## 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 An c kelmannsplatz 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

........................................................................................................ Page 2 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

........................................................................................................... Page 3 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

........................................................................................................... Page 4 Test Facility Study No. 459926

## LIST OF FIGURES

Figure 1 : Cage Plan 33

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

............................................... Page 5 Test Facility Study No. 459926

## 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

.................................................................. Page 6 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

........................................ Page 7 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 Page 10 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 peri od of at least 28 days. Three groups of 5 male and 5 female Han Wistar rats were administer ed Alcohols, C18-22, distn. residue s 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 we ight as the treated animals. Animals were monitored regularly for viability and for signs of ill health or reaction to treatment. The following activities were measur ed 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), functi onal 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 we re unaffected by treatment. There were no treatment-related ocular findings. There were no treatment-related haematology, coa gulation or clinical chemistry changes. There were no necropsy or histology findings attri buted to treatment. In conclusion, repeat oral administration of Al cohols, C18-22, distn. re sidues 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-Eff ect-Level (NOEL) in this study. Page 11 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 w ith 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 De partment 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 th is study as this route has been defined by the Sponsor as a possible route of human exposure. Th e 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 wa s 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 Germa ny GmbH, Anckelmannsplatz 1, Hamburg 20537, Germany and was conducted at Charles Rive r, 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 Histopathol ogy Evaluation): 25 March 2010 Study Completion Date: See Complian ce Statement page for date of Study Director’s signature

6. EXPERIMENTAL PROCEDURE

6.1. Test Item Alcohols, C18-22, distn. re sidues (CAS No. 1160164-88-4). A shipment of 900 g of Alcohols, C18-22, dist n. residues; CAS No. 1160164-88-4 (Batch No. 03585/MA; product code: 59B1RN2) was receiv ed 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 e xpiry date of August 2013 were provided by SASOL Germany GmbH. Page 12 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 characte ristics, which appropriately defined the batch from which Alcohols, C18-2 2, 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 synthesi s, fabrication or derivation we re the responsibility of the Sponsor. A reference sample (approximately 100 mg) of Alcohols, C18-22, distn. residues was taken and stored under the conditions specif ied 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 visibl y 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 cons istent across all groups. The formulations were prepared up to 8 days in advance and were stored at ambient la boratory 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 Da y 1 and during Week 4 of dosing. The samples were stored at ambient laboratory temperat ure in the dark prior to analysis. The samples were analysed at Charles River using a validated met hod (Charles River Study No. 425902). All samples analysed demonstrated satisfact ory accuracy and con centration (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). Page 13 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 week s 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 an imal was electronically tagged using a cylindrical, ‘glass-sealed’ microchip, whic h 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 pol ypropylene cages with stainless steel grid tops and solid bottom. Wood shavings (supplie d by Datesand, Manchester, UK) were used as bedding and were changed when necessary. All cages were equipped with metal food hoppe r and a polycarbonate water bottle with a Durethan® cap and stainless steel nozzle. A wooden chewstick (pr oduced by Tapvei Estonia OÜ, Harjumaa, Estonia) was placed in each cage for an environmental enrichment and replaced as necessary. Certific ates for bedding and chewsticks were retained within the study data. Analysis did not provide evidence of c ontamination 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 c ontrol 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 contro lled to provide a 12- hour light/dark cycle. (light hours being 0700-1900). Page 14 Test Facility Study No. 459926

## Temperature and humidity were monitored dail y. During the acclima tisation/pretrial and treatment periods, temperature was recorded be tween 19 to 23oC and humidity was recorded between 36 to 66%. On one occasion during th e 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, theref ore, considered not to have affected the outcome of the study.

6.2.5. Room Sanitation The walls, ceiling and other surfaces of the an imal 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 we re swept and then m opped with disinfectant solution (0.5% Tego 2000, supplied by Th. Goldsc hmidt 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. Ea ch batch of diet was routinely analysed by the supplier for various nu tritional components and ch emicals and microbiological contaminants.

Water taken from the domestic mains was f eely 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 di ssolved materials, h eavy metals, pesticide residues, pH, nitrates, nitrites and sel ected bacteria are periodically provided. Food and water analysis did not provide evid ence of contamination that might have prejudiced the outcome of the study. Certif icates 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 Page 15 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 af ter examination of pre liminary 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 vol ume 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 numbe rs (Day 2, etc.) also followed this pattern. Body weights recorded on the validated computer system on th e 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 pa ttern (i.e., body weights recorded on Day 2 of treatment were documented as Day 1 body weight s). Recording of food consumption and clinical signs also followed this pattern.

7.3. Treatment of Data This report contains serial observations pe rtaining to each day of the study before commencement of necropsy. It also contains serial observations rela ting 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. Page 16 Test Facility Study No. 459926

## 8.3. Additional Clinical Observations

All animals were examined for reaction to trea tment at regular hourly intervals throughout the day, starting immediately post dose, with particul ar attention being paid to the first few hours after dosing. Some clinical signs were not re corded at the specified timepoin t stated in Study Note 1. For example, clinical sign for Animal 11 was record ed beyond +4 h time segment (close to +5 h). These deviations were considered not to have a ffected the outcome or integrity of the study.

8.4. Detailed Functional Observations Once during Week 4, a more detailed examin ation 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. Befo re the independent technician entered the animal room to perform the examination, th e 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 electroni c identification chip. Page 17 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 - record ed 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 ru mp 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 Page 18 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 ta il 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, pr one 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 prin ts 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 de tectors. 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 retu rned 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 record ed in the above screening battery.

8.5. Body Weights Body weights were recorded twice during pret rial, then daily during the dosing period. Body weights are reported twice weekly, with the final body wei ght 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 monitore d on a weekly basis throughout the study. Page 19 Test Facility Study No. 459926

## 8.7. Ophthalmology Examinations The eyes of all animals (including spares) we re examined once during the pretrial period using an indirect ophthalmoscope after the applic ation of a mydriatic ag ent (1% Tropicamide, Mydriacyl ® 

## ). Anterior, lenticular and fundic areas were evaluated. An ophthalmoscopic examination was performe d 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 schedul ed haematology, coagulation and clinical chemistry were collected from all animals via the orbital sinus under isoflurane anaesthesia using a capillary tube, and tran sferred into plastic tubes cont aining anticoagulant prior to terminal kill.

8.8.2. Haematology Blood samples ( ca 0.5 mL) were taken into tubes cont aining 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 x10 12 

### /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 x10 9 

### /L 

## Page 20 Test Facility Study No. 459926

### Parameter Instrument/Methodology Unit

N eutrophils: (Neut) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Lymphocytes: (Lymph) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Monocytes: (Mono) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Eosinophils: (Eos) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Basophils: (Baso) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Large Unclassified Cells: (LUC) Bayer, ADVIA 120 haematology analyser x10 9 

### /L

Platelet Count: (Plat) Bayer, ADVIA 120 haematology analyser x10 9 

### /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 fi nal 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 thromboplas tin 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 

## Page 21 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 Al bumin 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 Chemistr y 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 Chemistr y 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 Chemistr y Analyser using indirect Ion Selective Electrode. Application of th e 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 "C linical 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 duri ng 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 appear ance 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 expos ure to a rising concentration of carbon dioxide. Immediately after death, each an imal was weighed and the exsanguinated by severance of major blood vessels. A random orde r was used for the necropsy of the animals.

8.9.2. Gross Necropsy Necropsy was performed for all animals under th e 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 examin ation to include body orifices (ears, nostrils, mouth, anus, and vulva ) and cranial, thoracic and abdominal organs and tissues. All gross lesions were recorded in descrip tive 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 indivi dual 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 buffe red 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 includ ing 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 th e 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) an d evaluated by a pathologist. An internal peer review was undertaken. An appropriate ly qualified and experienced veterinary pathologist validated the conc lusions of the Study Pathologist , by independently assessing the microscope slides.

9. ELECTRONIC DATA ACQUISITION AND SYSTEMS

In addition to the built-in software of labor atory devices and instru ments, 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/Histopat hology: PLACES 2000 1.1 Page 27 Test Facility Study No. 459926

## 9.1. Statistical Analysis Unless otherwise stated, all statistical test s were two-sided and performed at the 5% significance level using in-house software. Ma les 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, coagul ation, clinical chemistry and selected urinalysis, motor activity and quantitative FO B measurement data were analysed for homogeneity of variance using the ‘F-Max' test. If the group variances appeared homogeneous, a parametric ANOVA was used a nd 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 va riances 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 Ma x test due to zero standard deviation in at least one group, the n on-parametric ANOVA resu lts were reported. Organ weights were analysed using ANOVA as above and by analysis of covariance (ANCOVA) using terminal kill body weight as covariate. In additi on, organ weights as a percentage of terminal body weight were anal ysed using ANOVA as above as an exploratory analysis.

In circumstances where the variances in th e ANCOVA remain heterogeneous following log or square root transformations, the data was subject ed to a rank transformati on prior to analysis. Where it was not possible to perform the F-Ma x 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 significan ce 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 (e xtended to ± 15%) indicating accepta ble accuracy of formulations.

10.2. Observations

10.2.1. Mortality and Clinical Ob servations (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 consid ered not to be relate d to treatment with Alcohols, C18-22, distn. residues.

There were no treatment-re lated 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 treat ed groups generally resemb led those displayed by their respective Controls, with similar overall activity values reported for each sex. Slight variances from Control values were not ed throughout the timepoints. However, due to a lack of statistical significance, consistenc y between sexes, evidence of a dose-related response or further corroborating data, it was co nsidered that these differences were not treatment related.

10.2.2.3. Quantitative Functional Observ ations (Table 3; Appendix 6) All treated groups closely resembled their resp ective 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 cons idered 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 wa s 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 sta tistical significance on Day 7. However, this was considered not to be a treatment-related effect because this difference was consistent from the beginning of pr etrial period until the end of dosing period.

10.2.5. Ophthalmology (Appendix 11)

There were no treatment-re lated 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 male s, but the changes did not attain statistical significance. The aetio logy of the slight disturbances in monocyte counts in animals receiving the test item is unclear, but th e 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 occurr ed when compared with Controls, some of which attained statistical significance. These di fferences 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 obser ved 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 Cont rol values were noted for seve ral parameters across male and female treated groups. However, due to a l ack of a dose-related response, statistical significance or any further supportive evidence, th ese 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 cha nges in the urinalysis data.

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

There were no treatment-relate d 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 weight s. As this finding did not demonstrate a dose-related response and as no histopathological changes corr elated, 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 we re those commonly seen in rats of this age and strain at Charles River, Preclinic al Services Edinburgh.

10.2.9. Histopathology (Table 13; Appendix 17) There were no histopathological find ings considered to be relate d to treatment with Alcohols, C18-22, distn. residues. All findings recorded were typi cal background findings for rats of this age and strain at Charles River, Preclinic al 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 toxic ity being noted. Therefore, the dose of 1000 mg/kg/day was considered to be a No-Obser ved-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



## 1Page 33Test 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 3 

### Alcohols, 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 1

2 3 4



### DayBody Weight (g) 

## 2Page 34Test 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 3 

### Alcohols, 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 1

2 3 4



### DayBody Weight (g) 

## 2Page 35Test 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 Grooming

n 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



## 1Page 36Test Facility Study No. 459926

## (continued) 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 Grooming

n 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



## 1Page 37Test 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



## 2Page 38Test Facility Study No. 459926

## (continued) 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

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



## 2Page 39Test 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 

## 3Page 40Test 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 

## 3Page 41Test 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 

## 3Page 42Test 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 

## 3Page 43Test 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



## 4Page 44Test Facility Study No. 459926

## (continued) 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

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



## 4Page 45Test 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



## 5Page 46Test Facility Study No. 459926

## (continued) 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

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



## 5Page 47Test 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

----------- Mono x10Ä/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



## 6Page 48Test Facility Study No. 459926

## (continued) 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

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



## 6Page 49Test Facility Study No. 459926

## (continued) 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

----------- Mono x10Ä/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



## 6Page 50Test Facility Study No. 459926

## (continued) 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

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



## 6Page 51Test 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



## 7Page 52Test Facility Study No. 459926

## (continued) 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

AG-R Na mmol/L K mmol/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



## 7Page 53Test Facility Study No. 459926

## (continued) 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

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



## 7Page 54Test Facility Study No. 459926

## (continued) 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

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



## 7Page 55Test Facility Study No. 459926

## Table Urinalysis: Group Mean Values

Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 

### 0 2

---------- 

### 100 3 Alcohols, 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



## 8Page 56Test Facility Study No. 459926

## (continued) Table Urinalysis: Group Mean Values

Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 

### 0 2

---------- 

### 100 3 Alcohols, 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



## 8Page 57Test 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



## 9Page 58Test Facility Study No. 459926

## (continued) 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

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



## 9Page 59Test Facility Study No. 459926

## (continued) 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 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



## 9Page 60Test Facility Study No. 459926

## (continued) 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

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



## 9Page 61Test 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



## 10Page 62Test Facility Study No. 459926

## (continued) 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

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



## 10Page 63Test Facility Study No. 459926

## (continued) 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 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



## 10Page 64Test Facility Study No. 459926

## (continued) 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

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



## 10Page 65Test 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



## 11Page 66Test Facility Study No. 459926

## (continued) 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

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



## 11Page 67Test Facility Study No. 459926

## (continued) 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 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



## 11Page 68Test Facility Study No. 459926

## (continued) 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

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



## 11Page 69Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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100 3 Alcohols, C18-22 300 4

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1000 

## Table Summary of Necropsy Findings

GROUP TOTALS Males Females NECROPSY FINDINGS GROUP Grp 1 Grp 2 Gr p 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 

## 12Page 70Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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1000 

## Table (continued) Summary of Necropsy Findings

GROUP TOTALS Males Females NECROPSY FINDINGS GROUP Grp 1 Grp 2 Gr p 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 

## 12Page 71Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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----------

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 Contro l: * 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 

## 13Page 72Test 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 Contro l: * 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 

## 13Page 73Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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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 Contro l: * 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 

## 13Page 74Test 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 Contro l: * 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 

## 13Page 75Test 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 Contro l: * 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 

## 13Page 76Test 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 Contro l: * 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 

## 13Page 77Test 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 Contro l: * 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 

## 13Page 78Test 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 Contro l: * 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 

## 13Page 79Test 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 Contro l: * 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 

## 13Page 80Test 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 Contro l: * 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 

## 13Page 81Test 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 

## 3Page 85Test 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 4Page 86Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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100 3 Alcohols, C18-22 300 4

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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 

## 4Page 87Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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100 3 Alcohols, C18-22 300 4

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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 

## 4Page 88Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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100 3 Alcohols, C18-22 300 4

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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 

## 4Page 89Test Facility Study No. 459926

### Group Test Item Dosage (mg/kg/day) :
:
: 1 Control 0 2

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100 3 Alcohols, C18-22 300 4

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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 

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## 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 

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## 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 

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## Appendix Individual Clinical Signs: F unctional Observation Battery

Detailed Functional Observations
In this appendix, the data is presented as it is obtained from the computerised syst em. The data reported combines observation s collected from 3 environments noted as:
(a) = standardised arena (c) = cage-side (H) = observation in the hand
For operational reasons the in-life data captu re system has been set up to record the first day of treatment as Day 0. As a co nsequence 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. Anim al numbers in this appen dix relate to their ne urotoxicity number 6Page 93Test Facility Study No. 459926

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

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## Appendix (continued) Individual Clinical Signs: F unctional 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 

## 6Page 111Test 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: F unctional 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 

## 6Page 112Test 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: F unctional 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 

## 6Page 113Test 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: F unctional 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 

## 6Page 114Test 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: F unctional 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 

## 6Page 115Test 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: F unctional 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 

## 6Page 116Test 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: F unctional 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 

## 6Page 117Test 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: F unctional 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 

## 6Page 118Test 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: F unctional 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 

## 6Page 119Test 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: F unctional 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 

## 6Page 120Test 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: F unctional 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 

## 6Page 121Test 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: F unctional 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 

## 6Page 122Test 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: F unctional 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 

## 6Page 123Test 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: F unctional 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 

## 6Page 124Test 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: F unctional 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 

## 6Page 125Test 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: F unctional 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 

## 6Page 126Test 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: F unctional 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 

## 6Page 127Test 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: F unctional 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 

## 6Page 128Test 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: F unctional 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 

## 6Page 129Test 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: F unctional 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 

## 6Page 130Test 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 Grooming

n 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



## 7Page 131Test 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 Grooming

n 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. 

## 7Page 132Test 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. 

## 8Page 133Test 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. 

## 8Page 134Test 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



## 9Page 135Test 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



## 9Page 136Test 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. 

## 10Page 137Test 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. 

## 10Page 138Test 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 

## 11Page 139Test 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 

## 11Page 140Test 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

---------- Mono x10Ä/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



## 12Page 141Test 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

Plat x10Ä/L PT

s 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



## 12Page 142Test 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

---------- Mono x10Ä/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



## 12Page 143Test 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

Plat x10Ä/L PT

s 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



## 12Page 144Test 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

---------- Mono x10Ä/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. 

## 12Page 145Test 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

Plat x10Ä/L PT

s 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



## 12Page 146Test 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

---------- Mono x10Ä/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



## 12Page 147Test 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

Plat x10Ä/L PT

s 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



## 12Page 148Test 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



## 13Page 149Test 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

AG-R Na mmol/L K mmol/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. 

## 13Page 150Test 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



## 13Page 151Test 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

AG-R Na mmol/L K mmol/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. 

## 13Page 152Test 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



## 14Page 153Test 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

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



## 14Page 154Test 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



## 14Page 155Test 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

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



## 14Page 156Test Facility Study No. 459926

## 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. 

## 15Page 157Test Facility Study No. 459926

## 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. 

## 15Page 158Test Facility Study No. 459926

## 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



## 15Page 159Test Facility Study No. 459926

## 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. 

## 15Page 160Test Facility Study No. 459926

## 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



## 15Page 161Test Facility Study No. 459926

## 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



## 15Page 162Test Facility Study No. 459926

## 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. 

## 15Page 163Test Facility Study No. 459926

## 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. 

## 15Page 164Test Facility Study No. 459926

## 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. 

## 16Page 165Test Facility Study No. 459926

## 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. 

## 16Page 166Test Facility Study No. 459926

## 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



## 16Page 167Test Facility Study No. 459926

## 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. 

## 16Page 168Test Facility Study No. 459926

## 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



## 16Page 169Test Facility Study No. 459926

## 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

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



## 16Page 170Test Facility Study No. 459926

## 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. 

## 16Page 171Test Facility Study No. 459926

## 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. 

## 16Page 172Test Facility Study No. 459926

## 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 Page 173 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 cong estion/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 : Reddene d, 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 : Reddene d, 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 : Reddene d, 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 : Reddene d, 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 : Reddene d, 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 : Reddene d, 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 : Reddene d, 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 

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## 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 an terior 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 

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## 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, ri ght 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) : A gonal congestion/haemorrhage, (accounts for necropsy finding) PARATHYROID GLAND : Only one examined PITUITARY GLAND : Only an terior 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 

## 17 Page 197 Test Facility Study No. 459926