TEST FACILITY: 

SPONSOR: 

FINAL REPORT

Test Facility Study No. 459926, Report No. 31261

Alcohols, C18-22, Distn. Residues (CAS No. 1160164-88-4): A 28 Day Oral

(Gavage) Toxicity Study in Rats

Charles River

Tranent

Edinburgh

EH33 2NE

UK

SASOL Germany GmbH

Anckelmannsplatz 1

Hamburg 20537

Germany

Page 1 of 197
TABLE OF CONTENTS 

TABLE OF CONTENTS ................................................................................................ 2

LIST OF FIGURES ........................................................................................................ 5

LIST OF TABLES .......................................................................................................... 6

LIST OF APPENDICES ................................................................................................ 7

1. COMPLIANCE STATEMENT.................................................................................. 8

2. QUALITY ASSURANCE STATEMENT ................................................................. 9

3. RESPONSIBLE PERSONNEL .................................................................................. 10

4. SUMMARY .................................................................................................................. 11

5. INTRODUCTION........................................................................................................ 12

6. EXPERIMENTAL PROCEDURE............................................................................. 12

6.1. Test Item ................................................................................................................... 12

6.1.1. Vehicle .................................................................................................................... 13

6.1.2. Test Item Formulation .......................................................................................... 13

6.1.3. Formulation Analysis ............................................................................................ 13

6.2. Animals and Management ....................................................................................... 13

6.2.1. Acclimatisation ...................................................................................................... 14

6.2.2. Allocation to Dose Group ..................................................................................... 14

6.2.3. Animal Identification ............................................................................................ 14

6.2.4. Room Environment ............................................................................................... 14

6.2.5. Room Sanitation .................................................................................................... 15

6.2.6. Diet and Water ...................................................................................................... 15

7. EXPERIMENTAL DESIGN....................................................................................... 15

7.1. Dose Levels, Route, Duration and Method of Administration ............................ 16

7.2. Definition of ‘Day’ .................................................................................................... 16

7.3. Treatment of Data .................................................................................................... 16

8. OBSERVATIONS ........................................................................................................ 16

 

 

 

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Test Facility Study No. 459926
8.1. Mortality / Moribundity Checks ............................................................................. 16

8.2. Detailed Physical Examination ............................................................................... 16

8.3. Additional Clinical Observations ........................................................................... 17

8.4. Detailed Functional Observations .......................................................................... 17

8.4.1. Cage side Observations ......................................................................................... 17

8.4.2. Observations in a Standardized Area (2 min Observation): ............................. 18

8.4.3. Functional Tests: ................................................................................................... 18

8.5. Body Weights ............................................................................................................ 19

8.6. Food Consumption ................................................................................................... 19

8.6.1. Water Consumption .............................................................................................. 19

8.7. Ophthalmology Examinations ................................................................................ 20

8.8. Clinical Pathology .................................................................................................... 20

8.8.1. Sample Collection .................................................................................................. 20

8.8.2. Haematology .......................................................................................................... 20

8.8.3. Coagulation ............................................................................................................ 21

8.8.4. Clinical Chemistry ................................................................................................ 22

8.8.5. Urinalysis ............................................................................................................... 23

8.9. Terminal Procedures ............................................................................................... 25

8.9.1. Scheduled Euthanasia ........................................................................................... 25

8.9.2. Gross Necropsy ...................................................................................................... 25

8.9.3. Organ Weights ....................................................................................................... 25

8.9.4. Tissue Collection and Preservation ..................................................................... 25

8.9.5. Bone Marrow ......................................................................................................... 27

8.9.6. Histology and Histopathology .............................................................................. 27

9. ELECTRONIC DATA ACQUISITION AND SYSTEMS....................................... 27

9.1. Statistical Analysis ................................................................................................... 28

10. RESULTS ................................................................................................................... 29

10.1. Formulation Analysis ............................................................................................. 29

10.2. Observations ........................................................................................................... 29

 

 

 

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Test Facility Study No. 459926
10.2.1. Mortality and Clinical Observations ................................................................. 29

10.2.2. Detailed Functional Observations ..................................................................... 29

10.2.3. Body Weights ....................................................................................................... 29

10.2.4. Food Consumption .............................................................................................. 30

10.2.5. Ophthalmology .................................................................................................... 30

10.2.6. Clinical Pathology ............................................................................................... 30

10.2.7. Organ Weights ..................................................................................................... 31

10.2.8. Gross Necropsy .................................................................................................... 31

10.2.9. Histopathology ..................................................................................................... 31

11. CONCLUSION........................................................................................................... 32

 

 

 

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LIST OF FIGURES 

Figure 1 : Cage Plan .......................................................................................................... 33

Figure 2 : Body Weights Graph (g) : Group Mean Values ............................................... 34

 

 

 

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LIST OF TABLES 

Table 1 : Neurotoxicity Screening: Detailed Functional Observations: Group 

Mean Values ..................................................................................................................... 36

Table 2 : Neurotoxicity Screening: Motion Activity (Movements / 5 minutes) : 

Group Mean Values .......................................................................................................... 38

Table 3 : Functional Observations: Group Mean Values .................................................. 40

Table 4 : Body Weights (g): Group Mean Values ............................................................ 44

Table 5 : Food Consumption (g/animal/day): Group Mean Values .................................. 46

Table 6 : Haematology and Coagulation: Group Mean Values ........................................ 48

Table 7 : Clinical Chemistry: Group Mean Values ........................................................... 52

Table 8 : Urinalysis: Group Mean Values ........................................................................ 56

Table 9 : Absolute Organ Weights (g): Group Mean Values ........................................... 58

Table 10 : Relative Organ Weights (% Body Weight): Group Mean Values ................... 62

Table 11 : Organ Weights (Covariance Analysis): Group Mean Values .......................... 66

Table 12 : Summary of Necropsy Findings ...................................................................... 70

Table 13 : Summary of Histological Findings .................................................................. 72

 

 

 

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Test Facility Study No. 459926
LIST OF APPENDICES 

Appendix 1 : Certificate of Analysis ................................................................................. 82

Appendix 2 : Certificate of Analysis - Diet ...................................................................... 83

Appendix 3 : Formulation Analysis .................................................................................. 85

Appendix 4 : Individual Clinical Observations ................................................................. 86

Appendix 5 : Functional Observation Battery Animal Numbers ...................................... 92

Appendix 6 : Individual Clinical Signs: Functional Observation Battery ........................ 93

Appendix 7 : Neurotoxicity Screening: Detailed Functional Observations: 

Individual Values .............................................................................................................. 131

Appendix 8 : Neurotoxicity Screening: Motion Activity (Movements / 5 minutes): 

Individual Values .............................................................................................................. 133

Appendix 9 : Body Weights (g): Individual Values ......................................................... 135

Appendix 10 : Food Consumption (g/animal/day): Individual Values ............................. 137

Appendix 11 : Ophthalmoscopy: Individual Findings ...................................................... 139

Appendix 12 : Haematology and Coagulation: Individual Values ................................... 141

Appendix 13 : Clinical Chemistry: Individual Values ...................................................... 149

Appendix 14 : Urinalysis: Individual Values .................................................................... 153

Appendix 15 : Absolute Organ Weights (g): Individual Values ....................................... 157

Appendix 16 : Relative Organ Weights (% Body Weight): Individual Values ................ 165

Appendix 17 : Individual Necropsy and Histological Findings ........................................ 173

 

 

 

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Test Facility Study No. 459926


3. RESPONSIBLE PERSONNEL 

Study Director: Gyula Szucs DVM PhD DABT

Report Compilation: Ben Foster BSc

Peter Wilton BSc

Senior Animal Technician: Colin MacFarlane

Veterinary Officers: 

(Under the Supervision of) 

David Robb BVMS CertLAS MRCVS

Dispensary: 

(Under the supervision of) 

Ahmed Tahraoui BEng MSc PhD

Test Item Formulation Analysis: Elaine Rogers BSc

Clinical Pathology: 

(Under the supervision of) 

Geoff Burns BSc PhD CBiol MSB 

Statistical Analysis: 

(Under the supervision of) 

Marion Thom MSc

Pathologist: Morven Petersen-Jones BVMS MRCVS

Peer Reviewing Pathologist Sydney Mukaratirwa BVSc, MSc, PhD, 

DipRCPath

Quality Assurance Cheryl Rennie MSc 

Paul Davidson BSc

Sponsor’s Study Monitor: Dr Hans Certa

Peer Review: Adam Woolley MSc DABT FRCPath 

ERT CBiol MSB 

ForthTox Limited 

 

 

 

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Test Facility Study No. 459926
4. SUMMARY 

Alcohols, C18-22, distn. residues is a chemical being produced by the Sponsor. 

The objective of this study was to asses the potential toxicity of the test item following oral 

(gavage) administration for a period of at least 28 days. Three groups of 5 male and 5 female 

Han Wistar rats were administered Alcohols, C18-22, distn. residues orally at doses levels of 

100, 300 or 1000 mg/kg/day for a period of 28 days. A similarly constituted control group 

received the vehicle, 1% carboxymethylcellulose (medium viscosity) with 0.2% Tween 80 at 

the same dose volume of 10 mL/kg body weight as the treated animals. 

Animals were monitored regularly for viability and for signs of ill health or reaction to 

treatment. The following activities were measured and recorded at pre-determined intervals 

from pretrial until the completion of the study: body weights, food consumption, observations 

(clinical, detailed functional, standardised arena and cage), functional tests, ophthalmic 

examinations, haematology, coagulation, clinical chemistry, urinalysis, gross necropsy, organ 

weights and histopathology. 

There were no treatment-related clinical signs. 

No treatment-related effects were observed during the detailed functional observation 

investigations. 

Body weights and food consumption were unaffected by treatment. 

There were no treatment-related ocular findings. 

There were no treatment-related haematology, coagulation or clinical chemistry changes. 

There were no necropsy or histology findings attributed to treatment. 

In conclusion, repeat oral administration of Alcohols, C18-22, distn. residues to Han Wistar 

rats for 28 days at dose levels up to1000 mg/kg/day was considered to be well tolerated with 

no obvious evidence of toxicity being noted. Therefore, the dose of 1000 mg/kg/day was 

considered to be a No-Observed-Effect-Level (NOEL) in this study. 

 

 

 

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Test Facility Study No. 459926
5. INTRODUCTION 

Alcohols, C18-22, distn. residues is a chemical being produced by the Sponsor. 

The objective of this study was to asses the potential toxicity of the test item following 

repeated daily oral (gavage) administration for 28 days. 

This study was designed to be compliant with the OECD (Guideline No. 407), Directive 

96/54/E.C.B.7 and EPA OPPTS guideline 870.3050. 

This study was conducted in accordance with the OECD Principles of Good Laboratory 

Practice as set forth by the United Kingdom Department of Health and as accepted by 

Regulatory Authorities throughout the European Community, United States of America (FDA 

and EFA) and Japan (MHLW, MAFF and METI). 

The oral administration route was selected for this study as this route has been defined by the 

Sponsor as a possible route of human exposure. The rat was selected as the test model as it is 

accepted by regulatory authorities as a relevant animal model for toxicity studies, high quality 

animals are readily available and a large amount of background pathology data is available in 

this species. The number of animals used was considered to be necessary to assure an 

adequate number of animals at the end of the treatment period to yield meaningful results. 

The study was sponsored by SASOL Germany GmbH, Anckelmannsplatz 1, Hamburg 20537, 

Germany and was conducted at Charles River, Tranent, Edinburgh, EH33 2NE, UK. 

Study timings were: 

Study Initiation: 06 January 2010 

Animal Arrival: 12 January 2010 

Experimental Start Date: 20 January 2010 

(Commencement of pretrial period) 

First day of dosing: 27 January 2010 

Necropsy: 24 February 2010 

Completion of Experimental Work 

(Completion of Histopathology Evaluation): 25 March 2010 

Study Completion Date: See Compliance Statement page for date of 

 Study Director’s signature 

6. EXPERIMENTAL PROCEDURE 

6.1. Test Item 

Alcohols, C18-22, distn. residues (CAS No. 1160164-88-4). 

A shipment of 900 g of Alcohols, C18-22, distn. residues; CAS No. 1160164-88-4 (Batch No. 

03585/MA; product code: 59B1RN2) was received from SASOL Germany GmbH on 11 

September 2009. The test item was described as a waxy solid with yellowish colour. A 

purity value of 100% by definition and an expiry date of August 2013 were provided by 

SASOL Germany GmbH. 

 

 

 

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Test Facility Study No. 459926
Alcohols, C18-22, distn. residues was stored at ambient temperature, in the dark. 

The identity, strength, purity and composition, or other characteristics, which appropriately 

defined the batch from which Alcohols, C18-22, distn. residues for this study was drawn, was 

determined by SASOL Germany GmbH (Appendix 1). Stability of Alcohols, C18-22, distn. 

residues and methods of synthesis, fabrication or derivation were the responsibility of the 

Sponsor. 

A reference sample (approximately 100 mg) of Alcohols, C18-22, distn. residues was taken 

and stored under the conditions specified for the bulk of the test item. 

6.1.1. Vehicle 

The vehicle used was 1% carboxymethylcellulose (medium viscosity) with 0.2% Tween 80. 

6.1.2. Test Item Formulation 

A weighed amount of Alcohols, C18-22, distn. residues was suspended in an appropriate 

amount of vehicle, 1% carboxymethylcellulose (medium viscosity) with 0.2% Tween 80 and 

mixed using a Silverson Mixer until a visibly homogeneous suspension was obtained. The 

formulations were magnetically stirred for at least 60 min prior to and during sampling and 

splitting. All formulations were magnetically stirred for at least 30 min prior to dosing and 

continuously during dosing, with the exception of Group 4, which was stirred for at least 60 

min before dosing. Starting with Week 2 dosing preparations for all groups were stirred for 

60 min before dosing to make the procedure consistent across all groups. The formulations 

were prepared up to 8 days in advance and were stored at ambient laboratory temperature in 

the dark. 

After dosing, any remaining formulation was discarded. 

6.1.3. Formulation Analysis 

Triplicate (2 mL) samples of formulations from all groups were taken for analysis with regard 

to accuracy and concentration intended for Day 1 and during Week 4 of dosing. The samples 

were stored at ambient laboratory temperature in the dark prior to analysis. 

The samples were analysed at Charles River using a validated method (Charles River Study 

No. 425902). 

All samples analysed demonstrated satisfactory accuracy and concentration (Appendix 3). 

6.2. Animals and Management 

A total of 22 male and 22 female Han Wistar CRL:WI (Han) rats, approximately 6 weeks of 

age, were obtained from Charles River UK Ltd., Margate, Kent on 12 January 2010. On 

despatch, the males weighed between 153 to 160 g and the females between 131 to 140 g. 

On Day 1, the animals weighed between 221 to 259 g (males) and between 165 to 191 g 

(females). 

 

 

 

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Test Facility Study No. 459926
6.2.1. Acclimatisation 

The animals were allowed to acclimatise to the conditions described below for approximately 

2 weeks before commencement of treatment. During this period their health status was 

assessed by daily observation. During the weeks before the commencement of treatment, 

body weight and food consumption measurements were recorded. 

6.2.2. Allocation to Dose Group 

On arrival from the suppliers, the animals were introduced to cages on racks sequentially. 

Control animals were housed on a separate rack (Figure 1). 

6.2.3. Animal Identification 

For individual identification purposes, each animal was electronically tagged using a 

cylindrical, ‘glass-sealed’ microchip, which was subcutaneously implanted in the 

interscapular region. Each coded microchip was assigned a study number for unique animal 

identification. 

Each animal was given a cage card which identified that animal by study number, cage 

number, animal number, sex and treatment group. The cage cards were colour-coded 

according to treatment group. 

Additionally, each animal was given a second cage card which identified that animal by study 

number, neurotox identification, animal number and sex. This card was not colour coded. 

6.2.4. Room Environment 

The animals were housed inside a barriered rodent facility. 

All animals were housed in groups of up to 3 per cage and by dose group in UK Home 

Office-approved (61 x 43.5 x 24 cm) suspended polypropylene cages with stainless steel grid 

tops and solid bottom. Wood shavings (supplied by Datesand, Manchester, UK) were used as 

bedding and were changed when necessary. 

All cages were equipped with metal food hopper and a polycarbonate water bottle with a 

Durethan® cap and stainless steel nozzle. A wooden chewstick (produced by Tapvei Estonia 

OÜ, Harjumaa, Estonia) was placed in each cage for an environmental enrichment and 

replaced as necessary. Certificates for bedding and chewsticks were retained within the study 

data. Analysis did not provide evidence of contamination that might have prejudiced the 

outcome of the study. 

The animal room was kept at a positive pressure with respect to the outside by its own supply 

of fresh filtered air, with a minimum of 15 air changes per hour, which was passed to the 

outside, not recirculated. There was automatic control of temperature. Target values within 

the animal room were 21oC (target range 19-23oC) for temperature, 55% (target range 40-

70%) for relative humidity. Lighting was controlled to provide a 12-hour light/dark cycle. 

(light hours being 0700-1900). 

 

 

 

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Test Facility Study No. 459926
Temperature and humidity were monitored daily. During the acclimatisation/pretrial and 

treatment periods, temperature was recorded between 19 to 23oC and humidity was recorded 

between 36 to 66%. On one occasion during the pretrial period, the relative humidity was 

recorded outside the acceptable range (36%). This deviation from the acceptance range had 

no overt effect upon any animal and was, therefore, considered not to have affected the 

outcome of the study. 

6.2.5. Room Sanitation 

The walls, ceiling and other surfaces of the animal room were washed with disinfectant 

solution once each week during the study. 

Cages, hoppers and bottles were changed as necessary during the study. 

Each day on completion of work, floors were swept and then mopped with disinfectant 

solution (0.5% Tego 2000, supplied by Th. Goldschmidt and Company Limited, Tego House, 

Middlesex, England, UK). 

6.2.6. Diet and Water 

Rat and Mouse (modified) No. 1 Expanded SQC diet (Special Diets Services Limited, 

Witham, Essex, England, UK) was available. Each batch of diet was routinely analysed by 

the supplier for various nutritional components and chemicals and microbiological 

contaminants. 

Water taken from the domestic mains was feely available throughout the study, except during 

urine collection. The quality of water supply is stipulated by regulations published by the UK 

government and certificates of analysis for dissolved materials, heavy metals, pesticide 

residues, pH, nitrates, nitrites and selected bacteria are periodically provided. 

Food and water analysis did not provide evidence of contamination that might have 

prejudiced the outcome of the study. Certificates for each are presented in Appendix 2. 

7. EXPERIMENTAL DESIGN 

Animals were allocated to dose groups as follows: 

Animals Group Treatment (mg/kg/day) Males Females 

1 0 1-5 21-25 

2 100 6-10 26-30 

3 300 11-15 31-35 

4 1000 16-20 36-40 

Extra animals were numbered as follows: 

 Males 41, 42 

 Females: 43, 44 

 

 

 

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Test Facility Study No. 459926
Extra animals were not required and not regarded as part of the study, however they were 

retained in the animal room until the end of the dosing period, when they were removed. 

7.1. Dose Levels, Route, Duration and Method of Administration 

The dose levels were selected by the Sponsor after examination of preliminary studies carried 

out by the Sponsor. 

The oral route of administration was selected for this study as this route was defined by the 

Sponsor as a possible route of human exposure. 

The animals were dosed once daily by oral gavage, 7 days per week for at least 28 days up to 

the day prior to termination. A constant volume of 10 mL/kg body weight was used based on 

the animal’s body weight recorded before dosing. 

The control animals received vehicle only, at the same volume as the treated animals. 

Due to incorrect body weight, animal 22F (Group 1) was miss dosed on Day 23 and received 

1.8 mL vehicle instead of 2.2 mL. The lower dosing volume given on a single occasion to 

this control animal was considered not to have affected the outcome or integrity of the study. 

7.2. Definition of ‘Day’ 

The first day (Day 1) started at midnight before the first administration and continued until 24 

hours later; subsequent day numbers (Day 2, etc.) also followed this pattern. Body weights 

recorded on the validated computer system on the day treatment started were classified as 

‘Day 0’ body weights, related to the number of days of treatment completed. Subsequently 

body weight recordings also followed this pattern (i.e., body weights recorded on Day 2 of 

treatment were documented as Day 1 body weights). Recording of food consumption and 

clinical signs also followed this pattern. 

7.3. Treatment of Data 

This report contains serial observations pertaining to each day of the study before 

commencement of necropsy. It also contains serial observations relating to the pretrial 

period, unless otherwise stated below. 

8. OBSERVATIONS 

8.1. Mortality / Moribundity Checks 

All animals were checked early morning and as late as practical each day for viability. 

8.2. Detailed Physical Examination 

Once each week all animals received a detailed clinical examination, including appearance, 

movement and behaviour patterns, skin and hair condition, eyes and mucus membranes, 

respiration and excreta. 

 

 

 

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Test Facility Study No. 459926
8.3. Additional Clinical Observations 

All animals were examined for reaction to treatment at regular hourly intervals throughout the 

day, starting immediately post dose, with particular attention being paid to the first few hours 

after dosing. 

Some clinical signs were not recorded at the specified timepoint stated in Study Note 1. For 

example, clinical sign for Animal 11 was recorded beyond +4 h time segment (close to +5 h). 

These deviations were considered not to have affected the outcome or integrity of the study. 

8.4. Detailed Functional Observations 

Once during Week 4, a more detailed examination was made of all animals. These 

examinations were conducted by a technician not involved in the dosing procedures or in the 

collection of body weight and food consumption data, and were performed at an 

approximately standardised time of day. Before the independent technician entered the 

animal room to perform the examination, the cage cards showing treatment group were 

removed from each cage, leaving the second pre-prepared card as the neurotoxicity animal 

identifier. In each cage, one or two animals had their tails marked to allow the technician to 

identify each animal. 

8.4.1. Cage side Observations 

Posture/condition on first approach (animal undisturbed), checking for: 

Prostration 

 Lethargy 

 Writhing 

 Circling 

 Breathing abnormalities 

 Gait abnormalities 

 Tremor 

 Fasciculation 

 Convulsions 

 Biting (of cage components or self mutilating) 

 Vocalisations 

 Piloerection 

Ease of removal from the cage. 

Body temperature was taken and recorded from the implanted electronic identification chip. 

 

 

 

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Test Facility Study No. 459926
Condition of the eyes, checked for: 

 Pupillary function 

 Miosis 

 Mydriasis 

 Exophthalmos 

 Encrustation 

 Lacrimation 

Condition of the coat 

Presence of salivation 

Overall ease of handling 

8.4.2. Observations in a Standardized Area (2 min Observation): 

Latency (time to first locomotory movement) 

 Level of mobility 

 Rearing 

 Grooming 

 Urination/defecation 

 Arousal (level of alertness) 

Posture, tremor/convulsions, vocalisation, piloerection - recorded as for cage 

side observations 

 Palpebral closure 

 Gait abnormalities 

 Stereotypy (excessive repetition of behaviours) and/or unusual behaviours 

8.4.3. Functional Tests: 

Once during the treatment period (Week 4), the following additional functional tests were 

performed. These assessments were performed at an approximately standardized time of day. 

Reaction to sudden sound (click above the head) 

Reaction to touch on the rump with a blunt probe 

Grip strength: 

This was measured using a method derived from that of Meyer et al (1979). A 

strain gauge was used, to which a wire pull-bar was attached. Once the animal 

had gripped the bar, the body was pulled until its grasp was broken; the strain 

gauge recorded the force required. The procedure was repeated 3 times for the 

forelimbs and 3 times for the hind limbs, and the mean fore and hind grip 

strengths calculated. 

Pain perception: 

This was assessed by measurement of the tail flick response, using a technique 

based on the method devised by D`Amour and Smith (1941). The apparatus 

 

 

 

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Test Facility Study No. 459926
used shone a calibrated infra-red heat source onto the tail and automatically 

measured the reaction time of the animal (accurate to 0.1 s). It was ensured 

that no visible injury to the tail was caused during this test. 

Landing Foot Splay: 

Corn oil was applied to the hind paws of each animal. The animal was then 

held in a horizontal, prone position with the nose ca 30 cm above a bench 

surface covered with absorbent paper. When the animal was calm, it was 

dropped. The distance between the prints of the central footpads was 

measured and the average measurement recorded. The procedure was repeated 

3 times. If the rat did not land properly on its feet, this was recorded. 

Motor activity: 

 Each animal was placed in an individual monitoring cage, scanned by a motion 

sensor utilising infra-red pyroelectric detectors. Movement was detected in 

3 dimensions everywhere in the cage, and was differentiated into large and 

small movements. Each animal was monitored for one session of 1 h, activity 

counts being recorded over successive periods of 5 min each. Motor activity 

data was not recorded as indicated in SOP/ROD/019. The times when animals 

were placed into the battery and returned to home cage was recorded in the 

Log Book. This deviation from the SOP was considered not to have affected 

the outcome or integrity of the study. 

Other physical/functional abnormalities: 

Any other abnormality not already recorded in the above screening battery. 

8.5. Body Weights 

Body weights were recorded twice during pretrial, then daily during the dosing period. 

Body weights are reported twice weekly, with the final body weight being taken on the day of 

necropsy (Day 29). 

8.6. Food Consumption 

The quantity of food consumed by each cage of animals was measured and recorded twice 

each week, starting one week before the start of the treatment period up until the end of the 

dosing period. 

8.6.1. Water Consumption 

Water consumption was visually monitored on a weekly basis throughout the study. 

 

 

 

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Test Facility Study No. 459926
8.7. Ophthalmology Examinations 

The eyes of all animals (including spares) were examined once during the pretrial period 

using an indirect ophthalmoscope after the application of a mydriatic agent (1% Tropicamide, 

Mydriacyl®). Anterior, lenticular and fundic areas were evaluated. 

An ophthalmoscopic examination was performed on all Control and Group 4 animals during 

Week 4. 

8.8. Clinical Pathology 

8.8.1. Sample Collection 

Blood samples (approximately 2.5 mL) for scheduled haematology, coagulation and clinical 

chemistry were collected from all animals via the orbital sinus under isoflurane anaesthesia 

using a capillary tube, and transferred into plastic tubes containing anticoagulant prior to 

terminal kill. 

8.8.2. Haematology 

Blood samples (ca 0.5 mL) were taken into tubes containing EDTA as anticoagulant and 

assayed for: 

Parameter Instrument/Methodology Unit 

 

Haemoglobin: 

(Hb) 

Bayer, ADVIA 120 haematology analyser 

 

g/dL 

 

Red Blood Cell Count: 

(RBC) 

Bayer, ADVIA 120 haematology analyser 

 

x1012/L 

 

Haematocrit: 

(Hct) 

Bayer, ADVIA 120 haematology analyser 

 

L/L 

 

Mean Cell Haemoglobin: 

(MCH) 

Bayer, ADVIA 120 haematology analyser 

 

pg 

 

Mean Cell Volume: 

(MCV) 

Bayer, ADVIA 120 haematology analyser 

 

fL 

 

Mean Cell Haemoglobin Concentration: 

(MCHC) 

Bayer, ADVIA 120 haematology analyser 

 

g/dL 

 

Red Cell Distribution Width: 

(RDW) 

Bayer, ADVIA 120 haematology analyser 

 

% 

 

Reticulocytes: 

(Ret) 

Bayer, ADVIA 120 haematology analyser 

 

% 

 

White Blood Cell Count: 

(WBC) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

 

 

 

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Test Facility Study No. 459926
Parameter Instrument/Methodology Unit 

 

Neutrophils: 

(Neut) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Lymphocytes: 

(Lymph) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Monocytes: 

(Mono) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Eosinophils: 

(Eos) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Basophils: 

(Baso) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Large Unclassified Cells: 

(LUC) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

Platelet Count: 

(Plat) 

Bayer, ADVIA 120 haematology analyser 

 

x109/L 

 

A blood smear was prepared from each haematology specimen. The smears were labelled, 

stained, stored and archived. 

8.8.3. Coagulation 

Approximately 0.45 mL of blood was taken into tubes containing 0.05 mL (w/v) trisodium 

citrate as anticoagulant. The final sample volume was as close as possible to 0.5 mL to give a 

final concentration of 0.38% (blood to citrate ratio of 9:1). The samples were assessed for: 

Parameter Instrument/Methodology Unit 

 

Prothrombin Time: 

(PT) 

Instrumentation Laboratory, ACL Advance coagulation analyser 

A high sensitivity calcium thromboplastin for the simultaneous in vitro 

determination of PT and fibrinogen in plasma 

s 

 

Activated Partial 

Thromboplastin Time: 

(APTT) 

Instrumentation Laboratory, ACL Advance coagulation analyser 

Cephalin with micronized silica for the in vitro determination of APTT 

in plasma 

s 

 

 

 

 

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Test Facility Study No. 459926
8.8.4. Clinical Chemistry 

Approximately 1.5 mL of blood was taken into tubes containing lithium heparin. The 

samples were then centrifuged and assayed for: 

Parameter Instrument/Methodology Unit 

 

Alkaline Phosphatase: 

(ALP) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

IFCC Methods 

iu/L 

 

Alanine Aminotransferase: 

(ALT) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

IFCC Methods 

iu/L 

 

Aspartate 

Aminotransferase: 

(AST) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

IFCC Methods 

iu/L 

 

Lactate Dehydrogenase: 

(LDH) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

IFCC Methods. 

iu/L 

 

Creatine Phosphokinase: 

(CPK) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Szasz G et al. Clin Chem 1976;22:650 

iu/L 

 

Urea: 

(Urea) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Kinetic UV Assay developed from Talke H, Schubert GE. Klin Wschr 

1965;43:174-175. 

mmol/L 

 

Glucose: 

(Glu) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Schmidt F H 1961 Klin Wschr 39:1244 

mmol/L 

 

Total Bilirubin: 

(T.Bil) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit. 

Jendrassik-Grof method. Jendrassik L et al. Biochem Z 1938;297:81. 

μmol/L 

 

Cholesterol: 

(Chol) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Cooper G R et al 1968, Clin Chem 34 8 (B) B95-B105 

mmol/L 

 

Total Protein: 

(TP) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Colorimetric assay for the formation of protein - biuret reagent complex. 

g/L 

 

Albumin: 

(Alb) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Doumas B.T. et al 1971, Clin Chem Acta 31:87 

g/L 

 

Globulin: 

(Glob) 

Calculated by subtraction of the Albumin concentration from the Total 

Protein concentration. 

g/L 

 

Albumin Globulin Ratio: 

(AG-R) 

Calculated using Clinical Chemistry Plasma/Serum Total Protein and 

Albumin Concentrations 

Calculated Parameter (Albumin/(Total Protein-Albumin)) 

 

Sodium: 

(Na) 

Roche P Module Clinical Chemistry Analyser using indirect Ion 

Selective Electrode 

Application of the Nernst equation to an electrode with crown ether 

membrane type. 

mmol/L 

 

 

 

 

Page 22

Test Facility Study No. 459926
Parameter Instrument/Methodology Unit 

 

Potassium: 

(K) 

Roche P Module Clinical Chemistry Analyser using indirect Ion 

Selective Electrode 

Application of the Nernst equation to an electrode with valinomycin 

liquid membrane type. 

mmol/L 

 

Chloride: 

(Cl) 

Roche P Module Clinical Chemistry Analyser using indirect Ion 

Selective Electrode. Application of the Nernst equation to an electrode 

with quaternary ammonium salt ion exchanger. 

mmol/L 

 

Phosphate: 

(Phos) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Herny, R.J. 1974. pg 723 in "Clinical Chemistry" 2nd Edition. 

mmol/L 

 

Calcium: 

(Ca) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit 

Gindler E M and King J D 1972, Am. J. Clin. Pathol. 58:376 

mmol/L 

 

Creatinine: 

(Crea) 

Roche P Module Clinical Chemistry Analyser using Roche Test Kit. 

Modified from Bartels et al 1972, Clin Chem Acta 37:193 

μmol/L 

 

8.8.5. Urinalysis 

Samples were collected from all animals during Week 4, over a 4 h period, with the animals 

being housed in individual metabolism cages. Animals were deprived of food and water 

during this period. 

Parameter Instrument/Methodology Unit 

 

Urine Colour: 

(UCol) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser capable of detecting 23 different colour tones. 

Wavelength reflectance method of urine test strips 

 

Urine Specific Gravity: 

(S.G.) 

Manual assessment using a refractometer. 

 

 

Urine Volume: 

(UVol) 

Determined by weighing the urine sample. 1g = 1mL. 

 

mL 

 

Urine pH: 

(UpH) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

 

Urinary Protein: 

(UProt) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

Urinary Glucose: 

(UGl) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

 

 

 

Page 23

Test Facility Study No. 459926
Parameter Instrument/Methodology Unit 

 

Urinary Ketones: 

(UKet) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

Urobilinogen: 

(Uro) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

Urinary Bilirubin: 

(U.Bi) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

Blood Pigments: 

(BP) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

mg/dL 

 

Urinary Leukocytes: 

(Leu) 

Aution JET 9UB test strips measured using a Menarini Diagnostics, 

Aution Jet AJ4270 analyser 

Wavelength reflectance method of urine test strips 

cells/μL 

 

Urine: Epithelial cells: 

(Mic.E) 

Kova Staining 

Phase contrast microscopy 

 

Urine: Crystals: 

(Mic.Cr) 

Kova Staining 

Phase contrast microscopy 

 

Urine: White Blood Cells: 

(Mic.W) 

Kova Staining 

Phase contrast microscopy 

 

Urine: Red Blood Cells: 

(Mic.R) 

Kova Staining 

Phase contrast microscopy 

 

Urine: Organisms: 

(Mic.O) 

Kova Staining 

Phase contrast microscopy 

 

Urine: Casts: 

(Mic.C) 

Kova Staining 

Phase contrast microscopy 

 

Urine: Other 

Abnormalities: 

(Mic.A) 

Kova Staining 

Phase contrast microscopy 

 

Urine Turbidity: 

(UTb) 

Visual appraisal of urine appearance with scoring system 

 

 

 Score for Qualitative urine tests is: 

 0 = negative 

 1 = trace amount 

 2 = small amount 

 3 = large amount 

 

 

 

 

Page 24

Test Facility Study No. 459926
Parameter Instrument/Methodology Unit 

 

 Code for Urine Colour 

 3 = yellow 

 5 = light orange 

 18 = red 

 20 = light brown 

 22 = dark brown 

 

8.9. Terminal Procedures 

8.9.1. Scheduled Euthanasia 

All animals were sacrificed on Day 29 by exposure to a rising concentration of carbon 

dioxide. Immediately after death, each animal was weighed and the exsanguinated by 

severance of major blood vessels. A random order was used for the necropsy of the animals. 

8.9.2. Gross Necropsy 

Necropsy was performed for all animals under the guidance of a veterinary pathologist, who 

visited the post mortem room on the day of necropsy and remained on-call throughout the 

necropsy session. 

The necropsy consisted of a complete external and internal examination to include body 

orifices (ears, nostrils, mouth, anus, and vulva) and cranial, thoracic and abdominal organs 

and tissues. 

All gross lesions were recorded in descriptive terms, including location(s), size (in mm), 

shape, colour, consistency and number. 

8.9.3. Organ Weights 

The organs marked ‘x’ in the ‘Weighed’ column in the table below were weighed from all 

animals before sampling and preservation. 

Paired organs were weighed separately and the sum of the individual organs used for 

reporting purposes. Terminal body weights were used for organ weight analysis. 

8.9.4. Tissue Collection and Preservation 

Representative samples of the tissues listed in the table below were taken from all animals 

and fixed in 10% neutral buffered formalin, unless otherwise stated. Carcasses were 

discarded after checking. 

 

 

 

Page 25

Test Facility Study No. 459926
Tissues collected Weighed Examined Comments 

Abnormal Tissue - x - 

Adrenal x 2 x x - 

Aortic Arch - x - 

Brain x x Forebrain, midbrain and cerebellum 

Epididymis x 2 x x - 

Eye x 2 

- x 

Both eyes with optic nerves were fixed in 

Davidson's fluid. One only was processed and 

examined histologically. 

Femoral Bone (including stifle 

joint) - x - 

Gastro-intestinal Tract: 

 Stomach 

 Duodenum 

 Jejunum 

 Ileum 

 Caecum 

 Colon 

 Rectum 

- 

- 

- 

- 

- 

- 

- 

x 

x 

x 

x 

x 

x 

x 

Opened at necropsy and the mucosa examined. 

Harderian Gland x 2 - x Both fixed in Davidson’s fluid. Only one was 

processed and examined. 

Heart x x - 

Kidney x 2 x x - 

Liver x x - 

Lung x x Perfused after weighing; left and right lobes 

examined including bronchi. 

Marrow Smear (femur) 

- x 

Duplicate smears air-dried and fixed in methanol. 

One smear was evaluated by a veterinary 

pathologist (see section 8.9.7). 

Mesenteric Lymph Node x x - 

Microchip implant - - Retained for identification purposes. 

Oesophagus - x - 

Ovary x 2 x x - 

Pancreas - x - 

Pituitary gland x x - 

Prostate gland x x - 

Sciatic Nerve - x - 

Seminal Vesicles - x - 

Skeletal muscle - x - 

Skin + Mammary Gland - x - 

Spinal Cord - x Cervical, thoracic and lumbar, samples taken. 

Spleen x x - 

Sternum + rib - x Including costochondral junction. Sternum only 

(including a section of bone marrow) evaluated. 

Submandibular Lymph Node x x - 

Submaxillary and Sublingual 

Salivary Gland x 2 x x Only one was processed and examined. 

Testis x 2 x x Fixed in Modified Davidson’s Fixative. 

Thymus x x - 

Thyroid with Parathyroid x 2 x x Weighed after fixation. 

Tongue - x - 

Trachea - x - 

 

 

 

Page 26

Test Facility Study No. 459926
Tissues collected Weighed Examined Comments 

Urinary Bladder - x Contracted bladders distended with fixative; 

epithelial surface examined after fixation. 

Uterus and cervix x x - 

Vagina - x - 

8.9.5. Bone Marrow 

Duplicate bone marrow smears were taken at necropsy. One bone marrow smear was stained 

for Groups 1 and 4 using May-Grunwald-Giemsa as the Romanowsky stain in the Pathology 

Department and evaluated microscopically by the pathologist. The unstained second smear 

was retained in the Pathology Department as a contingency. 

8.9.6. Histology and Histopathology 

Tissues marked 'x' in the 'Examined' column in the table in Section 8.9.4. were processed to 

paraffin wax blocks from all animals in Groups 1 and 4. Sections were cut 4-6 μm thick, 

stained with haematoxylin and eosin (H & E) and evaluated by a pathologist. An internal 

peer review was undertaken. An appropriately qualified and experienced veterinary 

pathologist validated the conclusions of the Study Pathologist, by independently assessing the 

microscope slides. 

9. ELECTRONIC DATA ACQUISITION AND SYSTEMS 

In addition to the built-in software of laboratory devices and instruments, the following 

software programs were used: 

Dose Formulation: DISPENSE 7.0.3.7 

 

Documentum: 5.3 (Web based) 

 

Clinical Pathology Laboratory 

Information Management System 

(LIMS): 

 Nautilus 2003 Release 2 

 

Chromatography Data Collection 

and Processing (Formulation 

Analysis) 

 Atlas 2002 R1 

 

In-life Data Collection and 

Reporting: 

 PROVANTIS release 14 

 

Organ Weights/Histopathology: PLACES 2000 1.1 

 

 

 

Page 27

Test Facility Study No. 459926
9.1. Statistical Analysis 

Unless otherwise stated, all statistical tests were two-sided and performed at the 5% 

significance level using in-house software. Males and females were analysed separately. 

Pairwise comparisons were only performed against the control group (Group 1). The 

following pairwise comparisons were performed: 

 Control Group vs Group 2 

 Control Group vs Group 3 

 Control Group vs Group 4 

Body weight, food consumption, haematology, coagulation, clinical chemistry and selected 

urinalysis, motor activity and quantitative FOB measurement data were analysed for 

homogeneity of variance using the ‘F-Max' test. If the group variances appeared 

homogeneous, a parametric ANOVA was used and pairwise comparisons were made using 

Fisher’s F protected LSD method via Student's t test ie pairwise comparisons were made only 

if the overall F-test was significant. If the variances were heterogeneous, log or square root 

transformations were used in an attempt to stabilise the variances. If the variances remained 

heterogeneous, then a Kruskal-Wallis non-parametric ANOVA was used and pairwise 

comparisons were made using chi squared protection (via z tests, the non-parametric 

equivalent of Student's t test).

In circumstances where it was not possible to perform the F Max test due to zero standard 

deviation in at least one group, the non-parametric ANOVA results were reported. 

Organ weights were analysed using ANOVA as above and by analysis of covariance 

(ANCOVA) using terminal kill body weight as covariate. In addition, organ weights as a 

percentage of terminal body weight were analysed using ANOVA as above as an exploratory 

analysis. 

In circumstances where the variances in the ANCOVA remain heterogeneous following log or 

square root transformations, the data was subjected to a rank transformation prior to analysis. 

Where it was not possible to perform the F-Max test due to the small sample size (ie less than 

3 animals in any group), the untransformed parametric ANCOVA results were reported. 

In the ANOVA and ANCOVA summary tables, the results of the analysis were reported 

indicating the level of statistical significance of each pairwise comparison as follows: 

Histological incidence data were analysed using Fisher’s Exact Probability Test. 

 a = p<0.05, b= p<0.01 and c= p<0.001 

 

 

 

Page 28

Test Facility Study No. 459926
10. RESULTS 

10.1. Formulation Analysis (Appendix 3) 

On all sampling occasions, the concentration of Alcohols, C18-22, distn. residues was inside 

the acceptance criteria (extended to ± 15%) indicating acceptable accuracy of formulations. 

10.2. Observations 

10.2.1. Mortality and Clinical Observations (Appendix 4) 

One Group 2 female (Animal 29) died during the orbital sinus sampling, prior to termination 

on Day 29. The death of this animal was considered not to be related to treatment with 

Alcohols, C18-22, distn. residues. 

There were no treatment-related clinical signs. 

10.2.2. Detailed Functional Observations 

10.2.2.1.Detailed Clinical Observations (Table 1; Appendices 5 to 7) 

There were no inter-group differences noted with regard to any detailed clinical observations, 

in either sex. 

10.2.2.2.Motor Activity (Table 2; Appendix 8) 

Motor activity profiles of treated groups generally resembled those displayed by their 

respective Controls, with similar overall activity values reported for each sex. 

Slight variances from Control values were noted throughout the timepoints. However, due to 

a lack of statistical significance, consistency between sexes, evidence of a dose-related 

response or further corroborating data, it was considered that these differences were not 

treatment related. 

10.2.2.3.Quantitative Functional Observations (Table 3; Appendix 6) 

All treated groups closely resembled their respective Controls for the parameters assessed, 

and it was considered that there were no treatment-related differences in either sex. 

10.2.3. Body Weights (Table 4; Appendix 9) 

There were no changes in body weight or body weight gain that were considered to be related 

to treatment with Alcohols, C18-22, distn. residues. 

Body weight was slightly lower in females receiving 300 or 1000 mg/kg/day than Controls 

throughout the pretrial and dosing period. This was considered not to be a treatment-related 

effect because this difference was consistent from the beginning of pretrial period until the 

end of dosing period and the body weight gain in these groups was similar to or superior to 

controls. 

 

 

 

Page 29

Test Facility Study No. 459926
10.2.4. Food Consumption (Table 5; Appendix 10) 

Food consumption was unaffected by treatment with Alcohols, C18-22, distn. residues. 

Food intake of females receiving 1000 mg/kg/day was slightly lower than Controls 

throughout the pretrial and dosing period. The changes attained statistical significance on 

Day 7. However, this was considered not to be a treatment-related effect because this 

difference was consistent from the beginning of pretrial period until the end of dosing period. 

10.2.5. Ophthalmology (Appendix 11) 

There were no treatment-related ocular findings. 

All findings and incidences were considered to be representative of the normal background 

findings observed at Charles River, Preclinical Services Edinburgh. 

10.2.6. Clinical Pathology 

10.2.6.1.Haematology and Coagulation (Table 6; Appendix 12) 

There were no treatment-related clinical haematology changes. 

Slightly low monocyte counts were observed in all females receiving the test item. There was 

also a tendency for lower monocyte counts in males, but the changes did not attain statistical 

significance. The aetiology of the slight disturbances in monocyte counts in animals 

receiving the test item is unclear, but the changes showed no clear evidence of a dose 

response relationship and are considered to be of insufficient magnitude to be of toxicological 

significance. Furthermore, all monocyte counts in treated animals were within the historical 

control background range. 

A number of other inter-group differences occurred when compared with Controls, some of 

which attained statistical significance. These differences were minor, confined to one sex or 

lacked dosage-relationship. Consequently, these differences were attributable to biological 

variation. 

10.2.6.2.Clinical Chemistry (Table 7; Appendix 13) 

There were no treatment-related clinical chemistry changes. 

High creatine phosphokinase activity was observed in males receiving 1000 mg/kg/day, 

however, this was considered to be the result of an individual Group 4 male (Animal 16) for 

which an unusually high value was recorded, thereby producing an artificially high group 

mean value for comparison. 

Other slight variances from Control values were noted for several parameters across male and 

female treated groups. However, due to a lack of a dose-related response, statistical 

significance or any further supportive evidence, these variances were considered not to be 

related to treatment. 

 

 

 

Page 30

Test Facility Study No. 459926
10.2.6.3.Urinalysis (Table 8; Appendix 14) 

There were no treatment-related changes in the urinalysis data. 

10.2.7. Organ Weights (Tables 9 to 11; Appendices 15 and 16) 

There were no treatment-related organ weight changes. 

Slightly high testes weights were observed in males receiving 100 or 1000 mg/kg/day. The 

changes attained statistical significance following absolute and covariate analysis, but not for 

body weight-relative organ weights. As this finding did not demonstrate a dose-related 

response and as no histopathological changes correlated, therefore, the statistical differences 

were considered not to reflect a toxic effect. 

10.2.8. Gross Necropsy (Table 12; Appendix 17) 

There were no treatment-related necropsy findings. 

All other necropsy findings noted were those commonly seen in rats of this age and strain at 

Charles River, Preclinical Services Edinburgh. 

10.2.9. Histopathology (Table 13; Appendix 17) 

There were no histopathological findings considered to be related to treatment with Alcohols, 

C18-22, distn. residues. 

All findings recorded were typical background findings for rats of this age and strain at 

Charles River, Preclinical Services Edinburgh. 

 

 

 

Page 31

Test Facility Study No. 459926
11. CONCLUSION 

It was concluded that repeat oral administration of Alcohols, C18-22, distn. residues to Han 

Wistar rats for 28 days at dose levels up to1000 mg/kg/day was considered to be well 

tolerated with no obvious evidence of toxicity being noted. Therefore, the dose of 

1000 mg/kg/day was considered to be a No-Observed-Effect-Level (NOEL) in this study. 

 

 

 

Page 32

Test Facility Study No. 459926
Figure 

Cage Plan 

Rack No. 1 Rack No. 2 Rack No. 3 Rack No. 4 

 

1 

1, 2, 3 

1M 

 

 3 

6, 7, 8 

2M 

5 

11, 12, 13 

3M 

7 

16, 17, 18 

4M 

 9 

21, 22, 23 

1F 

 15 

36, 37, 38 

4F 

13 

31, 32, 33 

3F 

11 

26, 27, 28 

2F 

2 

4, 5 

1M 

 

 4 

9, 10 

2M 

6 

14, 15 

3M 

8 

19, 20 

4M 

 10 

24, 25 

1F 

 16 

39, 40 

4F 

14 

34, 35 

3F 

12 

29, 30 

2F 

 

 

Cage No 

Animal No. 

Group/Sex 

1

Page 33

Test Facility Study No. 459926
Figure

Body Weights Graph (g) : Group Mean Values - Males

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

180

200

220

240

260

280

300

320

340 -7 -4 0 3 7 10 14 17 21 24 28 1234

Day Body Weight (g)

 2

Page 34

Test Facility Study No. 459926
Figure (continued)

Body Weights Graph (g) : Group Mean Values - Females

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

160

170

180

190

200

210

220

230

240 -7 -4 0 3 7 10 14 17 21 24 28 1234

Day Body Weight (g)

 2

Page 35

Test Facility Study No. 459926
Table

Neurotoxicity Screening: Detailed Functional Observations: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Latency

s Sectors n Rears n Groomingn Faec Pellets n Pools Urine n Foot Splay mm

Fore Grip

g

Hind Grip

g

Tail Flick

s Temp°C

1M Mean

 SD

 n

 0

 0

 5

 26

 7

 5

 9

 2

 5

 0

 0

 5

 1

 1

 5

 1

 1

 5

 103

 20

 5

 696

 136

 5

 385

 79

 5

 4.8

 2.3

 4

 38.6

 0.4

 5

2M Mean

 SD

 n

 0

 0

 5

 18

 9

 5

 8

 5

 5

 0

 0

 5

 0

 1

 5

 2

 2

 5

 106

 16

 5

 672

 122

 5

 428

 72

 5

 3.2

 0.6

 4

 38.2

 0.9

 5

3M Mean

 SD

 n

 0

 0

 5

 13

 7

 5

 6

 3

 5

 0

 0

 5

 1

 1

 5

 4

 2

 5

 100

 17

 5

 713

 227

 5

 381

 112

 5

 3.7

 1.0

 5

 38.6

 0.5

 5

4M Mean

 SD

 n

 0

 0

 5

 17

 6

 5

 8

 3

 5

 0

 0

 5

 0

 0

 5

 2

 1

 5

 114

 31

 5

 678

 158

 5

 381

 32

 5

 3.4

 0.8

 5

 38.4

 0.6

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 1

Page 36

Test Facility Study No. 459926
Table (continued)

Neurotoxicity Screening: Detailed Functional Observations: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Latency

s Sectors n Rears n Groomingn Faec Pellets n Pools Urine n Foot Splay mm

Fore Grip

g

Hind Grip

g

Tail Flick

s Temp°C

1F Mean

 SD

 n

 0

 0

 5

 25

 14

 5

 10

 4

 5

 0

 0

 5

 0

 1

 5

 2

 3

 5

 98

 31

 5

 638

 108

 5

 300

 23

 5

 3.5

 0.8

 5

 38.8

 0.3

 5

2F Mean

 SD

 n

 0

 0

 5

 27

 6

 5

 11

 3

 5

 0

 0

 5

 0

 0

 5

 2

 1

 5

 108

 22

 5

 624

 148

 5

 336

 47

 5

 4.3

 1.1

 5

 38.7

 1.3

 5

3F Mean

 SD

 n

 0

 0

 5

 27

 12

 5

 10

 3

 5

 0

 0

 5

 0

 0

 5

 0

 0

 5

 104

 17

 5

 662

 82

 5

 309

 59

 5

 3.4

 0.7

 5

 38.2

 0.3

 5

4F Mean

 SD

 n

 0

 0

 5

 30

 11

 5

 10

 3

 5

 0

 0

 5

 0

 0

 5

 3

 5

 5

 101

 8

 5

 696

 85

 5

 315

 45

 5

 3.7

 0.4

 5

 38.2

 0.8

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 1

Page 37

Test Facility Study No. 459926
Table

Neurotoxicity Screening: Motion Activity (Movements / 5 minutes) : Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Minutes

1-5 6-10 11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 Overall

1M Mean

 SD

 n

 63

 11

 5

 71

 10

 5

 68

 10

 5

 57

 27

 5

 57

 25

 5

 35

 29

 5

 23

 34

 5

 12

 11

 5

 4

 3

 5

 21

 25

 5

 16

 26

 5

 14

 19

 5

 441

 111

 5

2M Mean

 SD

 n

 51

 10

 5

 56

 6

 5

 59

 10

 5

 60

 13

 5

 37

 21

 5

 21

 19

 5

 38

 24

 5

 20

 20

 5

 7

 3

 5

 2

 2

 5

 4

 4

 5

 2

 3

 5

 357

 70

 5

3M Mean

 SD

 n

 60

 11

 5

 61

 10

 5

 66

 16

 5

 58

 25

 5

 43

 25

 5

 33

 31

 5

 16

 24

 5

 9

 16

 5

 1

 2

 5

 12

 19

 5

 17

 34

 5

 14

 30

 5

 390

 128

 5

4M Mean

 SD

 n

 57

 14

 5

 61

 15

 5

 64

 10

 5

 60

 11

 5

 68

 10

 5

 57

 13

 5

 33

 23

 5

 6

 7

 5

 7

 5

 5

 7

 9

 5

 7

 2

 5

 3

 3

 5

 432

 72

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 2

Page 38

Test Facility Study No. 459926
Table (continued)

Neurotoxicity Screening: Motion Activity (Movements / 5 minutes) : Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Minutes

1-5 6-10 11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 Overall

1F Mean

 SD

 n

 60

 11

 5

 66

 8

 5

 70

 14

 5

 57

 14

 5

 68

 12

 5

 66

 23

 5

 54

 34

 5

 53

 21

 5

 45

 36

 5

 39

 37

 5

 22

 31

 5

 22

 20

 5

 622

 123

 5

2F Mean

 SD

 n

 48

 11

 5

 58

 10

 5

 60

 7

 5

 65

 8

 5

 69

 14

 5

 63

 11

 5

 55

 15

 5

 43

 36

 5

 34

 34

 5

 23

 21

 5

 19

 27

 5

 16

 21

 5

 553

 77

 5

3F Mean

 SD

 n

 58

 7

 5

 68

 9

 5

 64

 17

 5

 68

 5

 5

 35

 33

 5

 31

 32

 5

 22

 27

 5

 30

 43

 5

 26

 23

 5

 24

 30

 5

 26

 29

 5

 21

 26

 5

 473

 159

 5

4F Mean

 SD

 n

 48

 7

 5

 59

 10

 5

 69

 17

 5

 65

 13

 5

 44

 26

 5

 43

 27

 5

 41

 29

 5

 56

 23

 5

 31

 28

 5

 6

 6

 5

 10

 8

 5

 9

 7

 5

 482

 123

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 2

Page 39

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:::

1

Control 0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table 

Functional Observations: Group Mean Values 

Group/Sex Observation 1M 2M 3M 4M 

General Behaviour (c), awake/alert 4 5 5 5 

General Behaviour (c), asleep/at rest 1 - - - 

Posture/gait (c), normal 5 5 5 5 

Piloerection (c), absent 5 5 5 5 

Respiration (c), normal 5 5 5 5 

Biting(c), absent 5 5 5 5 

Spontaneous vocalisation (c), absent 5 5 5 5 

Abnormal movements (c), absent 5 5 5 5 

Behaviour normal on removal from cage 5 5 5 5 

Pupillary reflex, normal 5 5 5 5 

Eye(s), normal 5 5 5 5 

Coat (H), normal 5 5 5 5 

Salivation (H), absent 5 5 5 5 

General handling, behaviour normal 5 5 5 5 

Polyuria (a), absent 5 5 5 5 

Diarrhoea (a), absent 5 5 5 5 

Alertness (a), normal 5 5 5 5 

(a) = Observation in arena 

(c) = Observation in cage 

(H) = Observation when handled 3

Page 40

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:::

1

Control 0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Functional Observations: Group MeanValues 

Group/Sex Observation 1M 2M 3M 4M 

Posture/gait (a), normal 5 5 5 5 

Respiration (a), normal 5 5 5 5 

Vocalisation (a), absent 5 4 5 5 

Vocalisation (a), present during handling - 1 - - 

Palpebral closure (a) absent 5 5 5 5 

Involuntary leaping (a), absent 5 5 5 5 

Biting(a), absent 5 5 5 5 

Piloerection (a), absent 5 5 5 5 

Abnormal movements (a), absent 5 5 5 5 

Normal reaction to tactile stimulus (a) 5 4 5 5 

No reaction to tactile stimulus (a) - 1 - - 

Normal reaction to auditory stimulus (a) 5 5 5 5 

No other cageside findings 5 5 5 5 

No other arena findings 5 5 5 5 

Total number of animals observed 5 5 5 5 

(a) = Observation in arena 

(c) = Observation in cage 

(H) = Observation when handled 3

Page 41

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:::

1

Control 0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Functional Observations: Group MeanValues 

Group/Sex Observation 1F 2F 3F 4F 

General Behaviour (c), awake/alert 5 4 5 4 

General Behaviour (c), asleep/at rest - 1 - 1 

Posture/gait (c), normal 5 5 5 5 

Piloerection (c), absent 5 5 5 5 

Respiration (c), normal 5 5 5 5 

Biting(c), absent 5 5 5 5 

Spontaneous vocalisation (c), absent 5 5 5 5 

Abnormal movements (c), absent 5 5 5 5 

Behaviour normal on removal from cage 5 5 5 5 

Pupillary reflex, normal 5 5 5 5 

Eye(s), normal 5 5 5 5 

Coat (H), normal 5 5 5 5 

Salivation (H), absent 5 5 5 5 

General handling, behaviour normal 5 5 5 5 

Polyuria (a), absent 5 5 5 5 

Diarrhoea (a), absent 5 5 5 5 

Alertness (a), normal 5 5 5 5 

(a) = Observation in arena 

(c) = Observation in cage 

(H) = Observation when handled 3

Page 42

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:::

1

Control 0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Functional Observations: Group MeanValues 

Group/Sex Observation 1F 2F 3F 4F 

Posture/gait (a), normal 5 5 5 5 

Respiration (a), normal 5 5 5 5 

Vocalisation (a), absent 5 5 5 5 

Palpebral closure (a) absent 5 5 5 5 

Involuntary leaping (a), absent 5 5 5 5 

Biting(a), absent 5 5 5 5 

Piloerection (a), absent 5 5 5 5 

Abnormal movements (a), absent 5 5 5 5 

Normal reaction to tactile stimulus (a) 5 5 5 5 

Normal reaction to auditory stimulus (a) 5 5 5 5 

No other cageside findings 5 5 5 5 

No other arena findings 5 5 5 5 

Total number of animals observed 5 5 5 5 

(a) = Observation in arena 

(c) = Observation in cage 

(H) = Observation when handled 3

Page 43

Test Facility Study No. 459926
Table

Body Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -7 -4 0 3 7 10 14 17 21 24 28 Change

0 - 28

1M Mean

 SD

 n

202.4

 3.5

 5

218.5

 6.3

 5

239.4

 7.5

 5

249.6

 9.0

 5

263.9

 9.9

 5

275.8

 10.7

 5

286.6

 10.4

 5

294.7

 12.7

 5

304.0

 11.2

 5

308.9

 11.3

 5

317.8

 10.9

 5

 78.3

 5.8

 5

2M Mean

 SD

 n

204.8

 5.9

 5

221.8

 7.3

 5

239.4

 5.6

 5

248.3

 5.4

 5

264.7

 5.2

 5

274.4

 6.1

 5

284.1

 6.0

 5

293.6

 7.6

 5

302.8

 7.7

 5

311.3

 10.9

 5

321.1

 11.4

 5

 81.7

 10.7

 5

3M Mean

 SD

 n

200.1

 3.2

 5

219.0

 5.0

 5

238.8

 7.9

 5

248.4

 9.4

 5

265.7

 12.6

 5

275.3

 13.4

 5

287.1

 15.3

 5

297.1

 13.9

 5

304.7

 15.4

 5

312.0

 15.5

 5

321.0

 17.3

 5

 82.2

 11.0

 5

4M Mean

 SD

 n

198.6

 11.3

 5

216.6

 12.8

 5

238.2

 15.3

 5

247.4

 17.0

 5

265.0

 18.2

 5

276.3

 21.5

 5

291.2

 21.7

 5

299.7

 22.6

 5

308.6

 26.8

 5

315.9

 26.8

 5

325.7

 28.8

 5

 87.5

 15.3

 5

Group /

 sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 4

Page 44

Test Facility Study No. 459926
Table (continued)

Body Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -7 -4 0 3 7 10 14 17 21 24 28 Change

0 - 28

1F Mean

 SD

 n

164.4

 6.5

 5

171.8

 6.6

 5

181.5

 6.4

 5

189.9

 7.6

 5

200.7

 8.2

 5

204.9

 8.7

 5

213.7

 9.3

 5

216.4

 10.6

 5

220.2

 11.0

 5

221.7

 6.6

 5

223.6

 12.2

 5

 42.1

 9.1

 5

2F Mean

 SD

 n

166.6

 8.3

 5

175.9

 5.3

 5

184.8

 6.4

 5

193.3

 7.8

 5

199.9

 9.8

 5

203.4

 11.1

 5

211.1

 10.1

 5

217.8

 14.6

 5

221.3

 15.5

 5

221.7

 13.0

 5

230.4

 15.8

 5

 45.7

 9.8

 5

3F Mean

 SD

 n

161.3

 6.1

 5

164.9

 8.2

 5

173.8

 8.6

 5

182.3

 12.7

 5

189.5

 13.0

 5

196.9

 10.4

 5

203.4

 10.7

 5

204.8

 9.0

 5

208.8

 10.9

 5

208.0

 12.7

 5

217.3

 11.4

 5

 43.5

 6.6

 5

4F Mean

 SD

 n

160.6

 7.0

 5

169.7

 5.6

 5

177.5

 6.5

 5

183.2

 8.7

 5

189.5

 7.9

 5

193.1

 8.1

 5

199.9

 7.6

 5

205.5

 11.1

 5

209.7

 11.4

 5

214.3

 11.0

 5

217.2

 12.3

 5

 39.7

 6.5

 5

Group /

 sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 4

Page 45

Test Facility Study No. 459926
Table

Food Consumption (g/animal/day): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -4 0 3 7 10 14 17 21 24 28

1M Mean

 SD

 n

 21.9

 0.4

 2

 22.8

 0.4

 2

 22.9

 0.3

 2

 23.0

 0.5

 2

 22.4

 1.3

 2

 22.9

 0.7

 2

 22.0

 0.3

 2

 22.7

 0.8

 2

 22.0

 0.8

 2

 21.2

 1.1

 2

2M Mean

 SD

 n

 21.8

 0.3

 2

 22.4

 0.2

 2

 22.1

 0.6

 2

 23.5

 0.5

 2

 22.3

 0.1

 2

 22.9

 0.6

 2

 22.4

 0.2

 2

 22.4

 0.8

 2

 22.4

 1.2

 2

 21.7

 1.5

 2

3M Mean

 SD

 n

 21.8

 1.5

 2

 23.1

 1.2

 2

 23.3

 1.8

 2

 24.4

 1.2

 2

 23.4

 1.3

 2

 24.0

 0.9

 2

 23.3

 0.4

 2

 23.1

 0.4

 2

 22.7

 0.6

 2

 22.4

 0.3

 2

4M Mean

 SD

 n

 21.1

 1.1

 2

 22.1

 1.6

 2

 22.0

 1.9

 2

 23.4

 0.8

 2

 22.2

 2.3

 2

 23.5

 1.5

 2

 22.6

 2.0

 2

 22.7

 1.6

 2

 22.1

 1.0

 2

 20.1

 3.0

 2

Group /

 sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 5

Page 46

Test Facility Study No. 459926
Table (continued)

Food Consumption (g/animal/day): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -4 0 3 7 10 14 17 21 24 28

1F Mean

 SD

 n

 16.9

 0.0

 2

 17.9

 0.6

 2

 17.5

 1.0

 2

 18.7

 0.2

 2

 17.5

 0.3

 2

 19.4

 0.4

 2

 17.8

 0.6

 2

 18.6

 0.8

 2

 18.4

 1.0

 2

 17.7

 1.2

 2

2F Mean

 SD

 n

 17.5

 1.1

 2

 17.1

 0.4

 2

 17.0

 1.1

 2

 18.1

 0.6

 2

 16.5

 0.1

 2

 18.8

 0.1

 2

 18.4

 0.8

 2

 18.5

 0.1

 2

 17.5

 0.2

 2

 17.3

 0.2

 2

3F Mean

 SD

 n

 16.4

 1.5

 2

 17.1

 1.5

 2

 17.6

 0.5

 2

 18.5

 0.2

 2

 17.3

 1.0

 2

 19.7

 0.7

 2

 18.9

 2.3

 2

 20.5

 2.1

 2

 20.2

 3.7

 2

 18.7

 0.3

 2

4F Mean

 SD

 n

 15.0

 0.6

 2

 15.7

 0.0

 2

 15.4

 0.0

 2

 16.7Æ

 0.3

 2

 15.7

 0.6

 2

 17.6

 0.0

 2

 17.0

 0.8

 2

 17.5

 0.2

 2

 16.2

 0.8

 2

 16.4

 0.0

 2

Group /

 sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 5

Page 47

Test Facility Study No. 459926
Table

Haematology and Coagulation: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

----------- Neut ----------- Lymph----------- Monox10Ä/L

Eos

----------- Baso----------- LUC----------- 1M Mean

 SD

 n

 15.7

 0.5

 5

 8.69

 0.20

 5

 0.448

 0.014

 5

 18.1

 0.7

 5

 51.6

 1.1

 5

 35.1

 0.9

 5

 12.0

 1.8

 5

 2.2

 0.1

 5

 9.28

 2.10

 5

 0.98

 0.12

 5

 7.89

 1.91

 5

 0.17

 0.06

 5

 0.12

 0.03

 5

 0.03

 0.01

 5

 0.08

 0.03

 5

2M Mean

 SD

 n

 15.5

 0.5

 3

 8.39

 0.16

 3

 0.440

 0.014

 3

 18.5

 0.6

 3

 52.5

 1.5

 3

 35.2

 0.6

 3

 11.5

 1.1

 3

 2.2

 0.3

 3

 7.98

 0.96

 3

 0.76

 0.15

 3

 6.89

 0.75

 3

 0.13

 0.06

 3

 0.12

 0.03

 3

 0.02

 0.00

 3

 0.07

 0.01

 3

3M Mean

 SD

 n

 15.5

 0.2

 5

 8.45

 0.38

 5

 0.444

 0.013

 5

 18.3

 0.8

 5

 52.6

 1.8

 5

 34.9

 0.7

 5

 11.6

 1.3

 5

 2.2

 0.3

 5

 8.65

 1.09

 5

 1.12

 0.24

 5

 7.16

 0.92

 5

 0.13

 0.03

 5

 0.14

 0.04

 5

 0.02

 0.01

 5

 0.08

 0.01

 5

4M Mean

 SD

 n

 15.2

 0.7

 4

 8.40

 0.54

 4

 0.443

 0.022

 4

 18.2

 1.0

 4

 52.8

 1.7

 4

 34.3

 0.8

 4

 12.2

 2.3

 4

 2.4

 0.4

 4

 7.31

 1.37

 4

 0.81

 0.25

 4

 6.21

 1.27

 4

 0.10

 0.02

 4

 0.11

 0.04

 4

 0.02

 0.01

 4

 0.06

 0.01

 4

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 6

Page 48

Test Facility Study No. 459926
Table (continued)

Haematology and Coagulation: Group Mean Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PT

 s

 APTT

 s 1M Mean

 SD

 n

 776

 158

 5

 14

 0

 5

 23

 2

 3

2M Mean

 SD

 n

 887

 41

 3

 15Æ

 1

 4

 23

 1

 3

3M Mean

 SD

 n

 850

 46

 5

 15

 1

 4

 25

 2

 3

4M Mean

 SD

 n

 803

 69

 4

 15

 1

 4

 24

 1

 3

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 6

Page 49

Test Facility Study No. 459926
Table (continued)

Haematology and Coagulation: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

----------- Neut ----------- Lymph----------- Monox10Ä/L

Eos

----------- Baso----------- LUC----------- 1F Mean

 SD

 n

 14.4

 0.4

 5

 7.91

 0.34

 5

 0.411

 0.013

 5

 18.2

 0.4

 5

 52.0

 0.9

 5

 35.1

 0.4

 5

 11.1

 0.7

 5

 2.6

 0.5

 5

 6.42

 0.98

 5

 1.16

 0.51

 5

 4.92

 0.92

 5

 0.16

 0.03

 5

 0.10

 0.01

 5

 0.01

 0.01

 5

 0.06

 0.02

 5

2F Mean

 SD

 n

 14.7

 0.5

 5

 7.86

 0.21

 5

 0.409

 0.020

 5

 18.7

 0.3

 5

 52.0

 1.6

 5

 35.8

 0.7

 5

 10.9

 0.5

 5

 2.4

 0.1

 5

 5.07

 0.76

 5

 0.88

 0.08

 5

 3.97

 0.74

 5

 0.08Ç

 0.02

 5

 0.11

 0.05

 5

 0.01

 0.01

 5

 0.03Å

 0.01

 5

3F Mean

 SD

 n

 14.4

 0.6

 5

 7.76

 0.49

 5

 0.406

 0.023

 5

 18.6

 1.0

 5

 52.4

 1.0

 5

 35.4

 1.4

 5

 11.7

 0.7

 5

 3.2Å

 0.5

 5

 6.16

 1.62

 5

 0.92

 0.44

 5

 5.00

 1.62

 5

 0.10Æ

 0.03

 5

 0.08

 0.04

 5

 0.02

 0.01

 5

 0.06

 0.02

 5

4F Mean

 SD

 n

 15.0

 0.6

 4

 7.81

 0.26

 4

 0.416

 0.013

 4

 19.2

 0.5

 4

 53.3

 1.1

 4

 36.2

 0.9

 4

 11.5

 1.6

 4

 2.1

 0.3

 4

 5.84

 0.83

 4

 0.75

 0.18

 4

 4.83

 0.85

 4

 0.07Ç

 0.03

 4

 0.12

 0.06

 4

 0.02

 0.00

 4

 0.06

 0.02

 4

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 6

Page 50

Test Facility Study No. 459926
Table (continued)

Haematology and Coagulation: Group Mean Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PT

 s

 APTT

 s 1F Mean

 SD

 n

 840

 69

 5

 15

 0

 5

 22

 1

 4

2F Mean

 SD

 n

 913

 79

 5

 15

 1

 4

 23

 -

 1

3F Mean

 SD

 n

 841

 125

 5

 15

 1

 5

 23

 1

 5

4F Mean

 SD

 n

 757

 331

 4

 14

 1

 3

 22

 1

 3

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 6

Page 51

Test Facility Study No. 459926
Table

Clinical Chemistry: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

ALP

iu/L

ALT

iu/L

AST

iu/L

LDH

iu/L

CPK

iu/L

Urea

mmol/L

Glu

mmol/L

T.Bil

μmol/L

Chol

mmol/L

TP

g/L

Alb

g/L

Glob

g/L

1M Mean

 SD

 n

 136

 20

 5

 53

 11

 5

 76

 17

 5

 398

 547

 5

 347

 345

 5

 6.2

 0.6

 5

 9.92

 2.14

 5

 1.7

 0.0

 5

 1.5

 0.3

 5

 60

 2

 5

 41

 2

 5

 19

 2

 5

2M Mean

 SD

 n

 145

 19

 5

 51

 12

 5

 71

 18

 5

 303

 278

 5

 338

 292

 5

 5.9

 0.2

 5

 9.73

 1.22

 5

 1.7

 0.0

 5

 1.5

 0.4

 5

 61

 2

 5

 43

 1

 5

 18

 1

 5

3M Mean

 SD

 n

 146

 39

 5

 45

 10

 5

 65

 4

 5

 200

 95

 5

 182

 45

 5

 6.2

 0.6

 5

 10.24

 0.95

 5

 1.8

 0.2

 5

 1.4

 0.2

 5

 62

 2

 5

 44

 2

 5

 18

 2

 5

4M Mean

 SD

 n

 134

 11

 5

 42

 6

 5

 72

 25

 5

 268

 168

 5

 724

 1165

 5

 5.9

 0.6

 5

 10.10

 0.92

 5

 1.7

 0.0

 5

 1.6

 0.2

 5

 60

 2

 5

 42

 2

 5

 18

 2

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 7

Page 52

Test Facility Study No. 459926
Table (continued)

Clinical Chemistry: Group Mean Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

AG-R Na

mmol/L Kmmol/L

Cl

mmol/L

Phos

mmol/L

Ca

mmol/L

Crea

μmol/L

1M Mean

 SD

 n

 2.2

 0.2

 5

 143

 0

 5

 4.4

 0.3

 5

 103

 1

 5

 1.96

 0.14

 5

 2.62

 0.07

 5

 28

 1

 5

2M Mean

 SD

 n

 2.4

 0.2

 5

 143

 1

 5

 4.4

 0.6

 5

 105

 2

 5

 1.94

 0.10

 5

 2.64

 0.02

 5

 28

 2

 5

3M Mean

 SD

 n

 2.4

 0.3

 5

 144

 1

 5

 4.2

 0.1

 5

 104

 1

 5

 1.81

 0.13

 5

 2.67

 0.05

 5

 30

 4

 5

4M Mean

 SD

 n

 2.4

 0.3

 5

 145Æ

 1

 5

 4.2

 0.4

 5

 105

 1

 5

 2.13

 0.21

 5

 2.65

 0.03

 5

 29

 2

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 7

Page 53

Test Facility Study No. 459926
Table (continued)

Clinical Chemistry: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

ALP

iu/L

ALT

iu/L

AST

iu/L

LDH

iu/L

CPK

iu/L

Urea

mmol/L

Glu

mmol/L

T.Bil

μmol/L

Chol

mmol/L

TP

g/L

Alb

g/L

Glob

g/L

1F Mean

 SD

 n

 82

 14

 5

 50

 18

 5

 74

 11

 5

 135

 24

 5

 324

 289

 5

 6.5

 0.7

 5

 8.36

 0.63

 5

 1.7

 0.0

 5

 1.4

 0.3

 5

 64

 3

 5

 47

 3

 5

 17

 1

 5

2F Mean

 SD

 n

 74

 16

 5

 36

 8

 5

 59

 5

 5

 160

 9

 5

 127

 64

 5

 6.3

 0.8

 5

 8.47

 1.04

 5

 1.7

 0.0

 5

 1.6

 0.3

 5

 66

 6

 5

 48

 3

 5

 18

 2

 5

3F Mean

 SD

 n

 103

 22

 5

 43

 7

 5

 71

 17

 5

 144

 19

 5

 204

 167

 5

 6.5

 1.6

 5

 8.92

 0.68

 5

 1.7

 0.0

 5

 1.5

 0.3

 5

 62

 4

 5

 44

 4

 5

 18

 3

 5

4F Mean

 SD

 n

 90

 31

 5

 36

 5

 5

 68

 15

 5

 227

 175

 5

 411

 463

 5

 5.9

 0.3

 5

 8.42

 0.40

 5

 1.7

 0.0

 5

 1.5

 0.1

 5

 63

 1

 5

 47

 1

 5

 17

 2

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 7

Page 54

Test Facility Study No. 459926
Table (continued)

Clinical Chemistry: Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

AG-R Na

mmol/L

K

mmol/L

Cl

mmol/L

Phos

mmol/L

Ca

mmol/L

Crea

μmol/L

1F Mean

 SD

 n

 2.9

 0.3

 5

 143

 1

 5

 3.6

 0.4

 5

 106

 1

 5

 1.40

 0.11

 5

 2.63

 0.04

 5

 30

 3

 5

2F Mean

 SD

 n

 2.7

 0.1

 5

 144

 1

 5

 3.5

 0.2

 5

 106

 1

 5

 1.45

 0.33

 5

 2.70

 0.09

 5

 32

 2

 5

3F Mean

 SD

 n

 2.4

 0.4

 5

 144

 1

 5

 3.4

 0.1

 5

 106

 1

 5

 1.52

 0.11

 5

 2.62

 0.07

 5

 29

 3

 5

4F Mean

 SD

 n

 2.9

 0.4

 5

 143

 1

 5

 3.9

 0.5

 5

 105

 2

 5

 1.52

 0.12

 5

 2.63

 0.04

 5

 30

 3

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 7

Page 55

Test Facility Study No. 459926
Table

Urinalysis: Group Mean Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

S.G. UVol

mL

UpH

1M Mean

 SD

 n

 1.043

 0.010

 5

 1.3

 0.3

 5

 8.2

 1.0

 5

2M Mean

 SD

 n

 1.046

 0.024

 5

 0.8

 0.6

 5

 8.8

 0.3

 5

3M Mean

 SD

 n

 1.057

 0.008

 4

 0.7

 0.7

 5

 8.1

 0.9

 4

4M Mean

 SD

 n

 1.056

 0.014

 5

 1.0

 0.5

 5

 8.2

 1.0

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 8

Page 56

Test Facility Study No. 459926
Table (continued)

Urinalysis: Group Mean Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

S.G. UVol

mL

UpH

1F Mean

 SD

 n

 1.045

 0.022

 4

 0.7

 0.8

 5

 7.9

 1.0

 4

2F Mean

 SD

 n

 1.043

 0.009

 5

 0.7

 0.6

 5

 8.3

 0.8

 5

3F Mean

 SD

 n

 1.030

 0.013

 5

 1.4

 0.6

 5

 7.2

 0.6

 5

4F Mean

 SD

 n

 1.048

 0.024

 5

 0.7

 0.5

 5

 7.9

 1.1

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 8

Page 57

Test Facility Study No. 459926
Table

Absolute Organ Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent)

1M Mean

 SD

 n

 316

 10

 5

 0.0564

 0.0102

 5

 1.96

 0.08

 5

 1.0119

 0.0867

 5

 1.08

 0.12

 5

 2.15

 0.15

 5

 12.38

 1.00

 5

 1.47

 0.09

 5

 0.0946

 0.0281

 5

 0.1415

 0.0883

 5

2M Mean

 SD

 n

 316

 12

 5

 0.0606

 0.0083

 5

 1.97

 0.07

 5

 1.0437

 0.0982

 5

 1.08

 0.06

 5

 2.23

 0.14

 5

 12.58

 2.12

 5

 1.44

 0.11

 5

 0.1001

 0.0255

 5

 0.1338

 0.0331

 5

3M Mean

 SD

 n

 318

 18

 5

 0.0584

 0.0003

 3

 1.94

 0.07

 5

 1.0444

 0.0849

 5

 1.03

 0.07

 5

 2.13

 0.07

 5

 13.06

 1.43

 5

 1.47

 0.22

 5

 0.0828

 0.0217

 5

 0.2083

 0.1394

 5

4M Mean

 SD

 n

 324

 29

 5

 0.0575

 0.0089

 5

 1.94

 0.08

 5

 1.0814

 0.0865

 5

 1.08

 0.10

 5

 2.21

 0.14

 5

 12.28

 1.44

 5

 1.44

 0.19

 5

 0.1173

 0.0147

 5

 0.1657

 0.1092

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 9

Page 58

Test Facility Study No. 459926
Table (continued)

Absolute Organ Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

1M Mean

 SD

 n

 0.008

 0.002

 5

 0.380

 0.072

 5

 0.52

 0.03

 5

 0.5185

 0.0791

 5

 3.10

 0.19

 5

 0.482

 0.090

 5

 0.0193

 0.0053

 5

2M Mean

 SD

 n

 0.009

 0.002

 5

 0.375

 0.070

 5

 0.61

 0.10

 5

 0.5271

 0.0597

 5

 3.47Æ

 0.15

 5

 0.424

 0.118

 5

 0.0197

 0.0028

 5

3M Mean

 SD

 n

 0.008

 0.002

 5

 0.342

 0.052

 5

 0.50

 0.09

 5

 0.5107

 0.0234

 5

 3.18

 0.18

 5

 0.405

 0.039

 5

 0.0194

 0.0034

 5

4M Mean

 SD

 n

 0.008

 0.002

 5

 0.348

 0.103

 5

 0.57

 0.09

 5

 0.5556

 0.0291

 5

 3.40Æ

 0.07

 5

 0.511

 0.123

 5

 0.0203

 0.0029

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 9

Page 59

Test Facility Study No. 459926
Table (continued)

Absolute Organ Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries

1F Mean

 SD

 n

 224

 9

 5

 0.0814

 0.0074

 5

 1.86

 0.07

 5

 0.83

 0.15

 5

 1.65

 0.14

 5

 8.40

 0.45

 5

 1.18

 0.12

 5

 0.1254

 0.0472

 5

 0.1183

 0.0239

 5

 0.093

 0.006

 5

2F Mean

 SD

 n

 228

 13

 4

 0.0798

 0.0147

 4

 1.84

 0.07

 4

 0.82

 0.06

 4

 1.64

 0.07

 4

 7.99

 0.79

 4

 1.14

 0.08

 4

 0.1095

 0.0199

 4

 0.1295

 0.0651

 4

 0.114

 0.030

 4

3F Mean

 SD

 n

 212

 13

 5

 0.0904

 0.0132

 5

 1.89

 0.06

 5

 0.85

 0.07

 5

 1.67

 0.13

 5

 8.26

 0.67

 5

 1.27

 0.19

 5

 0.1207

 0.0345

 5

 0.0979

 0.0235

 5

 0.100

 0.017

 5

4F Mean

 SD

 n

 214

 10

 5

 0.0836

 0.0081

 5

 1.89

 0.03

 5

 0.77

 0.06

 5

 1.59

 0.08

 5

 7.55

 0.36

 5

 1.21

 0.09

 5

 0.1146

 0.0419

 5

 0.1176

 0.0662

 5

 0.092

 0.007

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 9

Page 60

Test Facility Study No. 459926
Table (continued)

Absolute Organ Weights (g): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Spleen

Salivary

 Gland Thymus Thyroid Uterus

1F Mean

 SD

 n

 0.011

 0.002

 5

 0.45

 0.07

 5

 0.4035

 0.0103

 5

 0.430

 0.057

 5

 0.0211

 0.0017

 5

 0.61

 0.19

 5

2F Mean

 SD

 n

 0.012

 0.002

 4

 0.44

 0.04

 4

 0.3913

 0.0246

 4

 0.491

 0.089

 4

 0.0209

 0.0025

 4

 0.53

 0.05

 4

3F Mean

 SD

 n

 0.010

 0.001

 5

 0.48

 0.05

 5

 0.3800

 0.0301

 5

 0.480

 0.112

 5

 0.0190

 0.0018

 5

 0.74

 0.32

 5

4F Mean

 SD

 n

 0.011

 0.003

 5

 0.45

 0.06

 5

 0.3818

 0.0263

 5

 0.452

 0.144

 5

 0.0194

 0.0035

 5

 0.62

 0.34

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 9

Page 61

Test Facility Study No. 459926
Table

Relative Organ Weights (% Body Weight): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Pituitary

1M Mean

 SD

 n

 0.01778

 0.00279

 5

 0.619

 0.014

 5

 0.31991

 0.02396

 5

 0.340

 0.030

 5

 0.680

 0.034

 5

 3.916

 0.296

 5

 0.464

 0.021

 5

 0.02997

 0.00916

 5

 0.04443

 0.02650

 5

 0.0026

 0.0008

 5

2M Mean

 SD

 n

 0.01921

 0.00291

 5

 0.623

 0.014

 5

 0.33010

 0.02625

 5

 0.342

 0.013

 5

 0.706

 0.038

 5

 3.974

 0.591

 5

 0.456

 0.020

 5

 0.03160

 0.00750

 5

 0.04237

 0.01076

 5

 0.0029

 0.0006

 5

3M Mean

 SD

 n

 0.01833

 0.00121

 3

 0.610

 0.025

 5

 0.32949

 0.03596

 5

 0.324

 0.033

 5

 0.670

 0.031

 5

 4.098

 0.247

 5

 0.463

 0.064

 5

 0.02624

 0.00759

 5

 0.06485

 0.04106

 5

 0.0025

 0.0006

 5

4M Mean

 SD

 n

 0.01797

 0.00390

 5

 0.603

 0.061

 5

 0.33455

 0.02211

 5

 0.333

 0.024

 5

 0.684

 0.051

 5

 3.796

 0.376

 5

 0.444

 0.037

 5

 0.03652

 0.00619

 5

 0.05022

 0.02999

 5

 0.0026

 0.0007

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 10

Page 62

Test Facility Study No. 459926
Table (continued)

Relative Organ Weights (% Body Weight): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

1M Mean

 SD

 n

 0.1198

 0.0206

 5

 0.164

 0.014

 5

 0.16403

 0.02527

 5

 0.981

 0.039

 5

 0.1525

 0.0281

 5

 0.00609

 0.00151

 5

2M Mean

 SD

 n

 0.1186

 0.0212

 5

 0.192

 0.029

 5

 0.16708

 0.02082

 5

 1.099

 0.064

 5

 0.1337

 0.0344

 5

 0.00626

 0.00106

 5

3M Mean

 SD

 n

 0.1074

 0.0145

 5

 0.156

 0.031

 5

 0.16083

 0.00806

 5

 1.001

 0.070

 5

 0.1275

 0.0132

 5

 0.00609

 0.00103

 5

4M Mean

 SD

 n

 0.1072

 0.0303

 5

 0.175

 0.016

 5

 0.17249

 0.01677

 5

 1.057

 0.097

 5

 0.1575

 0.0323

 5

 0.00625

 0.00053

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 10

Page 63

Test Facility Study No. 459926
Table (continued)

Relative Organ Weights (% Body Weight): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries Pituitary

1F Mean

 SD

 n

 0.03641

 0.00464

 5

 0.829

 0.058

 5

 0.371

 0.069

 5

 0.734

 0.070

 5

 3.750

 0.303

 5

 0.526

 0.066

 5

 0.05618

 0.02165

 5

 0.05305

 0.01202

 5

 0.0415

 0.0035

 5

 0.0050

 0.0009

 5

2F Mean

 SD

 n

 0.03531

 0.00839

 4

 0.808

 0.056

 4

 0.361

 0.041

 4

 0.720

 0.061

 4

 3.500

 0.185

 4

 0.502

 0.038

 4

 0.04826

 0.01036

 4

 0.05782

 0.03205

 4

 0.0497

 0.0112

 4

 0.0054

 0.0011

 4

3F Mean

 SD

 n

 0.04298

 0.00861

 5

 0.897

 0.078

 5

 0.401

 0.053

 5

 0.791

 0.072

 5

 3.894

 0.140

 5

 0.603

 0.115

 5

 0.05729

 0.01714

 5

 0.04664

 0.01320

 5

 0.0476

 0.0100

 5

 0.0048

 0.0007

 5

4F Mean

 SD

 n

 0.03908

 0.00264

 5

 0.886

 0.037

 5

 0.358

 0.022

 5

 0.745

 0.011

 5

 3.534

 0.117

 5

 0.564

 0.031

 5

 0.05338

 0.01781

 5

 0.05429

 0.02810

 5

 0.0430

 0.0037

 5

 0.0050

 0.0012

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 10

Page 64

Test Facility Study No. 459926
Table (continued)

Relative Organ Weights (% Body Weight): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Spleen

Salivary

 Gland Thymus Thyroid Uterus

1F Mean

 SD

 n

 0.200

 0.034

 5

 0.18000

 0.00732

 5

 0.1923

 0.0285

 5

 0.00942

 0.00098

 5

 0.275

 0.093

 5

2F Mean

 SD

 n

 0.191

 0.010

 4

 0.17198

 0.01371

 4

 0.2146

 0.0301

 4

 0.00922

 0.00143

 4

 0.234

 0.031

 4

3F Mean

 SD

 n

 0.228

 0.021

 5

 0.18002

 0.02034

 5

 0.2250

 0.0437

 5

 0.00900

 0.00140

 5

 0.350

 0.157

 5

4F Mean

 SD

 n

 0.208

 0.018

 5

 0.17907

 0.01658

 5

 0.2101

 0.0617

 5

 0.00910

 0.00165

 5

 0.294

 0.182

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 10

Page 65

Test Facility Study No. 459926
Table

Organ Weights (Covariance Analysis): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent)

1M Mean

 SE

 n

 319

 -

 5

 0.0562

 0.0039

 5

 1.96

 0.03

 5

 1.0164

 0.0379

 5

 1.08

 0.04

 5

 2.16

 0.05

 5

 12.49

 0.58

 5

 1.48

 0.06

 5

 0.0942

 0.0106

 5

 0.1469

 0.0419

 5

2M Mean

 SE

 n

 319

 -

 5

 0.0604

 0.0039

 5

 1.97

 0.03

 5

 1.0485

 0.0379

 5

 1.09

 0.04

 5

 2.24

 0.05

 5

 12.70

 0.58

 5

 1.46

 0.06

 5

 0.0997

 0.0106

 5

 0.1396

 0.0420

 5

3M Mean

 SE

 n

 319

 -

 5

 0.0584

 0.0050

 3

 1.94

 0.03

 5

 1.0455

 0.0378

 5

 1.03

 0.04

 5

 2.13

 0.05

 5

 13.08

 0.58

 5

 1.48

 0.06

 5

 0.0828

 0.0106

 5

 0.2096

 0.0418

 5

4M Mean

 SE

 n

 319

 -

 5

 0.0578

 0.0040

 5

 1.93

 0.03

 5

 1.0710

 0.0383

 5

 1.06

 0.04

 5

 2.19

 0.05

 5

 12.02

 0.59

 5

 1.41

 0.06

 5

 0.1181

 0.0107

 5

 0.1531

 0.0424

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 11

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Test Facility Study No. 459926
Table (continued)

Organ Weights (Covariance Analysis): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

1M Mean

 SE

 n

 0.008

 0.001

 5

 0.383

 0.033

 5

 0.52

 0.04

 5

 0.5191

 0.0244

 5

 3.11

 0.07

 5

 0.487

 0.042

 5

 0.0195

 0.0016

 5

2M Mean

 SE

 n

 0.009

 0.001

 5

 0.379

 0.033

 5

 0.61

 0.04

 5

 0.5278

 0.0244

 5

 3.47Æ

 0.07

 5

 0.429

 0.042

 5

 0.0199

 0.0016

 5

3M Mean

 SE

 n

 0.008

 0.001

 5

 0.343

 0.032

 5

 0.50

 0.04

 5

 0.5109

 0.0244

 5

 3.18

 0.07

 5

 0.406

 0.042

 5

 0.0194

 0.0016

 5

4M Mean

 SE

 n

 0.008

 0.001

 5

 0.339

 0.033

 5

 0.56

 0.04

 5

 0.5543

 0.0247

 5

 3.39Å

 0.07

 5

 0.500

 0.042

 5

 0.0199

 0.0016

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 11

Page 67

Test Facility Study No. 459926
Table (continued)

Organ Weights (Covariance Analysis): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries

1F Mean

 SE

 n

 219

 -

 5

 0.0842

 0.0045

 5

 1.86

 0.03

 5

 0.83

 0.05

 5

 1.64

 0.05

 5

 8.23

 0.22

 5

 1.19

 0.06

 5

 0.1267

 0.0183

 5

 0.1220

 0.0228

 5

 0.092

 0.008

 5

2F Mean

 SE

 n

 219

 -

 4

 0.0844

 0.0052

 4

 1.85

 0.03

 4

 0.82

 0.05

 4

 1.63

 0.06

 4

 7.70

 0.25

 4

 1.16

 0.07

 4

 0.1116

 0.0213

 4

 0.1357

 0.0266

 4

 0.112

 0.009

 4

3F Mean

 SE

 n

 219

 -

 5

 0.0866

 0.0046

 5

 1.88

 0.03

 5

 0.84

 0.05

 5

 1.68

 0.05

 5

 8.49

 0.22

 5

 1.26

 0.06

 5

 0.1190

 0.0188

 5

 0.0929

 0.0234

 5

 0.101

 0.008

 5

4F Mean

 SE

 n

 219

 -

 5

 0.0808

 0.0045

 5

 1.88

 0.03

 5

 0.76

 0.05

 5

 1.60

 0.05

 5

 7.72

 0.22

 5

 1.20

 0.06

 5

 0.1133

 0.0183

 5

 0.1139

 0.0228

 5

 0.093

 0.008

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 11

Page 68

Test Facility Study No. 459926
Table (continued)

Organ Weights (Covariance Analysis): Group Mean Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Spleen

Salivary

 Gland Thymus Thyroid Uterus

1F Mean

 SE

 n

 0.011

 0.001

 5

 0.44

 0.03

 5

 0.4056

 0.0113

 5

 0.403

 0.043

 5

 0.0215

 0.0011

 5

 0.66

 0.12

 5

2F Mean

 SE

 n

 0.012

 0.001

 4

 0.42

 0.03

 4

 0.3948

 0.0132

 4

 0.444

 0.050

 4

 0.0217

 0.0013

 4

 0.61

 0.14

 4

3F Mean

 SE

 n

 0.010

 0.001

 5

 0.50

 0.03

 5

 0.3772

 0.0116

 5

 0.517

 0.044

 5

 0.0184

 0.0011

 5

 0.68

 0.12

 5

4F Mean

 SE

 n

 0.011

 0.001

 5

 0.46

 0.03

 5

 0.3797

 0.0113

 5

 0.479

 0.043

 5

 0.0190

 0.0011

 5

 0.57

 0.12

 5

Group / sex

Significantly different from Group 1:a=p<0.05,b=p<0.01,c=p<0.001

 11

Page 69

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table 

Summary of Necropsy Findings 

GROUP TOTALS 

 Males Females 

NECROPSY FINDINGS GROUP Grp 1 Grp 2 Grp 3 Grp 4 Grp 1 Grp 2 Grp 3 Grp 4 

 DOSE Con. 100 300 1000 Con. 100 300 1000 

 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg 

 /day /day /day /day /day /day 

 

GENERAL COMMENTS 

 

Number of animals necropsied 5 5 5 5 5 5 5 5 

 

LUNG 

Pale 1 

Dark focus 2 1 1 

Dark 1 

Reddened 1 2 1 2 1 

 

LYMPH NODE (MANDIBULAR) 

 

Reddened 1 

SKIN AND SUBCUTIS 

Scab 1 

Hair loss 1 

The absence of a numeral indicates that the lesion specified was not identified 

Pathology File Ref.: PLAFOR_459926_MAC_LL_KEEP1.SPL

12

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Necropsy Findings 

 

GROUP TOTALS 

 Males Females 

NECROPSY FINDINGS GROUP Grp 1 Grp 2 Grp 3 Grp 4 Grp 1 Grp 2 Grp 3 Grp 4 

 DOSE Con. 100 300 1000 Con. 100 300 1000 

 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg 

 /day /day /day /day /day /day 

 

THYMUS 

 

Speckled 1 

 

UTERUS 

Dilated, with fluid, both horns 1 1 

The absence of a numeral indicates that the lesion specified was not identified 

Pathology File Ref.: PLAFOR_459926_MAC_LL_KEEP1.SPL

12

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table 

Summary of Histological Findings 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

ADRENAL GLAND (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

AORTA (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

BONE MARROW (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

BRAIN (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

CAECUM (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

COLON (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

DUODENUM (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

EPIDIDYMIS (5) (5) 

No abnormality detected 4 5 

Sperm granuloma 1 0 

 

EYE (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

FEMUR (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

HARDERIAN GLAND (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

HEART (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

ILEUM (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

JEJUNUM (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

JOINT (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

KIDNEY (5) (5) (5) (5) 

 

No abnormality detected 4 4 5 3 

Basophilic tubules 1 1 0 0 

Inflammatory cell foci, cortical 0 0 0 1 

Mineralisation, corticomedullary 0 0 0 1 

 

LIVER (5) (5) (5) (5) 

 

No abnormality detected 5 5 4 4 

Inflammatory cell infiltration, focal 0 0 1 1 

 

LUNG (5) (5) (5) (5) 

 

No abnormality detected 5 4 5 5 

Inflammatory cell infiltration, perivascular 0 1 0 0 

 

LYMPH NODE (MANDIBULAR) (5) (5) (5) (5) 

 

No abnormality detected 4 5 5 5 

Reactive hyperplasia 1 0 0 0 

 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

LYMPH NODE (MESENTERIC) (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

MAMMARY GLAND (5) (5) (4) (5) 

No abnormality detected 5 5 4 5 

OESOPHAGUS (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

OPTIC NERVE (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

OVARY (5) (5) 

No abnormality detected 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

Page 76

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

PANCREAS (ENDOCRINE) (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

PANCREAS (EXOCRINE) (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

PARATHYROID GLAND (5) (4) (5) (5) 

No abnormality detected 5 4 5 5 

PITUITARY GLAND (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

PROSTATE (5) (5) 

No abnormality detected 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

RECTUM (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

SALIVARY GLAND (SUBLINGUAL) (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

SALIVARY GLAND (SUBMAXILLARY) (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

SCIATIC NERVE (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

SEMINAL VESICLE (5) (5) 

No abnormality detected 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

SKELETAL MUSCLE (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

SKIN AND SUBCUTIS (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

SPINAL CORD (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

SPLEEN (5) (5) (5) (5) 

No abnormality detected 4 5 4 5 

Extramedullary haemapoiesis 1 0 1 0 

 

STERNUM (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

STOMACH (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

TESTIS (5) (5) 

No abnormality detected 5 5 

THYMUS (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

THYROID GLAND (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

TONGUE (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

Page 80

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Table (continued) 

Summary of Histological Findings 

 

 GROUP TOTALS 

 Males Females 

HISTOLOGICAL FINDINGS GROUP Grp 1 Grp 4 Grp 1 Grp 4 

 DOSE Con. 1000 Con. 1000 

 mg/kg mg/kg 

 /day /day 

 

TRACHEA (5) (5) (5) (5) 

 

No abnormality detected 5 5 5 5 

 

URINARY BLADDER (5) (5) (5) (5) 

No abnormality detected 5 5 5 5 

UTERUS (5) (5) 

No abnormality detected 5 5 

Oestrus dilation 1 1 

 

VAGINA (5) (5) 

 

No abnormality detected 5 5 

Oestrous cycle: oestrus 1 1 

Oestrous cycle: metoestrus 3 0 

Oestrous cycle: dioestrus 1 4 

 

Significantly different from the Control: * P<0.05, ** P<0.01, *** P<0.001 

Figures in brackets represent the number of animals from which this tissue was examined 

microscopically 

Pathology File Ref.: PLAFOR_459926_MIC_MPJ_KEEP1.SPL

13

Page 81

Test Facility Study No. 459926
Appendix 

Certificate of Analysis 1

 

 

 

Page 82

Test Facility Study No. 459926
Appendix 

Certificate of Analysis - Diet 

2

 

 

 

Page 83

Test Facility Study No. 459926
Appendix (continued) 

Certificate of Analysis - Water

2

 

 

 

Page 84

Test Facility Study No. 459926
Appendix 

Formulation Analysis 

Dose 

Group Timepoint 

Theoretical 

Concentration 

(mg/mL) 

Found Concentrations 

(mg/mL) 

(Individual Values) 

Mean Found 

Concentration 

(mg/mL) 

CV 

% 

% Difference from 

Theoretical Concentration 

 

1 Week 1 0 0 0 0 0 N/A N/A 

 

2 Week 1 10 9.51 11.3 11.2 10.7 9.4 +7.0 

3 Week 1 30 31.2 33.3 35.5 33.3 6.5 +11.0 

4 Week 1 100 112 110 122 115 5.6 +15.0 

1 Week 4 0 0 0 0 0 N/A N/A 

2 Week 4 10 8.99 9.59 9.65 9.41 3.9 -5.9 

3 Week 4 30 26.7 25.0 27.0 26.2 4.1 -12.7 

4 Week 4 100 94.3 104 99.8 99.4 4.9 -0.6 

Week 1 (prepared 26 January 2010) 

Week 4 ( prepared 16 February 2010) 

N/A = Not Applicable 

3

Page 85

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix 

Individual Clinical Observations 

Key to Appendix 

Day 0 = First day of treatment 

4

Page 86

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Observations 

Sex Group Animal Observation Days 

 M 1 1 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 1 2 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 1 3 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 1 4 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 1 5 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 2 6 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 2 7 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 2 8 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 2 9 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

4

Page 87

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Observations 

Sex Group Animal Observation Days 

 M 2 9 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 2 10 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 3 11 General Observation, No Abnormality Detected. -7-0,7 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 One scab(s) on, dorsal neck 14,21,28 

 terminal kill. 28 

 M 3 12 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 3 13 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 3 14 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 3 15 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 4 16 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 4 17 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

4

Page 88

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Observations 

Sex Group Animal Observation Days 

 M 4 17 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 4 18 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 4 19 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 M 4 20 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 1 21 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 1 22 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 1 23 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 1 24 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 1 25 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

4

Page 89

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Observations 

Sex Group Animal Observation Days 

 F 1 25 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 2 26 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 2 27 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 2 28 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 2 29 General Observation, No Abnormality Detected. -7-0,7,14,21 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 Unscheduled removal, anaesthetic death. 28 

 F 2 30 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 3 31 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 3 32 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 3 33 General Observation, No Abnormality Detected. -7-0,14,21,28 

4

Page 90

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Observations 

Sex Group Animal Observation Days 

 F 3 33 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 One scab(s) on, dorsal neck 7 

 terminal kill. 28 

 F 3 34 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 3 35 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 4 36 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 4 37 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 4 38 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 4 39 General Observation, No Abnormality Detected. -7-0,7,14,21,28 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 terminal kill. 28 

 F 4 40 General Observation, No Abnormality Detected. -7 

 No dosing abnormalities. 0(Pre)-6(+1h),7(Pre)-13(+1h), 

 14(Pre)-20(+1h),21(Pre)-27(+1h) 

 One bald area(s). 21,28 

 One scab(s) on, dorsal neck 0,7,14 

 terminal kill. 28 

4

Page 91

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix 

Functional Observation Battery Animal Numbers 

Group / 

Sex 

Animal 

No. 

Neurotoxicity 

No. 

Group / 

Sex 

Animal 

No. 

Neurotoxicity 

No. 

 

1M 1 6 1F 21 24 

 2 5 22 26 

 3 4 23 25 

 4 13 24 33 

 5 14 25 34 

 

2M 6 11 2F 26 31 

 7 10 27 32 

 8 12 28 30 

 9 18 29 38 

 10 17 30 37 

 

3M 11 9 3F 31 27 

 12 8 32 29 

 13 7 33 28 

 14 16 34 36 

 15 15 35 35 

 

4M 16 1 4F 36 22 

 17 2 37 23 

 18 3 38 21 

 19 20 39 39 

 20 19 40 40 

 

5

Page 92

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix 

Individual Clinical Signs: Functional Observation Battery 

Detailed Functional Observations 

In this appendix, the data is presented as it is obtained from the computerised system. The data reported combines observations 

collected from 3 environments noted as: 

(a) = standardised arena 

(c) = cage-side 

(H) = observation in the hand 

For operational reasons the in-life data capture system has been set up to record the first day of treatment as Day 0. As a consequence 

the day number in this appendix differs by one day compared to the rest of the report. 

Due to the limitations of the in-life data capture system, these observations have been regarded as a single activity, Week 4. 

The dose group number reported in Appendix 6 for all animals is ‘1’ for confidentiality purposes. Animal numbers in this appendix 

relate to their neurotoxicity number 

6

Page 93

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

Sex Group Animal Observation Week 

 M 1 1 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 2 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

6

Page 94

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 2 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 3 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

6

Page 95

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 3 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 4 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

6

Page 96

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 4 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 5 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

6

Page 97

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 5 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 6 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), asleep/at rest. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

6

Page 98

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 6 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 7 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

6

Page 99

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 7 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 8 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

6

Page 100

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 8 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 9 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

6

Page 101

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 9 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 10 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

6

Page 102

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 10 No reaction to tactile stimulus(a) 4 

 M 1 11 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 12 Alertness(a), normal. 4 

 Biting(c), absent. 4 

6

Page 103

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 12 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 13 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

6

Page 104

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 13 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 14 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

6

Page 105

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 14 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 15 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

6

Page 106

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 15 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 16 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

6

Page 107

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 16 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 17 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

6

Page 108

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 17 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 18 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), present during handling. 4 

 abnormal movements(a), absent. 4 

6

Page 109

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 18 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 19 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

6

Page 110

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 19 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 M 1 20 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

6

Page 111

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 M 1 20 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 21 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), asleep/at rest. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 22 Alertness(a), normal. 4 

6

Page 112

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 22 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 23 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

6

Page 113

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 23 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 24 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

6

Page 114

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 24 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 25 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

6

Page 115

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 25 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 26 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

6

Page 116

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 26 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 27 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

6

Page 117

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 27 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 28 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

6

Page 118

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 28 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 29 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

6

Page 119

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 29 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 30 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

6

Page 120

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 30 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 31 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

6

Page 121

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 32 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 33 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 33 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 34 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 34 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 35 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 35 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 36 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 36 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 37 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 37 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 38 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), asleep/at rest. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

6

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Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 38 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

 F 1 39 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

6

Page 128

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 39 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 No reaction to tactile stimulus(a) 4 

 F 1 40 Alertness(a), normal. 4 

 Biting(c), absent. 4 

 Coat (H), normal. 4 

 Diarrhoea(a), absent. 4 

 General behaviour(c), awake/alert. 4 

 General handling, behaviour normal. 4 

 No other arena findings. 4 

 No other cageside findings. 4 

 Palpebral closure(a), absent. 4 

 Piloerection(a), absent. 4 

 Piloerection(c), absent. 4 

 Polyuria(a), absent. 4 

 Posture/Gait(a), normal. 4 

 Posture/gait(c), normal. 4 

 Respiration(a), normal. 4 

 Respiration(c), normal. 4 

 Salivation (H), absent. 4 

 Spontaneous vocalisation(c), absent. 4 

 Vocalisation(a), absent. 4 

 abnormal movements(a), absent. 4 

 abnormal movements(c), absent. 4 

 Normal reaction to auditory stimulus(a) 4 

 biting(a), absent. 4 

 eye(s), normal. 4 

6

Page 129

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Individual Clinical Signs: Functional Observation Battery 

 Sex Group Animal Observation Week 

 F 1 40 involuntary leaping(a), absent. 4 

 pupillary reflex, normal. 4 

 Behaviour normal on removal from cage. 4 

 Normal reaction to tactile stimulus(a) 4 

6

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Test Facility Study No. 459926
Appendix

Neurotoxicity Screening: Detailed Functional Observations: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Latency

s Sectors n Rears n Groomingn Faec Pellets n Pools Urine n Foot Splay mm

Fore Grip

g

Hind Grip

g

Tail Flick

s Temp°C

1M 1 0 33 7 0 0 0 94 655 355 8.1 38.9

2 0 28 8 0 0 2 85 601 349 2.8 38.9

3 0 32 9 0 1 2 135 693 524 4.1 38.0

4 0 20 11 0 0 1 93 602 327 - 38.5

5 0 16 10 0 3 0 108 930 369 4.2 38.6

2M 6 0 24 11 0 0 4 129 569 363 2.5 38.6

7 0 13 8 0 0 5 92 667 537 3.6 38.9

8 0 31 15 0 0 0 116 578 365 2.9 38.9

9 0 13 7 0 2 0 94 871 456 - 37.7

10 0 9 1 0 0 2 98 676 420 3.8 36.9

3M 11 0 10 9 0 1 4 105 320 261 3.2 38.6

12 0 24 9 0 3 7 121 899 294 5.3 38.6

13 0 10 4 0 0 4 99 817 440 2.7 38.5

14 0 7 6 0 0 1 98 787 537 3.5 39.4

15 0 14 4 0 2 6 75 743 375 3.8 37.9

4M 16 0 9 8 0 1 1 126 885 412 3.0 37.5

17 0 22 11 1 0 4 119 667 364 3.1 38.9

18 0 15 8 0 0 3 75 533 421 3.3 39.0

19 0 14 4 0 0 1 155 784 355 2.9 38.4

20 0 25 10 0 0 3 93 521 355 4.8 38.3

Group / sex Animal

 No.

- = Non Measurable

 7

Page 131

Test Facility Study No. 459926
Appendix (continued)

Neurotoxicity Screening: Detailed Functional Observations: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Latency

s Sectors n Rears n Groomingn Faec Pellets n Pools Urine n Foot Splay mm

Fore Grip

g

Hind Grip

g

Tail Flick

s Temp°C

1F 21 0 4 4 0 0 1 49 493 290 2.9 38.7

22 0 32 13 0 0 0 92 731 278 2.5 38.6

23 0 33 13 0 0 0 130 680 301 4.3 39.2

24 0 19 11 0 0 1 110 731 339 3.9 38.6

25 0 38 11 0 2 6 111 555 291 4.0 39.1

2F 26 0 30 10 0 0 2 118 436 301 4.2 39.1

27 0 31 16 0 0 3 85 523 276 3.1 39.6

28 0 31 8 0 0 2 132 816 350 4.1 36.5

29 0 24 10 0 0 4 84 673 361 3.9 39.3

30 0 18 9 0 0 0 122 672 393 6.2 39.2

3F 31 0 7 6 0 0 0 119 743 358 4.5 38.0

32 0 34 13 0 0 0 99 586 241 3.6 38.6

33 0 36 14 0 0 0 125 677 289 2.8 38.2

34 0 27 8 0 1 1 89 735 382 2.9 38.0

35 0 29 9 0 0 0 89 568 275 3.3 38.4

4F 36 0 25 11 0 0 5 105 596 371 3.3 37.7

37 0 49 13 0 0 0 96 754 299 4.1 39.3

38 0 22 6 1 0 11 112 810 334 3.4 37.1

39 0 28 10 0 0 0 91 661 250 4.0 38.3

40 0 25 8 0 0 0 99 660 321 3.8 38.6

Group / sex Animal

 No.

 7

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Test Facility Study No. 459926
Appendix

Neurotoxicity Screening: Motion Activity (Movements / 5 minutes): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Minutes

1-5 6-10 11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 Overall

1M 1 50 77 60 78 66 30 0 8 6 10 5 4 394

2 80 76 69 59 70 76 16 28 1 8 8 0 491

3 63 55 76 74 67 49 83 19 1 24 62 20 593

4 56 77 55 10 12 3 7 4 4 63 1 3 295

5 67 68 79 66 68 16 9 1 6 0 5 45 430

2M 6 47 53 51 58 62 2 3 1 10 0 0 0 287

7 50 65 64 76 50 35 38 7 7 6 0 1 399

8 68 60 63 58 42 46 57 47 8 2 6 0 457

9 41 50 46 41 16 14 64 36 1 2 10 4 325

10 49 53 70 67 13 7 28 10 8 0 4 6 315

3M 11 71 68 90 75 54 27 4 1 0 2 0 0 392

12 47 50 46 63 57 59 12 37 5 46 78 67 567

13 56 50 71 61 60 8 3 0 0 1 0 1 311

14 55 63 59 77 42 69 58 1 2 12 8 1 447

15 72 73 66 16 0 0 3 4 0 0 0 0 234

4M 16 40 39 53 66 74 49 11 1 6 4 7 4 354

17 73 79 67 69 83 61 37 5 11 2 7 0 494

18 69 55 77 65 59 69 69 10 0 4 8 0 485

19 51 70 69 57 63 68 32 16 11 24 5 8 474

20 53 61 56 41 63 40 15 0 9 2 10 3 353

Group / sex Animal

 No.

 8

Page 133

Test Facility Study No. 459926
Appendix (continued)

Neurotoxicity Screening: Motion Activity (Movements / 5 minutes): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Minutes

1-5 6-10 11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 Overall

1F 21 50 72 59 55 57 66 39 66 59 28 15 12 578

22 76 76 93 70 87 31 4 30 84 75 9 6 641

23 64 59 59 69 69 94 89 74 69 82 76 15 819

24 50 57 64 56 67 75 55 31 8 5 3 20 491

25 60 67 73 36 59 63 82 66 5 7 5 56 579

2F 26 46 60 71 74 81 67 35 6 28 0 3 18 489

27 66 62 56 60 77 49 45 12 1 17 66 52 563

28 45 41 62 75 76 66 73 94 78 28 8 2 648

29 37 65 57 59 61 78 63 53 59 55 6 7 600

30 47 63 55 59 48 55 57 48 4 14 10 3 463

3F 31 55 58 39 69 77 55 19 0 4 0 0 0 376

32 66 60 56 62 9 6 14 14 13 42 8 0 350

33 55 78 69 68 0 15 0 3 61 68 70 54 541

34 50 75 78 68 26 6 6 29 16 7 10 5 376

35 63 68 79 75 61 75 69 105 38 3 42 44 722

4F 36 49 62 87 81 75 77 72 65 62 3 18 15 666

37 55 70 52 47 18 22 15 59 1 0 0 19 358

38 37 43 59 66 57 37 5 65 32 6 6 3 416

39 51 62 59 73 15 64 63 15 5 6 11 3 427

40 48 60 87 59 56 14 48 74 57 16 17 7 543

Group / sex Animal

 No.

 8

Page 134

Test Facility Study No. 459926
Appendix

Body Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -7 -4 0 3 7 10 14 17 21 24 28 Change

0 - 28

1M 1 197.0 213.9 226.9 237.7 250.1 262.5 273.2 279.4 290.4 295.8 304.6 77.7

2 205.1 220.5 239.5 243.7 258.6 270.1 281.4 288.4 300.8 306.7 317.6 78.1

3 200.9 210.0 246.2 259.8 275.7 290.7 299.5 309.3 314.5 324.6 330.8 84.6

4 203.7 224.4 240.5 250.9 265.6 274.6 284.8 290.1 297.6 302.0 309.9 69.4

5 205.4 223.5 244.1 256.0 269.7 281.0 294.0 306.5 316.6 315.5 326.0 81.9

2M 6 206.0 220.1 239.2 245.3 265.3 271.3 287.6 298.9 309.3 324.4 333.0 93.8

7 206.8 227.2 240.6 253.0 268.8 280.5 285.1 294.0 302.5 310.2 324.6 84.0

8 203.7 219.8 240.7 254.0 267.3 279.9 286.7 298.2 311.2 319.0 329.2 88.5

9 211.7 230.4 246.1 248.3 266.3 274.2 287.4 296.6 298.4 306.6 312.9 66.8

10 195.7 211.7 230.5 241.0 255.7 265.9 273.5 280.4 292.5 296.3 305.8 75.3

3M 11 198.3 215.0 234.4 241.7 257.0 264.4 270.8 284.3 284.6 295.0 299.0 64.6

12 196.9 219.0 240.8 252.9 271.7 285.0 297.8 306.4 313.2 320.0 325.9 85.1

13 205.2 227.4 251.0 261.8 283.8 292.3 306.6 314.6 324.8 332.0 345.0 94.0

14 199.4 217.4 237.3 247.9 264.5 274.0 286.2 298.0 305.0 315.0 324.2 86.9

15 200.5 216.0 230.3 237.9 251.7 260.6 274.0 282.4 296.1 298.0 310.8 80.5

4M 16 198.2 218.3 245.1 257.1 273.9 289.3 306.3 315.7 329.6 336.5 351.1 106.0

17 187.6 207.2 225.1 230.7 249.0 258.7 271.9 278.9 282.6 288.5 294.8 69.7

18 213.6 231.9 258.5 269.4 290.1 304.2 317.5 328.5 341.2 349.5 359.3 100.8

19 205.8 225.1 241.2 249.6 266.1 277.1 293.1 298.3 307.1 312.7 321.5 80.3

20 188.0 200.7 221.0 230.1 246.1 252.1 267.0 276.9 282.5 292.2 301.7 80.7

Group /

 sex Animal 

No.

Day 0 = first day test item administered

 9

Page 135

Test Facility Study No. 459926
Appendix (continued)

Body Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -7 -4 0 3 7 10 14 17 21 24 28 Change

0 - 28

1F 21 167.3 168.3 176.3 192.3 204.6 211.1 215.8 219.6 225.5 219.3 224.3 48.0

22 162.6 172.8 182.8 186.6 201.2 198.5 208.2 220.7 220.3 226.5 231.4 48.6

23 161.6 179.8 188.1 192.4 201.4 202.7 212.0 203.3 205.8 214.6 221.5 33.4

24 156.7 162.7 173.5 178.8 187.3 195.8 203.9 208.6 214.5 217.6 204.5 31.0

25 173.9 175.6 186.9 199.2 209.1 216.4 228.4 230.0 234.9 230.5 236.5 49.6

2F 26 165.6 177.1 189.0 194.3 202.6 201.7 211.6 218.7 220.5 222.7 238.4 49.4

27 168.7 167.5 177.2 188.9 196.6 204.6 212.4 212.4 214.4 210.6 214.2 37.0

28 177.7 181.6 190.7 206.4 215.7 221.4 226.4 235.2 242.4 239.5 250.5 59.8

29 154.6 175.0 178.4 186.6 191.9 192.3 198.6 196.5 200.8 207.7 214.4 36.0

30 166.3 178.5 188.5 190.2 192.5 197.0 206.7 226.0 228.6 228.1 234.6 46.1

3F 31 156.7 157.4 165.1 178.2 185.6 189.5 196.6 196.4 200.1 199.5 213.8 48.7

32 159.7 160.0 170.3 165.9 175.1 187.8 196.4 202.3 208.3 207.8 217.2 46.9

33 171.9 172.8 179.7 197.3 203.7 209.5 216.2 216.3 221.2 216.8 226.3 46.6

34 159.5 159.7 168.0 177.3 180.6 190.9 194.1 196.9 196.3 192.2 200.3 32.3

35 158.5 174.8 185.7 192.9 202.6 206.9 213.8 212.2 218.1 223.6 228.9 43.2

4F 36 151.6 164.9 170.3 174.6 181.7 184.3 190.1 187.4 191.1 198.9 203.4 33.1

37 155.2 164.3 176.3 178.5 186.0 197.5 206.8 208.9 213.3 217.6 221.1 44.8

38 168.2 177.4 187.5 196.9 202.6 203.4 206.3 217.9 222.1 228.5 233.3 45.8

39 162.0 168.5 174.0 180.1 186.9 194.6 202.6 206.5 210.1 209.4 206.4 32.4

40 165.9 173.5 179.2 185.7 190.4 185.6 193.7 206.8 211.9 217.1 221.7 42.5

Group /

 sex Animal 

No.

Day 0 = first day test item administered

 9

Page 136

Test Facility Study No. 459926
Appendix

Food Consumption (g/animal/day): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -4 0 3 7 10 14 17 21 24 28

1M 1 21.6 22.5 23.1 23.3 23.3 23.4 22.2 23.2 22.5 21.9

2 22.1 23.1 22.7 22.6 21.4 22.4 21.8 22.1 21.4 20.4

2M 3 22.0 22.5 22.5 23.8 22.4 23.3 22.5 23.0 23.2 22.7

4 21.6 22.2 21.7 23.1 22.2 22.5 22.2 21.8 21.5 20.6

3M 5 22.8 23.9 24.6 25.2 24.3 24.6 23.6 23.4 23.1 22.2

6 20.7 22.2 22.0 23.5 22.4 23.3 23.0 22.8 22.2 22.6

4M 7 21.8 23.2 23.3 24.0 23.8 24.5 24.0 23.8 22.8 22.2

8 20.3 21.0 20.6 22.8 20.5 22.4 21.2 21.5 21.4 18.0

Group /

 sex Cage 

No.

 10

Page 137

Test Facility Study No. 459926
Appendix (continued)

Food Consumption (g/animal/day): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Day

 -4 0 3 7 10 14 17 21 24 28

1F 9 16.9 17.4 16.8 18.5 17.3 19.1 17.4 18.0 17.7 16.8

10 16.9 18.3 18.2 18.8 17.7 19.6 18.2 19.2 19.1 18.5

2F 11 16.7 17.4 17.8 18.5 16.4 18.9 17.8 18.4 17.6 17.4

12 18.2 16.8 16.2 17.7 16.5 18.7 18.9 18.5 17.3 17.1

3F 13 15.3 16.0 17.2 18.6 16.6 19.2 17.2 19.0 17.5 18.9

14 17.4 18.1 17.9 18.3 18.0 20.2 20.5 21.9 22.8 18.5

4F 15 15.4 15.7 15.4 16.9 16.1 17.6 17.6 17.3 16.8 16.4

16 14.6 15.7 15.4 16.5 15.3 17.6 16.4 17.6 15.6 16.4

Group /

 sex Cage 

No.

 10

Page 138

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix 

Ophthalmoscopy: Individual Findings 

Group / 

Sex 

Animal 

No. Pretrial Week 4 

1M 1 N N 

 2 N N 

 3 N N 

 4 N LE: Corneal erosion, several superficial in Anterior Area 

RE: N 

 5 N N 

2M 6 N - 

 7 N - 

 8 N - 

 9 N - 

 10 N - 

3M 11 N - 

 12 N - 

 13 N - 

 14 N - 

 15 N - 

4M 16 N N 

 17 N N 

 18 N N 

 19 N N 

 20 N N 

N Normal 

LE Left Eye 

RE Right Eye 

- Not applicable 

11

Page 139

Test Facility Study No. 459926
Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

----------

100

3

Alcohols, C18-22

300

4

----------

1000

Appendix (continued) 

Ophthalmoscopy: Individual Findings 

Group / 

Sex 

Animal 

No. Pretrial Week 4 

1F 21 N N 

 22 N N 

 23 N N 

 24 N N 

 25 N N 

2F 26 N - 

 27 N - 

 28 N - 

 29 N - 

 30 N - 

3F 31 N - 

 32 N - 

 33 N - 

 34 N - 

 35 N - 

4F 36 N RE: Pale area around optic disk of fundus 

LE: N 

 37 N N 

 38 N N 

 39 N N 

 40 N N 

N Normal 

LE Left Eye 

RE Right Eye 

- Not applicable 

11

Page 140

Test Facility Study No. 459926
Appendix

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

---------- Neut ---------- Lymph---------- Monox10Ä/L

Eos

---------- Baso---------- LUC---------- 1M 1 15.5 8.56 0.439 18.1 51.3 35.3 12.1 2.2 11.58 1.11 9.93 0.26 0.17 0.04 0.07

2 15.4 8.77 0.441 17.5 50.3 34.9 11.4 2.1 7.00 0.79 5.87 0.15 0.11 0.02 0.06

3 16.3 8.47 0.447 19.3 52.8 36.5 15.0 2.2 10.87 0.96 9.43 0.21 0.12 0.03 0.12

4 15.3 8.66 0.442 17.6 51.0 34.5 11.2 2.1 7.19 1.01 5.93 0.11 0.08 0.02 0.04

5 16.2 8.99 0.473 18.0 52.7 34.2 10.5 2.2 9.74 1.05 8.31 0.14 0.10 0.03 0.11

2M 6 - - - - - - - - - - - - - - - 7 15.0 8.32 0.424 18.1 51.0 35.5 12.8 2.3 8.28 0.83 7.07 0.19 0.11 0.02 0.06

8 15.9 8.27 0.446 19.2 53.9 35.6 10.8 2.4 8.75 0.87 7.53 0.13 0.15 0.02 0.06

9 - - - - - - - - - - - - - - - 10 15.6 8.57 0.451 18.2 52.6 34.6 10.9 1.8 6.91 0.59 6.06 0.08 0.09 0.02 0.08

Group / sex Animal

 No.

Animals 6 and 9 clotted haematology sample

 12

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Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PTs APTT s 1M 1 871 14 24 2 825 14 - 3 889 14 - 4 502 14 25 5 793 15 21

2M 6 - 15 - 7 903 15 22 8 840 15 24 9 - - - 10 917 16 23

Group / sex Animal

 No.

Animals 2, 3 and 6 insufficient sample to obtain APTT results

Animals 6 and 9 clotted haematology sample

Animal 9 unable to obtain PT or APTT results. poor quality sample

 12

Page 142

Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

---------- Neut ---------- Lymph---------- Monox10Ä/L

Eos

---------- Baso---------- LUC---------- 3M 11 15.4 8.37 0.439 18.4 52.4 35.2 13.9 2.2 9.85 1.16 8.33 0.12 0.14 0.04 0.06

12 15.4 8.93 0.456 17.3 51.1 33.9 11.0 2.1 8.67 1.14 7.08 0.15 0.19 0.03 0.09

13 15.8 8.62 0.459 18.3 53.2 34.4 10.8 2.0 6.91 0.84 5.76 0.13 0.10 0.01 0.08

14 15.2 8.43 0.429 18.0 50.9 35.4 11.6 2.0 8.66 0.96 7.34 0.09 0.17 0.02 0.08

15 15.5 7.90 0.436 19.6 55.2 35.6 10.6 2.7 9.16 1.48 7.30 0.16 0.11 0.02 0.09

4M 16 16.3 8.98 0.474 18.2 52.8 34.4 10.5 2.3 7.91 1.16 6.47 0.10 0.11 0.02 0.06

17 - - - - - - - - - - - - - - - 18 14.9 8.07 0.437 18.5 54.1 34.1 11.5 2.7 8.77 0.66 7.79 0.12 0.12 0.02 0.06

19 14.7 8.71 0.438 16.8 50.4 33.4 11.0 1.9 6.98 0.80 5.83 0.11 0.16 0.02 0.07

20 14.9 7.82 0.421 19.1 53.8 35.4 15.6 2.7 5.57 0.62 4.75 0.08 0.06 0.01 0.05

Group / sex Animal

 No.

Animal 17 clotted haematology sample

 12

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Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PTs APTT s 3M 11 797 - - 12 889 15 25

13 819 15 - 14 905 15 23

15 839 14 26

4M 16 711 15 - 17 - - - 18 857 14 23

19 854 15 25

20 790 15 24

Group / sex Animal

 No.

Animal 17 clotted haematology sample

Animal 11 insuficient sample for analysis

Animals 13 and 16 insufficient sample to obtain APTT results

Animal 17 insufficient sample to obtain PT and APTT results

 12

Page 144

Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

---------- Neut ---------- Lymph---------- Monox10Ä/L

Eos

---------- Baso---------- LUC---------- 1F 21 14.7 8.14 0.426 18.0 52.3 34.5 11.9 2.4 6.93 0.80 5.73 0.20 0.11 0.02 0.07

22 13.8 7.37 0.391 18.7 53.1 35.3 11.4 2.7 7.19 1.27 5.57 0.15 0.11 0.01 0.06

23 14.5 8.23 0.417 17.6 50.7 34.8 9.9 1.9 4.99 0.54 4.17 0.13 0.09 0.02 0.05

24 14.5 7.98 0.412 18.2 51.7 35.2 11.3 2.6 7.16 1.36 5.43 0.18 0.10 0.01 0.08

25 14.6 7.84 0.409 18.6 52.2 35.6 10.9 3.4 5.82 1.85 3.69 0.13 0.10 0.01 0.04

2F 26 14.7 7.77 0.420 18.9 54.0 34.9 10.4 2.4 5.42 0.90 4.28 0.08 0.12 0.01 0.04

27 15.2 8.09 0.429 18.8 53.0 35.6 11.5 2.5 4.48 0.94 3.37 0.08 0.07 0.01 0.02

28 13.8 7.57 0.376 18.3 49.7 36.7 11.2 2.3 4.30 0.83 3.26 0.08 0.10 0.01 0.03

29 14.7 7.85 0.409 18.8 52.1 36.0 10.4 2.5 4.97 0.95 3.85 0.06 0.06 0.00 0.04

30 14.9 8.03 0.413 18.5 51.4 36.0 11.2 2.2 6.18 0.76 5.08 0.11 0.18 0.02 0.03

Group / sex Animal

 No.

 12

Page 145

Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PTs APTT s 1F 21 865 15 - 22 891 15 23

23 906 15 22

24 793 15 21

25 745 15 23

2F 26 791 15 - 27 953 16 23

28 886 - - 29 937 15 - 30 998 15 -

Group / sex Animal

 No.

Animals 21, 26, 29 and 30 insufficient sample to obtain APTT results

Animals 28 insufficient sample for analysis

 12

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Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Hb

g/dL

RBC

x1012/L

Hct

L/L

MCH

pg

MCV

fL

MCHC

g/dL

RDW

%

Ret

%

WBC

---------- Neut ---------- Lymph---------- Monox10Ä/L

Eos

---------- Baso---------- LUC---------- 3F 31 14.0 7.58 0.396 18.4 52.2 35.3 11.5 3.2 7.31 0.57 6.46 0.11 0.07 0.02 0.07

32 15.0 7.85 0.415 19.1 52.9 36.1 11.8 2.4 7.54 0.76 6.52 0.13 0.06 0.02 0.06

33 15.1 8.46 0.442 17.8 52.3 34.0 11.2 3.6 5.26 1.52 3.50 0.06 0.11 0.01 0.06

34 13.6 7.80 0.397 17.5 50.8 34.4 12.8 3.5 3.75 0.50 3.10 0.07 0.04 0.01 0.03

35 14.2 7.10 0.381 20.0 53.6 37.4 11.2 3.5 6.96 1.23 5.41 0.11 0.13 0.02 0.06

4F 36 - - - - - - - - - - - - - - - 37 14.5 7.78 0.405 18.6 52.1 35.8 10.4 2.2 4.85 0.61 4.08 0.04 0.07 0.02 0.04

38 15.0 7.79 0.426 19.2 54.6 35.1 10.5 2.4 5.92 0.85 4.65 0.10 0.20 0.02 0.09

39 15.8 8.15 0.429 19.4 52.7 36.9 13.8 2.0 5.72 0.94 4.53 0.06 0.12 0.02 0.05

40 14.8 7.52 0.404 19.7 53.7 36.8 11.2 1.7 6.88 0.58 6.05 0.09 0.09 0.02 0.05

Group / sex Animal

 No.

Animal 36 clotted haematology sample

 12

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Test Facility Study No. 459926
Appendix (continued)

Haematology and Coagulation: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Plat

x10Ä/L

 PTs APTT s 3F 31 810 15 23

32 712 15 23

33 860 14 24

34 782 16 23

35 1043 15 22

4F 36 - - - 37 831 14 22

38 1152 15 21

39 690 14 22

40 354 - -

Group / sex Animal

 No.

Animal 36 clotted haematology sample

Animals 36 and 40 unable to obtain PT or APTT results. poor sample quality

 12

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Test Facility Study No. 459926
Appendix

Clinical Chemistry: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

ALP

iu/L

ALT

iu/L

AST

iu/L

LDH

iu/L

CPK

iu/L

Urea

mmol/L

Glu

mmol/L

T.Bil

μmol/L

Chol

mmol/L

TP

g/L

Alb

g/L

Glob

g/L

1M 1 165 71 73 132 227 6.5 7.85 <1.7 1.8 63 43 20

2 134 48 61 146 149 5.7 12.58 <1.7 1.6 60 42 18

3 135 45 63 195 189 7.1 11.18 <1.7 1.3 61 39 21

4 110 46 104 1375 961 5.5 7.64 <1.7 1.7 58 41 17

5 138 55 79 142 208 6.0 10.34 <1.7 1.2 60 42 18

2M 6 168 70 103 799 844 5.7 7.83 <1.7 1.6 59 43 16

7 120 48 62 192 145 5.7 10.48 <1.7 1.2 61 43 18

8 137 50 66 144 150 6.1 10.10 <1.7 1.2 60 42 18

9 157 37 61 176 329 5.8 10.93 <1.7 1.4 60 42 18

10 142 50 62 203 224 6.1 9.30 <1.7 2.2 63 44 19

3M 11 203 38 58 123 144 5.4 10.81 <1.7 1.2 62 45 17

12 160 38 68 366 257 5.9 9.02 <1.7 1.3 64 44 20

13 98 61 67 159 186 6.1 10.34 <1.7 1.7 60 42 18

14 132 42 62 172 170 6.8 9.62 2.1 1.4 61 41 20

15 139 47 68 180 155 6.9 11.43 <1.7 1.3 63 46 17

4M 16 121 50 117 539 2801 5.3 10.89 <1.7 1.4 59 42 16

17 144 40 64 316 371 5.2 10.89 <1.7 1.5 59 41 18

18 123 45 58 125 161 6.3 10.27 <1.7 1.8 62 41 21

19 145 37 59 209 151 6.6 8.69 <1.7 1.6 60 42 18

20 138 36 62 152 138 6.0 9.76 <1.7 1.5 62 45 17

Group / sex Animal

 No.

T.Bil (<1.7) lower than limits of assay, 1.7 used for group men analysis

 13

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Test Facility Study No. 459926
Appendix (continued)

Clinical Chemistry: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

AG-R Na

mmol/L Kmmol/L

Cl

mmol/L

Phos

mmol/L

Ca

mmol/L

Crea

μmol/L

1M 1 2.2 143 4.2 103 1.98 2.71 28 2 2.3 143 4.3 102 1.92 2.59 27 3 1.8 143 4.3 104 1.78 2.67 27 4 2.4 143 4.9 104 1.93 2.52 27 5 2.4 143 4.1 104 2.17 2.59 30

2M 6 2.7 144 5.4 107 1.87 2.61 26 7 2.3 144 4.3 104 1.81 2.67 29 8 2.3 142 4.0 103 2.05 2.64 29 9 2.3 144 4.4 106 2.04 2.66 27

10 2.3 143 4.1 104 1.93 2.63 30

3M 11 2.7 145 4.1 105 1.92 2.71 28

12 2.2 144 4.2 103 1.70 2.71 28

13 2.3 143 4.3 104 1.97 2.60 31

14 2.1 143 4.2 104 1.68 2.63 26

15 2.7 143 4.2 105 1.79 2.69 36

4M 16 2.6 145 4.7 107 2.38 2.62 28

17 2.3 144 4.3 104 2.32 2.65 27

18 2.0 145 4.3 105 2.06 2.69 33

19 2.3 144 4.2 105 1.90 2.64 29

20 2.6 146 3.6 105 2.01 2.64 30

Group / sex Animal

 No.

 13

Page 150

Test Facility Study No. 459926
Appendix (continued)

Clinical Chemistry: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

ALP

iu/L

ALT

iu/L

AST

iu/L

LDH

iu/L

CPK

iu/L

Urea

mmol/L

Glu

mmol/L

T.Bil

μmol/L

Chol

mmol/L

TP

g/L

Alb

g/L

Glob

g/L

1F 21 81 27 71 156 817 6.2 7.50 <1.7 1.7 67 51 16

22 104 43 71 164 261 7.4 7.90 <1.7 1.1 66 50 17

23 67 43 65 134 114 5.6 8.95 <1.7 1.2 60 46 15

24 77 63 69 112 119 6.7 8.69 <1.7 1.8 64 45 18

25 83 73 92 111 310 6.5 8.77 <1.7 1.3 63 45 18

2F 26 50 42 63 176 238 6.4 7.28 <1.7 1.3 63 46 17

27 82 23 61 156 120 6.3 9.38 <1.7 1.4 68 50 18

28 87 38 51 155 84 7.3 9.22 <1.7 1.5 75 53 21

29 88 37 55 161 85 5.0 9.06 <1.7 2.0 61 45 16

30 65 42 63 154 109 6.3 7.39 <1.7 1.8 64 47 17

3F 31 108 48 71 166 484 5.4 7.95 <1.7 1.6 60 45 15

32 131 42 66 130 111 5.4 9.06 <1.7 1.4 63 45 18

33 74 32 67 164 233 8.2 8.61 <1.7 1.4 67 48 19

34 114 50 98 137 110 8.4 9.72 <1.7 1.1 57 41 16

35 88 45 52 125 81 5.3 9.28 <1.7 1.9 63 39 23

4F 36 119 33 66 303 451 5.7 8.05 <1.7 1.5 61 45 17

37 51 36 60 146 140 6.2 8.94 <1.7 1.4 63 48 15

38 63 39 58 106 118 5.8 8.74 <1.7 1.5 65 46 19

39 118 29 61 82 145 5.7 8.23 <1.7 1.5 63 46 17

40 98 41 93 500 1203 6.3 8.12 <1.7 1.4 63 48 15

Group / sex Animal

 No.

T.Bil (<1.7) lower than limits of assay, 1.7 used for group men analysis

 13

Page 151

Test Facility Study No. 459926
Appendix (continued)

Clinical Chemistry: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

AG-R Na

mmol/L Kmmol/L

Cl

mmol/L

Phos

mmol/L

Ca

mmol/L

Crea

μmol/L

1F 21 3.2 144 3.7 108 1.40 2.63 31

22 3.0 144 3.0 104 1.51 2.70 34

23 3.2 142 3.6 106 1.22 2.60 32

24 2.5 143 4.1 105 1.46 2.62 28

25 2.6 142 3.7 106 1.41 2.59 27

2F 26 2.7 145 3.5 105 1.92 2.65 32

27 2.7 146 3.3 107 1.25 2.64 34

28 2.5 144 3.4 106 1.06 2.86 33

29 2.8 144 3.3 106 1.40 2.65 28

30 2.8 142 3.9 105 1.63 2.69 31

3F 31 2.9 145 3.3 106 1.51 2.62 27

32 2.5 145 3.4 105 1.53 2.64 28

33 2.6 145 3.5 108 1.53 2.69 34

34 2.5 144 3.3 105 1.66 2.51 27

35 1.7 142 3.6 105 1.36 2.62 28

4F 36 2.7 144 4.3 107 1.56 2.61 28

37 3.3 143 3.7 106 1.41 2.66 33

38 2.5 143 3.4 102 1.62 2.65 34

39 2.7 143 3.7 105 1.38 2.68 30

40 3.3 141 4.6 106 1.63 2.57 27

Group / sex Animal

 No.

 13

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Test Facility Study No. 459926
Appendix

Urinalysis: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

UCol S.G. UVol

mL

UpH UProt

mg/dL

UGl

mg/dL

UKet

mg/dL

Uro

mg/dL

U.Bi

mg/dL

BP

mg/dL

Leu

cells/μL

1M 1 3 1.038 1.8 8.5 70 0 0 0.2 0.0 0.00 75

2 18 1.056 1.4 8.5 100 0 5 0.2 0.0 0.00 75

3 3 1.030 1.4 8.5 30 0 0 0.2 0.0 0.00 25

4 3 1.042 1.2 9.0 100 0 0 0.2 0.0 0.00 25

5 3 1.050 0.9 6.5 100 0 5 1.0 0.0 0.00 75

2M 6 18 1.068 0.1 9.0 >400 0 5 1.0 0.0 0.00 500

7 5 1.048 0.6 9.0 100 0 5 0.2 0.0 0.00 75

8 3 1.017 1.2 8.5 30 0 0 0.2 0.0 0.00 25

9 22 1.070 0.3 8.5 100 0 5 0.2 0.0 0.00 75

10 5 1.028 1.6 9.0 50 0 0 0.2 0.0 0.00 25

3M 11 - - <0.1 - - - - - - - - 12 18 1.048 1.8 9.0 70 0 5 0.2 0.0 0.00 25

13 18 1.066 0.4 8.5 100 0 5 0.2 0.0 0.00 75

14 5 1.060 0.5 8.0 150 0 5 0.2 0.0 0.00 75

15 3 1.054 0.7 7.0 70 0 5 0.2 0.0 0.00 75

4M 16 5 1.039 1.6 8.5 100 0 5 0.2 0.0 0.00 75

17 3 1.064 0.4 6.5 100 0 10 2.0 0.0 0.00 75

18 20 1.066 0.7 9.0 100 0 5 1.0 0.0 0.00 75

19 18 1.068 0.7 8.0 150 0 10 0.2 0.0 0.00 75

20 5 1.044 1.4 9.0 70 0 0 0.2 0.0 0.00 25

Group / sex Animal

 No.

Animal 11 insufficient sample for analysis

 14

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Test Facility Study No. 459926
Appendix (continued)

Urinalysis: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Mic.E Mic.Cr Mic.W Mic.R Mic.O Mic.C Mic.A UTb

1M 1 0 1 0 0 1 0 0 0 2 0 1 0 0 1 0 0 0 3 0 1 0 0 1 0 0 0 4 0 1 0 0 1 0 0 0 5 0 1 0 0 1 0 0 0

2M 6 0 1 0 0 1 0 0 0 7 0 1 0 0 1 0 0 0 8 0 1 0 0 1 0 0 0 9 0 1 0 0 1 0 0 0

10 0 1 0 0 1 0 0 0

3M 11 - - - - - - - 0

12 0 1 0 0 1 0 0 0

13 0 1 0 0 1 0 0 0

14 0 1 0 0 1 0 0 0

15 0 1 0 0 1 0 0 0

4M 16 0 1 0 0 1 0 0 0

17 0 1 0 0 1 0 0 0

18 0 1 0 0 1 0 0 0

19 0 1 0 0 1 0 0 0

20 0 1 0 0 1 0 0 0

Group / sex Animal

 No.

Animal 11 insufficient sample for analysis

 14

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Test Facility Study No. 459926
Appendix (continued)

Urinalysis: Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

UCol S.G. UVol

mL

UpH UProt

mg/dL

UGl

mg/dL

UKet

mg/dL

Uro

mg/dL

U.Bi

mg/dL

BP

mg/dL

Leu

cells/μL

1F 21 5 1.034 1.3 8.0 30 0 0 0.2 0.0 0.00 25

22 3 1.074 0.3 6.5 70 0 5 1.0 0.0 0.00 25

23 18 1.050 0.1 9.0 100 0 5 0.2 0.0 0.00 25

24 - - <0.1 - - - - - - - - 25 3 1.022 1.8 8.0 10 0 0 0.2 0.0 0.00 25

2F 26 3 1.036 0.3 7.0 30 0 0 0.2 0.0 0.00 25

27 18 1.048 0.4 9.0 70 0 0 0.2 0.0 0.00 25

28 5 1.036 1.7 8.5 30 0 0 0.2 0.0 0.00 25

29 22 1.056 0.1 9.0 100 0 0 0.2 0.0 0.00 25

30 5 1.041 0.9 8.0 30 0 0 0.2 0.0 0.00 25

3F 31 3 1.052 0.7 6.5 70 0 5 2.0 0.0 0.00 25

32 5 1.032 1.0 7.0 10 0 0 0.2 0.0 0.00 25

33 3 1.024 1.4 7.0 20 0 0 0.2 0.0 0.00 25

34 5 1.020 1.5 8.0 10 0 0 0.2 0.0 0.00 0

35 3 1.024 2.2 7.5 400 0 0 0.2 0.0 0.00 500

4F 36 5 1.040 0.6 9.0 30 0 0 0.2 0.0 0.00 25

37 5 1.084 0.3 6.5 100 10 10 2.0 0.0 0.00 75

38 3 1.026 1.2 8.0 20 0 0 0.2 0.0 0.00 25

39 3 1.032 0.3 7.0 20 0 0 0.2 0.0 0.00 25

40 18 1.060 1.2 9.0 50 0 0 0.2 0.0 0.00 25

Group / sex Animal

 No.

Animal 24 insufficient sample for analysis

 14

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Appendix (continued)

Urinalysis: Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Mic.E Mic.Cr Mic.W Mic.R Mic.O Mic.C Mic.A UTb

1F 21 0 1 0 0 1 0 0 0

22 0 1 0 0 1 0 0 0

23 0 1 0 0 1 0 0 0

24 - - - - - - - 0

25 0 1 0 0 1 0 0 0

2F 26 0 1 0 0 1 0 0 0

27 0 1 0 0 1 0 0 1

28 0 1 0 0 1 0 0 2

29 0 1 0 0 1 0 0 0

30 0 1 0 0 1 0 0 0

3F 31 0 1 0 0 1 0 0 0

32 0 1 0 0 1 0 0 0

33 0 1 0 0 1 0 0 0

34 0 1 0 0 1 0 0 0

35 0 1 0 0 1 0 0 1

4F 36 0 1 0 0 1 0 0 0

37 0 1 0 0 1 0 0 0

38 0 1 0 0 1 0 0 1

39 0 1 0 0 1 0 0 0

40 0 1 0 0 1 0 0 0

Group / sex Animal

 No.

Animal 24 insufficient sample for analysis

 14

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Appendix

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent)

1M 1 304 0.0522 1.90 0.8874 1.00 1.97 12.68 1.40 0.1290 0.1162

2 317 0.0472 1.93 1.0980 1.04 2.14 12.44 1.36 0.0657 0.0548

3 328 0.0733 2.09 0.9776 1.12 2.18 13.87 1.55 0.1200 0.2905

4 309 0.0511 1.92 1.0076 0.96 2.09 11.52 1.47 0.0812 0.1322

5 323 0.0580 1.94 1.0890 1.26 2.38 11.39 1.56 0.0770 0.1140

2M 6 330 0.0505 2.05 1.0300 1.09 2.39 15.43 1.58 0.0879 0.1144

7 315 0.0660 2.00 1.1600 1.11 2.38 14.12 1.48 0.0910 0.1290

8 325 0.0620 2.00 1.1280 1.13 2.12 10.86 1.49 0.1421 0.1488

9 308 0.0705 1.86 0.9612 1.09 2.17 11.95 1.32 0.1036 0.1814

10 302 0.0538 1.93 0.9392 0.98 2.10 10.53 1.34 0.0758 0.0953

Group / sex Animal

 No.

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

1M 1 0.008 0.331 0.50 0.4444 2.83 0.404 0.0157

2 0.006 0.331 0.50 0.4860 3.25 0.374 0.0149

3 0.006 0.389 0.50 0.5742 3.31 0.528 0.0282

4 0.011 0.345 0.58 0.6278 3.04 0.589 0.0182

5 0.010 0.502 0.51 0.4600 3.08 0.517 0.0197

2M 6 0.007 0.350 0.74 0.5143 3.49 0.488 0.0177

7 0.012 0.403 0.67 0.6200 3.42 0.271 0.0173

8 0.009 0.463 0.55 0.4861 3.55 0.580 0.0187

9 0.009 0.273 0.48 0.4687 3.24 0.365 0.0241

10 0.009 0.387 0.60 0.5466 3.65 0.416 0.0208

Group / sex Animal

 No.

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent)

3M 11 298 0.0582 1.92 1.0829 1.13 2.11 12.12 1.35 0.1038 0.2800

12 326 0.0281 1.91 1.0170 1.06 2.05 13.52 1.31 0.0494 0.1196

13 343 0.0587 2.03 1.0750 1.01 2.25 15.38 1.61 0.0828 0.4213

14 317 0.0582 1.99 0.9122 0.96 2.11 12.13 1.80 0.1002 0.1176

15 306 0.0470 1.84 1.1350 0.97 2.11 12.14 1.30 0.0780 0.1030

4M 16 350 0.0623 2.06 1.1649 1.14 2.31 13.08 1.55 0.1140 0.3555

17 295 0.0670 1.98 1.1010 1.08 2.26 12.95 1.44 0.1210 0.1410

18 359 0.0480 1.85 1.1540 1.20 2.36 13.56 1.69 0.1040 0.1180

19 318 0.0479 1.88 1.0244 0.95 2.03 11.87 1.25 0.1407 0.1374

20 298 0.0623 1.94 0.9628 1.01 2.09 9.96 1.27 0.1067 0.0764

Group / sex Animal

 No.

Animal 12 right adrenal gland lost at necropsy; therefore, excluded from statistical analysis

Animal 15 right adrenal gland incomplete weight; therefore excluded from statistical analysis

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

3M 11 0.005 0.367 0.60 0.4895 3.10 0.412 0.0157

12 0.008 0.352 0.37 0.5077 3.19 0.365 0.0246

13 0.009 0.403 0.54 0.5192 3.32 0.423 0.0170

14 0.007 0.325 0.48 0.5463 2.91 0.456 0.0197

15 0.010 0.263 0.49 0.4910 3.36 0.367 0.0198

4M 16 0.008 0.474 0.60 0.5677 3.37 0.685 0.0244

17 0.011 0.387 0.54 0.5880 3.36 0.363 0.0170

18 0.007 0.306 0.71 0.5580 3.46 0.452 0.0211

19 0.007 0.376 0.51 0.5557 3.33 0.573 0.0211

20 0.008 0.197 0.48 0.5088 3.49 0.484 0.0179

Group / sex Animal

 No.

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries

1F 21 224 0.0780 1.95 1.06 1.88 7.94 1.33 0.0950 0.1230 0.083

22 228 0.0780 1.80 0.90 1.56 8.81 1.10 0.1794 0.1296 0.096

23 217 0.0883 1.91 0.68 1.53 8.61 1.12 0.1727 0.1277 0.093

24 216 0.0900 1.85 0.80 1.67 8.74 1.28 0.1030 0.1350 0.100

25 237 0.0727 1.77 0.72 1.59 7.89 1.06 0.0771 0.0762 0.093

2F 26 225 0.0753 1.75 0.77 1.60 7.32 1.21 0.0998 0.1258 0.101

27 214 0.1002 1.86 0.90 1.73 7.51 1.13 0.1349 0.2214 0.114

28 245 0.0654 1.83 0.81 1.64 9.07 1.19 0.1143 0.0989 0.155

29 211 0.0797 1.73 0.94 1.49 10.24 1.35 0.0689 0.0806 0.086

30 228 0.0781 1.91 0.80 1.58 8.06 1.04 0.0889 0.0719 0.085

Group / sex Animal

 No.

Animal 29 died during blood sampling procedure; data not included in group mean values

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Spleen

Salivary

 Gland Thymus Thyroid Uterus

1F 21 0.012 0.41 0.3890 0.508 0.0237 0.63

22 0.013 0.55 0.4059 0.419 0.0200 0.50

23 0.011 0.48 0.3972 0.468 0.0212 0.94

24 0.012 0.44 0.4130 0.384 0.0213 0.45

25 0.008 0.36 0.4125 0.373 0.0192 0.55

2F 26 0.012 0.46 0.3751 0.507 0.0236 0.50

27 0.014 0.39 0.4104 0.447 0.0223 0.60

28 0.014 0.47 0.4143 0.607 0.0198 0.54

29 0.012 0.37 0.4509 0.451 0.0156 1.02

30 0.009 0.42 0.3655 0.402 0.0180 0.49

Group / sex Animal

 No.

Animal 29 died during blood sampling procedure; data not included in group mean values

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

 Body

Weight (g) Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries

3F 31 206 0.0791 1.84 0.79 1.66 8.00 1.10 0.0897 0.1273 0.096

32 213 0.0939 1.90 0.78 1.55 8.33 1.10 0.1580 0.0800 0.079

33 227 0.0790 1.88 0.88 1.60 8.64 1.26 0.0790 0.0960 0.094

34 194 0.1109 1.99 0.96 1.67 7.28 1.55 0.1337 0.1150 0.123

35 220 0.0890 1.86 0.82 1.88 9.06 1.34 0.1430 0.0710 0.109

4F 36 198 0.0749 1.87 0.73 1.47 6.93 1.11 0.1107 0.0752 0.092

37 217 0.0941 1.86 0.84 1.62 7.63 1.31 0.0741 0.0677 0.097

38 227 0.0897 1.94 0.82 1.69 7.66 1.25 0.1820 0.2268 0.096

39 213 0.0816 1.91 0.73 1.62 7.86 1.24 0.1197 0.1332 0.095

40 214 0.0779 1.88 0.71 1.56 7.68 1.12 0.0866 0.0852 0.079

Group / sex Animal

 No.

 15

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Appendix (continued)

Absolute Organ Weights (g): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Pituitary Spleen

Salivary

 Gland Thymus Thyroid Uterus

3F 31 0.008 0.53 0.3865 0.494 0.0178 1.12

32 0.011 0.49 0.4148 0.380 0.0188 0.36

33 0.011 0.54 0.3320 0.552 0.0175 0.52

34 0.011 0.41 0.3785 0.354 0.0221 0.67

35 0.010 0.45 0.3880 0.618 0.0186 1.02

4F 36 0.009 0.36 0.3725 0.333 0.0171 1.22

37 0.007 0.47 0.3994 0.652 0.0234 0.38

38 0.013 0.51 0.3394 0.530 0.0151 0.56

39 0.012 0.47 0.3979 0.301 0.0191 0.47

40 0.013 0.42 0.3998 0.443 0.0224 0.45

Group / sex Animal

 No.

 15

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Appendix

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Pituitary

1M 1 0.01717 0.625 0.29191 0.329 0.648 4.171 0.461 0.04243 0.03822 0.0026

2 0.01489 0.609 0.34637 0.328 0.675 3.924 0.429 0.02073 0.01729 0.0019

3 0.02235 0.637 0.29805 0.341 0.665 4.229 0.473 0.03659 0.08857 0.0018

4 0.01654 0.621 0.32608 0.311 0.676 3.728 0.476 0.02628 0.04278 0.0036

5 0.01796 0.601 0.33715 0.390 0.737 3.526 0.483 0.02384 0.03529 0.0031

2M 6 0.01530 0.621 0.31212 0.330 0.724 4.676 0.479 0.02664 0.03467 0.0021

7 0.02095 0.635 0.36825 0.352 0.756 4.483 0.470 0.02889 0.04095 0.0038

8 0.01908 0.615 0.34708 0.348 0.652 3.342 0.458 0.04372 0.04578 0.0028

9 0.02289 0.604 0.31208 0.354 0.705 3.880 0.429 0.03364 0.05890 0.0029

10 0.01781 0.639 0.31099 0.325 0.695 3.487 0.444 0.02510 0.03156 0.0030

Group / sex Animal

 No.

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

1M 1 0.1089 0.164 0.14618 0.931 0.1329 0.00516

2 0.1044 0.158 0.15331 1.025 0.1180 0.00470

3 0.1186 0.152 0.17506 1.009 0.1610 0.00860

4 0.1117 0.188 0.20317 0.984 0.1906 0.00589

5 0.1554 0.158 0.14241 0.954 0.1601 0.00610

2M 6 0.1061 0.224 0.15585 1.058 0.1479 0.00536

7 0.1279 0.213 0.19683 1.086 0.0860 0.00549

8 0.1425 0.169 0.14957 1.092 0.1785 0.00575

9 0.0886 0.156 0.15218 1.052 0.1185 0.00782

10 0.1281 0.199 0.18099 1.209 0.1377 0.00689

Group / sex Animal

 No.

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain

Epididy-

 mides Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Pituitary

3M 11 0.01953 0.644 0.36339 0.379 0.708 4.067 0.453 0.03483 0.09396 0.0017

12 0.00862 0.586 0.31196 0.325 0.629 4.147 0.402 0.01515 0.03669 0.0025

13 0.01711 0.592 0.31341 0.294 0.656 4.484 0.469 0.02414 0.12283 0.0026

14 0.01836 0.628 0.28776 0.303 0.666 3.826 0.568 0.03161 0.03710 0.0022

15 0.01536 0.601 0.37092 0.317 0.690 3.967 0.425 0.02549 0.03366 0.0033

4M 16 0.01780 0.589 0.33283 0.326 0.660 3.737 0.443 0.03257 0.10157 0.0023

17 0.02271 0.671 0.37322 0.366 0.766 4.390 0.488 0.04102 0.04780 0.0037

18 0.01337 0.515 0.32145 0.334 0.657 3.777 0.471 0.02897 0.03287 0.0019

19 0.01506 0.591 0.32214 0.299 0.638 3.733 0.393 0.04425 0.04321 0.0022

20 0.02091 0.651 0.32309 0.339 0.701 3.342 0.426 0.03581 0.02564 0.0027

Group / sex Animal

 No.

Animal 12 right adrenal gland lost at necropsy; therefore, excluded from statistical analysis

Animal 15 right adrenal gland incomplete weight; therefore, excluded from statistical analysis

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Prostate Spleen

Salivary

 Gland Testes Thymus Thyroid

3M 11 0.1232 0.201 0.16426 1.040 0.1383 0.00527

12 0.1080 0.113 0.15574 0.979 0.1120 0.00755

13 0.1175 0.157 0.15137 0.968 0.1233 0.00496

14 0.1025 0.151 0.17233 0.918 0.1438 0.00621

15 0.0859 0.160 0.16046 1.098 0.1199 0.00647

4M 16 0.1354 0.171 0.16220 0.963 0.1957 0.00697

17 0.1312 0.183 0.19932 1.139 0.1231 0.00576

18 0.0852 0.198 0.15543 0.964 0.1259 0.00588

19 0.1182 0.160 0.17475 1.047 0.1802 0.00664

20 0.0661 0.161 0.17074 1.171 0.1624 0.00601

Group / sex Animal

 No.

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries Pituitary

1F 21 0.03482 0.871 0.473 0.839 3.545 0.594 0.04241 0.05491 0.0371 0.0054

22 0.03421 0.789 0.395 0.684 3.864 0.482 0.07868 0.05684 0.0421 0.0057

23 0.04069 0.880 0.313 0.705 3.968 0.516 0.07959 0.05885 0.0429 0.0051

24 0.04167 0.856 0.370 0.773 4.046 0.593 0.04769 0.06250 0.0463 0.0056

25 0.03068 0.747 0.304 0.671 3.329 0.447 0.03253 0.03215 0.0392 0.0034

2F 26 0.03347 0.778 0.342 0.711 3.253 0.538 0.04436 0.05591 0.0449 0.0053

27 0.04682 0.869 0.421 0.808 3.509 0.528 0.06304 0.10346 0.0533 0.0065

28 0.02669 0.747 0.331 0.669 3.702 0.486 0.04665 0.04037 0.0633 0.0057

29 - - - - - - - - - - 30 0.03425 0.838 0.351 0.693 3.535 0.456 0.03899 0.03154 0.0373 0.0039

Group / sex Animal

 No.

Animal 29 died during blood sampling procedure

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day) ::: 1

Control 0 2---------- 100 3Alcohols, C18-22

300 4

---------- 1000

Spleen

Salivary

 Gland Thymus Thyroid Uterus

1F 21 0.183 0.17366 0.2268 0.01058 0.281

22 0.241 0.17803 0.1838 0.00877 0.219

23 0.221 0.18304 0.2157 0.00977 0.433

24 0.204 0.19120 0.1778 0.00986 0.208

25 0.152 0.17405 0.1574 0.00810 0.232

2F 26 0.204 0.16671 0.2253 0.01049 0.222

27 0.182 0.19178 0.2089 0.01042 0.280

28 0.192 0.16910 0.2478 0.00808 0.220

29 - - - - - 30 0.184 0.16031 0.1763 0.00789 0.215

Group / sex Animal

 No.

Animal 29 died during blood sampling procedure

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Adrenals Brain Heart Kidneys Liver Lung

L Node 

(Mandib)

L Node 

(Mesent) Ovaries Pituitary

3F 31 0.03840 0.893 0.383 0.806 3.883 0.534 0.04354 0.06180 0.0466 0.0039

32 0.04408 0.892 0.366 0.728 3.911 0.516 0.07418 0.03756 0.0371 0.0052

33 0.03480 0.828 0.388 0.705 3.806 0.555 0.03480 0.04229 0.0414 0.0048

34 0.05716 1.026 0.495 0.861 3.753 0.799 0.06892 0.05928 0.0634 0.0057

35 0.04045 0.845 0.373 0.855 4.118 0.609 0.06500 0.03227 0.0495 0.0045

4F 36 0.03783 0.944 0.369 0.742 3.500 0.561 0.05591 0.03798 0.0465 0.0045

37 0.04336 0.857 0.387 0.747 3.516 0.604 0.03415 0.03120 0.0447 0.0032

38 0.03952 0.855 0.361 0.744 3.374 0.551 0.08018 0.09991 0.0423 0.0057

39 0.03831 0.897 0.343 0.761 3.690 0.582 0.05620 0.06254 0.0446 0.0056

40 0.03640 0.879 0.332 0.729 3.589 0.523 0.04047 0.03981 0.0369 0.0061

Group / sex Animal

 No.

 16

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Appendix (continued)

Relative Organ Weights (% Body Weight): Individual Values

Group

Test Item

Dosage (mg/kg/day)

:

:

:

1

Control

0

2

---------- 100

3

Alcohols, C18-22

300

4

---------- 1000

Spleen

Salivary

 Gland Thymus Thyroid Uterus

3F 31 0.257 0.18762 0.2398 0.00864 0.544

32 0.230 0.19474 0.1784 0.00883 0.169

33 0.238 0.14626 0.2432 0.00771 0.229

34 0.211 0.19510 0.1825 0.01139 0.345

35 0.205 0.17636 0.2809 0.00845 0.464

4F 36 0.182 0.18813 0.1682 0.00864 0.616

37 0.217 0.18406 0.3005 0.01078 0.175

38 0.225 0.14952 0.2335 0.00665 0.247

39 0.221 0.18681 0.1413 0.00897 0.221

40 0.196 0.18682 0.2070 0.01047 0.210

Group / sex Animal

 No.

 16

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Appendix 

Individual Necropsy and Histological Findings 

Abbreviations used 

ADR = Adrenal Gland PCEX = Pancreas (Exocrine) 

AOR = Aorta PIT = Pituitary Gland 

BRA = Brain PRO = Prostate 

CAE = Caecum REC = Rectum 

COL = Colon SCI = Sciatic Nerve 

DUO = Duodenum SEM = Seminal Vesicle 

EPI = Epididymis SGSM = Salivary Gland (Submaxillary) 

EYE = Eye SGSL = Salivary Glands (Submandibular) 

FEM = Femur SKI = Skin and Subcutis 

HAR = Harderian Glands SKM = Skeletal Muscle 

HEA = Heart SPL = Spleen 

ILE = Ileum SPN = Spinal Cord 

JEJ = Jejunum STO = Stomach 

JNT = Joint STR = Sternum 

KID = Kidney TES = Testis 

LIV = Liver THM = Thymus 

LUN = Lung THR = Thyroid Gland 

LNMA = Mandibular Lymph Nodes TOG = Tongue 

LNMS = Mesenteric Lymph Nodes TRA = Trachea 

MAM = Mammary Gland URB = Urinary Bladder 

MAR = Marrow Smear UTE = Uterus 

OES = Oesophagus VAG = Vagina 

OPT = Optic Nerve 

OVA = Ovary 

PAR = Parathyroid Gland 

PCEN = Pancreas (Endocrine) 

 

17

 

 

 

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Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

TREATMENT: Group 1 (Control) MALES 

ANIMAL NO: FINDINGS: 

 1 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 THYMUS : Speckled, (both lobes) 

 HISTOLOGICAL FINDINGS: 

 THYMUS : Agonal congestion/haemorrhage, 

 (relates to necropsy finding) 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PAR , PIT , PRO , REC , SGSL, 

 SGSM, SCI , SEM , SKM , SKI , SPN , 

 SPL , STR , STO , TES , THM , THR , 

 TOG , TRA , URB 

 2 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 LYMPH NODE (MANDIBULAR) : Reactive hyperplasia, mild 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 174

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) MALES 

ANIMAL NO: FINDINGS: 

 2 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMS, MAM , OES , OPT , PCEN, PCEX, 

 PAR , PIT , PRO , REC , SGSL, SGSM, 

 SCI , SEM , SKM , SKI , SPN , SPL , 

 STR , STO , TES , THM , THR , TOG , 

 TRA , URB 

 3 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 KIDNEY : Basophilic tubules, minimal 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , PCEN, PCEX, 

 PAR , PIT , PRO , REC , SGSL, SGSM, 

 SCI , SEM , SKM , SKI , SPN , SPL , 

 STR , STO , TES , THM , THR , TOG , 

 TRA , URB 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 175

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) MALES 

ANIMAL NO: FINDINGS: 

 4 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

 HISTOLOGICAL FINDINGS: 

 EPIDIDYMIS : Sperm granuloma, unilateral, 

 moderate 

 LUNG : No histological correlation with 

 necropsy finding 

 PARATHYROID GLAND : Only one examined 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , PCEN, PCEX, 

 PAR , PIT , PRO , REC , SGSL, SGSM, 

 SCI , SEM , SKM , SKI , SPN , SPL , 

 STR , STO , TES , THM , THR , TOG , 

 TRA , URB 

 5 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 ADRENAL GLAND : Only one medulla examined 

 SPLEEN : Extramedullary haemapoiesis, minimal 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 176

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) MALES 

ANIMAL NO: FINDINGS: 

 5 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PAR , PIT , PRO , REC , SGSL, 

 SGSM, SCI , SEM , SKM , SKI , SPN , 

 STR , STO , TES , THM , THR , TOG , 

 TRA , URB 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 177

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

TREATMENT: Group 2 (100 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 6 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 7 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Pale, all lobes 

 Dark focus, all lobes, red, (up to 1 

 mm) 

 8 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

 9 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 178

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 2 (100 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 10 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

 Dark focus, all lobes, many, red, (up 

 to 3 mm) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 179

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

TREATMENT: Group 3 (300 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 11 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 SKIN AND SUBCUTIS : Scab, (dorsal neck, 2 mm) 

 12 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 13 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 14 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 180

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 3 (300 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 15 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 181

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

TREATMENT: Group 4 (1000 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 16 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PAR , PIT , PRO , REC , SGSL, 

 SGSM, SCI , SEM , SKM , SKI , SPN , 

 SPL , STR , STO , TES , THM , THR , 

 TOG , TRA , URB 

 17 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 PARATHYROID GLAND : Tissue absent from section. No more 

 available 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PIT , PRO , REC , SGSL, SGSM, 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 182

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 4 (1000 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 17 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 SCI , SEM , SKM , SKI , SPN , SPL , 

 STR , STO , TES , THM , THR , TOG , 

 TRA , URB 

 18 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Dark focus, all lobes, red, (up to 2 

 mm, slight) 

 HISTOLOGICAL FINDINGS: 

 KIDNEY : Basophilic tubules, minimal 

 LUNG : Agonal congestion/haemorrhage, 

 (relates to necropsy finding) 

 Inflammatory cell infiltration, 

 perivascular, minimal 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , LIV , LNMA, LNMS, 

 MAM , OES , OPT , PCEN, PCEX, PAR , 

 PIT , PRO , REC , SGSL, SGSM, SCI , 

 SEM , SKM , SKI , SPN , SPL , STR , 

 STO , TES , THM , THR , TOG , TRA , 

 URB 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 183

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 4 (1000 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 19 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PAR , PIT , PRO , REC , SGSL, 

 SGSM, SCI , SEM , SKM , SKI , SPN , 

 SPL , STR , STO , TES , THM , THR , 

 TOG , TRA , URB 

 20 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 PARATHYROID GLAND : Only one examined 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EPI , EYE , FEM , HAR , HEA , 

 ILE , JEJ , JNT , KID , LIV , LUN , 

 LNMA, LNMS, MAM , OES , OPT , PCEN, 

 PCEX, PAR , PIT , PRO , REC , SGSL, 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 184

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 4 (1000 mg/kg/day) MALES 

ANIMAL NO: FINDINGS: 

 20 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 SGSM, SCI , SEM , SKM , SKI , SPN , 

 SPL , STR , STO , TES , THM , THR , 

 TOG , TRA , URB 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 185

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) FEMALES 

ANIMAL NO: FINDINGS: 

 21 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 ADRENAL GLAND : Only one medulla examined 

 LIVER : Inflammatory cell infiltration, 

 focal, minimal 

 VAGINA : Oestrous cycle: metoestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LUN , LNMA, LNMS, 

 MAM , OES , OPT , OVA , PCEN, PCEX, 

 PAR , PIT , REC , SGSL, SGSM, SCI , 

 SKM , SKI , SPN , SPL , STR , STO , 

 THM , THR , TOG , TRA , URB , UTE , 

 VAG 

 22 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 HEART : Only one atria examined 

 SPLEEN : Extramedullary haemapoiesis, minimal 

 VAGINA : Oestrous cycle: metoestrus 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 186

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) FEMALES 

ANIMAL NO: FINDINGS: 

 22 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

 SCI , SKM , SKI , SPN , STR , STO , 

 THM , THR , TOG , TRA , URB , UTE , 

 VAG 

 23 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

 UTERUS : Dilated, with fluid, both horns, (2 

 mm, clear) 

 HISTOLOGICAL FINDINGS: 

 LUNG : No histological correlation with 

 necropsy finding 

 MAMMARY GLAND : Tissue absent from section. No more 

 available 

 UTERUS : Oestrus dilation, (relates to 

 necropsy finding) 

 VAGINA : Oestrous cycle: oestrus 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 187

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) FEMALES 

ANIMAL NO: FINDINGS: 

 23 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, OES , OPT , OVA , PCEN, PCEX, 

 PAR , PIT , REC , SGSL, SGSM, SCI , 

 SKM , SKI , SPN , SPL , STR , STO , 

 THM , THR , TOG , TRA , URB , UTE , 

 VAG 

 24 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

 HISTOLOGICAL FINDINGS: 

 LUNG : No histological correlation with 

 necropsy finding 

 VAGINA : Oestrous cycle: dioestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

 SCI , SKM , SKI , SPN , SPL , STR , 

 STO , THM , THR , TOG , TRA , URB , 

 UTE , VAG 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 188

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 1 (Control) FEMALES 

ANIMAL NO: FINDINGS: 

 25 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 PARATHYROID GLAND : Only one examined 

 VAGINA : Oestrous cycle: metoestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

 SCI , SKM , SKI , SPN , SPL , STR , 

 STO , THM , THR , TOG , TRA , URB , 

 UTE , VAG 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 189

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 2 (100 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 26 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 27 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 28 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 29 Found Dead 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Reddened, all lobes 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 190

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 2 (100 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 30 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 191

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 3 (300 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 31 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 UTERUS : Dilated, with fluid, both horns, (2 

 mm, clear) 

 32 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 33 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 34 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 192

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 3 (300 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 35 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 193

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 4 (1000 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 36 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 KIDNEY : Mineralisation, corticomedullary, 

 minimal 

 PARATHYROID GLAND : Only one examined 

 UTERUS : Oestrus dilation 

 VAGINA : Oestrous cycle: oestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , LIV , LUN , LNMA, LNMS, 

 MAM , OES , OPT , OVA , PCEN, PCEX, 

 PAR , PIT , REC , SGSL, SGSM, SCI , 

 SKM , SKI , SPN , SPL , STR , STO , 

 THM , THR , TOG , TRA , URB , UTE , 

 VAG 

 37 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Dark, all lobes 

 HISTOLOGICAL FINDINGS: 

 LUNG : No histological correlation with 

 necropsy finding 

 PARATHYROID GLAND : Only one examined 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 194

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 

TREATMENT: Group 4 (1000 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 37 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 VAGINA : Oestrous cycle: dioestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

 SCI , SKM , SKI , SPN , SPL , STR , 

 STO , THM , THR , TOG , TRA , URB , 

 UTE , VAG 

 38 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 ADRENAL GLAND : Only one medulla examined 

 PARATHYROID GLAND : Only one examined 

 VAGINA : Oestrous cycle: dioestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

(CONTINUED) 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 195

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

 TREATMENT: Group 4 (1000 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 38 (CONTINUED) 

 HISTOLOGICAL FINDINGS: 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 SCI , SKM , SKI , SPN , SPL , STR , 

 STO , THM , THR , TOG , TRA , URB , 

 UTE , VAG 

 39 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : All tissues normal 

 HISTOLOGICAL FINDINGS: 

 PITUITARY GLAND : Only anterior lobe examined 

 VAGINA : Oestrous cycle: dioestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , KID , LIV , LUN , LNMA, 

 LNMS, MAM , OES , OPT , OVA , PCEN, 

 PCEX, PAR , PIT , REC , SGSL, SGSM, 

 SCI , SKM , SKI , SPN , SPL , STR , 

 STO , THM , THR , TOG , TRA , URB , 

 UTE , VAG 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

17

 

 

 

Page 196

Test Facility Study No. 459926
Appendix (continued) 

Individual Necropsy and Histological Findings 

TREATMENT: Group 4 (1000 mg/kg/day) FEMALES 

ANIMAL NO: FINDINGS: 

 40 Terminal Kill 

 Day of Necropsy: 29 

 NECROPSY FINDINGS: 

 GENERAL COMMENTS : Tissues not listed below were normal 

 LUNG : Dark focus, right cranial lobe, red, 

 (one, 2 mm) 

 LYMPH NODE (MANDIBULAR) : Reddened 

 SKIN AND SUBCUTIS : Hair loss, (dorsal neck) 

 HISTOLOGICAL FINDINGS: 

 KIDNEY : Inflammatory cell foci, cortical, 

 minimal 

 LIVER : Inflammatory cell infiltration, 

 focal, minimal 

 LUNG : No histological correlation with 

 necropsy finding 

 LYMPH NODE (MANDIBULAR) : Agonal congestion/haemorrhage, 

 (accounts for necropsy finding) 

 PARATHYROID GLAND : Only one examined 

 PITUITARY GLAND : Only anterior lobe examined 

 SKIN AND SUBCUTIS : No histological correlation with 

 necropsy finding 

 THYROID GLAND : Only one examined 

 VAGINA : Oestrous cycle: dioestrus 

 ORGANS EXAMINED AND NO ABNORMALITY DETECTED: 

 ADR , AOR , MAR , BRA , CAE , COL , 

 DUO , EYE , FEM , HAR , HEA , ILE , 

 JEJ , JNT , LUN , LNMA, LNMS, MAM , 

 OES , OPT , OVA , PCEN, PCEX, PAR , 

 PIT , REC , SGSL, SGSM, SCI , SKM , 

 SKI , SPN , SPL , STR , STO , THM , 

 THR , TOG , TRA , URB , UTE , VAG 

Pathology File Ref.: MICLIS_459926_LL_KEEP1.SPL 

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