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EC number: 247-979-2 | CAS number: 26761-45-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,3-epoxypropyl neodecanoate
- EC Number:
- 247-979-2
- EC Name:
- 2,3-epoxypropyl neodecanoate
- Cas Number:
- 26761-45-5
- Molecular formula:
- C13H24O3
- IUPAC Name:
- (oxiran-2-yl)methyl 2,2-dimethyloctanoate
- Reference substance name:
- Neodecanoic acid, 2-oxiarnylmethyl ester
- IUPAC Name:
- Neodecanoic acid, 2-oxiarnylmethyl ester
- Details on test material:
- As per 2,3-epoxyporpyl neodecanoate IUCLID 4 Data Set, Section 1-1.4, 2003.
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- See Section 1.2 and 1.4.
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Species: Rat
Strain: Wistar HanTM
Sub-strain: RccHanTMzWIST
Source of supply: Envigo RMS (UK) Ltd., Oxon, UK
Number: 80
Sex: Males and females
Age: Approximately 7 weeks on arrival
Weight Range: Males 188 — 235 g and Females 143 — 186 g - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Environmental conditions will be maintained within the following target parameters:
Target temperature: 22 +/- 3 °C
Target humidity: 30 to 70%
Lighting: Twelve hours of continuous artificial light in each twenty-four hour
period
Ventilation: At least fifteen air changes per hour
Animals will be housed in accordance with the ‘Code of Practice for the Housing and Care of
Animals Used in Scientific Procedures’ and in alignment with the United Kingdom Home
Office recommendations and requirements.
Animals were gang-housed in groups of up to four by sex in polypropylene cages with stainless steel mesh lids and furnished with softwood flake bedding (Datesand Ltd., Cheshire, UK).
Certificates of analysis for the bedding will be provided by the supplier.
The bedding is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity ofthe study.
Diet and Water
The animals were provided with Rodent 2014C Teklad Global Certified Pelleted Diet (Envigo RMS (UK) Ltd., Oxon, UK) and tap water ad libitum.
Drinking water is routinely analyzed (at least annually) and certificates of analysis for diet will be provided by the supplier.
The diet and drinking water are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity ofthe study.
Environmental Enrichment
The animals were provided with environmental enrichment items: wooden chew blocks and cardboard fun tunnels (Datesand Ltd., Cheshire, UK) or suitable alternatives. Any alternatives used will be documented in the raw data for the study.
Certificates of analysis for the environmental enrichment items will be provided by the supplier.
These enrichment items are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity ofthe study.
Pre—Test Procedures
Acclimatization Period
From arrival to the start of treatment was nine days A proportion ofthe animals will be weighed to confirm arrival body weights are ofthe correct specification.
Allocation
Animals were allocated to dose groups using a randomization procedure based on body weight at least five days prior to the start oftreatment. Animals were weighed on Day — 2 to ensure group mean are within an acceptable range.
Identification
Each animal was uniquely identified within the study by ear-punch. A color-coded cage card will be prepared with details of test item, study number, dose level, sex, numbers of animals, route of administration and Study Director responsible for the study.
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- Once daily, by gavage, using a stainless steel dosing cannula attached to a graduated syringe for ninety consecutive days.
- Vehicle:
- arachis oil
- Details on oral exposure:
- Animals will be allocated to test groups as follows:
Dose groups Group Size Animal Numbers Treatment Necropsy
& Sex Males Females period Day
1. Control 10 male & 10 female 1-10 11-20 90 days 91
2. 100 mg/kg bw/d 10 male & 10 female 21-30 31-40 90 days 91
3. 300 mg/kg bw/d 10 male & 10 female 41-50 51-60 90 days 91
4. 1000 mg/kg bw/d 10 male & 10 female 61-70 71-80 90 days 91 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For the purpose of this study the test item was prepared at the appropriate concentrations as a solution in Arachis oil BP. The stability and homogeneity of the test item formulations were determined by Envigo Research Limited, Shardlow, UK, Analytical Services as part of this study. Results from the previous study show the formulations to be stable for at least 23 days when stored at approximately 4 °C in the dark. Formulations were therefore prepared fortnightly and stored at approximately 4 °C in the dark.
Samples of each test item formulation were taken on two occasions during the study and analyzed for concentration of 2,3-epoxypropyl neodecanoate at Envigo Research Limited, Shardlow, UK, Analytical Services. The method used for analysis of formulations and the results obtained are given in Annex 2. The results indicate that the prepared formulations were within 95-100% of the nominal concentration. - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Once per day
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- Morbidity/Mortality Inspection
Twice daily, early and late during the working period.
Clinical Observations
All animals were examined for overt signs of toxicity, ill-health or behavioral change immediately before dosing, up to thirty minutes post dosing and one hour after dosing. All observations were recorded.
Body Weights
Individual body weights were recorded on Day 1 (prior to dosing) and at weekly intervals thereafter. Body weights were also recorded at terminal kill.
Food Consumption
Food consumption was recorded for each cage group at weekly intervals throughout the study. Food conversion efficiency was calculated retrospectively.
Water Consumption
Water intake was measured and recorded daily for each cage group during the first two weeks of the study and during Weeks 10 to 11.
Specialist Evaluations
Functional Observations
Prior to the start of treatment and at weekly intervals thereafter, all animals were observed for signs of functional/behavioral toxicity. During Week 12 functional performance tests were also performed on all animals together with an assessment of sensory reactivity to different stimuli.
Behavioral Assessment
Detailed individual clinical observations were performed for each animal using a purpose built arena. The following parameters were observed:
Gait Hyper/Hypothermia
Tremors Skin color
Twitches Respiration
Convulsions Palpebral closure
Bizarre/Abnormal/Stereotypic behavior Urination
Salivation Defecation
Pilo-erection Transfer arousal
Exophthalmia Tail elevation
Lachrymation
This test was developed from the methods used by Irwin (1968) and Moser et al (1988). The scoring system used is outlined in The Key to Scoring System and Explanation for Behavioral Assessments and Sensory Reactivity Tests.
Ophthalmoscopy
The eyes of all animals were examined pre-treatment and before termination of treatment (during Week 12). The eyes of all surviving control and high dose animals were examined before termination of treatment (during Week 12). Examinations included observation of the anterior structures of the eye, pupillary and corneal blink reflex. Following pupil dilation with 0.5% Tropicamide solution (Mydriacyl® 0.5%, Alcon Laboratories (UK) Ltd., Pentagon Park, Boundary Way, Hemel Hampstead, Hertfordshire), detailed examination of the internal structure of the eye using a direct ophthalmoscope was performed.
In-life Sampling and Analysis
Hematological and blood chemical investigations were performed on all surviving animals from each test and control group at the end of the study (Day 90). Blood samples were obtained from the lateral tail vein. Where necessary repeat samples were obtained by cardiac puncture prior to necropsy on Day 91. Animals were not fasted prior to sampling.
Hematology
Hemoglobin (Hb)
Erythrocyte count (RBC)
Hematocrit (Hot)
Erythrocyte indices
- mean corpuscular hemoglobin (MCH)
- mean corpuscular volume (MCV)
- mean corpuscular hemoglobin concentration (MCHC)
Total leucocyte count (WBC)
Differential leucocyte count
- neutrophils (Neut)
- lymphocytes (Lymph)
- monocytes (Mono)
- eosinophils (Eos)
- basophils (Bas)
Prothrombin time (CT)
Platelet count (PLT)
Activated partial thromboplastin time (APTT)
Reticulocyte count* (Retic)
*Blood film will be prepared but only examined at Study Director’s discretion
Blood Chemistry
Urea Inorganic phosphorus (P)
Glucose Aspartate aminotransferase (ASAT)
Total protein (Tot.Prot.) Alanine aminotransferase (ALAT)
Albumin Alkaline phosphatase (AP)
Albumin/Globulin (A/G) ratio (by calculation) Creatinine (Creat)
Sodium (Na+) Total cholesterol (Chol)
Potassium (K+) Total bilirubin (Bili)
Chloride (Cl-) Bile acids
Calcium (CaH) - Sacrifice and pathology:
- On completion of the dosing period all surviving animals were killed by intravenous overdose of a suitable barbiturate agent followed by exsanguination.
All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded.
Gross Examination
Full external and internal macroscopic examination of all animals.
Organ Weights
The following organs, removed from animals that were killed at the end of the study, were dissected free from fat and weighed before fixation:
Adrenals Ovaries
Brain Spleen
Epididymides Testes
Heart Thymus
Kidneys Uterus
Liver
Histopathology
Samples of the following tissues were removed from all animals and preserved in buffered 10% formalin, except where stated:
Adrenals Ovaries
Aorta (thoracic) Pancreas
Bone & bone marrow (femur including stifle joint)• Pituitary
Bone & bone marrow (sternum) Prostate
Brain (including cerebrum, cerebellum and pons) Rectum
Caecum Salivary glands (submaxillary)
Colon Sciatic nerve
Duodenum Seminal vesicles
Epididymides ♦ Skin
Esophagus Spinal cord (cervical, mid-thoracic
Eyes* and lumbar)
Gross lesions Spleen
Heart Stomach
Ileum (including Peyer’s patches) Testes ♦
Jejunum Thymus
Kidneys Thyroid/Parathyroid
Liver Tongue•
Lungs (with bronchi) # Trachea
Lymph nodes (mandibular and mesenteric) Urinary bladder
Mammary glands Uterus (with cervix)
Muscle (skeletal)• Vagina
• Retained only and not processed
* Eyes fixed in Davidson’s fluid
♦ Preserved in Modified Davidson’s fluid
# Lungs were inflated to approximately normal inspiratory volume with buffered 10% formalin before immersion in fixative
• Retained only and not processed
All tissues were dispatched to the Test Site (Propath UK Ltd, Willow Court, Netherwood Road, Rotherwas, Hereford, HR2 6JU) for processing (Principal Investigator: N Fower). All tissues from control and 1000 mg/kg bw/day dose group animals were prepared as paraffin blocks, sectioned at a nominal thickness of 5 µm and stained with Hematoxylin and Eosin for subsequent microscopic examination. Any macroscopically observed lesions were also processed.
Since there were indications of treatment-related changes, examination was subsequently extended to include similarly prepared sections of liver and thyroid gland (both sexes), kidney (males only) from animals in the low and intermediate groups.
Pathology
Microscopic examination was conducted by the Study Pathologist (W Henderson). A peer review of the findings observed was conducted by V Mowat at Envigo CRS Limited, Woolley Road, Alconbury, Huntingdon, Cambridgeshire, PE28 4HS. A complete histopathology phase report is presented in Annex 1 and represents the consensus view of both pathologists. - Statistics:
- Data Evaluation
Data were processed to give summary incidence or group mean and standard deviation values where appropriate. All data were summarized in tabular form.
Statistical Analysis
Where considered appropriate, quantitative data was subjected to statistical analysis to detect the significance of intergroup differences from control; statistical significance was achieved at a level of p<0.05. Statistical analysis was performed on the following parameters:
Grip Strength, Motor Activity, Body Weight Change, Hematology, Blood Chemistry, Absolute Organ Weights, Body Weight-Relative Organ Weights.
Data were analyzed using the decision tree from the ProvantisTM Tables and Statistics Module as detailed as follows:
Where appropriate, data transformations were performed using the most suitable method. The homogeneity of variance from mean values was analyzed using Bartlett’s test. Intergroup variances were assessed using suitable ANOVA, or if required, ANCOVA with appropriate covariates. Any transformed data were analyzed to find the lowest treatment level that showed a significant effect using the Williams Test for parametric data or the Shirley Test for non-parametric data. If no dose response was found but the data shows non-homogeneity of means, the data were analyzed by a stepwise Dunnett’s (parametric) or Steel (non-parametric) test to determine significant difference from the control group. Where the data were unsuitable for these analyses, pair-wise tests was performed using the Student t-test (parametric) or the Mann-Whitney U test (non-parametric).
Probability values (p) are presented as follows:
p<0.01 **
p<0.05 *
p>0.05 (not significant)
Results and discussion
Results of examinations
- Description (incidence and severity):
- Incidences of increased salivation were evident in animals of either sex treated with 300 or 1000 mg/kg bw/day throughout the treatment period and, to a lesser extent, in males treated with 100 mg/kg bw/day. Observation of this nature are commonly observed following the oral administration of an unpalatable or slightly irritant test item and, in isolation, are considered not to be associated with systemic toxicity.
Incidental findings included two males and one female treated with 1000 mg/kg bw/day, and two males treated with 300 mg/kg bw/day showed sporadic instances of noisy respiration during the treatment period. Isolated instances of hunched posture, staining around the mouth and scab formations followed by fur loss were also evident at 1000 mg/kg bw/day. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There were two unscheduled deaths on the study; two control females.
On Day 38 of treatment, one control female (No. 14) was killed in extremis due to a physical injury to the tail (55mm of skin was missing). There were no clinical signs or body weight issues prior to death. There were no further macroscopic findings at necropsy.
A further control female (No. 16) died during the blood sampling procedure on Day 90 of treatment. There were no clinical signs or macroscopic necropsy findings. - Description (incidence and severity):
- There were no adverse effects to body weight development at 100, 300 or 1000 mg/kg bw/day.
Males at 1000 mg/kg bw/day showed comparable body weight gains to controls during the first three weeks of treatment. For the majority of the remaining treatment period these males showed statistically significantly lower (p<0.05 - p<0.01) group mean body weight gains compared to controls, as a number of animals showed low body weight gains during this time. This resulted in overall body weight gains to be 16% lower than controls, as all the animals showed body weight gains this reduction was considered to be associated with biological variation.
At 300 mg/kg bw/day, males also showed some fluctuation in body weight gains during the treatment period. These fluctuations resulted in overall body weight gains to be slightly lower (5%) than controls.
Females treated with 300 or 1000 mg/kg bw/day generally showed similar body weight gains to controls, however, the overall body weight gain for these animals was 7% and 3% lower than controls.
Animals of either sex treated with 100 mg/kg bw/day generally showed no effects to treatment in relation to controls. On some occasions these animals exceeded the weights gains of the controls. Therefore the overall body weight gains were 15% and 7% higher than controls (males and females respectively). - Description (incidence and severity):
- There were no adverse effects detected for food consumption or food conversion efficiency at 100, 300 or 1000 mg/kg bw/day.
- Description (incidence and severity):
- Gravimetric measuring of water intake was performed during weeks 1, 2, 10 and 11 of treatment. An increase in water intake was apparent in animals of either sex treated with 1000 mg/kg bw/day of approximately 25%. This would correlate with the frequency and severity of the increased salivation in these animals.
- Description (incidence and severity):
- Ophthalmoscopic examination of surviving animals of both sexes from the control and animals from the 1000 mg/kg bw/day dose group during Week 12 of the treatment period did not indicate any treatment-related differences.
- Description (incidence and severity):
- At 1000 mg/kg bw/day, males showed a statistically significant reduction in hemaglobin (Hb) (p<0.01), erythrocyte count (RBC) (p<0.05) and hematocrit (Hct) (p<0.05) compared to controls. The majority of the individual values for each parameter were below the background control ranges which may indicate hemolytic anemia influenced by the histopathological changes to the liver.
There was considered to be no toxicological significant differences in hematology parameters for both sexes at 100 or 300 mg/kg bw/day or for females at 1000 mg/kg bw/day. Females treated with 100 mg/kg bw/day showed a statistically significant increase (p<0.05) in mean corpuscular hemaglobin concentration (MCHC) compared to controls. All individual values were within the background control ranges; albeit at the upper end of the range which could have influenced the statistical significance and as there were no histopathological correlates, it is considered that this finding is of no toxicological significance. - Description (incidence and severity):
- All treatment dose groups for males and females showed an increase in bilirubin (p<0.05 – p<0.01) with the exception of 100 mg/kg bw/day females. Animals of either sex did not show a dose related response and the majority of individual values were within the background control ranges. Two male and three female control values were actually below historical control values. However, increased bilirubin can be associated with the reductions in Hb, Hct and RBC in the 1000 mg/kg bw/day males.
At 1000 mg/kg bw/day males displayed an increase in alkaline phosphatase (AP) and bile acid (p<0.01 and p<0.05, respectively) when compared to controls. The majority of individual values were within the background control ranges, however, these elevations may be associated to the histopathological changes of the liver.
Males treated with 100 or 300 mg/kg bw/day showed a statistically significant reduction in albumin/globulin ratio (p<0.05) without a dose related response. The majority of the individual values were below the background control ranges and without a similar response at the higher dose level, this finding is considered to be of no toxicological significance.
Females treated with 300 or 1000 mg/kg bw/day showed a reduction in urea (p<0.05) in a dose related manner. The majority of individual values were within the background control range and with no histopathological correlates this finding was considered to be of no toxicological importance. The 1000 mg/kg bw/day females also had a reduction in phosphorus (p<0.05) in a dose related response, the majority of individual values were within the background control ranges; however, four control values were above these ranges and may influenced the statistical significance attained due to the higher group mean of the controls. Therefore the significance of this finding is considered to be of no toxicological importance. - Description (incidence and severity):
- A number of animals treated at 1000 mg/kgbw/day showed sporadic instances of increased salivation during behavioral assessments in the treatment period with a range of severity from slight to extreme. These observations correlate with the daily clinical observations evident at this dosage. In isolation one female treated at 1000 mg/kg bw/day showed hunched posture during these assessments on Weeks 3 to 6 and exhibited decreased respiratory rate during Week 3.
No observations were detected for animals treated with 100 or 300 mg/kg bw/day.
There were no toxicological changes in the functional parameters measured at 100, 300 or 1000 mg/kg bw/day.
Females treated with 100 mg/kg bw/day showed a statistically significant increase (p<0.05) in overall motor activity. Without similar effects at the higher dose levels and in the absence of any clinical signs of neurotoxicity, the intergroup difference was considered not to be of toxicological importance.
Intergroup differences observed in the scores for sensory reactivity did not indicate any effect of treatment for either sex at 100, 300 or 1000 mg/kg bw/day. - Description (incidence and severity):
- Kidney: Males treated with 300 or 1000 mg/kg bw/day showed an increase (p<0.05 and p<0.01, respectively) in both absolute and relative kidney weights compared to controls. The individual values for one and eight males (300 or 1000 mg/kg bw/day, respectively) showed absolute kidneys weights were above the background control ranges. The values for relative kidney weights showed that two and all ten males treated with 300 and 1000 mg/kg bw/day, respectively were above the background control ranges.
An increase was also evident in the corresponding female kidney weights at 300 and 1000 mg/kg bw/day (p<0.01) compared to controls. The individual absolute values showed that 2/10 kidneys weights from each dose group were above the background control ranges, showing a dose related response. Relative values also showed a dose related increase with four and eight females exceeding the background control ranges. The increase may be related to the increase of water intake but with no histopathological correlates this finding is considered to be of no toxicological significance.
Liver: All male treated dose groups showed an increase (p<0.05 - p<0.01) in absolute liver weight compared to controls, without a dose relationship present. The individual values of five, four and seven males (100, 300 and 1000 mg/kg bw/day, respectively) showed their liver weights were above the background control ranges. A further review of these liver weights relative to terminal body weight indicated six, eight and all ten males exceeded the background control ranges (100, 300 and 1000 mg/kg bw/day, respectively) although one control male value was also above historical control values. The corresponding females treated with 100, 300 or 1000 mg/kg bw/day also showed an increase (p<0.05 - p<0.01) in liver weights both absolute and relative to terminal body weight in a dose related response. Absolute individual values for females treated with 100 or 300 mg/kg bw/day were all within the background control ranges and all 1000 mg/kg bw/day values were above this range. The relative individual values showed that two, five and all ten females (100, 300 and 1000 mg/kg bw/day, respectively). The increase in liver weight for both males and females at 1000 mg/kg bw/day is considered to be associated with the histopathological changes.
Testes: At 1000 mg/kg bw/day males showed a statistically significant increase (p<0.05) in testis weights compared to controls for both absolute and relative organ weights. The individual values indicated that 3/10 and 6/10 values were above the normal background ranges for absolute and relative weights, respectively and with no histopathological correlates this finding was considered to be of no toxicological significance. It is also noted that 3/10 control absolute testis weights were above historical control values. - Description (incidence and severity):
- Kidney
Increased hyaline droplets, granular casts and multifocal basophilic tubules or nephropathy were present in all males treated with 1000 mg/kg bw/day. The hyaline droplet formation extended to all males at 300 mg/kg bw/day with 5/10 males also showing granular casts and tubular basophilia. Hyaline droplet formation was seen in 4/10 males at 100 mg/kg bw/day. Hyaline droplet accumulation is specific to the male rat and is not generally considered to be significant in man. However, multifocal basophilic tubules/nephropathy and granular casts, generally considered to be associated with the hyaline droplet accumulation, are considered to be adverse.
Liver
Hepatocellular hypertrophy, mainly in the centrilobular area was present in 4/10 males and 5/10 females treated with 1000 mg/kg bw/day. One male at 100 mg/kg bw/day was also found to have this condition. These changes are suggestive of an adaptive response to mixed function oxidase induction in the liver and correlates with the increase in organ weights
Thyroid Glands
Hypertrophy of the follicular epithelium was present in 6/10 males and 5/10 females treated with 1000 mg/kg bw/day. It was also observed amongst 6/10 males and 1/10 females at 300 mg/kg bw/day and 3/10 males and 1/10 females at 100 mg/kg bw/day. The hypertrophy was considered likely to be linked to the histopathological change in the liver where the underlying mechanism is considered to be increased hepatic clearance of thyroid hormones, causing compensatory hypertrophy of follicular cells.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effect
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
KEY TO TABLES AND APPENDICES
M Male
F Female
Pre Immediately before dosing
Post Post dosing (up to 30 minutes)
1h One hour post dosing
A.M. ante meridiem
S.D. Standard deviation
N Number of animals
Abs Gain Absolute body weight gain between base period and end of the analysis period
% Gain Percentage body weight gain between base period and end of the analysis period
% Food Efficiency
Statistical Footnotes:
* Significantly different from control group p<0.05
** Significantly different from control group p<0.01
n Data not appropriate for statistical analysis
Organ Weights Footnotes:
Epididys Epididymides
Bodywt Body weight
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS
1. NEUROLOGIC
These parameters are the first to be evaluated when the animal is placed in the arena:
1.1 Transfer Arousal (Time to Movement) and Locomotion
-2 = animal stays in one place
-1 = slow, deliberate movement
0 = moderate, undisturbed investigation of environment
1 = active progression around arena
2 = darting movements
1.2 Tail Elevation
0 = flattened
1 = rigidly horizontally extended
2 = rigidly diagonally elevated
3 = rigidly vertical
4 = diagonally retrograde (past vertical)
2. GAIT AND CO-ORDINATION
Tiptoe Hindlimbs raised on tiptoe during movement
High stepping Forelimbs lifted high during movement
Spastic Shuffling of limbs
Waddling Lateral movements
Dysmetric Unco-ordinated movement with tremors
Splayed Thighs splayed outwards, animal appears crouched
Scissor Forelimbs cross over when extended
Ataxic
Lack of co-ordinated movement of trunk, pelvis and limbs.
Observation graded: Slight
Moderate (does not fall)
Extreme (falls repeatedly)
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)
3. CNS EXCITATION
3.1 Tremors
These are general involuntary movements of the muscles
Exertion only occurs during movement
Rest only occurs when animal is resting
Whole body
Head only
Body only
Tail only
When present, any observation is also graded:
Slight
Moderate
Extreme
3.2 Twitches
Identified as brief, coarse jerks of body or limbs - observation graded:
Slight
Moderate
Extreme
3.3 Convulsions
Clonic Convulsions with alternate contraction and relaxation of muscles
Running excitement Often accompanied by clonic convulsions
Champing Clonus of the paws only
Hopping Animal repeatedly “hops” into the air
Asphyxeal Terminal convulsion, results in death from respiratory failure
Tonic Seizure in which the head, body and limbs are arched backwards
Emprosthotonus Seizure where the head, body and limbs are arched forwards
3.4 Bizarre Behavior
Any bizarre behavior is recorded using a unique code.
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)
4. AUTONOMIC
Salivation* Excessive visible wetness around the mouth
Pilo-erection* Fur stands up - marked cases are described as “puff ball” appearance
Exophthalmia Bulging eyes
Lachrymation Tear staining (clear fluid)
Chromodacryorrhea (red/pink fluid)
Hyperthermia
Hypothermia
Skin color* Blue (cyanotic)
Redness of extremities
Skin pallor
Respiration Decreased respiratory rate
Gasping
Increased rate
Labored
Noisy
Palpebral closure Degree of eyelid closure e.g. ptosis - observation is graded:
Slight
Moderate
Severe
Urination and defecation During the study this can only be observed as urogenital wetness and/or diarrhoea. In the open arena, the number of occasions that the animal defecates/urinates is recorded
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)
5. MANIPULATIVE TESTS
Performed in the open arena:
5.1 Grasp Response
The animal is grasped around the body and its reaction is scored:
0 = no response
1 = animal struggles slightly but becomes passive
2 = animal repeatedly struggles with/without vocalization
3 = animal struggles violently with/without vocalization
4 = animal attempts to bite operator
5.2 Vocalization
The number of vocalizations exhibited by the animal during handling.
5.3 Toe Pinch
On handling one toe of a hindfoot is lightly pressed with a pair of forceps:
-3 = no response
-2 = animal shows awareness of actions
-1 = withdrawal
0 = rapid withdrawal with single vocalization
1 = rapid withdrawal with multiple vocalizations
5.4 Tail Pinch
Whilst animal is in the arena, the end of the tail is lightly pressed with forceps:
-2 = no response
-1 = animal freezes/shows awareness of grasping
0 = animal attempts to escape/struggles with none or single vocalization
1 = animal struggles violently with multiple vocalizations
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)
5.5 Finger Approach
Whilst animal is in the arena the operator moves one finger towards the animal:
-1 = animal is oblivious to approach
0 = animal is aware of finger but is unmoved
1 = head sways from side to side
2 = moves towards finger
3 = investigates finger by moving onto it
5.6 Touch Escape
Whilst animal is in the arena the operator runs his finger down the body of the animal:
-2 = no response
-1 = animal twitches ears, investigates finger
0 = animal crouches
1 = animal moves away but is unhurried
2 = animal moves away as if startled
5.7 Pupil Reflex
The animal is placed in a darkened area to allow the pupils to dilate. A light beam is shone into each eye separately and the pupil is observed for immediate constriction.
The response recorded:
-2 = no response
-1 = sluggish
0 = normal
KEY TO SCORING SYSTEM AND EXPLANATION FOR BEHAVIORAL ASSESSMENTS AND SENSORY REACTIVITY TESTS (CONTINUED)
5.8 Blink Reflex (Palpebral Closure)
The operator attempts to touch the eye of the rat, the response is recorded:
-2 = no response
-1 = sluggish
0 = normal blink reflex
1 = rapid or repeated eye blink
5.9 Startle Reflex
A sharp sudden noise is produced by a noise generator or finger snap or similar. Each animal is held lightly but firmly facing the origin of the noise. The response is recorded:
-1 = no response
0 = normal
1 = hyper-responsive
FIGURES
Figure 1 Group Mean Body Weights for Males
Figure 2 Group Mean Body Weights for Females
Figure 3 Group Mean Food Consumptions for Males
Figure 4 Group Mean Food Consumptions for Females
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TABLES
Table 1 Summary Incidence of Daily Clinical Observations
Day Numbers Relative to Start Date
Sex: Male
Group 1 Group 2 Group 3 Group 4
0(Control) 100 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/day
Scheduled kill
Number of Animals 10 10 10 10
Days from ƒ to 91 91 91 91 91 91 91 91
Increased salivation
Number of Animals . 9 10 10
Days from ƒ to . 18 90 2 90 1 90
Noisy respiration
Number of Animals . . 2 2
Days from ƒ to . . 56 78 80 89
Hunched posture
Number of Animals . . . 1
Days from ƒ to . . . 40 40
Table 1 (continued) Summary Incidence of Daily Clinical Observations
Day Numbers Relative to Start Date
Sex: Female
Group 1 Group 2 Group 3 Group 4
0(Control) 100 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/day
Damaged Tail
Number of Animals 1 . . .
Days from ƒ to 38 38 . . .
Scab#
Number of Animals . . . 2
Days from ƒ to . . . 63 68
Killed `in extremis'
Number of Animals 1 . . .
Days from ƒ to 38 38 . . .
Scheduled kill
Number of Animals 8 10 10 10
Days from ƒ to 91 91 91 91 91 91 91 91
Found dead
Number of Animals 1 . . .
Days from ƒ to 90 90 . . .
Staining around the mouth
Number of Animals . . . 1
Days from ƒ to . . . 63 63
Increased salivation
Number of Animals . . 10 10
Days from ƒ to . . 6 90 1 90
# = Scab on back or dorsal surface
Table 1 (continued) Summary Incidence of Daily Clinical Observations
Day Numbers Relative to Start Date
Sex: Female
Group 1 Group 2 Group 3 Group 4
0(Control) 100 mg/kg bw/day 300 mg/kg bw/day 1000 mg/kg bw/day
Noisy respiration
Number of Observations . . . 4
Number of Animals . . . 2
Days from ƒ to . . . 20 74
Generalised fur loss
Number of Observations . . . 14
Number of Animals . . . 2
Days from ƒ to . . . 69 75
Table 2 Summary Incidence of Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group
(Sex) Clinical Sign Severity -1 7 14 21 28 35 42 49 56 63 70 77 84 89
1(M) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 10 10 10 10 10 10 10 10 10 10 10
1(F) ANIMALS ALIVE 10 10 10 10 10 10 9 9 9 9 9 9 9 9
ANIMALS NORMAL 10 10 10 10 10 10 9 9 9 9 9 9 9 9
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 2 (continued) Summary Incidence of Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group
(Sex) Clinical Sign Severity -1 7 14 21 28 35 42 49 56 63 70 77 84 89
2(M) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 10 10 10 10 10 10 10 10 10 10 10
2(F) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 10 10 10 10 10 10 10 10 10 10 10
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 2 (continued) Summary Incidence of Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group
(Sex) Clinical Sign Severity -1 7 14 21 28 35 42 49 56 63 70 77 84 89
3(M) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 10 10 10 10 10 10 10 10 10 10 10
3(F) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 10 10 10 10 10 10 10 10 10 10 10
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 2 (continued) Summary Incidence of Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group
(Sex) Clinical Sign Severity -1 7 14 21 28 35 42 49 56 63 70 77 84 89
4(M) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 8 10 10 10 10 10 10 9 10 10 10 10
Autonomic ƒ Salivation Slight . . 2 . . . . . . 1 . . . .
TOTAL . . 2 . . . . . . 1 . . . .
4(F) ANIMALS ALIVE 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ANIMALS NORMAL 10 10 10 5 6 7 8 8 8 9 9 10 10 10
Respiration ƒ Decreased Rate Present . . . 1 . . . . . . . . . .
TOTAL . . . 1 . . . . . . . . . .
Autonomic ƒ Salivation Slight . . . . 1 1 1 1 1 . . . . .
Moderate . . . 1 1 . . . 1 1 1 . . .
Extreme . . . 4 2 2 1 1 . . . . . .
TOTAL . . . 5 4 3 2 2 2 1 1 . . .
Hunched posture Present . . . 1 1 1 1 . . . . . . .
TOTAL . . . 1 1 1 1 . . . . . . .
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.2 0.2 0.0
S.D. 0.0 0.4 0.6 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.1 0.2 0.0
S.D. 0.0 0.3 0.4 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.6 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.5 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.1 0.0 0.0 0.0
S.D. 0.3 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 3 (continued) Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Transfer Urinƒ Defƒ Tail elƒ
Group arousal ation ecation evation
(Sex)
1(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 4 Group Mean Functional Test Values and Standard Deviations
Test 1 Test 1 Test 2 Test 2 Test 3 Test 3 Overall Overall Last 20% Last 20%
Group Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb activity mobile activity mobile
(Sex) g g g g g g
1(M) Mean 588.8 333.9 788.2 358.3 831.7 253.1 452.2 0.0n 12.0 0.0n
S.D. 187.8 109.2 453.9 104.0 392.6 113.3 99.5 0.0 20.9 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 777.4 402.5 817.4 351.6 665.6 299.8 535.1 0.0n 25.3 0.0n
S.D. 300.4 140.8 429.3 162.5 252.2 156.1 141.3 0.0 33.3 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 558.4 371.1 731.0 345.9 707.1 270.2 522.2 0.0n 17.7 0.0n
S.D. 207.2 217.1 386.7 183.2 345.2 84.0 109.7 0.0 15.4 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 604.7 271.5 636.3 291.6 687.8 213.3 460.4 0.0n 53.3 0.0n
S.D. 342.9 122.4 262.0 124.1 357.7 96.2 107.7 0.0 63.5 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
General Footnote: Unit = Time (seconds) for Motor Activity Assessments
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 4 (continued) Group Mean Functional Test Values and Standard Deviations
Test 1 Test 1 Test 2 Test 2 Test 3 Test 3 Overall Overall Last 20% Last 20%
Group Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb activity mobile activity mobile
(Sex) g g g g g g
1(F) Mean 905.9 215.4 892.6 368.6 945.1 280.6 531.3 0.0n 53.3 0.0n
S.D. 225.9 126.3 331.8 167.6 351.0 184.4 116.2 0.0 48.4 0.0
N 9 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 957.7 332.1 940.8 372.8 957.7 378.0 701.6* 0.0n 50.7 0.0n
S.D. 205.8 116.8 292.1 213.7 352.7 100.3 131.4 0.0 79.4 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 963.4 236.6 989.2 406.2 1001.7 374.4 564.4 0.0n 47.6 0.0n
S.D. 279.7 121.1 293.2 134.6 240.4 189.0 100.8 0.0 68.3 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 761.4 272.1 940.4 360.9 782.3 275.4 480.4 0.0n 51.5 0.0n
S.D. 324.0 118.9 178.0 202.8 229.3 103.0 126.8 0.0 74.9 0.0
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
General Footnote: Unit = Time (seconds) for Motor Activity Assessments
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 5 Summary Incidence of Sensory Reactivity Assessments (Scores)
Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
Group response isation pinch pinch approach escape reflex reflex reflex
(Sex)
1(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
2(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
3(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
4(M) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 5 (continued) Summary Incidence of Sensory Reactivity Assessments (Scores)
Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
Group response isation pinch pinch approach escape reflex reflex reflex
(Sex)
1(F) Mean 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
2(F) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
3(F) Mean 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
4(F) Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 6 Group Mean Body Weight Values
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group
(Sex) 1 8 15 22 29 36 43 50 57 64 71 78 85 91
1(M) Mean 205.5 236.7 260.6 282.5 303.2 319.7 335.5 349.3 360.8 369.7 381.9 392.1 397.5 404.8
S.D. 9.6 12.3 14.3 14.8 16.9 18.3 20.8 22.2 21.6 23.2 21.2 23.9 24.2 25.0
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(M) Mean 204.7 242.5 270.7 297.9 321.4 338.3 358.7 373.4 386.2 397.1 408.8 418.8 426.0 435.1
S.D. 12.7 15.5 17.1 18.5 20.8 25.2 24.8 25.0 26.3 26.4 26.2 28.1 29.9 31.1
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(M) Mean 203.9 235.1 257.4 279.2 293.9 311.5 325.1 339.1 349.9 360.8 370.4 377.9 384.7 392.9
S.D. 7.5 10.9 14.8 14.9 19.2 18.2 18.8 18.8 19.0 20.7 21.2 22.9 26.0 26.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(M) Mean 203.2 233.8 258.2 278.1 295.4 310.1 320.8 332.8 341.2 348.4 356.9 362.4 366.4 371.6
S.D. 7.2 12.2 17.5 21.2 25.6 26.5 28.0 30.8 30.9 32.6 33.2 34.5 37.4 37.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 6 (continued) Group Mean Body Weight Values
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group
(Sex) 1 8 15 22 29 36 43 50 57 64 71 78 85 91
1(F) Mean 165.1 179.7 185.9 196.4 204.8 209.3 213.7 218.1 222.2 226.3 228.3 225.3 229.0 236.1
S.D. 11.6 13.7 14.9 16.0 20.1 17.4 19.0 19.5 23.3 22.9 20.0 20.3 22.0 17.9
N 10 10 10 10 10 10 9 9 9 9 9 9 9 8
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(F) Mean 166.3 182.8 188.5 200.1 207.2 214.1 219.3 224.6 229.0 231.5 236.0 237.8 239.7 240.0
S.D. 9.4 8.9 12.7 12.7 14.8 14.1 14.9 15.1 18.2 17.8 16.3 16.5 18.8 15.5
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(F) Mean 165.2 178.2 188.0 198.0 203.5 207.3 212.4 216.8 219.6 223.3 226.1 224.3 228.1 229.6
S.D. 7.9 11.5 15.0 16.6 16.7 17.6 16.1 17.0 18.1 19.1 17.9 19.2 19.0 19.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(F) Mean 162.8 176.1 187.2 200.3 205.4 207.8 214.0 220.0 220.4 224.9 226.5 226.3 229.5 229.9
S.D. 8.0 10.7 11.8 12.8 16.3 14.4 15.2 13.8 16.9 15.8 16.8 15.4 18.1 17.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 7 Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Abs %
Gain Gain
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85 1 1
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91 91 91
1(M) Mean 31.2 23.9 21.9 20.7 16.5 15.8 13.8 11.5 8.9 12.2 10.2 5.4 7.3 199.3 97.0
S.D. 4.0 3.8 3.8 2.9 2.5 3.9 3.6 1.8 2.1 4.4 3.4 4.6 2.8 18.9 8.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
2(M) Mean 37.8* 28.2 27.2* 23.5 16.9 20.4 14.7 12.8 10.9 11.7 10.0 7.2 9.1 230.4 112.6
S.D. 3.6 5.4 3.7 4.3 6.5 3.2 4.0 2.7 4.5 3.5 3.4 3.2 3.9 21.9 8.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
3(M) Mean 31.2 22.3 21.8 14.7 17.6 13.6 14.0 10.8 10.9 9.6 7.5 6.8 8.2 189.0 92.7
S.D. 7.9 6.9 5.0 7.6 7.2 4.2 2.7 3.1 3.6 3.0 3.4 6.5 5.7 22.8 10.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
4(M) Mean 30.6 24.4 19.9 17.3 14.7 10.7** 12.0 8.4* 7.2 8.5* 5.5** 4.0 5.2 168.4 82.7
S.D. 6.3 7.0 5.0 6.5 3.3 2.8 5.1 3.1 4.4 2.0 3.8 5.9 3.2 33.5 15.2
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 7 (continued) Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Abs %
Gain Gain
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85 1 1
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91 91 91
1(F) Mean 14.6 6.2 10.5 8.4 4.5 5.6 4.4 4.1 4.1 2.0 ƒ3.0 3.7 2.9 69.0 41.4
S.D. 5.2 2.7 5.3 7.3 5.3 2.2 5.3 6.7 3.4 4.2 2.9 4.6 3.5 14.4 8.5
N 10 10 10 10 10 9 9 9 9 9 9 9 8 8 8
2(F) Mean 16.5 5.7 11.6 7.1 6.9 5.2 5.3 4.4 2.5 4.5 1.8 1.9 0.3 73.7 44.4
S.D. 5.5 4.8 5.5 4.4 3.9 3.5 5.2 4.0 3.4 4.1 5.8 5.7 6.2 11.2 6.8
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
3(F) Mean 13.0 9.8 10.0 5.5 3.8 5.1 4.4 2.8 3.7 2.8 ƒ1.8 3.8 1.5 64.4 38.8
S.D. 5.9 7.9 7.8 5.6 4.6 6.0 5.4 3.9 4.7 3.4 5.8 3.7 4.9 14.3 7.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
4(F) Mean 13.3 11.1 13.1 5.1 2.4 6.2 6.0 0.4 4.5 1.6 ƒ0.2 3.2 0.4 67.1 41.2
S.D. 7.3 6.5 5.3 5.5 7.7 5.7 5.3 5.0 5.0 5.5 5.5 5.3 5.4 13.8 8.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 8 Group Mean Food Consumptions
Day Numbers Relative to Start Date
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(M) Mean 20.3 18.7 19.6 20.4 20.6 20.5 20.1 19.4 19.6 19.2 19.9 18.6 18.0
N 10 10 10 10 10 10 10 10 10 10 10 10 10
2(M) Mean 22.7 20.9 21.6 22.0 22.0 21.8 21.3 21.2 21.7 20.7 21.5 20.8 20.5
N 10 10 10 10 10 10 10 10 10 10 10 10 10
3(M) Mean 20.4 19.3 20.0 20.7 20.4 20.2 20.0 19.8 20.0 19.3 19.8 19.1 18.8
N 10 10 10 10 10 10 10 10 10 10 10 10 10
4(M) Mean 19.7 19.7 20.5 20.5 20.5 20.4 20.3 19.8 20.4 20.4 19.8 18.6 19.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10
Food Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 8 (continued) Group Mean Food Consumptions
Day Numbers Relative to Start Date
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(F) Mean 14.5 13.9 15.7 16.3 15.9 15.0 15.1 15.5 15.6 13.5 14.2 14.6 14.4
N 10 10 10 10 10 10 9 9 9 9 9 9 9
2(F) Mean 14.8 14.4 16.1 15.4 15.9 15.3 15.4 15.0 15.3 14.6 14.9 14.6 14.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10
3(F) Mean 14.2 14.2 15.8 16.1 15.1 14.7 14.7 14.6 14.4 13.8 13.9 14.4 14.1
N 10 10 10 10 10 10 10 10 10 10 10 10 10
4(F) Mean 12.8 14.2 15.9 15.9 15.4 14.9 15.1 14.8 14.8 14.1 14.1 14.4 14.2
N 10 10 10 10 10 10 10 10 10 10 10 10 10
Food Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 9 Food Efficiency
Day Numbers Relative to Start Date
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(M) Mean 22.0 18.6 16.0 14.5 11.4 11.0 9.9 8.5 6.5 9.1 7.2 4.2 6.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
2(M) Mean 23.8 19.3 18.0 15.3 11.0 13.4 9.9 8.6 7.2 8.1 6.6 4.9 6.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
3(M) Mean 21.8 16.4 15.6 10.1 12.3 9.6 10.0 7.8 7.8 7.1 5.4 4.9 7.4
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
4(M) Mean 22.1 17.5 13.8 12.0 10.3 7.5 8.4 6.1 5.1 6.0 3.9 3.0 4.5
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 9 (continued) Food Efficiency
Day Numbers Relative to Start Date
Group From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(F) Mean 14.4 6.4 9.5 7.4 4.0 5.3 4.1 3.8 3.8 2.2 ƒ3.1 3.7 3.2
N 10 10 10 10 10 9 9 9 9 9 9 9 8
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
2(F) Mean 15.9 5.5 10.3 6.6 6.2 4.7 5.0 4.1 2.3 4.4 1.7 1.9 0.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
3(F) Mean 13.0 9.4 9.0 4.8 3.6 5.0 4.2 2.8 3.7 2.9 ƒ1.9 3.8 1.6
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
4(F) Mean 14.7 11.2 11.9 4.5 2.2 6.1 5.5 0.3 4.4 1.6 ƒ0.3 3.2 0.4
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 1 2 3 4 5 6 7 8 9 10
(Sex) To: 2 3 4 5 6 7 8 9 10 11
1(M) Mean 24.7 22.8 27 24.3 24.9 27.4 25.2 25.1 25.8 24.4
N 10 10 10 10 10 10 10 10 10 10
2(M) Mean 24.6 22.6 26 24.7 24.3 26.2 25.3 22.8 24.6 24.9
N 10 10 10 10 10 10 10 10 10 10
3(M) Mean 23 21.6 24.7 22.2 22.7 25.7 22.5 22.3 22.6 23.2
N 10 10 10 10 10 10 10 10 10 10
4(M) Mean 29.4 28.9 31.1 26.7 26.6 28.4 26.5 28.7 31.5 31.6
N 10 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 (continued) Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 11 12 13 14 64 65 66 67 68
(Sex) To: 12 13 14 15 65 66 67 68 69
1(M) Mean 21.5 24.8 24.9 24.1 24.7 24.2 23 23.1 26
N 10 10 10 10 10 10 10 10 10
2(M) Mean 21.9 23.8 23.1 23.1 29.4 25.5 26.1 24.9 27.8
N 10 10 10 10 10 10 10 10 10
3(M) Mean 19.7 25.1 22.8 22 24.4 24.6 23.1 21.9 25.2
N 10 10 10 10 10 10 10 10 10
4(M) Mean 28.1 31.5 32.4 29.7 34.7 34 34.4 29.5 35.6
N 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 (continued) Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 69 70 71 72 73 74 75 76 77
(Sex) To: 70 71 72 73 74 75 76 77 78
1(M) Mean 27.8 23.2 25 26 25.6 22.5 28.5 26 21.1
N 10 10 10 10 10 10 10 10 10
2(M) Mean 30.7 24.6 26.3 27.7 30.4 24.5 27.1 27.5 23.7
N 10 10 10 10 10 10 10 10 10
3(M) Mean 38.2 23.4 24.3 25.8 29.9 23.4 25.9 26.8 21.4
N 10 10 10 10 10 10 10 10 10
4(M) Mean 38.3 28.6 33.4 33.9 33 27.6 30.7 34.5 27.4
N 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 (continued) Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 1 2 3 4 5 6 7 8 9 10
(Sex) To: 2 3 4 5 6 7 8 9 10 11
1(F) Mean 16 19.4 18.7 18.5 19 18.2 21.4 19.4 18.5 16.6
N 10 10 10 10 10 10 10 10 10 10
2(F) Mean 17.2 19.3 19.6 18.9 21.3 16.8 19.8 19.5 22.1 16.2
N 10 10 10 10 10 10 10 10 10 10
3(F) Mean 16.9 20.3 19.1 20.8 18.7 16.7 18 20.8 19.5 19.6
N 10 10 10 10 10 10 10 10 10 10
4(F) Mean 24.2 24.1 22.4 22.9 24.8 21.4 22.3 26.1 27.9 24.1
N 10 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 (continued) Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 11 12 13 14 64 65 66 67 68
(Sex) To: 12 13 14 15 65 66 67 68 69
1(F) Mean 22.5 19.8 16.9 21.1 23.4 22.9 22.3 22.3 30.1
N 10 10 10 10 9 9 9 9 9
2(F) Mean 20.5 18.5 18.7 18.6 19.8 22.3 19.4 18.9 22.3
N 10 10 10 10 10 10 10 10 10
3(F) Mean 21.2 17.4 17.4 21.5 21.1 18.4 18.9 18.8 22.2
N 10 10 10 10 10 10 10 10 10
4(F) Mean 24.9 28.3 25.4 28 25.1 24.7 24.2 27.3 32
N 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 10 (continued) Group Mean Daily Water Consumptions
Day Numbers Relative to Start Date
Group From: 69 70 71 72 73 74 75 76 77
(Sex) To: 70 71 72 73 74 75 76 77 78
1(F) Mean 21.2 24 23 24.6 21.3 28 27.9 12.9 19.2
N 9 9 9 9 9 9 9 9 9
2(F) Mean 19 20.3 19.5 22.1 18.9 22.5 21.2 18 21.6
N 10 10 10 10 10 10 10 10 10
3(F) Mean 15.5 20.1 19.5 22.5 17 21.9 22 18.6 16.4
N 10 10 10 10 10 10 10 10 10
4(F) Mean 23.9 25.4 25.8 26.4 24.7 25.4 28.1 21.7 21.6
N 10 10 10 10 10 10 10 10 10
Water Consumption = g/animal/day.
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 11 Group Mean Hematological Values
Group Hb RBC Hct MCH MCV MCHC WBC Neut
(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l
1(M) Mean 16.15 8.611 44.74 18.63 52.04 35.80 8.91 2.440
S.D. 1.12 0.771 3.39 1.16 1.75 1.12 2.53 0.702
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(M) Mean 15.81 8.279 43.87 19.14 53.09 35.64 8.64 2.066
S.D. 1.91 0.985 4.76 1.24 2.14 1.43 2.52 0.768
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(M) Mean 16.49 8.913 46.27 18.50 51.95 35.63 8.64 2.150
S.D. 0.53 0.253 1.33 0.59 1.58 0.76 1.54 0.564
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(M) Mean 15.17** 8.259* 43.28* 18.39 52.44 35.07 8.36 2.061
S.D. 0.56 0.353 1.49 0.72 2.07 0.52 2.69 0.844
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 11 (continued) Group Mean Hematological Values
Group Lymph Mono Eos Bas CT PLT APTT
(Sex) 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds
1(M) Mean 6.402 0.000n 0.069 0.000n 9.77 565.9 14.99
S.D. 1.891 0.000 0.086 0.000 0.60 59.7 1.29
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
2(M) Mean 6.565 0.000n 0.010 0.000n 9.85 510.0 15.10
S.D. 1.807 0.000 0.023 0.000 0.75 196.0 1.90
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
3(M) Mean 6.443 0.000n 0.048 0.000n 10.27 545.8 14.88
S.D. 1.042 0.000 0.086 0.000 0.79 94.7 1.68
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
4(M) Mean 6.254 0.000n 0.045 0.000n 9.64 614.9 14.11
S.D. 2.015 0.000 0.055 0.000 0.50 83.7 1.46
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 11 (continued) Group Mean Hematological Values
Group Hb RBC Hct MCH MCV MCHC WBC Neut
(Sex) g/dl 10^12/l % pg fl g/dl 10^9/l 10^9/l
1(F) Mean 14.97 7.994 42.79 18.77 53.54 34.93 6.28 1.603
S.D. 0.86 0.573 2.80 0.55 1.28 0.30 2.03 0.643
N 9 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(F) Mean 14.66 7.707 41.34 19.06 53.72 35.43* 6.07 1.416
S.D. 1.20 0.638 3.51 0.82 1.97 0.39 2.21 0.681
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(F) Mean 14.17 7.390 40.45 19.16 54.65 35.04 6.39 1.683
S.D. 2.19 1.060 6.05 0.74 1.70 0.38 2.30 0.652
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(F) Mean 14.09 7.628 40.51 18.45 53.04 34.78 6.12 1.547
S.D. 2.02 1.087 6.00 0.64 1.54 0.59 2.05 0.653
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 11 (continued) Group Mean Hematological Values
Group Lymph Mono Eos Bas CT PLT APTT
(Sex) 10^9/l 10^9/l 10^9/l 10^9/l Seconds 10^9/l Seconds
1(F) Mean 4.652 0.000n 0.023 0.000n 9.44 511.3 14.06
S.D. 1.524 0.000 0.048 0.000 0.42 77.7 1.49
N 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
2(F) Mean 4.599 0.000n 0.055 0.000n 9.09 603.4 15.81
S.D. 1.590 0.000 0.128 0.000 0.89 125.7 2.06
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
3(F) Mean 4.675 0.000n 0.033 0.000n 9.11 513.7 13.56
S.D. 1.825 0.000 0.065 0.000 0.77 193.0 1.27
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
4(F) Mean 4.570 0.000n 0.005 0.000n 9.04 542.5 14.77
S.D. 1.576 0.000 0.016 0.000 0.63 199.5 2.00
N 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 12 Group Mean Blood Chemical Values
Tot.
Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++
(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l
1(M) Mean 32.1 174.9 6.652 3.48 1.099 146.5 5.271 94.7 2.412
S.D. 3.4 25.6 0.592 0.29 0.038 2.3 0.901 13.2 0.186
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(M) Mean 35.6 178.2 6.802 3.40 1.010* 147.2 6.112 86.7 2.175
S.D. 11.8 48.8 0.794 0.27 0.079 3.2 1.645 33.0 0.275
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(M) Mean 31.7 160.5 7.027 3.53 1.017* 148.2 5.778 87.9 2.174
S.D. 5.3 36.5 0.778 0.32 0.082 3.6 1.412 16.4 0.318
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(M) Mean 30.9 156.4 7.115 3.67 1.075 147.2 5.502 98.9 2.563
S.D. 5.9 47.9 0.403 0.12 0.084 2.4 0.926 5.9 0.138
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 12 (continued) Group Mean Blood Chemical Values
Group P ASAT ALAT AP Creat Chol Bili Bile Acid
(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl µmol/l
1(M) Mean 2.04 95.2 57.0 114.5 0.712 88.2 0.061 13.11
S.D. 0.38 26.7 7.1 44.7 0.116 12.7 0.032 6.42
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(M) Mean 2.28 98.2 69.3 108.0 0.766 100.7 0.104* 11.00
S.D. 0.52 33.3 36.0 30.7 0.277 16.5 0.034 7.56
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(M) Mean 2.25 90.2 62.0 130.0 0.772 99.4 0.083* 12.28
S.D. 0.40 24.3 12.7 33.0 0.181 15.9 0.049 5.35
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(M) Mean 2.12 73.3 64.8 168.2** 0.751 99.6 0.107** 19.31*
S.D. 0.37 19.3 30.6 57.0 0.104 14.2 0.026 4.98
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 12 (continued) Group Mean Blood Chemical Values
Tot.
Group Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++
(Sex) mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l
1(F) Mean 39.8 190.9 7.252 4.00 1.276 149.1 7.163 103.1 2.614
S.D. 7.2 50.3 1.226 0.49 0.186 4.9 5.772 8.4 0.449
N 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
2(F) Mean 41.8 177.7 7.249 4.02 1.277 150.3 4.914 103.8 2.738
S.D. 9.8 29.1 0.884 0.40 0.099 3.1 1.071 2.3 0.170
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
3(F) Mean 33.8* 160.2 6.884 3.88 1.313 150.2 4.718 103.2 2.668
S.D. 2.4 17.3 0.857 0.40 0.128 2.4 0.263 1.8 0.158
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
4(F) Mean 32.6* 172.0 6.681 3.80 1.326 150.5 5.184 104.2 2.670
S.D. 4.9 20.5 1.027 0.52 0.086 1.4 0.643 3.0 0.193
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 12 (continued) Group Mean Blood Chemical Values
Group P ASAT ALAT AP Creat Chol Bili Bile Acid
(Sex) mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl µmol/l
1(F) Mean 2.29 134.9 55.6 59.3 0.747 87.6 0.050 24.78
S.D. 0.90 89.9 7.2 32.1 0.080 16.5 0.039 20.53
N 9 9 9 9 9 9 9 9
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
2(F) Mean 1.90 95.5 53.1 58.5 0.766 85.7 0.061 16.29
S.D. 0.30 29.7 9.1 19.7 0.117 13.5 0.027 7.22
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
3(F) Mean 1.78 78.9 46.1 63.5 0.648 87.2 0.091** 23.42
S.D. 0.22 12.7 9.8 28.0 0.090 16.6 0.019 14.49
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
4(F) Mean 1.54* 111.2 77.7 77.8 0.673 92.8 0.085** 33.53
S.D. 0.47 82.1 65.5 32.0 0.126 21.4 0.017 14.33
N 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Table 13 Summary Incidence of Necropsy Findings
------------ MALES ------------
Removal Reason: TERMINAL SACRIFICE ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
0 100 300 1000
(Control) mg/kg bw/day
Number of Animals Examined : 10 10 10 10
Group : (1) (2) (3) (4)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Kidneys;
Submitted........................................................................................ (10) (10) (10) (10)
No Visible Lesions............................................................................... 10 10 8 2
Enlarged ........................................................................................ 0 0 0 1
Enlarged; both .................................................................................. 0 0 0 6
Mottled Appearance .............................................................................. 0 0 1 0
Mottled Appearance; both ........................................................................ 0 0 1 8
Table 13 (continued) Summary Incidence of Necropsy Findings
----------- FEMALES -----------
Removal Reason: TERMINAL SACRIFICE ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
0 100 300 1000
(Control) mg/kg bw/day
Number of Animals Examined : 8 10 10 10
Group : (1) (2) (3) (4)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Lungs (With Bronchi);
Submitted........................................................................................ (8) (10) (10) (10)
No Visible Lesions............................................................................... 8 8 9 10
Discolouration; red ............................................................................. 0 2 1 0
Uterus (With Cervix);
Submitted........................................................................................ (8) (10) (10) (10)
No Visible Lesions............................................................................... 7 10 10 9
Fluid Filled; left horn ......................................................................... 1 0 0 0
Damaged On Removal .............................................................................. 0 0 0 1
Table 14 Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weights
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
0 100 300 1000 0 100 300 1000
Control mg/kg bw/day Control mg/kg bw/day
ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ
Terminal Bodyweight ........... Mean (g) 404.8 433.7 392.9 371.6 236.1 240.0 229.6 229.9
S.D. 25.0 29.6 26.3 37.9 17.9 15.5 19.9 17.3
N 10 10 10 10 8 10 10 10
Adrenals ...................... Mean (g) 0.06869 0.07604 0.07258 0.06764 0.08043 0.08896 0.08249 0.08915
S.D. 0.01193 0.01285 0.01345 0.00995 0.01423 0.01396 0.01235 0.01702
N 10 10 10 10 8 10 10 10
Mean (%) 0.017 0.018 0.018 0.018 0.034 0.037 0.036 0.039
S.D. 0.003 0.003 0.003 0.002 0.006 0.006 0.005 0.006
N 10 10 10 10 8 10 10 10
Brain (Including Cerebrum,
Cerebellum And Pons) .......... Mean (g) 2.14393 2.16050 2.05979 2.00814 1.93270 1.93693 1.89383 1.91942
S.D. 0.08558 0.15077 0.11303 0.14578 0.10201 0.10207 0.10452 0.04539
N 10 10 10 10 8 10 10 10
Mean (%) 0.531 0.500 0.526 0.543 0.821 0.809 0.828 0.838
S.D. 0.034 0.045 0.036 0.043 0.057 0.053 0.048 0.052
N 10 10 10 10 8 10 10 10
Epididymides .................. Mean (g) 1.77581 1.86940 1.85847 1.80944
S.D. 0.25734 0.23312 0.21586 0.19020
N 10 10 10 10
Mean (%) 0.439 0.431 0.473 0.488
S.D. 0.056 0.045 0.048 0.042
N 10 10 10 10
Heart ......................... Mean (g) 1.20622 1.23805 1.17882 1.15097 0.83254 0.86468 0.78187 0.75357
S.D. 0.16646 0.12956 0.11417 0.15482 0.13036 0.13782 0.06172 0.07486
N 10 10 10 10 8 10 10 10
Mean (%) 0.300 0.287 0.301 0.310 0.352 0.359 0.343 0.328
S.D. 0.056 0.039 0.029 0.034 0.043 0.044 0.037 0.025
N 10 10 10 10 8 10 10 10
Table 14 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weights
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
0 100 300 1000 0 100 300 1000
Control mg/kg bw/day Control mg/kg bw/day
ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ
Kidneys ....................... Mean (g) 2.31104 2.55561 2.49304* 3.30525** 1.42424 1.48146 1.65941** 1.69022**
S.D. 0.29485 0.19343 0.29044 0.58588 0.15628 0.22463 0.19687 0.17709
N 10 10 10 10 8 10 10 10
Mean (%) 0.570 0.591 0.634* 0.889** 0.602 0.616 0.730** 0.734**
S.D. 0.051 0.050 0.055 0.126 0.031 0.078 0.136 0.041
N 10 10 10 10 8 10 10 10
Liver ......................... Mean (g) 13.9029 16.5572* 14.9857* 17.4792** 8.08426 8.81915* 9.03080** 11.8208**
S.D. 1.38539 2.18802 2.00284 1.82541 0.91180 0.87045 0.58299 0.79583
N 10 10 10 10 8 10 10 10
Mean (%) 3.430 3.818* 3.804* 4.719** 3.421 3.677* 3.950** 5.154**
S.D. 0.190 0.431 0.340 0.428 0.242 0.323 0.302 0.319
N 10 10 10 10 8 10 10 10
Ovaries ....................... Mean (g) 0.11970 0.12593 0.12323 0.12054
S.D. 0.02594 0.03372 0.04079 0.03466
N 8 10 10 10
Mean (%) 0.051 0.053 0.053 0.053
S.D. 0.012 0.014 0.016 0.017
N 8 10 10 10
Spleen ........................ Mean (g) 0.74130 0.75664 0.81136 0.76347 0.52904 0.54271 0.55121 0.57851
S.D. 0.11061 0.08432 0.18657 0.10154 0.07289 0.04957 0.07302 0.15533
N 10 10 10 10 8 10 10 10
Mean (%) 0.183 0.174 0.206 0.206 0.224 0.227 0.241 0.251
S.D. 0.023 0.012 0.042 0.024 0.028 0.023 0.030 0.061
N 10 10 10 10 8 10 10 10
Table 14 (continued) Group Mean Organ Weights with Corresponding Relative (% of Body Weight) Organ Weights
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ MALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ FEMALES ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
0 100 300 1000 0 100 300 1000
Control mg/kg bw/day Control mg/kg bw/day
ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒ
Testes ........................ Mean (g) 4.09113 4.13667 3.96420 4.26239*
S.D. 0.41532 0.34494 0.39764 0.54166
N 10 10 10 10
Mean (%) 1.010 0.956 1.010 1.152*
S.D. 0.075 0.080 0.091 0.130
N 10 10 10 10
Thymus ........................ Mean (g) 0.47385 0.47422 0.43132 0.42857 0.37523 0.39584 0.37713 0.38011
S.D. 0.08092 0.09994 0.08679 0.12761 0.04747 0.06394 0.09015 0.09023
N 10 10 10 10 8 10 9 10
Mean (%) 0.117 0.109 0.110 0.113 0.160 0.165 0.165 0.165
S.D. 0.018 0.021 0.019 0.024 0.025 0.028 0.030 0.034
N 10 10 10 10 8 10 9 10
Uterus (With Cervix) .......... Mean (g) 0.82161 0.86173 0.88616 0.88141
S.D. 0.29175 0.28757 0.30397 0.28429
N 8 10 10 10
Mean (%) 0.351 0.364 0.392 0.386
S.D. 0.127 0.139 0.154 0.125
N 8 10 10 10
APPENDICES
Appendix 1 Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
2 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
3 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
4 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
5 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
6 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
7 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
8 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
9 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
10 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
1(M) 1 No Abnormalities Detected X . X
Scheduled kill . . X
2 No Abnormalities Detected X . X
Scheduled kill . . X
3 No Abnormalities Detected X . X
Scheduled kill . . X
4 No Abnormalities Detected X . X
Scheduled kill . . X
5 No Abnormalities Detected X . X
Scheduled kill . . X
6 No Abnormalities Detected X . X
Scheduled kill . . X
7 No Abnormalities Detected X . X
Scheduled kill . . X
8 No Abnormalities Detected X . X
Scheduled kill . . X
9 No Abnormalities Detected X . X
Scheduled kill . . X
10 No Abnormalities Detected X . X
Scheduled kill . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X X X X X X X X X X
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected X X X X X X . . . . . . . . .
Damaged Tail+ . . . . . . X . . . . . . . .
Killed `in extremis' . . . . . . X . . . . . . . .
15 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X . X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
+ = approximately 55mm of tail skinned
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
12 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
13 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
14 No Abnormalities Detected . . . . . . . . . . . . . . .
Damaged Tail . . . . . . . . . . . . . . .
Killed `in extremis' . . . . . . . . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
16 No Abnormalities Detected X X X X X X X X X X X X X X X
Found dead . . . . . . . . . . . . . . .
17 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
18 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
19 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
20 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
1(F) 11 No Abnormalities Detected X . X
Scheduled kill . . X
12 No Abnormalities Detected X . X
Scheduled kill . . X
13 No Abnormalities Detected X . X
Scheduled kill . . X
14 No Abnormalities Detected . . .
Damaged Tail . . .
Killed `in extremis' . . .
15 No Abnormalities Detected X . X
Scheduled kill . . X
16 No Abnormalities Detected X . .
Found dead . X@ .
17 No Abnormalities Detected X . X
Scheduled kill . . X
18 No Abnormalities Detected X . X
Scheduled kill . . X
19 No Abnormalities Detected X . X
Scheduled kill . . X
20 No Abnormalities Detected X . X
Scheduled kill . . X
@ = Animal died during bleeding procedure
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X . . X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X . . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 21 No Abnormalities Detected X . X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X X . X .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X . X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
22 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X . X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
25 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X . X X X X . X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . X . . X
29 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X . . X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X X . . . . X . . X
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
23 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
24 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
29 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . X . . X
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
24 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
22 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
24 No Abnormalities Detected X X . X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . X
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
29 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected . X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . .
29 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
28 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
29 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
29 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
29 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
22 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
23 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
24 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
25 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
26 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
27 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
28 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
29 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
2(M) 21 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
22 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
23 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
24 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
25 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
26 No Abnormalities Detected X . X
Scheduled kill . . X
27 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
28 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
29 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(M) 30 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
2(M) 30 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
32 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
33 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
34 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
35 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
36 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
37 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
38 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
39 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
40 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
2(F) 31 No Abnormalities Detected X . X
Scheduled kill . . X
32 No Abnormalities Detected X . X
Scheduled kill . . X
33 No Abnormalities Detected X . X
Scheduled kill . . X
34 No Abnormalities Detected X . X
Scheduled kill . . X
35 No Abnormalities Detected X . X
Scheduled kill . . X
36 No Abnormalities Detected X . X
Scheduled kill . . X
37 No Abnormalities Detected X . X
Scheduled kill . . X
38 No Abnormalities Detected X . X
Scheduled kill . . X
39 No Abnormalities Detected X . X
Scheduled kill . . X
40 No Abnormalities Detected X . X
Scheduled kill . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
45 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
46 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
47 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
48 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
49 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . . .
43 No Abnormalities Detected X X X X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
45 No Abnormalities Detected X X X X X X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . . .
46 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
47 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
48 No Abnormalities Detected X X X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . X .
49 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
45 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
46 No Abnormalities Detected X . X X X X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . . .
47 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
48 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
49 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X X X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . X .
42 No Abnormalities Detected X X X X X X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . X .
43 No Abnormalities Detected X X X X . X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X X . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . X .
45 No Abnormalities Detected X X X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . X X . X .
46 No Abnormalities Detected X X X X . X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X X . X . . X .
47 No Abnormalities Detected X X X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . X .
48 No Abnormalities Detected X X X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . X . . X .
49 No Abnormalities Detected X X X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X . . X . X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
45 No Abnormalities Detected X . X X X . X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . X . . . . X . . . .
46 No Abnormalities Detected X . X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
47 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
48 No Abnormalities Detected X . . X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X . . X .
49 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
42 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
43 No Abnormalities Detected X . . . . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X . . X . . X . . . .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
45 No Abnormalities Detected X . . . . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X . . X . . X . . . .
46 No Abnormalities Detected X . X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
47 No Abnormalities Detected X . X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . X .
48 No Abnormalities Detected X . . . . X X . . X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X . . X X . X . . . .
49 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 41 No Abnormalities Detected X X X X . X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . . . . . .
42 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
43 No Abnormalities Detected X . . X . . X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . X X . X .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X . X X . . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X X . . . . . .
45 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
46 No Abnormalities Detected X . X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
47 No Abnormalities Detected X X X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . . . . X .
48 No Abnormalities Detected X . X X . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . . .
49 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X . X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
42 No Abnormalities Detected X . X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
43 No Abnormalities Detected X X X X . . . X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X X . . . . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X . X . X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . X . . . . . .
45 No Abnormalities Detected X . X X . X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
46 No Abnormalities Detected X . X X . X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
47 No Abnormalities Detected X . X X . X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . . . . . .
48 No Abnormalities Detected X . X X . X . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . .
49 No Abnormalities Detected X X X X . X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . X . . X
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
45 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
46 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
47 No Abnormalities Detected X X X X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . X . . X
48 No Abnormalities Detected X X X X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X X . X . . X . . X
49 No Abnormalities Detected X X X X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected . X . X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . . . . X . . X . . .
42 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
43 No Abnormalities Detected . X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected . X X X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . X . . . . . . . . X
45 No Abnormalities Detected . X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X . . X
46 No Abnormalities Detected . X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . . . . X . . X
47 No Abnormalities Detected . X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X . . .
48 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
49 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected . X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X . . .
45 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
46 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
47 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
48 No Abnormalities Detected . X . X X . X X . . X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . . . . X
49 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
45 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
46 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
47 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
48 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
49 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
42 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
43 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . X
45 No Abnormalities Detected X X X X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . X
46 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
47 No Abnormalities Detected X X X X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . X . . X
48 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
49 No Abnormalities Detected X X X X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
42 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
43 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
45 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
46 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
47 No Abnormalities Detected X X . X X . X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . .
48 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
49 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
42 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
43 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
45 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
46 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
47 No Abnormalities Detected X X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . .
48 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
49 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X . X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . X
43 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
Noisy respiration . . . . . . . . X . . . . . .
44 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
45 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
46 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
47 No Abnormalities Detected X X . X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . X
48 No Abnormalities Detected X X . X X . . X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . . . . X . . X
49 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
45 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
46 No Abnormalities Detected X X . . X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . .
47 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
48 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
49 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
42 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
43 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
Noisy respiration . . . . . . . . . . . . . . .
44 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
45 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
46 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
47 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
48 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
49 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
3(M) 41 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
42 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
43 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
44 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
45 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
46 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
47 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
48 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
49 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X . X X . X X . X X . . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X . . X . X X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X X X X . X X X X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . X X . X .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X . . X . X X . X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X . . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X . . . . X X . . X . . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X . . X X . X X . . .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(M) 50 No Abnormalities Detected X . . X . . X . . X X X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . . . . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X . . X . . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X X X X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected . X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected . X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X X . . X . . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X . . .
Noisy respiration . . X . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected . X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected . X . X X . . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X . . .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(M) 50 No Abnormalities Detected . . X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X . . . . . . X . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
3(M) 50 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
52 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
59 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X X X X X X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . X .
52 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X . X X X X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . X . . X .
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
59 No Abnormalities Detected X X X X X X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X X X X . X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . . . . . .
52 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X X X X X X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . . .
57 No Abnormalities Detected X . X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
58 No Abnormalities Detected X . X X . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . . .
59 No Abnormalities Detected X . X X X X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X . X X X X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . . . . X .
52 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . X .
56 No Abnormalities Detected X . X X . X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X . . X .
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X . X X X X X . X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . X X
59 No Abnormalities Detected X . X X . X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . . . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X . X X . X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . X . . . .
52 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . X .
54 No Abnormalities Detected X X X X X X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . . .
56 No Abnormalities Detected X . X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X .
57 No Abnormalities Detected X X X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . X .
58 No Abnormalities Detected X . . X . X X . X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X . . X X
59 No Abnormalities Detected X . X X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
52 No Abnormalities Detected X X X X X X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . X .
53 No Abnormalities Detected X . X X X X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X . X X . X X . X X X X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X X
57 No Abnormalities Detected X X X X . X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . . . . . .
58 No Abnormalities Detected . . X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X . . X . . X . . . . . X .
59 No Abnormalities Detected X . X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 51 No Abnormalities Detected X X X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . X . . X .
52 No Abnormalities Detected X . X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
53 No Abnormalities Detected X . X X X X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . X .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X . X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . . . . . .
56 No Abnormalities Detected X . X X . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . . .
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X . . X . X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . . . X . . . .
59 No Abnormalities Detected X . . X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X . X X . X . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . .
52 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
53 No Abnormalities Detected X X X X . X . X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . X . . . . . .
54 No Abnormalities Detected X . X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X . X X X X . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . X . . X . . .
57 No Abnormalities Detected X X X X X X . X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X . . X . X . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . X X . X . . .
59 No Abnormalities Detected X . X X . X . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
52 No Abnormalities Detected X X X X X X X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X X . X
53 No Abnormalities Detected X X . X X . X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X X . X
54 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
55 No Abnormalities Detected X X X X X X X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X X . X
56 No Abnormalities Detected X X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
57 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
58 No Abnormalities Detected X X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . X
59 No Abnormalities Detected X X X X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X X . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
52 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
53 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
57 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
58 No Abnormalities Detected X X . . X . X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . . . . X X . X
59 No Abnormalities Detected X X . X X . X X X . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . X . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
52 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
54 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
55 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
56 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
57 No Abnormalities Detected X X . X X . X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . .
58 No Abnormalities Detected X X . X X . . X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . . . . X . . .
59 No Abnormalities Detected X X . X X . . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . X
52 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
53 No Abnormalities Detected X X . X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . X
54 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
55 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
56 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
59 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
52 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
53 No Abnormalities Detected X X . X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . X
54 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
55 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
56 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
57 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
58 No Abnormalities Detected X X . X X . . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X . . .
59 No Abnormalities Detected X X . X X . X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
52 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
53 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
54 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
55 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
56 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
57 No Abnormalities Detected X X X X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . .
58 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
59 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
52 No Abnormalities Detected X X X X X X X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X X . X
53 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
54 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
55 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
56 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
57 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
58 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
59 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
52 No Abnormalities Detected X X . X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . X
53 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
54 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
55 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
56 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
57 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
58 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
59 No Abnormalities Detected X X X X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
52 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
53 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
54 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
55 No Abnormalities Detected X X X X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . . . . . . . .
56 No Abnormalities Detected X X . . X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . .
57 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
58 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
59 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 51 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
52 No Abnormalities Detected X X . X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . X
53 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
54 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
55 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
56 No Abnormalities Detected X X . X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . .
57 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
58 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
59 No Abnormalities Detected X X X X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
3(F) 51 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
52 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
53 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
54 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
55 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
56 No Abnormalities Detected . . X
Scheduled kill . . X
Increased salivation X . .
57 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
58 No Abnormalities Detected . . X
Scheduled kill . . X
Increased salivation X . .
59 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X . X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X . X X X X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X X X X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X . X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
3(F) 60 No Abnormalities Detected X . X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X X X . X . X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . X . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X X X X . X X . . X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X X . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
3(F) 60 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
3(F) 60 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
62 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X X X X X X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . . .
65 No Abnormalities Detected X X X X X X X X X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X X X . X X X X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . X . . X X
67 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
68 No Abnormalities Detected X . X X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X X X X . X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . X .
62 No Abnormalities Detected X . X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X .
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X X X X X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X X . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
65 No Abnormalities Detected X . X X . X X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . X X . . X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X . . X X
67 No Abnormalities Detected X X X X . X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . X .
68 No Abnormalities Detected X . X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X X X X . X X . X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . X . . X X
62 No Abnormalities Detected X . . X . X X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X X X . X X . . X X X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X X . . . . X X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X . X X X X X . . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . X X . . .
65 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
67 No Abnormalities Detected X . X X X X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X X . X .
68 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
62 No Abnormalities Detected . . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X . X X . X . . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . X X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X . X X . X X . . X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . . . . X .
65 No Abnormalities Detected X . . X . . . . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X X X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . . X . . . . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X X X X . X X . X X
67 No Abnormalities Detected X . X X . X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X . . X .
68 No Abnormalities Detected X . . X . X X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X X X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . X . . X . . X .
62 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X . X X . X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . . . . X .
65 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
67 No Abnormalities Detected X . X X . X X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X X . X .
68 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X . . . X X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X . . . X . . X . . X .
62 No Abnormalities Detected X . . . . . X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X X . X .
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X . . . . . X . . . . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X X X . . X .
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X . X X X X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . X .
65 No Abnormalities Detected X . . . . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . . . . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X X . X X
67 No Abnormalities Detected X . . . . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X . . X . . X X . X .
68 No Abnormalities Detected X . . . . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X X . X X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 61 No Abnormalities Detected X . X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X .
62 No Abnormalities Detected X . . X . . X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X .
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X . X X . X X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . . .
65 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
67 No Abnormalities Detected X . X X . X X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X X
68 No Abnormalities Detected X . . X . . X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X . X X . X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
62 No Abnormalities Detected X . . X . X . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X . . X . . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X . X . X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . X . . . . . X
65 No Abnormalities Detected X . . X . . . X . . X . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . . X X . X X X X
Hunched posture . . . . . . . . . . . . . X .
66 No Abnormalities Detected X . . X . . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . . X X . X X . X
67 No Abnormalities Detected X . . X . X . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . X . . X X . X
68 No Abnormalities Detected X . X X . . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
62 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . X X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
65 No Abnormalities Detected . X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected . X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X X . X
67 No Abnormalities Detected . X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X X . X
68 No Abnormalities Detected . X . X X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected . X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X X . X
62 No Abnormalities Detected . X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
65 No Abnormalities Detected X X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
67 No Abnormalities Detected X X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . X
68 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected . X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . X . . X . . X . . X
62 No Abnormalities Detected . X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
65 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected . X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X . . X
67 No Abnormalities Detected . X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . . . . X
68 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . X X . X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . .
62 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X . X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . . . . X
65 No Abnormalities Detected . X . . X . . X . . X . . X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . .
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected . X . X X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X X . X
67 No Abnormalities Detected X X . . X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . .
68 No Abnormalities Detected . X . . X . . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X . . X . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
62 No Abnormalities Detected X X . . X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . X X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
65 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
67 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
68 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X X X X X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . X . X . . X . . X
62 No Abnormalities Detected . X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
65 No Abnormalities Detected X X X . X . . X . . . . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . X . X X . X X X X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected . X . . X . . X . . X X . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . . X . X
67 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
68 No Abnormalities Detected . X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
62 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
65 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
67 No Abnormalities Detected X X . X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . .
68 No Abnormalities Detected X X . X X . X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
62 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
Noisy respiration . . . . . . . . . . . . . . X
63 No Abnormalities Detected X X . X X X . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
65 No Abnormalities Detected X X . . X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X . . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X . . X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X X . X . . X
67 No Abnormalities Detected X X . X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . .
68 No Abnormalities Detected . X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X . X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
62 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
64 No Abnormalities Detected X X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . . . . .
65 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X . X X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X . . X
67 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
68 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 61 No Abnormalities Detected X X X X X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . .
62 No Abnormalities Detected X X . . X X X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . . . . X . . X . . .
Noisy respiration . . . . . . . . . . . . . . .
63 No Abnormalities Detected . X . X X X X X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . . . . X X . X . . .
Noisy respiration . . . . . . . . . . . X . . .
64 No Abnormalities Detected X X . X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . . . . .
65 No Abnormalities Detected . X X X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . X X . X X . X X . X
Hunched posture . . . . . . . . . . . . . . .
66 No Abnormalities Detected X X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X X . X
67 No Abnormalities Detected . X X X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . . . . . . . X . . .
68 No Abnormalities Detected X X X . X X X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . X . . . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
4(M) 61 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
62 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
63 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
64 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
65 No Abnormalities Detected . . X
Scheduled kill . . X
Increased salivation X . .
Hunched posture . . .
66 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
67 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
68 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X X X X . X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X . . . . . . . . . .
70 No Abnormalities Detected X . X X . X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . . . X . . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X X X X X X X X X X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . X
70 No Abnormalities Detected X . X X . X X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X X X X . . X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X X . . . . X . . X .
70 No Abnormalities Detected X . . X . . X . . . . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X X X X . X X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected . . X X X X X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X . . . . . X X . X . . X X
70 No Abnormalities Detected . . . X . . X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
70 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X . X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
70 No Abnormalities Detected X . . X . . X . X X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(M) 69 No Abnormalities Detected X . X X . . X . X X . X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . . .
70 No Abnormalities Detected X . . X . X X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X X . X .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X . X X . X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
70 No Abnormalities Detected X . . X . X . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . X X . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X . X X . X X X X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X X . X
70 No Abnormalities Detected . X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . . . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected . X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . . . . X
70 No Abnormalities Detected . X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X X X X X X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . X
70 No Abnormalities Detected . X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X X X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X X . X
70 No Abnormalities Detected X X . . X . X X . X X . . X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X X . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . . . . X . . X
70 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X X X X . X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . .
70 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X X X X X X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . X . . X
70 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected . X . X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . . . . X . . . . . .
70 No Abnormalities Detected . X . X X . X X X X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . . . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X X X X X X X . X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . . . . .
70 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(M) 69 No Abnormalities Detected X X . X X X X X X X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . . . . X . . .
70 No Abnormalities Detected X X X X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
4(M) 69 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
70 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X X X X X X X . X X . X X X X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . X . . . .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X X X X . X X . X X X X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . . .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X X X X X X . X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . . . . . .
74 No Abnormalities Detected X X X X X X X X X X X X X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . . . . . .
75 No Abnormalities Detected X X X X . . X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X X . X . . . . . X .
76 No Abnormalities Detected X X X X X X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X X X X X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . . . . . . X . . X . . X .
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . X X X X X X X X . X X X X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . . . . X . . . .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X . X X . X X . X X . .
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X X X X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X . . X . . X .
74 No Abnormalities Detected X . X X X X X . . X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . . . . X X . X . . X .
75 No Abnormalities Detected X . X X . . X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X X . X .
76 No Abnormalities Detected X . X X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . X X . X X . X X X X X . X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X . . X . X X . X X . X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X .
74 No Abnormalities Detected X . X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X . . X .
75 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
76 No Abnormalities Detected X . . X . . X . . X . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X X X X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . X X . X X . X X . X X . X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X . X X . . X . X X . .
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X . . X X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X . . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . X X . . X . . X . . X .
74 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
75 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
76 No Abnormalities Detected X . . . . . . . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X X X X . X . . X X
Noisy respiration . . . . . . . . . . . . . X .
77 No Abnormalities Detected X . X . . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X . X X X . X X . X X . X X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . . X X X X X X X . X X . X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . . . . . . . X . . X .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . . X . X X . X X . . X . X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X X . X .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . . X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X . . X .
74 No Abnormalities Detected X . X X . X X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X X . X .
75 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
76 No Abnormalities Detected . . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X . X X . X X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X X . X X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . X X . X X . X X . X X . X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X . X X . . X . X X . X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X X . X . . X .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . X . . X .
74 No Abnormalities Detected X . . X . X X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . X . . X .
75 No Abnormalities Detected X . . X . X X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X . . X X
76 No Abnormalities Detected X . . X . . X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X . . X X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected . . . X . . X X X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation X X X . X X . . . . X . . X X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 71 No Abnormalities Detected X . . X . . X . X X X X X . X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . . . . X .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . . X . X X . X X X X X . X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X . . . . . X .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X X . X X . X X X X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . X . . . . . X .
74 No Abnormalities Detected X . . X . . X . X X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . X . . X X
75 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
76 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X . X X . X . X . X X . X X .
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X . X X . X . X . X X . X X .
Scab~ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X . X X . X . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X . . X
74 No Abnormalities Detected X . X X . X . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X X . X . . X
75 No Abnormalities Detected X . X X . . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . . X X . X X . X
76 No Abnormalities Detected X . X X . . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X . X X . . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . X . . X X . . X X . X X . X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . X X . . X . X X .
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X . X X . . X . X X .
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . X
74 No Abnormalities Detected X X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
75 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
76 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . X X . . X . X X X
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X . . .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X . X X . X X . X X X
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
74 No Abnormalities Detected X X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
75 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
76 No Abnormalities Detected . X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X . . X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . . X . X X . X X .
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X X X X . X X . X X .
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
74 No Abnormalities Detected X X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
75 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
76 No Abnormalities Detected X X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . X X . X X . X X .
Scab@ . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X . X X . X X . X X .
Scab# . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
74 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
75 No Abnormalities Detected . X . . X . . X X X X X . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . . . . . X . X
76 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected . X . . X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X . . X . . X
@ = Scab on back
# = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . X . . . . . . X X
Scab# . . . . . . . X X X X X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X . X X . X X . X . .
Scab@ . . . . . . . . . . . . . X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X . . X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . .
74 No Abnormalities Detected X X . X X . . X . X X . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X X X X
75 No Abnormalities Detected . X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X . . X
76 No Abnormalities Detected X X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected . X . X X . . X . . X . . . .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . X . . . . .
Increased salivation X . X . . X X . X X . X X X X
# = Scab on back
@ = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X X X X . X X . X . . . . .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . X X X X X
72 No Abnormalities Detected . . . . . . . . . . . . . . .
Scab@ X X X X X X X X X X . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . X X X X X
73 No Abnormalities Detected X X . X X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
74 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
75 No Abnormalities Detected . X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X X . X
76 No Abnormalities Detected . X . X X . X X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X . . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected . X . . X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X . . X . . X
@ = Scab on dorsal surface
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected . . . . . . . . . . . . . . .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . . . . X
Generalised fur loss X X X X X X X X X X X X X X X
72 No Abnormalities Detected . . . . . . . . . . . . . . .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
Generalised fur loss X X X X X X X X X X X X X X X
73 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
74 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
75 No Abnormalities Detected . X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X . . X X . X
76 No Abnormalities Detected X X . X X . X X . . . . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
Noisy respiration . . . . . . . . X X X X X . .
77 No Abnormalities Detected X X . X X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected . X . X X . X X . X X . X X .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
Generalised fur loss X . . . . . . . . . . . . . .
72 No Abnormalities Detected . X . X X . . X . X X . X X .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X . . X . . X
Generalised fur loss X . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
74 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
75 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
76 No Abnormalities Detected X X . . X . . X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . X X . X X . X X . X X X
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . .
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X . X X . X X X X X X
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . .
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X . X X . X X X X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . . . . X
74 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
75 No Abnormalities Detected X X . . X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X X . X X . X
76 No Abnormalities Detected X X . . X . X X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . .
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X . . X . X X . . X . . X X
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X X . X X . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 71 No Abnormalities Detected X X . . X . X X . X X . X X .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
72 No Abnormalities Detected X X . X X X X X . X X . X X .
Scab . . . . . . . . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
Generalised fur loss . . . . . . . . . . . . . . .
73 No Abnormalities Detected X X . X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . . . . X . . X . . X
74 No Abnormalities Detected X X X X X X X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . X . . X . . X
75 No Abnormalities Detected X X X X X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X X . X X . X . . X
76 No Abnormalities Detected X X X X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
77 No Abnormalities Detected X X X X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Staining around the mouth . . . . . . . . . . . . . . .
Increased salivation . . . . . X . . X X . X X . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
4(F) 71 No Abnormalities Detected X . X
Scab . . .
Scheduled kill . . X
Increased salivation . . .
Generalised fur loss . . .
72 No Abnormalities Detected X . X
Scab . . .
Scheduled kill . . X
Increased salivation . . .
Generalised fur loss . . .
73 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
74 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
75 No Abnormalities Detected . . X
Scheduled kill . . X
Increased salivation X . .
76 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
77 No Abnormalities Detected . . X
Scheduled kill . . X
Staining around the mouth . . .
Increased salivation X . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
Group Animal 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X X X X . . X . X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X X . X . . X . . X .
79 No Abnormalities Detected X X X X X X X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . . . . . . . X . . X .
80 No Abnormalities Detected X X X X . . X X X X . X X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . . . X X . . . . X . . X .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 6 6 6 7 7 7 8 8 8 9 9 9 10 10 10
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X . . X . . X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . X X . X X
79 No Abnormalities Detected X . X X . . X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X . . X X . X X
80 No Abnormalities Detected X . X X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 11 11 11 12 12 12 13 13 13 14 14 14 15 15 15
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X . . X . X X . . X . . X . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . X X . X X . X .
79 No Abnormalities Detected X . X X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X X . X X
80 No Abnormalities Detected X . . X . . X . . . . . . . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X X X X X X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 16 16 16 17 17 17 18 18 18 19 19 19 20 20 20
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X . X X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . X X . X X . X X
79 No Abnormalities Detected X . . . . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X X . X X
80 No Abnormalities Detected X . . . . . X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X X X X . X X . X . . X X
Noisy respiration . . . . . . . . . . . . . . X
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 21 21 21 22 22 22 23 23 23 24 24 24 25 25 25
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X . . X . . X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X . . X X . X X
79 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
80 No Abnormalities Detected . . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 26 26 26 27 27 27 28 28 28 29 29 29 30 30 30
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected . . . X . . X . X X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X . . X X . X X
79 No Abnormalities Detected . . . X . . X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X . . X X
80 No Abnormalities Detected . . . X . . X . . X . X X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X X X . X X . X X . X . . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 31 31 31 32 32 32 33 33 33 34 34 34 35 35 35
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h
4(F) 78 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
79 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
80 No Abnormalities Detected X . . X . . X . . X . . X . .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X X . X X . X X . X X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 36 36 36 37 37 37 38 38 38 38 39 39 39 40 40
(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h A.M. Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected X . X X . . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X X . . X X . X X . X
79 No Abnormalities Detected X . . X . X . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X X . X . . . X X . X X . X
80 No Abnormalities Detected X . X X . X . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . X . . X . . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 40 41 41 41 42 42 42 43 43 43 44 44 44 45 45
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected X X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X X . X
79 No Abnormalities Detected X X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X X . X
80 No Abnormalities Detected X X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 45 46 46 46 47 47 47 48 48 48 49 49 49 50 50
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X . . X
79 No Abnormalities Detected . X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X . . X
80 No Abnormalities Detected . X . . X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 50 51 51 51 52 52 52 53 53 53 54 54 54 55 55
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X X . X
79 No Abnormalities Detected . X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X X . X
80 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 55 56 56 56 57 57 57 58 58 58 59 59 59 60 60
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X . . X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . X X . X
79 No Abnormalities Detected . X . . X . . X . . X X . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X X . X X . . X . X
80 No Abnormalities Detected X X . . X . . X . . X X . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X X . . X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 60 61 61 61 62 62 62 63 63 63 64 64 64 65 65
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X . X X . . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X . . .
79 No Abnormalities Detected . X . X X . . X . X X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X . . .
80 No Abnormalities Detected . X . X X . . X . . X . X X X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X . . .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 65 66 66 66 67 67 67 68 68 68 69 69 69 70 70
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X . X X . . X . . X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X . . X
79 No Abnormalities Detected . X . X X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X . . X X . X
80 No Abnormalities Detected . X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 70 71 71 71 72 72 72 73 73 73 74 74 74 75 75
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected X X . X X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X . . X
79 No Abnormalities Detected X X . X X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X . . X X . X
80 No Abnormalities Detected X X . . X . X X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 75 76 76 76 77 77 77 78 78 78 79 79 79 80 80
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected X X . . X . . X . X X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X X . X . . X X . X
79 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
80 No Abnormalities Detected X X . . X . X X . X X . X X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X . . X . . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected X X . . X . X X . . X . . . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X X . X X X .
79 No Abnormalities Detected X X . . X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X X . X . . X X . X X . X
80 No Abnormalities Detected . X . . X . X X . X X . . . X
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . X X . X . . X . . X X X .
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 85 86 86 86 87 87 87 88 88 88 89 89 89 90 90
(Sex) Number Clinical Sign 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post
4(F) 78 No Abnormalities Detected . X X X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation X . . . . X . . X X . X X . X
79 No Abnormalities Detected X X . X X . X X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X . . X X . X X . X
80 No Abnormalities Detected X X . X X . . X . . X . . X .
Scheduled kill . . . . . . . . . . . . . . .
Increased salivation . . X . . X X . X X . X X . X
Noisy respiration . . . . . . . . . . . . . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 1 (continued) Individual Daily Clinical Observations
Day Numbers Relative to Start Date
(continued)
Group Animal 90 90 91
(Sex) Number Clinical Sign 1h P.M. A.M.
4(F) 78 No Abnormalities Detected . . X
Scheduled kill . . X
Increased salivation X . .
79 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
80 No Abnormalities Detected X . X
Scheduled kill . . X
Increased salivation . . .
Noisy respiration . . .
X = Present
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
1(M) 1 No Abnormalities Detected X X X X X X X X X X X X X X
2 No Abnormalities Detected X X X X X X X X X X X X X X
3 No Abnormalities Detected X X X X X X X X X X X X X X
4 No Abnormalities Detected X X X X X X X X X X X X X X
5 No Abnormalities Detected X X X X X X X X X X X X X X
6 No Abnormalities Detected X X X X X X X X X X X X X X
7 No Abnormalities Detected X X X X X X X X X X X X X X
8 No Abnormalities Detected X X X X X X X X X X X X X X
9 No Abnormalities Detected X X X X X X X X X X X X X X
10 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
1(F) 11 No Abnormalities Detected X X X X X X X X X X X X X X
12 No Abnormalities Detected X X X X X X X X X X X X X X
13 No Abnormalities Detected X X X X X X X X X X X X X X
14 No Abnormalities Detected X X X X X X . . . . . . . .
15 No Abnormalities Detected X X X X X X X X X X X X X X
16 No Abnormalities Detected X X X X X X X X X X X X X X
17 No Abnormalities Detected X X X X X X X X X X X X X X
18 No Abnormalities Detected X X X X X X X X X X X X X X
19 No Abnormalities Detected X X X X X X X X X X X X X X
20 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
2(M) 21 No Abnormalities Detected X X X X X X X X X X X X X X
22 No Abnormalities Detected X X X X X X X X X X X X X X
23 No Abnormalities Detected X X X X X X X X X X X X X X
24 No Abnormalities Detected X X X X X X X X X X X X X X
25 No Abnormalities Detected X X X X X X X X X X X X X X
26 No Abnormalities Detected X X X X X X X X X X X X X X
27 No Abnormalities Detected X X X X X X X X X X X X X X
28 No Abnormalities Detected X X X X X X X X X X X X X X
29 No Abnormalities Detected X X X X X X X X X X X X X X
30 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
2(F) 31 No Abnormalities Detected X X X X X X X X X X X X X X
32 No Abnormalities Detected X X X X X X X X X X X X X X
33 No Abnormalities Detected X X X X X X X X X X X X X X
34 No Abnormalities Detected X X X X X X X X X X X X X X
35 No Abnormalities Detected X X X X X X X X X X X X X X
36 No Abnormalities Detected X X X X X X X X X X X X X X
37 No Abnormalities Detected X X X X X X X X X X X X X X
38 No Abnormalities Detected X X X X X X X X X X X X X X
39 No Abnormalities Detected X X X X X X X X X X X X X X
40 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
3(M) 41 No Abnormalities Detected X X X X X X X X X X X X X X
42 No Abnormalities Detected X X X X X X X X X X X X X X
43 No Abnormalities Detected X X X X X X X X X X X X X X
44 No Abnormalities Detected X X X X X X X X X X X X X X
45 No Abnormalities Detected X X X X X X X X X X X X X X
46 No Abnormalities Detected X X X X X X X X X X X X X X
47 No Abnormalities Detected X X X X X X X X X X X X X X
48 No Abnormalities Detected X X X X X X X X X X X X X X
49 No Abnormalities Detected X X X X X X X X X X X X X X
50 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
3(F) 51 No Abnormalities Detected X X X X X X X X X X X X X X
52 No Abnormalities Detected X X X X X X X X X X X X X X
53 No Abnormalities Detected X X X X X X X X X X X X X X
54 No Abnormalities Detected X X X X X X X X X X X X X X
55 No Abnormalities Detected X X X X X X X X X X X X X X
56 No Abnormalities Detected X X X X X X X X X X X X X X
57 No Abnormalities Detected X X X X X X X X X X X X X X
58 No Abnormalities Detected X X X X X X X X X X X X X X
59 No Abnormalities Detected X X X X X X X X X X X X X X
60 No Abnormalities Detected X X X X X X X X X X X X X X
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
4(M) 61 No Abnormalities Detected X X X X X X X X X X X X X X
62 No Abnormalities Detected X X . X X X X X X X X X X X
Autonomic ƒ Salivation . . S . . . . . . . . . . .
63 No Abnormalities Detected X X X X X X X X X X X X X X
64 No Abnormalities Detected X X X X X X X X X X X X X X
65 No Abnormalities Detected X X X X X X X X X X X X X X
66 No Abnormalities Detected X X X X X X X X X X X X X X
67 No Abnormalities Detected X X X X X X X X X . X X X X
Autonomic ƒ Salivation . . . . . . . . . S . . . .
68 No Abnormalities Detected X X X X X X X X X X X X X X
69 No Abnormalities Detected X X X X X X X X X X X X X X
70 No Abnormalities Detected X X . X X X X X X X X X X X
Autonomic ƒ Salivation . . S . . . . . . . . . . .
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 2 (continued) Individual Behavioral Assessments (Observations)
Day Numbers Relative to Start Date
Group Animal
(Sex) Number Clinical Sign -1 7 14 21 28 35 42 49 56 63 70 77 84 89
4(F) 71 No Abnormalities Detected X X X X X X X X X X X X X X
72 No Abnormalities Detected X X X . X X X X X X X X X X
Autonomic ƒ Salivation . . . E . . . . . . . . . .
73 No Abnormalities Detected X X X X X X X X X X X X X X
74 No Abnormalities Detected X X X X X X X X X X X X X X
75 No Abnormalities Detected X X X . . . X . . X X X X X
Autonomic ƒ Salivation . . . E E E . S S . . . . .
76 No Abnormalities Detected X X X . . X X X . . . X X X
Autonomic ƒ Salivation . . . M M . . . M M M . . .
77 No Abnormalities Detected X X X X X X X X X X X X X X
78 No Abnormalities Detected X X X X X X X X X X X X X X
79 No Abnormalities Detected X X X . . . . X X X X X X X
Respiration ƒ Decreased Rate . . . X . . . . . . . . . .
Autonomic ƒ Salivation . . . E S S S . . . . . . .
Hunched posture . . . X X X X . . . . . . .
80 No Abnormalities Detected X X X . . . . . X X X X X X
Autonomic ƒ Salivation . . . E E E E E . . . . . .
X = Present E = Extreme M = Moderate S = Slight
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 1 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 1 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 2 0
49 0 0 0 0
50 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.2 0.0
S.D. 0.0 0.4 0.6 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 1 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 1 0 0
57 0 0 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: ƒ1 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 1 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 1 0
5 0 1 1 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.2 0.0
S.D. 0.0 0.3 0.4 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 1 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.1 0.0
S.D. 0.0 0.0 0.3 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 2 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 1 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 7 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 1 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 2 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.6 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 1 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 14 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 1 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 1 0 0
80 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.5 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 21 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 1 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 1 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 1 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 0 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 28 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
14 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 1 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 35 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 1 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 1 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 1 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 1 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 0 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 42 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 2 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 1 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 1 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 1 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 49 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 1 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 1 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 1 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 1 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 1 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 56 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 2 0 0
76 0 1 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.3 0.0 0.0
S.D. 0.0 0.7 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 1 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 1 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 63 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 1 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 1 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 1 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 1 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 70 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 1 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 1 0 0
55 0 0 0 0
56 0 0 0 0
57 0 1 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 77 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 1 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 1 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 1 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 0 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.1 0.0 0.0 0.0
S.D. 0.3 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 1 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 0 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 0 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 0 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 84 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 1 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(M) 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 0 0
7 0 0 0 0
8 0 0 0 0
9 0 0 0 0
10 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
1(F) 11 0 0 0 0
12 0 0 0 0
13 0 0 0 0
15 0 0 0 0
16 0 0 0 0
17 0 0 0 0
18 0 0 0 0
19 0 0 0 0
20 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(M) 21 0 0 0 0
22 0 0 0 0
23 0 0 0 0
24 0 0 0 0
25 0 0 0 0
26 0 0 0 0
27 0 1 0 0
28 0 0 0 0
29 0 0 0 0
30 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
2(F) 31 0 0 0 0
32 0 0 0 0
33 0 0 0 0
34 0 0 0 0
35 0 0 0 0
36 0 0 0 0
37 0 0 0 0
38 0 0 0 0
39 0 0 0 0
40 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(M) 41 0 0 0 0
42 0 0 0 0
43 0 0 0 0
44 0 0 0 0
45 0 0 0 0
46 0 1 0 0
47 0 0 0 0
48 0 0 0 0
49 0 0 0 0
50 0 1 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.2 0.0 0.0
S.D. 0.0 0.4 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
3(F) 51 0 0 0 0
52 0 0 0 0
53 0 0 0 0
54 0 0 0 0
55 0 0 0 0
56 0 0 0 0
57 0 0 0 0
58 0 0 0 0
59 0 0 0 0
60 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(M) 61 0 0 0 0
62 0 0 0 0
63 0 0 0 0
64 0 0 0 0
65 0 1 0 0
66 0 0 0 0
67 0 0 0 0
68 0 0 0 0
69 0 0 0 0
70 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.1 0.0 0.0
S.D. 0.0 0.3 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 3 (continued) Individual and Group Mean Behavioral Assessments (Scores)
Day: 89 Relative to Start Date
Group Animal Transfer Urinƒ Defƒ Tail elƒ
(Sex) Number arousal ation ecation evation
4(F) 71 0 0 0 0
72 0 0 0 0
73 0 0 0 0
74 0 0 0 0
75 0 0 0 0
76 0 0 0 0
77 0 0 0 0
78 0 0 0 0
79 0 0 0 0
80 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
1(M) 1 540 428 501 397 1540 342
2 591 347 421 343 375 175
3 426 299 968 416 499 182
4 676 539 321 253 471 201
5 1013 379 494 384 1269 324
6 455 275 1219 516 626 251
7 696 394 1562 433 735 109
8 485 202 1327 193 638 183
9 351 167 315 223 959 260
10 655 309 754 425 1205 504
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 588.8 333.9 788.2 358.3 831.7 253.1
S.D. 187.8 109.2 453.9 104.0 392.6 113.3
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
1(F) 11 807 101 769 417 741 137
12 661 237 524 217 518 293
13 1022 192 1363 174 1434 730
15 1422 525 1306 558 1444 252
16 826 236 805 593 983 113
17 689 196 822 503 592 270
18 967 128 653 131 624 211
19 880 120 1261 379 1033 174
20 879 204 530 345 1137 345
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 905.9 215.4 892.6 368.6 945.1 280.6
S.D. 225.9 126.3 331.8 167.6 351.0 184.4
N 9 9 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
2(M) 21 833 334 1270 521 617 333
22 996 577 561 518 986 614
23 697 112 535 164 591 217
24 817 409 753 326 807 175
25 529 451 417 302 955 495
26 473 315 241 177 996 375
27 706 501 1073 431 349 118
28 791 590 1181 347 538 266
29 1477 397 1564 595 416 210
30 455 339 579 135 401 195
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 777.4 402.5 817.4 351.6 665.6 299.8
S.D. 300.4 140.8 429.3 162.5 252.2 156.1
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
2(F) 31 696 468 861 550 1571 357
32 936 449 1174 364 923 379
33 1342 345 1248 111 857 342
34 789 345 402 217 553 213
35 885 171 1175 479 1123 511
36 918 267 1174 308 1100 287
37 879 497 662 167 993 482
38 818 160 628 178 337 297
39 1047 275 1135 731 822 511
40 1267 344 949 623 1298 401
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 957.7 332.1 940.8 372.8 957.7 378.0
S.D. 205.8 116.8 292.1 213.7 352.7 100.3
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
3(M) 41 416 212 545 401 228 156
42 929 789 1252 764 764 224
43 421 214 1474 137 499 265
44 531 143 696 149 784 183
45 304 274 559 350 1263 229
46 354 280 372 298 569 268
47 674 480 1037 470 1228 419
48 586 261 543 204 886 397
49 853 696 430 298 422 297
50 516 362 402 388 428 264
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 558.4 371.1 731.0 345.9 707.1 270.2
S.D. 207.2 217.1 386.7 183.2 345.2 84.0
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
3(F) 51 639 270 1164 343 1211 220
52 1044 289 1087 295 970 158
53 1241 190 869 453 1099 180
54 1189 289 1363 518 594 538
55 695 145 664 395 1060 343
56 771 161 546 376 911 296
57 541 128 762 313 1345 757
58 1300 520 1107 733 899 359
59 1001 265 891 319 684 341
60 1213 109 1439 317 1244 552
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 963.4 236.6 989.2 406.2 1001.7 374.4
S.D. 279.7 121.1 293.2 134.6 240.4 189.0
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
4(M) 61 347 134 1019 537 228 130
62 285 199 621 125 711 285
63 480 324 507 247 762 185
64 536 365 577 379 773 127
65 531 198 885 332 1518 122
66 472 159 250 217 279 180
67 509 384 566 134 806 338
68 894 337 1039 292 471 203
69 524 132 410 269 731 162
70 1469 483 489 384 599 401
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 604.7 271.5 636.3 291.6 687.8 213.3
S.D. 342.9 122.4 262.0 124.1 357.7 96.2
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 4 (continued) Individual and Group Mean Functional Test Values (Grip Strength)
Day: 84 Relative to Start Date
Group Animal Test 1 Test 1 Test 2 Test 2 Test 3 Test 3
(Sex) Number Forelimb Hindlimb Forelimb Hindlimb Forelimb Hindlimb
g g g g g g
4(F) 71 701 422 1007 227 525 239
72 605 494 806 596 972 381
73 318 213 973 145 494 169
74 1086 340 1080 426 915 415
75 505 146 787 581 667 389
76 1203 214 1210 677 933 328
77 484 122 1016 163 900 287
78 996 269 570 377 940 264
79 1177 299 967 285 429 151
80 539 202 988 132 1048 131
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 761.4 272.1 940.4 360.9 782.3 275.4
S.D. 324.0 118.9 178.0 202.8 229.3 103.0
N 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
1(M) 1 513 0 3 0
2 563 0 0 0
3 291 0 0 0
4 449 0 1 0
5 328 0 9 0
6 346 0 7 0
7 583 0 70 0
8 500 0 9 0
9 476 0 8 0
10 473 0 13 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 452.2 0.0 12.0 0.0
S.D. 99.5 0.0 20.9 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
1(F) 11 502 0 19 0
12 529 0 15 0
13 524 0 110 0
15 691 0 68 0
16 700 0 0 0
17 509 0 130 0
18 308 0 47 0
19 480 0 2 0
20 539 0 89 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 531.3 0.0 53.3 0.0
S.D. 116.2 0.0 48.4 0.0
N 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
2(M) 21 822 0 110 0
22 580 0 52 0
23 570 0 10 0
24 418 0 28 0
25 641 0 3 0
26 411 0 3 0
27 484 0 13 0
28 638 0 16 0
29 408 0 3 0
30 379 0 15 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 535.1 0.0 25.3 0.0
S.D. 141.3 0.0 33.3 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
2(F) 31 662 0 8 0
32 868 0 0 0
33 533 0 2 0
34 887 0 157 0
35 577 0 3 0
36 644 0 4 0
37 657 0 223 0
38 648 0 16 0
39 893 0 88 0
40 647 0 6 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 701.6 0.0 50.7 0.0
S.D. 131.4 0.0 79.4 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
3(M) 41 603 0 45 0
42 487 0 12 0
43 495 0 0 0
44 553 0 8 0
45 459 0 31 0
46 574 0 17 0
47 361 0 4 0
48 458 0 5 0
49 765 0 38 0
50 467 0 17 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 522.2 0.0 17.7 0.0
S.D. 109.7 0.0 15.4 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
3(F) 51 466 0 4 0
52 522 0 2 0
53 740 0 12 0
54 597 0 4 0
55 612 0 204 0
56 621 0 105 0
57 523 0 18 0
58 370 0 105 0
59 573 0 21 0
60 620 0 1 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 564.4 0.0 47.6 0.0
S.D. 100.8 0.0 68.3 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
4(M) 61 382 0 4 0
62 603 0 164 0
63 623 0 137 0
64 367 0 8 0
65 380 0 0 0
66 466 0 28 0
67 451 0 66 0
68 476 0 0 0
69 298 0 9 0
70 558 0 117 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 460.4 0.0 53.3 0.0
S.D. 107.7 0.0 63.5 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 5 (continued) Individual and Group Mean Functional Test Values (Motor Activity)
Day: 82 Relative to Start Date
Group Animal Overall Overall Last 20% Last 20%
(Sex) Number activity mobile activity mobile
4(F) 71 732 0 144 0
72 535 0 5 0
73 593 0 3 0
74 439 0 8 0
75 519 0 22 0
76 301 0 0 0
77 394 0 3 0
78 347 0 20 0
79 522 0 215 0
80 422 0 95 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 480.4 0.0 51.5 0.0
S.D. 126.8 0.0 74.9 0.0
N 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
1(M) 1 0 0 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0 0 0
3 0 0 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0 0 0
5 0 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0
8 0 0 0 0 0 0 0 0 0
9 0 0 0 0 0 0 0 0 0
10 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
1(F) 11 0 0 0 0 0 0 0 0 0
12 0 0 0 0 0 0 0 0 0
13 1 0 0 0 0 0 0 0 0
15 0 0 0 0 0 0 0 0 0
16 0 0 0 0 0 0 0 0 0
17 0 0 0 0 0 0 0 0 0
18 0 0 0 0 0 0 0 0 0
19 0 0 0 0 0 0 0 0 0
20 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
2(M) 21 0 0 0 0 0 0 0 0 0
22 0 0 0 0 0 0 0 0 0
23 0 0 0 0 0 0 0 0 0
24 0 0 0 0 0 0 0 0 0
25 0 0 0 0 0 0 0 0 0
26 0 0 0 0 0 0 0 0 0
27 0 0 0 0 0 0 0 0 0
28 0 0 0 0 0 0 0 0 0
29 0 0 0 0 0 0 0 0 0
30 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
2(F) 31 0 0 0 0 0 0 0 0 0
32 0 0 0 0 0 0 0 0 0
33 0 0 0 0 0 0 0 0 0
34 0 0 0 0 0 0 0 0 0
35 0 0 0 0 0 0 0 0 0
36 0 0 0 0 0 0 0 0 0
37 0 0 0 0 0 0 0 0 0
38 0 0 0 0 0 0 0 0 0
39 0 0 0 0 0 0 0 0 0
40 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
3(M) 41 0 0 0 0 0 0 0 0 0
42 0 0 0 0 0 0 0 0 0
43 0 0 0 0 0 0 0 0 0
44 0 0 0 0 0 0 0 0 0
45 0 0 0 0 0 0 0 0 0
46 0 0 0 0 0 0 0 0 0
47 0 0 0 0 0 0 0 0 0
48 0 0 0 0 0 0 0 0 0
49 0 0 0 0 0 0 0 0 0
50 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
3(F) 51 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0
53 0 0 0 0 0 0 0 0 0
54 0 0 0 0 0 0 0 0 0
55 0 0 0 0 0 0 0 0 0
56 0 0 0 0 0 0 0 0 0
57 0 0 0 0 0 0 0 0 0
58 0 0 0 0 0 0 0 0 0
59 0 0 0 0 0 0 0 0 0
60 0 0 0 1 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
4(M) 61 0 0 0 0 0 0 0 0 0
62 0 0 0 0 0 0 0 0 0
63 0 0 0 0 0 0 0 0 0
64 0 0 0 0 0 0 0 0 0
65 0 0 0 0 0 0 0 0 0
66 0 0 0 0 0 0 0 0 0
67 0 0 0 0 0 0 0 0 0
68 0 0 0 0 0 0 0 0 0
69 0 0 0 0 0 0 0 0 0
70 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 6 (continued) Individual and Group Mean Sensory Reactivity Assessments
Day: 84 Relative to Start Date
Group Animal Grasp Vocalƒ Toe Tail Finger Touch Pupil Blink Startle
(Sex) Number response isation pinch pinch approach escape reflex reflex reflex
4(F) 71 0 0 0 0 0 0 0 0 0
72 0 0 0 0 0 0 0 0 0
73 0 0 0 0 0 0 0 0 0
74 0 0 0 0 0 0 0 0 0
75 0 0 0 0 0 0 0 0 0
76 0 0 0 0 0 0 0 0 0
77 0 0 0 0 0 0 0 0 0
78 0 0 0 0 0 0 0 0 0
79 0 0 0 0 0 0 0 0 0
80 0 0 0 0 0 0 0 0 0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
S.D. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
1(M) 1 207 240 270 293 315 333 352 363 374 384 394 407 411 417
2 214 246 270 296 319 337 351 361 371 381 392 405 401 406
3 196 229 249 273 291 308 322 334 349 357 368 378 383 392
4 193 222 244 260 278 289 295 304 316 321 337 341 348 355
5 194 218 240 261 281 296 313 328 340 347 362 369 371 376
6 202 230 256 284 308 326 345 366 380 391 408 417 428 434
7 223 257 282 299 320 338 357 374 384 393 397 413 419 433
8 213 248 274 297 322 339 355 369 379 390 397 409 412 421
9 207 234 251 273 289 308 325 340 351 362 376 385 394 401
10 206 243 270 289 309 323 340 354 364 371 388 397 408 413
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 205.5 236.7 260.6 282.5 303.2 319.7 335.5 349.3 360.8 369.7 381.9 392.1 397.5 404.8
S.D. 9.6 12.3 14.3 14.8 16.9 18.3 20.8 22.2 21.6 23.2 21.2 23.9 24.2 25.0
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
1(F) 11 156 176 186 193 192 201 208 213 206 214 219 217 216 226
12 157 166 171 184 187 188 196 200 198 201 206 207 209 211
13 173 194 202 212 232 238 246 245 257 263 264 258 268 271
14 171 188 196 204 213 220 . . . . . . . .
15 162 176 184 188 205 211 217 216 227 232 230 227 227 230
16 143 153 158 167 167 180 183 186 187 196 201 193 195 .
17 168 186 189 192 208 211 215 213 225 226 227 224 228 231
18 186 200 209 225 233 226 233 245 250 253 250 249 247 245
19 165 183 187 205 213 217 222 231 236 240 237 237 246 246
20 170 175 177 194 198 201 203 214 214 212 221 216 225 229
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 165.1 179.7 185.9 196.4 204.8 209.3 213.7 218.1 222.2 226.3 228.3 225.3 229.0 236.1
S.D. 11.6 13.7 14.9 16.0 20.1 17.4 19.0 19.5 23.3 22.9 20.0 20.3 22.0 17.9
N 10 10 10 10 10 10 9 9 9 9 9 9 9 8
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
2(M) 21 206 246 274 306 327 340 359 370 379 390 396 406 414 418
22 209 251 278 305 335 361 380 399 410 425 434 451 459 463
23 206 242 277 299 321 339 366 379 390 404 416 427 441 456
24 201 241 267 292 317 335 353 368 382 389 401 408 416 423
25 198 230 253 283 307 323 340 354 367 377 391 395 399 410
26 195 229 255 279 295 302 326 349 360 377 390 400 405 417
27 198 236 276 304 330 344 362 372 384 395 412 424 432 441
28 211 249 276 309 328 356 374 390 406 421 428 437 445 458
29 188 223 245 268 291 301 323 334 347 352 364 373 375 379
30 235 278 306 334 363 382 404 419 437 441 456 467 474 479
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 204.7 242.5 270.7 297.9 321.4 338.3 358.7 373.4 386.2 397.1 408.8 418.8 426.0 434.4
S.D. 12.7 15.5 17.1 18.5 20.8 25.2 24.8 25.0 26.3 26.4 26.2 28.1 29.9 30.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
2(F) 31 176 196 205 209 221 230 238 241 248 252 257 251 257 259
32 170 188 197 218 230 236 238 248 254 258 258 271 277 264
33 176 184 197 208 211 213 221 225 229 225 237 240 229 235
34 173 183 189 205 210 214 219 225 231 233 239 241 238 240
35 174 194 204 209 217 226 234 231 242 243 247 241 248 250
36 153 177 182 188 188 203 214 214 212 220 227 226 225 235
37 168 181 179 194 206 209 212 223 230 231 233 236 241 236
38 153 175 178 188 190 200 205 206 207 214 215 215 216 217
39 155 166 165 177 186 191 191 199 198 199 208 216 218 218
40 165 184 189 205 213 219 221 234 239 240 239 241 248 246
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 166.3 182.8 188.5 200.1 207.2 214.1 219.3 224.6 229.0 231.5 236.0 237.8 239.7 240.0
S.D. 9.4 8.9 12.7 12.7 14.8 14.1 14.9 15.1 18.2 17.8 16.3 16.5 18.8 15.5
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
3(M) 41 197 226 245 265 277 286 299 307 316 323 327 332 337 340
42 199 236 247 265 265 294 312 328 342 358 367 375 384 390
43 212 226 256 280 301 314 326 340 352 363 373 377 373 393
44 201 226 246 268 288 302 317 332 344 355 366 367 378 380
45 210 250 284 310 331 347 362 375 386 398 406 415 428 437
46 220 258 282 293 307 319 338 350 361 374 385 398 414 416
47 200 230 249 277 299 311 326 342 356 361 368 376 374 386
48 202 230 245 264 278 297 308 326 339 348 360 370 372 385
49 199 237 264 289 308 331 345 358 366 382 391 401 409 417
50 199 232 256 281 285 314 318 333 337 346 361 368 378 385
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 203.9 235.1 257.4 279.2 293.9 311.5 325.1 339.1 349.9 360.8 370.4 377.9 384.7 392.9
S.D. 7.5 10.9 14.8 14.9 19.2 18.2 18.8 18.8 19.0 20.7 21.2 22.9 26.0 26.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
3(F) 51 174 187 200 213 214 215 226 236 238 236 242 245 245 248
52 155 168 174 178 187 197 202 203 209 211 216 210 216 219
53 166 177 177 196 198 203 200 209 210 215 212 211 215 213
54 173 179 183 195 207 210 210 217 223 224 225 230 237 229
55 149 155 165 172 174 170 183 187 184 183 190 190 192 189
56 164 182 185 187 200 208 209 207 215 226 226 217 224 230
57 168 186 193 202 198 207 215 218 214 224 229 224 222 230
58 170 191 202 226 230 236 233 245 248 252 252 258 259 258
59 163 168 185 197 202 201 210 215 219 218 224 224 227 231
60 170 189 216 214 225 226 236 231 236 244 245 234 244 249
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 165.2 178.2 188.0 198.0 203.5 207.3 212.4 216.8 219.6 223.3 226.1 224.3 228.1 229.6
S.D. 7.9 11.5 15.0 16.6 16.7 17.6 16.1 17.0 18.1 19.1 17.9 19.2 19.0 19.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
4(M) 61 191 216 232 248 252 270 281 292 297 302 310 313 308 315
62 206 243 263 283 308 319 327 334 343 352 361 361 360 363
63 203 227 241 254 266 279 290 296 306 308 318 318 320 324
64 203 235 271 299 317 331 341 360 363 379 387 391 400 410
65 193 212 231 245 264 273 279 288 297 305 310 319 323 330
66 206 236 264 283 296 310 322 332 344 355 361 367 383 386
67 198 234 258 285 304 323 334 351 364 367 378 386 389 391
68 212 248 279 302 328 345 362 375 385 395 403 409 413 423
69 209 246 274 295 311 325 335 355 362 367 378 390 398 403
70 211 241 269 287 308 326 337 345 351 354 363 370 370 371
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 203.2 233.8 258.2 278.1 295.4 310.1 320.8 332.8 341.2 348.4 356.9 362.4 366.4 371.6
S.D. 7.2 12.2 17.5 21.2 25.6 26.5 28.0 30.8 30.9 32.6 33.2 34.5 37.4 37.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 7 (continued) Individual and Group Mean Body Weights
Body Weights (g)
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
Day Numbers Relative to Start Date
Group Animal
(Sex) Number 1 8 15 22 29 36 43 50 57 64 71 78 85 91
4(F) 71 145 162 169 175 172 186 190 193 184 198 201 200 196 205
72 164 172 187 211 207 213 224 224 222 231 236 226 231 230
73 160 165 181 192 197 196 207 211 213 210 216 215 221 217
74 157 179 192 201 203 218 226 231 226 234 235 239 234 241
75 172 186 192 208 217 219 217 230 236 236 235 236 249 241
76 166 176 196 207 213 213 223 227 225 226 237 231 232 237
77 163 165 178 190 195 188 200 207 206 209 208 211 212 210
78 168 180 177 196 204 200 196 211 216 218 209 219 223 219
79 161 179 189 202 211 216 219 229 234 238 235 233 237 237
80 172 197 211 221 235 229 238 237 242 249 253 253 260 262
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Mean 162.8 176.1 187.2 200.3 205.4 207.8 214.0 220.0 220.4 224.9 226.5 226.3 229.5 229.9
S.D. 8.0 10.7 11.8 12.8 16.3 14.4 15.2 13.8 16.9 15.8 16.8 15.4 18.1 17.3
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(M) 1 33 30 23 22 18 19 11 11 10 10 13 4 6
2 32 24 26 23 18 14 10 10 10 11 13 ƒ4 5
3 33 20 24 18 17 14 12 15 8 11 10 5 9
4 29 22 16 18 11 6 9 12 5 16 4 7 7
5 24 22 21 20 15 17 15 12 7 15 7 2 5
6 28 26 28 24 18 19 21 14 11 17 9 11 6
7 34 25 17 21 18 19 17 10 9 4 16 6 14
8 35 26 23 25 17 16 14 10 11 7 12 3 9
9 27 17 22 16 19 17 15 11 11 14 9 9 7
10 37 27 19 20 14 17 14 10 7 17 9 11 5
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 31.2 23.9 21.9 20.7 16.5 15.8 13.8 11.5 8.9 12.2 10.2 5.4 7.3
S.D. 4.0 3.8 3.8 2.9 2.5 3.9 3.6 1.8 2.1 4.4 3.4 4.6 2.8
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
1(F) 11 20 10 7 ƒ1 9 7 5 ƒ7 8 5 ƒ2 ƒ1 10
12 9 5 13 3 1 8 4 ƒ2 3 5 1 2 2
13 21 8 10 20 6 8 ƒ1 12 6 1 ƒ6 10 3
14 17 8 8 9 7 . . . . . . . .
15 14 8 4 17 6 6 ƒ1 11 5 ƒ2 ƒ3 0 3
16 10 5 9 0 13 3 3 1 9 5 ƒ8 2 .
17 18 3 3 16 3 4 ƒ2 12 1 1 ƒ3 4 3
18 14 9 16 8 ƒ7 7 12 5 3 ƒ3 ƒ1 ƒ2 ƒ2
19 18 4 18 8 4 5 9 5 4 ƒ3 0 9 0
20 5 2 17 4 3 2 11 0 ƒ2 9 ƒ5 9 4
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 14.6 6.2 10.5 8.4 4.5 5.6 4.4 4.1 4.1 2.0 ƒ3.0 3.7 2.9
S.D. 5.2 2.7 5.3 7.3 5.3 2.2 5.3 6.7 3.4 4.2 2.9 4.6 3.5
N 10 10 10 10 10 9 9 9 9 9 9 9 8
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
2(M) 21 40 28 32 21 13 19 11 9 11 6 10 8 4
22 42 27 27 30 26 19 19 11 15 9 17 8 ƒ3
23 36 35 22 22 18 27 13 11 14 12 11 14 15
24 40 26 25 25 18 18 15 14 7 12 7 8 7
25 32 23 30 24 16 17 14 13 10 14 4 4 11
26 34 26 24 16 7 24 23 11 17 13 10 5 12
27 38 40 28 26 14 18 10 12 11 17 12 8 9
28 38 27 33 19 28 18 16 16 15 7 9 8 13
29 35 22 23 23 10 22 11 13 5 12 9 2 4
30 43 28 28 29 19 22 15 18 4 15 11 7 5
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 37.8 28.2 27.2 23.5 16.9 20.4 14.7 12.8 10.9 11.7 10.0 7.2 7.7
S.D. 3.6 5.4 3.7 4.3 6.5 3.2 4.0 2.7 4.5 3.5 3.4 3.2 5.4
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
2(F) 31 20 9 4 12 9 8 3 7 4 5 ƒ6 6 2
32 18 9 21 12 6 2 10 6 4 0 13 6 ƒ13
33 8 13 11 3 2 8 4 4 ƒ4 12 3 ƒ11 6
34 10 6 16 5 4 5 6 6 2 6 2 ƒ3 2
35 20 10 5 8 9 8 ƒ3 11 1 4 ƒ6 7 2
36 24 5 6 0 15 11 0 ƒ2 8 7 ƒ1 ƒ1 10
37 13 ƒ2 15 12 3 3 11 7 1 2 3 5 ƒ5
38 22 3 10 2 10 5 1 1 7 1 0 1 1
39 11 ƒ1 12 9 5 0 8 ƒ1 1 9 8 2 0
40 19 5 16 8 6 2 13 5 1 ƒ1 2 7 ƒ2
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 16.5 5.7 11.6 7.1 6.9 5.2 5.3 4.4 2.5 4.5 1.8 1.9 0.3
S.D. 5.5 4.8 5.5 4.4 3.9 3.5 5.2 4.0 3.4 4.1 5.8 5.7 6.2
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
3(M) 41 29 19 20 12 9 13 8 9 7 4 5 5 3
42 37 11 18 0 29 18 16 14 16 9 8 9 6
43 14 30 24 21 13 12 14 12 11 10 4 ƒ4 20
44 25 20 22 20 14 15 15 12 11 11 1 11 2
45 40 34 26 21 16 15 13 11 12 8 9 13 9
46 38 24 11 14 12 19 12 11 13 11 13 16 2
47 30 19 28 22 12 15 16 14 5 7 8 ƒ2 12
48 28 15 19 14 19 11 18 13 9 12 10 2 13
49 38 27 25 19 23 14 13 8 16 9 10 8 8
50 33 24 25 4 29 4 15 4 9 15 7 10 7
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 31.2 22.3 21.8 14.7 17.6 13.6 14.0 10.8 10.9 9.6 7.5 6.8 8.2
S.D. 7.9 6.9 5.0 7.6 7.2 4.2 2.7 3.1 3.6 3.0 3.4 6.5 5.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
3(F) 51 13 13 13 1 1 11 10 2 ƒ2 6 3 0 3
52 13 6 4 9 10 5 1 6 2 5 ƒ6 6 3
53 11 0 19 2 5 ƒ3 9 1 5 ƒ3 ƒ1 4 ƒ2
54 6 4 12 12 3 0 7 6 1 1 5 7 ƒ8
55 6 10 7 2 ƒ4 13 4 ƒ3 ƒ1 7 0 2 ƒ3
56 18 3 2 13 8 1 ƒ2 8 11 0 ƒ9 7 6
57 18 7 9 ƒ4 9 8 3 ƒ4 10 5 ƒ5 ƒ2 8
58 21 11 24 4 6 ƒ3 12 3 4 0 6 1 ƒ1
59 5 17 12 5 ƒ1 9 5 4 ƒ1 6 0 3 4
60 19 27 ƒ2 11 1 10 ƒ5 5 8 1 ƒ11 10 5
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 13.0 9.8 10.0 5.5 3.8 5.1 4.4 2.8 3.7 2.8 ƒ1.8 3.8 1.5
S.D. 5.9 7.9 7.8 5.6 4.6 6.0 5.4 3.9 4.7 3.4 5.8 3.7 4.9
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
4(M) 61 25 16 16 4 18 11 11 5 5 8 3 ƒ5 7
62 37 20 20 25 11 8 7 9 9 9 0 ƒ1 3
63 24 14 13 12 13 11 6 10 2 10 0 2 4
64 32 36 28 18 14 10 19 3 16 8 4 9 10
65 19 19 14 19 9 6 9 9 8 5 9 4 7
66 30 28 19 13 14 12 10 12 11 6 6 16 3
67 36 24 27 19 19 11 17 13 3 11 8 3 2
68 36 31 23 26 17 17 13 10 10 8 6 4 10
69 37 28 21 16 14 10 20 7 5 11 12 8 5
70 30 28 18 21 18 11 8 6 3 9 7 0 1
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 30.6 24.4 19.9 17.3 14.7 10.7 12.0 8.4 7.2 8.5 5.5 4.0 5.2
S.D. 6.3 7.0 5.0 6.5 3.3 2.8 5.1 3.1 4.4 2.0 3.8 5.9 3.2
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 8 (continued) Individual and Group Mean Body Weight Gains
Increase in Body Weight (g)
Day Numbers Relative to Start Date
Group Animal From: 1 8 15 22 29 36 43 50 57 64 71 78 85
(Sex) Number To: 8 15 22 29 36 43 50 57 64 71 78 85 91
4(F) 71 17 7 6 ƒ3 14 4 3 ƒ9 14 3 ƒ1 ƒ4 9
72 8 15 24 ƒ4 6 11 0 ƒ2 9 5 ƒ10 5 ƒ1
73 5 16 11 5 ƒ1 11 4 2 ƒ3 6 ƒ1 6 ƒ4
74 22 13 9 2 15 8 5 ƒ5 8 1 4 ƒ5 7
75 14 6 16 9 2 ƒ2 13 6 0 ƒ1 1 13 ƒ8
76 10 20 11 6 0 10 4 ƒ2 1 11 ƒ6 1 5
77 2 13 12 5 ƒ7 12 7 ƒ1 3 ƒ1 3 1 ƒ2
78 12 ƒ3 19 8 ƒ4 ƒ4 15 5 2 ƒ9 10 4 ƒ4
79 18 10 13 9 5 3 10 5 4 ƒ3 ƒ2 4 0
80 25 14 10 14 ƒ6 9 ƒ1 5 7 4 0 7 2
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 13.3 11.1 13.1 5.1 2.4 6.2 6.0 0.4 4.5 1.6 ƒ0.2 3.2 0.4
S.D. 7.3 6.5 5.3 5.5 7.7 5.7 5.3 5.0 5.0 5.5 5.5 5.3 5.4
N 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 9 Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
1 (M) 1 No abnormalities detected No abnormalities detected
2 No abnormalities detected No abnormalities detected
3 No abnormalities detected No abnormalities detected
4 No abnormalities detected No abnormalities detected
5 No abnormalities detected No abnormalities detected
6 No abnormalities detected No abnormalities detected
7 No abnormalities detected No abnormalities detected
8 No abnormalities detected No abnormalities detected
9 No abnormalities detected No abnormalities detected
10 No abnormalities detected No abnormalities detected
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
1 (F) 11 No abnormalities detected No abnormalities detected
12 No abnormalities detected No abnormalities detected
13 Both ppm Left ppm
14 Left ppm No abnormalities detected
15 No abnormalities detected No abnormalities detected
16 No abnormalities detected No abnormalities detected
17 No abnormalities detected Corneal Superficial opacity slight right
18 No abnormalities detected No abnormalities detected
19 No abnormalities detected No abnormalities detected
20 No abnormalities detected Left Eye: Superficial corneal opacity (Faint)
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
2 (M) 21 No abnormalities detected Not examined
22 No abnormalities detected Not examined
23 No abnormalities detected Not examined
24 No abnormalities detected Not examined
25 Corneal Opacity right Not examined
26 No abnormalities detected Not examined
27 No abnormalities detected Not examined
28 Left Eye: Lens, persistent hyaloid artery Not examined
29 Persistent pupillary membrane right Not examined
30 Persistent pupillary membrane right Not examined
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
2 (F) 31 No abnormalities detected Not examined
32 No abnormalities detected Not examined
33 No abnormalities detected Not examined
34 No abnormalities detected Not examined
35 No abnormalities detected Not examined
36 No abnormalities detected Not examined
37 Persistent pupillary membrane left Not examined
38 No abnormalities detected Not examined
39 No abnormalities detected Not examined
40 No abnormalities detected Not examined
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
3 (M) 41 No abnormalities detected Not examined
42 No abnormalities detected Not examined
43 No abnormalities detected Not examined
44 No abnormalities detected Not examined
45 No abnormalities detected Not examined
46 No abnormalities detected Not examined
47 No abnormalities detected Not examined
48 No abnormalities detected Not examined
49 No abnormalities detected Not examined
50 No abnormalities detected Not examined
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
3 (F) 51 No abnormalities detected Not examined
52 No abnormalities detected Not examined
53 No abnormalities detected Not examined
54 No abnormalities detected Not examined
55 No abnormalities detected Not examined
56 No abnormalities detected Not examined
57 No abnormalities detected Not examined
58 No abnormalities detected Not examined
59 No abnormalities detected Not examined
60 No abnormalities detected Not examined
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
4 (M) 61 No abnormalities detected No abnormalities detected
62 No abnormalities detected No abnormalities detected
63 No abnormalities detected No abnormalities detected
64 No abnormalities detected No abnormalities detected
65 No abnormalities detected No abnormalities detected
66 No abnormalities detected No abnormalities detected
67 No abnormalities detected No abnormalities detected
68 No abnormalities detected No abnormalities detected
69 No abnormalities detected No abnormalities detected
70 No abnormalities detected No abnormalities detected
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 9 (continued) Individual Ophthalmoscopic Examination
Group
(Sex) Animal
Number Pre-Test Observation Pre-Termination Observation
4 (F) 71 No abnormalities detected No abnormalities detected
72 No abnormalities detected No abnormalities detected
73 No abnormalities detected No abnormalities detected
74 No abnormalities detected No abnormalities detected
75 No abnormalities detected No abnormalities detected
76 No abnormalities detected No abnormalities detected
77 No abnormalities detected No abnormalities detected
78 No abnormalities detected No abnormalities detected
79 No abnormalities detected No abnormalities detected
80 No abnormalities detected No abnormalities detected
Dose Levels: Group 1 ƒ 0(Control) Group 2 100 mg/kg bw/day Group 3 300 mg/kg bw/day Group 4 1000 mg/kg bw/day
Appendix 10 Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
1(M) 1 16.5 8.32 44.1 19.8 53.0 37.5 6.8 29 1.97 71 4.83 0 0.00 0 0.00 0 0.00 484
2 16.4 8.94 45.8 18.3 51.2 35.7 9.6 24 2.30 76 7.30 0 0.00 0 0.00 0 0.00 579
3 16.3 7.03 39.6 21.4 56.3 38.1 14.1 30 4.23 69 9.73 0 0.00 1 0.14 0 0.00 592
4 16.4 9.18 46.4 17.8 50.6 35.2 7.9 30 2.37 70 5.53 0 0.00 0 0.00 0 0.00 605
5 13.2 7.45 38.1 17.7 51.1 34.6 5.3 34 1.80 65 3.45 0 0.00 1 0.05 0 0.00 537
6 16.5 9.03 46.5 18.2 51.5 35.4 9.4 24 2.26 74 6.96 0 0.00 2 0.19 0 0.00 497
7 16.5 8.96 46.2 18.4 51.5 35.7 10.1 24 2.42 76 7.68 0 0.00 0 0.00 0 0.00 618
8 17.6 9.27 49.4 18.9 53.3 35.6 8.7 32 2.78 67 5.83 0 0.00 1 0.09 0 0.00 632
9 16.0 8.95 45.9 17.9 51.3 34.8 10.8 23 2.48 75 8.10 0 0.00 2 0.22 0 0.00 629
10 16.1 8.98 45.4 17.9 50.6 35.4 6.4 28 1.79 72 4.61 0 0.00 0 0.00 0 0.00 486
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 16.15 8.611 44.74 18.63 52.04 35.80 8.91 27.8 2.440 71.5 6.402 0.0 0.000 0.7 0.069 0.0 0.000 565.9
S.D. 1.12 0.771 3.39 1.16 1.75 1.12 2.53 3.9 0.702 3.8 1.891 0.0 0.000 0.8 0.086 0.0 0.000 59.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
1(F) 11 14.7 7.47 41.6 19.7 55.7 35.4 7.5 34 2.55 66 4.95 0 0.00 0 0.00 0 0.00 581
12 13.3 6.95 36.9 19.1 53.1 35.2 1.2 18 0.22 82 0.98 0 0.00 0 0.00 0 0.00 379
13 15.1 7.75 43.2 19.5 55.7 34.9 6.5 31 2.02 69 4.49 0 0.00 0 0.00 0 0.00 557
14 . . . . . . . . . . . . . . . . . .
15 15.5 8.42 44.2 18.5 52.5 35.1 7.1 19 1.35 81 5.75 0 0.00 0 0.00 0 0.00 480
16 16.4 8.82 46.9 18.6 53.1 35.0 6.1 22 1.34 78 4.76 0 0.00 0 0.00 0 0.00 470
17 15.4 8.35 44.7 18.5 53.5 34.6 6.8 24 1.63 76 5.17 0 0.00 0 0.00 0 0.00 478
18 15.2 8.28 43.5 18.3 52.5 34.9 8.4 22 1.85 77 6.47 0 0.00 1 0.08 0 0.00 617
19 14.8 8.21 43.1 18.1 52.5 34.4 6.6 23 1.52 75 4.95 0 0.00 2 0.13 0 0.00 454
20 14.3 7.70 41.0 18.6 53.3 34.9 6.3 31 1.95 69 4.35 0 0.00 0 0.00 0 0.00 586
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 14.97 7.994 42.79 18.77 53.54 34.93 6.28 24.9 1.603 74.8 4.652 0.0 0.000 0.3 0.023 0.0 0.000 511.3
S.D. 0.86 0.573 2.80 0.55 1.28 0.30 2.03 5.7 0.643 5.6 1.524 0.0 0.000 0.7 0.048 0.0 0.000 77.7
N 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
2(M) 21 16.8 8.71 46.1 19.3 52.9 36.5 7.1 20 1.42 80 5.68 0 0.00 0 0.00 0 0.00 567
22 16.4 9.04 45.6 18.1 50.4 35.9 7.4 23 1.70 77 5.70 0 0.00 0 0.00 0 0.00 575
23 17.1 7.66 44.8 22.4 58.5 38.3 6.8 23 1.56 76 5.17 0 0.00 1 0.07 0 0.00 670
24 10.6 5.78 31.0 18.4 53.7 34.3 3.3 20 0.66 79 2.61 0 0.00 1 0.03 0 0.00 14
25 16.6 8.86 46.4 18.7 52.3 35.7 10.3 25 2.58 75 7.73 0 0.00 0 0.00 0 0.00 682
26 15.9 8.64 45.6 18.4 52.7 34.8 11.7 29 3.39 71 8.31 0 0.00 0 0.00 0 0.00 608
27 15.2 7.86 41.6 19.4 53.0 32.9 9.9 26 2.57 74 7.33 0 0.00 0 0.00 0 0.00 363
28 16.7 8.65 46.2 19.4 53.4 36.3 11.0 22 2.42 78 8.58 0 0.00 0 0.00 0 0.00 584
29 16.0 8.69 44.6 18.4 51.3 35.8 8.9 22 1.96 78 6.94 0 0.00 0 0.00 0 0.00 512
30 16.8 8.90 46.8 18.9 52.7 35.9 10.0 24 2.40 76 7.60 0 0.00 0 0.00 0 0.00 525
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 15.81 8.279 43.87 19.14 53.09 35.64 8.64 23.4 2.066 76.4 6.565 0.0 0.000 0.2 0.010 0.0 0.000 510.0
S.D. 1.91 0.985 4.76 1.24 2.14 1.43 2.52 2.8 0.768 2.6 1.807 0.0 0.000 0.4 0.023 0.0 0.000 196.0
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
2(F) 31 14.8 7.91 41.4 18.7 52.3 35.7 4.2 27 1.13 71 2.98 0 0.00 2 0.08 0 0.00 448
32 15.8 7.80 44.1 20.3 56.5 35.8 6.3 19 1.20 81 5.10 0 0.00 0 0.00 0 0.00 601
33 15.0 7.49 41.9 20.1 55.9 35.9 7.0 33 2.31 67 4.69 0 0.00 0 0.00 0 0.00 620
34 11.8 6.31 33.3 18.7 52.9 35.3 1.7 18 0.31 82 1.39 0 0.00 0 0.00 0 0.00 396
35 14.8 7.82 41.2 18.9 52.6 35.9 10.2 26 2.65 70 7.14 0 0.00 4 0.41 0 0.00 771
36 15.1 8.21 43.0 18.3 52.3 35.0 5.8 21 1.22 78 4.52 0 0.00 1 0.06 0 0.00 752
37 13.3 7.14 37.2 18.8 52.9 35.5 6.4 20 1.28 80 5.12 0 0.00 0 0.00 0 0.00 544
38 15.3 8.58 44.1 17.9 51.3 34.8 7.0 27 1.89 73 5.11 0 0.00 0 0.00 0 0.00 527
39 15.3 7.60 43.2 20.1 56.9 35.3 7.1 15 1.07 85 6.04 0 0.00 0 0.00 0 0.00 664
40 15.4 8.21 44.0 18.8 53.6 35.1 5.0 22 1.10 78 3.90 0 0.00 0 0.00 0 0.00 711
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 14.66 7.707 41.34 19.06 53.72 35.43 6.07 22.8 1.416 76.5 4.599 0.0 0.000 0.7 0.055 0.0 0.000 603.4
S.D. 1.20 0.638 3.51 0.82 1.97 0.39 2.21 5.4 0.681 5.9 1.590 0.0 0.000 1.3 0.128 0.0 0.000 125.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
3(M) 41 16.4 8.98 45.1 18.3 50.3 36.4 9.5 26 2.47 72 6.84 0 0.00 2 0.19 0 0.00 540
42 16.5 9.00 47.8 18.4 53.1 34.6 8.4 21 1.76 79 6.64 0 0.00 0 0.00 0 0.00 637
43 15.9 9.13 45.0 17.4 49.3 35.3 8.1 28 2.27 72 5.83 0 0.00 0 0.00 0 0.00 666
44 16.7 8.88 45.9 18.8 51.7 36.4 10.9 28 3.05 70 7.63 0 0.00 2 0.22 0 0.00 420
45 15.8 8.64 44.4 18.2 51.4 35.5 5.7 27 1.54 73 4.16 0 0.00 0 0.00 0 0.00 607
46 16.2 8.49 46.0 19.1 54.2 35.3 8.8 24 2.11 76 6.69 0 0.00 0 0.00 0 0.00 550
47 17.1 9.02 46.3 18.9 51.4 36.8 9.3 22 2.05 78 7.25 0 0.00 0 0.00 0 0.00 630
48 16.9 8.69 47.2 19.4 54.3 35.8 7.1 18 1.28 81 5.75 0 0.00 1 0.07 0 0.00 549
49 16.0 8.94 46.3 17.9 51.8 34.5 8.1 25 2.03 75 6.08 0 0.00 0 0.00 0 0.00 384
50 17.4 9.36 48.7 18.6 52.0 35.7 10.5 28 2.94 72 7.56 0 0.00 0 0.00 0 0.00 475
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 16.49 8.913 46.27 18.50 51.95 35.63 8.64 24.7 2.150 74.8 6.443 0.0 0.000 0.5 0.048 0.0 0.000 545.8
S.D. 0.53 0.253 1.33 0.59 1.58 0.76 1.54 3.4 0.564 3.6 1.042 0.0 0.000 0.8 0.086 0.0 0.000 94.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
3(F) 51 14.5 7.91 42.1 18.4 53.2 34.6 5.8 36 2.09 64 3.71 0 0.00 0 0.00 0 0.00 547
52 15.1 7.62 42.5 19.9 55.8 35.6 6.7 39 2.61 61 4.09 0 0.00 0 0.00 0 0.00 711
53 14.7 7.35 41.6 20.1 56.6 35.5 8.0 23 1.84 77 6.16 0 0.00 0 0.00 0 0.00 581
54 8.2 4.54 24.0 18.1 52.8 34.3 1.4 17 0.24 83 1.16 0 0.00 0 0.00 0 0.00 11
55 14.6 8.02 41.5 18.2 51.7 35.2 8.2 26 2.13 74 6.07 0 0.00 0 0.00 0 0.00 601
56 15.4 7.93 43.9 19.4 55.3 35.1 6.5 26 1.69 73 4.75 0 0.00 1 0.07 0 0.00 557
57 14.9 7.54 42.6 19.8 56.4 35.1 9.8 18 1.76 80 7.84 0 0.00 2 0.20 0 0.00 612
58 13.6 7.20 38.7 18.9 53.8 35.1 4.3 24 1.03 76 3.27 0 0.00 0 0.00 0 0.00 397
59 14.7 7.44 41.9 19.7 56.2 35.0 6.2 25 1.55 74 4.59 0 0.00 1 0.06 0 0.00 538
60 16.0 8.35 45.7 19.1 54.7 34.9 7.0 27 1.89 73 5.11 0 0.00 0 0.00 0 0.00 582
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 14.17 7.390 40.45 19.16 54.65 35.04 6.39 26.1 1.683 73.5 4.675 0.0 0.000 0.4 0.033 0.0 0.000 513.7
S.D. 2.19 1.060 6.05 0.74 1.70 0.38 2.30 6.9 0.652 6.7 1.825 0.0 0.000 0.7 0.065 0.0 0.000 193.0
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
4(M) 61 14.8 8.26 42.0 17.9 50.8 35.3 6.9 31 2.14 68 4.69 0 0.00 1 0.07 0 0.00 707
62 14.4 7.88 40.7 18.3 51.6 35.4 6.7 21 1.41 79 5.29 0 0.00 0 0.00 0 0.00 755
63 15.4 8.30 43.5 18.5 52.3 35.3 6.6 25 1.65 73 4.82 0 0.00 2 0.13 0 0.00 570
64 15.1 8.26 42.7 18.3 51.7 35.3 12.3 32 3.94 67 8.24 0 0.00 1 0.12 0 0.00 611
65 16.0 8.62 44.8 18.5 52.0 35.6 9.3 24 2.23 76 7.07 0 0.00 0 0.00 0 0.00 699
66 16.1 8.15 45.5 19.8 55.8 35.5 9.5 25 2.38 74 7.03 0 0.00 1 0.10 0 0.00 506
67 15.3 8.70 43.7 17.6 50.2 35.1 9.6 23 2.21 77 7.39 0 0.00 0 0.00 0 0.00 631
68 15.1 8.13 44.6 18.6 54.9 33.9 11.7 21 2.46 79 9.24 0 0.00 0 0.00 0 0.00 604
69 14.5 7.60 41.8 19.1 55.0 34.7 3.2 27 0.86 72 2.30 0 0.00 1 0.03 0 0.00 525
70 15.0 8.69 43.5 17.3 50.1 34.6 7.8 17 1.33 83 6.47 0 0.00 0 0.00 0 0.00 541
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 15.17 8.259 43.28 18.39 52.44 35.07 8.36 24.6 2.061 74.8 6.254 0.0 0.000 0.6 0.045 0.0 0.000 614.9
S.D. 0.56 0.353 1.49 0.72 2.07 0.52 2.69 4.6 0.844 5.0 2.015 0.0 0.000 0.7 0.055 0.0 0.000 83.7
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 10 (continued) Individual and Group Mean Hematological Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Hb RBC Hct MCH MCV MCHC WBC Neu% Neut Lym% Lymph Mon% Mono Eos% Eos Bas% Bas PLT
g/dl 10^12/l % pg fl g/dl 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l % 10^9/l 10^9/l
4(F) 71 8.5 4.74 24.2 17.8 50.9 35.0 2.3 25 0.58 75 1.73 0 0.00 0 0.00 0 0.00 21
72 14.6 8.03 41.6 18.2 51.8 35.1 6.9 38 2.62 62 4.28 0 0.00 0 0.00 0 0.00 602
73 14.6 7.90 41.6 18.4 52.6 35.0 6.8 25 1.70 75 5.10 0 0.00 0 0.00 0 0.00 588
74 14.4 7.99 40.8 18.0 51.1 35.2 8.4 19 1.60 81 6.80 0 0.00 0 0.00 0 0.00 690
75 15.7 8.25 44.6 19.0 54.1 35.1 4.5 29 1.31 70 3.15 0 0.00 1 0.05 0 0.00 590
76 14.3 7.63 41.1 18.7 53.8 34.7 4.4 22 0.97 78 3.43 0 0.00 0 0.00 0 0.00 470
77 14.2 7.22 40.2 19.7 55.7 35.4 8.0 27 2.16 73 5.84 0 0.00 0 0.00 0 0.00 706
78 14.4 7.61 41.4 19.0 54.5 34.8 8.1 27 2.19 73 5.91 0 0.00 0 0.00 0 0.00 489
79 15.2 8.51 45.5 17.9 53.4 33.5 7.3 21 1.53 79 5.77 0 0.00 0 0.00 0 0.00 683
80 15.0 8.40 44.1 17.8 52.5 34.0 4.5 18 0.81 82 3.69 0 0.00 0 0.00 0 0.00 586
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 14.09 7.628 40.51 18.45 53.04 34.78 6.12 25.1 1.547 74.8 4.570 0.0 0.000 0.1 0.005 0.0 0.000 542.5
S.D. 2.02 1.087 6.00 0.64 1.54 0.59 2.05 5.8 0.653 5.9 1.576 0.0 0.000 0.3 0.016 0.0 0.000 199.5
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
1(M) 1 10.2 16.0
2 10.5 15.2
3 9.5 15.1
4 9.4 13.9
5 9.2 14.0
6 8.9 16.1
7 10.6 14.8
8 9.6 16.5
9 10.4 16.0
10 9.4 12.3
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.77 14.99
S.D. 0.60 1.29
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
1(F) 11 9.9 14.0
12 9.9 17.1
13 9.6 13.2
14 . .
15 9.8 14.2
16 8.9 11.6
17 9.2 13.2
18 9.7 14.9
19 8.9 13.9
20 9.1 14.4
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.44 14.06
S.D. 0.42 1.49
N 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
2(M) 21 9.9 18.5
22 9.7 13.3
23 11.0 14.4
24 9.6 18.3
25 8.8 15.2
26 8.9 13.3
27 9.8 15.0
28 10.8 15.4
29 9.4 14.1
30 10.6 13.5
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.85 15.10
S.D. 0.75 1.90
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
2(F) 31 8.9 16.3
32 9.9 16.3
33 7.8 16.5
34 7.9 18.9
35 9.9 15.2
36 8.7 12.7
37 9.8 18.2
38 9.3 13.0
39 8.4 14.1
40 10.3 16.9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.09 15.81
S.D. 0.89 2.06
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
3(M) 41 9.4 15.3
42 11.2 13.1
43 10.3 14.4
44 9.8 15.3
45 11.6 18.5
46 10.2 15.4
47 11.2 15.6
48 9.6 12.7
49 9.8 13.2
50 9.6 15.3
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 10.27 14.88
S.D. 0.79 1.68
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
3(F) 51 10.1 15.2
52 8.5 14.2
53 8.7 14.3
54 8.4 12.5
55 10.3 14.7
56 8.5 14.7
57 9.7 13.6
58 8.3 12.4
59 8.8 11.3
60 9.8 12.7
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.11 13.56
S.D. 0.77 1.27
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
4(M) 61 10.3 12.9
62 9.5 14.8
63 10.2 13.2
64 9.2 15.2
65 10.3 16.3
66 9.5 12.3
67 9.2 15.4
68 8.9 12.2
69 9.9 15.3
70 9.4 13.5
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.64 14.11
S.D. 0.50 1.46
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 11 (continued) Individual and Group Mean Coagulation Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number CT APTT
Seconds Seconds
4(F) 71 9.9 16.5
72 8.7 13.2
73 9.9 15.2
74 8.5 12.0
75 8.9 15.6
76 9.1 16.4
77 8.7 18.3
78 9.8 14.7
79 8.8 13.0
80 8.1 12.8
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 9.04 14.77
S.D. 0.63 2.00
N 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
1(M) 1 30 168 7.14 3.7 1.06 147 5.04 92 2.08 2.3 88 61 90 0.69 102 0.02
2 33 158 6.74 3.6 1.14 150 5.24 106 2.57 2.2 76 54 130 0.69 90 0.05
3 33 199 5.71 3.0 1.09 147 4.46 79 2.38 1.3 100 60 94 0.56 75 0.07
4 33 170 7.04 3.7 1.12 149 5.09 94 2.35 2.1 152 63 94 0.65 95 0.00
5 25 188 5.42 2.9 1.17 147 4.28 102 2.32 1.7 75 40 74 0.59 72 0.05
6 32 146 6.80 3.6 1.10 145 5.96 101 2.62 2.4 129 54 90 0.79 91 0.09
7 39 203 6.85 3.5 1.07 147 6.97 65 2.38 2.5 93 63 83 0.98 76 0.06
8 32 216 6.79 3.5 1.09 143 4.75 105 2.21 1.7 68 53 130 0.73 75 0.10
9 33 139 6.97 3.7 1.11 147 6.43 99 2.56 2.3 74 60 134 0.74 104 0.08
10 31 162 7.06 3.6 1.04 143 4.49 104 2.65 1.9 97 62 226 0.70 102 0.09
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 32.1 174.9 6.652 3.48 1.099 146.5 5.271 94.7 2.412 2.04 95.2 57.0 114.5 0.712 88.2 0.061
S.D. 3.4 25.6 0.592 0.29 0.038 2.3 0.901 13.2 0.186 0.38 26.7 7.1 44.7 0.116 12.7 0.032
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
1(F) 11 51 151 9.16 4.6 0.99 142 21.03 81 1.83 3.8 360 72 0 0.69 93 0.00
12 32 164 5.48 3.3 1.50 153 4.26 105 2.27 1.3 151 49 35 0.62 62 0.07
13 38 152 7.14 3.9 1.21 147 4.05 107 2.61 1.4 76 50 57 0.72 109 0.10
14 . . . . . . . . . . . . . . .
15 47 169 7.07 3.7 1.11 151 5.76 105 2.49 2.4 110 61 100 0.75 87 0.00
16 48 308 9.26 4.9 1.13 154 11.86 104 3.51 3.7 161 58 45 0.88 109 0.00
17 31 182 6.70 3.8 1.34 147 3.73 107 2.65 2.3 72 52 83 0.81 85 0.07
18 39 234 6.49 3.9 1.55 157 4.52 107 2.61 1.9 103 53 46 0.82 68 0.07
19 37 179 7.25 4.2 1.39 146 4.15 106 2.81 1.8 87 52 72 0.75 78 0.06
20 35 179 6.72 3.7 1.26 145 5.11 106 2.75 2.0 94 53 96 0.68 97 0.08
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 39.8 190.9 7.252 4.00 1.276 149.1 7.163 103.1 2.614 2.29 134.9 55.6 59.3 0.747 87.6 0.050
S.D. 7.2 50.3 1.226 0.49 0.186 4.9 5.772 8.4 0.449 0.90 89.9 7.2 32.1 0.080 16.5 0.039
N 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
2(M) 21 65 206 6.94 3.5 1.02 148 8.23 107 2.08 2.3 84 56 107 1.39 116 0.08
22 33 219 6.78 3.4 1.00 144 4.81 105 2.08 2.1 92 53 102 0.65 102 0.13
23 31 205 7.83 3.7 0.91 144 4.82 93 1.77 2.4 85 80 116 0.64 115 0.15
24 34 184 5.80 3.1 1.14 147 5.69 101 2.27 1.9 118 51 75 0.60 81 0.07
25 30 268 5.93 3.1 1.08 155 6.09 106 2.45 1.9 180 167 75 0.67 86 0.06
26 29 145 7.00 3.6 1.06 148 5.41 104 2.47 2.3 64 64 132 0.66 86 0.10
27 26 174 5.71 2.9 1.03 148 4.78 101 1.80 1.8 99 68 71 0.49 85 0.06
28 28 155 6.85 3.5 1.03 147 4.50 50 2.11 2.0 66 41 120 0.69 104 0.13
29 47 110 7.17 3.5 0.95 147 7.68 94 2.60 2.5 109 50 110 1.14 101 0.13
30 33 116 8.01 3.7 0.88 144 9.11 6 2.12 3.6 85 63 172 0.73 131 0.13
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 35.6 178.2 6.802 3.40 1.010 147.2 6.112 86.7 2.175 2.28 98.2 69.3 108.0 0.766 100.7 0.104
S.D. 11.8 48.8 0.794 0.27 0.079 3.2 1.645 33.0 0.275 0.52 33.3 36.0 30.7 0.277 16.5 0.034
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
2(F) 31 37 165 7.45 4.3 1.39 151 3.94 103 2.79 1.6 70 55 55 0.72 109 0.10
32 51 173 8.25 4.2 1.20 150 5.60 105 2.82 1.9 85 72 46 0.83 91 0.02
33 42 178 8.25 4.3 1.07 149 4.19 99 2.99 2.2 70 56 55 0.83 91 0.08
34 38 192 6.24 3.6 1.37 150 3.95 104 2.49 1.6 119 40 36 0.69 70 0.07
35 38 146 7.43 4.2 1.31 145 4.45 106 2.71 2.0 80 51 56 0.69 84 0.04
36 41 150 7.26 4.0 1.20 150 4.63 105 2.67 2.1 117 62 110 0.74 85 0.04
37 40 156 6.07 3.4 1.27 157 4.87 104 2.51 1.6 132 51 48 0.68 83 0.06
38 37 247 5.90 3.4 1.37 152 5.62 104 2.61 1.7 145 52 55 0.72 61 0.08
39 65 179 8.02 4.5 1.27 151 7.45 101 2.92 2.5 73 44 60 1.06 99 0.03
40 29 191 7.62 4.3 1.32 148 4.44 107 2.87 1.8 64 48 64 0.70 84 0.09
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 41.8 177.7 7.249 4.02 1.277 150.3 4.914 103.8 2.738 1.90 95.5 53.1 58.5 0.766 85.7 0.061
S.D. 9.8 29.1 0.884 0.40 0.099 3.1 1.071 2.3 0.170 0.30 29.7 9.1 19.7 0.117 13.5 0.027
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
3(M) 41 36 221 7.16 3.4 0.92 144 8.24 80 2.04 2.6 128 82 129 1.06 81 0.08
42 29 161 6.91 3.6 1.07 151 4.99 92 2.47 1.9 66 53 131 0.70 91 0.06
43 31 154 7.28 3.6 1.00 148 5.17 106 2.03 1.8 101 68 131 0.70 115 0.09
44 30 135 7.93 3.8 0.91 144 4.56 60 2.11 2.7 111 74 89 0.71 109 0.00
45 30 180 7.05 3.6 1.02 147 4.54 88 2.36 2.1 74 52 139 0.74 93 0.10
46 28 172 5.22 2.7 1.09 147 5.66 98 1.76 1.7 118 79 74 0.60 71 0.05
47 28 153 7.99 3.8 0.90 156 5.83 101 1.60 2.2 91 46 113 0.66 99 0.19
48 28 89 7.32 3.7 1.04 149 8.13 60 2.51 2.9 91 54 176 0.69 107 0.06
49 45 140 6.55 3.5 1.12 150 6.31 95 2.43 2.2 58 55 179 1.15 104 0.11
50 32 200 6.86 3.6 1.10 146 4.35 99 2.43 2.4 64 57 139 0.71 124 0.09
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 31.7 160.5 7.027 3.53 1.017 148.2 5.778 87.9 2.174 2.25 90.2 62.0 130.0 0.772 99.4 0.083
S.D. 5.3 36.5 0.778 0.32 0.082 3.6 1.412 16.4 0.318 0.40 24.3 12.7 33.0 0.181 15.9 0.049
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
3(F) 51 35 151 6.37 3.4 1.16 153 5.23 104 2.56 1.6 71 40 65 0.57 79 0.09
52 33 140 8.62 4.6 1.17 150 4.29 106 2.86 2.1 67 41 70 0.78 111 0.11
53 32 157 7.61 4.4 1.37 150 4.78 103 2.79 2.0 70 60 72 0.66 91 0.12
54 34 132 6.37 3.6 1.31 151 4.73 103 2.41 1.6 86 28 30 0.61 108 0.07
55 34 178 7.44 4.0 1.17 148 4.56 104 2.77 1.4 91 55 107 0.74 93 0.10
56 37 158 6.46 3.8 1.43 151 4.78 100 2.61 1.8 99 49 40 0.59 76 0.09
57 37 172 5.71 3.4 1.44 148 4.89 102 2.53 1.7 84 53 36 0.54 55 0.07
58 32 157 6.15 3.7 1.53 154 4.81 105 2.53 1.7 64 40 42 0.54 77 0.11
59 35 190 6.86 3.8 1.25 146 4.39 104 2.77 2.0 66 55 110 0.73 97 0.08
60 29 167 7.25 4.1 1.30 151 4.72 101 2.85 1.9 91 40 63 0.72 85 0.07
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 33.8 160.2 6.884 3.88 1.313 150.2 4.718 103.2 2.668 1.78 78.9 46.1 63.5 0.648 87.2 0.091
S.D. 2.4 17.3 0.857 0.40 0.128 2.4 0.263 1.8 0.158 0.22 12.7 9.8 28.0 0.090 16.6 0.019
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
4(M) 61 35 153 6.83 3.7 1.18 146 4.32 103 2.49 1.4 66 59 177 0.69 91 0.11
62 37 163 7.16 3.6 1.03 147 5.31 102 2.56 2.0 61 53 141 0.83 119 0.14
63 33 163 7.06 3.7 1.12 152 4.72 99 2.68 1.7 69 58 146 0.71 114 0.10
64 26 126 7.41 3.7 1.01 144 5.19 97 2.58 2.3 58 54 103 0.58 116 0.11
65 35 172 7.45 3.7 0.99 146 6.85 102 2.22 2.1 75 48 125 0.81 93 0.07
66 21 127 7.19 3.8 1.10 146 6.18 96 2.62 2.3 84 79 304 0.75 93 0.08
67 38 70 7.51 3.6 0.94 145 7.17 84 2.64 2.5 86 52 196 0.97 85 0.14
68 23 179 7.32 3.8 1.07 149 5.01 102 2.71 2.5 60 58 182 0.76 95 0.10
69 29 259 6.13 3.4 1.21 147 5.08 99 2.52 2.5 119 147 122 0.71 79 0.08
70 32 152 7.09 3.7 1.10 150 5.19 105 2.61 1.9 55 40 186 0.70 111 0.14
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 30.9 156.4 7.115 3.67 1.075 147.2 5.502 98.9 2.563 2.12 73.3 64.8 168.2 0.751 99.6 0.107
S.D. 5.9 47.9 0.403 0.12 0.084 2.4 0.926 5.9 0.138 0.37 19.3 30.6 57.0 0.104 14.2 0.026
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 12 (continued) Individual and Group Mean Blood Chemical Values
Day: 90 Relative to Start Date
Group Animal Tot.
(Sex) Number Urea Glucose Prot. Albumin A/G Na+ K+ Clƒ Ca++ P ASAT ALAT AP Creat Chol Bili
mg/dl mg/dl g/dl g/dl Ratio mmol/l mmol/l mmol/l mmol/l mmol/l IU/l IU/l IU/l mg/dl mg/dl mg/dl
4(F) 71 33 187 5.47 3.2 1.44 149 5.85 101 2.28 1.6 291 259 52 0.53 73 0.08
72 29 151 7.42 4.1 1.21 150 4.53 109 2.77 1.5 68 56 95 0.77 118 0.08
73 37 167 7.87 4.3 1.22 150 6.27 106 2.79 2.1 110 57 89 0.95 102 0.06
74 37 152 5.58 3.2 1.37 153 5.92 102 2.44 1.3 230 89 95 0.60 60 0.07
75 25 167 8.22 4.7 1.31 152 4.71 103 2.90 1.3 58 63 138 0.65 129 0.12
76 25 169 7.47 4.2 1.25 150 4.33 105 2.84 2.3 49 42 73 0.66 100 0.08
77 35 165 6.05 3.6 1.44 149 5.00 102 2.55 1.0 87 70 49 0.56 100 0.08
78 34 159 5.64 3.3 1.41 149 5.32 104 2.65 1.1 89 38 26 0.61 74 0.10
79 39 220 6.13 3.5 1.32 152 5.05 101 2.74 1.1 78 62 62 0.62 80 0.08
80 32 183 6.96 3.9 1.29 151 4.86 109 2.74 2.1 52 41 99 0.78 92 0.10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Mean 32.6 172.0 6.681 3.80 1.326 150.5 5.184 104.2 2.670 1.54 111.2 77.7 77.8 0.673 92.8 0.085
S.D. 4.9 20.5 1.027 0.52 0.086 1.4 0.643 3.0 0.193 0.47 82.1 65.5 32.0 0.126 21.4 0.017
N 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ ƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
1(M) 1 17.8
2 11.5
3 14.8
4 10.3
5 5.8
6 2.2
7 13.1
8 11.5
9 22.6
10 21.5
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 13.11
S.D. 6.42
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
1(F) 11 0.4
12 9.2
13 11.9
15 33.8
16 26.7
17 28.4
18 10.4
19 32.7
20 69.5
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 24.78
S.D. 20.53
N 9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
2(M) 21 11.5
22 4.6
23 3.9
24 27.4
25 4.0
26 11.0
27 3.9
28 11.5
29 15.2
30 17.0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 11.00
S.D. 7.56
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
2(F) 31 17.4
32 14.0
33 18.5
34 3.8
35 12.3
36 32.9
37 15.6
38 18.6
39 14.6
40 15.2
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 16.29
S.D. 7.22
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
3(M) 41 14.6
42 6.4
43 16.9
44 8.0
45 10.6
46 4.6
47 8.9
48 20.0
49 18.8
50 14.0
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 12.28
S.D. 5.35
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
3(F) 51 27.5
52 6.6
53 47.7
54 21.3
55 21.9
56 20.0
57 19.9
58 16.3
59 47.7
60 5.3
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 23.42
S.D. 14.49
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
4(M) 61 22.7
62 27.9
63 26.2
64 11.4
65 18.8
66 16.4
67 18.9
68 17.2
69 17.7
70 15.9
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 19.31
S.D. 4.98
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 13 (continued) Individual and Group Mean Bile Acid Values
Day: 90 Relative to Start Date
Group Animal
(Sex) Number Bile Acid
µmol/l
4(F) 71 28.9
72 38.3
73 26.8
74 31.9
75 56.0
76 57.3
77 25.8
78 8.9
79 31.9
80 29.5
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 33.53
S.D. 14.33
N 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 14 Individual Necropsy Findings
Group: 1 Dose Level: 0 (Control) Sex: Male
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
1 TERMINAL SACRIFICE 91 (13) No abnormalities detected
2 TERMINAL SACRIFICE 91 (13) No abnormalities detected
3 TERMINAL SACRIFICE 91 (13) No abnormalities detected
4 TERMINAL SACRIFICE 91 (13) No abnormalities detected
5 TERMINAL SACRIFICE 91 (13) No abnormalities detected
6 TERMINAL SACRIFICE 91 (13) No abnormalities detected
7 TERMINAL SACRIFICE 91 (13) No abnormalities detected
8 TERMINAL SACRIFICE 91 (13) No abnormalities detected
9 TERMINAL SACRIFICE 91 (13) No abnormalities detected
10 TERMINAL SACRIFICE 91 (13) No abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 1 Dose Level: 0 (Control) Sex: Female
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
11 TERMINAL SACRIFICE 91 (13) No abnormalities detected
12 TERMINAL SACRIFICE 91 (13) No abnormalities detected
13 TERMINAL SACRIFICE 91 (13) No abnormalities detected
14 KILLED IN EXTREMIS 38 (6) Gross Lesions: Tail missing approx 55mm of skin .
Gross Lesions; Tail
All remaining tissues had no abnormalities detected
15 TERMINAL SACRIFICE 91 (13) No abnormalities detected
16 FOUND DEAD@ 90 (13) No abnormalities detected
17 TERMINAL SACRIFICE 91 (13) No abnormalities detected
18 TERMINAL SACRIFICE 91 (13) Uterus (With Cervix): Left horn filled with dark yellow fluid
Uterus (With Cervix); left horn; Fluid Filled
All remaining tissues had no abnormalities detected
19 TERMINAL SACRIFICE 91 (13) No abnormalities detected
20 TERMINAL SACRIFICE 91 (13) No abnormalities detected
@ = Died during bleeding procedure
Appendix 14 (continued) Individual Necropsy Findings
Group: 2 Dose Level: 100 mg/kg bw/day Sex: Male
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
21 TERMINAL SACRIFICE 91 (13) No abnormalities detected
22 TERMINAL SACRIFICE 91 (13) No abnormalities detected
23 TERMINAL SACRIFICE 91 (13) No abnormalities detected
24 TERMINAL SACRIFICE 91 (13) No abnormalities detected
25 TERMINAL SACRIFICE 91 (13) No abnormalities detected
26 TERMINAL SACRIFICE 91 (13) No abnormalities detected
27 TERMINAL SACRIFICE 91 (13) No abnormalities detected
28 TERMINAL SACRIFICE 91 (13) No abnormalities detected
29 TERMINAL SACRIFICE 91 (13) No abnormalities detected
30 TERMINAL SACRIFICE 91 (13) No abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 2 Dose Level: 100 mg/kg bw/day Sex: Female
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
31 TERMINAL SACRIFICE 91 (13) No abnormalities detected
32 TERMINAL SACRIFICE 91 (13) No abnormalities detected
33 TERMINAL SACRIFICE 91 (13) No abnormalities detected
34 TERMINAL SACRIFICE 91 (13) No abnormalities detected
35 TERMINAL SACRIFICE 91 (13) Lungs (With Bronchi); Discolouration; red
All remaining tissues had no abnormalities detected
36 TERMINAL SACRIFICE 91 (13) No abnormalities detected
37 TERMINAL SACRIFICE 91 (13) No abnormalities detected
38 TERMINAL SACRIFICE 91 (13) No abnormalities detected
39 TERMINAL SACRIFICE 91 (13) No abnormalities detected
40 TERMINAL SACRIFICE 91 (13) Lungs (With Bronchi); Discolouration; red
All remaining tissues had no abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 3 Dose Level: 300 mg/kg bw/day Sex: Male
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
41 TERMINAL SACRIFICE 91 (13) No abnormalities detected
42 TERMINAL SACRIFICE 91 (13) No abnormalities detected
43 TERMINAL SACRIFICE 91 (13) No abnormalities detected
44 TERMINAL SACRIFICE 91 (13) Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
45 TERMINAL SACRIFICE 91 (13) No abnormalities detected
46 TERMINAL SACRIFICE 91 (13) Kidneys; Mottled Appearance
All remaining tissues had no abnormalities detected
47 TERMINAL SACRIFICE 91 (13) No abnormalities detected
48 TERMINAL SACRIFICE 91 (13) No abnormalities detected
49 TERMINAL SACRIFICE 91 (13) No abnormalities detected
50 TERMINAL SACRIFICE 91 (13) No abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 3 Dose Level: 300 mg/kg bw/day Sex: Female
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
51 TERMINAL SACRIFICE 91 (13) No abnormalities detected
52 TERMINAL SACRIFICE 91 (13) No abnormalities detected
53 TERMINAL SACRIFICE 91 (13) No abnormalities detected
54 TERMINAL SACRIFICE 91 (13) No abnormalities detected
55 TERMINAL SACRIFICE 91 (13) Lungs (With Bronchi); Discolouration; red
All remaining tissues had no abnormalities detected
56 TERMINAL SACRIFICE 91 (13) No abnormalities detected
57 TERMINAL SACRIFICE 91 (13) No abnormalities detected
58 TERMINAL SACRIFICE 91 (13) No abnormalities detected
59 TERMINAL SACRIFICE 91 (13) No abnormalities detected
60 TERMINAL SACRIFICE 91 (13) Thymus; Lost On Removal
All remaining tissues had no abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 4 Dose Level: 1000 mg/kg bw/day Sex: Male
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
61 TERMINAL SACRIFICE 91 (13) No abnormalities detected
62 TERMINAL SACRIFICE 91 (13) Kidneys; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
63 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
64 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
65 TERMINAL SACRIFICE 91 (13) No abnormalities detected
66 TERMINAL SACRIFICE 91 (13) Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
67 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
68 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
69 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
70 TERMINAL SACRIFICE 91 (13) Kidneys; both; Enlarged
Kidneys; both; Mottled Appearance
All remaining tissues had no abnormalities detected
Appendix 14 (continued) Individual Necropsy Findings
Group: 4 Dose Level: 1000 mg/kg bw/day Sex: Female
Animal Death
No. Mode Of Death Day (Week) Observation(s)
ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ
71 TERMINAL SACRIFICE 91 (13) Uterus (With Cervix); Damaged On Removal
All remaining tissues had no abnormalities detected
72 TERMINAL SACRIFICE 91 (13) No abnormalities detected
73 TERMINAL SACRIFICE 91 (13) No abnormalities detected
74 TERMINAL SACRIFICE 91 (13) Eyes (Including Retina And Optic Nerve); right; Damaged On Removal
All remaining tissues had no abnormalities detected
75 TERMINAL SACRIFICE 91 (13) No abnormalities detected
76 TERMINAL SACRIFICE 91 (13) No abnormalities detected
77 TERMINAL SACRIFICE 91 (13) No abnormalities detected
78 TERMINAL SACRIFICE 91 (13) No abnormalities detected
79 TERMINAL SACRIFICE 91 (13) No abnormalities detected
80 TERMINAL SACRIFICE 91 (13) No abnormalities detected
Appendix 15 Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Epididyƒ
(Sex) Number Adrenals Brain mides Heart Kidneys Liver Spleen Testes Thymus
g g g g g g g g g
1(M) 1 0.0710 2.2013 1.9736 1.1731 2.6280 14.4692 0.7806 4.4275 0.5551
2 0.0848 2.0404 1.9943 1.2695 2.3479 13.7406 0.8545 4.0088 0.5102
3 0.0768 2.2499 1.4498 1.1802 2.1483 13.5443 0.7325 3.7382 0.3172
4 0.0488 2.1286 1.7535 1.5944 2.0494 11.7284 0.6308 3.7973 0.4602
5 0.0622 2.0496 1.6001 1.0712 2.0810 12.6761 0.5781 3.7088 0.4717
6 0.0619 2.1165 2.1275 1.3117 2.5537 15.2633 0.7485 4.2724 0.5298
7 0.0856 2.2878 1.8638 1.1820 2.8720 16.5821 0.8823 4.6332 0.5103
8 0.0744 2.1965 1.6937 1.0766 2.2774 13.0264 0.5827 4.2690 0.5592
9 0.0576 2.0735 1.3330 0.9914 1.9216 13.3874 0.8423 3.4326 0.3533
10 0.0638 2.0952 1.9688 1.2121 2.2311 14.6113 0.7807 4.6235 0.4715
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.06869 2.14393 1.77581 1.20622 2.31104 13.90291 0.74130 4.09113 0.47385
S.D. 0.01193 0.08558 0.25734 0.16646 0.29485 1.38539 0.11061 0.41532 0.08092
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Epididyƒ
(Sex) Number Adrenals Brain mides Heart Kidneys Liver Spleen Testes Thymus
g g g g g g g g g
2(M) 21 0.0877 2.0015 1.6799 1.0746 2.3544 18.9689 0.7704 4.1355 0.4398
22 0.0818 1.8396 2.3464 1.3909 2.7572 18.4010 0.8354 4.5414 0.5880
23 0.0841 2.3278 1.9196 1.1462 2.9044 19.8013 0.8329 3.9790 0.4407
24 0.0648 2.1941 1.6877 1.3781 2.4457 16.8889 0.6404 4.4820 0.5120
25 0.0601 2.2060 1.8355 1.4093 2.5637 14.6436 0.6831 3.6194 0.3377
26 0.0571 2.1365 1.6736 1.1676 2.4363 14.6205 0.7287 4.3127 0.4509
27 0.0753 2.1823 2.0999 1.0549 2.4451 14.3401 0.7260 3.8987 0.6757
28 0.0963 2.3646 2.0605 1.1997 2.3105 14.8845 0.8731 4.6395 0.4894
29 0.0837 2.1452 1.6797 1.2895 2.6009 14.4985 0.6463 3.7735 0.3631
30 0.0695 2.2074 1.7112 1.2697 2.7379 18.5250 0.8301 3.9850 0.4449
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.07604 2.16050 1.86940 1.23805 2.55561 16.55723 0.75664 4.13667 0.47422
S.D. 0.01285 0.15077 0.23312 0.12956 0.19343 2.18802 0.08432 0.34494 0.09994
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Epididyƒ
(Sex) Number Adrenals Brain mides Heart Kidneys Liver Spleen Testes Thymus
g g g g g g g g g
3(M) 41 0.0390 1.8513 1.4775 0.9974 1.9386 11.3205 0.6865 3.2027 0.3799
42 0.0780 2.1653 1.9650 1.1340 2.2169 12.2522 0.5992 3.9465 0.3595
43 0.0758 1.9337 1.9211 1.0227 2.5070 16.8999 1.1062 4.4905 0.4055
44 0.0749 2.2001 1.7094 1.3195 2.7980 14.3626 0.8172 3.5869 0.4443
45 0.0870 2.1186 2.0050 1.3042 2.9066 17.5065 1.1034 4.0719 0.5781
46 0.0746 2.0199 1.8867 1.1285 2.5510 16.5276 0.7232 3.5841 0.5041
47 0.0862 2.1267 1.5779 1.2272 2.6950 15.5207 0.6131 4.0283 0.3879
48 0.0726 2.1557 2.0159 1.2317 2.4734 14.4575 0.9079 4.1210 0.3037
49 0.0728 2.0429 1.8354 1.1318 2.5903 16.3136 0.8830 4.2484 0.4033
50 0.0649 1.9837 2.1908 1.2912 2.2536 14.6960 0.6739 4.3617 0.5469
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.07258 2.05979 1.85847 1.17882 2.49304 14.98571 0.81136 3.96420 0.43132
S.D. 0.01345 0.11303 0.21586 0.11417 0.29044 2.00284 0.18657 0.39764 0.08679
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Epididyƒ
(Sex) Number Adrenals Brain mides Heart Kidneys Liver Spleen Testes Thymus
g g g g g g g g g
4(M) 61 0.0695 1.8342 1.7376 0.8864 2.6044 14.3982 0.7258 4.1783 0.3090
62 0.0542 1.9283 1.6202 1.0685 2.9039 15.5445 0.6382 4.2708 0.4157
63 0.0661 1.9824 1.7244 0.9315 3.0643 15.4188 0.7223 3.6897 0.2775
64 0.0780 1.9593 2.0561 1.1800 3.5856 19.0785 0.7695 5.5233 0.5312
65 0.0572 1.8921 1.4669 1.1991 2.6337 18.2618 0.6633 3.6693 0.2125
66 0.0650 1.9720 1.7875 1.1985 3.1151 17.2268 0.8692 4.2350 0.5210
67 0.0664 2.1842 1.9907 1.3848 4.3960 18.2680 0.9726 4.0282 0.4718
68 0.0846 2.0974 1.7974 1.1980 3.4205 17.4858 0.8057 3.9285 0.6025
69 0.0775 2.3090 2.0624 1.1434 3.2449 19.4229 0.7864 4.4263 0.5338
70 0.0579 1.9225 1.8512 1.3195 4.0841 19.6869 0.6817 4.6745 0.4107
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Mean 0.06764 2.00814 1.80944 1.15097 3.30525 17.47922 0.76347 4.26239 0.42857
S.D. 0.00995 0.14578 0.19020 0.15482 0.58588 1.82541 0.10154 0.54166 0.12761
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Uterus
(Sex) Number Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus & Cervix
g g g g g g g g g
1(F) 11 0.0820 1.9486 0.7293 1.2587 8.7413 0.1396 0.5649 0.3715 0.7017
12 0.0825 1.9267 0.8732 1.2745 6.6249 0.0870 0.4434 0.4166 0.9550
13 0.1020 2.0695 1.0484 1.6835 9.7591 0.1029 0.5848 0.3705 0.5405
15 0.0917 1.7070 0.6620 1.3233 7.6394 0.1360 0.5450 0.4390 0.6248
17 0.0558 1.9588 0.7315 1.3296 7.8127 0.1035 0.3968 0.3212 0.5996
18 0.0830 1.9236 0.9537 1.4876 7.7140 0.1529 0.5860 0.3964 1.3989
19 0.0661 1.9740 0.8862 1.5991 8.2948 0.0921 0.5166 0.3910 0.7068
20 0.0803 1.9534 0.7760 1.4376 8.0879 0.1436 0.5948 0.2956 1.0456
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.08043 1.93270 0.83254 1.42424 8.08426 0.11970 0.52904 0.37523 0.82161
S.D. 0.01423 0.10201 0.13036 0.15628 0.91180 0.02594 0.07289 0.04747 0.29175
N 8 8 8 8 8 8 8 8 8
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Uterus
(Sex) Number Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus & Cervix
g g g g g g g g g
2(F) 31 0.0811 1.8694 0.9021 1.5634 9.0947 0.1145 0.5262 0.3900 0.5619
32 0.0773 1.9699 1.0124 1.3854 9.0929 0.0869 0.5662 0.3992 0.6351
33 0.0979 1.9407 0.7492 1.4768 8.6351 0.1081 0.5746 0.4041 1.1425
34 0.1076 1.9194 0.7518 1.3780 8.6728 0.1220 0.5771 0.3050 1.0300
35 0.0960 2.0302 1.0119 1.7445 10.2470 0.1159 0.5923 0.4155 0.6859
36 0.0944 1.8850 0.7760 1.5070 8.7932 0.1730 0.5417 0.5066 0.7842
37 0.0787 2.0142 0.7989 1.4151 8.9720 0.1064 0.5466 0.4892 0.8788
38 0.0623 1.9714 0.7383 1.2563 6.7257 0.1212 0.4452 0.3701 0.5700
39 0.0901 1.7060 0.7855 1.1602 9.2205 0.1123 0.5865 0.3419 1.4729
40 0.1042 2.0631 1.1207 1.9279 8.7376 0.1990 0.4707 0.3368 0.8560
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.08896 1.93693 0.86468 1.48146 8.81915 0.12593 0.54271 0.39584 0.86173
S.D. 0.01396 0.10207 0.13782 0.22463 0.87045 0.03372 0.04957 0.06394 0.28757
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Uterus
(Sex) Number Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus & Cervix
g g g g g g g g g
3(F) 51 0.1019 1.9243 0.7459 1.6331 8.6338 0.1468 0.6768 0.5098 1.2871
52 0.0954 1.9022 0.8857 1.3568 9.5565 0.1594 0.5017 0.3961 0.6076
53 0.0818 1.9432 0.7735 1.7009 8.9409 0.0548 0.5305 0.2836 0.9078
54 0.0892 1.9153 0.6547 1.5448 9.4766 0.1755 0.4614 0.3147 0.8595
55 0.0709 1.6216 0.7330 2.0581 7.6488 0.0723 0.5313 0.3073 1.3182
56 0.0766 1.9606 0.8055 1.4733 9.3450 0.0927 0.5006 0.3000 0.5400
57 0.0744 1.9310 0.7805 1.6545 8.9119 0.1174 0.4971 0.4490 0.5523
58 0.0795 1.9959 0.8167 1.8003 8.8725 0.1132 0.5949 0.5042 0.7177
59 0.0619 1.8327 0.8160 1.5704 9.4541 0.1329 0.6673 0.3295 1.2604
60 0.0933 1.9115 0.8072 1.8019 9.4679 0.1673 0.5505 0.8110
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.08249 1.89383 0.78187 1.65941 9.03080 0.12323 0.55121 0.37713 0.88616
S.D. 0.01235 0.10452 0.06172 0.19687 0.58299 0.04079 0.07302 0.09015 0.30397
N 10 10 10 10 10 10 10 9 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 15 (continued) Individual and Group Mean Organ Weights
Day: 91 Relative to Start Date
Group Animal Uterus
(Sex) Number Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus & Cervix
g g g g g g g g g
4(F) 71 0.0825 1.9182 0.7526 1.4615 10.9325 0.1657 0.4820 0.3725 0.6496
72 0.1016 1.9085 0.7802 1.6727 11.4118 0.0934 0.5522 0.3268 0.5507
73 0.0660 1.8725 0.7454 1.5968 11.0088 0.1107 0.5934 0.3517 1.1367
74 0.1078 1.9200 0.6964 1.7894 12.5055 0.1376 0.4810 0.3753 0.7575
75 0.0912 1.9763 0.8405 1.7881 13.3983 0.1583 0.5810 0.2816 1.4720
76 0.0846 1.9760 0.7317 1.9287 12.5221 0.0604 0.9680 0.3435 0.9121
77 0.0751 1.8306 0.6811 1.4574 11.2270 0.0967 0.4203 0.4362 0.8196
78 0.0968 1.9032 0.6422 1.6744 11.9829 0.1628 0.5463 0.3450 1.0714
79 0.0683 1.9582 0.7690 1.5685 11.3205 0.1062 0.4814 0.3569 0.8696
80 0.1176 1.9307 0.8966 1.9647 11.8984 0.1136 0.6795 0.6116 0.5749
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 0.08915 1.91942 0.75357 1.69022 11.82078 0.12054 0.57851 0.38011 0.88141
S.D. 0.01702 0.04539 0.07486 0.17709 0.79583 0.03466 0.15533 0.09023 0.28429
N 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Epididys Heart Kidneys Liver Spleen Testes Thymus
g % % % % % % % % %
1(M) 1 417 0.0170 0.5279 0.4733 0.2813 0.6302 3.4698 0.1872 1.0618 0.1331
2 406 0.0209 0.5026 0.4912 0.3127 0.5783 3.3844 0.2105 0.9874 0.1257
3 392 0.0196 0.5740 0.3698 0.3011 0.5480 3.4552 0.1869 0.9536 0.0809
4 355 0.0137 0.5996 0.4939 0.4491 0.5773 3.3038 0.1777 1.0697 0.1296
5 376 0.0165 0.5451 0.4256 0.2849 0.5535 3.3713 0.1538 0.9864 0.1255
6 434 0.0143 0.4877 0.4902 0.3022 0.5884 3.5169 0.1725 0.9844 0.1221
7 433 0.0198 0.5284 0.4304 0.2730 0.6633 3.8296 0.2038 1.0700 0.1179
8 421 0.0177 0.5217 0.4023 0.2557 0.5410 3.0942 0.1384 1.0140 0.1328
9 401 0.0144 0.5171 0.3324 0.2472 0.4792 3.3385 0.2100 0.8560 0.0881
10 413 0.0154 0.5073 0.4767 0.2935 0.5402 3.5378 0.1890 1.1195 0.1142
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 404.8 0.01693 0.53114 0.43858 0.30007 0.56994 3.43015 0.18298 1.01028 0.11699
S.D. 25.0 0.00254 0.03382 0.05648 0.05627 0.05112 0.18964 0.02349 0.07489 0.01822
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Epididys Heart Kidneys Liver Spleen Testes Thymus
g % % % % % % % % %
2(M) 21 418 0.0210 0.4788 0.4019 0.2571 0.5633 4.5380 0.1843 0.9894 0.1052
22 456 0.0179 0.4034 0.5146 0.3050 0.6046 4.0353 0.1832 0.9959 0.1289
23 456 0.0184 0.5105 0.4210 0.2514 0.6369 4.3424 0.1827 0.8726 0.0966
24 423 0.0153 0.5187 0.3990 0.3258 0.5782 3.9926 0.1514 1.0596 0.1210
25 410 0.0147 0.5380 0.4477 0.3437 0.6253 3.5716 0.1666 0.8828 0.0824
26 417 0.0137 0.5124 0.4013 0.2800 0.5842 3.5061 0.1747 1.0342 0.1081
27 441 0.0171 0.4949 0.4762 0.2392 0.5544 3.2517 0.1646 0.8841 0.1532
28 458 0.0210 0.5163 0.4499 0.2619 0.5045 3.2499 0.1906 1.0130 0.1069
29 379 0.0221 0.5660 0.4432 0.3402 0.6863 3.8255 0.1705 0.9956 0.0958
30 479 0.0145 0.4608 0.3572 0.2651 0.5716 3.8674 0.1733 0.8319 0.0929
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 433.7 0.01757 0.49998 0.43120 0.28694 0.59093 3.81805 0.17419 0.95591 0.10910
S.D. 29.6 0.00303 0.04475 0.04487 0.03870 0.05025 0.43141 0.01159 0.07976 0.02057
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Epididys Heart Kidneys Liver Spleen Testes Thymus
g % % % % % % % % %
3(M) 41 340 0.0115 0.5445 0.4346 0.2934 0.5702 3.3296 0.2019 0.9420 0.1117
42 390 0.0200 0.5552 0.5038 0.2908 0.5684 3.1416 0.1536 1.0119 0.0922
43 393 0.0193 0.4920 0.4888 0.2602 0.6379 4.3002 0.2815 1.1426 0.1032
44 380 0.0197 0.5790 0.4498 0.3472 0.7363 3.7796 0.2151 0.9439 0.1169
45 437 0.0199 0.4848 0.4588 0.2984 0.6651 4.0061 0.2525 0.9318 0.1323
46 416 0.0179 0.4856 0.4535 0.2713 0.6132 3.9730 0.1738 0.8616 0.1212
47 386 0.0223 0.5510 0.4088 0.3179 0.6982 4.0209 0.1588 1.0436 0.1005
48 385 0.0189 0.5599 0.5236 0.3199 0.6424 3.7552 0.2358 1.0704 0.0789
49 417 0.0175 0.4899 0.4401 0.2714 0.6212 3.9121 0.2118 1.0188 0.0967
50 385 0.0169 0.5152 0.5690 0.3354 0.5854 3.8171 0.1750 1.1329 0.1421
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 392.9 0.01839 0.52571 0.47308 0.30059 0.63383 3.80354 0.20598 1.00995 0.10957
S.D. 26.3 0.00286 0.03603 0.04804 0.02896 0.05474 0.34015 0.04197 0.09109 0.01915
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Epididys Heart Kidneys Liver Spleen Testes Thymus
g % % % % % % % % %
4(M) 61 315 0.0221 0.5823 0.5516 0.2814 0.8268 4.5709 0.2304 1.3264 0.0981
62 363 0.0149 0.5312 0.4463 0.2944 0.8000 4.2822 0.1758 1.1765 0.1145
63 324 0.0204 0.6119 0.5322 0.2875 0.9458 4.7589 0.2229 1.1388 0.0856
64 410 0.0190 0.4779 0.5015 0.2878 0.8745 4.6533 0.1877 1.3471 0.1296
65 330 0.0173 0.5734 0.4445 0.3634 0.7981 5.5339 0.2010 1.1119 0.0644
66 386 0.0168 0.5109 0.4631 0.3105 0.8070 4.4629 0.2252 1.0972 0.1350
67 391 0.0170 0.5586 0.5091 0.3542 1.1243 4.6721 0.2487 1.0302 0.1207
68 423 0.0200 0.4958 0.4249 0.2832 0.8086 4.1338 0.1905 0.9287 0.1424
69 403 0.0192 0.5730 0.5118 0.2837 0.8052 4.8196 0.1951 1.0983 0.1325
70 371 0.0156 0.5182 0.4990 0.3557 1.1008 5.3064 0.1837 1.2600 0.1107
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 371.6 0.01823 0.54332 0.48840 0.31018 0.88911 4.71940 0.20610 1.15151 0.11335
S.D. 37.9 0.00228 0.04296 0.04156 0.03393 0.12646 0.42793 0.02404 0.13043 0.02451
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus rus & Ce
g % % % % % % % % %
1(F) 11 226 0.0363 0.8622 0.3227 0.5569 3.8678 0.0618 0.2500 0.1644 0.3105
12 211 0.0391 0.9131 0.4138 0.6040 3.1398 0.0412 0.2101 0.1974 0.4526
13 271 0.0376 0.7637 0.3869 0.6212 3.6011 0.0380 0.2158 0.1367 0.1994
15 230 0.0399 0.7422 0.2878 0.5753 3.3215 0.0591 0.2370 0.1909 0.2717
17 231 0.0242 0.8480 0.3167 0.5756 3.3821 0.0448 0.1718 0.1390 0.2596
18 245 0.0339 0.7851 0.3893 0.6072 3.1486 0.0624 0.2392 0.1618 0.5710
19 246 0.0269 0.8024 0.3602 0.6500 3.3719 0.0374 0.2100 0.1589 0.2873
20 229 0.0351 0.8530 0.3389 0.6278 3.5318 0.0627 0.2597 0.1291 0.4566
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 236.1 0.03413 0.82121 0.35204 0.60225 3.42058 0.05093 0.22420 0.15978 0.35109
S.D. 17.9 0.00569 0.05740 0.04292 0.03120 0.24244 0.01157 0.02811 0.02483 0.12717
N 8 8 8 8 8 8 8 8 8 8
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus rus & Ce
g % % % % % % % % %
2(F) 31 259 0.0313 0.7218 0.3483 0.6036 3.5115 0.0442 0.2032 0.1506 0.2169
32 264 0.0293 0.7462 0.3835 0.5248 3.4443 0.0329 0.2145 0.1512 0.2406
33 235 0.0417 0.8258 0.3188 0.6284 3.6745 0.0460 0.2445 0.1720 0.4862
34 240 0.0448 0.7997 0.3133 0.5742 3.6137 0.0508 0.2405 0.1271 0.4292
35 250 0.0384 0.8121 0.4048 0.6978 4.0988 0.0464 0.2369 0.1662 0.2744
36 235 0.0402 0.8021 0.3302 0.6413 3.7418 0.0736 0.2305 0.2156 0.3337
37 236 0.0333 0.8535 0.3385 0.5996 3.8017 0.0451 0.2316 0.2073 0.3724
38 217 0.0287 0.9085 0.3402 0.5789 3.0994 0.0559 0.2052 0.1706 0.2627
39 218 0.0413 0.7826 0.3603 0.5322 4.2296 0.0515 0.2690 0.1568 0.6756
40 246 0.0424 0.8387 0.4556 0.7837 3.5519 0.0809 0.1913 0.1369 0.3480
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 240.0 0.03714 0.80910 0.35935 0.61645 3.67672 0.05273 0.22672 0.16543 0.36397
S.D. 15.5 0.00593 0.05316 0.04404 0.07781 0.32281 0.01435 0.02323 0.02813 0.13852
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus rus & Ce
g % % % % % % % % %
3(F) 51 248 0.0411 0.7759 0.3008 0.6585 3.4814 0.0592 0.2729 0.2056 0.5190
52 219 0.0436 0.8686 0.4044 0.6195 4.3637 0.0728 0.2291 0.1809 0.2774
53 213 0.0384 0.9123 0.3631 0.7985 4.1976 0.0257 0.2491 0.1331 0.4262
54 229 0.0390 0.8364 0.2859 0.6746 4.1383 0.0766 0.2015 0.1374 0.3753
55 189 0.0375 0.8580 0.3878 1.0889 4.0470 0.0383 0.2811 0.1626 0.6975
56 230 0.0333 0.8524 0.3502 0.6406 4.0630 0.0403 0.2177 0.1304 0.2348
57 230 0.0323 0.8396 0.3393 0.7193 3.8747 0.0510 0.2161 0.1952 0.2401
58 258 0.0308 0.7736 0.3166 0.6978 3.4390 0.0439 0.2306 0.1954 0.2782
59 231 0.0268 0.7934 0.3532 0.6798 4.0927 0.0575 0.2889 0.1426 0.5456
60 249 0.0375 0.7677 0.3242 0.7237 3.8024 0.0672 0.2211 0.3257
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 229.6 0.03603 0.82779 0.34255 0.73012 3.94998 0.05325 0.24081 0.16480 0.39198
S.D. 19.9 0.00512 0.04826 0.03718 0.13565 0.30159 0.01639 0.03047 0.03004 0.15376
N 10 10 10 10 10 10 10 10 9 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
Appendix 16 (continued) Individual and Group Mean Relative Organ Weights
Day: 91 Relative to Start Date
Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative
(Sex) Number Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Spleen Thymus rus & Ce
g % % % % % % % % %
4(F) 71 205 0.0402 0.9357 0.3671 0.7129 5.3329 0.0808 0.2351 0.1817 0.3169
72 230 0.0442 0.8298 0.3392 0.7273 4.9617 0.0406 0.2401 0.1421 0.2394
73 217 0.0304 0.8629 0.3435 0.7359 5.0732 0.0510 0.2735 0.1621 0.5238
74 241 0.0447 0.7967 0.2890 0.7425 5.1890 0.0571 0.1996 0.1557 0.3143
75 241 0.0378 0.8200 0.3488 0.7420 5.5595 0.0657 0.2411 0.1168 0.6108
76 237 0.0357 0.8338 0.3087 0.8138 5.2836 0.0255 0.4084 0.1449 0.3849
77 210 0.0358 0.8717 0.3243 0.6940 5.3462 0.0460 0.2001 0.2077 0.3903
78 219 0.0442 0.8690 0.2932 0.7646 5.4716 0.0743 0.2495 0.1575 0.4892
79 237 0.0288 0.8262 0.3245 0.6618 4.7766 0.0448 0.2031 0.1506 0.3669
80 262 0.0449 0.7369 0.3422 0.7499 4.5414 0.0434 0.2594 0.2334 0.2194
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Mean 229.9 0.03867 0.83827 0.32805 0.73447 5.15357 0.05292 0.25099 0.16525 0.38559
S.D. 17.3 0.00598 0.05243 0.02508 0.04082 0.31859 0.01676 0.06087 0.03398 0.12460
N 10 10 10 10 10 10 10 10 10 10
ƒƒƒƒƒƒ ƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ ƒƒƒƒƒƒƒƒ
Dose Levels: Group 1 ƒ 0(Control) Group 2 ƒ 100 mg/kg bw/day Group 3 ƒ 300 mg/kg bw/day Group 4 ƒ 1000 mg/kg bw/day
ANNEXES
Annex 1 Histopathology Phase Report
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Annex 2 Analytical Investigations
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Annex
Applicant's summary and conclusion
- Conclusions:
- The oral administration of 2,3-epoxypropyl neodecanoate to rats over 90 consecutive days at dose levels of 100, 300, or 1000 mg/kg bw/day resulted in non-adverse treatment related effects at all dose levels. The histopathological changes observed in the kidneys were considered adverse at dose levels of 300 mg/kg bw/day and above for males only. Other findings from treated groups were considered to be either adaptive change or not toxicologically significant. Therefore a No Observed Adverse Effect Level was established at 100 mg/kg bw/day for males and 1000 mg/kg bw/day for females.
- Executive summary:
Introduction
The study was designed to investigate the systemic toxicity of the test item and is compatible with the following regulatory guidelines:
• The OECD Guidelines for Testing of Chemicals No. 408 "Subchronic Oral Toxicity - Rodent: 90 Day Study” (Adopted 21 September 1998).
This study was also designed to be compatible with Commission Regulation (EC) No 440/2008 of 30 May 2008, laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
Methods
The test item was administered by gavage to three groups, each of ten male and ten female Wistar Han™:RccHan™:WIST strain rats, for up to ninety consecutive days, at dose levels of 100, 300 and 1000 mg/kg bw/day. A control group of ten males and ten females was dosed with vehicle alone (Arachis oil BP) over the same treatment period.
Clinical signs, functional observations, body weight change, dietary intake and water consumption were monitored during the study. Hematology and blood chemistry were evaluated for all surviving animals at the end of the study. Ophthalmoscopic examination was also performed on all surviving control group and high dose animals.
All animals were subjected to gross necropsy examination and histopathological evaluation of selected tissues from all control and high dose animals (Groups 1 and 4) as well as gross lesions from all animals was performed. Histopathological evaluation of the liver and thyroid gland for both sexes and kidneys for males only extended to the low and intermediate dose groups.
Results
Mortality
There were no deaths related to treatment.
Two control group females prematurely died; one female (No. 14) was killed in extremis due to a physical injury to the tail on Day 38 and a further female (No. 16) died during the blood sampling procedure on Day 90 of treatment.
Clinical Observations
Increased salivation was evident in animals of either sex treated with 300 or 1000 mg/kg bw/day throughout the treatment period and to a lesser extent in males treated with 100 mg/kg bw/day.
Behavioral Assessment
A number of animals showed sporadic instances of increased salivation during behavioral assessments in the treatment period with a range of severity from slight to extreme. These observations correlate with the daily clinical observations evident.
Functional Performance Tests
There were no toxicological changes in the functional parameters measured.
Sensory Reactivity Assessments
There were no toxicological changes in the sensory parameters measured.
Body Weight
There were no effects for body weight development at 100, 300 or 1000 mg/kg bw/day. Overall weight gain for males was lower than controls at 1000 mg/kg bw/day.
Food Consumption
There were no effects detected for food consumption or food conversion efficiency at 100, 300 or 1000 mg/kg bw/day.
Water Consumption
An increase in water intake was apparent in animals of either sex treated with 1000 mg/kg bw/day of approximately 25%. This would correlate with the frequency and severity of the increased salivation in these animals. No such effects were apparent in animals treated with 100 or 300 mg/kg bw/day.
Ophthalmoscopy
There were no treatment related ocular effects detected.
Hematology
At 1000 mg/kg bw/day males showed a statistically significant reduction in hemaglobin (Hb) (p<0.01), erythrocyte count (RBC) (p<0.05) and hematocrit (Hct) (p<0.05) compared to controls. The majority of the individual values for each parameter were below the background control ranges which may indicate hemolytic anemia influenced by the histopathological changes to the liver.
Blood Chemistry
All treatment dose groups for males and females showed an increase in bilirubin (p<0.05 - p<0.01) with the exception of 100 mg/kg bw/day females. Animals of either sex did not show a dose related response and the majority of individual values were within the background control ranges. However, increased bilirubin can be associated with the reductions in Hb, Hct and RBC for males at 1000 mg/kg bw/day.
At 1000 mg/kg bw/day males displayed an increase in alkaline phosphatase (AP) and bile acid (p<0.01 and p<0.05, respectively) when compared to controls. The majority of individual values were within the background control ranges, however, these elevations may be associated to the histopathological changes of the liver.
Necropsy
Treatment-related abnormalities were as follows:
At 1000 mg/kg bw/day seven males had kidneys which were both enlarged and eight males had kidneys with mottled appearance. In addition two males at 300 mg/kg bw/day also had mottled appearance of the kidneys.
Organ Weights
Kidney: Males treated with 300 or 1000 mg/kg bw/day showed an increase (p<0.05 and p<0.01, respectively) in both absolute and relative kidney weights compared to controls. An increase was also evident in the corresponding female kidney weights at 300 and 1000 mg/kg bw/day (p<0.01) compared to controls.
Liver: All male treated dose groups showed an increase (p<0.05 - p<0.01) in absolute liver weight compared to controls, without a dose relationship present. The corresponding females treated with 100, 300 or 1000 mg/kg bw/day also showed an increase (p<0.05 - p<0.01) in liver weights both absolute and relative to terminal body weight in a dose related response.
Histopathology
Treatment-related microscopic findings are as follows:
Kidney
Increased hyaline droplets, granular casts and multifocal basophilic tubules or nephropathy were present in all males at 1000 mg/kg bw/day. Hyaline droplet formation extended to all males and 4/10 males at 300 and 100 mg/kg bw/day. Granule casts and multifocal basophilic tubules was seen in 5/10 males at 300 mg/kg bw/day.
Liver
Hepatocellular hypertrophy, mainly in the centrilobular area was present in 4/10 males and 5/10 females at 1000 mg/kg bw/day and 1 male at 100 mg/kg bw/day.
Thyroid Glands
Hypertrophy of the follicular epithelium was present in 6/10 males and 5/10 females at 1000 mg/kg bw/day. This finding extended to 6/10 males and 1/10 females at 300 mg/kg bw/day and 3/10 males and 1/10 females at 100 mg/kg bw/day.
Conclusion
The oral administration of 2,3-epoxypropyl neodecanoate to rats over 90 consecutive days at dose levels of 100, 300, or 1000 mg/kg bw/day resulted in non-adverse treatment related effects at all dose levels. The histopathological changes observed in the kidneys were considered adverse at dose levels of 300 mg/kg bw/day and above for males only. Other findings from treated groups were considered to be either adaptive change or not toxicologically significant. Therefore a No Observed Adverse Effect Level was established at 100 mg/kg bw/day for males and 1000 mg/kg bw/day for females.
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