 0.3 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 332SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 4 Individual and Group Mean Functional Test Values (Grip Strength)Day: 41 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) 1 793 225 1269 285 747 4222 1075 228 1574 326 958 4003 774 322 503 291 659 2824 1439 656 756 467 1160 4905 1325 547 1024 800 978 298ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 1081.2 395.6 1025.2 433.8 900.4 378.4S.D. 302.0 195.8 420.1 217.6 199.1 87.4N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 333Appendix 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) 13 541 129 706 296 940 26014 885 303 806 345 812 38915 924 108 737 207 1042 62218 888 387 830 141 699 32119 769 230 565 226 649 207ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 801.4 231.4 728.8 243.0 828.4 359.8S.D. 156.8 117.3 104.4 79.4 163.8 161.6N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 334SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 41 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 1408 506 1033 541 1179 59026 841 625 962 476 1479 31827 927 536 1312 434 786 35628 830 652 412 327 660 48729 677 553 639 321 666 239ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 936.6 574.4 871.6 419.8 954.0 398.0S.D. 278.5 61.6 351.3 95.4 361.9 139.8N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 335Appendix 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 1257 546 1359 549 924 57741 466 334 995 199 508 29242 960 386 1013 308 806 33344 1347 569 611 371 1133 41146 740 148 419 244 763 280ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 954.0 396.6 879.4 334.2 826.8 378.6S.D. 364.1 171.7 369.2 136.6 228.8 122.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 336SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 41 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 1231 484 618 128 1175 56250 913 286 630 312 1066 54151 965 599 826 347 616 56152 1259 414 1193 493 1429 22453 1272 341 910 496 987 359ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 1128.0 424.8 835.4 355.2 1054.6 449.4S.D. 174.1 122.7 236.1 152.0 296.5 152.1N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 337Appendix 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) 61 1254 450 832 566 1273 62162 717 316 1411 859 652 28465 748 420 893 323 828 38867 722 348 1005 395 520 18770 800 369 1233 970 952 248ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 848.2 380.6 1074.8 622.6 845.0 345.6S.D. 229.2 54.2 242.3 283.4 290.6 170.4N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 338SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)Day: 41 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) 73 822 148 1035 147 1091 56874 750 485 955 770 823 43275 1244 916 878 349 933 48276 1279 505 906 298 1100 40677 1217 393 1071 661 1481 551ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 1062.4 489.4 969.0 445.0 1085.6 487.8S.D. 254.5 277.5 82.5 260.7 249.4 71.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 339Appendix 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) 85 1025 272 974 348 1308 50486 1120 716 1335 984 1069 49690 569 207 739 338 708 46791 656 324 653 357 700 11896 1397 627 1506 415 625 312ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 953.4 429.2 1041.4 488.4 882.0 379.4S.D. 341.3 227.2 370.4 278.7 294.1 165.6N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 340SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 5 Individual and Group Mean Functional Test Values (Motor Activity)Day: 41 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile1(M) 1 118 0 11 02 274 0 79 03 291 0 0 04 254 0 6 05 471 0 29 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 281.6 0.0 25.0 0.0S.D. 126.0 0.0 32.1 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 341Appendix 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) 13 423 2 9 014 546 1 49 015 310 0 4 018 492 4 53 019 562 3 87 1ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 466.6 2.0 40.4 0.2S.D. 103.0 1.6 34.3 0.4N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 342SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 41 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile2(M) 25 316 1 86 026 205 0 6 027 284 3 0 028 386 0 118 029 527 0 11 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 343.6 0.8 44.2 0.0S.D. 121.4 1.3 54.1 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 343Appendix 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) 37 373 4 6 041 469 1 19 042 369 2 3 044 422 2 2 046 681 1 117 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 462.8 2.0 29.4 0.0S.D. 128.6 1.2 49.4 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 344SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 41 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile3(M) 49 364 0 41 050 177 0 11 051 344 1 5 052 289 1 9 053 219 0 9 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 278.6 0.4 15.0 0.0S.D. 79.9 0.5 14.7 0.0N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 345Appendix 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) 61 227 0 14 062 296 1 10 065 204 4 110 267 240 1 102 070 580 2 77 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 309.4 1.6 62.6 0.4S.D. 155.0 1.5 47.8 0.9N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 346SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)Day: 41 Relative to Start DateGroup Animal Overall Overall Last 20% Last 20%(Sex) Number activity mobile activity mobile4(M) 73 604 3 148 174 240 0 23 075 499 1 17 076 323 0 0 077 336 2 4 0ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 400.4 1.2 38.4 0.2S.D. 147.5 1.3 62.0 0.4N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 347Appendix 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) 85 603 7 88 386 464 4 127 090 481 5 19 191 15 0 5 096 372 3 100 1ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒMean 387.0 3.8 67.8 1.0S.D. 223.6 2.6 53.1 1.2N 5 5 5 5ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 348SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 6 Individual and Group Mean Sensory Reactivity AssessmentsDay: 41 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 349Appendix 6 (continued) Individual and Group Mean Sensory 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 0 014 0 0 0 0 0 0 0 0 015 0 0 0 0 0 0 0 0 018 0 0 0 0 0 0 0 0 019 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 350SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 6 (continued) Individual and Group Mean Sensory Reactivity AssessmentsDay: 41 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 0 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 351Appendix 6 (continued) Individual and Group Mean Sensory 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 0 041 0 0 0 0 0 0 0 0 042 0 0 0 0 0 0 0 0 044 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 352SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 6 (continued) Individual and Group Mean Sensory Reactivity AssessmentsDay: 41 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 0 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 0.0 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 353Appendix 6 (continued) Individual and Group Mean Sensory 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) 61 0 0 0 0 0 0 0 0 062 0 0 0 0 0 0 0 0 065 0 0 0 0 0 0 0 0 067 0 0 0 0 0 0 0 0 070 0 1 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 354SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 6 (continued) Individual and Group Mean Sensory Reactivity AssessmentsDay: 41 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 355Appendix 6 (continued) Individual and Group Mean Sensory 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) 85 0 0 0 0 0 0 0 0 086 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 0 096 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 356SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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) 1 317 340 360 371 385 395 3962 317 332 347 362 376 388 3863 333 356 363 379 382 394 3844 319 344 357 366 372 380 3695 330 355 376 385 374 382 3886 340 360 383 388 393 408 4137 333 354 372 378 392 410 4188 335 358 374 367 368 390 3919 323 338 355 360 369 382 38710 315 329 342 342 353 370 36111 316 336 353 359 365 371 35312 334 351 371 385 398 407 408ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 326.0 346.1 362.8 370.2 377.3 389.8 387.8S.D. 9.0 10.9 12.6 13.5 13.2 13.6 19.8N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 357Appendix 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) 25 332 353 371 386 400 420 42526 324 348 362 365 378 392 39527 335 353 366 375 391 398 40828 320 335 349 358 370 380 38429 331 350 375 382 388 401 40430 313 329 351 359 370 379 38531 327 342 362 366 376 384 38632 328 343 359 364 377 391 39633 321 338 353 356 359 372 37334 314 341 361 370 367 381 37535 329 349 365 368 367 374 38436 325 332 334 340 354 371 379ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 324.9 342.8 359.0 365.8 374.8 386.9 391.2S.D. 6.9 8.1 11.0 12.2 13.3 14.3 15.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 358SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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) 49 335 341 359 379 390 404 40750 329 348 375 360 371 379 39751 313 315 335 322 319 351 37152 326 340 355 333 333 373 38553 333 355 374 387 402 416 41854 322 336 356 369 389 395 40455 329 347 367 376 388 402 41056 331 355 368 372 376 395 39657 315 331 357 356 389 408 40858 306 327 344 335 353 365 36259 302 319 340 345 360 372 37460 315 329 340 349 364 375 380ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 321.3 336.9 355.8 356.9 369.5 386.3 392.7S.D. 10.9 13.2 13.7 20.5 25.0 19.8 17.9N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 359Appendix 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) 73 324 341 355 362 380 394 39774 315 336 346 352 364 372 36875 323 327 336 345 364 381 39076 326 339 356 366 388 400 39777 332 352 370 371 385 401 40978 315 328 332 345 353 362 36879 321 342 350 349 362 369 37680 331 361 377 383 400 412 42181 336 357 371 374 387 403 40882 333 352 367 363 375 387 39083 346 367 383 400 411 438 44984 324 334 342 349 364 382 388ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 327.2 344.7 357.1 363.3 377.8 391.8 396.8S.D. 8.9 13.0 16.5 16.9 17.3 21.0 23.1N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 360SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 151(F) 13 208 223 23514 211 225 23715 202 207 22016 213 220 22617 206 249 25718 206 223 23619 201 206 21920 207 211 21221 205 220 22822 207 218 21923 195 202 20824 213 223 235ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 206.2 218.9 227.7S.D. 5.1 12.3 13.4N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 361Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 152(F) 37 204 206 22338 201 206 20939 200 207 21140 203 212 22141 195 205 22142 194 206 22043 199 217 22744 195 211 22345 212 227 23246 204 215 23047 209 225 23548 214 221 228ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 202.5 213.2 223.3S.D. 6.6 7.8 7.8N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 362SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 153(F) 61 205 206 22562 201 214 22563 217 220 23164 208 219 23665 202 217 22666 208 224 23067 207 216 22468 207 224 23569 217 221 23670 200 211 21971 204 209 21072 213 228 231ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 207.4 217.4 227.3S.D. 5.7 6.6 7.6N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 363Appendix 7 (continued) Individual and Group Mean Body WeightsBody Weights (g)ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒDay Numbers Relative to Start DateGroup Animal(Sex) Number 1 8 154(F) 85 192 201 20886 198 205 21387 199 207 21588 210 226 23789 206 216 22190 200 207 22191 201 208 21992 200 213 21493 212 225 23594 191 188 19095 199 206 20996 210 223 237ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒMean 201.5 210.4 218.3S.D. 6.8 11.0 13.6N 12 12 12ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 364SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 41(F) 13 237 256 286 364 261 26714241264297374 26828315 219 251 280 355 248 26816 TLL 230 259 285 352 253 25917 274 301 333 409 291 30918 236 261 288 345 274 27719 214 246 275 354 243 26120 219 244 272 327 233 24721 NP 228 258 250 255 . .22 222 257 291 359 251 27023 206 235 260 323 232 23724 242 265 308 381 278 293Mean 230.9 258.1 288.6 358.5 257.9 271.2S.D. 18.5 16.9 19.5 24.2 19.8 21.0N 11 11 11 11 10 10Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 365Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 42(F) 37 223 253 274 317 272 27738220246277343 23724639 224 249 278 343 269 28040 224 244 276 330 236 24641214251280347 24025542 217 248 282 347 250 27643 232 255 291 353 245 26244223257298378 27128345 235 257 288 348 271 28146 225 264 306 369 289 29447 236 264 294 358 251 27348 240 271 311 379 270 285Mean 226.1 254.9 287.9 351.0 258.4 271.5S.D. 8.0 8.2 12.3 18.2 17.3 15.7N 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 366SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 43(F) 61 219 258 293 358 253 28262220253289367 25526063 232 268 304 386 255 27364 240 277 318 385 289 30265 223 260 295 368 276 28566 233 268 304 388 255 26767 228 251 285 353 260 27368 226 261 294 351 254 28369 NP 231 262 261 266 . .70 218 244 273 333 259 26771 218 240 256 311 239 25272 246 274 310 378 281 287Mean 227.5 259.5 292.8 361.6 261.5 275.5S.D. 9.4 11.8 17.3 24.0 14.5 14.0N 11 11 11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 367Appendix 7 (continued) Individual and Group Mean Body WeightsGroup(Sex)AnimalNumberBody Weights (g) DayAfter Mating Lactation0 7 14 20 1 44(F) 85 194 220 241 296 220 24186212237269342 26026687 219 249 285 331 272 27188 247 265 290 357 251 27889226254282327 26627590 221 255 287 344 268 28391 219 252 291 366 267 28092224261287321 28027993 236 273 307 387 282 29694 194 212 236 292 219 23395 218 242 264 286 257 25796 243 274 306 383 292 301Mean 221.1 249.5 278.8 336.0 261.2 271.7S.D. 16.4 19.2 22.5 33.9 22.5 20.1N 12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 368SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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 23 20 11 14 10 12 15 15 15 14 12 ƒ23 23 7 16 3 12 ƒ104 25 13 9 6 8 ƒ115 25 21 9 ƒ11 8 66 20 23 5 5 15 57 21 18 6 14 18 88 23 16 ƒ7 1 22 19 15 17 5 9 13 510 14 13 0 11 17 ƒ911 20 17 6 6 6 ƒ1812 17 20 14 13 9 1ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 20.1 16.7 7.4 7.1 12.5 ƒ1.9S.D. 4.0 4.3 6.5 7.3 4.8 8.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 369Appendix 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 21 18 15 14 20 526 24 14 3 13 14 327 18 13 9 16 7 1028 15 14 9 12 10 429 19 25 7 6 13 330 16 22 8 11 9 631 15 20 4 10 8 232 15 16 5 13 14 533 17 15 3 3 13 134 27 20 9 ƒ3 14 ƒ635 20 16 3 ƒ1 7 1036 7 2 6 14 17 8ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 17.8 16.3 6.8 9.0 12.2 4.3S.D. 5.1 5.8 3.5 6.3 4.1 4.4N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 370SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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 6 18 20 11 14 350 19 27 ƒ15 11 8 1851 2 20 ƒ13 ƒ3 32 2052 14 15 ƒ22 0 40 1253 22 19 13 15 14 254 14 20 13 20 6 955 18 20 9 12 14 856 24 13 4 4 19 157 16 26 ƒ1 33 19 058 21 17 ƒ9 18 12 ƒ359 17 21 5 15 12 260 14 11 9 15 11 5ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 15.6 18.9 1.1 12.6 16.8 6.4S.D. 6.4 4.7 13.1 9.5 9.9 7.2N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 371Appendix 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 17 14 7 18 14 374 21 10 6 12 8 ƒ475 4 9 9 19 17 976 13 17 10 22 12 ƒ377 20 18 1 14 16 878 13 4 13 8 9 679 21 8 ƒ1 13 7 780 30 16 6 17 12 981 21 14 3 13 16 582 19 15 ƒ4 12 12 383 21 16 17 11 27 1184 10 8 7 15 18 6ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒMean 17.5 12.4 6.2 14.5 14.0 5.0S.D. 6.7 4.4 5.9 3.9 5.4 4.6N 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 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 372SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 151(F) 13 15 1214 14 1215 5 1316 7 617 43 818 17 1319 5 1320 4 121 15 822 11 123 7 624 10 12ƒƒƒƒ ƒƒƒƒMean 12.8 8.8S.D. 10.5 4.5N 12 12ƒƒƒƒ ƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 373Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 152(F) 37 2 1738 5 339 7 440 9 941 10 1642 12 1443 18 1044 16 1245 15 546 11 1547 16 1048 7 7ƒƒƒƒ ƒƒƒƒMean 10.7 10.2S.D. 4.9 4.8N 12 12ƒƒƒƒ ƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 374SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 153(F) 61 1 1962 13 1163 3 1164 11 1765 15 966 16 667 9 868 17 1169 4 1570 11 871 5 172 15 3ƒƒƒƒ ƒƒƒƒMean 10.0 9.9S.D. 5.5 5.3N 12 12ƒƒƒƒ ƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 375Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)Day Numbers Relative to Start DateGroup Animal From: 1 8(Sex) Number To: 8 154(F) 85 9 786 7 887 8 888 16 1189 10 590 7 1491 7 1192 13 193 13 1094 ƒ3 295 7 396 13 14ƒƒƒƒ ƒƒƒƒMean 8.9 7.8S.D. 4.9 4.4N 12 12ƒƒƒƒ ƒƒƒƒDose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 376SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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)1319 30 78 6 49 1271423 33 77 15 56 1331532 29 75 20 61 13616 TLL29 26 67 6 55 1221727 32 76 18 59 1351825 27 57 3 52 1091932 29 79 18 61 1402025 28 55 14 53 10821 NP30 -8 5 . 22 272235 34 68 19 69 1372329 25 63 5 54 1172423 43 73 15 66 139Mean27.2 30.5 69.8 13.3 57.7 127.5S.D.4.8 5.0 8.5 6.3 6.1 11.8N11 11 11 10 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 377Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter Mating Lactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 202(F)3730 21 43 5 51 943826 31 66 9 57 1233925 29 65 11 54 1194020 32 54 10 52 1064137 29 67 15 66 1334231 34 65 26 65 1304323 36 62 17 59 1214434 41 80 12 75 1554522 31 60 10 53 1134639 42 63 5 81 1444728 30 64 22 58 1224831 40 68 15 71 139Mean28.8 33.0 63.1 13.1 61.8 124.9S.D.6.0 6.0 8.7 6.3 9.8 16.7N12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 378SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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)6139 35 65 29 74 1396233 36 78 5 69 1476336 36 82 18 72 1546437 41 67 13 78 1456537 35 73 9 72 1456635 36 84 12 71 1556723 34 68 13 57 1256835 33 57 29 68 12569 NP31 -1 5 30 357026 29 60 8 55 1157122 16 55 13 38 937228 36 68 6 64 132Mean31.9 33.4 68.8 14.1 65.3 134.1S.D.6.1 6.4 9.7 8.2 11.4 18.7N11 11 11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 379Appendix 8 (continued) Individual and Group Mean Body Weight GainsIncrease in Body Weight (g)DaysCumulative Body Weight Change (g)DaysAfter Mating Lactation After MatingGroup(sex)AnimalNumberFrom: 0 7 14 1 0 0To: 7 14 20 4 14 204(F) 8526 21 55 21 47 1028625 32 73 6 57 1308730 36 46 -1 66 1128818 25 67 27 43 1108928 28 45 9 56 1019034 32 57 15 66 1239133 39 75 13 72 1479237 26 34 -1 63 979337 34 80 14 71 1519418 24 56 14 42 989524 22 22 0 46 689631 32 77 9 63 140Mean28.4 29.3 57.3 10.5 57.7 114.9S.D.6.5 5.8 18.2 8.7 10.8 24.2N12 12 12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 380SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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) 13241428251424 25 30301522 23 273016TLL27 26 31141725 27 31391824 25 272719212326292020 21 222721 NP23 22 21.2222 23 27272321 22 24242421 26 3325Mean22.8 23.1 27.8 28.3S.D.2.13.43.34.2N11 11 11 10Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 381Appendix 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) 3723 23 26243820 22 24183922 25 29284019 22 24184123 23 25284221 14 28364320 22 24254425 28 31274522 25 29304626 31 323847212425324823 26 2629Mean21.9 23.6 26.8 27.8S.D.2.1 4.0 2.9 6.3N12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 382SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 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) 6124 24 25346222 25 29286325 27 30286427 28 303965252732326624 25 28306722 24 2731682314283569NP22 20 207020 23 262771192023267224 24 2823Mean23.1 23.8 27.8 30.3S.D.2.2 3.8 2.6 4.6N11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 383Appendix 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)8517 20 21318620 22 26308723 26 30308822 24 26368923 24 27299022 23 26339121 27 31319225 27 29239327 27 31379417 20 222495212324179628 28 2928Mean22.2 24.3 26.6 29.1S.D.3.4 2.8 3.3 5.5N12 12 1212Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 384SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 10 Individual Mating Performance, Fertility and Gestation LengthsGroup: 1 Dose Level: 0 (Control)Paired Animal Number Pre-Coital Interval (Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)13 F 1 M26 PT 3+ P231⁄214 F 2 M24 PT 3+ P231⁄215 F 3 M13 PT 2+ P2316 F 4 M35 PT H 3+ P (TLL)231⁄217 F 5 M11PV 3+ P221⁄218 F 6 M23 PT 3+ P231⁄219 F 7 M15 PT H 3+ P2320 F 8 M44 PT 1+ P2321 F 9 M1PV 1+ NP.22 F 10 M36 PT H 3+ P231⁄223 F 11 M24 PT H 3+ P231⁄224 F 12 M33 PT 3+ P231⁄2SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 385Appendix 10 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 2 Dose Level: 30 mg/kg bw/dayPaired Animal Number Pre-Coital Interval (Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)37 F 25 M13 PT H 3+ P2338 F 26 M45 PT 1+ P221⁄239 F 27 M46 PT 2+ P2340 F 28 M33 PT H 3+ P231⁄241 F 29 M13 PT 3+ P2242 F 30 M16 PT H 2+ P2343 F 31 M32 PT 2+ P231⁄244 F 32 M25 PT H 2+ P231⁄245 F 33 M35 PT 2+ P231⁄246 F 34 M16 PT H 1+ P221⁄247 F 35 M35 PT H 3+ P231⁄248 F 36 M42 PT H 1+ P221⁄2PROJECT NUMBER: 41104692RPAGE 386SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 10 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 3 Dose Level: 300 mg/kg bw/dayPaired Animal Number Pre-Coital Interval (Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)61 F 49 M 1 4 PT 2+ P2362 F 50 M 2 5 PT H 3+ P231⁄263 F 51 M 3 2 PT 2+ P231⁄264 F 52 M 3 6 PT H 3+ P231⁄265 F 53 M 2 1 PT 2+ P241⁄266 F 54 M 3 5 PT 3+ P231⁄267 F 55 M 3 4 PT 3+ P231⁄268 F 56 M 2 6 PT 2+ P241⁄269 F 57 M 1 3 PT 1+ NP.70 F 58 M 1 4 PT H 1+ P2371 F 59 M 3 3 PT 3+ P231⁄272 F 60 M 4 4 PT H 3+ P221⁄2SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 387Appendix 10 (continued) Individual Mating Performance, Fertility and Gestation LengthsGroup: 4 Dose Level: 1000 mg/kg bw/dayPaired Animal Number Pre-Coital Interval (Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days)85 F 73 M22 PT PV 1+ P2286 F 74 M24 PT H 1+ P2287 F 75 M32 PT PV 1+ P231⁄288 F 76 M32 PT 3+ P231⁄289 F 77 M36 PT 3+ P231⁄290 F 78 M15 PT H 3+ P2291 F 79 M34 PT 3+ P231⁄292 F 80 M45 PT H 3+ P2393 F 81 M34 PT H 2+ P231⁄294 F 82 M44 PT 2+ P221⁄295 F 83 M46 PT 3+ P2396 F 84 M26 PT H 3+ P231⁄2PROJECT NUMBER: 41104692RPAGE 388SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 11 Individual and Group Mean Litter Size and Litter WeightsGroup: 1 Dose Level: 0(Control)Animal/LitterNumberNumber ofCorporaLuteaNumber 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 Females1317 15 14 14 14 81.8 106.2 6.0 5.4 7.8 7.0 1.8 1.61414 14 14 14 14 80.6 113.0 5.9 5.6 8.2 7.9 2.3 2.31514 14 12 12 12 80.9 116.7 6.9 6.4 9.9 9.4 3.0 3.016 TLL17 17 14 14 82.6 . 6.1 5.8 . . . .1718 18 18 18 18 97.2 131.3 5.5 5.3 7.4 7.2 1.9 1.91811 11 10 10 10 61.0 86.5 6.2 6.0 8.8 8.5 2.6 2.51916 16 14 12 12 74.5 103.9 6.3 6.1 8.8 8.6 2.5 2.42012 12 12 12 12 74.8 104.5 6.2 6.2 8.9 8.6 2.6 2.421 NP. . . . . . . . . . . . .2217 12 11 11 10 72.6 98.0 6.8 6.4 10.0 9.5 3.2 3.12314 14 13# 13# 13 66.3 99.8 5.5 5.6 7.8 7.6 2.3 2.02417 16 15 15 15 82.1 108.3 5.5 5.4 7.2 7.2 1.7 1.8Mean15.0 14.2 13.3 13.1 13.0 77.18 106.82 6.08 5.85 8.47 8.15 2.39 2.30S.D.2.4 2.1 2.3 2.3 2.4 9.92 11.98 0.51 0.43 0.96 0.92 0.49 0.50N10 10 10 10 10 10 10 10 10 10 10 10 10# = One offspring not observed until Day 3SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 389Appendix 11 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 2 Dose Level: 30 mg/kg bw/dayAnimal/LitterNumberNumber ofCorporaLuteaNumber 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 Females3712 6 6 6 6 42.3 66.7 7.1 7.1 11.2 11.0 4.2 3.93815 15 15 15 12 78.3 88.6 5.5 4.9 7.7 6.9 2.2 2.03911 11 10 10 10 67.3 99.0 6.9 6.6 10.1 9.8 3.2 3.14013 13 12 11 9 61.5 76.9 5.8 5.4 8.6 8.5 2.8 3.14116 15 15 15 15 79.0 104.1 5.4 5.2 7.0 6.9 1.6 1.84213 13 12 12 12 78.1 113.6 6.6 6.2 9.5 9.2 2.9 3.14315 15 14 14 14 78.6 107.9 6.0 5.3 8.2 7.4 2.2 2.04415 15 15 14 14 79.4 105.1 5.8 5.5 7.7 7.2 1.9 1.84515 14 12 12 12 69.6 96.7 5.9 5.5 8.2 7.7 2.3 2.24617 15 14 14 13 77.5 109.9 5.9 5.2 8.9 8.0 3.0 2.84716 16 16 16 16 84.5 117.1 5.5 5.1 7.6 7.1 2.1 2.04816 16 14 14 14 80.6 111.5 5.9 5.7 8.2 7.8 2.3 2.2Mean14.5 13.7 12.9 12.8 12.3 73.06 99.76 6.02 5.63 8.57 8.12 2.55 2.49S.D.1.8 2.8 2.8 2.8 2.8 11.64 15.36 0.54 0.65 1.20 1.27 0.70 0.68N12 12 12 12 12 12 12 12 12 12 12 12 12PROJECT NUMBER: 41104692RPAGE 390SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 11 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 3 Dose Level: 300 mg/kg bw/dayAnimal/LitterNumberNumber ofCorporaLuteaNumber 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 Females6115 15 15 15 15 89.3 125.5 6.3 5.7 8.8 8.1 2.5 2.46216 16 15 15 15 89.4 114.8 6.3 5.6 7.8 7.5 1.5 1.96317 17 16 16 12 98.4 108.3 6.3 6.0 9.1 8.8 2.9 2.86418 15 13 13 13 95.1 128.5 7.4 7.0 10.1 9.5 2.6 2.56512 12 11 11 11 76.8 118.3 7.2 6.7 11.0 10.3 3.8 3.76617 17 16 16 16 94.7 133.7 6.0 5.8 8.3 8.4 2.4 2.66716 16 14 14 14 82.7 114.3 6.1 5.7 8.3 8.0 2.2 2.36812 12 11 11 11 78.6 114.8 7.4 7.0 10.7 10.3 3.3 3.369 NP27011 11 10 10 10 67.5 98.7 6.9 6.5 10.3 9.3 3.4 2.87116 14 12 12 12 65.1 88.1 5.7 5.2 7.7 7.1 2.0 1.97214 14 13 13 12 73.2 95.6 5.8 5.5 8.1 7.8 2.3 2.3Mean14.9 14.5 13.3 13.3 12.8 82.80 112.78 6.48 6.07 9.11 8.65 2.63 2.58S.D.2.3 2.1 2.1 2.1 1.9 11.47 14.18 0.62 0.63 1.19 1.10 0.67 0.55N11 11 11 11 11 11 11 11 11 11 11 11 11SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 391Appendix 11 (continued) Individual and Group Mean Litter Size and Litter WeightsGroup: 4 Dose Level: 1000 mg/kg bw/dayAnimal/LitterNumberNumber ofCorporaLuteaNumber 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 Females8512 11 11 11 11 63.9 91.8 6.1 5.1 8.7 7.4 2.6 2.38613 13 12 12 11 67.2 93.2 5.8 5.0 8.6 8.0 2.8 3.08711 11 9 9 9 62.5 94.3 6.9 7.0 10.4 10.7 3.5 3.78817 17 14 13 12 81.5 114.2 6.5 6.1 9.8 9.3 3.3 3.28915 9 9 9 9 62.5 92.4 7.0 6.9 10.3 10.2 3.3 3.39014 12 11 11 11 67.1 104.5 6.3 6.0 9.9 9.2 3.6 3.29115 13 13 13 13 82.4 107.3 6.3 6.4 8.2 8.3 1.9 1.99210 9 4 4 4 30.2 48.0 7.9 7.4 12.7 11.8 4.8 4.39317 16 16 16 16 98.7 124.8 6.5 5.8 8.1 7.4 1.7 1.69411 11 10 10 10 57.7 81.6 6.0 5.6 8.4 8.0 2.4 2.49510 5 3 3 3 21.1 33.6 7.2 7.0 11.5 11.1 4.3 4.19615 14 13 13 13 78.7 104.7 6.2 5.9 8.1 8.0 2.0 2.0Mean13.3 11.8 10.4 10.3 10.2 64.46 90.87 6.54 6.19 9.56 9.10 3.02 2.91S.D.2.5 3.3 3.8 3.7 3.7 21.55 26.23 0.60 0.76 1.48 1.51 0.97 0.88N12 12 12 12 12 12 12 12 12 12 12 12 12PROJECT NUMBER: 41104692RPAGE 392SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 12 Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex (%)ViabilityIndex (%)1(F)1312 7 100 100140 0 100 100150 14 100 10016 TLL0 18 100 0170 0 100 100180 9 100 100190 13 86 100200 0 100 10021 NP. . . .2229 8 100 91230 7 100 100246 6 100 100Mean4.7 6.4 98.6 99.1S.D.9.5 5.1 4.5 2.9N10 10 10 10Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 393Appendix 12 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex (%)ViabilityIndex (%)2(F) 37 50 0 100 10038 0 0 100 8039 0 9 100 10040 0 8 92 8241 6 0 100 10042 0 8 100 10043 0 7 100 10044 0 0 93 10045 7 14 100 10046 12 7 100 9347 0 0 100 10048 0 13 100 100Mean6.2 5.4 98.8 96.2S.D.14.3 5.2 2.9 7.4N12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 394SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 12 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex (%)ViabilityIndex (%)3(F)610 0 100 100620 6 100 100630 6 100 756417 13 100 100650 8 100 100660 6 100 100670 13 100 100680 8 100 10069 NP100 . . .700 9 100 1007113 14 100 100720 7 100 92Mean2.7 8.3 100.0 97.0S.D.6.0 4.1 0.0 7.7N11 11 11 11Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 395Appendix 12 (continued) Individual and Group Mean Implantation Losses and Survival IndicesGroup(Sex)LitterNumberPreImplantationLoss (%)Post -ImplantationLoss (%)LiveBirthIndex (%)ViabilityIndex (%)4(F)858 0 100 100860 8 100 92870 18 100 100880 18 93 928940 0 100 1009014 8 100 1009113 0 100 1009210 56 100 100936 0 100 100940 9 100 1009550 40 100 100967 7 100 100Mean12.4 13.6 99.4 98.7S.D.16.2 17.5 2.1 3.1N12 12 12 12Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 396SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 13 Individual and Group Mean Sex 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 10 4 71 10 4 71 10 4 7114 8 6 57 8 6 57 8 6 5715 8 4 67 8 4 67 8 4 6716 TLL 4 10 29 4 10 29 . . .17 9 9 50 9 9 50 9 9 5018 5 5 505550555019 8 6 57 6 6 50 6 6 5020 5 7 42 5 7 42 5 7 4221 NP22 6 5 55 6 5 55 6 4 6023 7 6 54 7 6 54 7 6 5424 8 7 53 8 7 53 8 7 53Mean 55.6 54.9 55.4S.D. 8.5 8.6 8.8N 10 10 10SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 397Appendix 13 (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 2 674267426738 8 7 53 8 7 53 7 5 5839 4 6 40 4 6 40 4 6 4040 7 5 586555545641 7 8 47 7 8 47 7 8 4742 9 3 75 9 3 75 9 3 7542 6 8 43 6 8 43 6 8 4344 9 6 60 8 6 57 8 6 5745 9 3 75 9 3 75 9 3 7546 7 7 50 7 7 50 7 6 5447 7 9 44 7 9 44 7 9 4448 5 9 3659365936Mean 53.9 53.4 54.2S.D. 13.2 13.1 13.1N 12 12 12PROJECT NUMBER: 41104692RPAGE 398SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 13 (continued) Individual and Group Mean Sex Ratio Values for OffspringGroup: 3 Dose Level: 300 mg/kg bw/dayLitter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male61 6 9 40 6 9 40 6 9 4062 8 7 53 8 7 53 8 7 5363 10 6 63 10 6 63 8 4 6764 9 4 69 9 4 69 9 4 6965 7 4 64 7 4 64 7 4 6466 12 4 75124751247567 7 7 50 7 7 50 7 7 5068 4 7 36 4 7 36 4 7 3669 NP . . .......70 6 4 60 6 4 60 6 4 6071 5 7 42 5 7 42 5 7 4272 5 8 38 5 8 38 5 7 42Mean 53.7 53.7 54.3S.D. 13.4 13.4 13.4N 11 11 11SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 399Appendix 13 (continued) Individual and Group Mean Sex Ratio Values for OffspringGroup: 4 Dose Level: 1000 mg/kg bw/dayLitter NumberSex Ratio ( 

# Post Partum) Day:At birth14Male Female % Male Male Female % Male Male Female % Male85 8 3 738373837386 9 3 75 9 3 75 9 2 8287 6 3 67 6 3 67 6 3 6788 5 8 385838574289 5 4 56 5 4 56 5 4 5690 5 6 45 5 6 45 5 6 4591 6 7 46 6 7 46 6 7 4692 1 3 25 1 3 25 1 3 2593 9 7 56 9 7 56 9 7 5694 5 5 50 5 5 50 5 5 5095 1 2 33 1 2 33 1 2 3396 6 7 4667466746Mean 50.9 50.9 51.7S.D. 15.3 15.3 16.1N 12 12 12PROJECT NUMBER: 41104692RPAGE 400SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 14 Individual Clinical Signs for OffspringGroup: 1 Dose Level: 0 (Control)Litter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum13 No Abnormalities Detected14 No Abnormalities Detected15 No Abnormalities Detected16 TLL 4M 10F (Whole litter) Missing 217 No Abnormalities Detected18 No Abnormalities Detected19 2M Found dead Pre Day 120 No Abnormalities Detected21 NP.22 F7 Missing 423 No Abnormalities Detected24 No Abnormalities DetectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 401Appendix 14 (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 M6 F14 F15 Missing 239 No Abnormalities Detected40 1M Found dead 1M6 Swollen abdomen 1Missing 2M7 Small 1Missing 241 No Abnormalities Detected42 No Abnormalities Detected43 No Abnormalities Detected44 1M Found dead Pre Day 18M 6F (Whole litter) Cold Pre Day 1-145 No Abnormalities Detected46 F11 Bruising to neck region 1F12 Missing 347 F11 Small 4-548 No Abnormalities DetectedPROJECT NUMBER: 41104692RPAGE 402SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 14 (continued) Individual Clinical Signs for OffspringGroup: 3 Dose Level: 300 mg/kg bw/dayLitter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum61No Abnormalities Detected62No Abnormalities Detected63M6 M7 F13 F14 Missing 264No Abnormalities Detected65No Abnormalities Detected66No Abnormalities Detected67No Abnormalities Detected68No Abnormalities Detected69 NP.70No Abnormalities Detected71No Abnormalities Detected72F7 Missing 2SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 403Appendix 14 (continued) Individual Clinical Signs for OffspringGroup: 4 Dose Level: 1000 mg/kg bw/dayLitter Number Affected Offspring Sex and Identity Clinical Observation Day 

# Post Partum85F11 Swollen snout 1-3Small 1-586F10 Cold 1Small 1-3Missing 487No Abnormalities Detected881M Found dead 1F13 Missing 489No Abnormalities Detected90No Abnormalities Detected91No Abnormalities Detected92No Abnormalities Detected93F16 Small 4-594No Abnormalities Detected95No Abnormalities Detected96No Abnormalities DetectedPROJECT NUMBER: 41104692RPAGE 404SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 15 Individual and Group Mean Reflexological Responses for OffspringGroup: 1 Dose Level: 0 (Control)LitterNumberSurface righting(Day 1 

# Post Partu m)Number of offspring% passedexamined passed1314 14 100.01414 14 100.01512 10 83.316 TLL14 14 100.01718 18 100.01810 9 90.01912 12 100.02012 12 100.021 NP. . .2211 10 90.92312 10 83.32415 14 93.3Mean94.6S.D.6.8N11SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 405Appendix 15 (continued) Individual and GroupMean Reflexological Responses for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Partum)Number of offspring% passedexamined passed37 6 6 100.038 15 13 86.739 10 8 80.040 11 10 90.941 15 15 100.042 12 10 83.343 14 14 100.044 14 12 85.745 12 11 91.746 14 14 100.047 16 14 87.548 14 13 92.9Mean91.6S.D.7.2N12PROJECT NUMBER: 41104692RPAGE 406SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 15 (continued) Individual and GroupMean Reflexological Responses for OffspringGroup: 3 Dose Level: 300 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Par t u m)Number of offspring% passedexamined passed6115 15 100.06215 11 86.76316 15 93.86413 13 100.06511 11 100.06616 16 100.06714 14 100.06811 11 100.069 NP. . .7010 8 80.07112 12 100.07213 12 92.3Mean94.5S.D.9.4N11SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 407Appendix 15 (continued) Individual and GroupMean Reflexological Responses for OffspringGroup: 4 Dose Level: 1000 mg/kg bw/dayLitterNumberSurface righting(Day 1 

# Post Partum)Number of offspring% passedexamined passed8511 11 100.08612 11 91.7879 9 100.08813 13 100.0899 9 100.09011 9 81.89113 13 100.0924 4 100.09316 16 100.09410 10 100.0953 3 100.09613 13 100.0Mean97.8S.D.5.6N12PROJECT NUMBER: 41104692RPAGE 408SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 16 Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 16.6 9.35 50.3 17.8 53.8 33.1 5.9 10 0.59 90 5.31 0 0.00 0 0.00 0 0.00509ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2 6 16.6 9.18 51.1 18.1 55.7 32.5 11.2 33 3.70 67 7.50 0 0.00 0 0.00 0 0.00517ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3 6 16.9 9.10 51.8 18.5 56.9 32.6 9.8 14 1.37 86 8.43 0 0.00 0 0.00 0 0.00486ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4 6 16.9 8.94 51.3 18.9 57.3 33.0 7.3 12 0.88 87 6.35 1 0.07 0 0.00 0 0.00595ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ5 6 15.9 8.95 48.5 17.7 54.2 32.7 6.8 22 1.50 77 5.24 0 0.00 1 0.07 0 0.00539Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 409Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 12.5 6.60 38.2 19.0 57.8 32.8 8.3 36 2.99 64 5.31 0 0.00 0 0.00 0 0.00864ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ14 6 13.4 6.97 41.0 19.2 58.7 32.8 8.8 27 2.38 73 6.42 0 0.00 0 0.00 0 0.00955ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ15 6 13.2 7.11 40.4 18.5 56.8 32.7 8.7 14 1.22 86 7.48 0 0.00 0 0.00 0 0.00900ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ18 6 14.2 7.52 44.2 18.9 58.8 32.1 5.6 15 0.84 85 4.76 0 0.00 0 0.00 0 0.00923ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ19 6 11.5 5.91 35.3 19.4 59.7 32.5 6.0 40 2.40 60 3.60 0 0.00 0 0.00 0 0.00919Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 410SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 15.4 8.35 46.8 18.5 56.1 32.9 10.5 12 1.26 88 9.24 0 0.00 0 0.00 0 0.00689ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ26 6 16.8 9.39 51.5 17.9 54.9 32.7 9.0 17 1.53 82 7.38 1 0.09 0 0.00 0 0.00616ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ27 6 15.4 9.04 47.3 17.1 52.3 32.6 9.1 22 2.00 78 7.10 0 0.00 0 0.00 0 0.00705ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ28 6 15.5 8.77 46.8 17.7 53.3 33.1 9.0 9 0.81 91 8.19 0 0.00 0 0.00 0 0.00579ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ29 6 17.5 9.76 53.4 18.0 54.7 32.8 10.1 8 0.81 92 9.29 0 0.00 0 0.00 0 0.00536Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 411Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 14.3 7.56 42.6 18.9 56.4 33.5 4.0 16 0.64 84 3.36 0 0.00 0 0.00 0 0.0065ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ41 6 13.8 7.84 42.4 17.5 54.0 32.5 5.6 31 1.74 69 3.86 0 0.00 0 0.00 0 0.00898ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ42 6 12.9 7.09 39.5 18.2 55.8 32.6 7.0 37 2.59 63 4.41 0 0.00 0 0.00 0 0.00993ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ44 6 13.0 6.94 40.7 18.8 58.6 32.1 7.2 21 1.51 79 5.69 0 0.00 0 0.00 0 0.00 1032ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ46 6 13.2 7.01 40.1 18.9 57.1 33.1 6.1 49 2.99 51 3.11 0 0.00 0 0.00 0 0.00 1073Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 412SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 15.8 8.84 48.3 17.8 54.6 32.7 4.2 25 1.05 74 3.11 0 0.00 1 0.04 0 0.00548ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ50 6 16.2 9.02 49.5 17.9 54.9 32.7 9.4 18 1.69 82 7.71 0 0.00 0 0.00 0 0.00763ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ51 6 15.3 8.74 47.7 17.5 54.6 32.1 6.9 29 2.00 71 4.90 0 0.00 0 0.00 0 0.00583ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ52 6 15.3 8.73 47.1 17.5 54.0 32.4 6.4 14 0.90 85 5.44 0 0.00 1 0.06 0 0.00636ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ53 6 16.8 9.44 50.7 17.8 53.7 33.1 7.3 8 0.58 90 6.57 0 0.00 2 0.15 0 0.00472Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 413Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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) 61 6 13.1 7.12 40.4 18.4 56.7 32.5 6.2 22 1.36 78 4.84 0 0.00 0 0.00 0 0.00736ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ62 6 10.7 5.67 33.7 18.8 59.4 31.7 9.2 38 3.50 62 5.70 0 0.00 0 0.00 0 0.00 1017ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ65 7 13.8 7.02 41.3 19.7 58.8 33.5 3.9 41 1.60 59 2.30 0 0.00 0 0.00 0 0.00864ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ67 7 13.7 7.43 41.9 18.5 56.5 32.7 4.9 40 1.96 60 2.94 0 0.00 0 0.00 0 0.00892ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ70 6 13.9 7.09 41.9 19.6 59.1 33.1 6.8 26 1.77 73 4.96 1 0.07 0 0.00 0 0.00948Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 414SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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 6 13.7 7.53 41.3 18.2 54.9 33.2 4.6 12 0.55 88 4.05 0 0.00 0 0.00 0 0.00513ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ74 6 16.5 9.29 50.5 17.8 54.4 32.6 5.4 23 1.24 75 4.05 0 0.00 2 0.11 0 0.00580ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ75 6 12.9 7.23 39.0 17.8 53.9 33.0 7.8 10 0.78 90 7.02 0 0.00 0 0.00 0 0.00461ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ76 6 15.2 8.49 46.0 17.9 54.2 33.0 6.2 21 1.30 77 4.77 0 0.00 2 0.12 0 0.00567ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ77 6 15.7 8.86 47.7 17.7 53.9 32.8 6.0 8 0.48 91 5.46 0 0.00 1 0.06 0 0.00534Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 415Appendix 16 (continued) Individual Haematological ValuesGroup Animal(Sex) Number Week 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) 85 6 7.4 3.95 22.4 18.8 56.7 33.2 2.5 28 0.70 71 1.78 0 0.00 1 0.03 0 0.0011ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ86 6 14.1 7.52 43.5 18.7 57.9 32.4 5.4 22 1.19 78 4.21 0 0.00 0 0.00 0 0.00710ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ90 6 14.0 7.81 42.8 17.9 54.8 32.6 5.3 34 1.80 64 3.39 0 0.00 2 0.11 0 0.00825ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ91 7 13.6 6.98 41.3 19.5 59.2 33.0 5.5 41 2.26 59 3.25 0 0.00 0 0.00 0 0.00771ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ96 6 14.8 7.91 45.3 18.7 57.2 32.6 5.8 29 1.68 71 4.12 0 0.00 0 0.00 0 0.00976Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 416SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 17 Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds1(M) 1 6 10.1 19.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ2 6 10.3 18.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ3 6 10.2 15.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ4 6 9.1 13.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ5 6 8.9 10.7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 417Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds1(F) 13 6 9.3 12.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ14 6 11.3 19.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ15 6 9.5 13.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ18 6 10.1 18.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ19 6 8.6 14.8Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 418SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds2(M) 25 6 9.3 13.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ26 6 10.1 16.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ27 6 9.6 15.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ28 6 9.4 15.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ29 6 10.2 17.9Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 419Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds2(F) 37 6 . .ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ41 6 9.1 13.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ42 6 9.5 16.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ44 6 9.5 15.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ46 6 9.2 16.1Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 420SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds3(M) 49 6 9.1 12.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ50 6 10.4 16.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ51 6 9.9 16.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ52 6 9.1 15.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ53 6 10.1 14.9Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 421Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds3(F) 61 6 9.4 10.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ62 6 9.2 16.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ65 7 9.7 14.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ67 7 11.1 16.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ70 6 9.4 14.9Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 422SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds4(M) 73 6 9.1 10.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ74 6 9.9 13.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ75 6 9.1 15.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ76 6 9.7 14.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ77 6 10.2 12.6Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 423Appendix 17 (continued) Individual Coagulation ValuesGroup Animal(Sex) Number Week CT APTTNumber Seconds Seconds4(F) 85 6 10.3 16.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ86 6 9.5 17.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ90 6 9.3 16.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ91 7 10.5 16.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ96 6 9.1 13.7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 424SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 18 Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 69 150 7.10 3.7 1.10 145 7.14 101 2.70 2.1 113 66 189 1.06 98 0.12ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ2 6 49 170 7.25 3.8 1.10 149 4.42 101 2.66 2.1 85 55 155 0.81 81 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ3 6 52 180 6.65 3.8 1.34 143 4.22 102 2.56 1.6 136 64 170 0.69 58 0.11ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ4 6 56 177 7.15 4.1 1.31 147 5.06 102 2.77 2.5 123 69 121 0.89 75 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ5 6 53 191 5.84 3.1 1.14 146 4.63 99 2.57 2.2 91 59 123 0.59 88 0.08Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 425Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 43 119 6.53 3.7 1.31 143 4.27 100 2.63 1.5 76 82 90 0.63 81 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ14 6 49 126 6.68 4.0 1.46 150 4.68 104 2.64 1.8 78 68 126 0.66 61 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ15 6 49 128 5.93 3.6 1.51 145 5.44 104 2.60 2.0 110 99 159 0.71 73 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ18 6 45 144 6.39 3.9 1.58 144 4.34 101 2.56 1.8 74 61 93 0.64 50 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ19 6 52 116 5.94 3.6 1.52 143 4.85 103 2.55 1.2 90 92 100 0.68 124 0.09Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 426SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 43 176 6.98 3.5 1.03 143 4.43 99 2.64 2.0 94 60 112 0.75 90 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ26 6 53 174 6.76 3.7 1.23 148 4.33 103 2.69 2.1 86 66 146 0.77 104 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ27 6 49 195 6.42 3.6 1.25 143 4.39 102 2.49 1.4 131 77 157 0.78 76 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ28 6 54 173 6.45 3.6 1.26 147 5.15 103 2.55 1.9 112 67 128 0.85 77 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ29 6 49 175 6.34 3.4 1.13 147 5.13 101 2.58 1.7 152 65 116 0.69 80 0.06Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 427Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 57 176 5.52 3.5 1.69 146 5.31 102 2.39 1.1 243 67 133 0.61 84 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ41 6 77 164 5.73 3.1 1.16 144 5.58 104 2.71 1.0 135 132 53 1.12 56 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ42 6 54 117 6.22 3.8 1.55 147 4.46 106 2.51 1.6 140 90 134 0.64 79 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ44 6 49 162 5.76 3.6 1.72 148 3.96 104 2.60 1.8 106 79 204 1.15 67 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ46 6 53 160 6.35 3.7 1.36 144 4.28 104 2.54 1.2 84 111 275 0.73 82 0.07Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 428SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 46 141 6.32 3.7 1.39 151 4.70 107 2.72 2.1 122 54 262 0.69 75 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ50 6 44 117 6.60 3.6 1.17 150 4.89 102 2.53 2.5 118 67 126 0.73 78 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ51 6 47 184 5.77 3.3 1.35 148 4.73 102 2.54 1.8 148 78 128 0.63 90 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ52 6 44 143 6.65 3.9 1.46 148 4.52 102 2.73 2.3 109 74 154 0.69 79 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ53 6 58 193 5.84 3.5 1.47 145 4.60 100 2.47 2.0 149 52 110 0.65 84 0.04Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 429Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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) 61 6 53 112 6.22 3.8 1.60 147 4.55 105 2.52 0.8 103 88 129 0.62 82 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ62 6 53 138 5.13 3.1 1.51 144 4.55 104 2.25 0.8 186 75 139 0.90 74 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ65 7 46 135 6.17 3.6 1.38 144 3.85 103 2.53 1.3 89 70 92 0.65 78 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ67 7 49 138 6.44 3.7 1.37 143 3.95 100 2.54 1.6 78 64 117 0.65 70 0.05ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ70 6 48 128 6.29 3.8 1.49 147 4.33 104 2.55 1.2 113 77 244 0.85 90 0.06Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 430SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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 6 55 148 5.48 3.4 1.65 144 4.70 99 2.63 1.9 135 60 112 0.57 83 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ74 6 37 152 6.29 3.7 1.47 148 4.34 102 2.56 1.9 121 43 129 0.64 81 0.09ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ75 6 51 166 6.09 3.5 1.40 146 4.72 101 2.66 1.9 171 91 154 0.58 68 0.07ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ76 6 39 183 6.48 3.7 1.34 143 4.24 98 2.62 1.9 81 65 206 0.67 75 0.12ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ77 6 55 166 6.16 3.5 1.30 148 6.08 101 2.69 2.5 197 109 137 0.69 68 0.09Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 431Appendix 18 (continued) Individual Blood Chemical ValuesGroup Animal Tot.(Sex) Number Week 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) 85 6 55 137 4.82 3.2 1.92 144 5.29 102 2.15 0.6 133 68 155 0.53 67 0.08ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ86 6 50 147 6.20 3.8 1.59 145 4.51 101 2.47 1.0 92 82 110 0.71 88 0.10ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ90 6 51 141 6.15 3.5 1.36 145 4.15 103 2.50 0.8 81 83 334 0.66 76 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ91 7 43 162 5.70 3.4 1.45 144 4.20 105 2.25 0.8 88 78 107 0.69 62 0.06ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ96 6 64 122 6.60 3.9 1.48 153 5.70 107 2.65 0.1 192 90 192 0.89 99 0.10Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 432SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 19 Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l1(M) 1 6 4.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ2 6 7.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ3 6 5.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ4 6 9.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ5 6 29.7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 433Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l1(F) 13 6 7.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ14 6 9.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ15 6 5.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ18 6 8.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ19 6 26.8Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 434SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l2(M) 25 6 5.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ26 6 7.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ27 6 6.3ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ28 6 19.7ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ29 6 4.7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 435Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l2(F) 37 6 4.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ41 6 23.2ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ42 6 15.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ44 6 29.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ46 6 5.3Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 436SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l3(M) 49 6 6.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ50 6 6.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ51 6 3.9ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ52 6 26.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ53 6 4.1Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 437Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l3(F) 61 6 6.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ62 6 29.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ65 7 13.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ67 7 5.0ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ70 6 6.7Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 438SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l4(M) 73 6 4.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ74 6 8.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ75 6 9.5ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ76 6 16.1ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ77 6 33.6Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 439Appendix 19 (continued) Individual Bile Acid ValuesGroup Animal(Sex) Number Week Bile AcidNumberμmol/l4(F) 85 6 7.6ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ86 6 10.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ90 6 19.8ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ91 7 8.4ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ96 6 11.6Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 440SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 20 Individual Necropsy Findings for OffspringGroup: 1 Dose Level: 0 (Control)Litter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partum)Offspring Sex &NumberMacroscopic ObservationTotal Numberof OffspringMacroscopic Observation13 10M 4F No abnormalities detected14 8M 6F No abnormalities detected15 8M 4F No abnormalities detected16 TLL . .17 9M 9F No abnormalities detected185M 5F No abnormalities detected19 Pre Day 1 2M Autolytic changes detected 6M 6F No abnormalities detected20 5M 7F No abnormalities detected21 NP . .22 6M 4F No abnormalities detected23 7M 6F No abnormalities detected24 8M 7F No abnormalities detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 441Appendix 20 (continued) Individual Necropsy Findings for OffspringGroup: 2 Dose Level: 30 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partum)Offspring Sex &NumberMacroscopic ObservationTotal Number ofOffspringMacroscopic Observation37 4M 2F No abnormalities detected38 7M 5F No abnormalities detected39 4M 6F No abnormalities detected40 1 1M Autolytic changes detected 5M 4F No abnormalities detected41 7M 8F No abnormalities detected429M 3F No abnormalities detected43 6M 8F No abnormalities detected44 Pre Day 1 1M Autolytic changes detected 8M 6F No abnormalities detected45 9M 3F No abnormalities detected46 7M 6F No abnormalities detected47 F11 Small7M 8F No abnormalities detected48 5M 9F No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 442SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 20 (continued) Individual Necropsy Findings for OffspringGroup: 3 Dose Level: 300 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partum)Offspring Sex &NumberMacroscopic ObservationTotal Number ofOffspringMacroscopic Observation61 6M 9F No abnormalities detected62 8M 7F No abnormalities detected63 8M 4F No abnormalities detected64 9M 4F No abnormalities detected65 M6 Enlarged kidneys, left kidney fluid filled6M 4F No abnormalities detected6612M 4F No abnormalities detected67 7M 7F No abnormalities detected68 4M 7F No abnormalities detected69 NP . .70 6M 4F No abnormalities detected71 5M 7F No abnormalities detected72 5M 7F No abnormalities detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 443Appendix 20 (continued) Individual Necropsy Findings for OffspringGroup: 4 Dose Level: 1000 mg/kg bw/dayLitter NumberInterim DeathsTerminal killNecropsy Day ( 

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Partum)Offspring Sex &NumberMacroscopic ObservationTotal Number ofOffspringMacroscopic Observation85 F11 Small8M 2F No abnormalities detected86 9M 2F No abnormalities detected87 6M 3F No abnormalities detected88 1 1M Autolytic changes detected 5M 7F No abnormalities detected89 5M 4F No abnormalities detected905M 6F No abnormalities detected91 6M 7F No abnormalities detected92 1M 3F No abnormalities detected93 F16 Small9M 6F No abnormalities detected94 5M 5F No abnormalities detected95 1M 2F No abnormalities detected96 6M 7F No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 444SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 21 Individual Necropsy FindingsGroup: 1 Dose Level: 0 (Control) Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ1 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) Seminal Vesicles; right horn; SmallAll remaining tissues had no abnormalities detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 445Appendix 21 (continued) Individual Necropsy FindingsGroup: 1 Dose Level: 0 (Control) Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ13 SCHEDULED KILL 43 (7) No abnormalities detected14 SCHEDULED KILL 43 (7) No abnormalities detected15 SCHEDULED KILL 43 (7) No abnormalities detected16 SCHEDULED KILL 45 (7) No abnormalities detected17 SCHEDULED KILL 52 (8) Kidneys: Left Kidney RetainedKidneys; left; Increased Pelvic SpaceUrinary Bladder; Mineral Calculi: Mineral Calculi deposit approx 8mm x 3mm in size found in UrinaryBladderAll remaining tissues had no abnormalities detected18 SCHEDULED KILL 43 (7) No abnormalities detected19 SCHEDULED KILL 43 (7) No abnormalities detected20 SCHEDULED KILL 46 (7) No abnormalities detected21 SCHEDULED KILL 42 (6) No abnormalities detected22 SCHEDULED KILL 45 (7) No abnormalities detected23 SCHEDULED KILL 43 (7) No abnormalities detected24 SCHEDULED KILL 44 (7) No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 446SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 21 (continued) Individual Necropsy FindingsGroup: 2 Dose Level: 30 mg/kg bw/day Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ25 SCHEDULED KILL 43 (7) No abnormalities detected26 SCHEDULED KILL 43 (7) No abnormalities detected27 SCHEDULED KILL 43 (7) Brain (Including Cerebrum, Cerebellum And Pons); Damaged On RemovalAll 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 detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 447Appendix 21 (continued) Individual Necropsy FindingsGroup: 2 Dose Level: 30 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ37 SCHEDULED KILL 43 (7) No abnormalities detected38 SCHEDULED KILL 45 (7) No abnormalities detected39 SCHEDULED KILL 46 (7) No abnormalities detected40 SCHEDULED KILL 45 (7) No abnormalities detected41 SCHEDULED KILL 42 (6) No abnormalities detected42 SCHEDULED KILL 43 (7) No abnormalities detected43 SCHEDULED KILL 44 (7) No abnormalities detected44 SCHEDULED KILL 43 (7) No abnormalities detected45 SCHEDULED KILL 44 (7) No abnormalities detected46 SCHEDULED KILL 42 (6) No abnormalities detected47 SCHEDULED KILL 44 (7) No abnormalities detected48 SCHEDULED KILL 45 (7) No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 448SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 21 (continued) Individual Necropsy FindingsGroup: 3 Dose Level: 300 mg/kg bw/day Sex: MaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ49 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) Epididymides; SmallTestes; SmallTestes; FlaccidAll remaining tissues had no abnormalities detected58 SCHEDULED KILL 43 (7) No abnormalities detected59 SCHEDULED KILL 43 (7) No abnormalities detected60 SCHEDULED KILL 43 (7) No abnormalities detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 449Appendix 21 (continued) Individual Necropsy FindingsGroup: 3 Dose Level: 300 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ61 SCHEDULED KILL 43 (7) No abnormalities detected62 SCHEDULED KILL 43 (7) No abnormalities detected63 SCHEDULED KILL 45 (7) No abnormalities detected64 SCHEDULED KILL 45 (7) No abnormalities detected65 SCHEDULED KILL 44 (7) No abnormalities detected66 SCHEDULED KILL 45 (7) No abnormalities detected67 SCHEDULED KILL 44 (7) No abnormalities detected68 SCHEDULED KILL 44 (7) No abnormalities detected69 SCHEDULED KILL 42 (6) No abnormalities detected70 SCHEDULED KILL 43 (7) No abnormalities detected71 SCHEDULED KILL 44 (7) No abnormalities detected72 SCHEDULED KILL 45 (7) No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 450SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 21 (continued) Individual Necropsy FindingsGroup: 4 Dose Level: 1000 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) Lungs (With Bronchi); ReddenedSpleen; DarkAll remaining tissues had 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) No abnormalities detected82 SCHEDULED KILL 43 (7) No abnormalities detected83 SCHEDULED KILL 43 (7) No abnormalities detected84 SCHEDULED KILL 43 (7) No abnormalities detectedSODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 451Appendix 21 (continued) Individual Necropsy FindingsGroup: 4 Dose Level: 1000 mg/kg bw/day Sex: FemaleAnimal DeathNo. Mode Of Death Day (Week) Observation(s)ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ85 SCHEDULED KILL 43 (7) No abnormalities detected86 SCHEDULED KILL 43 (7) No abnormalities detected87 SCHEDULED KILL 45 (7) No abnormalities detected88 SCHEDULED KILL 45 (7) No abnormalities detected89 SCHEDULED KILL 45 (7) No abnormalities detected90 SCHEDULED KILL 42 (6) No abnormalities detected91 SCHEDULED KILL 44 (7) Gross Lesions; right fore limb; Mass: Mass found under right fore limb. Mass approx 23mm x 27mm in size.Mass appears to be fibrous.All remaining tissues had no abnormalities detected92 SCHEDULED KILL 46 (7) No abnormalities detected93 SCHEDULED KILL 45 (7) No abnormalities detected94 SCHEDULED KILL 45 (7) No abnormalities detected95 SCHEDULED KILL 46 (7) No abnormalities detected96 SCHEDULED KILL 43 (7) No abnormalities detectedPROJECT NUMBER: 41104692RPAGE 452SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 22 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 0.0875 2.1078 1.8353 0.9967 2.5122 12.4609 0.0117 0.5562 2.1988 0.8087 4.5132 0.3810 0.0135ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 0.0611 2.1690 1.3994 1.0165 2.1695 10.6724 0.0092 0.5617 2.4649 0.8087 3.6135 0.4904 0.0250ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 0.0722 2.0614 1.8459 0.9466 2.4793 13.1714 0.0098 0.5873 2.6073 0.8074 4.2701 0.3341 0.0160ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 0.0664 1.8938 1.3025 0.9711 2.1503 11.3238 0.0087 0.5849 2.2154 0.5620 3.1762 0.3582 0.0128ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 0.0539 2.0062 1.3944 1.0483 2.5625 12.3118 0.0117 0.7326 2.1156 0.6311 3.9926 0.3962 0.0204ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 1.7266 0.0125 0.6634 2.4086 3.9067ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 1.5928 0.0107 0.6932 2.4216 4.0443ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 1.4798 0.0091 0.6600 2.3866 3.7491ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 1.3355 0.0109 0.6928 1.9355 3.3366ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 1.5751 0.0119 0.7801 2.3889 4.3972ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 1.2066 0.0093 0.6030 2.2663 3.5189ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 1.3338 0.0108 0.7116 2.5657 3.6156Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 453Appendix 22 (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 0.0757 2.1643 1.6035 1.0824 2.4102 12.7258 0.0106 0.8147 2.2111 0.7892 4.0980 0.6063 0.0212ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 0.0620 2.1242 1.3489 0.9368 1.9835 11.6257 0.0085 0.5815 2.5333 0.7133 3.7120 0.4773 0.0210ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 0.0897 2.0944 1.7319 1.1370 2.4670 14.1766 0.0140 0.7817 2.4463 0.6366 3.4187 0.3280 0.0191ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 0.0531 1.9758 1.3426 0.9463 2.1277 10.8200 0.0089 0.5927 2.1263 0.6800 3.5398 0.4694 0.0211ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 0.0970 2.0767 1.4128 0.9721 2.2574 11.8584 0.0143 0.5318 2.4213 0.7024 3.8784 0.4725 0.0186ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 1.1860 0.0118 0.6153 1.8402 3.8159ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 1.9084 0.0125 0.6216 1.3412 3.3909ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 1.3886 0.0139 0.4748 1.8401 3.8649ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 1.3474 0.0105 0.6983 2.2684 3.4729ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 1.3282 0.0112 0.7269 2.5704 3.6698ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 1.8589 0.0106 0.9261 1.4983 4.1610ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 1.3079 0.0081 0.6222 2.1254 3.6624Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 454SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 22 (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 0.1057 1.9627 1.4805 1.2769 2.3286 11.5397 0.0061 0.6524 2.7266 0.8312 3.7350 0.3407 0.0216ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 0.0774 1.9889 1.3082 0.9539 2.1117 10.4316 0.0123 0.5004 3.0011 0.7788 3.8981 0.3454 0.0169ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 0.0686 2.0279 1.3504 1.0892 2.1057 11.3268 0.0107 0.5542 2.1865 0.6756 3.6956 0.4420 0.0138ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 0.0788 1.9699 1.5609 1.0438 2.5069 12.8452 0.0090 0.4864 1.9200 0.7129 3.8825 0.4544 0.0212ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 0.0847 2.2670 1.3202 1.0852 2.6392 12.7066 0.0117 0.4971 2.4256 0.6425 3.9176 0.4973 0.0241ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 1.3895 0.0099 0.7303 2.6158 3.6659ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 1.4823 0.0108 0.5493 1.6350 3.9922ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 2.2286 0.0107 0.7530 2.2260 3.5490ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 0.6639 0.0149 0.4797 1.7791 1.1726ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 1.1203 0.0095 0.6207 1.9972 2.9348ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 1.2938 0.0129 0.6308 2.4870 3.7805ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 1.8302 0.0100 0.7923 2.1920 3.9850Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 455Appendix 22 (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 0.0779 2.0182 1.5059 1.0182 2.2149 11.8538 0.0096 0.5460 2.1770 0.7374 3.6536 0.4636 0.0188ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 0.0825 1.9871 1.7418 1.0161 2.2697 10.8327 0.0095 0.5516 2.3644 0.6672 3.3687 0.2892 0.0199ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 0.0732 2.0183 1.5511 0.8636 2.2425 10.7655 0.0074 0.5176 1.7267 0.8337 3.8090 0.3680 0.0216ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 0.0912 2.0806 1.4507 1.0336 2.1849 10.5340 0.0071 0.3493 1.5121 0.7592 3.7071 0.5078 0.0204ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 0.0817 2.1307 1.5608 1.1705 2.3597 13.5553 0.0084 0.6496 2.1260 0.8092 4.2807 0.4959 0.0228ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 1.3549 0.0068 0.4928 1.8824 3.6576ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 1.4418 0.0088 0.6079 1.7389 4.3941ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 1.6325 0.0089 0.8111 2.4837 3.3114ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 1.2944 0.0083 0.5877 1.9276 3.7675ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 1.3713 0.0060 0.5678 2.8650 3.7983ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 1.3544 0.0108 0.9381 2.2804 3.8681ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 1.4647 0.0093 0.4432 1.6911 4.2270Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 456SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 22 (continued) Individual Organ WeightsGroup Animal Uterus(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus & Cervix ThyroidNumber g g g g g g g g g g g1(F) 13 43 0.1295 1.8897 0.8308 1.7485 11.5786 0.1255 0.0120 0.6631 0.1441 0.9736 0.0121ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ14 43 0.1086 1.8195 0.7839 1.6588 11.2761 0.1310 0.0120 0.7481 0.4033 0.8544 0.0137ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ15 43 0.0964 2.0051 0.9259 1.7478 10.9172 0.1510 0.0119 0.6456 0.1806 0.6426 0.0124ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ16 45 0.1543 0.0138 0.9148ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ17 52 0.0707 0.0205 0.8985ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ18 43 0.1093 1.8468 1.0451 1.8787 11.0962 0.1424 0.0139 0.5887 0.3666 0.5866 0.0157ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ19 43 0.0845 1.9016 0.8338 1.5770 11.8395 0.1261 0.0118 0.5916 0.2549 0.6878 0.0108ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ20 46 0.1147 0.0103 0.5930ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ21 42 0.1121 0.0124 0.5968ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ22 45 0.1109 0.0123 0.5224ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ23 43 0.1085 0.0151 0.7904ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ24 44 0.1250 0.0174 0.8450Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 457Appendix 22 (continued) Individual Organ WeightsGroup Animal Uterus(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus & Cervix ThyroidNumber g g g g g g g g g g g2(F) 37 43 0.1082 1.8504 0.8893 1.5833 10.4163 0.1302 0.0098 0.6424 0.4218 0.6055 0.0242ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ38 45 0.1008 0.0131 0.6234ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ39 46 0.1260 0.0145 0.5906ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ40 45 0.0709 0.0135 0.6797ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ41 42 0.0983 1.8270 0.9266 1.6874 11.7426 0.1006 0.0135 0.4768 0.1905 0.6644 0.0120ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ42 43 0.1043 1.9336 0.8342 1.7642 11.1932 0.1053 0.0154 0.8020 0.2647 0.8020 0.0204ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ43 44 0.1026 0.0109 0.6993ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ44 43 0.0910 1.9219 0.8845 1.7542 11.0636 0.1419 0.0188 0.5254 0.2499 0.8296 0.0145ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ45 44 0.1195 0.0132 0.6846ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ46 42 0.0766 1.8167 0.9743 1.8305 11.6301 0.1488 0.0180 0.6934 0.2338 0.7984 0.0153ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ47 44 0.1069 0.0180 0.7340ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ48 45 0.1220 0.0162 0.6290Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 458SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 22 (continued) Individual Organ WeightsGroup Animal Uterus(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus & Cervix ThyroidNumber g g g g g g g g g g g3(F) 61 43 0.1026 1.8768 0.8517 1.7236 11.3829 0.1264 0.0153 0.7043 0.2457 0.7798 0.0137ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ62 43 0.0835 1.9642 0.9241 1.5115 10.7765 0.1335 0.0175 0.7505 0.2777 0.6077 0.0172ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ63 45 0.1225 0.0149 0.6687ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ64 45 0.1291 0.0114 0.6484ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ65 44 0.1109 2.0416 0.9458 1.9688 11.6347 0.1337 0.0178 0.7444 0.2512 0.8442 0.0207ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ66 45 0.1267 0.0153 0.6543ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ67 44 0.0985 1.7680 0.8347 1.5151 10.6159 0.1095 0.0151 0.5604 0.1959 0.6974 0.0123ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ68 44 0.1088 0.0151 0.6491ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ69 42 0.1152 0.0124 0.4533ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ70 43 0.0877 1.9869 0.8003 1.5990 10.4439 0.1220 0.0187 0.6548 0.2272 0.7264 0.0215ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ71 44 0.0901 0.0102 0.7418ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ72 45 0.1208 0.0153 0.6094Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 459Appendix 22 (continued) Individual Organ WeightsGroup Animal Uterus(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus & Cervix ThyroidNumber g g g g g g g g g g g4(F) 85 43 0.0886 1.8726 0.6732 1.5354 8.6337 0.1198 0.0136 0.6658 0.2116 0.6706 0.0147ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ86 43 0.0971 1.8671 0.8776 1.5988 10.4339 0.1140 0.0146 0.7037 0.3319 0.6890 0.0233ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ87 45 0.1252 0.0152 0.6132ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ88 45 0.1121 0.0169 0.5779ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ89 45 0.1285 0.0133 0.4728ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ90 42 0.1044 1.9250 0.8206 1.7748 12.2692 0.1105 0.0201 0.5856 0.2340 0.7106 0.0172ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ91 44 0.1169 1.7696 0.9812 1.7212 11.8048 0.1356 0.0125 0.7981 0.1833 0.7313 0.0164ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ92 46 0.1487 0.0122 0.5638ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ93 45 0.1252 0.0170 0.8012ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ94 45 0.0955 0.0125 0.4305ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ95 46 0.1239 0.0091 0.4835ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ96 43 0.1074 1.9072 0.9519 1.8013 11.4212 0.1404 0.0156 0.5856 0.3040 0.8857 0.0220Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 460SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 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 43 396 0.0221 0.5323 0.4635 0.2517 0.6344 3.1467 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 386 0.0158 0.5619 0.3625 0.2633 0.5620 2.7649 0.0024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 384 0.0188 0.5368 0.4807 0.2465 0.6457 3.4301 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 369 0.0180 0.5132 0.3530 0.2632 0.5827 3.0688 0.0024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 388 0.0139 0.5171 0.3594 0.2702 0.6604 3.1731 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 413 0.4181 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 418 0.3811 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 391 0.3785 0.0023ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 387 0.3451 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 361 0.4363 0.0033ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 353 0.3418 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 408 0.3269 0.0026Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 461Appendix 23 (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 0.1405 0.5553 0.2042 1.1397 0.0962 0.0034ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ2 43 0.1455 0.6386 0.2095 0.9361 0.1270 0.0065ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ3 43 0.1529 0.6790 0.2103 1.1120 0.0870 0.0042ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ4 43 0.1585 0.6004 0.1523 0.8608 0.0971 0.0035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ5 43 0.1888 0.5453 0.1627 1.0290 0.1021 0.0053ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ6 43 0.1606 0.5832 0.9459ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ7 43 0.1658 0.5793 0.9675ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ8 43 0.1688 0.6104 0.9588ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ9 43 0.1790 0.5001 0.8622ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ10 43 0.2161 0.6617 1.2181ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ11 43 0.1708 0.6420 0.9969ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ12 43 0.1744 0.6288 0.8862Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 462SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 (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 43 425 0.0178 0.5092 0.3773 0.2547 0.5671 2.9943 0.0025ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 395 0.0157 0.5378 0.3415 0.2372 0.5022 2.9432 0.0022ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 408 0.0220 0.5133 0.4245 0.2787 0.6047 3.4747 0.0034ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 384 0.0138 0.5145 0.3496 0.2464 0.5541 2.8177 0.0023ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 404 0.0240 0.5140 0.3497 0.2406 0.5588 2.9352 0.0035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 385 0.3081 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 386 0.4944 0.0032ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 396 0.3507 0.0035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 373 0.3612 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 375 0.3542 0.0030ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 384 0.4841 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 379 0.3451 0.0021Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 463Appendix 23 (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 0.1917 0.5203 0.1857 0.9642 0.1427 0.0050ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ26 43 0.1472 0.6413 0.1806 0.9397 0.1208 0.0053ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ27 43 0.1916 0.5996 0.1560 0.8379 0.0804 0.0047ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ28 43 0.1543 0.5537 0.1771 0.9218 0.1222 0.0055ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ29 43 0.1316 0.5993 0.1739 0.9600 0.1170 0.0046ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ30 43 0.1598 0.4780 0.9911ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ31 43 0.1610 0.3475 0.8785ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ32 43 0.1199 0.4647 0.9760ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ33 43 0.1872 0.6082 0.9311ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ34 43 0.1938 0.6854 0.9786ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ35 43 0.2412 0.3902 1.0836ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ36 43 0.1642 0.5608 0.9663Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 464SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 (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 43 407 0.0260 0.4822 0.3638 0.3137 0.5721 2.8353 0.0015ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 397 0.0195 0.5010 0.3295 0.2403 0.5319 2.6276 0.0031ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 371 0.0185 0.5466 0.3640 0.2936 0.5676 3.0530 0.0029ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 385 0.0205 0.5117 0.4054 0.2711 0.6511 3.3364 0.0023ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 418 0.0203 0.5423 0.3158 0.2596 0.6314 3.0399 0.0028ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 404 0.3439 0.0025ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 410 0.3615 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 396 0.5628 0.0027ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 408 0.1627 0.0037ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 362 0.3095 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 374 0.3459 0.0034ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 380 0.4816 0.0026Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 465Appendix 23 (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 0.1603 0.6699 0.2042 0.9177 0.0837 0.0053ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ50 43 0.1260 0.7559 0.1962 0.9819 0.0870 0.0043ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ51 43 0.1494 0.5894 0.1821 0.9961 0.1191 0.0037ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ52 43 0.1263 0.4987 0.1852 1.0084 0.1180 0.0055ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ53 43 0.1189 0.5803 0.1537 0.9372 0.1190 0.0058ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ54 43 0.1808 0.6475 0.9074ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ55 43 0.1340 0.3988 0.9737ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ56 43 0.1902 0.5621 0.8962ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ57 43 0.1176 0.4361 0.2874ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ58 43 0.1715 0.5517 0.8107ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ59 43 0.1687 0.6650 1.0108ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ60 43 0.2085 0.5768 1.0487Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 466SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 (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 43 397 0.0196 0.5084 0.3793 0.2565 0.5579 2.9858 0.0024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 368 0.0224 0.5400 0.4733 0.2761 0.6168 2.9437 0.0026ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 390 0.0188 0.5175 0.3977 0.2214 0.5750 2.7604 0.0019ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 397 0.0230 0.5241 0.3654 0.2604 0.5504 2.6534 0.0018ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 409 0.0200 0.5210 0.3816 0.2862 0.5769 3.3143 0.0021ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 368 0.3682 0.0018ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 376 0.3835 0.0023ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 421 0.3878 0.0021ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 408 0.3173 0.0020ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 390 0.3516 0.0015ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 449 0.3016 0.0024ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 388 0.3775 0.0024Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 467Appendix 23 (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 0.1375 0.5484 0.1857 0.9203 0.1168 0.0047ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ74 43 0.1499 0.6425 0.1813 0.9154 0.0786 0.0054ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ75 43 0.1327 0.4427 0.2138 0.9767 0.0944 0.0055ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ76 43 0.0880 0.3809 0.1912 0.9338 0.1279 0.0051ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ77 43 0.1588 0.5198 0.1978 1.0466 0.1212 0.0056ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ78 43 0.1339 0.5115 0.9939ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ79 43 0.1617 0.4625 1.1686ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ80 43 0.1927 0.5900 0.7866ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ81 43 0.1440 0.4725 0.9234ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ82 43 0.1456 0.7346 0.9739ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ83 43 0.2089 0.5079 0.8615ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ84 43 0.1142 0.4359 1.0894Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 468SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 (continued) Individual 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 43 266 0.0487 0.7104 0.3123 0.6573 4.3529 0.0472 0.0045 0.2493 0.0542 0.0045 0.3660ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ14 43 285 0.0381 0.6384 0.2751 0.5820 3.9565 0.0460 0.0042 0.2625 0.1415 0.0048 0.2998ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ15 43 266 0.0362 0.7538 0.3481 0.6571 4.1042 0.0568 0.0045 0.2427 0.0679 0.0047 0.2416ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ16 45 250 0.0617 0.0055 0.3659ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ17 52 314 0.0225 0.0065 0.2861ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ18 43 286 0.0382 0.6457 0.3654 0.6569 3.8798 0.0498 0.0049 0.2058 0.1282 0.0055 0.2051ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ19 43 260 0.0325 0.7314 0.3207 0.6065 4.5537 0.0485 0.0045 0.2275 0.0980 0.0042 0.2645ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ20 46 258 0.0445 0.0040 0.2298ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ21 42 261 0.0430 0.0048 0.2287ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ22 45 271 0.0409 0.0045 0.1928ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ23 43 248 0.0437 0.0061 0.3187ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ24 44 296 0.0422 0.0059 0.2855Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 469Appendix 23 (continued) Individual 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 43 278 0.0389 0.6656 0.3199 0.5695 3.7469 0.0468 0.0035 0.2311 0.1517 0.0087 0.2178ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ38 45 246 0.0410 0.0053 0.2534ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ39 46 285 0.0442 0.0051 0.2072ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ40 45 250 0.0284 0.0054 0.2719ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ41 42 265 0.0371 0.6894 0.3497 0.6368 4.4312 0.0380 0.0051 0.1799 0.0719 0.0045 0.2507ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ42 43 273 0.0382 0.7083 0.3056 0.6462 4.1001 0.0386 0.0056 0.2938 0.0970 0.0075 0.2938ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ43 44 245 0.0419 0.0044 0.2854ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ44 43 276 0.0330 0.6963 0.3205 0.6356 4.0086 0.0514 0.0068 0.1904 0.0905 0.0053 0.3006ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ45 44 271 0.0441 0.0049 0.2526ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ46 42 298 0.0257 0.6096 0.3269 0.6143 3.9027 0.0499 0.0060 0.2327 0.0785 0.0051 0.2679ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ47 44 275 0.0389 0.0065 0.2669ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ48 45 286 0.0427 0.0057 0.2199Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/dayPROJECT NUMBER: 41104692RPAGE 470SODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)Appendix 23 (continued) Individual 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 43 286 0.0359 0.6562 0.2978 0.6027 3.9800 0.0442 0.0053 0.2463 0.0859 0.0048 0.2727ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ62 43 260 0.0321 0.7555 0.3554 0.5813 4.1448 0.0513 0.0067 0.2887 0.1068 0.0066 0.2337ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ63 45 275 0.0445 0.0054 0.2432ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ64 45 318 0.0406 0.0036 0.2039ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ65 44 281 0.0395 0.7265 0.3366 0.7006 4.1405 0.0476 0.0063 0.2649 0.0894 0.0074 0.3004ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ66 45 278 0.0456 0.0055 0.2354ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ67 44 273 0.0361 0.6476 0.3058 0.5550 3.8886 0.0401 0.0055 0.2053 0.0718 0.0045 0.2555ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ68 44 288 0.0378 0.0052 0.2254ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ69 42 267 0.0431 0.0046 0.1698ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ70 43 266 0.0330 0.7470 0.3009 0.6011 3.9263 0.0459 0.0070 0.2462 0.0854 0.0081 0.2731ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ71 44 251 0.0359 0.0041 0.2955ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ72 45 296 0.0408 0.0052 0.2059Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/daySODIUM GLUCOHEPTONATE (EC 250-480-2): ORAL (GAVAGE)COMBINED REPEAT DOSE TOXICITY STUDY WITHREPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 422)PROJECT NUMBER: 41104692RPAGE 471Appendix 23 (continued) Individual 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 43 236 0.0375 0.7935 0.2853 0.6506 3.6583 0.0508 0.0058 0.2821 0.0897 0.0062 0.2842ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ86 43 269 0.0361 0.6941 0.3262 0.5943 3.8788 0.0424 0.0054 0.2616 0.1234 0.0087 0.2561ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ87 45 278 0.0450 0.0055 0.2206ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ88 45 284 0.0395 0.0060 0.2035ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ89 45 277 0.0464 0.0048 0.1707ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ90 42 280 0.0373 0.6875 0.2931 0.6339 4.3819 0.0395 0.0072 0.2091 0.0836 0.0061 0.2538ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ91 44 281 0.0416 0.6298 0.3492 0.6125 4.2010 0.0483 0.0044 0.2840 0.0652 0.0058 0.2602ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ92 46 283 0.0525 0.0043 0.1992ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ93 45 302 0.0415 0.0056 0.2653ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ94 45 236 0.0405 0.0053 0.1824ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ95 46 255 0.0486 0.0036 0.1896ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ96 43 297 0.0362 0.6422 0.3205 0.6065 3.8455 0.0473 0.0053 0.1972 0.1024 0.0074 0.2982Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 30 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 531



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 537



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 551



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

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# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 24 (continued) Histopathology Phase Report

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# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 569



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 570 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 571



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 572 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 573



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 574 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 575



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 576 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 577



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 578 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 579



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 580 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 581



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 582 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 583



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 584 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 585



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 586 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 587



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 588 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 589



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PAGE 590 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 24 (continued) Histopathology Phase Report

# PROJECT NUMBER: 41104692R PAGE 591



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 25 Chemical Analysis of Test Item Formulations, Methods and Results

1. METHOD OF ANALYSIS

1.1 Summary



# The concentration of Sodium Glucoheptonate (EC 250-480-2) in the test item

formulations was determined by direct injection into a mass spectrometer (MS) using an

external standard technique.

1.2 Samples



# The test item formulations were diluted with mobile phase to give a final, theoretical test

item concentration of approximately 0.001 mg/ml.

1.3 Standards



# Standard solutions of test item were prepared in mobile phase at a nominal

concentration of 0.001 mg/ml.

1.4 Procedure



# The standards and samples were analysed by (MS) using the following conditions:

HPLC System : Agilent Technologies 1200 MSD, incorporating

autosampler and workstation

Mass selective detector

Source : electrospray

Fragmentation energy : 100 volts

Polarity : negative

Mode : single ion mode with 225 amu

Gas temperature : 350oC

Drying gas : 12 litre/minute

Nebuliser pressure : 40 psi

Capillary voltage : 4000 volts

Gain : 1

Column : N/A

Mobile phase : methanol: water: ammonia (50:50:0.1, v/v/v)

Flow rate : 0.5 ml/min

Injection volume : 10 μl

Retention time : approximately 0.2 minutes

# PAGE 592 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 25 (continued) Chemical Analysis of Test Item Formulations, Methods

and Results

1.5 Homogeneity Determinations



# The test item formulations were assessed visually.

1.6 Verification of Test Item Formulation Concentrations



# The test item formulations were sampled and analysed within four days of preparation.

2. RESULTS



# The test item formulations were deemed homogeneous by visual inspection.

2.1 Verification of Concentration of Test Item Formulations

Week Number Nominal Concentration

(mg/ml) Concentration Found

(mg/ml) (expressed as % of

nominal)

1 0 ND -

11.9 13.2 111

118.8 106.2 89

396 484 122

2 0 ND -

11.9 11.2 94

118.8 133.9 113

396 384 97

3 0 ND -

11.9 12.7 106

118.8 114.1 96

396 374 94

5 0 ND -

11.9 13.4 113

118.8 131.7 111

396 412 104

6 0 ND -

11.9 12.1 102

118.8 120.2 101

396 410 104

7 0 ND -

11.9 11.6 97

118.8 118.1 99

396441 443 112

ND = none detected

- = not applicable

# PROJECT NUMBER: 41104692R PAGE 593



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 25 (continued) Chemical Analysis of Test Item Formulations, Methods

and Results

3. METHOD VALIDATION

3.1 Linearity



# A range of standard solutions covering the concentration range 0 to 0.00218 mg/ml, were

prepared and analysed.

The detector response was shown to be linear up to 0.00218 mg/ml.

Standard Concentration (mg/ml) Peak Area (units)

0.000 0.000

0.000546 2.851x10 4



# 0.000873 4.143x10 4



# 0.00109 5.092x10 4



# 0.00131 5.499x10 4



# 0.00218 9.109x10 4



# Slope 4.081x10 7



# Intercept 3.687x10 3



# Correlation Coefficient (r) 0.996



# The results are presented graphically in Figure 1.

3.2 Specificity



# The diluent solvent mobile phase and a blank Distilled Water (control) were analysed.

The results are shown in the following table:

Sample Concentration Found

Mobile Phase None detected

Distilled Water(control) None detected



# Analysis of the solvent and a blank Distilled Water (control) produced no signal that

interfered with the signal due to the test item.

# PAGE 594 PROJECT NUMBER: 41104692R



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RAT (OECD 422)



# Appendix 25 (continued) Chemical Analys is of Test Item Formulations, Methods

and Results

3.3 Accuracy



# Samples of Distilled Water were accurately fortified with known amounts of test item, and

analysed:

Fortification

(mg/g) Concentration Found

(mg/g) %

Recovered Mean Recovery

(%)

5.50 5.66 103

105

5.48 5.83 106

502 494 99

103

492 531 108



# The analytical method has been considered to be sufficiently accurate for the purpose of

this study. The test sample results have not been corrected for recovery.

3.4 Conclusion



# The analytical method has been satisfactorily validated in terms of linearity, specificity

and accuracy for the purposes of the study.

# PROJECT NUMBER: 41104692R PAGE 595



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 25 (continued) Chemical Analysis of Test Item Formulations, Methods

and Results

Figure 1 Linearity of Detector Response

# PAGE 596 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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# Appendix 26 Study Plan

# PROJECT NUMBER: 41104692R PAGE 597



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 598 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 599



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 600 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 601



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 602 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 603



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 604 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 605



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 606 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 607



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 608 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 609



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 610 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 611



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 612 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 613



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 614 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 615



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 616 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PROJECT NUMBER: 41104692R PAGE 617



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 26 (continued) Study Plan

# PAGE 618 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 27 Histology Processing Phase Test Site Quality Assurance Statement

# PROJECT NUMBER: 41104692R PAGE 619



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 28 Histology Processing Phase Test Site Statement of Compliance

# PAGE 620 PROJECT NUMBER: 41104692R



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RAT (OECD 422)



# Appendix 29 Histology Processing Phase Test Site Statement of GLP

Compliance

# PROJECT NUMBER: 41104692R PAGE 621



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 30 Statement of GLP Compliance in Accordance with Directive

2004/9/EC

# PAGE 622 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 31 Certificates of Analysis of Diet Used

# PROJECT NUMBER: 41104692R PAGE 623



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 31 (continued) Certificates of Analysis of Diet Used

# PAGE 624 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 31 (continued) Certificates of Analysis of Diet Used

# PROJECT NUMBER: 41104692R PAGE 625



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

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RAT (OECD 422)



# Appendix 32 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 visual 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) - determined by visual assessment of 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

# PAGE 626 PROJECT NUMBER: 41104692R



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# Appendix 32 (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 autoanalyser mmol/l

Potassium (K+) - estimated by ISE electrode No. 0018263500 and ILab 600 autoanalyser 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. 0018252140

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 kit No. 0018254640

and ILab 600 auto-analyser mg/dl

Bile acids (Bile) - estimated by Randox Kit No. B13863 and ILab 600 auto-analyser μ mol/l

# PROJECT NUMBER: 41104692R PAGE 627



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 33 Normal Ranges for Reproduc tive Parameters in the Pregnant and

Lactating Female Wistar Han TM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. A PPROXIMATE AGE: Fourteen to Nineteen weeks

UPDATED: November 2011

Range * No. of Animals

MATING & GESTATION

Pre-Coital Interval ( Da y s ) 1 - 5 209

( 2 ) ( 1 )

Gestation Len g ths ( Da y s ) 21.8 - 23.5 213

( 22.7 ) ( 0.4 )

FOOD CONSUMPTIONS (g/rat/day)

Gestation Da y s 0 - 7 15 - 23 208

( 19 ) ( 2 )

Gestation Da y s 7 - 14 17 - 25 208

( 21 ) ( 2 )

Gestation Da y s 14 - 20 19 - 27 206

( 23 ) ( 2 )

Lactation Da y s 1 - 4 18 - 36 196

( 27 ) ( 4 )

BODY WEIGHT CHANGE (g)

Gestation Da y s 0 - 7 13 - 35 208

( 24 ) ( 5 )

Gestation Da y s 7 - 14 16 - 36 180

( 26 ) ( 5 )

Gestation Da y s 14 - 20 44 - 81 179

( 63 ) ( 9 )

Lactation Da y s 1 - 4 -3 - 24 209

( 10 ) ( 7 )

CORPORA LUTEA &

IMPLANTATIONS

Cor p ora Lutea ( Number ) 10 - 19 208

( 15 ) ( 2 )

Implantations (Number) 9 - 18 208

( 13 ) ( 2 )

Pre-Im p lantation loss ( % ) 0 - 27 200

( 8 ) ( 10 )

Post-Im p lantation loss ( % ) 0 - 24 207

(7) (8)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# PAGE 628 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 34 Normal Ranges for Offspring Parameters in the Wistar HanTM:

RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. A GE: 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 Da y 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 m ean and standard deviat ion respectively)

# PROJECT NUMBER: 41104692R PAGE 629



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 35 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 A PPROXIMATE 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)

Retics (%) 3.4 - 6.2 5 5.9 - 11.4 5

(4.8) (0.7) (8.6) (1.4)

Meth (%) 1.05 - 1.72 5 0.29 - 1.11 3

(1.60) (1.39) (0.70) (0.21)

* Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# PAGE 630 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 35 (continued) Normal Ranges for Haematological and Blood Chemical

Values in the Wistar HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. A PPROXIMATE AGE: Eighteen weeks

UPDATED: November 2011 PHASE: Prior to Termination

BLOOD CHEMISTRY Male Female

Range* No. of

Animals Range* No. of

Animals

Urea (mg/dl) 35 - 58 71 37 - 63 67

(46) (6) (50) (7)

Glucose (mg/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)

Na+ (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 (mg/dl) 0.56 - 0.87 71 0.59 - 0.81 65

(0.71) (0.08) (0.70) (0.06)

Chol (mg/dl) 56 - 102 68 51 - 78 58

(79) (12) (64) (7)

Bili (mg/dl) 0.00 - 0.16 65 0.00 - 0.11 75

(0.08) (0.04) (0.06) (0.03)

Bile Acids (μmol/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 m ean and standard deviat ion respectively)

# PROJECT NUMBER: 41104692R PAGE 631



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# Appendix 36 Normal Ranges for Functi onal Performance Assessments in the

Wistar HanTM:RccHanTM:WIST Strain Rat

SUPPLIER: Harlan Laboratories U.K. Ltd. A PPROXIMATE AGE: Eighteen weeks

UPDATED: October 2009

FUNCTIONAL PERFORMANCE TESTS Male Female

Range 

# * No. of

Animals Range* No. of

Animals

MOTOR ACTIVITY

OVERALL ACTIVITY 73 - 558 23 256 - 789 25

(315) (121) (522) (133)

OVERALL MOBILE ACTIVITY 0.0 - 1.7 26 0.0 - 11.7 26

(0.4) (0.6) (4.5) (3.6)

FINAL 20% OVERALL ACTIVITY 0.0 - 27.9 22 19 - 150 20

(8.8) - (9.6) (84) (33)

FINAL 20% MOBILE ACTIVITY 0.0 - 0.0 26 0.0 - 1.2 25

(0.0) (0.0) (0.2) (0.5)

FORELIMB GRIP STRENGTH 574 - 1704 86 417 - 1294 85

(1139) (282) (855) (219)

HINDLIMB GRIP STRENGTH 149 - 699 88 126 - 545 78

(424) (137) (335) (105)

SENSORY REACTIVITY SCORES Incidence

Male

n = 30 Female

n = 29

GRASP RESPONSE: 0 30 29

VOCALISATION: 0 28 15

: 1 2 12

: 2 0 1

: 3 0 1

TOE PINCH: 0 30 29

TAIL PINCH: 0 30 29

FINGER APPROACH: 0 30 29

TOUCH ESCAPE: 0 30 27

: 1 0 2

PUPIL REFLEX: -1 1 0

: 0 29 29

BLINK REFLEX: 0 30 29

STARTLE REFLEX: 0 30 29



# * Range = mean ± 2 standard deviations

(values in brackets indicate group mean and standard deviation respectively)

# PAGE 632 PROJECT NUMBER: 41104692R



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# 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. A PPROXIMATE 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 m ean and standard deviat ion respectively)

# PROJECT NUMBER: 41104692R PAGE 633



# SODIUM GLUCOHEPTONATE (EC 250-480-2): OR AL (GAVAGE) COMBINED REPEAT DOSE

TOXICITY STUDY WITH REPRODUCTION/DEVELOPM ENTAL TOXICITY SCREENING TEST IN THE

RAT (OECD 422)



# 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. A PPROXIMATE 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)